Search PubMed⌕ Search

Biomedical subjects

Y Ravindranath

Publications and source records attributed to Y Ravindranath.

At least 91 records · Page 5Linked to original sources
PubMed1987

Two new variants of glucose-6-phosphate dehydrogenase associated with hereditary non-spherocytic hemolytic anemia: G6PD Wayne and G6PD Huron.

Two new deficient variants of glucose-6-phosphate dehydrogenase (G6PD) causing hereditary nonspherocytic hemolytic anemia (HNSHA) are described. Both of these are unique and they have been named G6PD Wayne and G6PD Huron. Patients with G6PD Wayne underwent splenectomy and no objective improvement was noted. The patients with G6PD Huron were under medical observation for a considerable period of time without the diagnosis of G6PD deficiency being entertained because the family was of Northern European origin. Since sporadic variants of G6PD causing HNSHA show no special racial predilection, the diagnosis of G6PD deficiency should always be considered in patients with this syndrome.

Adolescent↗
PubMed1987

Combined etoposide and 5-azacitidine in children and adolescents with refractory or relapsed acute nonlymphocytic leukemia: a Pediatric Oncology Group Study.

An intensive regimen of combined etoposide (VP-16) and 5-azacitidine (5-Az) was used to treat 96 children and adolescents with refractory or relapsed acute nonlymphocytic leukemia (ANLL). Patients were given two sequential five-day courses of VP-16, 250 mg/m2 for three days, followed by 5-Az, 300 mg/m2 for two days. An additional five-day course was administered if marrow aplasia was not evident by day 13. A complete remission rate of 45% was achieved with a median of two courses of VP-16 and 5-Az. The outcome of induction therapy was not influenced by prior treatment, blast cell morphology, or disease status on study entry (refractory or relapsed). Twenty-seven patients have relapsed after remission periods of 35 to 920 days (median, 110 days); seven others are free of leukemia for up to 519 days. The effectiveness of VP-16/5-Az combination therapy in patients refractory to anthracyclines and cytarabine indicates a potential role for these compounds in first-line treatment of patients with ANLL.

Adolescent↗
PubMed1987

Erythrocyte age-dependent changes of membrane protein 4.1: studies in transient erythroblastopenia.

In high resolution sodium dodecyl sulfate-gel electrophoresis, the red cell protein, band 4.1, separates into a and b forms, which are closely sequence related polypeptides. In membranes from patients with hemolytic anemia, the relative amount of band 4.1b is increased, which has led to a suggestion that the relative proportion of these two 4.1 forms might be age dependent (Sauberman N, Fortier NL, Fairbanks GF, O'Connor RJ, Snyder LM 1979 Biochim Biophys Acta 556:292-313). We have measured the relative proportions of bands 4.1a and b in the red cells of seven patients with transient erythroblastopenia of childhood. In this disease, temporary cessation of erythroid cell production occurs, and the circulating red cells represent an aged cohort of erythrocytes. At diagnosis, the band 4.1 of red cell membranes was nearly entirely in the a form, and as reticulocyte levels rose during recovery, the predominant form became 4.1b. After recovery, the a/b ratio returned to normal. A transient period of moderate reticulocytosis and high levels of 4.1a could be detected in some cases, presumably marking the beginning of the recovery phase. These results support the proposal that the 4.1 band ratio is an internal marker of cell age in the human erythrocyte.

Blood Proteins↗
PubMed1986

T-cell acute lymphoblastic leukemia with natural killer cell phenotype.

To determine the type and proportion of cases within that type of acute lymphoblastic leukemia (ALL) that has a natural killer (NK) cell phenotype, we examined leukemic blasts from 31 children with ALL (14 with T-ALL, 17 with non-T-ALL) for expression of antigens detected by NK-specific monoclonal antibodies Leu 11b, Leu 7, and 1G2 (an antibody we have developed that cross-reacts with Leu 7). None of the patients had leukemic blasts that reacted with Leu 11b. However, leukemic blasts from four T-ALL patients were 1G2+ and/or Leu 7+. Blasts from two of these had spontaneous lytic activity against standard NK target cell line K562; blasts from one killed K562 only when incubated with interferon; blasts from the other had no lytic activity against K562 but did manifest antibody-dependent cell-mediated cytotoxicity against antibody-coated cells from NK-resistant cell line SB. Blasts from all four Leu 7+ patients had L2 morphology. In one, the leukemic blasts had azurophilic cytoplasmic granules similar to those found in NK-enriched normal populations of large granular lymphocytes. These findings suggest that a significant proportion of T-cell acute lymphoblastic leukemias may be malignancies of NK cell origin.

