No evidence for the existence of a specific progesterone receptor in human mononuclear leukocytes was obtained as judged by the results of competition experiments where a progesterone receptor-specific ligand [ 3H ] Org 2058 was used .

No evidence for the existence of a specific <protein>progesterone receptor</protein> in <cell_type>human mononuclear leukocytes</cell_type> was obtained as judged by the results of competition experiments where a progesterone receptor-specific ligand [ 3H ] Org 2058 was used .


Medroxyprogesterone acetate and megestrol acetate also induced glucocorticoid-like effects on the lymphocyte functions .

Medroxyprogesterone acetate and megestrol acetate also induced glucocorticoid-like effects on the <cell_type>lymphocyte</cell_type> functions .


These included inhibition of the proliferative responses to the T-cell mitogens concanavalin A and phytohaemagglutinin and an enhanced accumulation of immunoglobulin secreting cells in pokeweed mitogen-stimulated cultures .

These included inhibition of the proliferative responses to the <protein>T-cell mitogens</protein> <protein>concanavalin A</protein> and <protein>phytohaemagglutinin</protein> and an enhanced accumulation of <cell_type>immunoglobulin secreting cells</cell_type> in <cell_line>pokeweed mitogen-stimulated cultures</cell_line> .


The progestin effect appears to be mediated through a radiosensitive ( suppressor ) subpopulation of T lymphocytes .

The progestin effect appears to be mediated through a radiosensitive ( suppressor ) subpopulation of <cell_type>T lymphocytes</cell_type> .


In contrast , the synthetic progestins related structurally to 19-nortestosterone , norethisterone and d-norgestrel , were virtually devoid of binding affinity towards the glucocorticoid receptor nor did they measurably influence the in vitro lymphocyte functions .

In contrast , the synthetic progestins related structurally to 19-nortestosterone , norethisterone and d-norgestrel , were virtually devoid of binding affinity towards the <protein>glucocorticoid receptor</protein> nor did they measurably influence the in vitro <cell_type>lymphocyte</cell_type> functions .


These studies demonstrate that certain progestins in common clinical use probably possess inherent glucocorticoid activity and suggest that side effects attributable to this character ( e.g. suppression of the pituitary-adrenal axis ) might be expected when these compounds are used in pharmacological doses .


Metabolic and ultrastructural aspects of the in vitro lysis of chronic lymphocytic leukemia cells by glucocorticoids .

Metabolic and ultrastructural aspects of the in vitro lysis of <cell_type>chronic lymphocytic leukemia cells</cell_type> by glucocorticoids .


Human chronic lymphocytic leukemia ( CLL ) cells like prothymocytes and immunoactivated T-lymphocytes are readily lysed in vitro by pharmacological concentrations of glucocorticoids such as cortisol , whereas peripheral blood lymphocytes and thymocytes are unaffected by the hormone .

<cell_type>Human chronic lymphocytic leukemia ( CLL ) cells</cell_type> like <cell_type>prothymocytes</cell_type> and <cell_type>immunoactivated T-lymphocytes</cell_type> are readily lysed in vitro by pharmacological concentrations of glucocorticoids such as cortisol , whereas <cell_type>peripheral blood lymphocytes</cell_type> and <cell_type>thymocytes</cell_type> are unaffected by the <protein>hormone</protein> .


In this study , metabolic and ultrastructural aspects of the cortisol-induced killing process of CLL cells are recorded .

In this study , metabolic and ultrastructural aspects of the cortisol-induced killing process of <cell_type>CLL cells</cell_type> are recorded .


In vitro lysis was found to be temperature dependent and was detected only after 6 to 8 hr incubation with cortisol by means of the trypan blue exclusion test .


However , 30 min of incubation with cortisol at either 37 degrees or 4 degrees followed by the removal of the hormone was still sufficient to induce the lytic process .

However , 30 min of incubation with cortisol at either 37 degrees or 4 degrees followed by the removal of the <protein>hormone</protein> was still sufficient to induce the lytic process .


Ultrastructural studies demonstrated sequential changes in the cytoplasm , including swelling of mitochondria and cytoplasmic decompartmentalization , followed by loss of surface microvilli with the appearance of `` holes '' in the cell membrane , and subsequent condensation of nuclear chromatin .

Ultrastructural studies demonstrated sequential changes in the cytoplasm , including swelling of mitochondria and cytoplasmic decompartmentalization , followed by loss of surface microvilli with the appearance of `` holes '' in the cell membrane , and subsequent condensation of <dna>nuclear chromatin</dna> .


The large holes in the membrane appearing after 6 hr of incubation with the hormone may be the cause for the penetration of the viable stain into the dead cells , as seen by light microscopy .

The large holes in the membrane appearing after 6 hr of incubation with the <protein>hormone</protein> may be the cause for the penetration of the viable stain into the <cell_type>dead cells</cell_type> , as seen by light microscopy .


Addition of metabolic inhibitors including actinomycin D , puromycin , and cycloheximide following administration of cortisol resulted in inhibition of the cell lysis .


An excess of an antagonist such as cortexolone was found to inhibit the cortisol-induced cytolysis of the CLL cells .

An excess of an antagonist such as cortexolone was found to inhibit the cortisol-induced cytolysis of the <cell_line>CLL cells</cell_line> .


It is suggested that the glucocorticoid-induced lysis of human CLL cells is similar to the phenomenon observed in rat or murine lymphocytes and is mediated by interaction of the steroid molecule with the cytoplasmic receptor .

It is suggested that the glucocorticoid-induced lysis of <cell_line>human CLL cells</cell_line> is similar to the phenomenon observed in <cell_type>rat or murine lymphocytes</cell_type> and is mediated by interaction of the steroid molecule with the <protein>cytoplasmic receptor</protein> .


The resulting complex appears to activate specific gene ( s ) the products of which eventually cause cytolysis .

The resulting complex appears to activate specific <dna>gene</dna> ( s ) the products of which eventually cause cytolysis .


Glucocorticoid receptors in lymphoid tumors .

<protein>Glucocorticoid receptors</protein> in lymphoid tumors .


There is a range of levels of glucocorticoid receptor numbers seen in the various subclasses of acute lymphatic leukemia ( ALL ) .

There is a range of levels of <protein>glucocorticoid receptor</protein> numbers seen in the various subclasses of acute lymphatic leukemia ( ALL ) .


This variability can not be explained by the known correlation between active cell proliferation and an increase in the number of receptors , since the tumors with the highest growth fraction ( i.e. , Burkitt 's lymphoma and T-cell leukemia ) tend to have lower average receptor numbers than do tumors with lower growth fractions such as common ALL .


All clinical specimens from patients with lymphatic leukemia have some measurable level of glucocorticoid receptors ; therefore , the resistance seen in vivo can not be explained by the lack of receptors .

All clinical specimens from patients with lymphatic leukemia have some measurable level of <protein>glucocorticoid receptors</protein> ; therefore , the resistance seen in vivo can not be explained by the lack of receptors .


However , there has been a positive correlation , in our hands , with receptor level and prognosis .


On the basis of in vitro models , it is proposed that perhaps the high receptor cell lines ( i.e. , common ALL of childhood ) have relative stability of their genetic material making glucocorticoid-resistant mutations less likely to occur in patients with these cells than in low-receptor cell lines ( i.e. , T-cell leukemia ) .

On the basis of in vitro models , it is proposed that perhaps the <cell_line>high receptor cell lines</cell_line> ( i.e. , common ALL of childhood ) have relative stability of their genetic material making glucocorticoid-resistant mutations less likely to occur in patients with these cells than in <cell_line>low-receptor cell lines</cell_line> ( i.e. , T-cell leukemia ) .


This greater genetic variability in the low-receptor lines could account for the earlier emergence of clinical glucocorticoid resistance in these patients .

This greater genetic variability in the <cell_line>low-receptor lines</cell_line> could account for the earlier emergence of clinical glucocorticoid resistance in these patients .


[ Tumor histology and steroid receptors in breast carcinoma ]

[ Tumor histology and <protein>steroid receptors</protein> in breast carcinoma ]


In Specimens of 115 patients with breast cancer 4 tumorparameters ( tumorsize , tumorboder , nucleargrade , lymphocytic stromal reaction ) 3 features of regional lymphnodes ( sinushistiocytosis , T-cellreaction , lymphnode metastases ) and estrogen and progesteron receptors were determined .

In Specimens of 115 patients with breast cancer 4 tumorparameters ( tumorsize , tumorboder , nucleargrade , lymphocytic stromal reaction ) 3 features of regional lymphnodes ( sinushistiocytosis , T-cellreaction , lymphnode metastases ) and <protein>estrogen and progesteron receptors</protein> were determined .


A strong sinushistiocytosis and T-cellreaction could be verified mainly in metastases in free lymphnodes .


The steroid receptor content does not correlate with histological parameters

The <protein>steroid receptor</protein> content does not correlate with histological parameters


Aldosterone-receptor deficiency in pseudohypoaldosteronism .

<protein>Aldosterone-receptor</protein> deficiency in pseudohypoaldosteronism .


Pseudohypoaldosteronism , a syndrome characterized by salt wasting and failure to thrive , usually presents in infancy as high urinary levels of sodium despite hyponatremia , hyperkalemia , hyperreninemia , and elevated aldosterone levels .


We have investigated this syndrome for the possibility of abnormal Type I or `` mineralocorticoid-like '' receptors , which have intrinsic steroid specificity indistinguishable from that of renal mineralocorticoid receptors and are found in many tissues and cells , including mononuclear leukocytes .

We have investigated this syndrome for the possibility of <protein>abnormal Type I</protein> or <protein>`` mineralocorticoid-like '' receptors</protein> , which have intrinsic steroid specificity indistinguishable from that of <protein>renal mineralocorticoid receptors</protein> and are found in many tissues and <cell_type>cells</cell_type> , including <cell_type>mononuclear leukocytes</cell_type> .


We have studied three patients with pseudohypoaldosteronism : the 28-year-old index case in Melbourne ( Patient 1 ) and two siblings in Munich , eight and two years of age ( Patients 2 and 3 ) ; clinically , Patient 3 had a less severe case than his sister .


Percoll-separated control monocytes bound [ 3H ] aldosterone with high affinity ( Kd approximately 3 nM ) and limited capacity ( 150 to 600 sites per cell ) .

<cell_type>Percoll-separated control monocytes</cell_type> bound [ 3H ] aldosterone with high affinity ( Kd approximately 3 nM ) and limited capacity ( 150 to 600 sites per cell ) .


On repeated examination , no [ 3H ] aldosterone binding was found in monocytes from Patients 1 and 2 ; in Patient 3 , the levels were 62 sites per cell , more than 2 S.D. below those of the control .

On repeated examination , no [ 3H ] aldosterone binding was found in <cell_type>monocytes</cell_type> from Patients 1 and 2 ; in Patient 3 , the levels were 62 sites per cell , more than 2 S.D. below those of the control .


Levels in the parents of the Munich patients ( first cousins ) were normal .


It appears that pseudohypoaldosteronism is caused by a Type I receptor defect , that the defect may be complete or partial , that transmission may be autosomal recessive , and that the study of patients with pseudohypoaldosteronism may indicate physiologic roles for Type I receptors in nonepithelial tissues .

