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Biomedical subjects

B Lal

Publications and source records attributed to B Lal.

At least 37 records · Page 2Linked to original sources

Endothelial cell implantation and survival within experimental gliomas.

The delivery of therapeutic genes to primary brain neoplasms opens new opportunities for treating these frequently fatal tumors. Efficient gene delivery to tissues remains an important obstacle to therapy, and this problem has unique characteristics in brain tumors due to the blood-brain and blood-tumor barriers. The presence of endothelial mitogens and vessel proliferation within solid tumors suggests that genetically modified endothelial cells might efficiently transplant to brain tumors. Rat brain endothelial cells immortalized with the adenovirus E1A gene and further modified to express the beta-galactosidase reporter were examined for their ability to survive implantation to experimental rat gliomas. Rats received 9L, F98, or C6 glioma cells in combination with endothelial cells intracranially to caudate/putamen or subcutaneously to flank. Implanted endothelial cells were identified by beta-galactosidase histochemistry or by polymerase chain reaction in all tumors up to 35 days postimplantation, the latest time examined. Implanted endothelial cells appeared to cooperate in tumor vessel formation and expressed the brain-specific endothelial glucose transporter type 1 as identified by immunohistochemistry. The proliferation of implanted endothelial cells was supported by their increased number within tumors between postimplantation days 14 and 21 (P = 0.015) and by their expression of the proliferation antigen Ki67. These findings establish that genetically modified endothelial cells can be stably engrafted to growing gliomas and suggest that endothelial cell implantation may provide a means of delivering therapeutic genes to brain neoplasms and other solid tumors. In addition, endothelial implantation to brain may be useful for defining mechanisms of brain-specific endothelial differentiation.

Adenovirus E1A Proteins↗

Development of endogenous beta-galactosidase and autofluorescence in rat brain microvessels: implications for cell tracking and gene transfer studies.

Cell transplantation is commonly used in studies of CNS development, tumor biology, and gene therapy. Fluorescent dyes and the E. coli lacZ reporter gene are used to identify transplanted cells in host tissues. The usefulness of these methods depends on host autofluorescence and beta-galactosidase (beta-Gal) activity. Our interest in the CNS vasculature led us to examine vascular autofluorescence and beta-Gal activity in postnatal and adult rat brains. Brains were perfusion-fixed (3.7% paraformaldehyde), cryoprotected, and cryostat-sectioned (12 microns). Autofluorescent vessel profiles were quantitated in sections using rhodamine filter sets and beta-Gal-positive vessels were quantitated under bright-field after incubation of sections with X-Gal chromogenic substrate for 1-18 hr at 37 degrees C. Multifocal vessel autofluorescence appeared in postnatal Day (PND) 18 Lewis rats (0.6 +/- 0.4 vessels/field) and increased tenfold in adults (6.8 +/- 0.3/field). The numbers of beta-Gal-positive vessels in PND 18 and adult sections incubated with X-Gal for 18 hr were 21.1 +/- 1.7 and 119 +/- 17, respectively. Host beta-Gal staining was similar to that produced by implanted endothelial cells expressing the bacterial lacZ reporter gene. Reducing incubation times in X-Gal to less than 4 hr eliminated endogenous staining and retained lacZ-specific staining. The presence of vascular autofluorescence and endogenous beta-Gal activity must be considered when either fluorescence- or lacZ-dependent cell markers are used in rat brain.

Animals↗

Aluminum ingestion alters behaviour and some neurochemicals in rats.

