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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 667 records · Page 37Linked to original sources

Cancer in mice: effects of prednisolone or mepacrine alone and with cytotoxic drugs.

WHT/Ht mice were transplanted s.c. with NC carcinoma, and the tumours were excised after 2 weeks. The mice were treated orally throughout the experiments with prednisolone 500 micrograms kg-1 or mepacrine 3.6 mg kg-1, starting the day after tumour transplantation or, with prednisolone, the day after tumour excision. In some experiments the mice were also treated with the cytotoxic drugs methotrexate 2 mg kg-1 and melphalan 1.4 mg kg-1. The excised tumours were weighed; some of them, and samples of serum, were extracted for prostanoids which were measured by radioimmunoassay. The chemotherapy lengthened the survival of the mice, but prednisolone or mepacrine had little or no effect on survival, metastasis, the response to chemotherapy, tumour size or the formation of tumour prostanoids.

6-Ketoprostaglandin F1 alpha↗

Muscle strength in healthy white and Asian subjects: the relationship of quadriceps maximum voluntary contraction to age, sex, body build and vitamin D.

1. The maximum voluntary isometric contraction (MVC) of the dominant quadriceps muscle was measured in 136 healthy White and 172 healthy Hindu Asian subjects resident in London, using a specially designed chair equipped with a force measuring load cell. 2. Males were stronger than females, and for both sexes MVC declined with age. From age 20 to 60 the annual decline in MVC ranged from 0.56% in White males to 1.5% in female Asians. 3. White subjects were stronger than Asian subjects even after correcting for the effect of age, height, weight and sex in a multi-factorial analysis. 4. Only in males did MVC correlate with height and weight. Asian women were more obese than any other group, and showed an increase in body mass index with age. 5. Twenty-two per cent of Asian subjects had marked vitamin D deficiency (plasma 25-hydroxycholecalciferol less than 10 nmol/1). There was no correlation between MVC, and plasma 25-hydroxycholecalciferol.

Adult↗

Group C Niemann-Pick disease: faulty regulation of low-density lipoprotein uptake and cholesterol storage in cultured fibroblasts.

Incubation of mutant Niemann-Pick C fibroblasts with low-density lipoprotein (LDL) resulted in excessive internalization of lipoprotein and extensive cellular over-accumulation of unesterified cholesterol. The uptake of LDL by the mutant cells appeared to occur through the classic LDL receptor pathway and internalized lipoprotein was processed in lysosomes. Lipoprotein uptake into mutant cells was associated with delays in the initiation of established cellular cholesterol homeostatic responses. Subcellular fractionation of mutant Niemann-Pick C fibroblasts accumulating LDL-cholesterol showed excess unesterified sterol to be localized in the light lysosome-light membrane region of a Percoll gradient, and revealed that cholesterol storage was associated with a specific alteration in the normal profiles of lysosomal marker enzymes.

Cells, Cultured↗

Constancy of the front surface desiccation times for Igel 67 lenses in vivo.

A simple method for judging the desiccation of a hydrophilic lens, while on the eye, is described. This involves subjective determination of the loss in "crispness" and "regularity" of the keratometer mire reflected off the anterior lens surface in between blinks. The time interval between a complete blink and the moment of loss of regularity of the reflex was monitored over a 6 month period for subjects wearing a commercially available 67% water content contact lens. This time interval appears to remain constant, and is, on average, comparable with the normal interblink period.

Contact Lenses, Hydrophilic↗

Changes in corneal topography and tear film stability due to a single Meibomian cyst.

Lid pressure may affect corneal curvature. A change in lid pressure due to a Meibomian cyst may cause a change in corneal topography and possibly in refractive status. External infection or epithelial surface disruption may affect the stability of the precorneal tear film by causing changes in tear formation or an increase in the rate of evaporation of water from this film. This report concerns a male patient who showed changes in corneal topography and tear film stability due to a Meibomian cyst.

Cornea↗

Analysis of human skin surface lipid during treatment with anti-androgens.

