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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 523 records · Page 29Linked to original sources
PubMed1993

Novel selection and genetic characterisation of an etoposide-resistant human leukaemic CCRF-CEM cell line.

We have studied the genetic alterations acquired during selection of a cloned human leukaemic cell line (CEM/VP-1) that is 15-fold more resistant to the anticancer topoisomerase II-inhibitor etoposide than parental CCRF-CEM cells. CEM/VP-1 cells exhibit an 'atypical MDR' phenotype: cross resistance to other topo II inhibitors (but not Vinca alkaloids) and expression of a drug-resistant topo II activity. Cytogenetic and molecular studies revealed that the cell line carried multiple genetic changes affecting TOP2 genes encoding both topo II alpha and beta isoforms. CEM/VP-1 was diploid, 47,XX,+20, and appears to have been preferentially selected from a 1% diploid subpopulation present in the tetraploid parental cells. The same chromosomal abnormalities were present in resistant and sensitive cells except for an acquired 3p- change most likely deleting one TOP2 beta allele. PCR/DNA sequence analysis and allele-specific hybridisation showed that one of two TOP2 alpha alleles expressed in CEM/VP-1 cells had acquired a Lys-797-->Asn codon change. This mutation lies close to the catalytic Tyr-804 residue of the protein and may interfere with drug-induced trapping of the cleavable complex. Alternatively, it could exert a loss of function phenotype. CEM/VP-1 cells did not exhibit codon 449 or 486 TOP2 alpha mutations in the ATP binding domain reported in two other resistant cell lines. Diploid selection and multiple changes observed in CEM/VP-1 cells appear to be consequences of the recessive phenotype of at-MDR. These results may be useful in approaching the mechanisms of clinical resistance.

Base Sequence↗
PubMed1993

IFN-gamma and TNF-alpha secretion by CD4+ and CD8+ TCR alpha beta + T-cell clones derived early after allogeneic bone marrow transplantation.

Secretion of the potentially antileukaemic cytokines IFN-gamma and TNF-alpha was investigated for CD4+ and CD8+ TCR alpha beta + T-cell clones derived from 4 leukaemia patients 3-6 weeks after allogeneic BMT. We investigated cytokine secretion in response to the activation signal accessory cells+phytohaemagglutinin+Interleukin 2. All clones derived after BMT were capable of IFN-gamma and TNF-alpha secretion, and both for CD4+ (n = 96) and CD8+ (n = 8) T cells quantities of IFN-gamma and TNF-alpha were significantly correlated with one another. When comparing the overall results for posttransplant and normal T-cell clones derived from 2 bone marrow donors (n = 65), both CD4+ and CD8+ TCR alpha beta + T-cell clones showed increased IFN-gamma production, and CD4+ but not CD8+ clones showed a decreased TNF-alpha secretion. The results suggest that noncytotoxic T cells derived after allogeneic BMT can produce IFN-gamma and TNF-alpha and may thus be capable of mediating antileukaemic effects.

Adult↗
PubMed1993

The influence of vitamins and trace element supplements on the stability of the pre-corneal tear film.

The tear stability af 60 normal healthy subjects was measured and repeated 10 days later. Using a double-blind protocol, during the interim period 2/3 of the subjects (the treatment groups) took a commercially available daily dietary supplement and the remaining 1/3 acted as controls. The recommended daily dose was applied to the treatment groups. 20 of the treatment group took a daily dietary supplement of a mixture consisting of vitamins (e.g. A, B1, B2, B6, E) and trace elements (e.g. calcium iron, manganese), the other 20 took purely vitamin C tablets. The tear stability of both treated groups increased, however, the multi-vitamin and trace element group demonstrated the more consistent and individually predictable improvement. Within this group, the characteristics of the regression line correlating the initial mean (x) and final mean (y) tear stabilities were, y = 5.94 + 1.02x. The tear stability of the control group individuals did not significantly change.

Adult↗
PubMed1993

Activities of potential therapeutic and prophylactic antibiotics against blood culture isolates of viridans group streptococci from neutropenic patients receiving ciprofloxacin.