Effect of aluminum (Al) has been investigated on the brain of rats exposed to this metal (500 mg Al/liter in drinking water) daily for 180 days. A significant reduction in the spontaneous locomotor activity was noticed after 90 and 180 days of Al exposure to the rats, the magnitude of the change being almost identical at both the time intervals. Aluminum exposure also produced significant deficits in acquisition and retention of learned response in active avoidance situation, these changes being time dependent. A significant retardation of the extinction of the learned task was noted in Al exposed rats especially at 180 days. There was significant increase in the lipid peroxidation and decrease in the activity of Mg(2+)-ATPase and Na+,K(+)-ATPase in the brain of rats at 180 days after Al exposure. The increase in the contents of the metal was maximum in rest of the brain region (87% of control) followed by hippocampus and cerebral cortex (59% of controls), cerebellum and corpus striatum (43% and 44% of controls, respectively) after 180 days. Whether Al is responsible to initiate neurotoxic effects by producing changes in the structure and function of the plasma membrane needs further investigations.

Adenosine Triphosphatases↗

Effect of endosulfan (thiodan) on vitellogenesis and its modulation by different hormones in the vitellogenic catfish Clarias batrachus.

This programme was planned in order to study the reproductive dysfunction caused by endosulfan in the fish Clarias batrachus with special reference to vitellogenesis. Vitellogenin was measured by radioimmunoassay. Endosulfan caused a drastic reduction in the plasma vitellogenin which was partially reversed by estradiol-17 beta (E2) in intact and ovariectomized fish. Hormones in combination were more effective than any single hormone in overcoming the impact of endosulfan. Triiodothyronine (T3), ovine luteinizing hormone releasing hormone (oLHRH) were effective in minimizing the effect of endosulfan whereas cortisol (F) and ovine somatotropic hormone (oStH) did not reduce the effect of endosulfan. Amongst the combined hormone treatments, E2 + oLHRH and E2 + T3 were the most potent in overcoming the effect of endosulfan on vitellogenesis.

Animals↗

Thyroid physiology impairment by malathion in the freshwater catfish Clarias batrachus.

Effects of malathion on serum and glandular thyroxine (T4), triiodothyronine (T3), the T3/T4 ratio, peroxidase activity, and extrathyroidal conversion of T4 to T3 have been studied in the freshwater catfish Clarias batrachus during the prespawning and spawning phases of its annual reproductive cycle. Malathion inhibited T4 secretion in the kidney, but accelerated T4 synthesis in the pharyngeal thyroid. This pesticide also inhibited the extrathyroidal conversion of T4 to T3 in serum during both the studied phases.

Animals↗

Effect of endosulfan on thyroid physiology in the freshwater catfish, Clarias batrachus.

Effects of endosulfan on thyroid physiology have been studied in the female freshwater catfish. Clarias batrachus during the pre-spawning and spawning phases of its annual reproductive cycle. Effects of endosulfan varied with the length (96 h and 16 days) of exposure, reproductive status of the fish and organ. The 96-h endosulfan exposure significantly increased the level of thyroxine (T4) in serum and pharyngeal thyroid follicles concurrent with induction of peroxidase activity. However, triiodothyronine (T3) level and T3/T4 ratio decreased in serum and pharyngeal thyroid gland. No change was noticed in any of these parameters in the anterior kidney but in the posterior kidney endosulfan reduced T3 and T3/T4 ratio without affecting T4 levels and peroxidase activity. Sixteen days of endosulfan treatment also had a similar impact, except that it did not influence the studied parameters in pharyngeal thyroid.

Animals↗

Carbaryl-induced thyroid dysfunction in the freshwater catfish Clarias batrachus.

Freshwater female catfish, Clarias batrachus, were exposed to sublethal concentrations of carbaryl (12 mg/liter for 96 hr and 5 mg/liter for 16 days) during the prespawning and spawning phases of their annual reproductive cycle. The effects on the levels of thyroxine (T4) and triiodothyronine (T3), the T3/T4 ratio, and the extrathyroidal conversion of T4 to T3 were studied in serum, pharyngeal thyroid, and anterior and posterior kidney. Carbaryl exposure for 96 hr suppressed T4 but elevated T3 and the T3/T4 ratio in serum during both phases of experimentation. However, 16 days exposure caused a decline in T4 as well as in T3 and in the T3/T4 ratio. In the pharyngeal thyroid, carbaryl increased T4 as well as peroxidase activity and decreased T3 and the T3/T4 ratio. Its treatment for 96 hr did not elicit any change in the parameters studied in the anterior kidney, whereas in the posterior kidney it suppressed the levels of T4 and T3, peroxidase activity, and the T3/T4 ratio. However, carbaryl exposure for 16 days provoked increases in T4 and peroxidase activity but decreases in T3 and the T3/T4 ratio in anterior kidney. In posterior kidney, it did not change T4 and peroxidase activity, but decreased T3 and the T3/T4 ratio. It also stimulated extrathyroidal conversion of T4 to T3.

