An experiment in patient-physician communication.
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Biomedical subjects
Publications and source records attributed to R Singh.
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Angiotensin II (Ang II) was infused into a lateral cerebral ventricle of male Sprague-Dawley rats and its effects on blood pressure, water balance and specific [125I]Ang II binding to brain and adrenal tissues were studied. The infusion was maintained at a rate of 500 ng/microliter/h for 6 days using subcutaneously implanted osmotic minipumps. A control group was infused intracerebroventricularly (i.c.v.) with 0.9% saline at a rate of 1 microliter/h for 6 days. Angiotensin II treated rats showed a four-fold increase in water intake and urine volume and a moderate increase in blood pressure; these effects were not observed in rats given saline i.c.v. There was no significant difference in [125I]Ang II binding site density or binding affinity in either the hypothalamus-thalamus-septum-midbrain (HTSM) or the brainstem between Ang II-treated and saline-treated groups. In addition, [125I]Ang II binding sites in the adrenals were also unaffected by i.c.v. infusion of Ang II. The results suggest that brain Ang II receptors are unresponsive to increased Ang II levels in cerebrospinal fluid.
Several carrier systems and targeting agents have been considered as means of delivering enzymes and drugs to specific tissues or cells. In this report insulin is shown to be effective in delivering enzyme-albumin conjugates to cells and tissues rich in insulin receptors. The complex is transported into cells by a process that resembles receptor-mediated endocytosis and can be identified in a lysosomal fraction. The enzyme-albumin-insulin complex retains its enzymatic activity and its ability to bind antibodies to insulin. It also has a hypoglycemic effect; however, plasma glucose concentrations can be maintained by glucose administration.
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Since the extent of in vitro experiments with human pituitary adenoma cells is often limited by the small number of cells isolated from surgical specimens, ways to obtain more cells are of interest. In this study we made use of tumor tissue removed by aspiration through a suction tube during transsphenoidal surgery. Fifteen out of 28 adenomas could be dispersed without enzymatic treatment. The other 13 adenomas were mildly treated with Dispase. The large number of red blood cells present in the suction tube were removed by Ficoll-Isopaque density centrifugation. More than 90% of the adenoma cells were recovered from the interphase fraction. This material, in contrast with fragments obtained with a forceps, yielded 35.9 (+/-9.0) X 10(6) cells (mean +/- SE, n = 28). Usually less than 10% of these cells were mononuclear leucocytes. Pituitary hormones other than those hypersecreted in vivo were not found in the incubation media; only small amounts of LH were found in 5 out of 25 adenomas. A linear relationship was found between cell concentration and hormone secretion, both for PRL and GH. In vitro hormone secretion by the adenoma cells was in good agreement with in vivo dynamic tests. In longterm culture, GH and ACTH secretion by the adenoma cells declined, while PRL secretion was fairly constant. It is concluded that large numbers of dispersed pituitary adenoma cells can be obtained from the material removed by suction during transsphenoidal operation.(ABSTRACT TRUNCATED AT 250 WORDS)
In this work, the effect of chronic intraperitoneal administration of chlorpromazine (5 and 10 mg/kg) on the antioxidant enzymes superoxide dismutase (SOD), catalase (CA), glutathione reductase (GR), and glutathione peroxidase (GP); lipid peroxidation; and lipofuscin accumulation in the brains of rats ages 6, 9, and 12 months was studied. Chlorpromazine increased the activities of SOD, GR, and GP in particulate fraction from cerebrum, cerebellum, and brain stem in a dose-dependent manner. While GR and SOD associated with soluble fraction increased, GP associated with soluble fraction was not affected. CA did not change after chlorpromazine administration in any regions of the brain of rats from all age groups. Chlorpromazine, thus, had a somewhat different action on antioxidant enzymes in different subcellular fractions. Chlorpromazine inhibited lipid peroxidation, both in vivo and in vitro, and it also inhibited accumulation of lipid peroxidation fluorescent products (lipofuscin), which was studied histochemically and biochemically as well. The data indicate that chlorpromazine inhibition of lipid peroxidation and of accumulation of lipofuscin can result from elevation of the activity of brain antioxidant enzymes.
Male Sprague-Dawley rats were maintained on either a normal or low-sodium diet for 5 weeks to examine whether dietary sodium restriction alters angiotensin II (Ang II) receptors. The receptor sites in the hypothalamus-thalamus-septum (H-T-S) region of the brain, the adrenal glands and bladder visceral smooth muscle were measured by saturation isotherm binding assays using 125I-Ang II. Compared to control rats, the low-sodium diet group showed a smaller weight gain, reduced water intake, elevated hematocrit, and decreased urinary sodium concentration. In addition, sodium-depleted rats had a 10-fold elevation in plasma renin activity. However, neither binding affinity of 125I-Ang II to the brain H-T-S region nor its density was significantly different between the two groups. In contrast, both the 125I-Ang II binding density and dissociation constant in the adrenal gland were significantly elevated, while the binding density of 125-I-Ang II in the bladder smooth muscle was significantly decreased in the sodium-restricted group. These results suggest that dietary sodium depletion does not alter Ang II receptors in the rat brain areas wherein Ang II exerts the majority of its central actions.
