Search PubMed⌕ Search

Biomedical subjects

J Reddy

Publications and source records attributed to J Reddy.

At least 19 recordsLinked to original sources
PubMed2001

IL-2-induced tumor necrosis factor (TNF)-beta expression: further analysis in the IL-2 knockout model, and comparison with TNF-alpha, lymphotoxin-beta, TNFR1 and TNFR2 modulation.

IL-2 induces the stimulation of inflammatory and immune reactions, and the apoptosis of antigen-activated cells. However, the molecular basis of these pleiotropic functions is largely unknown. We have previously reported that IL-2 induces genes involved in cytoskeleton organization, oncogene regulation and transcriptional control. In an IL-2-dependent cell line, we have also shown that IL-2 induces tumor necrosis factor (TNF)-beta mRNA through the Jak-STAT pathway. Here, we first demonstrate in vitro that IL-2 induces mature and partially spliced TNF-beta mRNA in the splenocytes and lymph node cells of both IL-2(-/-) and IL-2(+/-) mice. Under the same experimental conditions, IL-2 is seen to induce TNF-alpha mRNA. mRNA expression is followed by semiquantitative RT-PCR and this analysis is then extended in vivo by studying different lymphoid organs from IL-2(-/-)animals. Strikingly, the expression of TNF-beta mRNA is noted to be extremely low in the spleens and lymph nodes of IL-2(-/-) mice. Similarly, TNF-alpha, lymphotoxin (LT)-beta, TNFR1 and TNFR2 mRNA levels are also low in the spleens of IL-2(-/-) animals, whereas IFN-gamma and IL-4 mRNA levels remain unaffected in these animals. The experimental values are significantly different (P < or = 0.05) from those of control IL-2(+/-) animals. Western blot analysis of TNF-alpha expression confirmed and extended the results at the protein level. For the first time, we demonstrate that IL-2 directly or indirectly regulates genes of the TNF-TNFR family in secondary lymphoid organs. Furthermore, IL-2(-/-) animals in which thymopoiesis is unaffected show normal expression of these genes. Altogether, our data further define the pleiotropic effects of IL-2 at the molecular level.

Animals↗
PubMed1999

Microbial conversion of indene to indandiol: a key intermediate in the synthesis of CRIXIVAN.

Indene is oxidized to mixtures of cis- and trans-indandiols and related metabolites by Pseudomonas putida and Rhodococcus sp. isolates. Indene metabolism is consistent with monooxygenase and dioxygenase activity. P. putida resolves enantiomeric mixtures of cis-1,2-indandiol by further selective oxidation of the 1R, 2S-enantiomer yielding high enantiomeric purity of cis-(1S, 2R)-indandiol, a potential intermediate in the synthesis of indinavir sulfate (CRIXIVAN), a protease inhibitor used in the treatment of AIDS. Molecular cloning of P. putida toluene dioxygenase in Escherichia coli confirmed the requirement for the dihydrodiol dehydrogenase in resolving racemic mixtures of cis-indandiol. Rhodococcus sp. isolates convert indene to cis-(1S, 2R)-indandiol at high initial enantiomeric excess and one isolate also produces trans-(1R, 2R)-indandiol, suggesting the presence of monooxygenase activity. Scale up and optimization of the bioconversions to these key synthons for chiral synthesis of potential intermediates for commercial manufacture of indinavir sulfate are described.

Drug Design↗
PubMed1999

Development of a bioconversion process for production of cis-1S,2R-indandiol from indene by recombinant Escherichia coli constructs.

Recombinant Escherichia coli cells expressing the toluene dioxygenase (TDO) genes from Pseudomonas putida convert indene to cis-1S,2R-indandiol, a potentially important intermediate for the chemical synthesis of the HIV-1 protease inhibitor, Crixivan. A bioconversion process was developed through optimization of medium composition and reaction conditions at the shake-flask and 23-1 fermentor scales. A cis-1,2-indandiol productivity of approx. 1000 mg/l was achieved with construct TDO123, which represents a 50-fold increase over the initial titer. Varying the bioconversion conditions did not change the enantiomeric excess (e.e.) for the 1S,2R enantiomer from about 30%, suggesting that toluene dioxygenase intrinsically converts indene to 1S,2R- and 1R,2S-indandiols at a ratio of 2:1. Further inclusion of the Pseudomonas dehydrogenase gene in construct D160-1 led to the production of chirally pure cis-1S,2R-indandiol (e.e. > 99%) as a result of the selective degradation of the 1R,2S enantiomer, with the overall yield (650 mg/l) proportionally reduced. A single stage process was developed for D160-1 and scaled up to the 23-1 fermentor, achieving a cis-1S,2R-indandiol titer of 1200 mg/l.

