Search PubMed⌕ Search

Biomedical subjects

C B Smith

Publications and source records attributed to C B Smith.

At least 217 records · Page 12Linked to original sources

Androgen receptors in the prostate of the Rhesus monkey.

The presence of an androgen receptor protein in the supernatant preparation of the prostate from Rhesus monkey (macaca mulatta) is described. The molecular weight of this receptor protein was found to be 2.8 - 2.9 X 10(5) daltons. The levels of free and bound androgen receptors were measured in the caudal and cranial lobes of the prostate by an exchange assay using methyltrienolone (R1881). The concentration of the free binding sites in the caudal lobe ranged between 3.7 - 23.7 fmol/mg proteial binding sites in the caudal lobe ranged between 36.0 - 112.7 and in the cranial between 21.2 - 55.0 fmol/mg. The bound receptor ranged between 43.3 - 109.0 and 19.1 - 47.3 fmol/mg protein for caudal and cranial lobes respectively. The level of both bound and free receptors was found to be significantly higher in the caudal lobe. This data suggests that the two lobes of the prostate in the Rhesus monkey can be equated with the two zones of the human prostate in respect of androgen responsiveness.

Animals↗

Identification of an androgen receptor in the cytosol of the female Mastomys prostate.

An in vivo and in vitro study was carried out on the prostate from the female Praomys (Mastomys) natalensis to identify and characterize the binding of androgens within the cytoplasm. The labelled cytosol was prepared and subjected to gel exclusion chromatography and density gradient centrifugation. A macromolecular protein associated with the radioactivity was isolated on Sephadex G-200. Subsequent analysis of the steroid receptor complex showed that the major part of the radioactive steroid (64 percent) was dihydrotestosterone. This binding was inhibited by unlabelled testosterone and could not be demonstrated in liver cytosol. Characterization of this dihydrotestosterone receptor complex revealed a sedimentation coefficient of 4.6 s in the presence of a high salt solution (0.4 M KCl). The complex aggregated in the absence of 0.4 M KCl and sedimented preferentially from 5.6-7.4 s together with polydisperse aggregates of higher sedimentation coefficients. The use of this animal as an experimental model for hormonal studies on the prostate is suggested.

Animals↗

The effect of antiandrogens and stilboestrol on the cytosol receptor in rat prostate.

The effects of 4 antiandrogens and stilboestrol on the cytosol receptor of the rat ventral prostate have been compared. Equimolar doses of cyproterone acetate, chlormadinone acetate, SC 9022 and flutamide inhibited the binding of dihydrotestosterone to the receptor complex in vivo by 44 to 50% whereas stilboestrol had no effect. In the in vitro studies an equimolar concentration produced similar effects to those observed in vivo with the exception of flutamide which had no effect. This technique provides a method for assessing and comparing the effectiveness of antiandrogens on the androgen receptor complex of the prostate.

Androgen Antagonists↗

Differential androgen uptake by the lobes of the rhesus monkey prostate.

The prostate of the rhesus monkey (Mucacca mulatta) consists of a cranial and a caudal lobe. The uptake of [3H] testosterone by these 2 lobes has been measured and compared with control tissues. A significantly higher uptake of radioactivity was found in the caudal lobe when compared to cranial as well as other control tissues. The uptake of radioactivity by the caudal and cranial lobes was suppressed when unlabelled testosterone was introduced into the incubation media. The relationship between these 2 lobes of the monkey prostate and the central and peripheral zones of the human prostate is described.

Animals↗

Norepinephrine release in isolated arteries induced by K-free solution.

Helical strips from arteries with a rich sympathetic innervation (rat tail and femoral, and dog mesenteric arteries) develop a sustained contracture when exposed to a K-free physiological salt solution (PSS). The contracture can be blocked by phentolamine and does not occur in arteries whose nerve terminals have been destroyed with 6-hydroxydopamine. The temporal relationship between force development and efflux of NE was determined. Helical strips of rat tail arteries or dog mesenteric arteries were incubated in PSS containing 1-norepinephrine-7-3H([3H]NE). They were then transferred to a superfusion system which allowed isometric recordings and collection of the superfusate for the estimation of [3H]NE content. Following exposure to a K-free PSS force development paralleled NE release and both parameters were potentiated by ouabain. These data demonstrate that this neurogenic mechanism plays a most important role in the K-free contracture of the vascular smooth muscle studied. It is in accord with the observation that NE is released by adrenergic nerves following inhibition of Na+-K+-ATPase.

Animals↗

Effect of cocaine and desmethylimipramine on the uptake, retention and metabolism of 3H-5-hydroxytryptamine in rat brain slices.

