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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 451 records · Page 25Linked to original sources
PubMed1995

Localization of serotonin-4 receptors in the striatonigral pathway in rat brain.

Rats were injected unilaterally with 6-hydroxydopamine either in the medial forebrain bundle or in the dorsolateral substantia nigra. Another group was injected unilaterally with kainate in the striatum. The loss of neurons was assessed by a reduction in tyrosine hydroxylase-like immunoreactivity for dopaminergic neurons, and choline acetyltransferase-like and glutamate decarboxylase-like immunoreactivities for cholinergic and GABAergic neurons, respectively. Brain sections also were analysed by autoradiography on 20 micron sections with the radio-iodinated serotonin-4 receptor antagonist [125I]SB 207710 [Brown A. M. et al. (1993) Br. J. Pharmac. 110, 10P]. Kainate injections in the striatum resulted in loss of choline acetyltransferase- and glutamate decarboxylase-like immunoreactive cell bodies in this area. There was also a decrease in glutamate decarboxylase-like immunoreactivity on the ipsilateral side in the substantia nigra and entopeduncular nucleus. These changes were accompanied by substantial (> 50%) decreases in [125I]SB 207710 binding in both the ipsilateral striatum (confined to the lesioned area) and substantia nigra, with no change in either the nucleus accumbens or the globus pallidus. There was also significant loss of [125I]SB 207710 binding in the ipsilateral entopeduncular nucleus. 6-Hydroxydopamine lesions placed either in the medial forebrain bundle or in the substantia nigra failed to decrease [125I]SB 207710 binding in any of these areas, although there was total loss of tyrosine hydroxylase-like immunoreactive terminals in the striatum and cell bodies in the nigra. We conclude that serotonin-4 receptors are present on projection neurons, both on their perikarya in the striatum and terminals in the nigra and entopeduncular nucleus. It is likely that these receptors are located on the GABAergic projection neurons and possibly on cholinergic and GABAergic interneurons. However, serotonin-4 receptors are not located on dopaminergic neurons, either on their cell bodies in the substantia nigra or terminals in the striatum.

Animals↗
PubMed1995

The molecular biology of androgenic 17 beta-hydroxysteroid dehydrogenases.

The enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) catalyzes the 17 beta-oxidation/reduction of C18- and C19-steroids in a variety of tissues. Three human genes encoding isozymes of 17 beta-HSD, designated 17 beta-HSD types 1, 2 and 3 have been cloned. 17 beta-HSD type 1 (also referred to as estradiol 17 beta-dehydrogenase) catalyzes the conversion of estrone to estradiol, primarily in the ovary and placenta. The 17 beta-HSD type 2 is expressed to high levels in the liver, secretory endometrium and placenta. The type 2 isozyme catalyzes the oxidation of androgens and estrogens equally efficiently. Also, the enzyme possesses 20 alpha-HSD activity demonstrated by its ability to convert 20 alpha-dihydroprogesterone to progesterone. Testicular 17 beta-HSD type 3 catalyzes the conversion of androstenedione to testosterone, dehydroepiandrosterone to 5-androstenediol and estrone to estradiol. The 17 beta-HSD3 gene is mutated in male pseudohermaphrodites with the genetic disease 17 beta-HSD deficiency.

17-Hydroxysteroid Dehydrogenases↗
PubMed1995

Comparison of methods of assessing response of Paget's disease to bisphosphonate therapy.

Bisphosphonates have been shown to be effective in suppressing the elevated bone turnover found in Paget's disease of bone. In theory, the major determinants of post-treatment bone turnover are the initial disease activity and the rate of decline in bone turnover with therapy. In the present study, we examined the rate of decrease of alkaline phosphatase and hydroxyproline (expressed as a half-life) and showed this to be superior to percentage changes in bone turnover as a marker of response. The combination of pre-treatment alkaline phosphatase and the alkaline phosphatase half-life and pre-treatment hydroxyproline and the hydroxyproline half-life were the best models to predict post-treatment bone turnover (multiple r = 0.75, r2 = 0.56, p < 0.0001; and r = 0.71, r2 = 0.51, p < 0.0001, respectively). In addition, measurement of the half-lives of these markers of bone turnover may allow prospective changes to be made during treatment so that maximal disease suppression can be achieved.