It appears that pseudohypoaldosteronism is caused by a Type I receptor defect , that the defect may be complete or partial , that transmission may be autosomal recessive , and that the study of patients with pseudohypoaldosteronism may indicate physiologic roles for <protein>Type I receptors</protein> in nonepithelial tissues .


Glucocorticoid inhibition of urokinase-like plasminogen activators in cultured human lymphoblasts .

Glucocorticoid inhibition of <protein>urokinase-like plasminogen activators</protein> in <cell_line>cultured human lymphoblasts</cell_line> .


Two human lymphoblast cell lines , LICR-LON-HMy2 ( HMy2 cells ) and GM4672A cells , are moderately growth inhibited by dexamethasone ( 1 , 4-pregnadien-9-fluoro-16 alpha-methyl-11 beta , 17 alpha , 21-triol-3 , 20-dione ) ( Dex ) .

Two <cell_line>human lymphoblast cell lines</cell_line> , <cell_line>LICR-LON-HMy2</cell_line> ( <cell_line>HMy2 cells</cell_line> ) and <cell_line>GM4672A cells</cell_line> , are moderately growth inhibited by dexamethasone ( 1 , 4-pregnadien-9-fluoro-16 alpha-methyl-11 beta , 17 alpha , 21-triol-3 , 20-dione ) ( Dex ) .


Both cell types secrete a urokinase ( UK ) -like plasminogen activator ( PA ) .

Both cell types secrete a <protein>urokinase ( UK ) -like plasminogen activator</protein> ( <protein>PA</protein> ) .


Treatment of both HMy2 and GM4672A cells with Dex for 1-4 days inhibits extracellular PA activity in a concentration-dependent manner , being half-maximal at approximately 1 X 10 ( -9 ) M .

Treatment of both <cell_line>HMy2 and GM4672A cells</cell_line> with Dex for 1-4 days inhibits extracellular <protein>PA</protein> activity in a concentration-dependent manner , being half-maximal at approximately 1 X 10 ( -9 ) M .


Inhibition of PA in both cell types is specific for active glucocorticoids , and this specificity parallels the ability of various steroids to bind to glucocorticoid receptors .

Inhibition of <protein>PA</protein> in both cell types is specific for active glucocorticoids , and this specificity parallels the ability of various steroids to bind to <protein>glucocorticoid receptors</protein> .


HMy2 cell PA is fully suppressible by Dex , whereas up to one third of the activator expressed by GM4672A cells is resistant to glucocorticoid inhibition .

<cell_line>HMy2 cell</cell_line> <protein>PA</protein> is fully suppressible by Dex , whereas up to one third of the activator expressed by <cell_line>GM4672A cells</cell_line> is resistant to glucocorticoid inhibition .


Mixing experiments using a UK standard and conditioned media from Dex-treated cells suggest an absence of glucocorticoid-inducible inhibitors to UK or plasmin in both cell types .

Mixing experiments using a UK standard and conditioned media from <cell_line>Dex-treated cells</cell_line> suggest an absence of <protein>glucocorticoid-inducible inhibitors</protein> to <protein>UK</protein> or <protein>plasmin</protein> in both cell types .


However , conditioned media from Dex-treated GM4672A cells inhibits a portion of the homologous cellular activator in conditioned media from control GM4672A cells .

However , conditioned media from <cell_line>Dex-treated GM4672A cells</cell_line> inhibits a portion of the homologous cellular activator in conditioned media from control <cell_line>GM4672A cells</cell_line> .


Thus , low levels of glucocorticoid-inducible inhibitors may contribute to , but can not fully account for , Dex inhibition of GM4672A PA activity .

Thus , low levels of <protein>glucocorticoid-inducible inhibitors</protein> may contribute to , but can not fully account for , Dex inhibition of <protein>GM4672A PA</protein> activity .


Glucocorticoid-inducible inhibitors in HMy2 cells are either totally absent or are present at undetectable levels .

<protein>Glucocorticoid-inducible inhibitors</protein> in <cell_line>HMy2 cells</cell_line> are either totally absent or are present at undetectable levels .


Thus , regulation of UK-like PAs in HMy2 and GM4672A cells differs with respect to the extent to which glucocorticoids inhibit constitutively expressed activator levels , as well as the possible contribution of glucocorticoid-inducible inhibitors to the regulatory process in GM4672A cells .

Thus , regulation of <protein>UK-like PAs</protein> in <cell_line>HMy2 and GM4672A cells</cell_line> differs with respect to the extent to which glucocorticoids inhibit <protein>constitutively expressed activator</protein> levels , as well as the possible contribution of <protein>glucocorticoid-inducible inhibitors</protein> to the regulatory process in <cell_line>GM4672A cells</cell_line> .


Characterization of aldosterone binding sites in circulating human mononuclear leukocytes .

Characterization of aldosterone binding sites in <cell_type>circulating human mononuclear leukocytes</cell_type> .


Aldosterone binding sites in human mononuclear leukocytes were characterized after separation of cells from blood by a Percoll gradient .

Aldosterone binding sites in <cell_line>human mononuclear leukocytes</cell_line> were characterized after separation of cells from blood by a Percoll gradient .


After washing and resuspension in RPMI-1640 medium , cells were incubated at 37 degrees C for 1 h with different concentrations of [ 3H ] aldosterone plus a 100-fold concentration of RU-26988 ( 11 alpha , 17 alpha-dihydroxy-17 beta-propynylandrost-1 , 4 , 6-trien-3-one ) , with or without an excess of unlabeled aldosterone .


Aldosterone binds to a single class of receptors with an affinity of 2.7 +/- 0.5 nM ( means +/- SD , n = 14 ) and a capacity of 290 +/- 108 sites/cell ( n = 14 ) .


The specificity data show a hierarchy of affinity of desoxycorticosterone = corticosterone = aldosterone greater than hydrocortisone greater than dexamethasone .


The results indicate that mononuclear leukocytes could be useful for studying the physiological significance of these mineralocorticoid receptors and their regulation in humans .

The results indicate that <cell_type>mononuclear leukocytes</cell_type> could be useful for studying the physiological significance of these <protein>mineralocorticoid receptors</protein> and their regulation in humans .


Mineralocorticoid and glucocorticoid receptors in circulating mononuclear leukocytes of patients with primary hyperaldosteronism .

<protein>Mineralocorticoid and glucocorticoid receptors</protein> in <cell_type>circulating mononuclear leukocytes</cell_type> of patients with primary hyperaldosteronism .


Mineralocorticoid and glucocorticoid receptors were measured in circulating mononuclear leukocytes in 5 patients affected by Conn 's syndrome ( 3 cases of bilateral adrenal hyperplasia and 2 cases of adenoma plus unilateral hyperplasia ) .

<protein>Mineralocorticoid and glucocorticoid receptors</protein> were measured in <cell_type>circulating mononuclear leukocytes</cell_type> in 5 patients affected by Conn 's syndrome ( 3 cases of bilateral adrenal hyperplasia and 2 cases of adenoma plus unilateral hyperplasia ) .


The number of the binding sites per cell resulted significantly lower ( 189 +/- 114 , mean +/- SD ) , as compared with the normal controls ( 298 +/- 105 ) .


The affinity of aldosterone for the receptor was found to be not different than that of healthy control subjects .


The capacity and the affinity of dexamethasone for glucocorticoid receptors ranged in the normal values .

The capacity and the affinity of dexamethasone for <protein>glucocorticoid receptors</protein> ranged in the normal values .


These data suggest a possible down-regulation of mineralocorticoid receptors in humans .

These data suggest a possible down-regulation of <protein>mineralocorticoid receptors</protein> in humans .


Short-term and long-term effects of estrogen on lymphoid tissues and lymphoid cells with some remarks on the significance for carcinogenesis .

Short-term and long-term effects of estrogen on lymphoid tissues and <cell_type>lymphoid cells</cell_type> with some remarks on the significance for carcinogenesis .


Estrogens have long been thought to play a role in regulating the immune system .


The difference in some types of immune responses between males and females is well-known , as is the pronounced thymic involution induced by exogenous estrogens .


Estrogens stimulate some aspects of macrophage activity and , depending on dose and mitogen , inhibit or stimulate lymphocyte proliferative response in vitro .

Estrogens stimulate some aspects of <cell_type>macrophage</cell_type> activity and , depending on dose and <protein>mitogen</protein> , inhibit or stimulate lymphocyte proliferative response in vitro .


Another example is the estrogen effect on the delayed type hypersensitivity response .


A broad review is given of such estrogen effects on lymphoid tissue and immune response .

A broad review is given of such estrogen effects on <cell_type>lymphoid tissue</cell_type> and immune response .


Most of the studies published so far are phenomenological .


However , the recent description of estrogen receptors in the thymus and in some lymphocyte subpopulations , as well as a deeper understanding of regulating factors in the immune system , open the possibility of a more detailed understanding of the estrogen mechanism of interference .

However , the recent description of <protein>estrogen receptors</protein> in the thymus and in some <cell_line>lymphocyte subpopulations</cell_line> , as well as a deeper understanding of regulating factors in the immune system , open the possibility of a more detailed understanding of the estrogen mechanism of interference .


Estrogen effects in adults are reversible .


After treating neonatal mice with the synthetic estrogen diethylstilbestrol ( DES ) , disturbances are induced in lymphocyte populations and lymphocyte functions which are permanent and irreversible .

After treating neonatal mice with the synthetic estrogen diethylstilbestrol ( DES ) , disturbances are induced in <cell_line>lymphocyte populations</cell_line> and <cell_type>lymphocyte</cell_type> functions which are permanent and irreversible .


Lymphocytes from adult , neonatally DES-treated female mice have a reduced mitogen response to ConA and LPS ( T and B cell mitogen ) and the delayed type hypersensitivity response is depressed .

<cell_type>Lymphocytes</cell_type> from adult , neonatally DES-treated female mice have a reduced mitogen response to <protein>ConA</protein> and <protein>LPS</protein> ( <protein>T and B cell mitogen</protein> ) and the delayed type hypersensitivity response is depressed .


A detailed analysis demonstrated a decreased T helper cell population .

A detailed analysis demonstrated a decreased <cell_type>T helper cell</cell_type> population .


The activity of Natural Killer cells is permanently reduced and this functional impairment is related to a decreased number of these cells , in turn determined at the bone marrow level .

The activity of <cell_type>Natural Killer cells</cell_type> is permanently reduced and this functional impairment is related to a decreased number of these cells , in turn determined at the bone marrow level .


The same animals have an increased sensitivity to chemical carcinogens ( methylcholanthrene ) and they spontaneously develop epithelial changes in the uterine cervix which morphologically are similar to adenocarcinoma .


The association between estrogen-associated malignancy and estrogen effects in lymphocyte functions deserves further study .

The association between estrogen-associated malignancy and estrogen effects in <cell_type>lymphocyte</cell_type> functions deserves further study .


Drugs affecting the hormonal receptors of normal and leukaemic peripheral leucocytes .

Drugs affecting the hormonal receptors of <cell_type>normal and leukaemic peripheral leucocytes</cell_type> .


The authors investigated the behaviour of steroid hormone uptake in leukaemic cells ( CML , CLL , AML , ALL ) , in basal conditions and after incubation with drugs which modify the cellular concentration of cAMP , PGE and PGF .

