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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 253 records · Page 14Linked to original sources

Lysyl oxidase, cellular senescence and tumor suppression.

Replicative senescence may provide a mechanism of tumor suppression and tumor suppressor genes of the extracellular matrix, like lysyl oxidase, may play a role in cellular senescence. To test this hypothesis and determine whether the extracellular matrix may serve as a marker, the steady-state levels of human lysyl oxidase, alpha-I type III collagen and beta-actin transcripts were assessed in various cell lines during in vitro passage. Northern hybridization analysis showed a significant increase in the levels of progeria fibroblast extracellular matrix mRNAs immediately preceding senescence. The levels of these mRNAs were unaffected in age-matched normal fibroblast and fetal fibroblast cell lines.

Actins↗

The action of 5-fluorouracil on human HT29 colon cancer cells grown in SCID mice: mitosis, apoptosis and cell differentiation.

This study investigates the effects of the anti-metabolite 5-fluorouracil (5-FU) on the human colon cancer line HT29 (10(7) cells per dose) grown subcutaneously in severe combined immunodeficient (SCID) mice. The efficacy of 5-FU was quantitatively evaluated by comparing the tumour weight, mitotic and apoptotic tumour cell indices and the expression of the Ki-67 nuclear antigen in drug-treated animals and control animals. The tumour cell carbohydrates were assessed using a lectin panel. A significant reduction in the tumour weight was found 4 days after initial 5-FU treatment. 5-FU treatment reduced the percentages of mitoses but increased the apoptotic index in the tumour cells. In addition, 5-FU induced an increase in the signet ring cell population and an increased binding for lectins specific for N-acetylgalactosamine and galactose. However, the vast majority of signet ring cells were negative for Ki-67. The results of this study indicate that continuous treatment with 5-FU for 4 days targets metabolic processes relevant for both cell division and apoptosis. The relative increase in the signet ring population can be explained by the fact that the more proliferation-active stem cell population of the tumour is the primary target of the therapy. The lectin-binding patterns reflect these changes and are therefore differentiation linked.

Animals↗

Differential carcinogenicity of benzo[a]pyrene in male and female CD-1 mouse lung.

Benzo[a]pyrene (BaP) is known to induce tumors in lung, forestomach, and skin in experimental animals. Earlier studies have suggested that glutathione S-transferase pi (GST pi) is involved in the detoxification of the "ultimate" carcinogenic metabolite of BaP, 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). The constitutive expression of GST pi in the liver of the male CD-1 mouse is higher than that of the female, and BHA has been shown to preferentially induce GST pi in the female as compared with the male mouse. The present studies were therefore designed to compare the susceptibility of male and female CD-1 mice to the carcinogenic effects of BaP and the protective effect of BHA. Results of these studies show that the female CD-1 mice are more susceptibile to the carcinogenic effect of BaP than the males and that the attenuation of BaP-induced carcinogenesis by BHA appears to be restricted only to the females.

Adenocarcinoma↗

Inhibitory effect of Tripterygium wilfordii multiglycoside on increased glomerular albumin permeability in vitro.

BACKGROUND: Tripterygium wilfordii Hook F is a medicinal plant used for the treatment of glomerulonephritis in China. We studied the effect of Tripterygium wilfordii multiglycoside (TWG) on glomerular albumin permeability (Palbumin) in vitro. METHODS: Isolated rat glomeruli were incubated with protamine (600 micrograms/ml) for 30 min, or with human recombinant tumour necrosis factor (TNF-alpha 0.4 ng/ml), superoxide (10 units/ml), or serum from a focal segmental glomerular sclerosis (FSGS) patient for 10 min at 37 degrees C. TWG, 1 mg/ml, was added in parallel tubes to study the effect on Palbumin. Control glomeruli were incubated under identical conditions. The albumin reflection coefficient (sigma albumin) was calculated from the change in glomerular volume in response to an applied oncotic gradient. Convectional permeability (Palbumin) was calculated as (1 - sigma albumin). RESULTS: Compared with controls, protamine increased the Palbumin of glomeruli (0.83 +/- 0.05, n = 25, vs 0.18 +/- 0.03, n = 20); pretreatment with TWG blocked this effect (0.13 +/- 0.04, n = 25). TNF-alpha also increased the Palbumin (0.79 +/- 0.04, n = 24 vs 0.04 +/- 0.07, n = 19); preincubation with TWG blocked this effect (0.03 +/- 0.09, n = 24). Palbumin of glomeruli incubated with xanthine and xanthine oxidase, resulting in the production of superoxide, also increased as compared to controls (0.85 +/- 0.04, n = 15 vs 0.08 +/- 0.05, n = 14); TWG blocked this effect as well (0.21 +/- 0.08, n = 14). FSGS serum also increased Palbumin of glomeruli significantly (0.88 +/- 0.02, n = 49 vs 0.00 +/- 0.02, n = 49); preincubation with TWG blocked this effect (0.05 +/- 0.07, n = 30). TWG by itself had no effect on Palbumin (0.19 +/- 0.10, n = 15). CONCLUSIONS: Our results show that TWG blocks protamine, TNF-alpha, superoxide, and FSGS serum-mediated increase in glomerular albumin permeability in vitro. We conclude that reduction of proteinuria by Tripterygium wilfordii multiglycoside in various kinds of glomerular diseases in vivo might be due to protection of the glomerular filtration barrier.

