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Biomedical subjects

S Kulkarni

Publications and source records attributed to S Kulkarni.

At least 127 records · Page 7Linked to original sources
PubMed1997

Antilymphocyte globulin (ALG) or antithymocyte globulin (ATG) with methylprednisone and oxymethalone in aplastic anaemia.

From 1986 to 1994 we treated 26 patients of aplastic anaemia between 6 to 61 years age group with ATG/ALG, Methylprednisone and Oxymethalone. Five had very severe aplastic anaemia, 16 had severe and 5 nonsevere disease. Disease was associated with hepatitis in 5 patients and with pregnancy and drug use in 2 patients each. In others no cause could be ascertained. A total of 31 courses of treatment were given (range 1-3 courses per patient). Nine patients had complete response (34.62%) and 3 had partial response (11.54%) with an overall response rate of 46.16%. Four patients died within 2 months of starting the treatment. The median follow up was 24 months (range 6-102 months) with an overall survival probality of 45% at 2 yr. At the time of evaluation 12 patients have died, 9 are alive disease-free and 5 are alive with disease. The side effects associated with therapy were tolerable and did not require cessation of therapy in any patient. We conclude that ATG/ALG with Methylprednisone and Oxymethalone is beneficial to significant number of patients with aplastic anaemia.

Adolescent↗
PubMed1996

Characterization of peptide-oligonucleotide heteroconjugates by mass spectrometry.

Two peptide-oligothymidylic acids, prepared by joining an 11 residue synthetic peptide containing one internal carboxyl group (Asp side chain) to amino-linker-5'pdT6 and amino-linker-5'pdT10 oligonucleotides, were analyzed by matrix-assisted laser desorption/ionization (MALDI) on a linear time-of-flight mass spectrometer and by electrospray ionization (ESI) on a triple-quadrupole system. These synthetic compounds model peptide-nucleic acid heteroconjugates encountered in antisense research and in studies that use photochemical crosslinking to investigate molecular aspects of protein-nucleic acid interactions. MALDI and ESI sensitivities for the two hybrid compounds were found to be similar respectively to their sensitivities for the pure oligonucleotide parts. In general, MALDI proved to be less affected by sample impurities and more sensitive than ESI, while ESI on the quadrupole produced greater mass accuracy and resolution than MALDI on the time-of-flight instrument. A hybrid's behavior in a MALDI-matrix or an ESI-spray-solvent was found to be governed mainly by the oligonucleotide. A single positive ESI tandem mass spectrum of the peptide-dT6 accounted for the heteroconjugate's entire primary structure including the point of the oligonucleotide's covalent attachment to the peptide.

Amino Acid Sequence↗
PubMed1996

Disruption of epithelial gamma delta T cell repertoires by mutation of the Syk tyrosine kinase.

Chimeric mice in which lymphocytes are deficient in the Syk tyrosine kinase have been created. Compared with Syk-positive controls, mice with Syk -/- lymphocytes display substantial depletion of intraepithelial gamma delta T cells in the skin and gut, with developmental arrest occurring after antigen receptor gene rearrangement. In this dependence on Syk, subsets of intraepithelial gamma delta T cells are similar to B cells, but distinct from splenic gamma delta T cells that develop and expand in Syk-deficient mice. The characteristic associations of certain T-cell receptor V gamma/V delta gene rearrangements with specific epithelia are also disrupted by Syk deficiency.

Animals↗
PubMed1996

Expression of human recombinant beta 2-microglobulin by Aspergillus nidulans and its activity.

The light chain of HLA class I protein (beta 2m) has been expressed in Aspergillus nidulans. The cDNA of beta 2m was modified using the polymerase chain reaction to include overlapping extensions for its subsequent fusion into an Aspergillus vector. This fusion resulted in beta 2m cDNA being flanked by the Aspergillus awamori glucoamylase promoter and the Aspergillus niger glucoamylase terminator. Expression of beta 2m was induced by the addition of starch to the culture medium. In preliminary mass culture trials, 177 micrograms/liter of f beta 2m were obtained in 60-liter fermentations. N-terminal sequencing of purified human beta 2m produced in fungi (f beta 2m) revealed that 28% of the purified protein was of proper sequence and 61% of the protein had an additional serine and lysine residue derived from the C-terminus of the fungal leader. Purified f beta 2m from culture supernatants appeared biochemically similar to beta 2m obtained from human urine (u beta 2m) as seen in immunoblot analysis. Functionally, f beta 2m effectively interacted as a subunit of class I MHC molecules. This was seen both in a sandwich ELISA for detecting properly folded HLA class I heavy chain and in assays showing cell-surface beta 2m exchange into the mouse class I MHC H-2Kd. In these experiments the biological activity of f beta 2m was indistinguishable from u beta 2m. The successful expression of biologically active beta 2m in A. nidulans suggests that fungal systems might be useful for the production of other active components of the HLA class I MHC complex.

Aspergillus nidulans↗
PubMed1996

Neurologic sequelae in high risk infants--a three year follow up.

