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Biomedical subjects

A Nandi

Publications and source records attributed to A Nandi.

35 records · Page 2Linked to original sources

Interrelation of xanthine oxidase and dehydrogenase and L-gulonolactone oxidase in animal tissues.

There is a correlation between phylogeny and the activities of L-gulonolactone oxidase (LGO), the key enzyme responsible for ascorbic acid (AH2) synthesis in animals and total xanthine oxidase and dehydrogenase [XOD(D/O)], the enzyme responsible for the production of endogenous superoxide radical (O2-.). LGO appears in the kidneys of amphibians and reptiles but livers of mammals. XOD(D/O) also is present mainly in the kidneys of amphibians and reptiles and livers of mammals. AH2 is a potential scavenger of O2-. and it appears that tissue specific expression of LGO takes place to counteract the endogenous O2-. toxicity. The interrelation of XOD(D/O) and LGO was also observed in the liver of rats during prenatal to postnatal development.

Animals↗

Erythroid-specific nuclease-hypersensitive sites flanking the human beta-globin domain.

Recent evidence suggests that DNA sequences from the region lying 5' of the human epsilon-globin gene are important for erythroid-specific expression of human beta-like globin genes. This region, as well as a region 20 kilobases (kb) downstream from the beta-globin gene, contains a set of developmentally stable, DNase I-superhypersensitive sites that are thought to reflect a chromatin structure supporting active globin gene expression. We have analyzed the chromatin structure in these two regions in a wide variety of nonerythroid and erythroid cells. The study included analysis of chromatin structure changes occurring during globin gene activation in mouse erythroleukemia-human nonerythroid cell hybrids. The results identified a hypersensitive site (III) 14.8 kb upstream of the epsilon-globin gene that was strictly correlated with active globin gene transcription. Interestingly, a multipotent human embryonal carcinoma cell line exhibited a hypersensitive site (IV) 18.4 kb upstream of epsilon-globin that was absent in all other nonerythroid cells examined, suggesting that chromatin structure changes at specific hypersensitive sites during embryonic development may also be important in globin gene repression.

Cell Line↗

Successful pregnancy following bone marrow transplantation for leukaemia.

We report three pregnancies with successful outcomes in two women following allogeneic bone marrow transplantation (BMT) for acute leukaemia using high dose melphalan alone as conditioning therapy. The increasing application and success of BMT together with the instigation of conditioning regimens that do not include total body irradiation should increase such cases. These and previous cases document that a normal outcome of pregnancy is likely in these patients.

Adult↗

Treatment of relapsed and refractory acute leukaemia with high-dose cytosine arabinoside and etoposide.

A total of 65 patients under the age of 55 with acute leukaemia received high-dose cytosine arabinoside (Ara-C) in combination with high-dose etoposide without an anthracycline. Complete remission rates for patients with relapsed or refractory acute myelogenous leukaemia (AML) were 15/25 (60%) and 11/16 (69%), respectively. The complete remission rate for patients with refractory or relapsed acute lymphoblastic leukaemia (ALL) was 10/18 (56%). The treatment-related mortality was 17%. Nine patients whose leukaemia relapsed after matched allogeneic, sibling bone-marrow transplantation (BMT) were also treated in this way; the treatment-related mortality in this group was high (7/9) and the duration of remission in the two patients who responded, too short to justify this intensive treatment in such patients. Similarly, patients who underwent BMT after achieving a complete remission with high-dose Ara-C and etoposide did very poorly, only one patient surviving well and disease-free at 8 months. The important finding in this study was the high complete remission rate rapidly obtained in patients with relapsed or refractory AML without using an anthracycline.

Adult↗

High dose melphalan, BCNU and etoposide with autologous bone marrow transplantation for Hodgkin's disease.

Thirty-eight patients with previously treated Hodgkin's disease were given high dose combination chemotherapy using melphalan and BCNU and autologous bone marrow transplantation. In 25 patients etoposide was added in conventional dosage. During the course of the study the dose of melphalan was increased from 80 to 140 mg m-2 and the dose of BCNU from 300 to 600 mg m-2. The response rate was 76% with 53% complete remission. Forty-five per cent of the patients are free of disease at 4-20 months follow-up. There were eight (26%) treatment-related deaths due to lung damage (seven cases) and irreversible cardiac failure (one case). Fatal lung damage occurred only in patients receiving 600 mg m-2 of BCNU with high dose melphalan. The dose of BCNU given with high dose melphalan should not exceed 500 mg m-2. This treatment is effective against relapsed Hodgkin's disease but must be used cautiously. The best time for its use remains to be determined.