Cloning, Molecular↗
PubMed1999

In memoriam

Explore the source record for details and available documents.

Journal Article↗
PubMed1998

Secondary metabolite scale-up to minimize homolog impurity levels

A mutant strain of Streptomyces hygroscopicus was found to produce up to 9.0 units/L of an immunoregulant precursor, immunomycin, with up to 3.5% of a lower homolog impurity under either dual fed-batch or batch conditions. Glycerol and valine were key nutrients influencing productivity and impurity levels. Soybean oil was successfully substituted for glycerol as a carbon source to minimize shot additions to batch culture. The remainder of the production medium was composed largely of defined components with the exception of yeast extract. Valine limitation increased lower homolog formation while decreasing higher homolog formation; excess valine decreased lower homolog formation below 2-3% while increasing higher homolog formation. Higher homolog formation in the presence of valine seemed to be slower than lower homolog formation in the absence of valine. Valine was believed to be the major butyrate precursor; consequently its availability influenced the impurity profile. A preliminary cost analysis suggests that elimination of added valine from the cultivation and replacement of glycerol with soybean oil can result in a 6.6-fold reduction in media costs relative to the original fed-batch process. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗
PubMed1997

Congenital dermoid cyst of the tongue.

True dermoid cysts of the oral cavity are rare, usually presenting as midline swellings in the floor of the mouth and occasionally elsewhere in the oral cavity. This report describes the diagnosis and management of a congenital dermoid cyst of the lateral aspect of the body of the tongue in a 10-year-old girl. The theories of the pathogenesis of this cyst during embryogenesis of the tongue are also reviewed.

Child↗
PubMed1997

Process optimization for large-scale production of TGF-alpha-PE40 in recombinant Escherichia coli: effect of medium composition and induction timing on protein expression.

The effects of medium composition and induction timing on expression of a chimeric fusion protein TGF-alpha-PE40 (TP-40) in Escherichia coli strain RR1 were examined using a complex medium at several fermentor scales. Two distinctive phases in E. coli catabolism were identified during fermentation based on preferential utilization between protein hydrolysate and glycerol. Maximum specific and volumetric productivities were achieved by inducing the culture when the cells were switching substrate utilization from protein hydrolysate to glycerol. By increasing the yeast extract concentration in the production medium, initiation of the catabolic switch was delayed until high cell mass was achieved. The final titer of TP-40 at the 15-L fermentation scale was doubled from 400 mg L-1 to 850 mg L-1 by increasing the yeast extract concentration from 1% to 4% (w/v) and delaying the time of induction. This fermentation process was rapidly scaled up in 180-L and 800-L fermentors, achieving TP-40 titers of 740 and 950 mg L-1, respectively.

Antineoplastic Agents↗
PubMed1996

Long-term immunosuppression without corticosteroids after orthotopic liver transplantation: a positive therapeutic aim.

Long-term treatment with corticosteroids after orthotopic liver transplantation (OLT) may cause adverse effects, particularly hypertension, diabetes, and bone disease. The results of steroid withdrawal from long-term immunosuppression in 114 patients after OLT was reviewed. Initial treatment was with corticosteroids, azathioprine, and cyclosporine A in 76.3% and with antithymocyte globulin in 17.5%. Corticosteroids were stopped in 96 patients (84.2%) during mean follow-up of 6.7 +/- 3.9 months, and acute rejection subsequently developed in 8. By comparison 7 of 18 patients, in whom corticosteroids were continued, developed acute rejection. Six of these had received blood group (ABO)-compatible nonidentical grafts. Rates for retransplantation in the steroid withdrawal and nonwithdrawal groups were 4.2% and 22.2%, respectively, and mortality in the two groups was 14.6% and 44.4%, respectively. Azathioprine was not given or withdrawn in 28 patients in the group from which corticosteroids were also withdrawn, with no adverse effect. Diabetes mellitus improved following corticosteroid withdrawal, but there was no improvement in hypertension. We conclude that corticosteroids can be safely withdrawn in the majority of patients after OLT.

