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Conformations of model peptides in membrane-mimetic environments.
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The influence of a membrane environment on the conformational energetics of a polypeptide chain has been investigated through studies of model peptides in a variety of membrane-mimetic media. Nuclear magnetic resonance (NMR) and circular dichroism (CD) data have been obtained for the peptides in bulk hydrophobic solvents, normal micelles, and reversed micelles. Several hydrophobic peptides which are sparingly soluble in water have been solubilized in aqueous sodium dodecyl sulfate (SDS) solution. NMR and CD data indicate that the micelle-solubilized peptides experience an environment with the conformational impact of bulk methanol, and have decreased conformational freedom. The site of residence of the peptides interacting with the micelles appears to be near the surfactant head groups, in a region permeated by water, and not in the micelle core. Strongly hydrophilic peptides have been solubilized in nonpolar solvents by reversed micelles. These peptides are located in small water pools in close association with the head groups of the surfactant. NMR and CD data show that there is a conformational impact of this interfacial water region on peptide solubilizates distinct from that of bulk water.
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10,003,902
Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue.
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10,003,903
The cytotoxic peptide from honeybee venom, melittin, and a synthetic peptide analogue of it lyse human erythrocytes in a biphasic process. The kinetics of the lysis in 0.30 M sucrose, 0.01 M sodium phosphate, pH 7.30 at 4 degrees C were investigated. Our results show that melittin rapidly binds to the outer surface of the erythrocyte membrane, and the surface-bound monomers produce transient openings through which approximately 40 hemoglobin molecules can escape. Concomitantly, the melittin loses its ability to effect the process, presumably by translocation through the bilayer. The half-life for this process is 1.2 min. In a much slower process, dimers of this internalized melittin again produce transient membrane openings in a steady state. On a molar basis, the synthetic peptide analogue produces a fast process comparable to that caused by melittin, but is more efficient in the slow phase. Escape of hemoglobin and of carbonic anhydrase through the openings is diffusion controlled. These results suggest that the functional units necessary for the activity of melittin-like cytotoxic peptides are a 20 amino acid amphiphilic alpha-helix with a hydrophobic:hydrophilic ratio greater than 1 and a short segment with a high concentration of positive charges.
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10,003,904
Comparative effects of melittin and its hydrophobic and hydrophilic fragments on bilayer organization by Raman spectroscopy.
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10,003,905
For bilayer systems consisting of 1,2-dimyristoyl phosphatidylcholine (DMPC) incubated with melittin, a polypeptide capable of integrating itself within the membrane, temperature profiles derived from Raman spectroscopic data indicate the existence of an immobilized lipid annulus surrounding the polypeptide. In particular, temperature profiles derived from C--H, C--D and C--C stretching mode parameters for 25:1, 14:1 and 10:1 lipid:protein mole ratios exhibit two order-disorder transitions. The primary (lower) gel to liquid crystalline phase transition is depressed when polypeptide concentration is increased. The concentration-independent higher temperature transition is associated with a fluidization of the immobilized boundary lipids present at the lipid-polypeptide interface within the bilayer. We estimate that five to seven lipids are involved in this discrete boundary layer around the inserted membrane component. The behavior of the intrinsic hydrophobic (residues 1-19) and of the extrinsic hydrophilic (residues 20-26) portions of melittin in the bilayer is compared with the properties of the intact polypeptide. We emphasize evidence that both intrinsic and extrinsic components immobilize lipids contiguous to the polypeptide.
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10,003,906
The structure of melittin in the form I crystals and its implication for melittin's lytic and surface activities.
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10,003,907
Melittin from bee venom is water-soluble, yet integrates into membranes and lyses cells. Each melittin chain consists of 26 amino acid residues and in aqueous salt solutions it exists as a tetramer. We have determined the molecular structure of the tetramer in two crystal forms grown from concentrated salt solutions. In both crystal forms the melittin polypeptide is a bent alpha-helical rod, with the "inner" surface largely consisting of hydrophobic sidechains and the "outer" surface consisting of hydrophilic side chains. Thus, the helix is strongly amphiphilic. In the tetramer, four such helices contribute their hydrophobic side chains to the center of the molecule. The packing of melittin tetramers is also very similar in the two crystal forms: they are packed in planar layers with the outsides forming hydrophilic surfaces and the insides (the centers of melittin tetramers) forming a hydrophobic surface. We suggest that the surface activity of melittin can be rationalized in terms of these surfaces. The lytic activity of melittin can also be interpreted in terms of the molecular structure observed in the crystals: the hydrophobic inner surface of a melittin helix may integrate into the apolar region of a bilayer with the helix axis approximately parallel to the plane of the bilayer, and with the hydrophilic surface exposed to the aqueous phase. This integration would be expected to disrupt the bilayer because of melittin helix would penetrate only a short distance into it. Additionally, the integration of melittin from one side of a bilayer would produce a surface area difference across the bilayer, perhaps leading to lysis. In this view, melittin is distinct from membrane proteins that penetrate evenly into both leaflets of a bilayer or exactly halfway through a bilayer, and hence we refer to melittin as a surface-active protein.
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10,003,908
Structure and function of an acetylcholine receptor.
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10,003,909
Structural analysis of an acetylcholine receptor from Torpedo californica leads to a three-dimensional model in which a "monomeric" receptor is shown to contain subunits arranged around a central ionophoretic channel, which in turn traverses the entire 110 A length of the molecule. The receptor extends approximately 15 A on the cytoplasmic side, 55 A on the synaptic side of the membrane. The alpha-bungarotoxin/agonist binding site is found to be approximately 55 A from the entrance to the central gated ion channel. A hypothesis for the mechanism of AcChR is presented which takes into account the structural and kinetic data, which is testable, and which serves as a focus for future studies on the agonist-induced structure change in AcChR.