Animals↗

Spontaneous perforation of the gallbladder during infancy diagnosed on hepatobiliary imaging.

Spontaneous gallbladder perforation is a very rare condition in infants. Most gallbladder perforations occur in adults, frequently due to trauma. Ultrasound, peritoneal lavage, and retrograde cholangiography may give indirect evidence of the possibility of this condition. There is no definitive diagnostic modality that can definitely determine the diagnosis in such cases. A case of gallbladder perforation with localized biliary ascites detected on radionuclide hepatobiliary imaging is presented.

Biliary Tract↗

Trichomoniasis in a postmenopausal woman cured after discontinuation of estrogen replacement therapy.

BACKGROUND: Epidemiologic and experimental data suggest that estrogen has a salutary effect on Trichomonas vaginalis. CASE: A metronidazole-allergic postmenopausal woman was cured of vaginal trichomoniasis in association with discontinuation of estrogen replacement therapy. CONCLUSION: Hormonal manipulation should be studied for the management of women with trichomoniasis who are allergic to metronidazole or who are infected with metronidazole-resistant strains of Trichomonas vaginalis.

Antitrichomonal Agents↗

Survival benefits of pulmonary cellular activation in AIDS patients with Pneumocystis infection.

Pneumocystis carinii pneumonia (PCP) is the most common life-threatening, opportunistic infection in patients with acquired immunodeficiency syndrome. Between 1984 and 1987, patients infected with human immunodeficiency virus (HIV) received bronchoalveolar lavages to confirm PCP diagnosis. Unstained slides containing bronchoalveolar cells from 20 of these patients were stored. Eight years after the last diagnostic bronchoalveolar lavage, blinded investigators immunohistochemically analyzed the unstained bronchoalveolar cells for the presence of proliferating cells and pneumocystic cysts. A significant association was found between the percentage of activated macrophages and patient survival after diagnostic bronchoalveolar lavage. On chart review, patients with higher CD4/CD8 ratios had significantly greater alveolar macrophage activation. The correlation of life span and pulmonary cellular activation in these cases (most predating retroviral therapy) suggests the importance of pulmonary cellular function to immunity and survival in patients infected with HIV.

AIDS-Related Opportunistic Infections↗

Unusual computed tomography appearance of Castleman disease.

A case is presented here of Castleman disease in an uncommon location. Ultrasonography demonstrated a large hypoechoic mass with multiple vascular channels. On computed tomography, the lesions with a nodular contour were located lateral to the carotid sheath on the right side, and demonstrated a variegated enhancement pattern.

Adult↗

An interesting unusual case of endometrial stromal sarcoma.

An interesting case with an unusual presentation of endometrial sarcoma is described. This patient presented with a history of continuous vaginal bleeding 3 months following a full term caesarean section and perception of an enlarging abdominal mass. The physical examination revealed an enlarged uterus with a leiomyoma though there was no evidence of the same at the time of the caesarean section. A laparotomy was undertaken and the patient was found to have a large tumor with multiple polypoidal growths invading the myometrium through to the serosa. This was proven to be an endometrial stromal sarcoma on histopathology.

Adult↗

Differences in dosimetry and toxicity between definitive and postprostatectomy radiation therapy.

PURPOSE: To compare the volumes of normal tissue irradiation and toxicity in patients treated with definitive radiation therapy or postprostatectomy radiation therapy. MATERIALS AND METHODS: Results were analyzed prospectively in 49 patients who underwent definitive or postprostatectomy radiation therapy after three-dimensional conformal treatment planning. Dose-volume histograms and the effective area irradiated were analyzed. Patient charts were reviewed and scored for acute and chronic toxicity. The mean bladder volume was 200 mL in the definitive group and 226 mL in the postprostatectomy group. The mean rectal volume was 87 mL in the definitive group and 81 mL in the postprostatectomy group. RESULTS: The dose to 25% of the rectal volume was 91% and 86% in the definitive and postprostatectomy groups, respectively. The dose to 25% of the bladder volume was 89% in the definitive group and 82% in the postprostatectomy group. The incidence of acute and chronic gastrointestinal and chronic genitourinary toxicity was similar in both groups, but acute genitourinary toxicity in the postprostatectomy group was significantly lower (P = .026). The volume of normal tissue irradiated was similar in both groups. Also, similar doses were delivered to the normal tissue. CONCLUSION: Differences in acute genitourinary toxicity are most likely secondary to radiation-induced prostatitis. Postprostatectomy radiation therapy is safe and is not associated with increased toxicity.