The authors investigated the behaviour of steroid hormone uptake in <cell_type>leukaemic cells</cell_type> ( <cell_line>CML</cell_line> , <cell_line>CLL</cell_line> , <cell_line>AML</cell_line> , <cell_line>ALL</cell_line> ) , in basal conditions and after incubation with drugs which modify the cellular concentration of cAMP , PGE and PGF .


The results demonstrated the presence in leukaemic cells of an alteration in the incorporation of steroid hormones .

The results demonstrated the presence in <cell_type>leukaemic cells</cell_type> of an alteration in the incorporation of steroid hormones .


This alteration was scarcely modified by incubation with theophylline , which increases cellular concentration of cAMP .

This alteration was scarcely modified by incubation with <protein>theophylline</protein> , which increases cellular concentration of cAMP .


On the other hand , it was moderately counteracted by thioproline and was evidently inhibited by flurbiprofen , which also reduced cellular concentrations of prostaglandins , particularly PGE2 , with the exception of PGF2 which showed a poor response .


Differences were observed in the behavior of hormonal uptake of CML , in contrast to that of AML , CLL and ALL peripheral leucocytes .

Differences were observed in the behavior of hormonal uptake of <cell_line>CML</cell_line> , in contrast to that of <cell_line>AML , CLL and ALL peripheral leucocytes</cell_line> .


Human breast cancer and impaired NK cell function .

Human breast cancer and impaired <cell_type>NK cell</cell_type> function .


Recent advances in tumor immunology have led to the discovery of a new lymphoid cell with unique antitumor activity .

Recent advances in tumor immunology have led to the discovery of a new <cell_type>lymphoid cell</cell_type> with unique antitumor activity .


Natural killer ( NK ) cells form an antitumor surveillance system and appear to be vital in preventing tumor growth and metastasis in animal models .

<cell_type>Natural killer ( NK ) cells</cell_type> form an antitumor surveillance system and appear to be vital in preventing tumor growth and metastasis in animal models .


We studied NK activity in patients with benign and malignant breast disease , using a chromium-51 release microtiter cytotoxicity assay with K562 cells as targets .

We studied <cell_type>NK</cell_type> activity in patients with benign and malignant breast disease , using a chromium-51 release microtiter cytotoxicity assay with <cell_line>K562 cells</cell_line> as targets .


Compared with benign controls , patients with malignancies had significantly depressed NK -mediated lysis ( P less than 0.01 ) .

Compared with benign controls , patients with malignancies had significantly depressed <cell_type>NK</cell_type> -mediated lysis ( P less than 0.01 ) .


Furthermore , lysis in those with advanced disease ( stages II , III , and IV ) was significantly less than in those with limited disease ( stage I ) ( P less than 0.01 ) .


NK activity was not correlated to estrogen or progesterone receptor states .

<cell_type>NK</cell_type> activity was not correlated to estrogen or progesterone receptor states .


Positive correlation of a depressed natural killer activity with the extent of tumor spread supports the concept of an NK cell immune surveillance system in breast cancer and emphasizes its importance in this malignancy .

Positive correlation of a depressed natural killer activity with the extent of tumor spread supports the concept of an <cell_type>NK cell</cell_type> immune surveillance system in breast cancer and emphasizes its importance in this malignancy .


Immunosuppressive effect of serum progesterone during pregnancy depends on the progesterone binding capacity of the lymphocytes .

Immunosuppressive effect of serum progesterone during pregnancy depends on the progesterone binding capacity of the <cell_type>lymphocytes</cell_type> .


Cytotoxic activity and progesterone binding capacity of the lymphocytes , together with serum progesterone concentrations , were determined in women with normal pregnancy or with a clinical diagnosis of threatened abortion or threatened premature labour .

Cytotoxic activity and progesterone binding capacity of the <cell_type>lymphocytes</cell_type> , together with serum progesterone concentrations , were determined in women with normal pregnancy or with a clinical diagnosis of threatened abortion or threatened premature labour .


The lymphocytes of women with threatened abortion or threatened premature labour showed significantly higher cytotoxic activity ( P less than 0.001 ) and significantly lower progesterone binding capacity ( P less than 0.001 ) than did lymphocytes obtained from the healthy pregnant women .

The lymphocytes of women with threatened abortion or threatened premature labour showed significantly higher cytotoxic activity ( P less than 0.001 ) and significantly lower progesterone binding capacity ( P less than 0.001 ) than did <cell_type>lymphocytes</cell_type> obtained from the healthy pregnant women .


Significant inverse correlation was found between progesterone binding capacity and cytotoxic activity of the lymphocytes ( P less than 0.001 ) , but the progesterone concentration of the pregnancy serum appeared to have no influence on the other two parameters .

Significant inverse correlation was found between progesterone binding capacity and cytotoxic activity of the <cell_type>lymphocytes</cell_type> ( P less than 0.001 ) , but the progesterone concentration of the pregnancy serum appeared to have no influence on the other two parameters .


The findings indicate that intact progesterone binding capacity of the lymphocytes is an essential factor for the manifestation of the blocking effect exerted by pregnancy serum on lymphocyte cytotoxicity in vitro .

The findings indicate that intact progesterone binding capacity of the <cell_type>lymphocytes</cell_type> is an essential factor for the manifestation of the blocking effect exerted by pregnancy serum on <cell_type>lymphocyte</cell_type> cytotoxicity in vitro .


Serum sex steroid and peptide hormone concentrations , and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon .

Serum sex steroid and peptide hormone concentrations , and endometrial estrogen and progestin receptor levels during administration of <protein>human leukocyte interferon</protein> .


Five normally cycling healthy women were given daily subcutaneous injections of human leukocyte interferon ( 3 X 10 ( 6 ) units/day ) from the 3rd through 23rd day of the menstrual cycle , and serum steroid and peptide hormone concentrations monitored at 3-day intervals during the treatment and the preceding control cycle .

Five normally cycling healthy women were given daily subcutaneous injections of <protein>human leukocyte interferon</protein> ( 3 X 10 ( 6 ) units/day ) from the 3rd through 23rd day of the menstrual cycle , and serum steroid and peptide hormone concentrations monitored at 3-day intervals during the treatment and the preceding control cycle .


Concentrations of cytosol and nuclear estrogen receptors ( ERC and ERN , respectively ) and progestin receptors ( PRC and PRN ) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle .

Concentrations of <protein>cytosol and nuclear estrogen receptors</protein> ( <protein>ERC</protein> and <protein>ERN</protein> , respectively ) and <protein>progestin receptors</protein> ( <protein>PRC</protein> and <protein>PRN</protein> ) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle .


In addition , an extensive monitoring of clinical chemical and hematological tests from the blood samples were performed .


Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle , suggesting that interferon interacts in vivo with the function of both FSH and LH .

Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle , suggesting that <protein>interferon</protein> interacts in vivo with the function of both FSH and LH .


No significant changes were observed in the serum peptide hormone concentrations measured ( FSH , LH , prolactin , insulin , growth hormone and TSH ) ; neither were the levels of endometrial ERC , ERN , PRC and PRN affected by interferon administration .

No significant changes were observed in the serum peptide hormone concentrations measured ( FSH , LH , prolactin , insulin , growth hormone and TSH ) ; neither were the levels of <protein>endometrial ERC , ERN , PRC and PRN</protein> affected by <protein>interferon</protein> administration .


As expected , interferon administration resulted in decreased leukocyte counts .

As expected , <protein>interferon</protein> administration resulted in decreased <cell_type>leukocyte</cell_type> counts .


Moreover , an increasing tendency in the activities of serum alkaline phosphatase and gamma-glutamyltransferase during the interferon therapy shows that interferon may slightly interfere with the liver function .

Moreover , an increasing tendency in the activities of <protein>serum alkaline phosphatase</protein> and <protein>gamma-glutamyltransferase</protein> during the <protein>interferon</protein> therapy shows that <protein>interferon</protein> may slightly interfere with the liver function .


These results suggest that one of the mechanisms by which interferon treatment may affect the growth of hormone-dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds .

These results suggest that one of the mechanisms by which <protein>interferon</protein> treatment may affect the growth of hormone-dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds .


[ Glucocorticoid receptor level in the blood leukocytes in different acute diseases ]

[ <protein>Glucocorticoid receptor</protein> level in the <cell_type>blood leukocytes</cell_type> in different acute diseases ]


Content of glucocorticoid receptors in cytosol of blood leukocytes , concentration of cortisol and amount of leukocytes in blood were studied in 20 patients with acute impairments within the second day of the disease .

Content of <protein>glucocorticoid receptors</protein> in cytosol of <cell_type>blood leukocytes</cell_type> , concentration of cortisol and amount of <cell_type>leukocytes</cell_type> in blood were studied in 20 patients with acute impairments within the second day of the disease .


Content of receptors in cytosol of blood leukocytes was studied using 3H-triamcinolone acetonide .


Distinct increase in amount of the leukocyte glucocorticoid receptors was found in patients with poisoning by dichlorethane and hypnotic drugs under conditions of acute myocardial infarction .

Distinct increase in amount of the <protein>leukocyte glucocorticoid receptors</protein> was found in patients with poisoning by dichlorethane and hypnotic drugs under conditions of acute myocardial infarction .


In acute pancreatitis content of the leukocyte receptors was not altered as compared with controls .

In acute pancreatitis content of the <protein>leukocyte receptors</protein> was not altered as compared with controls .


Concentration of endogenous cortisol was increased in blood of all the patients , except of the cases of acetate intoxication .


Reverse correlation was observed between concentration of cortisol in blood and content of glucocorticoid receptors in leukocytes .

Reverse correlation was observed between concentration of cortisol in blood and content of glucocorticoid receptors in <cell_type>leukocytes</cell_type> .


But in the patients with acute pancreatitis the decrease in content of leukocyte glucocorticoid receptors was not observed although there was an increase in cortisol concentration in blood .

But in the patients with acute pancreatitis the decrease in content of <protein>leukocyte glucocorticoid receptors</protein> was not observed although there was an increase in cortisol concentration in blood .


The role of glucocorticoid receptors in immunological processes under conditions of purulent complications and possibility to regulate the metabolism in leukocytes

The role of <protein>glucocorticoid receptors</protein> in immunological processes under conditions of purulent complications and possibility to regulate the metabolism in <cell_type>leukocytes</cell_type>


Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon .

Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of <cell_type>human macrophages</cell_type> without impairing their responsiveness to <protein>gamma interferon</protein> .


By exposing human blood-derived macrophages and alveolar macrophages in vitro to dexamethasone , we showed in these studies that glucocorticoids markedly suppress the antimicrobial activity of macrophages but not macrophage activation by lymphokines .

By exposing <cell_type>human blood-derived macrophages and alveolar macrophages</cell_type> in vitro to dexamethasone , we showed in these studies that glucocorticoids markedly suppress the antimicrobial activity of <cell_type>macrophages</cell_type> but not <cell_type>macrophage</cell_type> activation by <cell_type>lymphokines</cell_type> .


As little as 2.5 X 10 ( -8 ) mol/liter of dexamethasone prevented macrophages from inhibiting germination of Aspergillus spores or from eliminating ingested bacteria such as Listeria , Nocardia , or Salmonella .