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10,003,910
Influence of ionic strength on the dichroism properties of polynucleosomal fibers.
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10,003,911
Conformations of cyclic peptide/calcium complexes in solution.
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10,003,912
Interactions of DNA with divalent metal ions. I. 31P-NMR studies.
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10,003,913
Interactions of DNA with divalent metal ions. II. Proton relaxation enhancement studies.
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10,003,914
Interactions of DNA with divalent metal ions. III. Extent of metal binding: experiment and theory.
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10,003,915
Anomalous temperature dependence on frictional coefficients: diffusion and sedimentation measurement of low-density lipoproteins, albumin, and polystyrene latex.
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10,003,916
Intramolecular low-frequency vibrations in lysozyme by neutron time-of-flight spectroscopy.
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10,003,917
Fluorescent-labeled crosslinks in collagen: pyrenebutyrylhydrazine.
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10,003,918
Bone marrow cell count per cubic millimeter bone marrow: a new parameter for quantitating therapy-induced cytoreduction in acute leukemia.
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10,003,919
A new technique is introduced for determining the number of bone marrow cells per cubic millimeter marrow, providing an accurate and objective means for quantitating therapy-induced cytoreduction. The method requires a correction for admixed peripheral blood in bone marrow aspirates to measure the fraction of remaining pure marrow. While cell kinetic differences between blood, aspirates, and biopsies identify the proportion of contaminating blood cells, the ratio of red cell hematocrits in blood and aspirate gives the volume of trapped blood. By combining both procedures, bone marrow cell counts per unit volume pure marrow result (BMC/cu mm BM), which were found highly reproducible. Blast cell counts (BMBC/cu mm BM) were obtained by additional morphological differentiation. BMC and BMBC/cu mm BM were monitored in 16 patients with acute nonlymphoblastic leukemia treated with daunorubicin, cytosine arabinoside, and 6-thioguanine in combination and in 4 patients with end-stage acute leukemias and non-Hodgkin's lymphomas during high-dose thymidine therapy. Total and daily therapy-induced cytoreduction rates were significantly greater (P less than 0.01) in responders than nonresponders to either regimen. Changes in BMC/cu mm BM were also found representative for changes in BMBC/cu mm BM, since the majority of bone marrow cells were blasts. In acute leukemia. BMC/cu mm BM thus provides accurate and objective measurements of treatment efficacy in vivo and after short periods of drug exposure. Differences in cytoreduction rates within the group of responders also suggest possible prognostic implications.
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10,003,920
A liquid culture system for murine megakaryocyte progenitor cells.
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10,003,921
A liquid culture system is described for murine megakaryocyte progenitor cells (CFU-M) in the presence of pokeweed-mitogen-stimulated spleen-cell conditioned medium. There were dose-related responses between the number of CFU-M developed and the number of cells cultured and the dosage of conditioned medium in this liquid culture system. Murine CFU-M were abundantly cloned in this system an the plating efficiency was similar in comparison with that in a plasma clot system. The acetylcholinesterase-positive colonies (more than 4 acetylcholinesterase-positive cells) were clearly seen on day 3 of culture, and they reached a maximum (60.5 +/- 10.7/2 x 10(5) cells) on day 7 of culture. Ultrastructural analyses of megakaryocytic maturation in this system showed that a few megakaryocytes produced platelets that were released in the culture medium on day 5 of culture. This liquid culture system is suitable for the study of the dynamic process of the megakaryocyte-platelet system.
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10,003,922
Mechanism of dexamethasone inhibition of chemotactic factor induced granulocyte aggregation.
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10,003,923
The reaction of FMLP with granulocytes causes aggregation and degranulation and enhances adherence to endothelium. To evaluate whether prevention of granule extrusion could impair these granulocyte activities, granulocytes were treated with either dexamethasone or hydrocortisone prior to treatment with FMLP. Dexamethasone was added to suspensions of cytochalasin B-treated granulocytes; it markedly impaired the aggregation response of the granulocytes of FMLP. When cytochalasin-B was not used, granulocyte aggregation in response to FMLP or PMA was inhibited by dexamethasone. Although dexamethasone prevented aggregation of cells following stimulation with FMLP or PMA, it failed to prevent the aggregation of granulocytes induced by rabbit lactoferrin. Adherence of granulocytes to human endothelial monolayers was enhanced by FMLP; dexamethasone inhibited the enhancement. However, with the addition of human lactoferrin to the granulocytes exposed to dexamethasone, the cells were able to adhere as well to endothelium as the cells exposed to FMLP but free of dexamethasone. When cytochalasin-B-treated granulocytes were incubated with dexamethasone or hydrocortisone prior to the addition of FMLP, the subsequent release of lactoferrin was substantially blocked, whereas the release of the primary granule products, lysozyme and beta-glucuronidase, was attenuated but not completely blocked. Thus, corticosteroids might block chemotactic-factor-induced granulocyte aggregation by selectively preventing release of specific granule products that contribute to and sustain aggregation.
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10,003,924
Large granular lymphocytes in human peripheral blood: ultrastructural and cytochemical characterization of the granules.