Adolescent↗
PubMed1985

The structural organization of skeletal proteins influences lipid translocation across erythrocyte membrane.

In order to define the influence of skeletal protein organization on transmembrane phospholipid movement in erythrocyte membranes, we measured the translocation rate of lysophosphatidylcholine in pathologic red cells. A simple method based on the differential extraction of lysophosphatidylcholine from the red cell membrane by saline and albumin solutions was used to quantitate the translocation rate. Two groups of pathologic red cells were chosen for these studies: red cells with quantitative deficiencies of the skeletal proteins, spectrin and protein 4.1, and sickle erythrocytes in which controlled reorganization of the membrane was induced by hemoglobin polymerization. Marked increase in lipid translocation rate was seen in red cells having quantitative deficiencies of spectrin and protein 4.1. The magnitude of the increase in translocation rate in spectrin-deficient red cells was related to the magnitude of protein deficiency. Translocation rate in sickle erythrocyte membranes increased by 50% upon deoxygenation as a result of sickle hemoglobin polymerization. No increase in translocation rate was seen in normal cells upon deoxygenation. By manipulating the extent of membrane reorganization that occurred following deoxygenation of sickle cells, we have been able to show that skeletal reorganization induced by hemoglobin polymerization and not hemoglobin polymerization per se is responsible for the increase in translocation rate. Together, these findings imply that the structural organization of membrane skeletal proteins plays an important role in regulating the rate of transbilayer movement of lipids across the erythrocyte membrane.

Anemia, Sickle Cell↗
PubMed1985

Altered spectrin association and membrane fragility without abnormal spectrin heat sensitivity in a case of congenital hemolytic anemia.

In hereditary pyropoikilocytosis (HPP) and one type of hereditary elliptocytosis (HE), spectrin self-association is abnormal [5,7]. Spectrin extracted from normal erythrocyte membranes at 0 degree C is nearly all tetrameric, while in HPP and HE (type 1) a substantial amount of the extracted spectrin is dimeric. Abnormal reassociation of spectrin dimers to tetramers can also be demonstrated. We here report the case of a family in which the child has moderately severe hemolysis, with extreme microcytosis and poikilocytosis. The spectrin extracted at 0 degree C was predominately dimer. Parents had levels of dimer intermediate between patient and control values. The temperature dependence was normal for erythrocyte fragmentation; spectrin extractability; and circular dichroism of purified spectrin. Neither the patient nor either parent had elliptocytic red cells as judged from smears and scanning electron microscopy. The presence of substantial amounts of dimeric spectrin in the parents is consistent with a model in which each parent is heterozygous for a different nonassociating mutant spectrin, while the child has inherited a nonassociating molecule from each parent. In each individual, the degree of mechanical stability of the erythrocyte membrane, determined by ektacytometry, was proportional to the amount of tetramer found in the membrane. The description of this case is consistent with either HPP or a form of homozygous HE which is asymptomatic in the carrier state.

Anemia, Hemolytic, Congenital↗
PubMed1984

Idiopathic thrombocytopenic purpura in children. The case for management without corticosteroids.

Acute ITP in children under 13 years of age is generally a benign, self-limited condition with spontaneous recovery occurring within a matter of days or weeks. Our analysis of platelet data indicate no advantage in terms of rate of recovery when steroids are used. In fact, the median of 3 weeks and mean of 3 1/2 weeks from onset to recovery in the nonsteroid-treated children were significantly better than the corresponding figures in the steroid-treated group. In addition, while reducing the risk of intracranial hemorrhage is generally given as the chief therapeutic rationale for using steroids, we have not seen a single case of ICH among 465 consecutive cases of acute ITP in children, the majority (93%) of whom did not receive steroids. On the other hand, adolescents, as adults, with ITP often have the autoimmune (chronic) form of the disease. In this group, corticosteroids may be of at least transient benefit and should be used.

Acute Disease↗
PubMed1984

Congenital transcobalamin II deficiency presenting atypically with a low serum cobalamin level: studies demonstrating the coexistence of a circulating transcobalamin I (R binder) complex.