As little as 2.5 X 10 ( -8 ) mol/liter of dexamethasone prevented <cell_type>macrophages</cell_type> from inhibiting germination of Aspergillus spores or from eliminating ingested bacteria such as Listeria , Nocardia , or Salmonella .


Damage to macrophage function was inhibited by progesterone and appeared to be receptor-mediated .

Damage to <cell_type>macrophage</cell_type> function was inhibited by progesterone and appeared to be receptor-mediated .


In accordance with in vivo observations , dexamethasone required 24-36 h to suppress antimicrobial activity .


While glucocorticoids interfered with base-line activity of macrophages , dexamethasone concentrations comparable to drug levels in patients had no effect on macrophage activation .

While glucocorticoids interfered with base-line activity of <cell_type>macrophages</cell_type> , dexamethasone concentrations comparable to drug levels in patients had no effect on <cell_type>macrophage</cell_type> activation .


Proliferating lymphocytes and gamma-interferon thus increased the antimicrobial activity of phagocytes exposed to glucocorticoids over that of control cells .

Proliferating <cell_type>lymphocytes</cell_type> and <protein>gamma-interferon</protein> thus increased the antimicrobial activity of <cell_type>phagocytes</cell_type> exposed to glucocorticoids over that of control cells .


Macrophage activation and correction of the dexamethasone effect by gamma-interferon , however , was dependent on the pathogen .

Macrophage activation and correction of the dexamethasone effect by <protein>gamma-interferon</protein> , however , was dependent on the pathogen .


The lymphokine enhanced the antimicrobial activity of dexamethasone-treated macrophages against Listeria and Salmonella but not against Aspergillus or Nocardia .

The <protein>lymphokine</protein> enhanced the antimicrobial activity of <cell_line>dexamethasone-treated macrophages</cell_line> against Listeria and Salmonella but not against Aspergillus or Nocardia .


Dexamethasone-induced damage to the antimicrobial activity of human macrophages in vitro parallels observations that glucocorticoids render laboratory animals susceptible to listeriosis and aspergillosis by damaging resident macrophages .

Dexamethasone-induced damage to the antimicrobial activity of <cell_type>human macrophages</cell_type> in vitro parallels observations that glucocorticoids render laboratory animals susceptible to listeriosis and aspergillosis by damaging resident <cell_line>macrophages</cell_line> .


Suppression of macrophage antimicrobial activity should thus be considered when treating patients with glucocorticoids ; its prevention by gamma-interferon might be beneficial for some but not all pathogens .

Suppression of <cell_type>macrophage</cell_type> antimicrobial activity should thus be considered when treating patients with glucocorticoids ; its prevention by <protein>gamma-interferon</protein> might be beneficial for some but not all pathogens .


Interleukin 2 receptor ( Tac antigen ) expression in HTLV-I-associated adult T-cell leukemia .

<protein>Interleukin 2 receptor</protein> ( <protein>Tac antigen</protein> ) expression in HTLV-I-associated adult <cell_type>T-cell</cell_type> leukemia .


Interleukin-2 ( IL-2 ) is a lymphokine synthesized by some T-cells following activation .

<protein>Interleukin-2</protein> ( <protein>IL-2</protein> ) is a <protein>lymphokine</protein> synthesized by some <cell_type>T-cells</cell_type> following activation .


Resting T-cells do not express IL-2 receptors , but receptors are rapidly expressed on T-cells following interaction of antigens , mitogens , or monoclonal antibodies with the antigen-specific T-cell receptor complex .

Resting <cell_type>T-cells</cell_type> do not express <protein>IL-2 receptors</protein> , but receptors are rapidly expressed on <cell_type>T-cells</cell_type> following interaction of antigens , mitogens , or <protein>monoclonal antibodies</protein> with the <protein>antigen-specific T-cell receptor complex</protein> .


Using anti-Tac , a monoclonal antibody that recognizes the IL-2 receptor , the receptor has been purified and shown to be a Mr 33 , 000 peptide that is posttranslationally glycosylated to a Mr 55 , 000 mature form .

Using <protein>anti-Tac</protein> , a <protein>monoclonal antibody</protein> that recognizes the <protein>IL-2 receptor</protein> , the receptor has been purified and shown to be a Mr 33 , 000 peptide that is posttranslationally glycosylated to a Mr 55 , 000 mature form .


Normal resting T-cells and most leukemic T-cell populations do not express IL-2 receptors ; however , the leukemic cells of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the Tac antigen .

Normal resting <cell_type>T-cells</cell_type> and most <cell_line>leukemic T-cell populations</cell_line> do not express <protein>IL-2 receptors</protein> ; however , the <cell_type>leukemic cells</cell_type> of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the <protein>Tac antigen</protein> .


In human T-cell lymphotropic virus-I infected cells , the Mr 42 , 000 long open reading frame protein encoded in part by the pX region of this virus may act as a transacting transcriptional activator that induces IL-2 receptor gene transcription , thus providing an explanation for the constant association of IL-2 receptor expression with adult T-cell lymphotropic virus-I infection of lymphoid cells .

In <cell_type>human T-cell lymphotropic virus-I infected cells</cell_type> , the Mr 42 , 000 long <protein>open reading frame protein</protein> encoded in part by the <dna>pX region</dna> of this virus may act as a <protein>transacting transcriptional activator</protein> that induces <dna>IL-2 receptor gene</dna> transcription , thus providing an explanation for the constant association of <protein>IL-2 receptor</protein> expression with adult T-cell lymphotropic virus-I infection of <cell_type>lymphoid cells</cell_type> .


The constant expression of large numbers of IL-2 receptors which may be aberrant may play a role in the uncontrolled growth of adult T-cell leukemia cells .

The constant expression of large numbers of <protein>IL-2 receptors</protein> which may be aberrant may play a role in the uncontrolled growth of <cell_type>adult T-cell leukemia cells</cell_type> .


Two patients with Tac-positive adult T-cell leukemia have been treated with the anti-Tac .

Two patients with Tac-positive adult T-cell leukemia have been treated with the <protein>anti-Tac</protein> .


One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this monoclonal antibody directed toward this growth factor receptor .

One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this <protein>monoclonal antibody</protein> directed toward this <protein>growth factor receptor</protein> .


Lymphocyte glucocorticoid receptor binding in depressed patients with hypercortisolemia .

<cell_type>Lymphocyte</cell_type> <protein>glucocorticoid receptor</protein> binding in depressed patients with hypercortisolemia .


Despite elevated levels of serum and urinary cortisol , patients with depressive illness manifest none of the clinical stigmata of glucocorticoid excess .


This hypercortisolemia in the absence of clinical effects suggests a state of hormone resistance and could be mediated by alterations in the glucocorticoid receptor .

This hypercortisolemia in the absence of clinical effects suggests a state of hormone resistance and could be mediated by alterations in the <protein>glucocorticoid receptor</protein> .


Earlier studies have shown that small doses of glucocorticoids cause a decrease in glucocorticoid receptor binding in normal human lymphocytes .

Earlier studies have shown that small doses of glucocorticoids cause a decrease in <protein>glucocorticoid receptor</protein> binding in normal <cell_type>human lymphocytes</cell_type> .


White cells from depressed patients with significant hypercortisolemia would be expected to show a similar change in receptor concentration if peripheral tissues are adequately exposed to and sensitive to the hormone .


In this study we compared the binding of [ 3H ] dexamethasone to lymphocytes from normal subjects and depressed patients with hypercortisolemia .

In this study we compared the binding of [ 3H ] dexamethasone to <cell_type>lymphocytes</cell_type> from normal subjects and depressed patients with hypercortisolemia .


Lymphocytes from normal subjects had a mean receptor concentration of 10.2 +/- 0.66 fm/10 ( 6 ) cells ( S.E.M. ) and a dissociation constant of 4.8 +/- 0.47 nM .

<cell_type>Lymphocytes</cell_type> from normal subjects had a mean receptor concentration of 10.2 +/- 0.66 fm/10 ( 6 ) cells ( S.E.M. ) and a dissociation constant of 4.8 +/- 0.47 nM .


Lymphocytes from depressed patients with abnormal 0800 h serum cortisol after dexamethasone had a mean receptor concentration of 8.8 +/- 0.75 fm/10 ( 6 ) cells , which was not significantly different from that in lymphocytes from normal subjects or from depressed subjects with normal post-dexamethasone cortisol levels ( 9.4 +/- 0.95 fm/10 ( 6 ) cells ) .

<cell_type>Lymphocytes</cell_type> from depressed patients with abnormal 0800 h serum cortisol after dexamethasone had a mean receptor concentration of 8.8 +/- 0.75 fm/10 ( 6 ) cells , which was not significantly different from that in <cell_type>lymphocytes</cell_type> from normal subjects or from depressed subjects with normal post-dexamethasone cortisol levels ( 9.4 +/- 0.95 fm/10 ( 6 ) cells ) .


Lymphocytes from depressed patients with elevated urinary free cortisol excretion ( UFC ) also had normal receptor concentration and binding affinity for dexamethasone .

<cell_type>Lymphocytes</cell_type> from depressed patients with elevated urinary free cortisol excretion ( UFC ) also had normal receptor concentration and binding affinity for dexamethasone .


The lack of a change in lymphocyte glucocorticoid receptor concentration in the presence of cortisol excess suggests the possibility that hypercortisolemia in depressive illness represents a state of peripheral glucocorticoid resistance .

The lack of a change in <cell_type>lymphocyte</cell_type> <protein>glucocorticoid receptor</protein> concentration in the presence of cortisol excess suggests the possibility that hypercortisolemia in depressive illness represents a state of peripheral glucocorticoid resistance .


Structure and regulation of the glucocorticoid hormone receptor .

Structure and regulation of the <protein>glucocorticoid hormone receptor</protein> .


The glucocorticoid receptor is an intracellular protein which possesses three distinct domains , one that binds agonist and antagonist steroids , one that binds DNA , and one that binds anti-receptor antibodies and is required for glucocorticoid modulation of gene expression .

The <protein>glucocorticoid receptor</protein> is an <protein>intracellular protein</protein> which possesses three distinct domains , one that binds agonist and antagonist steroids , one that binds DNA , and one that binds <protein>anti-receptor antibodies</protein> and is required for glucocorticoid modulation of gene expression .


In intact cells , receptor number , affinity and activity can change in response to factors that bind to the receptor , or that act indirectly through ill-defined mechanisms which may include resumption or arrest of cell cycling and variations in intracellular calcium ion concentrations .


Some of these factors appear to exert their effect by controlling critical receptor properties such as ATP-dependent phosphorylation , integrity of thiol groups , and exposure of key amino acid residues .

Some of these factors appear to exert their effect by controlling critical receptor properties such as ATP-dependent phosphorylation , integrity of <protein>thiol groups</protein> , and exposure of <protein>key amino acid residues</protein> .


Glucocorticoid agonists promote the 'transformation ' of the receptor into the DNA-binding state , which is competent for modulating gene expression .


Glucocorticoid antagonists are steroids that interact with the receptor but either fail to produce a stable complex or produce a stable but inefficient complex .

Glucocorticoid antagonists are steroids that interact with the receptor but either fail to produce a <protein>stable complex</protein> or produce a <protein>stable but inefficient complex</protein> .


Although substituent groups that confer agonist or antagonist activity to the steroid have been identified , the molecular determinants of this difference at the receptor level remain unknown .