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10,003,925
Large granular lymphocytes (LGL) are defined as nonadherent mononuclear cells with cytoplasmic azurophilic granules, avid receptors for the Fc portion of IgG, and cytotoxic functions (NK or ADCC activities). In the present study, the granules of LGL isolated from human peripheral blood have been analyzed by enzyme cytochemistry and electron microscopy. It had been found that: (1) in the single cells, granules at different stages of maturation could be detected: in addition, packaging of the granules took place in the proximity of the Golgi apparatus, which is similar to that seen in secretory cell types. (2) Acid phosphatase (AP) was observed within the granules and the vesicles located in the Golgi area: the Golgi apparatus identified through its thiamine pyrophosphatase-positivity was consistently negative for AP. (3) Alpha naphthyl-acetate esterase (ANAE) activity was localized in the granules as well as on the membrane of LGL and monocytes. (4) The ANAE activity of LGL was of the monocytic and not of the lymphocytic type, as shown by NaF inhibition. (5) The LGL granules, although identifiable as primary lysosomes, were not involved in the process of phagocytosis, since LGL failed consistently to ingest latex particles or opsonized red cells.
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10,003,926
Abnormal deoxyuridine suppression test in congenital methylmalonic aciduria-homocystinuria without megaloblastic anemia: divergent biochemical and morphological bone marrow manifestations of disordered cobalamin metabolism in man.
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-0.02988787740468979, -0.07756511121988297, 0.02682451903820038, 0.07365349680185318, -0.07060866802930832, 0.038168445229530334, 0.05652875825762749, -0.021245276555418968, -0.01550113596022129, 0.03381254896521568, 0.0064560784958302975, 0.036048877984285355, 0.005974691826850176, 0.0674956887960434, 0.0618179589509964, -0.01692322827875614, -0.03953641653060913, -0.06425173580646515, -0.05447070673108101, 0.040483295917510986, 0.06652111560106277, -0.006094840355217457, -0.10118845850229263 ]
10,003,927
We studied two brothers (J.R. and M.R.) with the cobalamin D variant of congenital methylmalonic aciduria-homocystinuria, whose previously reported lack of megaloblastic anemia conflicted with current concepts of cobalamin's role in DNA synthesis and the "methyltetrahydrofolate (MTHF) trap" hypothesis. Both subjects were indeed hematologically normal, although J.R. had a mean corpuscular volume of 96 fl. However, both demonstrated abnormalities in the deoxyuridine suppression test. J.R. had an abnormal suppression value of 21.0% (normal less than 10%) that was correctable by adding hydroxocobalamin or folic acid in vitro but not MTHF. M.R. had normal suppression (8.9%), but demonstrated worsening (18.6%) when MTHF was added. J.R.'s classical deoxyuridine suppression pattern of cobalamin deficiency thus supports the trap hypothesis. However, his lack of comparable morphological changes suggests that impaired de novo thymidylate synthesis and the trap hypothesis, though valid, may not fully account for the megaloblastic maturation accompanying cobalamin deficiency. Equally noteworthy was the deleterious effect of MTHF on M.R.'s marrow, suggesting its potential usefulness as an in vitro "stress test" for latent cobalamin abnormality.
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10,003,928
Experimental candidiasis in neutropenic dogs: tissue burden of infection and granulocyte transfusion effects.
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10,003,929
The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis.
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10,003,930
We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.
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10,003,931
Effect of transfused reticulocytes on iron exchange.
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10,003,932
A animal model was developed whereby reticulocyte-rich blood was introduced into normal rats by exchange transfusion. Measurements of plasma iron turnover was made at similar plasma iron concentrations before and after exchange transfusions. High reticulocyte blood obtained from animals rendered iron deficient by diet or by treatment with phenylhydrazine resulted in a mean increase of 86% in internal iron exchange, while the plasma iron turnover was unaffected by exchange with normal red cells. Since iron input from reticuloendothelial cells could have increased due to breakdown of transfused cells, iron absorption was also measured. Within 1 hr and for a least 6 hr after exchange with high reticulocyte blood, mean absorption in six groups of animals was increased over control animals by 50%-130%. The increased plasma iron turnover and absorption was not mediated by a decrease in plasma iron or an increase in unsaturated iron-binding capacity. Indeed, a higher plasma iron and transferrin saturation augmented the movement of iron into the plasma from iron-donating tissues. It is proposed that the donation of iron by transferrin in some way immediately facilitates the procurement of more iron by transferrin.
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10,003,933
Monoclonal antibodies that detect differentiation surface antigens on human myelomonocytic cells.
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10,003,934
We describe here the production and characterization of several new monoclonal antibodies that recognize differentiation antigens present on human cells of the myelomonocytic lineage. The lineage and the stage specificities of our reagents (myeloid-, monocytic-, and myelomonocytic-specific) were determined on the basis of their reactivity with human cell lines and with human peripheral blood and bone marrow cells. Cross-competition experiments demonstrated that some of the antibodies react with the same or closely associated antigenic determinants. Five antigens have been identified in this way: one present on myeloid, one on monocytic, and three on both myeloid and monocytic cells. The possible relationship of our antibodies with other established monoclonal antibodies is discussed, in addition to their use in the in vitro study of the differentiation pathways of human hemopoietic cells and in the characterization of leukemias.
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10,003,935
Abnormal glucocorticoid receptors in acute leukemia cells.
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10,003,936
In normal tissues, 3H-triamcinolone acetonide (3H-TA) labeled glucocorticoid receptors can be resolved into 2 components by DEAE chromatography: peak I elutes at 0.04 M salt and peak II at 0.22 M salt. By glycerol gradient centrifugation, peak I is 3.5S and peak II is 8.5S. Peak I binds to DNA, while peak II does not. Blast cell 3H-TA-binding macromolecules in 27 of 62 cases of acute leukemia had DEAE binding characteristics identical to those of normal tissues; the remaining 35 cases were abnormal. In these cases there was either a single DEAE species eluting in the peak I area (30 cases) or multiple low-amplitude peaks eluting across the entire gradient (5 cases). The abnormal single peak material failed to bind to DNA in 5 cases (of 5 studied), whereas peak I material from 5 cases (of 5 studied), showing normal peak I-peak II ratios, bound normally to DNA. In 3 cases (of 3 studied), the abnormal single peak material had an S value of 2-2.5S, whereas in 5 cases with normal peak I-peak II ratios, the S values were 3.5S and 8.5S, respectively. We hypothesize that those leukemias with abnormal binder characteristics cannot respond to glucocorticoid therapy.