Uptake and metabolism of 3H-5-dydroxytryptamine (3H-5-HT) in slices of hypothalamus, brain stem caudate nucleus and parietal cortex were examined in vitro. The results indicate that 3H-5-HT taken up by neurons is firmly retained and that there are regional differences in the uptake and retention of 3H-5-HT. For example, the caudate had a significantly greater maximum rate of uptake and binding (Vmax) than the other brain areas tested, particularly the cortex. In contrast the caudate appeared to have the lowest apparent for 3H-5-HT uptake (Km). Uptake and retention of 3H-5-HT by four brain areas were markedly inhibited by cocaine and desmethylimipramine (DMI) in vitro. The inhibitory effect of both drugs was noncompetitive in nature, with exception of thct that cocaine and DMI failed to reduce the formation of 3H-5-hydroxy-indoleacetic acid despite ther potent blocking action of 3H-5-HT uptake suggests that a significant amount of 3H-5-HT is oxidatively deaminated at extraneouronal sites. This extraneuronal metabolism of 5-hydroxytryptamine may play an play an important role in regulating the action of this neurotransmitter.

Animals↗

Mechanism of potassium relaxation of arterial muscle.

Strips of arterial muscle were prepared from rat tail and femoral arteries and dog mesenteric arteries. All muscles developed a contracture slowly when exposed to a potassium-free solution, but relaxed rapidly when potassium was added to the bath to give a concentration as low as 0.1 mM. The slow contracture is caused by norepinephrine release from intrinsic nerve endings, but the rapid relaxation occurs while the norepinephrine concentration is still high. Contractions produced by exogenous norepinephrine or serotonin in a potassium-free bath were also made to relax by the addition of potassium. After several minutes these relaxations reversed abruptly and spontaneously to return to their original level of contraction. The rapid relaxation was found to be due to an electrogenic transport mechanism which caused hyperpolarization within several seconds after the addition of potassium. This hyperpolarization is believed to be caused by electrogenic ion transport since it exceeded the expected membrane potential based on the potential calculated from potassium concentrations, EK. Hyperpolarization declined within 5-15 min, allowing contraction to redevelop. Ouabain was found to prevent both the potassium-induced relaxation and the cessation of norepinephrine release. However, ouabain prevented relaxation as effectively in denervated as in innervated smooth muscle. We conclude that the initial relaxation of arterial smooth muscle that occurs when potassium is reintroduced into a potassium-free solution is caused by membrane hyperpolarization resulting from the enhanced activity of an electrogenic pump; it is not caused by cessation of norepinephrine release.

Animals↗

An X-ray diffraction investigation of age-related changes in the crystal structure of bone apatite.

Evidence relating to the existence of crystalline bone mineral in vivo is considered, and bone apatite crystal structure investigated using an x-ray powder diffraction technique. Specimens of femoral compacta excised post-mortem from male and female subjects ranging from 3 1/2 years to 87 years of age have been studied. Values of the ratio c/a of bone apatite crystal cell axes for females are significantly higher (p less than 0.05) than for males. Moreover, significant change of c/a with age is observed for males (p = 0.0005) but not for females (p = 0.30). Differences in c/a are interpreted as indicating substitution of constituent ions in the bone apatite crystals.

Adolescent↗

Infection control in small hospitals. Prevalence surveys in 18 institutions.

In prevalance surveys of 18 small hospitals in the intermountain region, 20.4% of the patients had community-acquired infections and 7.2% had infections acquired in the hospital. The types of nosocomial infections and patterns of antibiotic usage were similar to those encountered in large hospitals. In the small hospitals, 49% of the suspected bacterial infection were cultured, whereas at a nearby large hospital 77% were cultured. Seventeen of these small hospitals had an infection-control committee but these committees were unable to assess adequately the extent of their nosocomial infection problems. Monitoring of the environment with bacterial cultures was a frequent practice; overall, a ratio of one environmental culture was performed to each three diagnostic cultures. These results indicate the need to develop and evaluate nosocomial infection control programs in small hospitals.

Anti-Bacterial Agents↗

Haemophilus influenzae and haemophilus parainfluenzae in chronic obstructive pulmonary disease.

The importance of nonencapsulated strains of Haemophilus influenzae and H. parainfluenzae in the pathogenesis of chronic obstructive pulmonary disease (C.O.P.D.) has been investigated in 150 patients observed at two-month intervals from 1968 to 1975. H. influenzae was distinguished from H. parainfluenzae by demonstrating requirements for both X and V factors. H. influenzae was isolated more often from sputum cultures from patients with severe C.O.P.D. (13.8%) than from patients with mild disease (4.4%, P less than 0.01). In contrast, H. parainfluenzae was isolated with equal frequency from sputums of patients with mild (40%) or severe (43%) disease. H. influenzae was present in the sputum more often during exacerbations of acute respiratory illness (15.4%) than during sympton-free periods (9.6%, P less than 0.01), while isolation rates of H. parainfluenzae did not increase during periods of illness (35% versus 39%). Antigens specific for the H. influenzae species and for the H. parainfluenzae species were used in a complement-fixation test to detect antibody rises in sera collected from the patient population. Fourfold or greater rises in titre of antibodies to H. influenzae were detected on 76 occasions in 53 patients, and 46 of these rises were associated with acute respiratory illnesses. In contrast, no antibody rises were detected with the H. parainfluenzae antigen. These observations indicate that nonencapsulated strains of H. influenzae may have pathogenic potential in patients with C.O.P.D., whilst H. parainfluenzae should be considered as normal flora.

Antibodies, Bacterial↗

Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies.