Most in vitro and in vivo data on receptor regulation can be accommodated by postulating the existence of an intracellular cycle that involves five states of the receptor .


The active free receptor is phosphorylated , reduced , and presumably oligomeric ( state A ) .


Following binding of an agonist ( state B ) , it can become transformed by dissociation into its subunits and dephosphorylation ( state C ) .


The transformed receptor then interacts with chromatin ( state D ) .

The <protein>transformed receptor</protein> then interacts with <dna>chromatin</dna> ( state D ) .


Dissociation of the steroid and oxidation of receptor thiol group ( s ) lead to the inactive receptor form ( state E ) .

Dissociation of the steroid and oxidation of <protein>receptor thiol group</protein> ( s ) lead to the inactive receptor form ( state E ) .


Reduction and rephosphorylation of the receptor enable it to bind steroids again so that the cycle is closed .


Thermodynamics of steroid binding to the human glucocorticoid receptor .

Thermodynamics of steroid binding to the <protein>human glucocorticoid receptor</protein> .


The thermodynamics of the interaction of glucocorticoids with their receptor were studied in cytosol from human lymphoblastoid cells .

The thermodynamics of the interaction of glucocorticoids with their receptor were studied in cytosol from <cell_type>human lymphoblastoid cells</cell_type> .


The rate and affinity constants of dexamethasone and cortisol between 0 degree and 25 degrees C were calculated by curve-fitting from time-course and equilibrium kinetics .


The data were consistent with a simple reversible bimolecular interaction .


Arrhenius and Va n't Hoff plots were curvilinear for both steroids .


At equilibrium , the solution for the equation delta G = delta H - T X delta S ( eqn. 1 ) was ( in kJ X mol-1 ) -47 = 36 - 83 ( dexamethasone ) and -42 = -9 - 33 ( cortisol ) at 0 degree C .


Enthalpy and entropy changes decreased quasi-linearly with temperature such that , at 25 degrees C , the respective values were -50 = -75 + 25 and -43 = -48 + 5 .


Thus , for both steroids , the interaction was entropy-driven at low temperature and became entirely enthalpy-driven at 20 degrees C .


Thermodynamic values for the transition state were calculated from the rate constants .


For the forward reaction , eqn. ( 1 ) gave 45 = 84 - 39 ( dexamethasone ) and 46 = 60 - 14 ( cortisol ) at 0 degree C , and 44 = 24 + 20 ( dexamethasone ) and 46 = 28 + 18 ( cortisol ) at 25 degrees C .


These data fit quite well with a two-step model [ Ross & Subramanian ( 1981 ) Biochemistry 20 , 3096-3102 ] proposed for ligand-protein interactions , which involves a partial immobilization of the reacting species governed by hydrophobic forces , followed by stabilization of the complex by short-range interactions .


On the basis of this model , an analysis of the transition-state thermodynamics led to the conclusion that no more than half of the steroid molecular area is engaged in the binding process .


Cell cycle-related changes in number of T-lymphocyte receptors for glucocorticoids and insulin .

Cell cycle-related changes in number of <protein>T-lymphocyte receptors</protein> for glucocorticoids and insulin .


Enriched human peripheral T-lymphocytes were stimulated with PHA and examined for variations in insulin and glucocorticoid ( dexamethasone ) receptor numbers during the early phases of the cell cycle .

Enriched <cell_type>human peripheral T-lymphocytes</cell_type> were stimulated with PHA and examined for variations in insulin and glucocorticoid ( dexamethasone ) receptor numbers during the early phases of the cell cycle .


Cells in G0 , G1a and G1b phases , where the G1a - G1b transition is an Interleukin 2 dependent event , were quantitated by flow cytometry .

Cells in G0 , G1a and G1b phases , where the G1a - G1b transition is an <protein>Interleukin 2</protein> dependent event , were quantitated by flow cytometry .


Few but significant numbers of glucocorticoid receptors ( 2700/cell ) and no insulin receptors ( -1/cell ) were found in the resting ( G0 ) phase .

Few but significant numbers of <protein>glucocorticoid receptors</protein> ( 2700/cell ) and no <protein>insulin receptors</protein> ( -1/cell ) were found in the resting ( G0 ) phase .


As cells entered the G1a phase the specific binding of dexamethasone increased and of insulin took place .


Although the specific binding further increased as T-cells entered the G1b phase ( as measured at 44 h of incubation and using hydroxyurea-treated cells ) , the major changes in the specific binding of dexamethasone took place during the period 16 - 20 h after stimulation .

Although the specific binding further increased as <cell_type>T-cells</cell_type> entered the G1b phase ( as measured at 44 h of incubation and using <cell_line>hydroxyurea-treated cells</cell_line> ) , the major changes in the specific binding of dexamethasone took place during the period 16 - 20 h after stimulation .


Based on these findings , it is concluded that both receptor types ( cell membrane and cytoplasmic receptors ) are being formed and increased at G1 phase prior to cell proliferation , indicating the importance of G1 phase in immunoregulation .

Based on these findings , it is concluded that both receptor types ( <protein>cell membrane and cytoplasmic receptors</protein> ) are being formed and increased at G1 phase prior to cell proliferation , indicating the importance of G1 phase in immunoregulation .


Glucocorticoid receptors and cortico-sensitivity in a human clonal monocytic cell line , CM-SM .

<protein>Glucocorticoid receptors</protein> and cortico-sensitivity in a <cell_line>human clonal monocytic cell line</cell_line> , <cell_line>CM-SM</cell_line> .


CM-SM is a clonal line of human precursor mononuclear phagocytes inducible to macrophage differentiation in response to the tumor promoter phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) .

<cell_line>CM-SM</cell_line> is a <cell_line>clonal line</cell_line> of <cell_type>human precursor mononuclear phagocytes</cell_type> inducible to <cell_type>macrophage</cell_type> differentiation in response to the tumor promoter phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) .


Untreated CM-SM cells contain single class , high-affinity ( KD = 4.0 X 10 ( -9 ) M ) glucocorticoid-specific receptor sites ( approximately 60 , 000 per cell ) , as measured by a whole cell assay , at 37 degrees C , using [ 3H ] triamcinolone acetonide ( TA ) .


Exposure of CM-SM to dexamethasone ( DEX ) produced a progressive , dose- and time-related series of changes in CM-SM cell growth , saturation density , morphology , and functional properties , with half-maximal effects at about 10 ( -9 ) M for DEX .

Exposure of <cell_line>CM-SM</cell_line> to dexamethasone ( DEX ) produced a progressive , dose- and time-related series of changes in <cell_line>CM-SM</cell_line> cell growth , saturation density , morphology , and functional properties , with half-maximal effects at about 10 ( -9 ) M for DEX .


TA-receptor sites rapidly decreased ( about 70 % ) after DEX treatment , without any apparent change in steroid specificity and affinity .


After 5 days in culture with a saturating concentration ( 3.6 X 10 ( -8 ) M ) of hormone , the cells reached a saturation density of about 9.0 X 10 ( 6 ) viable cells/ml ( about 4.0 X 10 ( 6 ) viable cells/ml in the controls ) , while the modal volume of the resulting cell population was approximately 60 % , as compared to the volume of untreated cells .

After 5 days in culture with a saturating concentration ( 3.6 X 10 ( -8 ) M ) of hormone , the cells reached a saturation density of about 9.0 X 10 ( 6 ) viable cells/ml ( about 4.0 X 10 ( 6 ) viable cells/ml in the controls ) , while the modal volume of the resulting <cell_line>cell population</cell_line> was approximately 60 % , as compared to the volume of <cell_line>untreated cells</cell_line> .


DEX-treated cells appeared less differentiated than controls , as assessed by combined morphologic , antigenic , and cytoenzymatic analyses .

<cell_line>DEX-treated cells</cell_line> appeared less differentiated than controls , as assessed by combined morphologic , antigenic , and cytoenzymatic analyses .


DEX almost completely inhibited TPA activation of the following macrophage functions : adherency to the culture plate , expression of lysosomal enzymes , Fc and C3 receptors , and stimulation of phagocytosis .

DEX almost completely inhibited TPA activation of the following <cell_type>macrophage</cell_type> functions : adherency to the culture plate , expression of <protein>lysosomal enzymes</protein> , <protein>Fc and C3 receptors</protein> , and stimulation of phagocytosis .


After removal of DEX , the cells , within a few passages , returned to a state apparently identical to the untreated controls and could be induced to macrophage differentiation in response to TPA .

After removal of DEX , the cells , within a few passages , returned to a state apparently identical to the untreated controls and could be induced to <cell_type>macrophage</cell_type> differentiation in response to TPA .


Acute lymphoblastic leukemia in children : current status , controversies , and future perspective .


Disease-free survival ( DFS ) in childhood ALL is 60 % , and survival in good , average , and poor prognostic groups defined by initial WBC and age is 90 , 60 , and 45 % , respectively .


Additional immunological , morphological , biochemical , cytokinetic , and cytogenetic factors have been identified , illustrating the heterogeneity of ALL and its derivation from malignant clones at various stages of differentiation and with varying rates of proliferation .

Additional immunological , morphological , biochemical , cytokinetic , and cytogenetic factors have been identified , illustrating the heterogeneity of ALL and its derivation from <cell_line>malignant clones</cell_line> at various stages of differentiation and with varying rates of proliferation .


Of biologic importance , these factors may refine further the characteristic features of clinically-determined prognostic groups .


Multivariate analysis of large prospective trials with homogeneous therapy will be required to determine the independent prognostic importance of these factors .


Current treatment strategies in ALL include ( 1 ) tailoring therapy and its intensity to prognostic groups ; ( 2 ) multiple-drug combinations in induction ; ( 3 ) early use of intrathecal ( IT ) methotrexate ( MTX ) ; ( 4 ) CNS prophylaxis with IT MTX alone in good prognosis patients and combined cranial radiation ( CXRT ) , 1800 rads plus IT MTX , in average and poor prognosis patients .


Current studies show a CNS relapse rate of 5 % in all prognostic groups .


Late neuropsychological defects caused by cranial XRT and IT MTX have prompted programs designed to reduce the potential late toxicity of CNS prophylaxis .


More pronounced in younger children , these abnormalities include decreased IQ , visual-motor incoordination , poor performance in mathematics , and memory dysfunction .


Until 1980 , more intensive induction , consolidation , and maintenance therapy had failed to prolong DFS in children with a poor prognosis .


In West Germany ( Berlin-Frankfurt-Muenster protocol ) a 70 to 75 % DFS is seen in all patients regardless of initial WBC , suggesting that effective therapy will override prognostic factors .


Ultra-high-dose MTX , without cranial radiation , is also showing promise in poor prognosis patients .


Other issues include the optimal duration of therapy , the role of testicular biopsies , and prophylactic testicular radiation .


Recent studies suggest that prognostic factors lose their significance after 2 years of continuous complete remission and that 2 years of maintenance therapy is adequate .


Bilateral open-wedge testicular biopsies have identified occult testicular disease in 8 to 10 % of males .


A unified approach to children with leukemia/lymphoma , a group with a particularly poor prognosis , utilizing NHL-type therapy may be more effective than conventional ALL therapy .