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10,003,937
Effect of cell shape on extravascular hemolysis.
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10,003,938
Severe-glucose-6-phosphate dehydrogenase (G6PD) deficiency associated with chronic hemolytic anemia, granulocyte dysfunction, and increased susceptibility to infections: description of a new molecular variant (G6PD Barcelona).
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10,003,939
Molecular, kinetic, and functional studies were carried out on erythrocytes and leukocytes in a Spanish male with G6PD deficiency, congenital nonspherocytic hemolytic anemia (CNSHA), and increased susceptibility to infections. G6PD activity was absent in patient's red cells and was about 2% of normal in leukocytes. Molecular studies using standard methods (WHO, 1967) showed G6PD in the patient to have a slightly fast electrophoretic mobility at pH 8.0 with otherwise normal properties (heat stability at 46 degrees C, apparent affinity for substrates, optimum pH, and utilization of substrate analogues). Other tests showed the patient's granulocytes to engulf latex particles normally, but to have impaired reduction of nitroblue tetrazolium and ferricytochrome-c as well as reduced iodination. Chemotaxis and random migration of the patient's granulocytes were normal as were myeloperoxidase, leukocyte alkaline phosphatase (LAP), and ultrastructural features. The molecular characteristics of G6PD in the patient differed from those of all previously reported variants associated with CNSHA, so the present variant was provisionally called G6PD Barcelona to distinguish it from other G6PD variants previously described. Possible mechanisms for the severe deficiency of G6PD in erythrocytes and granulocytes was investigated by studies on the immunologic specific activity of the mutant enzyme.
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10,003,940
Assessment of red cell sodium transport in essential hypertension.
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10,003,941
Abnormal erythrocyte Na+ transport has been reported in patients with essential hypertension and some first-degree relatives. The two major techniques now employed for estimating Na+ transport--Na+/Li+ countertransport and Na+/K+ cotransport--are rather intricate and time consuming. Furthermore, the precise nature of the transport processes being measured is not clear. We have developed a simpler, more direct technique based on measurement of 22Na+ accumulation by erythrocytes. 22Na+ uptake by red cells from patients with essential hypertension averages twice normal. Indeed, of 21 patients with essential hypertension, only 2 patients had values within the upper end of the normal range. In 12 patients with secondary hypertension and no family history of essential hypertension, erythrocyte 22Na+ accumulation was within normal limits. Control experiments indicate that our technique for estimating red cell 22Na+ uptake is highly reproducible and shows little day-to-day variation. This procedure for the assessment of erythrocyte Na+ transport should be useful in differential diagnosis and the presymptomatic identification of individuals genetically prone to essential hypertension.
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10,003,942
Erythroid progenitors in polycythemia vera: demonstration of their hypersensitivity to erythropoietin using serum free cultures.
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10,003,943
A system for generating a variable mechanical impedance and its use in an investigation of the electromechanical properties of the B71 audiometric bone vibrator.
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10,003,944
A method of presenting a bone vibrator with a variable mechanical load is described. Reciprocal relationships between electrical and mechanical properties of the B71 vibrator have been investigated and it is concluded that the vibrator behaves as a linear, reversible electrodynamic system. The mechanical impedance of the vibrator has been measured in the frequency range 250-4000 Hz. The relevance of these measurements to audiometer calibration and to sound radiation from the vibrator is discussed.
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10,003,945
Different patterns of harmonics in frequency-following responses.
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10,003,946
Preliminary studies (Krogh et al., 1977) indicated pronounced intersubject differences with respect to harmonic distortion in the frequency-following responses (FFRs) elicited by high intensity, low frequency stimuli and recorded by means of surface electrodes from man. In the present investigation it was confirmed that the responses from 10 test subjects could be divided into three significantly different patterns on the basis of the relative amplitudes of the fundamental (first harmonic) and the second harmonic response component as measured by spectral analyses. In three of the subjects the ratio of the fundamental to the second harmonic was greater than 10 dB (which were termed a type I response). In five, the ratio was between 0 and 10 dB (type II response) and in two the second harmonic was equal to or greater than the fundamental (type III response). The possible causes of harmonic distortion if FFRs are discussed, but not definite explanation of the interindividual differences can be given. A psychoacoustical evaluation of the second harmonic distortion using a tone-on-tone octave masking technique (TOM) showed no correlation between TOM results and FFR type in 10 subjects.
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10,003,947
Problems encountered at work by people with severe acquired hearing loss.
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10,003,948
A structured questionnaire concerning problems encountered at work was administered to 88 adults of employment age suffering from acquired sensorineural hearing loss (60 dB +). While respondents were not likely to be out of work by virtue of their hearing loss, they found it difficult to cope at work for a variety of reasons. Information from a subsequent open-ended interview threw some light on the validity of the questionnaire and in particular illustrated the need to combine quantitative and qualitative methods of data collection.
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10,003,949
Frequency resolution and hearing loss.