Skin surface lipid was collected from the foreheads of patients during a study of anti-androgen therapy for acne, and analysed for free fatty acid composition and triglyceride fatty acids. Both sebum excretion rate and bacterial flora decreased during therapy but only the ratio of free fatty acid to total glyceride plus free fatty acid changed, falling in all groups during therapy. No differences in lipid composition were detected in relation to individual therapy but patients admitted at the start of the trial, had, overall, a different lipid composition to those admitted later and had lower surface microbial counts.

Acne Vulgaris↗

Metabolic degradation and synthesis of calcitriol in spontaneously hypertensive rat.

Plasma calcitriol concentration is unexpectedly low in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY) in view of previous findings of low plasma ionized calcium, hypophosphatemia, and hyperparathyroidism in SHR. Also, parathyroid hormone (PTH) and other exogenous stimuli cause a smaller increment in plasma calcitriol in SHR than in WKY. We investigated whether these differences in plasma calcitriol levels were due to decreased production rate (PR) or increased metabolic clearance rate (MCR) in SHR using the continuous infusion-isotope equilibration technique. In the basal state, MCR was 0.306 +/- 0.048 ml X min-1 X kg-1 in SHR and 0.284 +/- 0.026 ml X min-1 X kg-1 in WKY (P = NS). Estimated PR was lower in SHR (22.7 vs. 33.7 ng X day-1 X kg-1). With PTH infusion (3 U X h-1 X 100 g-1 for 20 h), MCR was 0.220 +/- 0.011 ml X min-1 X kg-1 in SHR and 0.256 +/- 0.017 ml X min-1 X kg-1 in WKY (P = NS). Measured PR was markedly lower in SHR (154 +/- 24 vs. 262 +/- 27 ng X day-1 X kg-1; P less than 0.02). Basal plasma PTH, total plasma calcium, and plasma inorganic phosphate were not different between SHR and WKY. Thus, SHR show diminished calcitriol production under basal condition and with PTH stimulation. MCR is not increased in SHR and does not appear to be influenced by PTH or the accompanying elevation in plasma calcium and calcitriol.

Animals↗

Production and degradation of calcitriol in renal failure rats.

We studied the metabolism of calcitriol in renal failure achieved by nephrectomy in three groups of rats. Group 1 (n = 7) had sham operation of nephrectomy. Group 2 (n = 8) had unilateral nephrectomy. Group 3 (n = 7) had 5/6 nephrectomy. Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were studied 3 wk after the surgery. Serum creatinine concentrations were increased after nephrectomy for groups 2 and 3. Endogenous plasma levels of calcitriol were not different between the rats with renal failure and the controls. MCR of calcitriol were decreased in renal failure rats compared with controls (group 1, 0.24 +/- 0.01; group 2, 0.20 +/- 0.01, P less than 0.01; group 3, 0.16 +/- 0.01 ml.min-1.kg-1, P less than 0.001). The MCR of calcitriol was correlated with the endogenous creatinine clearance by linear regression analysis (r = 0.72, P less than 0.001). The PR of calcitriol were also decreased in renal failure; however, the decreases were much less than the amount of renal tissue removed. We concluded that production of calcitriol is decreased in the remnant kidney. The decreased synthesis is associated with decreased degradation of calcitriol resulting in normal concentrations of calcitriol in mild to moderately severe renal failure.

Animals↗

Pararenal hematoma as a complication of vaginal hysterectomy. A case report.

Following a vaginal hysterectomy, a woman developed a pelvic hematoma that expanded in the retroperitoneum to the level of the right kidney. Such a complication, a pararenal hematoma after vaginal hysterectomy, has not been reported on previously. The cuff hematoma was demonstrated clearly by ultrasonography. However, the extent and dimensions of the retroperitoneal hematoma were disclosed only by computed tomographic (CT) scanning. We recommend that a the CT scan be considered in the evaluation of any large posthysterectomy pelvic hematoma.