All 47 sequential blood culture isolates of viridans group streptococci obtained from febrile neutropenic patients receiving quinolone prophylaxis were susceptible to vancomycin, teicoplanin, and imipenem. Resistance to benzylpenicillin (MIC for 50% of isolates [MIC50], 0.125 microgram/ml) and ceftazidime (MIC50, 4 micrograms/ml) was common. Most isolates were susceptible to amoxicillin, co-amoxiclav (amoxicillin-clavulanic acid at a 2:1 ratio by weight), azlocillin, clarithromycin, and erythromycin, with azithromycin showing comparable activity. The MIC90 of sparfloxacin was 1 microgram/ml; those for ciprofloxacin and ofloxacin were > 16 and 16 micrograms/ml, respectively.

Anti-Bacterial Agents↗
PubMed1993

Species of alpha-hemolytic streptococci possessing a C-polysaccharide phosphorylcholine-containing antigen.

An enzyme-linked immunosorbent assay technique was used to detect and quantify C-polysaccharide-like antigen in strains of alpha-hemolytic streptococci classified into species by following the latest taxonomic recommendations. C-polysaccharide-like antigen is found only in Streptococcus oralis, S. mitis, and S. pneumoniae, which are genetically closely related.

Antigens, Bacterial↗
PubMed1993

Study of the proliferation in human gastric mucosa after in vivo bromodeoxyuridine labelling.

Studies to measure human gastric crypt or gland cell proliferation may have a number of practical clinical applications in relation to both benign and malignant gastric conditions. Bromodeoxyuridine (BrdUrd) labels human gastric mucosal cells in the S phase. Computer aided data analysis of labelled mucosa allows static proliferative indices to be estimated, including the crypt labelling index (LI), the peak labelling position, the distribution of labelled cells and indirectly the crypt growth fraction. Multiparameter flow cytometric analysis of labelled nuclei allows the S phase duration (Ts) of mucosal cells to be estimated. Specimens of histologically normal gastric body (GB, n = 16) and antral mucosa (GA, n = 10) were obtained from 25 patients with gastric carcinomas who received a bolus dose of 250 mg BrdUrd between 3.0 and 15.7 hours before surgery. Tissue sections were stained by an immunohistochemical method and subjected to detailed counting of up to 50 longitudinal crypts per specimen. The total crypt labelling index was calculated by a grid counting method. A significant difference existed between the proliferative compartments of gastric antral and body mucosa measured by a number of criteria. The median lengths of the crypts were 137 cells (GB) and 188 cells (GA). The median peak labelling positions were cell 26 (GB) and cell 61 (GA) from the crypt orifice. The mean crypt labelling indices were 2.8% (GB) and 4.8% (GA). The mean Ts of GA cells was 7.7 hours and of GB cells was 10.8 hours.

Adult↗
PubMed1993

Streptokinase neutralisation titres up to 866 days after intravenous streptokinase for acute myocardial infarction.

OBJECTIVE: To follow the change in streptokinase neutralisation titres in a group of patients after treatment with streptokinase for acute myocardial infarction. DESIGN: Venous blood samples suitable for analysis were obtained up to 866 days after treatment with 1.5 million units of streptokinase in 189 patients. The ability of the patient's plasma to inhibit lysis of a thrombin clot by streptokinase was assessed. SETTING: A coronary care unit in a district general hospital. PATIENTS: A retrospective review of coronary care records and the district health authority computer showed that 329 patients who had received streptokinase were alive. All were invited for venepuncture and 220 (67%) attended. Satisfactory samples were obtained from 189 patients. RESULTS: Raised titres of antibody sufficient to neutralise a standard dose of 1.5 million units of streptokinase were found in 90% of patients. There was a fall in streptokinase neutralisation titre with increasing time after administration of streptokinase (r = -0.35, P < 0.0001) and though there was considerable variation among the group the neutralisation titre was higher than in the general population in all patients, even those who had received streptokinase at least two years previously. CONCLUSION: The ability of streptokinase to lyse a thrombin clot was appreciably inhibited in vitro by the plasma from patients who had received 1.5 million units of streptokinase. High streptokinase neutralisation titres persisted for a long time after the use of streptokinase as thrombolytic treatment for acute myocardial infarction. Readministration of streptokinase may not be efficacious for considerably longer than the one year currently advocated. Until the in vivo effects of streptokinase readministration are known a non-antigenic thrombolytic agent should be used instead.

Antibodies↗
PubMed1993

Asymptomatic acute pyelonephritis as a cause of acute renal failure in the elderly.