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10,003,950
Future scientific and diagnostic interest in frequency resolution requires an evaluation of the different methods that are available to measure it. We compared three methods: (1) pure-tone thresholds in broadband noise, (2) pure-tone thresholds in the presence of a fixed pure-tone masker and (3) psychoacoustical tuning curves. We additionally obtained estimates of temporal integration and of speech intelligibility in noise. Three subject groups were tested: 10 normals, 13 subjects with a noise-induced hearing loss and 18 subjects with a cochlear hearing loss but no history of noise exposure. Generally the three measures of frequency resolution show moderate agreement with each other. Poor frequency resolution is invariably associated with a pure-tone threshold loss. Temporal integration appears unrelated either to the pure-tone threshold loss or frequency resolution. Some of the measures of frequency resolution display significant correlation with speech intelligibility in noise. However, since both variables are correlated with pure-tone threshold loss the exact relationship between frequency resolution and speech intelligibility cannot be clearly established.
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10,003,951
Loudness adaptation: real or illusory.
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10,003,952
There is general agreement that, except at low sensation levels, the loudness of a continuous pure tone does not appear to change with time. By contrast, using a simultaneous dichotic loudness balancing procedure (SDLB) a substantial fall in loudness can be revealed. As a result it has been held that the latter does not represent a loudness loss in real terms but is a manifestation of some form of central binaural interaction possibly involving localization mechanisms. In two studies reported here, one involving a loudness scaling procedure using as a standard a reference tone of 65 dB (HL) and the other a loudness doubling procedure, a loudness loss has been clearly demonstrated following sustained stimulation with a continuous 60-dB (HL), 1000-Hz tone applied monaurally. The progression of the loudness loss with time follows a similar course to that found with the SDLB procedure. In consequence it is concluded that both represent a loudness loss in real terms and that inability to detect a change in loudness over time of a continuous tone results from the absence of any reference standard by which it can be judged.
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10,003,953
Calcification in pulmonary metastases.
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10,003,954
A large variety of neoplasms can produce calcified lung metastases. Three unusual examples are presented and the relevant literature is reviewed. Each case involves a neoplasm not previously reported to produce calcified lung metastases: malignant mesenchymoma, fibrosarcoma of the breast, and medullary carcinoma of the thyroid. The sarcomas are reported in the literature to develop calcified lung metastases are osteogenic sarcoma, chondrosarcoma, synovial sarcoma, and giant cell tumour. Among carcinomas, the papillary and mucinous adenocarcinomas are the histological types most likely to develop calcified lung metastases. The metastases of a number of other tumours have calcified after antineoplastic therapy. Calcification in metastases arises through a variety of mechanisms: bone formation in tumour osteoid, calcification and ossification of tumour cartilage, dystrophic calcification and ossification of tumour cartilage, dystrophic calcification and mucoid calcification. Since calcified lung metastases can strongly resemble granulomas or hamartomas, a reasonable suspicion of malignancy is necessary when evaluating calcified pulmonary nodules.
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10,003,955
The ultrasound diagnosis of emphysematous cholecystitis.
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10,003,956
Regional evaluation of the left ventricular wall motion by radionuclide ventriculography.
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10,003,957
ECG gated radionuclide ventriculography was performed in 85 patients with heart disease. From the analysis of time activity curves of each pixel, sets of parametric scans were displayed. Of 496 parametric scans, 192 were normal and 304 showed wall motion abnormalities. There was good correlation between the individual parametric scans (r greater than or equal to 0.815) and between parametric scans and contrast ventriculograms (r greater than or equal to 0.631) in the occurrence and extent of regional wall motion abnormalities. The highest sensitivity was revealed by the peak filling rate (relaxation velocity) scan. The best specificity was shown by scans using the amplitude and phase of the first Fourier element. Good results were obtained by a combination of four parametric images. The ability of the phase scan to detect local dyskinesis may be better than that of the contrast ventriculogram. Changes in parametric scans were related to, but preceded, impairment of left ventricular function (r greater than or equal to 0.513), It is concluded that parametric scans provide a reliable, objective and non-invasive method for regional evaluation of left ventricular function, of great use in the diagnosis of local wall motion abnormalities and their effect on the heart performance.
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10,003,958
Quantitative measurement of activity in small sources containing medium energy radionuclide: comparison of the gamma camera and the rectilinear scanner.
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10,003,959
The response of a gamma camera and a rectilinear scanner to small sources containing 131I was assessed from the point of view of thier suitability for measuring the activity of a source, as opposed to their capacity to produce well-resolved images. The influence of the size of the area over which counts were integrated, and of the size and depth of hte source, were investigated for both instruments. The results indicate that both instruments are dependent on these variables, though with the particular instruments investigated the dependence of the gamma camera is much more complex and difficult to define. The conclusions indicate that with these systems quantitative activity measurements are more readily achievable with the scanner than with the camera.
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10,003,960
Mechanisms of distribution of gallium 67 in mouse tumour hosts.
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10,003,961
In several mouse tumour models iron given parenterally not only inhibited the transport of 67Ga by plasma transferrin but also accelerated the binding of 67Ga in tumour tissue, particularly during the first hour after 67Ga injection. By 30 min, the tumour had already attained a high concentration though the 67Ga accumulated was still potentially reversible. With the passage of time equally high 67Ga concentrations were attained in tumour in iron-treated and untreated animals alike, and were maintained high as 67GA was totally cleared from the plasma. Given IV, 125-I-human transferrin was not preferentially bound in tumour whereas in muscle tissue loaded with transferrin, 67Ga was accumulated locally during the immediate post-injection phase and to an enhanced degree in iron-treated animals. A hypothesis is presented which, by drawing attention to the role of extravascular transferrin in binding and presenting 67Ga for cellular uptake, helps resolve the apparent contradictions between in vivo and cell culture findings.
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10,003,962
A light torch for the transillumination of female breast tissues.