( ABSTRACT TRUNCATED AT 400 WORDS )


Glucocorticoid receptor and in vitro sensitivity to steroid hormones in human lymphoproliferative diseases and myeloid leukemia .

<protein>Glucocorticoid receptor</protein> and in vitro sensitivity to steroid hormones in human lymphoproliferative diseases and myeloid leukemia .


The glucocorticoid receptor ( GR ) quantitation by a whole-cell assay and/or cytosol technique and the in vitro sensitivity to steroids have been assessed in peripheral blood cells from normal donors and patients with chronic lymphatic leukemia ( CLL ) , acute lymphoblastic leukemia ( ALL ) , lymphosarcoma cell leukemia ( LSCL ) , acute nonlymphatic leukemia ( ANLL ) , and chronic myeloid leukemia ( CML ) .

The <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) quantitation by a whole-cell assay and/or cytosol technique and the in vitro sensitivity to steroids have been assessed in <cell_type>peripheral blood cells</cell_type> from normal donors and patients with chronic lymphatic leukemia ( CLL ) , acute lymphoblastic leukemia ( ALL ) , lymphosarcoma cell leukemia ( LSCL ) , acute nonlymphatic leukemia ( ANLL ) , and chronic myeloid leukemia ( CML ) .


Within the lymphoproliferative diseases , ALL cells exhibited the highest GR concentration ( regardless of the method used ) and the highest in vitro inhibition of spontaneous [ 3H ] thymidine ( [ 3H ] TdR ) uptake by glucocorticoids .

Within the lymphoproliferative diseases , <cell_line>ALL cells</cell_line> exhibited the highest <protein>GR</protein> concentration ( regardless of the method used ) and the highest in vitro inhibition of spontaneous [ 3H ] thymidine ( [ 3H ] TdR ) uptake by glucocorticoids .


A significant relationship between GR concentration ( whole-cell assay ) and in vitro sensitivity to dexamethasone was also found .

A significant relationship between <protein>GR</protein> concentration ( whole-cell assay ) and in vitro sensitivity to dexamethasone was also found .


On the contrary , CLL cells presented the highest sensitivity to glucocorticoids in PHA-stimulated cell cultures .

On the contrary , <cell_line>CLL cells</cell_line> presented the highest sensitivity to glucocorticoids in <cell_line>PHA-stimulated cell cultures</cell_line> .


Cells from the only two ALL patients who did not undergo a remission after glucocorticoid-inclusive chemotherapy had both the lowest in vitro sensitivity to dexamethasone and the lowest GR concentration with whole-cell assay .


Concerning myeloid leukemia , ANLL patients had GR concentrations slightly higher than those found in the ALL group but exhibited the lowest degree of inhibition of spontaneous [ 3H ] TdR uptake by dexamethasone ( stimulatory effects occurred in some cases ) .

Concerning myeloid leukemia , ANLL patients had <protein>GR</protein> concentrations slightly higher than those found in the ALL group but exhibited the lowest degree of inhibition of spontaneous [ 3H ] TdR uptake by dexamethasone ( stimulatory effects occurred in some cases ) .


CML cells exhibited an inhibition degree by in vitro glucocorticoids significantly higher than that of ANLL cells but not different from that of lymphoproliferative diseases .

<cell_line>CML cells</cell_line> exhibited an inhibition degree by in vitro glucocorticoids significantly higher than that of <cell_line>ANLL cells</cell_line> but not different from that of lymphoproliferative diseases .


No clear relationship among GR pattern , in vitro cell sensitivity to glucocorticoids , and clinicohematologic parameters was observed in myeloid leukemia-bearing patients .


Glucocorticoid receptors and in vitro corticosensitivity of peanut-positive and peanut-negative human thymocyte subpopulations .

<protein>Glucocorticoid receptors</protein> and in vitro corticosensitivity of <cell_line>peanut-positive and peanut-negative human thymocyte subpopulations</cell_line> .


In 6 human thymus glands , the immature subset of thymocytes was separated from the more mature one , by differential peanut lectin agglutination .

In 6 human thymus glands , the immature subset of <cell_type>thymocytes</cell_type> was separated from the more mature one , by differential peanut lectin agglutination .


These 2 cell subpopulations were analyzed for glucocorticoid receptor content by using a whole cell assay , with ( 3H ) -triamcinolone acetonide as tracer .

These 2 cell subpopulations were analyzed for <protein>glucocorticoid receptor</protein> content by using a whole cell assay , with ( 3H ) -triamcinolone acetonide as tracer .


The unagglutinated thymocytes ( peanut negative ) contained about 2 times more receptor sites per cell than agglutinated ( peanut positive ) ones ( 7650 +/- 1550 S.D. verus 3195 +/- 896 S.D. ) .

The <cell_type>unagglutinated thymocytes</cell_type> ( peanut negative ) contained about 2 times more receptor sites per cell than agglutinated ( peanut positive ) ones ( 7650 +/- 1550 S.D. verus 3195 +/- 896 S.D. ) .


The affinity for steroid was similar in both cell subsets , as was the stereospecificity for glucocorticoids , the time-course of steroid-receptor association , and cytoplasmic to nuclear translocation .


Despite the greater number of glucocorticoid receptor sites , the peanut-negative thymocyte subpopulation did not differ from the peanut-positive one in its sensitivity to the inhibitory effects of triamcinolone acetonide , as determined by measurements of the incorporation of radiolabeled precursors of protein and DNA .

Despite the greater number of <protein>glucocorticoid receptor</protein> sites , the <cell_line>peanut-negative thymocyte subpopulation</cell_line> did not differ from the <cell_line>peanut-positive</cell_line> one in its sensitivity to the inhibitory effects of triamcinolone acetonide , as determined by measurements of the incorporation of radiolabeled precursors of protein and DNA .


Moreover , the peanut-negative subset appeared more resistant in vitro to the steroid-induced cell lysis as compared to the peanut-positive one .

Moreover , the <cell_line>peanut-negative subset</cell_line> appeared more resistant in vitro to the steroid-induced cell lysis as compared to the <cell_line>peanut-positive</cell_line> one .


Thus , our data suggest that glucocorticoid receptor density and corticosensitivity are not directly correlated and that the number of glucocorticoid receptor sites may be dependent on the degree of immunologic maturation

Thus , our data suggest that glucocorticoid receptor density and corticosensitivity are not directly correlated and that the number of <protein>glucocorticoid receptor</protein> sites may be dependent on the degree of immunologic maturation


Defective binding and function of 1 , 25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with end-organ resistance to 1 , 25-dihydroxyvitamin D .

Defective binding and function of <protein>1 , 25-dihydroxyvitamin D3 receptors</protein> in <cell_type>peripheral mononuclear cells</cell_type> of patients with end-organ resistance to 1 , 25-dihydroxyvitamin D .


Lectin-induced DNA synthesis by peripheral mononuclear cells from 17 normal donors was inhibited ( 40-60 % ) by 1 , 25-dihydroxyvitamin D3 ( 1 , 25 [ OH ] 2D3 ) at physiological concentrations ( 10 ( -10 ) -10 ( -9 ) M ) .

Lectin-induced DNA synthesis by <cell_type>peripheral mononuclear cells</cell_type> from 17 normal donors was inhibited ( 40-60 % ) by 1 , 25-dihydroxyvitamin D3 ( 1 , 25 [ OH ] 2D3 ) at physiological concentrations ( 10 ( -10 ) -10 ( -9 ) M ) .


The lymphocytes acquire specific receptors for 1 , 25 ( OH ) 2D3 upon activation by the lectins .

The <cell_type>lymphocytes</cell_type> acquire specific receptors for 1 , 25 ( OH ) 2D3 upon activation by the <protein>lectins</protein> .


This process precedes the inhibitory effect of 1 , 25 ( OH ) 2D3 .


We studied lymphocytes from six patients from four different kindreds with the syndrome of hereditary end-organ resistance to 1 , 25 ( OH ) 2D ( the so-called vitamin D-dependent rickets type II ) .

We studied <cell_type>lymphocytes</cell_type> from six patients from four different kindreds with the syndrome of hereditary end-organ resistance to 1 , 25 ( OH ) 2D ( the so-called vitamin D-dependent rickets type II ) .


In five patients ( three kindreds ) peripheral blood mononuclear cells did not acquire receptors for 1 , 25 ( OH ) 2D3 upon phytohemagglutinin-induced activation .

In five patients ( three kindreds ) <cell_type>peripheral blood mononuclear cells</cell_type> did not acquire receptors for 1 , 25 ( OH ) 2D3 upon phytohemagglutinin-induced activation .


Moreover , in contrast to normal lymphocytes , the mitogenic stimulation of these patients ' lymphocytes by phytohemagglutinin and concanavalin A was not inhibited by 1 , 25 ( OH ) 2D3 .

Moreover , in contrast to <cell_type>normal lymphocytes</cell_type> , the mitogenic stimulation of these patients ' <cell_type>lymphocytes</cell_type> by <protein>phytohemagglutinin</protein> and concanavalin A was not inhibited by 1 , 25 ( OH ) 2D3 .


Activated lymphocytes of the sixth patient from a fourth kindred exhibited normal binding of [ 3H ] 1 , 25 ( OH ) 2D3 but the hormone failed to inhibit the mitogenic stimulation .

Activated <cell_type>lymphocytes</cell_type> of the sixth patient from a fourth kindred exhibited normal binding of [ 3H ] 1 , 25 ( OH ) 2D3 but the hormone failed to inhibit the mitogenic stimulation .


A similar pattern of the vitamin D effector system was previously observed in fibroblasts cultured from skin biopsies of the same group of patients .


The conclusions from these findings are : ( a ) the inhibition of mitogenic stimulation by 1 , 25 ( OH ) 2D3 is mediated by specific functional receptors to the hormone ; and ( b ) the receptors for 1 , 25 ( OH ) 2D3 in mononuclear cells are probably controlled genetically by the same mechanisms as the effector system in well-characterized target organs of the hormone , such as intestine and kidney .

The conclusions from these findings are : ( a ) the inhibition of mitogenic stimulation by 1 , 25 ( OH ) 2D3 is mediated by <protein>specific functional receptors</protein> to the hormone ; and ( b ) the receptors for 1 , 25 ( OH ) 2D3 in <cell_type>mononuclear cells</cell_type> are probably controlled genetically by the same mechanisms as the effector system in well-characterized target organs of the hormone , such as intestine and kidney .


Glucocorticoid receptors of mononuclear leukocytes from myasthenia gravis patients .

<protein>Glucocorticoid receptors</protein> of <cell_type>mononuclear leukocytes</cell_type> from myasthenia gravis patients .


The present study was performed to analyse glucocorticoid receptor ( GR ) binding in peripheral blood mononuclear leukocytes ( MNL ) from 39 myasthenia gravis ( MG ) patients ( unoperated patients ( n = 13 ) , thymectomized patients ( n = 14 ) and patients receiving glucocorticoids : thymectomized ( n = 11 ) and unoperated ( n = 6 ] .

The present study was performed to analyse <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) binding in <cell_type>peripheral blood mononuclear leukocytes</cell_type> ( <cell_type>MNL</cell_type> ) from 39 myasthenia gravis ( MG ) patients ( unoperated patients ( n = 13 ) , thymectomized patients ( n = 14 ) and patients receiving glucocorticoids : thymectomized ( n = 11 ) and unoperated ( n = 6 ] .