Fifty-six brains from middle-aged and elderly normal as well as demented subjects and patients with provisional clinical diagnosis of other neurological and psychiatric diseases were assessed histologically. On this basis the specimens were classified into 14 diagnostic groups. A survey of potential indices of specific neurons has been carried out on these brains in which neurotransmitter-related enzymes, gamma-GTP (a potential index of capillaries) and specific proteins have been determined in up to 20 brain regions. In addition, the agonal state has been tentatively assessed by examining the post-mortem states of the circulatory and respiratory systems. CAT and gamma-GTP activities and the concentration of a soluble neuronal-type protein (neuronin S-5) were found to be relatively unaffected by the agonal state. When cases of senile dementia were compared to controls (matched with respect to the cause of death) the activity of CAT (the potential index of cholinergic neurons) appears to be reduced in the cerebral cortex. This is a preliminary finding, although a correlation was indicated between CAT activity and 'senile' morphological changes, the activity was markedly reduced in only 3 brains. However, despite inconsistencies in the literature (Karczmar, 1975) at least one pharmacological study on humans appears to show that the cholinergic system may be involved in age-related memory degeneration (Drachman and Leavitt, 1974). Cholinergic neurons may be abnormal in the other abiotrophies examined (Huntington's chorea, motor neuron disease and mixed vascular and senile dementia). gamma-GTP and neuronin S-5 (identical in most respects to the soluble acidic neuronal protein 14-3-2 of antigen alpha) were not reduced in senile dementia. The activities of brain decarboxylase (GAD and AAD) and the concentration of another soluble acidic brain protein (neuronin S-6) appear to be affected by the agonal state. This is remarkable because GAD and, in particular, neuronin S6, are relatively unaffected by post-mortem autolysis. As judged by the state of the extraneural systems which regulated the blood and oxygen supply to the brain it appears that terminal 'cerebral hypoxia' is responsible for the depletion of these brain constituents. This effect appears to be particularly marked in deep grey matter. In non-demented patients that die of bronchopneumonia, the areas of the cortex which are depleted in neuronin S-6 are consistent with the pattern of the 'selective vulnerability' of the cortex to hypoxia, suggesting that the terminal state can also affect the neocortex. If so, then this is particularly relevant to studies on senile dementia, for the effect of the terminal bronchopneumonia that so often occurs in these patients (and in patients with other abiotrophies) may be exacerbated by a terminal reduction in cerebral blood flow...

Adult↗

Interactions between viruses and bacteria in patients with chronic bronchitis.

The possibility that viral infections of the respiratory tract might predispose to bacterial colonization or infection was studied in 120 patients with chronic obstructive pulmonary disease and 30 control subjects; these individuals were observed for seven years. The ratio of the number of observed to the number of expected associations between viruses and bacteria was 2.43 (P = 0.037) for the pair influenza virus and Streptococcus pneumoniae and was 2.06 (P = 0.056) for influenza virus and Haemophilus influenzae. Consistently positive, but not significant, associations were detected between rhinovirus and herpes simplex virus infections and isolations of S. pneumoniae and H. influenzae. In contrast, isolations of the nonpathogenic Haemophilus parainfluenzae could not be related to prior viral infections. Significant rises in titer of antibody to H. influenzae were detected on 76 occasions, and 20 (26%) of these antibody rises were associated with viral or mycoplasmal infections during the preceding 120 days. The expected number of such associations was 8.34 (ratio of number observed to number expected, 2.40; P = 0.08). These results suggest that viral infections of the respiratory tract in patients with chronic obstructive pulmonary disease are associated with increased colonization by potentially pathogenic bacteria and may also predispose to infections with H. influenzae.

Antibodies, Bacterial↗

Cytotoxic activity of rheumatoid and normal lymphocytes against allogeneic and autologous synovial cells in vitro.

The possibility that lymphocytes from patients with rheumatoid arthritis (RA) might be sensitized to RA synovial cell antigens was investigated with a 51Cr release cytotoxicity assay. Peripheral blood lymphocytes from rheumatoid and normal donors were tested for cytotoxic activity against their own synovial cells and against allogeneic rheumatoid and nonrhemuatoid synovial cells. In the allogeneic studies, the degree of cytotoxicity was significantly influenced by the age in culture (passage number) of the synovial target cells (P less than 0.001). When the passage number of the target cells was considered in the analysis, rheumatoid lymphocytes were found to have greater cytotoxic activity than normal lymphocytes against young cultures (low passage number) of both RA and non-RA synovial cells (P = 0.0042). Differences in susceptibility to lysis between RA and non-RA synovial cells were more susceptible to both RA and normal lymphocyte-induced lysis than were non-RA synovial cells (P = 0.0048). No evidence of cytotoxicity was detected when lymphocytes from nine RA patients and two osteoarthritis patients were reacted against their own synovial cells. Although the data demonstrated an increased cytotoxic activity of peripheral blood lymphocytes from some RA patients against allogeneic synovial cells, the fact that this reactivity was seen against both non-RA and RA synovial cells and was not demonstrated against autologous synovial cells argues against the presence of an immunospecific response of RA lymphocytes to RA synovial cell antigens.

Adult↗