Animals↗

Cell mediated immune response of chicks following fowl adenovirus type-1 infection.

Cellular immune response of 6-week-old chickens infected with fowl adenovirus type-1 was evaluated by both in vivo and in vitro assay. In vitro assay, enumerating peripheral T lymphocyte by alphanaphthyl acetate esterase staining, revealed that cellular immunity appeared as early as 1 week post-infection and was maintained up to 5 weeks post-infection. In vivo assay by phytohaemagglutin skin test showed cellular immunity until 2 weeks post-infection. Thereafter no immunity was observed by this assay.

Adenoviridae Infections↗

Pesticides induced changes in circulating thyroid hormones in the freshwater catfish Clarias batrachus.

1. Effects of endosulfan, malathion and carbaryl on circulating T4, T3 and T3/T4 ratio in the freshwater catfish, C. batrachus have been studied during reproductively active phases, i.e. vitellogenic and post-vitellogenic phases of its annual reproductive cycle. 2. Endosulfan provoked a significant increase in T4 and a decrease in T3 as well as the T3/T4 ratio. 3. Malathion decreased T3 and T3/T4 ratio without altering the level of T4 in circulation. 4. Carbaryl caused a decline in the level of T4 and an elevation in T3 and T3/T4 ratio.

Animals↗

Cardiotoxicity and hypertension in rats after oral lead exposure.

The rats were exposed to lead (0.25, 0.5 and 1.0 per cent lead acetate through drinking water) for 90 days to study its effect on some physiological and morphological parameters of the cardiovascular system. Blood lead levels increased in a dose dependent manner but heart tissue showed rise at only two higher doses in exposed animals. The two higher doses of lead resulted in an increased arterial blood pressure and calcium influx in atrial trabeculae and papillary muscles. No marked pathological or histochemical changes were observed in heart tissue excepting congestion and slightly reduced activity of succinic dehydrogenase in the highest dosed group. It was concluded that lead exposure through drinking water may produce increased arterial blood pressure and minor changes in the myocardium. Whether these changes are mediated through the effect of lead on the calcium transport needs further investigation.

Administration, Oral↗

Adult Wilms' tumor: report of a case and review of the literature.

A 48 year old male presented with a one and a half year history of a progressively increasing, asymptomatic lump in the left hypochondrium and no history of hematuria. His general physical examination was unremarkable, and an abdominal examination revealed a large, firm, irregular and tender mass in the left hypochondrium extending into the lumbar region. Chest X-ray was normal. An intravenous urogram revealed a normally functioning right kidney with non-visualization of the left kidney. CT-scan of the abdomen revealed a large, mixed attenuating mass replacing the left kidney. At laparotomy, a large, fleshy, well-encapsulated tumor was found in the left kidney with no surrounding infiltration and a left radical nephrectomy was performed. Microscopic examination revealed a poorly differentiated tumor comprised of small round cells with focal areas of abortive embryonal tubular and glomerular differentiation suggestive of Wilms' tumor. The patient was advised chemotherapy and radiotherapy but he absconded and was lost to follow-up.

Humans↗

Effect of hexavalent chromium on testicular maturation in the rat.