A whole cell binding assay with 3 ( H ) dexamethasone was used .


GR mean values were significantly higher in the MNL of MG patients ( thymectomized or not ) not receiving glucocorticoid than in the MNL of healthy donors .

<protein>GR</protein> mean values were significantly higher in the <cell_type>MNL</cell_type> of MG patients ( thymectomized or not ) not receiving glucocorticoid than in the <cell_type>MNL</cell_type> of healthy donors .


Affinity was within the normal range .


Sex , age or clinical forms of illness did not influence the results .


In patients receiving prednisone ( Pd ) the GR values were significantly lower than in MG patients without Pd therapy , independent of Pd dose or time of administration .

In patients receiving prednisone ( Pd ) the <protein>GR</protein> values were significantly lower than in MG patients without Pd therapy , independent of Pd dose or time of administration .


No differences in receptor binding between normal subjects and MG patients receiving Pd have been found .


Immunological interference of high dose corticosteroids .


High-dose corticosteroids ( HDC ) will influence cellular as well as humoral participants of the immune response .


The lymphoid tissue will decrease in size and weight after prolonged treatment with HDC .


Lymphocyte functions will be impaired .


Reduced synthesis of B- as well as T-lymphocytes will be seen .

Reduced synthesis of <cell_type>B- as well as T-lymphocytes</cell_type> will be seen .


The inhibitory effect on B-cell function can be observed both as decreased serum levels of immunoglobulins and as impaired binding of antibodies and complement to the cellular surface .

The inhibitory effect on <cell_type>B-cell</cell_type> function can be observed both as decreased serum levels of <protein>immunoglobulins</protein> and as impaired binding of <protein>antibodies</protein> and complement to the cellular surface .


Reduced T-cell function indicated by impaired stimulation by PHA and porkweed as well as by impaired lymphokinin effects on leukocyte migration inhibition has been reported .

Reduced <cell_type>T-cell</cell_type> function indicated by impaired stimulation by <protein>PHA</protein> and <protein>porkweed</protein> as well as by impaired lymphokinin effects on <cell_type>leukocyte</cell_type> migration inhibition has been reported .


Reduced lymphocyte adherence to antigen and suppressed lymphocyte reaction have also been observed .


Humoral factors involved in chemotaxis , opsonisation , phagocytosis , vascular permeability leading to leakage of fluid and cells and factors involved in lysis of antigens are impaired .


This can be explained partly by the observed reduced complement activation via the alternative as well as the classical pathway in association with HDC therapy .


Acute processes with increased vascular permeability and accumulation of leukocytes as impairing factors could be influenced beneficially by HDC therapy .

Acute processes with increased vascular permeability and accumulation of <cell_type>leukocytes</cell_type> as impairing factors could be influenced beneficially by HDC therapy .


This positive effect can be seen in treatment of septic shock or rejection of a transplant .


However , if sepsis or rejection is not rapidly reversed , complications such as multisystem organ failure and bacteremia are prone to appear .


Identification of human leukemic glucocorticoid receptors using affinity labeling and anti-human glucocorticoid receptor antibodies .

Identification of <protein>human leukemic glucocorticoid receptors</protein> using affinity labeling and <protein>anti-human glucocorticoid receptor antibodies</protein> .


Antisera raised against human lymphoid glucocorticoid receptors were used in combination with the glucocorticoid receptor affinity label [ 3H ] dexamethasone 21-mesylate [ ( 3H ] DM ) to identify the glucocorticoid receptors of the human B-lymphoblastoid cell line IM-9 and the human T-cell leukemic cell line CEM-C7 .

Antisera raised against <protein>human lymphoid glucocorticoid receptors</protein> were used in combination with the glucocorticoid receptor affinity label [ 3H ] dexamethasone 21-mesylate [ ( 3H ] DM ) to identify the <protein>glucocorticoid receptors</protein> of the <cell_line>human B-lymphoblastoid cell line</cell_line> <cell_line>IM-9</cell_line> and the <cell_line>human T-cell leukemic cell line</cell_line> <cell_line>CEM-C7</cell_line> .


Antisera were obtained following immunization of New Zealand White rabbits with [ 3H ] triamcinolone acetonide [ ( 3H ] TA ) -glucocorticoid receptor complexes partially purified by two-stage DNA-cellulose chromatography .

Antisera were obtained following immunization of New Zealand White rabbits with <protein>[ 3H ] triamcinolone acetonide [ ( 3H ] TA ) -glucocorticoid receptor complexes</protein> partially purified by two-stage DNA-cellulose chromatography .


The presence of anti-human glucocorticoid receptor antibodies was verified by : ( a ) adsorption of [ 3H ] TA-receptor-antibody complexes to Protein A ; ( b ) a shift to higher apparent molecular weight in the elution position from Sephacryl S300 of [ 3H ] TA-receptor complexes incubated with immune serum ; and ( c ) the ability of immune serum to displace [ 3H ] TA-receptor complexes on sucrose gradients .

The presence of <protein>anti-human glucocorticoid receptor antibodies</protein> was verified by : ( a ) adsorption of <protein>[ 3H ] TA-receptor-antibody complexes</protein> to <protein>Protein A</protein> ; ( b ) a shift to higher apparent molecular weight in the elution position from Sephacryl S300 of <protein>[ 3H ] TA-receptor complexes</protein> incubated with immune serum ; and ( c ) the ability of immune serum to displace <protein>[ 3H ] TA-receptor complexes</protein> on sucrose gradients .


These antibodies also recognized rat liver and murine S49 cell glucocorticoid receptors .

These <protein>antibodies</protein> also recognized rat liver and <protein>murine S49 cell glucocorticoid receptors</protein> .


Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [ 3H ] DM-labeled IM-9 cytosol identified a major competable band with a molecular weight of approximately 90 , 000 , three minor competable components with molecular weights of approximately 78 , 000 , approximately 51 , 000 , and approximately 38 , 500 , and at least 21 other noncompetable components .


Following immunoprecipitation of [ 3H ] DM-labeled cytosol with immune serum , only the Mr 90 , 000 and 78 , 000 components were seen .


Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [ 3H ] DM-labeled CEM-C7 cytosol revealed a larger number of [ 3H ] DM-labeled components .


However , after immunoprecipitation of [ 3H ] DM-labeled CEM-C7 cytosol , a predominant competable component with a molecular weight of 90 , 000 was easily identified .


This component was markedly diminished when cytosols from the glucocorticoid receptor-deficient cell line ICR-27 were used .

This component was markedly diminished when cytosols from the <cell_line>glucocorticoid receptor-deficient cell line</cell_line> <cell_line>ICR-27</cell_line> were used .


Thus , the combination of affinity labeling and anti-human glucocorticoid receptor antibodies is capable of providing direct physical identification of human lymphoid glucocorticoid receptors .

Thus , the combination of affinity labeling and <protein>anti-human glucocorticoid receptor antibodies</protein> is capable of providing direct physical identification of <protein>human lymphoid glucocorticoid receptors</protein> .


Effect of thymosin on glucocorticoid receptor activity and glucocorticoid sensitivity of human thymocytes .

Effect of thymosin on <protein>glucocorticoid receptor</protein> activity and glucocorticoid sensitivity of <cell_type>human thymocytes</cell_type> .


Incubation with thymosin fraction 5 , ( TMS F5 at 300 micrograms/ml ) a partially purified thymic factor , reduced the steroid binding activity of human infant thymocytes from 9.6 +/- 2.1 fmole/ml to 5.0 +/- 2.0 fmole/ml .

Incubation with thymosin fraction 5 , ( TMS F5 at 300 micrograms/ml ) a partially purified thymic factor , reduced the steroid binding activity of <cell_type>human infant thymocytes</cell_type> from 9.6 +/- 2.1 fmole/ml to 5.0 +/- 2.0 fmole/ml .


The glucocorticoid receptor activity in normal infant thymocytes was found to be 2 , 146 +/- 726 ( s.d. ) sites per cell with dissociation constant of 1.4 +/- 0.6 X 10 ( -8 ) M .

The <protein>glucocorticoid receptor</protein> activity in normal infant thymocytes was found to be 2 , 146 +/- 726 ( s.d. ) sites per cell with dissociation constant of 1.4 +/- 0.6 X 10 ( -8 ) M .


TMS F5 also increased the resistance of human thymocytes to the cytolytic effect of dexamethasone ( 2.5 X 10 ( -8 ) M ) to 168.6 +/- 30.2 % of control ( P less than 0.01 ) .


In animals , medullary and peripheral blood T cells are more resistant to glucocorticoids than immature thymic T cells .

In animals , <cell_type>medullary and peripheral blood T cells</cell_type> are more resistant to glucocorticoids than <cell_type>immature thymic T cells</cell_type> .


The results show that thymosin can induce changes consistent with differentiation in human thymocytes .

The results show that thymosin can induce changes consistent with differentiation in <cell_type>human thymocytes</cell_type> .


These in vitro results are consistent with a physiological role of thymosin in intrathymic T cell maturation in man .


Incubation of a human malignant thymus derived T cell line ( MOLT 3 ) with TMS F5 also resulted in a significant reduction of the number of steroid binding sites to 44.2 +/- 15.3 % of control ( P less than 0.05 ) , but TMS F5 did not significantly reduce the glucocorticoid sensitivity of MOLT 3 cells .

Incubation of a <cell_line>human malignant thymus derived T cell line</cell_line> ( <cell_line>MOLT 3</cell_line> ) with TMS F5 also resulted in a significant reduction of the number of steroid binding sites to 44.2 +/- 15.3 % of control ( P less than 0.05 ) , but TMS F5 did not significantly reduce the glucocorticoid sensitivity of <cell_line>MOLT 3 cells</cell_line> .


Specific high-affinity receptors for 1 , 25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells : presence in monocytes and induction in T lymphocytes following activation .

<protein>Specific high-affinity receptors</protein> for 1 , 25-dihydroxyvitamin D3 in <cell_type>human peripheral blood mononuclear cells</cell_type> : presence in <cell_type>monocytes</cell_type> and induction in <cell_type>T lymphocytes</cell_type> following activation .


Human peripheral blood monocytes have high affinity binding sites for 1 , 25- ( OH ) 2D3 ( Kd 0.14 nM , sedimentation coefficient 3.7S ) .

<cell_type>Human peripheral blood monocytes</cell_type> have high affinity binding sites for 1 , 25- ( OH ) 2D3 ( Kd 0.14 nM , sedimentation coefficient 3.7S ) .


Resting human peripheral blood T lymphocytes , however , do not have a demonstrable 1 , 25- ( OH ) 2D3 receptor .

<cell_type>Resting human peripheral blood T lymphocytes</cell_type> , however , do not have a demonstrable <protein>1 , 25- ( OH ) 2D3 receptor</protein> .


After activation with phytohemagglutinin the T cells exhibit the receptor within 24 h , and this expression is blocked by cycloheximide .

After activation with <protein>phytohemagglutinin</protein> the <cell_type>T cells</cell_type> exhibit the receptor within 24 h , and this expression is blocked by cycloheximide .


The receptor in activated T lymphocytes has a sedimentation coefficient of 3.7S and a high affinity ( Kd 0.10 nM ) for the ligand .