Urinary tract infections in the elderly are common, often asymptomatic and usually benign. We report three patients who presented with acute renal failure due to acute pyelonephritis in the absence of clinical findings of infection or urinary tract obstruction. Blood and urine cultures grew Escherichia coli in two of the patients and in two patients renal biopsy confirmed acute pyogenic pyelonephritis. Antimicrobial therapy and haemodialysis led to improvement, though one patient subsequently died from an unrelated cause. We suggest that acute bacterial pyelonephritis should be considered as a cause of acute renal failure in the elderly. Clinical features of infection may be absent despite bacteraemia. Prompt diagnosis and intervention may avoid chronic renal failure in a group that has a less favourable outcome with long-term dialysis.

Acute Disease↗
PubMed1993

Effect of uric acid on plasma levels of 1,25(OH)2D in renal failure.

Previous studies from these laboratories have demonstrated that uremic biologic fluids contain substances that suppress 1,25(OH)2D metabolism. Among these substances, it was found that uric acid suppresses 1 alpha-hydroxylase activity and synthesis of 1,25(OH)2D in rats. In this study, the effect of uric acid on plasma concentrations of 1,25(OH)2D in patients with renal failure was examined. Nine patients with stable chronic renal failure (serum creatinine, 1.9 to 6.4 mg/dL) were studied. None of the patients received vitamin D supplementation. Plasma concentrations of Ca, P, parathyroid hormone, creatinine, uric acid, 1,25(OH)2D, and 25(OH)D were measured before and 1 wk after the patients received allopurinol, 300 mg daily. Plasma creatinine, Ca, P, parathyroid hormone, and 25(OH)D did not change before or after allopurinol treatment. However, plasma uric acid decreased significantly from 7.3 +/- 0.4 to 4.0 +/- 0.4 mg/dL (P < 0.01) and plasma concentration of 1,25(OH)2D rose from 30.8 +/- 2.7 to 38.2 +/- 4.8 pg/mL (P < 0.01) after the ingestion of allopurinol. Allopurinol itself did not appear to directly enhance 1 alpha-hydroxylase activity in rats. It was concluded that a short-term administration of allopurinol suppresses plasmic uric acid and increases plasma 1,25(OH)2D in patients with chronic mild to moderate renal failure.

Adult↗
PubMed1993

Drugs used in the treatment of metabolic bone disease. Clinical pharmacology and therapeutic use.

Osteoporosis is the most important metabolic bone disease and places an increasing burden on the healthcare system. The condition can be prevented by the early introduction of hormone replacement therapy. The role of bisphosphonates in achieving the same result is being actively explored. The attraction of preventing bone loss is that it preserves the micro-architecture of bone, and therefore its mechanical integrity. The great problem of treating the established condition is that substantial bone loss is accompanied by architectural disintegration. Replacing lost bone may not necessarily restore mechanical integrity and protect against fractures. The management of Paget's disease has been quite revolutionised by the introduction of the bisphosphonates. The condition is a result of a primary increase in osteoclastic bone resorption which can be corrected by bisphosphonates, with considerable symptomatic improvement. The increasing potency and safety margin of the newer agents has meant that the threshold for treatment has fallen. There is now potential for long term control of bone turnover with the hope of preventing late complications. Hypercalcaemia of malignancy is usually the result of both increased bone destruction and decreased urinary calcium excretion. These two components of hypercalcaemia demand different approaches to management. The general availability of an ever-expanding range of increasingly potent bisphosphonates has resulted in a dramatic improvement in the treatment of increased bone resorption associated with malignancy. Many types of tumour, either directly or indirectly, compromise the ability of the kidney to eliminate a calcium load derived from increased bone destruction. Calcitonin is the only agent which is currently available to counter this process.

Calcitonin↗
PubMed1993

Leiomyosarcoma of the vulva.

A case of Leiomyosarcoma of the vulva is presented. It is important to discuss diagnosis and treatment because of its rarity and usual presentation as a benign lesion. Radical vulvectomy with bilateral groin dissection was performed. Local recurrence occurred four years after surgery and was re-excised. At present, the patient is alive with no evidence of disease.

Female↗
PubMed1993

Induction of alpha-galactosidase in Penicillium ochrochloron by guar (Cyamopsis tetragonobola) gum.

