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Biomedical subjects

S R Patel

Publications and source records attributed to S R Patel.

At least 127 records · Page 7Linked to original sources

Calcium and vitamin D metabolism in spontaneously hypertensive rats.

We have studied the effect of dietary vitamin D restriction on serum levels of vitamin D metabolites in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Both WKY and SHR were fed a vitamin D-deficient or a vitamin D-supplemented diet beginning at 4 wk of age. In vitamin D-supplemented animals, the serum 1,25-dihydroxycholecalciferol [1,25(OH)2D3] concentration of WKY (55.4 +/- 6.6 pg/ml, n = 5) was similar to the level of SHR (46.3 +/- 5.9 pg/ml, n = 5). Plasma calcium concentration was not different between WKY and SHR. In animals fed a vitamin D-deficient diet, the serum concentration of 1,25-(OH)2D3 of SHR (23.0 +/- 1.3 pg/ml, n = 5) was significantly lower than that of WKY (67.6 +/- 4.6 pg/ml, n = 5, P less than 0.01). Plasma 25-hydroxycholecalciferol level was markedly decreased in both WKY (3.6 +/- 0.5 ng/ml, n = 7) and SHR (2.8 +/- 0.4 ng/ml). The SHR, but not the WKY, developed hypocalcemia (WKY, 9.68 mg/dl; SHR, 6.70 mg/dl). Despite hypocalcemia, fasting urinary Ca2+ excretion of SHR exceeded that of WKY. We conclude that the lower 1,25(OH)2D3 level in SHR fed a vitamin D-deficient diet may be due to a defect in the synthesis of 1,25(OH)2D3. The low level of 1,25(OH)2D3 is associated with renal wasting of calcium and hypocalcemia in SHR.

Animals↗

Immunochemical detection, physicochemical characterization and levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) in seminal plasma of men.

Pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the human uterine endometrium during the luteal phase of the menstrual cycle and early first trimester of pregnancy, has been detected by immunochemical techniques in seminal plasma. Biochemical analysis and immunoblotting has verified that immunoreactive alpha 2-PEG in seminal plasma exhibits properties identical to those of endometrial alpha 2-PEG, i.e. Concanavalin A-binding dimeric glycoprotein of native Mr 56,000, subunit Mr 28,000, average pI 4.7 and of alpha 2-mobility. Concentration of alpha 2-PEG in seminal plasma was 22.13 +/- 2.82 micrograms/ml (mean +/- s.e.m., n = 110) which compared to 12.02 +/- 1.65 micrograms/ml (mean +/- s.e.m., n = 48) found in amniotic fluid at 11-20 weeks of pregnancy, to 4.29 +/- 1.66 micrograms/ml (mean +/- s.e.m., n = 15) in uterine luminal fluid in women during the luteal phase and to 0.245 +/- 0.025 micrograms/ml (mean +/- s.e.m., n = 10) in sera at 10 weeks of pregnancy. This distribution is very different from that observed for pregnancy-associated placentally-derived serum proteins detected in seminal plasma. The source of alpha 2-PEG in seminal plasma is unknown but is unlikely to be the testis because of the normal levels observed in vasectomized men. In the endometrium alpha 2-PEG synthesis and secretion appears to be related to progesterone-dependent differentiation of the glandular epithelium. Therefore these observations suggest that a different mechanism of regulation of the gene for alpha 2-PEG operates in the male reproductive tract.

Chromatography↗

Amniotic fluid concentrations of secreted pregnancy-associated endometrial alpha 1- and alpha 2-globulins (alpha 1- and alpha 2-PEG).

The levels of pregnancy-associated endometrial alpha 1- and alpha 2-globulins (alpha 1- and alpha 2-PEG), the two major proteins synthesized and secreted by the endometrium in vitro, have been assayed in 210 amniotic fluid specimens obtained at termination of pregnancy or by amniocentesis, or at delivery. alpha 1-PEG was undetectable until week 10 and thereafter rose to peak levels between weeks 20 and 24. Levels fell 15-fold by week 35 but substantial amounts were still present at parturition. alpha 2-PEG was present at highest levels during early pregnancy, at weeks 6-15, but thereafter levels rapidly fell until during weeks 31-42 alpha 2-PEG was detectable in only 3 of 25 specimens. During weeks 15-20, when alpha 2-PEG levels fell and alpha 1-PEG levels rose, a high correlation was observed between the week of gestation and the log of the ratios of the concentration of these proteins. These observations provide the opportunity to assess the role of endometrial and decidual dysfunction in the aetiology of pregnancy disorders.

Amniotic Fluid↗

Protein synthesis and secretion by the human endometrium during the menstrual cycle and the effect of progesterone in vitro.