The receptor in <cell_type>activated T lymphocytes</cell_type> has a sedimentation coefficient of 3.7S and a high affinity ( Kd 0.10 nM ) for the ligand .


Effects of chronic glucocorticoid excess in man on insulin binding to circulating cells : differences between endogenous and exogenous hypercorticism .

Effects of chronic glucocorticoid excess in man on insulin binding to <cell_type>circulating cells</cell_type> : differences between endogenous and exogenous hypercorticism .


We measured [ 125I ] insulin binding to circulating monocytes or erythrocytes from 16 patients with chronic glucocorticoid excess , 9 chronically treated with prednisone and 7 with adrenocortical hyperfunction .

We measured [ 125I ] insulin binding to <cell_type>circulating monocytes or erythrocytes</cell_type> from 16 patients with chronic glucocorticoid excess , 9 chronically treated with prednisone and 7 with adrenocortical hyperfunction .


With monocytes , [ 125I ] insulin binding was iincreased in all patients .

With <cell_type>monocytes</cell_type> , [ 125I ] insulin binding was iincreased in all patients .


Analysis of binding data indicated that increased binding in patients treated with prednisone was due to an ncrease in receptor concentration , whereas in patients with adrenocortical hyperfunction , it was due to an increase in receptor affinity .


With erythrocytes from patients with adrenocortical hyperfunction there was an increase in receptor affinity and a decrease in receptor concentration , so that the binding of [ 125I ] insulin was normal .


The disparity of results between endogenous and exogenous hypercorticism , between the two cell types , and between the present studies and previous studies suggest that the effects of glucocorticoid excess on the insulin receptor are extremely complex and wide-ranging and that in this condition , extrapolations in humans from data with circulating cells to liver and muscle may not be appropriate .

The disparity of results between endogenous and exogenous hypercorticism , between the two cell types , and between the present studies and previous studies suggest that the effects of glucocorticoid excess on the <protein>insulin receptor</protein> are extremely complex and wide-ranging and that in this condition , extrapolations in humans from data with <cell_type>circulating cells</cell_type> to liver and muscle may not be appropriate .


Reduced level of cellular glucocorticoid receptors in patients with anorexia nervosa .

Reduced level of <protein>cellular glucocorticoid receptors</protein> in patients with anorexia nervosa .


Specific glucocorticoid receptors were measured in circulating mononuclear leukocytes from 12 patients with anorexia nervosa and 21 healthy control subjects .

Specific <protein>glucocorticoid receptors</protein> were measured in circulating <cell_type>mononuclear leukocytes</cell_type> from 12 patients with anorexia nervosa and 21 healthy control subjects .


Cells from patients were found to contain a significantly ( p less than 0.01 ) lower level of glucocorticoid receptor ( 3830 +/- 210 sites/cell , mean +/- SE ) than those from controls ( 4930 +/- 250 sites/cell ) .

Cells from patients were found to contain a significantly ( p less than 0.01 ) lower level of <protein>glucocorticoid receptor</protein> ( 3830 +/- 210 sites/cell , mean +/- SE ) than those from controls ( 4930 +/- 250 sites/cell ) .


A partial glucocorticoid receptor defect may well explain the abnormal cortisol metabolism and glucocorticoid resistance commonly found in patients with anorexia nervosa .

A partial <protein>glucocorticoid receptor</protein> defect may well explain the abnormal cortisol metabolism and glucocorticoid resistance commonly found in patients with anorexia nervosa .


Regulation of the glucocorticoid receptor in human lymphocytes .

Regulation of the <protein>glucocorticoid receptor</protein> in <cell_type>human lymphocytes</cell_type> .


The presence of a glucocorticoid receptor in human lymphocytes is well established , but factors affecting its regulation have not been described .

The presence of a <protein>glucocorticoid receptor</protein> in <cell_type>human lymphocytes</cell_type> is well established , but factors affecting its regulation have not been described .


Using a competitive binding whole cell assay , we have examined the binding of [ 3H ] -dexamethasone at 24 and 37 degrees C in untreated normal subjects and in healthy subjects taking various glucocorticoid preparations .


At 24 degrees C normal human lymphocytes had 6000 binding sites/cell and a dissociation constant of 4 x 10 ( -9 ) M .

At 24 degrees C <cell_type>normal human lymphocytes</cell_type> had 6000 binding sites/cell and a dissociation constant of 4 x 10 ( -9 ) M .


The administration of 1 mg of dexamethasone , 5 mg of prednisone , and 37.5 mg of cortisone acetate resulted in a 30 % decrease in binding sites after 1 week with no change in binding affinity .


No changes in the number of binding sites was noted before 1 week and the diminished number persisted for 1 week after discontinuation of glucocorticoid treatment .


Lymphocytes from hospitalized patients taking 40-60 mg of dexamethasone daily demonstrated the same change in number of binding sites that was seen in normal subjects taking 1 mg of dexamethasone .

<cell_type>Lymphocytes</cell_type> from hospitalized patients taking 40-60 mg of dexamethasone daily demonstrated the same change in number of binding sites that was seen in normal subjects taking 1 mg of dexamethasone .


When binding assays were carried out at physiologic temperature there was the same decrease in number of binding sites after dexamethasone administration , and in addition , there was a two-fold increase in binding affinity .


Glucocorticoid administration results in a time-dependent decrease in the number of lymphocyte glucocorticoid binding sites that is independent of the type of glucocorticoid administered .


This is the first in vivo demonstration that glucocorticoids modulate their own receptors in man .


Immunoglobulin localization in benign and malignant lesions of the human mammary gland .


Using direct imunofluorescence , lesions from 266 human breast specimens were studied for the presence of IgA , IgM , or IgG localization .


The lesions included benign elements from 66 subcutaneous mastectomy specimens in which the absence of simultaneous breast malignancy was documented , primary breast carcinomas from 153 mastectomy specimens , and 47 biopsies containing metastatic breast cancer .


A statistically significant association of IgA and IgM with benign lesions was contrasted to the association of IgG with malignant lesions .

A statistically significant association of <protein>IgA</protein> and <protein>IgM</protein> with benign lesions was contrasted to the association of <protein>IgG</protein> with malignant lesions .


In both primary and metastatic lesions , IgG localization was associated with estrogen-receptor-poor primary cancers as compared with estrogen-receptor-rich primary cancers .

In both primary and metastatic lesions , <protein>IgG</protein> localization was associated with estrogen-receptor-poor primary cancers as compared with estrogen-receptor-rich primary cancers .


Among primary breast cancer patients , IgG localization in the tumor correlated with relative lymphopenia .

Among primary breast cancer patients , <protein>IgG</protein> localization in the tumor correlated with relative lymphopenia .


A shorter disease-free interval was noted in association with IgG localization among the metastatic breast lesions .

A shorter disease-free interval was noted in association with <protein>IgG</protein> localization among the metastatic breast lesions .


No statistically significant association between stage of disease and immunoglobulin presence was demonstrable .


Moderate-to-severe intraductal epithelial hyperplasias were more often associated with immunoglobulin G localization that were other benign lesions

Moderate-to-severe intraductal epithelial hyperplasias were more often associated with <protein>immunoglobulin G</protein> localization that were other benign lesions


Correlation of steroid receptors with histologic differentiation in mammary carcinoma .

Correlation of <protein>steroid receptors</protein> with histologic differentiation in mammary carcinoma .


A Singapore experience .


Cancer of the breast is the most common tumor in females in Singapore , with the rate of 20.7 per 100 , 000 per year ( 1977 estimate ) , which is predicted to increase to 29.8 per 100 , 000 women per year by 1995 .


A detailed histopathologic review of 50 primary breast cancer tumors analyzed for estrogen receptor ( ER ) level was carried out and a variety of morphologic features correlated with ER results to identify any factors that will improve the management and prognosis for breast cancer .

A detailed histopathologic review of 50 primary breast cancer tumors analyzed for <protein>estrogen receptor</protein> ( <protein>ER</protein> ) level was carried out and a variety of morphologic features correlated with <protein>ER</protein> results to identify any factors that will improve the management and prognosis for breast cancer .


Cytosol was incubated with 3H-estradiol in the presence and absence of cold diethylstilbestrol , and bound and free hormone were separated by Dextran-coated charcoal method .


Tumors binding more than 5 fmol/mg cytosol protein were classified as ER -positive .

Tumors binding more than 5 fmol/mg <protein>cytosol protein</protein> were classified as <protein>ER</protein> -positive .


Progesterone receptor ( PR ) level was analyzed in some specimens with the use of a similar method .

<protein>Progesterone receptor</protein> ( <protein>PR</protein> ) level was analyzed in some specimens with the use of a similar method .


Most of the patients were Chinese ( 90 % ) .


Three patients were Malays , one was Indian , and one was European in this series .


Results indicated that there was strong correlation between ER level , age , and histologic grade of the tumors .

Results indicated that there was strong correlation between <protein>ER</protein> level , age , and histologic grade of the tumors .


No correlation existed between absence or presence of lymph node metastases and ER .

No correlation existed between absence or presence of lymph node metastases and <protein>ER</protein> .


Although there was a trend for ER -positive tumors to have a low-grade lymphocytic infiltration , the difference was not statistically significant .

Although there was a trend for <protein>ER</protein> -positive tumors to have a low-grade lymphocytic infiltration , the difference was not statistically significant .


Mononuclear cells infiltrating human mammary carcinomas : immunohistochemical analysis with monoclonal antibodies .

<cell_type>Mononuclear cells</cell_type> infiltrating human mammary carcinomas : immunohistochemical analysis with <protein>monoclonal antibodies</protein> .


Breast carcinomas were examined by the immunoperoxidase technique using antisera specific for lymphocyte subsets , monocytes , NK cells and major histocompatibility antigens ( HLA-A , -B , -C ; Ia-like ) .

Breast carcinomas were examined by the immunoperoxidase technique using antisera specific for <cell_type>lymphocyte subsets</cell_type> , <cell_type>monocytes</cell_type> , <cell_type>NK cells</cell_type> and <protein>major histocompatibility antigens</protein> ( <protein>HLA-A</protein> , <protein>-B</protein> , -C ; <protein>Ia-like</protein> ) .


Sixty-four per cent of the patients had a moderate or strong mononuclear cell infiltration , 77 % of the patients without mononuclear cell infiltration had receptors for estrogens as compared to 51 % of the patients with infiltration .

Sixty-four per cent of the patients had a moderate or strong mononuclear cell infiltration , 77 % of the patients without <cell_type>mononuclear cell</cell_type> infiltration had receptors for estrogens as compared to 51 % of the patients with infiltration .


The majority of the infiltrating mononuclear cells were T cells ; generally the OKT8 cells were predominant .

The majority of the <cell_type>infiltrating mononuclear cells</cell_type> were <cell_type>T cells</cell_type> ; generally the <cell_line>OKT8 cells</cell_line> were predominant .


The Leu 3A/OKT8 cell ratio was not related to histological type , tumor size , age of the patient or presence of metastases .


Some of the T cells had the Ia antigen and were thus probably activated .

Some of the T cells had the <protein>Ia antigen</protein> and were thus probably activated .


The B cells were either absent or less numerous than the T cells .

The <cell_type>B cells</cell_type> were either absent or less numerous than the T cells .


There was no relation between their distribution and the various parameters studied .