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10,003,963
The breast can be examined by transillumination with white light. The tissues transmit more light in te red and infrared part of the spectrum than in the blue. Images of the breast are normally recorded on colour infrared film. An alternative to photography is the use of a television camera sensitive to the near infrared, which can demonstrate lesions on a monitor in real time. This paper examines the limitations of the type of light torch used in recent investigations and describes a new version which should permit detection and imaging of smaller lesions.
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10,003,964
The effects of negative pions on spermatogonial survival in the mouse.
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10,003,965
A study of the radiation effects of pi-mesons on the testes of the mouse has been carried out using the pion beam at the SRC Rutherford Laboratory. The cell killing effects on type B and intermediate spermatogonia have been assessed and compared with the effects of 20-0 kVp X rays, delivered at the same dose rate. It was found that not only did irradiation of the testes not disturb the kinetics of spermatogenesis, but also the RBE for pions measured in the Bragg peak and on the plateau was not significantly different from unity. The comparison of this result with those of others using other pion beams is discussed.
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10,003,966
A comparison of thermal enhancement ratios for fast neutron and x irradiation of two normal tissues in rodents.
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10,003,967
The effects of a hyperthermal treatment of one hour on radiation damage to baby rat cartilage and mouse intestine were compared for 250 kVp X irradiation and cyclotron-produced neutron irradiation (mean energy of about 7.5 MeV). Heat, in the range 41.0 degrees C-43.0 degrees C, caused no observable gross tissue injury when given alone. When heat was given immediately before radiation, the radiation damage was enhanced. There was no qualitative differences between response after fast neutrons and after X rays. Thermal enhancement ratios (TER) were similar for the two tissues and were not affected by the type of radiation used. Thus, the relative biological effectiveness (RBE) of fast neutrons compared with X rays was not markedly altered by combining radiation with hyperthermia.
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10,003,968
A simple tissue-like ultrasound phantom material.
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10,003,969
Castleman's giant lymph node hyperplasia.
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10,003,970
Sonographic diagnosis of calcified thrombus of the inferior vena cava.
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10,003,971
Neural arch dysplasia of the sixth cervical vertebra associated with spinal cord compression.
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10,003,972
The ultrasonographic appearance of a trichobezoar.
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10,003,973
Does psychiatric illness affect the recurrence rate of genital herpes?
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-0.04049719125032425, -0.03972289711236954, -0.10043652355670929, -0.021643050014972687, -1.7115969086489713e-8, 0.05668196454644203, -0.04563284292817116, 0.047559190541505814, 0.03503761067986488, 0.042099788784980774, 0.0512675978243351, -0.019343489781022072, 0.03088993765413761, -0.024659670889377594, 0.002361562103033066, 0.04239208996295929, 0.018689800053834915, 0.03767336159944534, 0.013333545997738838, -0.034602150321006775, -0.03378742188215256, 0.030383817851543427, 0.05771748721599579, 0.006650324445217848, -0.08603859692811966, -0.03985818475484848, 0.03571125492453575, -0.00787164643406868, 0.0013992280000820756, -0.04721278324723244, 0.0739445686340332, 0.01935550384223461, 0.004934989847242832, -0.0023572787176817656, -0.14115148782730103, 0.08445283025503159, -0.008781161159276962, 0.0018972893012687564, 0.004792394582182169, -0.020660974085330963, -0.09939470142126083, 0.0166650228202343, 0.04815322533249855, 0.09353207051753998, -0.02447347529232502, 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10,003,974
The progress of 58 patients with first attacks of genital herpes was monitored for up to 30 weeks. The effects of sex (gender), age, social class, and non-psychotic psychiatric illness (as measured by the "general health questionnaire," GHQ) on the recurrence rate of herpes was studied. The recurrence rates, measured by the actuarial percentage recurrence-free curves, showed that the 29 patients with GHQ scores above 11 had a significantly higher recurrence rate than those who scored less than 11 (P = 0.002). There were no important differences between recurrence rates according according to sex, age, or social class. These findings suggest that non-psychotic states, such as anxiety or obsessionality resulting in GHQ scores above 12, may possibly cause an excess production of adrenergic substances which encourages reactivation of latent genital herpes. Thus, to lessen the recurrence rate in such patients, a psychological or chemical approach to treatment could be used to modify the autonomic sympathetic response.
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10,003,975
Cell-mediated immunity in HBeAg-positive homosexuals with chronic liver disease.
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10,003,976
Chronic liver disease developing after infection with the hepatitis B virus may be due to impairment of cell-mediated immunity (CMI). In a study of CMI by the lymphocyte transformation test to two mitogens and hepatitis B surface antigen (HBsAg) the response to the mitogens, phytohemagglutinin (PHA) and purified protein derivative (PPD), was normal in all of 15 male homosexuals with HBsAg-positive chronic liver disease, indicating a normal non-specific cellular immune response. By contrast, only one of the 15 patients showed a response to HBsAg, which may explain the high prevalence of chronic HBsAg carriage in these patients.
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10,003,977
Penicillin epileptogenesis in the rat: diffusion and the differential laminar sensitivity of the cortex cerebri.
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10,003,978
When penicillin is applied electrophoretically from a fluid-filled microelectrode into the substance of the somatosensory cortex of the rat under urethane anaesthesia, the latent period for production of interictal epileptic spikes is least when the electrode lies 0.7 mm below the cortical surface. With low electrophoretic currents of --50 to 100 nA the increase in latent period as the tip of the electrode is placed further and further away from this level can be quantitatively accounted for by the time taken for penicillin to diffuse and to reach a threshold concentration throughout a critical mass of tissue at the 0.7 mm level. With these low currents, the generators of the interictal spikes are confined to a band of cortex centred at the 0.7 mm level. This is true even when the penicillin is applied away from the sensitive layer; in this circumstance the duration of electrophoresis needed to evoke interictal spikes is greater but when they do eventually appear the spikes are generated at the 0.7 mm layer. Histologically, the sensitive layer has been identified as the deep part of layer III. So far as the generation of interictal spikes is concerned, there is no evidence that, with low electrophoretic currents, penicillin has effects other than at the deep part of layer III; all the available evidence indicates that the penicillin has to diffuse to this layer and produces its effects there.