Acute Disease↗

Direct effects of platelet-activating factor on glomerular capillary permeability.

Platelet-activating factor (PAF) is an important mediator of injury in acute renal failure and glomerulonephritis. Intrarenal infusion of PAF reduces glomerular filtration rate and renal plasma flow and increases glomerular permselectivity via its renal hemodynamic and/or immunologic effects. Direct effects of PAF on glomerular capillary permeability are not known. We studied the direct effects of PAF on mesangial contraction (a measure of filtration area), glomerular capillary hydraulic conductivity (L[p]) and capillary albumin permeability (P[albumin]). Glomeruli were isolated from Sprague-Dawley rats and incubated with or without various concentrations of PAF (10[-9], 10[-7] and 10[-5] M) for up to 5 h at 37 degrees C. Mesangial contraction (percent change in glomerular volume) was assessed from the gradual decrease in volume of glomeruli during 20 min of incubation with PAF. L(p) was calculated from the rate of change in glomerular volume during the 0.1 s of capillary expansion in response to a transcapillary oncotic gradient. P(albumin) was calculated from a change in relative volume of glomeruli in response to an oncotic gradient. Mesangial contraction was maximal after 20 min of incubation and was concentration dependent (5.2+/-0.9, 7.9+/-1.0 and 10.0+/-1.0%, respectively, with PAF 10(-9), 10(-7) and 10(-5) M). Incubation of glomeruli with PAF 10(-7) M for 60 min at 37 degrees C caused a significant decrease in L(p) (2.25+/-0.30 vs. control 3.12+/-0.28 microl x min(-1) x mm Hg(-1) x cm(-1), n = 5). P(albumin) of glomeruli incubated with PAF was unchanged up to 2 h but increased significantly with the highest concentration of PAF (10(-5) M) after 3 h of incubation (0.60+/-0.18, n=15, vs. control 0.00+/-0.08, n = 20), whereas lower concentrations of PAF (10[-7] or 10[-9] M) required at least 5 h of incubation with glomeruli to cause a significant increase in P(albumin) (0.45+/-0.09 and 0.48+/-0.07, respectively, n=15, vs. control 0.00+/-0.08, n=15). We conclude that PAF has multiple direct effects on glomerular functions, which are time dependent and may contribute to the altered capillary permeability in vivo.

Albumins↗

Minimal change nephrotic syndrome associated with extrarenal neurilemmoma.

Nephrotic syndrome may be associated not only with malignant neoplasia, but also rarely with benign solid tumours. Here we report a case of a young woman suffering from nephrotic syndrome, histologically classed as a minimal change glomerular lesion, associated with a posterior mediastinal neurilemmoma (ancient neurilemmoma). Surgical removal of the tumour led to complete cure of the nephrotic syndrome with total symptomatic improvement within 6 months. Scanning of the literature revealed only one case report of an association of spinal neurilemmoma with nephrotic syndrome.

Adult↗

Symptomatic adrenal myelolipoma. Clinicopathological analysis of 7 cases and brief review of the literature.

Seven cases of adrenal myelolipoma comprising 5.8% of total adrenal tumors are described with a male-to-female ratio of 1.3:1. Five were symptomatic, of which 4 had a palpable abdominal mass, 2 cases detected incidentally were associated with carcinoma of the uterine cervix and renal cell carcinoma, respectively. The average age and duration of symptoms at presentation were 56 years (range 38-70 years) and 3.16 months (range 1-9 months). A CT scan was done in all cases, of which 5 showed a nonenhancing mass lesion with fat density diagnosed as adrenal myelolipoma. However, in 1 case radiological diagnosis of liposarcoma was maintained because of the huge size of the lesion whereas in another case the lesion was missed because of associated renal cell carcinoma. Interestingly the right adrenal was involved in all cases and the weight varied from 7 to 2,000 g. No recurrence was noted in the follow-up period (ranging from 3 months to 10 years).

Adolescent↗

Tuberculous osteomyelitis.

Tuberculous osteomyelitis which does not involve a joint is uncommon and may fail to be diagnosed by an orthopaedic surgeon. We treated 28 lesions of tuberculous osteomyelitis in 25 patients between 1988 and 1995. The duration of symptoms was from two to 39 months, and most of our patients had been treated initially with non-steroidal anti-inflammatory drugs which failed to provide relief. Bone pain which does not promptly respond to analgesic medication is often due to infection or neoplasia. In the early stages, when plain radiographs are normal, MRI or CT may help to localise lesions. On plain radiographs, more advanced lesions may mimic chronic pyogenic osteomyelitis, Brodie's abscess, tumours or granulomatous lesions. Biopsy is mandatory to confirm the diagnosis, and antituberculous drugs are the mainstay of treatment. When operative findings at biopsy have the features of skeletal tuberculosis curettage of the affected bone may promote earlier healing.

Adolescent↗