Alkaline Phosphatase↗
PubMed1995

Small bowel bacterial overgrowth in systemic sclerosis: detection using direct and indirect methods and treatment outcome.

Twenty-four patients with proven systemic sclerosis and with symptoms suggestive of malabsorption (i.e. chronic diarrhoea and weight loss) were investigated for small bowel bacterial overgrowth. Of the patients selected, six were suffering from the diffuse form of the disease. Jejunal aspiration was performed in all patients, and in nine normal volunteers. A specially designed double-lumen sterile catheter was used for this purpose and was introduced via a gastroscope. Twenty of these patients underwent a glucose hydrogen breath test. Eight patients (33%) had significant bacterial counts: > 10(5) colony forming units per ml (cfu/ml) of jejunal fluid. Less than 10(2) cfu/ml were found in the jejunal fluid from the nine control subjects. Glucose hydrogen breath testing was positive in seven patients, all of whom had significant jejunal bacterial growth. Diarrhoea rather than weight loss was shown to be the symptom which correlated best with the presence of bacterial overgrowth. Ciprofloxacin was used in six patients whose diarrhoeal symptoms ceased dramatically within 48 h of commencing the antibiotic. Trimethoprim produced a partial response despite bacterial sensitivity. A disadvantage of the hydrogen breath test is that subsequent antibacterial therapy cannot be specific, as bacterial species, antibiotic sensitivity and resistance are unknown. Systemic sclerosis involving the small intestine in the past has been said to more prevalent in patients with diffuse disease, whereas this study showed a preponderance of patients with long-standing limited cutaneous systemic sclerosis and small bowel involvement.

Adult↗
PubMed1995

Refractive index and osmolality of human tears.

Tear osmolality measurement, as a basic index of lacrimal physiology, is technically difficult. We investigated a simple, digital nanoliter technique of critical angle refractive index measurement. After initial comparison of the techniques with aqueous NaCl (0.5 to 1.4%), 3 successive tear samples were obtained from each of 40 normal, noncontact lens wearing subjects, aged 17 to 63 years, for analysis by nanoliter osmometry and digital refractometry. In addition, tear lactoferrin concentration was estimated with the Lactoplate immunoassay. For the range of NaCl concentrations tested, osmolality and refractive index measurements were highly correlated with concentration, and with each other. For 0.9% NaClaq the mean value of osmolality was 292.0 mOsm/kg and refractive index was 1.33419. For human tears average values were found to be: for osmolality, 303.7 +/- 22.9 mOsm/kg; for refractive index, 1.33698 +/- 0.00110; and for lactoferrin level, 1.64 +/- 0.47 mg/ml. No statistically significant correlation was obtained between either refractive index or lactoferrin level and osmolality, but refractive index and lactoferrin level were significantly correlated (r = 0.64, p < 0.001). The high correlation of refractometry and osmolality for aqueous NaCl indicates comparability of the techniques for this solution, but this does not apply to human tears. Unlike tear osmolality, tear refractive index is dependent to a greater extent upon composition, as is suggested by its correlation with lactoferrin level. Therefore, refractometry is not acceptable as a direct alternative to osmometry in the assessment of lacrimal function.

Adolescent↗
PubMed1995

Stability of the precorneal tear film in Chinese, African, Indian, and Caucasian eyes.

The stability of the precorneal tear film was measured noninvasively in normal subjects from four diverse ethnic groups (Chinese, Africans, Indians, and Caucasians) all resident in the west of Scotland. Statistically significant differences were found to exist among the groups. The respective mean ( +/- SD) tear stabilities were: 9.8 s (3.9), 11.8 s (5.9), 16.4 s (6.9), and 19.9 s (8.3). Subjects were selected from an age range of 17 to 45 years.

Adolescent↗
PubMed1995

Synthesis of a mixture of cyclic peptides based on the Bowman-Birk reactive site loop to screen for serine protease inhibitors.