To identify markers of endometrial differentiation specimens of endometrium from the menstrual cycle were incubated in vitro with [35S]methionine, in the absence or presence of progesterone, and protein synthesis and secretion were studied by fluorographic analysis of one dimensional SDS/gradient polyacrylamide gels. Changes were demonstrated in the rate of synthesis and secretion of a number of endometrial proteins (EP) during the cycle and in response to progesterone. Endometrial proteins were classified into three groups: Group I-synthesized and secreted throughout the menstrual cycle and unaffected by progesterone exposure; Group II-synthesis and secretion associated with histological type of endometrium and unaffected by progesterone exposure, e.g. EP 13 (Mr 33,000) with proliferative, EP 15 (Mr 28,000) with secretory and EP 14 (Mr 32,000) with late secretory endometrium; Group III-synthesis and secretion regulated by progesterone exposure irrespective of source of endometrium, e.g. EP 9 (Mr 54,000) and 11 (Mr 45,000). The Group II proteins EP 14 and 15 were also the major secretory protein products of endometrium from first and second trimester pregnancy respectively, the native forms referred to as pregnancy-associated endometrial alpha 1- and alpha 2-globulins (alpha 1- and alpha 2-PEG). We conclude that EP 15 (alpha 2-PEG) represents a human analogue of uteroglobin.

Electrophoresis, Polyacrylamide Gel↗

Plasma 1,25(OH)2D3 response to parathyroid hormone, cyclic adenosine monophosphate, and phosphorus depletion in the spontaneously hypertensive rat.

Spontaneously hypertensive rats (SHR) have several abnormalities of calcium metabolism compared with normotensive control Wistar-Kyoto (WKY) rats. Previously the vitamin D metabolite 1,25-dihydroxycholecalciferol (1,25[OH]2D3) was found to be inappropriately low in SHR in view of their ionized hypocalcemia and hyperparathyroidism. We examined the responses of plasma 1,25(OH)2D3 to several known stimuli. Baseline plasma 1,25(OH)2D3 levels tended to be lower in SHR than WKY rats (51.5 +/- 4.3 vs. 82.3 +/- 14.1 pg/ml, P = 0.06). Infusion of a pharmacologic dose of parathyroid hormone (8 U/hr over a period of 17 hours) resulted in a plasma 1,25(OH)2D3 level of 504 +/- 77 pg/ml in SHR vs. 1016 +/- 211 pg/ml in WKY rats (P less than 0.03). Cyclic adenosine monophosphate infusion (1 mumol/hr/100 gm over a period of 17 hours) in thyroparathyroidectomized animals resulted in a 1,25(OH)2D3 level of 121 +/- 24 pg/ml in SHR vs. 557 +/- 26 pg/ml in WKY rats (P less than 0.01). After dietary phosphorus depletion for 3 weeks, SHR also had lower 1,25(OH)2D3 levels than WKY rats (83 +/- 13 vs. 300 +/- 42 pg/ml, P less than 0.001) even though a comparable degree of hypophosphatemia was achieved. Thus, the response of plasma 1,25(OH)2D3 levels to several known stimuli is submaximal in SHR as compared with WKY rats, suggesting defective synthesis or enhanced metabolic clearance of this hormone.

Animals↗

Investigation of the mechanism of decreased sensitivity of the rat seminal vesicle to norepinephrine by lithium.

Li+ is reported to reduce sensitivity of alpha-adrenergic receptors to NE. The present investigation was designed to investigate the mechanism of this decreased sensitivity on the rat isolated seminal vesicle. In innervated preparations, 1.35 X 10(-3) M Li+ (i) shifted the concentration-response curves of NE, methoxamine, ACh and BaCl2 to the right and reduced their maximum responses; (ii) antagonized the leftward shift and the enhancement of maximum responses to NE by cocaine (2.9 X 10(-4) M), and (iii) reduced only the maximum responses to KCl. In denervated preparations, 1.35 X 10 (-3) M Li+ shifted the concentration response curve of NE to the left without any change in the maximum responses. The antagonistic effects of Li+ on maximal responses to NE, ACh and KCl observed in innervated preparations were significantly increased in Ca++-free medium. Li+ (1.35 X 10(-3) M) increased NE uptake by the seminal vesicle significantly. It is concluded that decreased sensitivity of the seminal vesicle to NE by Li+ could be due to an increase in the uptake of NE and to a nonspecific postsynaptic spasmolytic action.

Acetylcholine↗

Simplified radioimmunoassay for triiodothyronine: evaluation of a new commercial kit.