Adrenal Cortex Hormones↗
PubMed1996

Alprazolam-induced hypomania.

OBJECTIVE: There are reports of alprazolam-induced hypomania/mania. Here is a case report of a patient who developed hypomania during treatment with alprazolam, but not with diazepam, another benzodiazepine derivative. CLINICAL PICTURE: The illness was of 2 months' duration and the patient received a diagnosis of anxious depression. Following treatment with alprazolam, the patient developed hypomania characterised by euphoria, overactivity, overtalkactivity, racing thoughts, oversocialisation, enhanced self-confidence and disturbed sleep. TREATMENT: Hypomania subsided when alprazolam was withdrawn. There was no recurrence with fluoxetine or diazepam that ameliorated the primary condition. OUTCOME: The patient was symptom-free on follow-up. CONCLUSIONS: Alprazolam can induce hypomania/mania and, perhaps, it differs from other benzodiazepines in its mode of action. Clinicians have to be alert to the possibility of their patients developing hypomania/mania while on alprazolam.

Adult↗
PubMed1995

Omeprazole inhibits growth of cancer cell line of colonic origin.

The direct effects of omeprazole on colonic cells has not been evaluated. Controversy exists regarding the potential adverse effects of omeprazole on cell proliferation. In order to mimic the in vivo situation in the patient treated with omeprazole, proliferation cell culture experiments were performed, monitoring directly the effects of gastrin and omeprazole both alone and in combination. Three colonic cancer cell lines were used, two with neuroendocrine features (NCI-H716, LCC-18) and one (DLD-1) not known to have these features. In these in vitro proliferation experiments, only the NCI-H716 colorectal cancer cell line responded to omeprazole by decreased proliferation (P < 0.05). The effect was concentration dependent shown for all doses of omeprazole used. Gastrin had a statistically significant effect on increasing proliferation in the NCS-H716 cell line alone but only at the highest concentration (10(-6) M). Omeprazole has a cytostatic effect on one of three colorectal cancer cell lines but the mechanism for this effect of omeprazole and its potential role in treatment awaits elucidation.

Cell Division↗
PubMed1992

Cryptococcal peritonitis in a CAPD patient.

A 50-year-old diabetic woman with end-stage renal disease, who had been on continuous ambulatory peritoneal dialysis for 8 months, developed peritonitis caused by Cryptococcus neoformans var. neoformans. The patient was completely asymptomatic and infection was confirmed by detection of budding yeast cells in Gram-stained smears of turbid peritoneal fluid. The infection was cleared after intravenous fluconazole with delayed removal of the catheter. Fluconazole may be a suitable alternative drug in treating cryptococcal peritonitis.

Cryptococcosis↗
PubMed1992

The WHO Oral Health goals for the year 2000 in South Africa.

This paper outlines a policy to attain the WHO Oral Health goals for the year 2000 by the implementation of primary and secondary prevention. The Republic of South Africa (RSA) with its complex political and social formation and an interesting mix of 1st and 3rd world populations provides the space for challenging and innovative approaches.

Adolescent↗
PubMed1991

Does trans-lesion synthesis explain the UV-radiation resistance of DNA synthesis in C. elegans embryos?

Over 10-fold larger fluences were required to inhibit both DNA synthesis and cell division in wild-type C. elegans embryos as compared with other model systems or C. elegans rad mutants. In addition, unlike in other organisms, the molecular weight of daughter DNA strands was reduced only after large, superlethal fluences. The molecular weight of nascent DNA fragments exceeded the interdimer distance by up to 19-fold, indicating that C. elegans embryos can replicate through non-instructional lesions. This putative trans-lesion synthetic capability may explain the refractory nature of UV radiation on embryonic DNA synthesis and nuclear division in C. elegans.

Animals↗