Adolescent↗

Different 3'-end processing produces two independently regulated mRNAs from a single H1 histone gene.

We describe the isolation of a mouse H1 histone gene that encodes two mRNA transcripts. One mRNA ends just beyond the coding region, near a highly conserved palindrome sequence typical of cell cycle-regulated histone genes. The level of this transcript is coupled to DNA replication. The second mRNA ends nearly 1 kilobase downstream near a polyadenylation signal. This mRNA is polyadenylylated, and its accumulation is not coupled to DNA replication. The two mRNAs are regulated independently and in some circumstances in opposite directions under several physiological conditions. The production of a polyadenylylated mRNA from an otherwise cell cycle-regulated histone gene may allow for continued synthesis of the histone protein when DNA synthesis ceases in nondividing cells.

Acetamides↗

Increase in clonogenic tumour cells in bone marrow of patients with multiple myeloma treated with vincristine, doxorubicin, and methylprednisolone.

The relation between clonogenic myeloma cells, assayed in vitro, and clinical status was studied in 20 patients with multiple myeloma before and after VAMP therapy (vincristine, doxorubicin, and methylprednisolone). 14 patients showed an improvement in clinical status, as judged by a fall in myeloma protein and a decrease in plasmacytoid myeloma cell infiltration in the bone marrow. However, in 11 of these 14, there was an increase in the number of clonogenic myeloma cells. This suggests that the treatment changed the myeloma cell population in the residual bone marrow. To be effective, subsequent chemotherapy should be aimed at destroying this population of myeloma cells.

Antineoplastic Combined Chemotherapy Protocols↗

Melphalan and total body irradiation (TBI) versus cyclophosphamide and TBI as conditioning for allogeneic matched sibling bone marrow transplants for acute myeloblastic leukaemia in first remission.

Between June 1981 and April 1986 63 patients with acute myeloid leukaemia (AML) in first remission and HLA-identical sibling donors were entered into a prospective study comparing cyclophosphamide (CY) + total body irradiation (TBI) with melphalan + TBI as conditioning therapy prior to transplantation. Thirty-six patients received CY/TBI and 27 received melphalan/TBI. The actuarial probability of remaining in remission for patients receiving melphalan/TBI was 94% compared with 66% following CY/TBI (p greater than 0.01). By including a comparable group of 41 patients with AML in first remission, conditioned with CY/TBI prior to the onset of the study, the greater anti-leukaemic effect of melphalan/TBI compared to CY/TBI was unchanged and statistically the chance of this being wrong is 1 in 10 (p less than 0.1). The overall survival in remission of both arms of the study was the same with 15/27 patients (55%) surviving in remission following melphalan/TBI compared with 19/36 patients (53%) following CY/TBI. The benefit obtained in reduced relapse was offset by the combined nephrotoxic effect of melphalan and cyclosporin which was not identified until the programme had been underway for a period of time. This shows that misinterpretation of 'no survival advantage' for the new treatment may occur due to unforeseen and preventable toxicities.

Actuarial Analysis↗

Characterization of a surrogate TATA box promoter that regulates in vitro transcription of the simian virus 40 major late gene.

The presence of a surrogate TATA box sequence located ca. 30 nucleotides upstream of the major late RNA start site at nucleotide position (np) 325 (Brady et al., Cell 31:625-633, 1982) has been confirmed, and its structural specificity has been determined by the generation of additional base substitution mutations at the KpnI restriction site (np 294) in cloned simian virus 40 DNA. Two mutants generated new RNA initiation sites upstream of the np 325 start site and continued to utilize the authentic start site, but with decreased efficiency. The replacement of either one or both cytosines by thymines at np 298 and np 299 specifically enhanced in vitro transcription from the np 325 start site by 430 and 800%, respectively. This enhancement was due to conversion of the simian virus 40 late promoter present in the wild-type virus to a sequence that is similar to the TATA box present in the simian virus 40 early promoter.

Base Sequence↗