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Biomedical subjects

T K Rao

Publications and source records attributed to T K Rao.

At least 37 records · Page 2Linked to original sources

The types of renal disease in the acquired immunodeficiency syndrome.

Between January 1982 and December 1986, among the 750 patients with the acquired immunodeficiency syndrome (AIDS) who were treated at two adjacent hospitals in New York City, 78 (10.4 percent) needed evaluation for renal disorders. Reversible acute renal failure due to nephrotoxic injury, ischemic injury, or both was present in 23 patients (30 percent) (Group I). The remaining 55 (70 percent) had massive proteinuria, azotemia, or both (AIDS-associated nephropathy; Group II), and irreversible uremia developed in 43. In an additional 18 patients, all of whom had a history of intravenous narcotic drug use, AIDS was diagnosed after the initiation of maintenance hemodialysis for chronic renal failure (Group III). Survival for more than six months after the onset of chronic uremia occurred in only two subjects in Group II; all patients in Group III died within three months of the diagnosis of AIDS. Death in the patients in Groups II and III followed a syndrome of "failure to thrive" characterized by inanition unresponsive to intensive nutritional support and hemodialysis. In contrast, 8 of 17 patients with acute renal failure (Group I) and a serum creatinine concentration above 6 mg per deciliter regained renal function (serum creatinine level, less than 2.0 mg per deciliter). Four of the seven lived for 10 to 24 months, whereas the other four died of sepsis within a month. Our observations suggest that maintenance hemodialysis is not effective in prolonging life either in patients with AIDS-associated nephropathy and uremia or in patients with end-stage renal failure in whom AIDS develops during the course of maintenance dialysis. Hemodialysis may be useful in the management of potentially reversible acute renal failure in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome.

Of the 92 patients with the acquired immunodeficiency syndrome (AIDS) who were seen at our institution over a two-year period, 9 acquired the nephrotic syndrome (urinary protein greater than 3.5 g per 24 hours) and 2 had azotemia with lesser amounts of urinary protein. Five of these 11 patients had a history of intravenous-heroin addiction, but in the remaining six, there were no known predisposing factors for nephropathy. In nine patients (including the six non-addicts) the course of renal disease was marked by rapid progression to severe uremia. Renal tissue examined by biopsy in seven patients and at autopsy in three revealed focal and segmental glomerulosclerosis with intraglomerular deposition of IgM and C3. In the 11th patient, renal biopsy revealed an increase in mesangial matrix and cells, with deposition of IgG and C3 consistent with a mild immune-complex glomerulonephritis, and severe interstitial nephritis. We conclude that focal and segmental glomerulosclerosis may be associated with AIDS and suggest that rapid deterioration to uremia may characterize this renal disease.

Acquired Immunodeficiency Syndrome↗

The distribution of dermal tumorigens in coal liquids: relationship of tumorigenicity and microbial mutagenicity.

Polycyclic aromatic hydrocarbons and/or their pyrolle derivatives were found to be the primary contributors to the skin tumorigenicity of the neutral fractions of two coal oils. Mutagenicity of the neutral fraction in Salmonella test strains was found to be due primarily to polycyclic aromatics containing polar substituents. Thus, the chemical classes responsible for skin tumorigenicity differ from those responsible for mutagenicity.

Animals↗

Renal ultrasound in acquired immune deficiency syndrome.

Ten patients with clinical and laboratory features of acquired immune deficiency syndrome (AIDS) underwent renal ultrasonography prior to biopsy because of proteinuria, azotemia, or uremia. Four patients had a history of intravenous heroin abuse and were considered separately so as to exclude it as a cause of nephropathy. Histological examination revealed focal segmental glomerulosclerosis (FSGS), which in patients with AIDS is characterized by rapid progression to severe uremia (though FSGS can also occur in several other forms of renal disease). The authors recommend that AIDS-associated FSGS be considered as a cause of type I parenchymal disease and suggest that serial sonograms may be useful in monitoring progressive renal involvement.

Acquired Immunodeficiency Syndrome↗

Increased serum angiotensin-converting enzyme in chronic renal disease.

Serum angiotensin-converting enzyme (SACE) was significantly elevated in 16 of 48 patients with various types of chronic renal disease not on hemodialysis [45.6 +/- (SD) 16.7 nmol/min/ml, p less than 0.001] and in 17 of 52 patients with chronic renal disease on maintenance hemodialysis (43.2 +/- 13.8, p less than 0.001) in comparison with 58 healthy adult controls (32.2 +/- 9.8). There was no significant relationship between SACE and renal function as indicated by serum creatinine and creatinine clearance, or the presence or absence of maintenance hemodialysis, except for a transiently increased elevation of SACE immediately post-dialysis due to hemoconcentration. There was a statistically insignificant positive correlation between SACE and 24-hour urinary protein excretion (r = 0.254, n = 21). Mean blood pressure measured in patients on maintenance hemodialysis was inversely related to SACE (p less than 0.05) following dialysis. Chronic renal disease irrespective of severity and therapy tends to be associated with elevated SACE and must be considered in the evaluation of sarcoidosis.