A new triiodothyronine (T3) radioimmunoassay kit offers simplicity of method, short incubation time, specificity, and reproducibility. 125I-labeled T3 and unknown serum (or standard) are added to alkaline buffered (pH 12.4) Sephadex G-25 columns; the T3 is freed of proteins with an alkaline buffer wash, antiserum is added, and the columns are incubated at room temperature for 2 h. "Free" hormone (i.e., unbound to antiserum) remains on the column after a second wash. The radioactivity on the column is counted and related to the total activity added. The T3 standards produced a straight line on log-logit plot; reactivity of analytical-grade thyroxine was 0.6% on weight basis; and the analytical recovery of T3 added to a T3-free serum was complete. Euthroid, hyperthyroid, and hypothyroid ranges were 0.74-2.64, 2.91-7.52, and 0-1.21 mug/liter, respectively. These values correlated well with both the clinical status of patients and with values obtained by an established radioimmunoassay method. The procedure is simply done; results may be obtained in less than 4 h.

Cross Reactions↗

New chemotherapeutic strategies for soft tissue sarcomas.

Advanced soft-tissue sarcomas are still incurable in the vast majority of patients. The currently available standard methods of treatment such as surgery, radiation therapy, and chemotherapy have a very modest impact on the natural history of advanced soft tissue sarcomas. Nevertheless, until new strategies become widely available and applicable to this disease, we are obligated to optimize the current resources and make the best use of these modalities. We discuss the approaches of standard chemotherapy used in a dose-intensive fashion (especially in high-risk patients at an earlier stage), attempts to find new drugs with activity in this disease, and tests of the concepts of anti-angiogenic and differentiation therapy. To improve cure rates, patients and physicians must be encouraged to participate in multidisciplinary clinical trials.

Antineoplastic Agents↗

The c-wave of the electroretinogram recorded under clinical conditions from rabbits.

To determine whether large and repeatable c-waves can be recorded from rabbits with equipment already in use in clinical electroretinographic laboratories, the Burian-Allen electrode, connected bipolarly or monopolarly, was used to record electroretinograms from pigmented rabbits. The Jet electrode was also used. The c-waves elicited by long-duration (4-second) stimuli were compared to those elicited by stroboscopic stimuli. In addition, the c-waves recorded with direct-coupled amplification were compared to those recorded with condenser-coupled amplification (one-half-amplitude bandpass=0.1 Hz). The b-wave amplitude was not altered by the amplifier coupling or by the two stimulus durations. The largest c-waves were elicited by 4-second-duration stimuli and recorded with direct-coupled amplification. Although the c-wave amplitude was reduced by stroboscopic stimuli and by condenser coupling, large and repeatable c-waves were elicited by stroboscopic stimuli and recorded with condenser-coupled amplification. A comparison of stimulus duration and amplifier coupling showed that the stimulus duration was more important in recording large-amplitude c-waves. Similar results were obtained with the Jet electrode. We conclude that repeatable and large c-waves can be elicited by a stroboscopic stimuli and can be recorded with condenser-coupled amplification with good low-frequency response from rabbits.

Animals↗

The benzodiazepine receptor inverse agonist RO 15-3505 reverses recent memory deficits in aged mice.

The benzodiazepine receptor partial inverse agonist RO 15-3505 was tested for its ability to improve impaired recent memory of aged mice. All mice successfully acquired a learning set for accurate identification of the correct arm of a T-maze and could perform with nearly 100% accuracy after 1-min delays. However, performance of the aged mice approached chance levels after 2-h delays. When injected just before testing on a series of 2-h retention tests, RO 15-3505 (from 2.5-3505 (from 2.5-10.0 mg/kg) resulted in a marked improvement of response accuracy. These results confirm the role of benzodiazepine receptor mechanisms in the modulation of memory processes, and suggest that the memory-facilitating effects RO 15-3505 or similar benzodiazepine receptor ligands may be generalized to aged rodents with impaired memory function.

Aging↗

Lung transplantation: the Cleveland Clinic experience.

BACKGROUND: Lung transplantation has been steadily developing as a therapeutic option for end-stage lung disease. METHODS: Retrospective analysis of all 26 patients who underwent lung transplantation at the Cleveland Clinic Foundation between February 1990 and February 1992. RESULTS: Nineteen single-lung transplantations and seven bilateral lung transplantations were performed. The 1-year actuarial survival for all recipients was 65%. A trend was noted towards better survival in recipients with emphysema (100%) and poorer survival in those with pulmonary hypertension (37.5%). Fungal sepsis and reimplantation lung injury were the most common causes of death, and most deaths (8 of 9) occurred within the first 4 weeks. Of 119 pulmonary complications, 82% occurred in the first 3 months, with infection (39%) and acute rejection (29%) being the most common. Bacterial and fungal infections occurred mainly in the first month, and cytomegalovirus infections occurred mainly in the second and third months. The majority of survivors have shown improvement in functional status. CONCLUSIONS: The early perioperative and 1-month post-transplantation period appears critical to long-term survival. Even though the complications are numerous, they are usually manageable, and, in general, do not result in long-term morbidity.

Adolescent↗