A peptide mixture containing 21 peptide sequences has been constructed to test the Bowman-Birk inhibitor reactive-site loop motif as the basis of inhibition for a range of serine proteases. The 21 peptides are all based on an 11 amino acid sequence designed from a Bowman-Birk like inhibitor reactive-site loop. Variation has been introduced at the P1 site of the loop, which has been randomised to include all the natural L-amino acids (except for cysteine), plus the non-natural L-amino acids ornithine and norleucine, The mixture of peptides was screened for specific binding to immobilised porcine pancreatic elastase, subtilisin BPN', alpha-chymotrypsin, trypsin, anhydro-alpha-chymotrypsin and anhydrotrypsin. Five peptides from the mixture bind to alpha-chymotrypsin, two of which also bind to anhydro-alpha-chymotrypsin, and two peptides bind trypsin, neither of which binds to anhydro-trypsin. The competitive inhibition constants (K(i)) and the rates of proteolytic hydrolysis of the individual peptides with their respective enzymes were determined. The rates of hydrolysis were found to vary widely and show little correlation with the K(i) values. In the case of the alpha-chymotrypsin inhibitors, the peptides with the lowest K(i) (0.1-0.05 mM) were the only peptides that bound to anhydro-alpha-chymotrypsin. However, no peptides bound to anhydrotrypsin, suggesting a fundamental difference in the way that alpha-chymotrypsin and trypsin are inhibited by these cyclic peptides.

Amino Acid Sequence↗
PubMed1995

Simplified PCR for detection of Haemophilus ducreyi and diagnosis of chancroid.

A simplified PCR was developed for detection of Haemophilus ducreyi in samples from chancroid patients. The strategy included a straightforward chloroform extraction sample preparation method, a one-tube nested PCR to minimize contamination risks, and a colorimetric method for detection of products. Primers were designed from published nucleotide sequences of the 16S rRNA gene of H. ducreyi, with longer outer primers for annealing at a higher temperature and shorter inner primers labelled with biotin and digoxigenin for binding with avidin and colorimetric detection. The PCR technique detected all 35 strains of H. ducreyi tested, from four different geographical regions, and was negative for other, related strains of bacteria and for the common contaminating bacteria tested. Of 25 samples from H. ducreyi culture-positive chancroid patients, 24 were PCR positive and 1 produced a weak reaction. Of 83 samples from clinical cases of chancroid in the Republic of South Africa, 69 were PCR positive. The sensitivity of PCR compared with that of clinical diagnosis was 83%. All 50 negative control samples were negative. Encouraging results were also obtained with a consecutive series of 25 genital ulcer patients in Tanzania, of whom 9 were PCR positive. The adaptations of this simplified PCR strategy, at the sensitivity and specificity levels obtained, mean it will be useful for detection of H. ducreyi in areas where the organism is endemic, particularly where testing by culture is difficult or impossible.

Base Sequence↗
PubMed1995

Quantitative expression of proliferating cell nuclear antigen by western blot (PCNAWB) in peripheral blasts correlates with remission induction in patients with acute myelogenous leukemia.

Proliferating cell nuclear antigen (PCNA) is a 36-kD nuclear protein that functions as a cofactor of delta DNA polymerase which is regulated in a cell cycle-dependent fashion. PCNA expression also increases when cells are actively engaged in DNA repair. We used Western blotting (WB) to measure the level of expression of PCNA in peripheral blasts of 36 adult acute myelogenous leukemia (AML) patients treated with Ara-C based induction regimens. PCNA levels correlated positively with the percentage of cells in S+G2M of the cell cycle. Logistic regression analysis revealed PCNA (beta = 4.5162; p = 0.0260) together with age (beta = 0.1777; p = 0.0364) as independent variables for remission induction: high PCNA levels were associated with poor response to induction therapy. PCNA expression was not, however, a predictor of survival in this subset of patients. We conclude that PCNA levels in this disease may be important for predicting response to Ara-C based remission induction chemotherapy.

Adult↗