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10,003,979
Behavioral correlates of sexual differentiation in the zebra finch song system.
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10,003,980
The capacity for song is masculinized in female zebra finches by exposure to 17 beta-estradiol at hatching, and requires continual exposure to androgen for its behavioral expression in the adult. The stereotypy of the song developed by estrogenized females can be as good as that of male song. The sexual dimorphism in behavioral capacity for song parallels morphological sex differences in the efferent motor pathway which participates in the production of song. Estradiol induces the cytoarchitectonic masculinization of the telencephalic nuclei within the motor system for song, and renders them able to respond morphologically when song is induced in estrogenized females by exposure to androgen as adults.
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10,003,981
Electrophysiological evidence for the topographical arrangement of taste and tactile neurons in the facial lobe of the channel catfish.
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10,003,982
Neural responses in the facial lobe of th channel catfish to chemical and mechanical stimulation of the external skin surface were studied electrophysiologically. Taste and tactile neurons in the lobe were organized in a somatotopic manner, which confirms the anatomical reports of the facial lobe in the bullhead catfish, but is markedly different from that of the Cyprinidae. The taste neurons were arranged generally in the more dorsal regions of the tactile sensitive areas and responded with highest frequency to L-alanine or L-arginine HCI among several amino acids tested. The mechanically responsive neurons in the deeper layer of the antero-medial portion of the lobe, possibly corresponding to the intermediate nucleus of the facial lobe, had large receptive fields ranging from 100 mm to the whole body surface; in addition, some of these neurons showed lateral inhibition. The present study revealed that the facial lobe of the channel catfish is a center not only for gustatory input, but also for tactile information.
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10,003,983
The termination of geniculocortical fibres in area 17 of the visual cortex in the macaque monkey.
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10,003,984
The termination of geniculocortical fibres within the different subdivisions of lamina IV in area 17 of the visual cortex of the monkey has been studied quantitatively with the electron microscope. In lamina IVC alpha the axon terminals of fibres coming from the magnocellular layers of the lateral geniculate nucleus (LGN) make significantly more synapses per bouton than those of fibres arising from the parvocellular layers and terminating in laminae IVA and IVC beta. In all parts of area 17 examined there was a clear difference in the relative proportions of multisynaptic geniculocortical boutons between the alpha and beta divisions of lamina IVC. Calculations have shown that a single cell in the magnocellular laminae of the LGN may make about 6 times as many synaptic contacts within lamina IV of the visual cortex than one in the parvocellular laminae. It has also been estimated that there are at least 500 million geniculocortical boutons, or 1200 million synapses, in lamina IVC alpha and 100 million boutons, 1200 million synapses, in lamina IVC beta for one hemisphere, giving an approximate total number of 1500 million boutons and 2400 million synapses.
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10,003,985
Physiological properties of expanded ipsilateral retinocollicular projection in neonatally enucleated albino rats.
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10,003,986
The olfactory bulb mitral cell responses in the gecko as studied by intracellular recording.
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10,003,987
The mitral cell odor-induced intracellular responses and the accompanying membrane resistance changes were studied in the gecko olfactory bulb. The mitral cells responded to odor either with depolarization or with hyperpolarization. The depolarization responses with hyperpolarization. The depolarization responses were accompanied by a resistance decrease. The hyperpolarization responses were accompanied by a resistance increase. The responses were enhanced by hyperpolarization and suppressed by depolarization of the membrane current. Two types of mitral cells were identified by procion yellow dye injection.
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10,003,988
Reticular neuron activities associated with locomotion in thalamic cats.
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10,003,989
Unit discharges of the reticular neurons and EMGs of extensors and flexors were recorded in the 4 limbs of thalamic cats during stepping on a motor-driven treadmill to study the functional role of the spino-bulbo-spinal (SBS) reflex in locomotion. (1) Reticular neurons showed alterations of increased or decreased discharge rate depending on the phase of the step cycle; they were divided into input (ascending), output (reticulospinal, R-S) and internuncial neurons underlying the SBS reflex. (2) R-S neurons showed increased spikes from the end o the stance to the beginning of the swing phase; in this period, flexor muscle EMGS were obtained. The spikes decreased or disappeared when extensor EMGs were observed. To analyze the relationship between activity in R-S neurons and flexor muscles, R-S neuron spikes were used for triggering and post-spike EMGs were averaged. Averaged EMGs of the correlated flexor revealed a 12 and 6 ms latency for hind- and forelimbs, respectively. Most R-S neurons elicited EMGs of flexor in muscles of one ipsilateral leg, some elicited flexor EMGs of both the ipsilateral fore-and hindlimbs. (3) Input neurons of the reticular formation from spinal ascending tracts fired spikes upon touching of the skin over the correlated limb. During stepping, they showed two types of response patterns: a burst discharge appeared for the leg which was swinging and touching the belt, the other pattern was of continuous discharges at the end of stance and at the beginning of swing phases. (4) Internuncial neurons which relay impulses between the input and output neurons also showed alternate firings depending on the phase of the step cycle. Spikes could be elicited by touching the skin over the 4 limbs. (5) The relationship among the activities of the 3 groups of reticular neurons was analyzed by the post- or pre-spike averaging technique and appropriate latency responses were obtained. (6) The results indicate that flexor EMGs were excited by cutaneous afferents via the SBS reflex in cats stepping on the treadmill. The role of the SBS reflex in locomotion is discussed.