Biopsy and/or autopsy material from lymphoreticular and other organs was studied in 8 children with suspected acquired immune deficiency syndrome (AIDS). One or both parents of each of these children had one or more of the recognized risk factors for AIDS, such as intravenous drug abuse, prostitution, Haitian origin. The following histologic patterns were noted in the lymph nodes: (1) follicular hyperplasia with normocellular paracortex, (2) follicular hyperplasia with depletion of paracortex, and (3) atrophy of follicles with depletion of paracortex. Lymphoid interstitial pneumonitis (LIP), a previously unreported lesion in AIDS, was present in 4 cases. It is suggested that the pulmonary lymphoid lesion may be part of a more generalized lymphoid hyperplasia involving B cells. The gross and microscopic features of the thymus, available in 2 of the 8 cases, indicated that the immunologic defect in these children was not of congenital type. Pathologic findings can be helpful in the diagnosis of the syndrome when correlated with clinical and immunologic features of suspected cases and of the pulmonary lesion. The latter is of importance in deciding the type of therapy to be given for the pulmonary disease process.
The long term (90 days) effects of medroxyprogesterone acetate (MPA) administration on the digestive and absorptive functions of the small gut have been investigated in female albino rats. The uptake of glucose and amino acids was found to be significantly increased while Ca++ uptake decreased following MPA treatment (35 mg/kg body weight). The observed increase in glucose uptake might be due to carrier mediated transport in enterocytes and not to a change in cell number. The Michaelis constant for glucose uptake was not altered by MPA. Activities of brush border membrane disaccharidases, leucine aminopeptidase and basolateral membrane enzyme Na+, K+-ATPase were significantly increased in response to MPA treatment. It was observed that these biochemical alterations caused by MPA in intestinal digestive and absorptive functions were reversible by 5 weeks after termination of the drug treatment. The action of the drug appears to closely resemble that of known effects of glucocorticoids on intestinal mucosa.
Effect of Medroxyprogesterone acetate (MPA) at a dose level of 35mg/Kg body weight per week for four weeks on the intestinal uptake of nutrients viz glucose, amino acids, (alanine and leucine), calcium and zinc has been investigated in protein-deficient female rats. The administration of MPA was found to enhance significantly the uptake of glucose and amino acids in both the pair-fed and the protein-deficient rats. In contrast, calcium uptake was depressed as a result of treatment with the drug as well as protein-deficiency. The uptake of zinc was not affected on drug administration. This steroidal contraceptive caused elevation in sodium-dependent glucose uptake, while the sodium-independent uptake remained unaltered. The kinetic parameters of glucose and leucine uptake indicate that MPA might be inducing the transport carrier protein of these nutrients as elevation in Vmax of these nutrients transport system was observed following its administration.
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GABA-transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSA-DH) activities were measured in the mitochondrial fractions from the cobalt- and FeCl3-induced chronic epileptogenic foci in the rat brain. Electroencephalographically, the FeCl3 epileptogenic focus remained active for a duration longer than that of the cobalt focus. In both the foci SSA-DH activity showed significant increases which were concomitant with the EEG epileptiform activity. In cobalt focus, the GABA-T activity fell whereas, in the FeCl3 focus it was unchanged. In cobalt focus fall in GABA-T activity seemed to be concomitant with EEG epileptiform discharge. The measurements of the enzyme activities in the mirror (secondary) foci showed that, except for a brief stimulation of SSA-DH activity in the mirror focus in FeCl3 epileptic animals, the enzyme activities remained unchanged. Possible significance of the observed enzymatic changes in the physiology of epileptogenic focus is discussed.
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The akinesia of the superior rectus muscle after retrobulbar administration of lidocaine was quantitatively compared to the akinesia after retrobulbar administration of a mixture of lidocaine and pancuronium bromide. Adult cats were given halothane general anesthesia and a limited orbitotomy was performed to facilitate exposure of the superior rectus muscle and its branch of the superior division of the oculomotor nerve. The superior rectus muscle was disinserted and connected to a myograph. A suprathreshold stimulus of 3 volts was then applied to the branch of the oculomotor nerve innervating the superior rectus muscle. The strength, measured in grams, of the superior rectus muscle contraction was then quantitated with the myograph. Subsequently, retrobulbar administration of the drug was given and at 10 minute intervals thereafter the suprathreshold electrical stimulus of 3 volts was reapplied to the nerve innervating the superior rectus muscle, and the strength of the contraction was recorded with the myograph. Retrobulbar administration of 0.5 cc of 2% lidocaine was compared with retrobulbar administration of a mixture of 0.5 cc of lidocaine 2% and 0.2 mg of pancuronium bromide at a dosage of 0.04 mg per kilogram. For the first 30 minutes of the experiment, each retrobulbar administration provided profound akinesia with a total absence of measurable muscular contraction, despite suprathreshold stimulation of the nerve. From 40 to 120 minutes following the retrobulbar administration, the combination of lidocaine 2% and pancuronium bromide was associated with persistent absence of measurable superior rectus contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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Hemagglutination and lytic infection of host cells by polyoma virus has been shown to require specific sialyloligosaccharide structures. The nature of the sialyloligosaccharide sequence recognized by three binding variants of polyoma virus, the large plaque (LP), small plaque (SP), and Py235 variants, was examined. Hemagglutination of native erythrocytes and erythrocytes derivatized with highly specific sialyltransferases to contain cell surface sialyloligosaccharides of defined sequence was compared for the three variants. In addition, soluble glycoprotein inhibitors of known sialyloligosaccharide structure were used to further elucidate the specificities of the three variants. There are important differences in the receptors for these variants. While all three appear to bind the structure NeuAc alpha 2,3Gal beta 1,3GalNAc the LP and Py235 variant bind the disialyl structure NeuAc alpha 2,3Gal beta 1,3(NeuAc alpha 2,6)GalNAc with much lower affinity than does the SP virus. It is suggested that polyoma virus adsorption to cells may depend on the cell surface content of at least three different sialyloligosaccharide sequences and the relative abilities of the virus variant to utilize them as receptor determinants.