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Biomedical subjects

R Iyer

Publications and source records attributed to R Iyer.

At least 55 records · Page 3Linked to original sources
PubMed1993

Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas.

We have screened the entire coding region of c-myc in a panel of Burkitt's lymphomas (BLs) and mouse plasmacytomas (PCTs). Contrary to the belief that c-myc is wild type in these tumours, we found that 65% of 57 BLs and 30% of 10 PCTs tested exhibit at least one amino acid (aa) substitution. These mutations were apparently homozygous in all BL cell lines tested and two tumour biopsies, implying that the mutations often occur before Myc/Ig translocation in BL. In PCTs, only the mutant c-myc allele was expressed indicating a functional homozygosity, but occurrence of mutations after the translocation. Many of the observed mutations are clustered in regions associated with transcriptional activation and apoptosis, and in BLs, they frequently occur at sites of phosphorylation, suggesting that the mutations have a pathogenetic role.

Alleles↗
PubMed1993

Extended triple intrathecal chemotherapy trial for prevention of CNS relapse in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE: The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis. PATIENTS AND METHODS: With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype. RESULTS: The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P < .001 overall). The difference is statistically significant for good-risk patients (P < .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome. CONCLUSION: TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Inotropic polyazapentalene sulmazole analogues.

Aryl substituted 1H-imidazo[1,2-a]imidazole 8, imidazo[2,1-b]thiazole 9, 1,4-dihydroimidazo[4,5-d]imidazole 11, and 1(2),4-dihydroimidazo[4,5-c]pyrazoles 12-17 have been prepared. An X-ray crystallographic study confirmed the structure of 8 and showed this analogue to exist as the 1H-tautomer. These heterocycles were evaluated as inotropic agents and analogues 12, 15, and 17 found to display inotropic properties which were less potent in vitro, but more potent in vivo, than those of sulmazole. Structure-activity relationships are discussed.

Animals↗
PubMed1991

Chronic myelomonocytic leukaemia (an analysis of fourteen consecutive cases).

Fourteen consecutive cases of chronic myelomonocytic leukaemia aged 6 to 73 (mean 40.5) years were reviewed to define the natural history of the disease and the risk of acute transformation. The common presenting features included anaemia, fever, purpura, and bleeding tendencies. Abnormal karyotypes were seen in 4 of 6 patients subjected to cytogenetic analysis. Low dose cytosine arabinoside achieved complete remission in two and partial remission in one, of the four patients treated with this modality. The mean survival was 5.6 (range 2-12) months and two patients) evolved to acute myeloid leukaemia. The long term survival with the present form of therapy in chronic myelomonocytic leukaemia is poor.

Adolescent↗
PubMed1989

Danazol in treatment of angio-immunoblastic lymphadenopathy.

The clinical manifestations of angio-immunoblastic lymphadenopathy (AILD) suggest that there is an abnormality in the immune system. Most patients with AILD die from opportunistic infections associated with lymphocyte depletion. As chemotherapy further increases the already high susceptibility of infections, the therapeutic management of AILD is difficult. The achievement of complete remission (CR) by the patient described here using a danazol-based regimen raises the hope that treatment of this disease with a noncytotoxic drug may be possible. The rationale behind and advantages of using danazol are discussed.

Danazol↗
PubMed1989

Corticosteroid-responsive pure red cell aplasia in rheumatoid arthritis and its association with pregnancy: a case report.

Pure red cell aplasia (PRCA) often occurs secondary to drug therapy for rheumatoid arthritis (RA). However, idiopathic PRCA in RA is very rare. Though different immunosuppressive therapies have been tried in the past with variable responses, there has been no case report in adults of favourable response to corticosteroids alone. We report a rare case of PRCA in RA, which responded to steroid therapy. Subsequently, the patient relapsed twice, during the first trimester of consecutive pregnancies. The association of PRCA with RA and pregnancy is discussed.

Adrenal Cortex Hormones↗
PubMed1986

Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial.

Children with sickle cell anemia have an increased susceptibility to bacterial infections, especially to those caused by Streptococcus pneumoniae. We therefore conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to test whether the regular, daily administration of oral penicillin would reduce the incidence of documented septicemia due to S.pneumoniae in children with sickle cell anemia who were under the age of three years at the time of entry. The children were randomly assigned to receive either 125 mg of penicillin V potassium (105 children) or placebo (110 children) twice daily. The trial was terminated 8 months early, after an average of 15 months of follow-up, when an 84 percent reduction in the incidence of infection was observed in the group treated with penicillin, as compared with the group given placebo (13 of 110 patients vs. 2 of 105; P = 0.0025), with no deaths from pneumococcal septicemia occurring in the penicillin group but three deaths from the infection occurring in the placebo group. On the basis of these results, we conclude that children should be screened in the neonatal period for sickle cell hemoglobinopathy and that those with sickle cell anemia should receive prophylactic therapy with oral penicillin by four months of age to decrease the morbidity and mortality associated with pneumococcal septicemia.

Administration, Oral↗
PubMed1986

Adult-type osteopetrosis presenting as carpal tunnel syndrome.

We describe a patient with adult-type osteopetrosis presenting as carpal tunnel syndrome. Radiographs demonstrated sclerosis of the carpal bones, bone biopsy revealed wide bone spicules containing areas of cartilage, and electrophysiologic studies confirmed the diagnosis of median nerve entrapment in the carpal tunnel. Any condition which alters the size or shape of the carpal canal or its contents may result in median nerve compression.

Bone and Bones↗
PubMed1985

Genetic predisposition to acute lymphocytic leukemia in American blacks. A Pediatric Oncology Group study.