High yields of extracellular alpha-galactosidase from fungal cultures were obtained by inducing enzyme production with guar gum (a galactomannan obtained from the seeds of Cyamopsis tetragonobola) as the sole carbon source. An alpha-galactosidase was isolated from the culture medium of Penicillium ochrochloron culture and purified 867-fold by CM-cellulose and Sephacryl S-200 column chromatography to apparent homogeneity. Gel-filtration data revealed an M(r) of 57,500, which was in close agreement with SDS/PAGE M(r) estimation, for a single band, of 60,200. The alpha-galactosidase activity is strictly dependent upon the pH and temperature of the incubation medium, being maximal at pH 4.5 and 55 degrees C respectively. This enzyme from P. ochrochloron was isolated and purified, devoid of beta-mannanase activity, which cleaves the main beta-mannan backbone of galactomannans and greatly diminishes its gel-promoting capacity. The properties of purified guar-gum-induced alpha-galactosidase activity in P. ochrochloron culture were evaluated in order to ascribe a possible application for alpha-galactosidase in the controlled generation of an improved guar-gum-based gel promoter.

Chromatography, Gel↗
PubMed1993

Detection of hormone-sensitive lipase in various tissues. II. Regulation in the rat testis by human chorionic gonadotropin.

Hormone-sensitive lipase (HSL) is an intracellular neutral lipase found in a variety of tissues, primarily in adipose and steroidogenic tissues, that hydrolyzes triglycerides and cholesteryl esters. In the rat testis steady-state levels of HSL mRNA increase dramatically during sexual maturation. In addition, HSL-like immunoreactive proteins of 84, -89, and -102 kD have been observed in sexually immature rats with additional -113 and -127 kD immunoreactive proteins expressed in mature animals. In the present studies the ability of human chorionic gonadotropin (hCG) to regulate the expression of HSL and HSL-like immunoreactive proteins in rat testes has been examined. Treatment of sexually immature rats with daily injections of hCG caused a gradual increase in HSL activity that reached an 80% rise (P < 0.01) after 5 days. This was paralleled by a 3-fold increase (P < 0.01) in the 84 kD protein representing the active HSL enzyme. The -89 kD immunoreactive protein was also increased -5-fold (P < 0.01) in parallel to the 84 kD protein and HSL activity. The -102 kD immunoreactive protein was increased by hCG treatment (P < 0.01); however, its expression did not follow changes in HSL activity or in the 84 and -89 kD immunoreactive proteins, peaking within 12 h and declining thereafter. The -113 and -127 kD immunoreactive proteins did not appear during the 5 days of hCG treatment. Steady-state levels of HSL mRNA increased 60-100% (P < 0.02) in parallel to the changes in HSL activity and in the 84 and -89 kD immunoreactive proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Detection of hormone-sensitive lipase in various tissues. I. Expression of an HSL/bacterial fusion protein and generation of anti-HSL antibodies.

Hormone-sensitive lipase (HSL) is an intracellular neutral lipase found in a variety of tissues, but primarily in adipose and steroidogenic tissues, that hydrolyzes triglycerides and cholesteryl esters. In the present studies, a portion of rat HSL cDNA was subcloned into a pET expression system and the resulting recombinant fusion protein was over-expressed in E. coli. The approximately 26 kD HSL/fusion protein was used to generate polyclonal antibodies in rabbits that recognize intact HSL (84 kD) in rat adipose tissue, ovary, adrenal, testis, heart, and lung, as well as in human adipose tissue. In addition, there was an approximately 89 kD protein observed in all rat tissues expressing the 84 kD protein. Unique to testes, there was an immunoreactive protein of approximately 102 kD in sexually immature rats, and additional immunoreactive proteins of approximately 113 kD and approximately 127 kD in sexually mature rats. The anti-HSL/fusion protein antibodies could remove approximately 60-80% of total neutral cholesterol esterase activity from extracts of rat adipose tissue and immunoprecipitated a single 84 kD protein after labeling of adipocytes with [32P]orthophosphate. The incorporation of 32P into the 84 kD HSL protein was stimulated 4-fold by incubation of adipocytes with isoproterenol. The half life of [35S]methionine-labeled HSL was approximately 4 h in normal rat adipocytes. The production of an HSL/fusion protein and generation of antibodies that recognize native HSL should be valuable tools in exploring the mechanisms regulating the expression of HSL activity and the function and localization of its immunoreactive proteins.

Adipose Tissue↗