Daily intraperitoneal administration of hexavalent chromium (Cr6+; 1, 2, and 3 mg/kg intraperitoneally as potassium dichromate) in weaned rats for an entire duration of 55 and 90 days of age produced dose- and duration-dependent enzymatic and pathologic alterations. At 55 days, the pathologic changes were not seen in testes of Cr6+ treated rats, but the activities of sorbitol dehydrogenase, lactic dehydrogenase, gamma-glutamyl transpeptidase, and glucose-6-phosphate dehydrogenase were significantly altered. When the treatment was prolonged to sexual maturity, that is, 90 days of age, the alterations in enzyme activities were greater, and there were dose-dependent pathologic changes in the testes of Cr(6+)-treated rats. These alterations suggest a risk to growing testes if rats are exposed to Cr6+ during the prepubertal stage of development, which, in turn, may disturb normal testicular physiology at adulthood.

Animals↗

Lead induced testicular hypersensitivity in stressed rats.

Rats were immobilized for 2 h and treated i.p. with lead Pb2+ (8 mg/kg/day) for 45 d to investigate the testicular effects of lead on rats kept under immobilization stress. Marked alteration in SDH. G6PDH activity, cholesterol and ascorbic acid contents and reduced sperm counts associated with marked pathological changes in the testis of rats were observed after combined treatment with lead and immobilization stress in comparison to either alone. An increase in the disturbances of testicular androgen synthesis seems to be responsible for enhanced testicular injury in lead induced stressed rats.

Animals↗

Effect of progestins, estradiol, and coenzymes NAD and NADPH on the interconversion of estradiol and estrone in rabbit uterus in vitro.

The biotransformation of estradiol (E2) and estrone (E1) in the uterus of rabbits treated with norgestrel (NG), norethindrone (NET), norethindrone acetate (NETA), progesterone (P4), and E2 either by subcutaneous injection in oil or by intrauterine steroid-releasing silastic implants was carried out under an in vitro short-term incubation system. The studies have shown that E2 stimulates 17 beta-hydroxysteroid dehydrogenase (17 beta-OHSD) much more than P4 as compared to untreated controls. The kinetic studies on E2 metabolism in the presence of added coenzyme NAD showed an initial rapid estrone formation and a gradual reconversion of E1 to E2. The addition of NADPH, ATP, and glucose-6-phosphate facilitates the reconversion of E1 to E2. The interconversion of E2 and estrone in the presence of coenzymes was five- to ten-fold higher in the endometrium than in the myometrium per milligram protein. Both E2 and progestins stimulate the uterine 17 beta-OHSD activity in rabbit uterus. This study further suggested that the hormone-induced metabolism of estradiol and estrone in the rabbit uterus is essentially modulated by the availability of coenzymes.

17-Hydroxysteroid Dehydrogenases↗

Lead induced testicular changes in protein malnourished rats.

The effect of concurrent low protein (8% casein) diet and lead (Pb) exposure (1 mg/ml lead acetate in drinking water) on testes of weaned rats up to 90 days of age was investigated Histopathological examination of testes of lead treated rats maintained on low protein diet revealed marked pathological changes associated with greatly reduced succinic dehydrogenase, glucose-6-phosphate dehydrogenase and adenosine triphosphatase activity as revealed histochemically compared to lead treated rats fed normal protein diet. It was concluded that higher accumulation of lead may be responsible for altering the enzyme levels and inducing the testicular degeneration to a greater extent in low protein fed rats compared to their counterpart controls.

Animals↗

Chronic cadmium-ethanol administration alters metal distribution and some biochemicals in rat brain.

The effects of cadmium (100 ppm through drinking water) and ethanol (5 g/kg by gastric gavage) administration on biogenic amines, metal distribution and certain enzymes in rat brain was investigated after 90 days of exposure. Co-exposure group revealed significant accumulation of cadmium and also increase in zinc levels compared to all the other groups. Ethanol alone decreased MAO activity and increased NE and 5-HT level while in combination with Cd, these effects were more magnified. It is, therefore, suggested that the persons consuming alcohol may be more prone to the neurotoxic effects of this metal.

Animals↗