Adult↗

Calcemic response to parathyroid hormone in spontaneously hypertensive rats: role of calcitriol.

Spontaneously hypertensive rats (SHR) display lower ionized calcium (Pca++) concentrations when compared with normotensive Wistar Kyoto rats (WKY). This could be attributable to renal wasting of calcium, decreased intestinal calcium absorption, or decreased bone resorption, processes that are integrated by the parathyroid hormone (PTH) and vitamin D systems. We have studied the calcemic response to PTH infusion (3 U/hr/100 gm) for 5 hours in 13-week-old SHR and WKY. Pre-PTH Pca++ concentration of nonfasted SHR (4.68 +/- 0.06 mg/dl, N = 8) was significantly lower than that of WKY (4.84 +/- 0.03, N = 8, P less than 0.05). Pca++ concentration rose in both nonfasted WKY and SHR at the end of PTH infusion, but the increment of Pca++ in SHR (0.29 +/- 0.05 mg/dl, N = 8) was lower than that in WKY (Pca++, 0.60 +/- 0.07 mg/dl, N = 8, P less than 0.01). Urinary calcium excretion (UcaV) and creatinine clearances (Ccr) before and after PTH infusion were not different between WKY and SHR. Despite an increased filtered load of calcium, UcaV was not greater in either WKY or SHR during the PTH infusion. Pretreatment of SHR with calcitriol 50 ng intravenous bolus injection, which had no effect on Pca++ concentration (0.02 +/- 0.03 mg/dl, N = 7), corrected the lower calcemic response to PTH in SHR, and the Pca++ increment was no longer different between WKY (0.57 +/- 0.07 mg/dl, N = 7) and SHR (0.62 +/- 0.09, N = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pathological and clinical study of Müller's muscle in Graves' ophthalmopathy.

Specimens of Müller's muscle from patients with Graves' disease were examined for evidence of morphologic, histochemical, immunohistochemical and electron microscopic changes. No scarring, significant inflammation or shared antigenicity between Müller's muscle and thyroglobulin-related antigens was found. There were moderate numbers of mast cells in 48 of 66 specimens. Computed tomography in 16 patients with Graves' ophthalmopathy showed enlargement of the superior rectus-levator complex in 17 of 28 orbits with lid retraction. However, no correlation was found between the amount of lid retraction and the degree of enlargement of the muscle complex.

Ciliary Body↗

Extensive squamous cell carcinoma of the conjunctiva presenting as orbital cellulitis: the hermit syndrome.

The authors present three cases of extensive squamous cell carcinoma of the conjunctiva invading the orbit and masquerading as orbital cellulitis. All cases were in elderly alcoholic men living in relative social isolation. Total exenteration of the orbit was required in all three cases. Only one patient has had long-term follow-up; he was well 5 years after presentation. The other two patients were well 15 and 5 months after surgery.

Aged↗

Anticonvulsant action of a kainate antagonist gamma-D-glutamyl aminomethylsulphonic acid injected focally into the substantia nigra and entopeduncular nucleus.

Focal injection of gamma-D-glutamylaminomethylsulphonic acid (GAMS) into basal ganglia areas, the substantia nigra and entopeduncular nucleus, protects against electroshock (50 mA, 60 Hz, 0.2 s) and pilocarpine (380 mg/kg i.p.) induced seizures in rats. GAMS infusion into substantia nigra pars reticulata significantly protects against generalised (5, 10 nmol) and limbic (10, 50 nmol) seizures. The highest dose of GAMS results in similar suppression of seizure activity following injection into substantia nigra pars compacta against generalised (10 nmol) and limbic (50 nmol) seizures. The anticonvulsant action of GAMS is less marked after infusion into the entopeduncular nucleus. High doses of GAMS are required to provide protection against electroshock test (10 nmol) and limbic (40 nmol) seizures. Protection against limbic and electroshock seizures is more pronounced after infusion of GAMS into substantia nigra than into the entopeduncular nucleus. The substantia nigra pars reticulata is particularly sensitive to the anticonvulsant action of GAMS suggesting that antagonism at the kainate receptor is functionally important.