Recent reports have shown an association between genes lying within the major histocompatibility complex (MHC), particularly HLA and factor B (Bf), and acute lymphocytic leukemia (ALL) in white children. The frequencies of Bf and complement component C4 phenotypes in 90 black American children with ALL were examined to determine if a genetic association existed. The Bf and C4 results for the black children with ALL were compared with frequencies in healthy black Americans from the same geographic region. The BfF allele was carried by 95.6% of the black ALL patients compared with 86.1% of the controls (P = 0.017; relative risk = 3.5). In contrast, only 2.2% of the patients with ALL were homozygous for BfS compared with 9.8% of the controls (P = 0.043; relative risk = 0.2). These findings are similar to those observed in white American children. The C4A6 phenotype was found in 11.9% of the black children with ALL compared with 0.6% of the controls (P = 0.0026; relative risk = 22.7). These findings represent the first reported association of a particular allele whose gene lies within the MHC with ALL in black American children. The results suggest that the occurrence of ALL in black American children may be partially due to a genetic influence.

Adenosine Monophosphate↗
PubMed1983

Hormonal responses to intravenous glucose and arginine in patients with pancreatitis.

19 subjects with an acute episode of pancreatitis, and 5 patients with chronic pancreatitis received intravenous glucose tolerance tests with measurement of glucose, insulin and glucagon. Patients recovering from acute pancreatitis demonstrated defects in their ability to dispose of a glucose load. 10 patients had overt glucose intolerance; of these, 4 were insulin-deficient, 3 had a loss of an acute insulin response to glucose, and 3 had marked hyperglucagonemia with normal to increased insulin levels. These abnormalities were seen in response both to intravenous glucose and intravenous arginine. Therefore, according to this study, at least three factors are clearly implicated in the production of glucose intolerance after an acute episode of pancreatitis: hypoinsulinemia, delayed insulin secretory response and hyperglucagonemia.

Acute Disease↗
PubMed1982

Selective modification of nuclear proteins by polycyclic aromatic hydrocarbons and by benzo[a]pyrene diol epoxides.

Metabolites of benzo[a]pyrene (B[a]P) have been shown to modify chromosomal proteins with great specificity. Using the (+) and (-) enantiomers of anti-B[a]P diol epoxide to label isolated nuclei we found a remarkable difference in the capacity of these two compounds to modify histones H2A and H3. The (+) enantiomer modified histones H2A and H3, while the (-) enantiomer, which was shown to modify mainly histone H2A, had a much lower affinity for histone H3. We have also examined the selective, modification of chromosomal proteins by different polycyclic aromatic hydrocarbons and it was observed that 7,12-dimethylbenz[a]-anthracene (DMBA), 3-methylcholanthrene (3-MC) and B[a]P showed qualitative similarities in terms of their protein binding. This suggests that stereospecific interactions leading to binding of reactive metabolites of DMBA, B[a]P and 3-MC to chromosomal proteins share common features.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1981

beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0].

Hemoglobin Vicksburg was discovered in a 6-year-old Black boy who had been anemic since infancy. Examination of his hemolysate revealed 87.5% Hb F, 2.4% Hb A2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated a deletion of leucine at beta 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The alpha/non-alpha biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and beta 0-thalassemia, Hb Vicksburg should have comprised the major portion of the hemolysate. Thus, Hb Vicksburg was synthesized at a rate considerably lower than would be expected on the basis of gene dosage. There was no reason to suspect abnormal translation of beta Vicksburg mRNA; in individuals with Hb St. Antoine (beta 74 and beta 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of beta 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of beta Vicksburg mRNA when measured by liquid hybridization analysis with beta cDNA. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for beta +-thalassemia is present in cis to the structural mutation.

Child↗
PubMed1981

Hypogonadism in idiopathic hemochromatosis. Endocrine studies.

The mechanism of hypogonadism was studied in a 63-year-old man with idiopathic hemochromatosis. Basal levels of thyroid, prolactin, cortisol, and growth hormones were normal and responded normally to appropriate provocative stimuli. Basal testosterone and gonadotropin levels were low. There was inadequate gonadotropin response to luteinizing hormone-releasing hormone and clomiphene citrate stimulation. Testosterone response to human chorionic gonadotropin was normal. Hypothalamic-pituitary dysfunction resulting in impaired gonadotropin secretion appears to be the cause of hypogonadism in hemochromatosis.

Follicle Stimulating Hormone↗
PubMed1980

Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers.

Blood nicotine and carboxyhaemoglobin (COHb) concentrations were studied in 330 smokers (206 women and 124 men). Blood nicotine concentrations in individual smokers varied from 25 to 444 nmol/l (4 to 72 ng/ml). The average concentration, 203 nmol/l (33 ng/ml), was the same in the men and the women, although cigarette consumption was higher in the men. Despite large differences in nicotine yield, there was no relation between blood nicotine concentration and the type of cigarette smoked: smokers of plain, untipped cigarettes (1.9 mg nicotine), cigarettes with unventilated filters (1.3 mg nicotine), and cigarettes with ventilated filters (0.8 mg nicotine) had similar blood nicotine concentrations. Cigarette consumption was also similar in these three groups. The correlation between blood nicotine concentration and nicotine yield of cigarette, though significant, was low (0.21, p < 0.001), showing that the nicotine yield of the cigarettes accounted for only 4.4% of the variation in blood nicotine concentrations. Similarly, the low correlation of 0.30 between COHb concentration and cigarette consumption suggests that cigarette consumption accounted for only 9% of the variation in the amount of smoke taken into the smokers' lungs. These results suggest that the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation. The findings of epidemiological studies showing lower risks with filter-tipped cigarettes may be attributable to other factors such as biases in the samples and changes in the quality and carcinogenicity of tobacco tar, rather than to reduced tar intake.

Carboxyhemoglobin↗