Adult↗

Enhancement of mutagenic activity in Salmonella by contraceptive steroids.

Two oral contraceptive steroids, mestranol and norethynodrel, were evaluated for mutagenicity in the Salmonella histidine reversion assay. The pure forms of the hormones were not mutagenic when tested with either missense (TA1535, TA100) or frameshift (TA98, TA1538, TA1537) strains. In vitro activation of the hormones with liver homogenates from rats induced either with phenobarbital or Aroclor did not influence these results. However, mestranol was capable of enhancing the mutation yield obtained by an ineffective subthreshold dose of 2-acetylaminofluorene. Dimethyl sulfoxide extracts of two contraceptive pills, Ovulen-21 (containing mestranol) or Enovid-E (containing mestranol or norethynodrel), also were nonmutagenic. But again, both these extracts were capable of enhancing the mutation yield induced with an ineffective dosage of 2-acetylaminofluorene and N-nitrosopiperidine. These studies point to the possible promotional effect and subsequent potential hazard to the female consumers who use these hormones as a means of pregnancy control.

Contraceptives, Oral↗

Preparation of oils for bacterial mutagenicity testing.

4 procedures used to prepare fossil-derived oils for bacterial mutagenicity testing have been examined. These are, (a) dewaxing by partitioning the oil between dimethyl sulfoxide (DMSO) and cyclohexane, (b) incorporating a surfactant to increase compatibility of the oil with the bioassay media, (c) directly slurrying the oil in DMSO, and (d) computing the mutagenicity of the oil by summing the contributions of individual chemical class fractions. DMSO slurries generally exhibit higher mutagenicities than computed by summing the contributions of chemical class fractions. Results of testing DMSO-slurries correlate (r = 0.87) well, however, with those obtained by summation. Mutagenicity results agree within a factor of two for the samples tested by 4 sample preparation procedures.

Animals↗

Mutagenicity of 4,4'-methylenedianiline derivatives in the Salmonella histidine reversion assay.

4,4'-Methylenedianiline and its derivatives were assayed for mutagenicity in the Salmonella/microsomal mutagenicity assay develop by Ames. A specificity to revert strain TA98 suggests a mechanism of frameshift mutagenesis. Liver microsomal preparations (S-9) from rats induced with phenobarbital were most effective for metabolic activation. Alkyl substitution of 4,4'-methylenedianiline did not alter its mutagenic activity; however, substitution of both positions ortho to the amino group eliminated mutagenic activity. Substitution with alkoxy-carbonyl groups eliminated mutagenic activity, whereas halogen substitution (chlorine, fluorine) enhanced the mutagenic activity. The results presented here show the use of structure-activity studies as predictive tools for the assessment of genotoxic properties of industrial chemicals.

Aniline Compounds↗

Characterization of mutagenic coal fly ash and extracts.

Post-electrostatic precipitator (ESP) fly ash samples were collected from a coal-fired electric power generation plant under three modes of plant operation: normal operation, a low NOx-emission mode of combustion, and operation with the ESP shorted-out. Results of chemical and physical characterization of the ashes were compared with bacterial mutagenicity bioassay to determine parameters or compounds correlating with bioactivity. The general physical properties, ultimate composition, and trace elemental and radiochemical species determined did not correlate with the mutagenicity. Only the presence of aromatic hydrocarbons and chemically derivatizable polar organic compounds appeared to be associated with mutagenicity of the fly ash.

Carbon↗

Structure activity studies with N-nitrosamines using Salmonella typhimurium and Escherichia coli.

Mutagenic activities of a large number of nitrosamines were determined using Salmonella histidine reversion and Escherichia coli arginine reversion assays. The cyclic nitrosamines exhibited a close correlation between their mutagenic and carcinogenic properties, while no such relationship was evident with the aliphatic nitrosamines. Substitution of cyclic nitrosamines with methyl, hydroxy and oxy groups did not alter the mutagenic activities. However, when positions alpha to the N-nitroso groups were substituted with methyl groups, the biological activity was eliminated. Substitution with halogens enhanced, whereas carboxyl substitution eliminated the biological activity. The E. coli assay not only substantiated the observations made with Salmonella, but also demonstrated mutagenic activity in the case of certain carcinogenic nitrosamines which were not mutagenic in the Salmonella assay.

Animals↗