Animals↗

Type C Niemann-Pick disease. Abnormal metabolism of low density lipoprotein in homozygous and heterozygous fibroblasts.

The esterification of cholesterol derived from human low density lipoprotein (LDL) or fetal bovine serum (FBS) was deficient in cultured fibroblasts from subjects with heterozygous and homozygous type C Niemann-Pick (NPC) disease. Failure to significantly esterify LDL-derived cholesterol resulted in abnormal accumulation of predominantly unesterified cholesterol in homozygous NPC fibroblasts. Compared with normal and homozygous fibroblasts, heterozygous NPC fibroblasts synthesized intermediate levels of cholesteryl ester during the initial 6 h of incubation with LDL. The rate of cholesterol esterification in heterozygous cells was normal when measured over a 24-h period of incubation with LDL. In addition to demonstrating a defect in cholesterol esterification, homozygous NPC fibroblasts accumulated more total cholesterol when incubated with LDL or FBS than normal fibroblasts accumulated. When heterozygous NPC fibroblasts were incubated with LDL or FBS, cellular accumulation of cholesterol reached levels that were high-normal or intermediary between levels observed in normal and homozygous NPC fibroblasts. The partial expression of these metabolic errors in the heterozygous genotype relevantly links these errors to the primary mutation of this disorder.

Cell Line↗

Type C Niemann-Pick disease. A parallel loss of regulatory responses in both the uptake and esterification of low density lipoprotein-derived cholesterol in cultured fibroblasts.

Low density lipoprotein (LDL) internalization by mutant type C Niemann-Pick (NPC) fibroblasts results in uptake of excess total cholesterol. Uptake of excess lipoprotein cholesterol appears to be mediated by the specific LDL receptor pathway. Associated with excessive LDL-cholesterol uptake is a lesion in early intracellular cholesteryl ester synthesis. In vitro acylCoA:cholesterol acyltransferase activity is normal in cell-free extracts of mutant cells. The ability of exogenous sterols to enhance intracellular esterification of [3H]mevalonate-derived [3H]cholesterol was severely limited in mutant cell cultures suggesting that in vivo activation and/or expression of activated acylCoA:cholesterol acyltransferase may be compromised by the primary mutation of type C Niemann-Pick disease. After 2 days of LDL uptake, rates of intracellular cholesteryl ester synthesis in mutant cells paralleled the rates of esterification in normal cells suggesting that specific early in vivo expression of the acyltransferase may be affected in this disorder.

Biological Transport↗

Olfactory bulbectomy protects against pilocarpine-induced motor limbic seizures in rats.

Systemic injection of pilocarpine (380 mg/kg) results in the development of motor limbic seizures in rats. Olfactory bulbectomy performed 7 days prior to pilocarpine administration has a strong protective effect against the seizures. Neuropathological changes which normally occur in this seizure model do not develop in the brains of bulbectomized animals.

Animals↗

Distribution of [3H]kainic acid and binding sites in the rat brain: in vivo and in vitro receptor autoradiography.

Brain sections incubated in vitro with alpha-[3H]kainic acid (KA; spec. act. 62.5 Ci/mmol), reveal a heterogeneous distribution of low and high affinity KA binding sites in the brain. The highest density of KA binding sites was localised to the hippocampus CA3 region and to superficial layers of the entorhinal cortex (3.8-6.0 mu Ci/g tissue). Intravenous injection of [3H]KA (1 mu Ci/g) reveals limited overall penetration of [3H]KA across the blood-brain barrier. However, a dense labelling of the hippocampus, entorhinal cortex and lateral septal regions (2.5-3.8 mu Ci/g tissue) was observed. Behaviourally, these rats exhibited mild limbic seizure activity possibly as a result of a direct action of KA in the hippocampus or entorhinal cortex.

Animals↗