A case of transcobalamin II deficiency with several unique features is described. The clinical presentation was typical, except for a slightly delayed age at presentation and the occurrence of apparent neurologic dysfunction from the beginning. The unusual biochemical feature was a low serum cobalamin level (97 pg/ml). Several cobalamin-binding protein abnormalities coexisted and antedated cobalamin therapy. Chief among these was the complexing of all serum R binder (transcobalamin I), leaving the patient with no detectable R binder. This defect appeared to be transient. Noteworthy, too, was a prominent binder of 70,000 mol wt that also carried the bulk of his serum cobalamin after therapy; it was prominent in his presumably heterozygous relatives too. The interrelationship between all these abnormalities is intriguing but unclear. The abnormality in transcobalamin II deficiency is clearly not limited solely to deficiency of transcobalamin II. It is also evident that this entity must now be considered in the differential diagnosis of low serum cobalamin levels in infancy.

Carrier Proteins↗
PubMed1983

Phenotypic change of acute monocytic leukemia to acute lymphoblastic leukemia on therapy.

Acute nonlymphocytic leukemias comprise most of the therapy-linked leukemias in cancer patients. We report here the unusual occurrence of acute lymphoblastic leukemia in a patient while on therapy for acute monocytic leukemia. The morphologic and histochemical studies were distinctly different between the initial presentation and the subsequent "relapse". At "relapse," the Philadelphia chromosome was not present, ruling out chronic myelogenous leukemia presenting in two morphologically different blastic phases. Cytogenetic and histochemical studies both at original presentation and at the time of relapse would be helpful in establishing the occurrence of a new leukemia.

Child↗
PubMed1982

Normal sister chromatid exchange frequency in long-term survivors with acute leukemia.

We hypothesized that the sister chromatid exchanges assay in acute leukemia long-term survivors may detect: (a) long-term effects of combined chemo- and radiotherapy; and possibly (b) those individuals with inherently deficient DNA repair. Accordingly, we determined the sister chromatid exchanges frequency in 26 blood specimens from 24 acute leukemia long-term survivors (patients) and 14 blood specimens from 13 control subjects (controls). The patients consisted of 23 children with acute lymphocytic and one child with acute myelocytic leukemia. The median length of chemotherapy was 5 years. Eighteen of the 24 patients also received prophylactic fractional central nervous system irradiation for the first 3 years of treatment, and one patient received therapeutic irradiation to the central nervous system. The median off-therapy period at the time of study was 2.5 years with a range of 0 to 7.5 years. The controls consisted of the parents of the patients and laboratory personnel. A mean exchange score per cell was established for each specimen (25 to 30 cells/specimen were scored), and it ranged from 3.0 to 9.7 in the patients and from 3.0 to 11.5 in the controls. A mean +/- S.D. calculated from those means was 6.0 +/- 1.8 for the patients and 6.9 +/- 2.8 for the controls. They were not significantly different. We conclude that chemo- and radiotherapy produced no persistent DNA alterations detectable by this method.

Child↗
PubMed1981

Long-term survivors of acute lymphoblastic leukemia--risk of relapse after cessation of therapy.

The results of cessation of therapy (COT) in 64 long-term survivors (disease-free survival of five years or more) of acute lymphoblastic leukemia (ALL) were analyzed to determine the incidence of relapse off therapy. Thirty-seven of the patients had intermittent central nervous system (CNS) prophylaxis. Total follow-up from diagnosis varied from 5.75 to 27.75 years. The median time off therapy was three years (range, 8 months to 26 years). Eighty-six percent (55/64) of the patients continue in their initial remission. Eight patients had relapse, and one patient had a morphologically different leukemia at recurrence. All the relapses occurred between five to eight years from diagnosis and the cumulative rate of relapse for the period was 0.14. There was no significant difference in the rate of relapse for those receiving CNS prophylaxis (0.08) versus those not receiving CNS prophylaxis (0.19). The difference in the relapse rates for boys (0.24) versus girls (0.04) was statistically significant (P = 0.04). Isolated testicular relapse (ITR) was not seen in any of the 34 boys. The present study confirms the earlier observations by others that relapse is uncommon in ALL patients remaining in remission longer than seven to eight years. ALL patients treated with intermittent CNS prophylaxis administered throughout the period of maintenance chemotherapy appear to be at no greater risk for relapse off therapy than those treated with high-dose initial cranial irradiation and intrathecal methotrexate. The longer duration of therapy and the use of a repetitive reinduction regimen for maintenance seem to be associated with a decreased risk of ITR after discontinuation of therapy for boys and men. There appears to be a small but definite risk of "second" leukemia in the long-term survivors of leukemia.

Antineoplastic Agents↗