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10,003,990
Estrogen receptors in the turtle brain.
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10,003,991
Estrogen binding activity in the CNS of the freshwater turtle, Chrysemys picta, was investigated using DNA-cellulose affinity chromatography. An estrogen binding component (EBC) with the characteristics of an estrogen receptor species was demonstrated in the brain cytosol extracts from both sexes. This EBC exhibited high affinity (K d = 10 -10 M), low capacity (n = 0.8 to 6.0 fmol/mg cytosol protein) and binding specificity. The bound estradiol-17 beta which adhered to DNA-cellulose was sensitive to excess synthetic and natural estrogens (DES, E2, E1 and E3) but not to progesterone and androgens (5 alpha- DHT and T). Specific estradiol-17 beta binding was not detected in plasma or non-target tissues such as lung, kidney and muscle. The topographic distribution of cytoplasmic EBC was similar in males and females, with binding highest in the hypothalamus-preoptic areas (HPOA) followed by the remaining forebrain (RFB). The mid/hindbrain (HB), consisting of the optic lobes, cerebellum and underlying brain stem had significantly lower concentrations of EBC. Monthly data (from May to October) suggest that variations in EBC concentrations occur during the year.
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10,003,992
Somatotopic organization of SI corticotectal projections in rats.
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10,003,993
The somatotopic organization of somatosensory (SI) cortical projections to the deep layers of the superior colliculus (SC) in rats was examined using neurophysiological micromapping methods. Electrical stimulation of SI produced SC unit responses at the same depths as did peripheral tactile stimulation, in SC laminae IV and VI; mapping of corticotectal projections was performed only in lamina IV. Antidromic activation of the pathway revealed that corticotectal cell bodies are located in SI layer V. Corticotectal projections were found to interconnect only those SI and collicular areas which have similar tactile receptive fields.
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10,003,994
Spatial properties of nociceptor sensitization following heat injury of the skin.
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10,003,995
A brief noxious heat stimulus applied to half of the receptive field of each cutaneous nociceptor resulted in most cases in the enhanced responsiveness of that half to subsequent heat stimuli (sensitization). No change in responsiveness to heat was observed in the other half of the receptive field, indicating that the effects of heat sensitization did not spread from the site of injury. In certain instances, the receptive field area increased, but the enlargement occurred only within the area of injury. The latter suggests the existence of outlying terminal endings of the parent axon that are normally unresponsive to non-injurious mechanical or heat stimuli but become responsive to these stimuli following injury.
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10,003,996
Functional properties of area 19 as compared to area 17 of the cat.
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10,003,997
Out of a total of 139 area 19 cells, 87 were examined quantitatively for their responses to stimuli moving at a wide range of velocities. The results were compared with those obtained on a sample of 106 area 17 cells (out of a total of 172) tested in the same way. It was found that both areas 19 and 17 prefer slow stimulus movement. However, area 17 responded well to velocities up to 4 degrees/s while response amplitudes of area 19 cells started to decrease for stimulus velocities over 0.3 degrees/s. In both areas, responsiveness to fast stimuli improved at higher eccentricities. The most frequently encountered velocity type in area 19 was the 'velocity broad band' (VBB) type, lacking velocity preference, while the rarest type was the 'velocity tuned' (VT) type. As in area 17 very few area 19 cells were found to prefer high velocities (velocity high pass type, VHP) and those that were encountered had peripheral receptive fields (RFs). Cells preferring exclusively low velocities (velocity low pass type, VLP) were less frequent in area 19 than in area 17 and were considerably more sluggish. Area 19 was also less direction and orientation selective than area 17. In contrast, end-stopping was very common in area 19 (66%) and more units were binocular as compared to area 17. On average firing rate during optimal stimulation was lower in area 19 than in area 17. These results are consistent with the notion that area 19 receives predominantly W-type input and is involved in form discrimination (low spatial frequencies) during fixation.
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10,003,998
Receptive field structure of area 19 as compared to area 17 of the cat.
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10,003,999
A total of 139 cells from area 19 along with a comparison sample of 172 cells from area 17 were classified using a system proposed by Orban and Kennedy, following Henry and consisting of 4 basic cell 'families', namely S, C, A and B, each having an end-stopped member: HS, HC, HA and HB. The two basic parameters separating the 4 families are firstly spatial overlap of ON and OFF subregions and secondly receptive field (RF) width. Spatial overlap was studied quantitatively in a number of these cells using multiple presentations of stationary slits or moving light and dark edges. RF width was determined quantitatively using bars moving at different velocities across the RF. It was found that cells with spatially nonoverlapping and overlapping subregions are present in both areas. S and HS cells, which show similarities with simple cells, were encountered in area 19 but they constituted only 18% of the population as opposed to 55% in area 17. C and HC cells, reminiscent of complex cells, were about as common in area 19 as in area 17. In both areas C cells were the only group which consistently discharged equally well or better in response to diffuse light turned on and off than when presented with light bars. A and B families formed a minority in both areas. Area 19 contained a larger proportion of nonoriented and undriveable units, as well as a special category of cells preferring stimuli with a width larger than the length ('rectangle cells'). RF width was generally larger in area 19 than in area 17 and its distribution in area 19 showed distinct peaks. In the part of area 19 subserving central vision these peaks appeared with a periodicity of 0.8 degrees, suggesting that cells in this zone are supplied by one or more rows of a uniform set of afferents having a RF center diameter of about 0.8 degrees. The identification of this population as W-relay cells is supported by the long latencies found in cells from this part of area 19. It is concluded that basic principles underlying the structure of the RF are similar in both areas 19 and 17.
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