OBJECTIVE: To determine the neurologic sequelae in high risk infants. DESIGN: A three year longitudinal follow up. SETTING: Inborn and outborn infants discharged from the Neonatal Special Care Unit (NSCU) of a referral hospital. METHODS: High risk infants were identified for follow up using predetermined risk criteria. A detailed neurodevelopmental examination was done 3 monthly in the first year and 6 monthly subsequently. The Amiel-Tison Method, Bayley Scales of Infant Development and Raval's Scale for social maturity were used. EEG was done in children with seizures. Hearing and ophthalmic assessments were done at 6 months. RESULTS: Three hundred and thirty six high risk infants and 70 normal control infants came for regular follow up. Out of these, 16 (4.8%) had cerebral palsy and 11 had associated mental retardation. Six other children had mental retardation without motor problems. None of the children in the control group had any neurological problems. Sensorineural hearing loss was present in 5 (1.5%) children while 1 subject had corfical blindness. Three children with cerebral palsy had infantile myoclonus, nine had generalized seizures and one child had a focal seizure. The incidence of seizure disorders was 3.9%. CONCLUSIONS: The incidence of major handicap in our study was low. Many of the risk factors which caused adverse outcome, could have been prevented by good antenatal and perinatal care.

Child Development↗
PubMed1996

Altered expression of the developmentally regulated NFI gene family during phorbol ester-induced differentiation of human leukemic cells.

The nuclear factor I (NFI) family of transcription/replication proteins is required for the cell type-specific expression of a number of cellular and viral genes. There are four evolutionarily conserved NFI genes (NFI-A, -B, -C and -X) that encode DNA-binding proteins of similar or identical DNA-binding specificity. To address the role of this family of highly conserved transcription/replication proteins in cell differentiation and development, we have assessed the expression of NFI proteins (by DNA binding) and mRNAs of each of the four NFI genes during the in vitro differentiation of several human leukemic cell lines. These cell lines differ in their pattern of differentiation upon exposure to the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA). In K562 and OCI/AML-3 cells, the levels of the four NFI mRNAs and the mobility of NFI-DNA complexes present in nuclear extracts changed during treatment with TPA. The TPA-induced change in mobility of NFI-DNA complexes in OCI/AML-3 cells was blocked by an inhibitor of protein synthesis, cycloheximide. These changes in NFI protein and mRNA expression appear to be cell type-or lineage-specific since no changes were seen during the TPA-induced differentiation of HL-60 or U937 cells. These studies indicate that although their DNA-binding specificities are similar, the proteins encoded by the four NFI genes may differ in their biological functions and play distinct roles in hematopoietic development.

Base Sequence↗
PubMed1995

Cardiac malformation in neonatal mice lacking connexin43.

Gap junctions are made up of connexin proteins, which comprise a multigene family in mammals. Targeted mutagenesis of connexin43 (Cx43), one of the most prevalent connexin proteins, showed that its absence was compatible with survival of mouse embryos to term, even though mutant cell lines showed reduced dye coupling in vitro. However, mutant embryos died at birth, as a result of a failure in pulmonary gas exchange caused by a swelling and blockage of the right ventricular outflow tract from the heart. This finding suggests that Cx43 plays an essential role in heart development but that there is functional compensation among connexins in other parts of the developing fetus.

Animals↗
PubMed1995

Drosophila nonmuscle myosin II is required for rapid cytoplasmic transport during oogenesis and for axial nuclear migration in early embryos.

The X-linked Drosophila gene spaghetti squash (sqh) encodes the regulatory light chain of nonmuscle myosin II. To assess the requirement for myosin II in oogenesis and early embryogenesis, we induced homozygous germline clones of the hypomorphic mutation sqh1 in otherwise heterozygous mothers. Developing oocytes in such sqh1 germline clones often failed to attain full size due to a defect in 'dumping', the rapid phase of cytoplasmic transport from nurse cells. In contrast to other dumpless mutants described to date, sqh1 egg chambers showed no evidence of ring canal obstruction, and no obvious alteration in the actin network. However the distribution of myosin II was abnormal. We conclude that the molecular motor responsible for cytoplasmic dumping is supplied largely, if not exclusively, by nurse cell myosin II and we suggest that regulation of myosin activity is one means by which cytoplasmic transport may be controlled during oocyte development. The eggs resulting from sqh1 clones, though smaller than normal, began development but exhibited an early defect in axial migration of cleavage nuclei towards the posterior pole of the embryo, in a similar manner to that seen in early cleavage eggs in which the actin cytoskeleton is disrupted. Thus both nurse cell dumping and axial migration require a maternally supplied myosin II.

Actins↗
PubMed1995

Evaluating efficiency of bone marrow harvest and its manipulation--role of CD 34 positivity.

We evaluated harvested marrow cells for total nucleated cells (27.49 x 10(9)), absolute 'lymphocyte' count (6.29 x 10(9)) and CD 34 positive cells (3.57 x 10(9)). The same parameters were studied after in vitro manipulation to remove RBCs and plasma. Reinfused WBCs contained 12.87 x 10(9) nucleated cells, 4.25 x 10(9) absolute 'lymphocyutes' and 3.34 x 10(9) CD 34 positive cells. The corresponding figures for loss during in vitro manipulation (tubing, RBCs and plasma) are 14.62 (53.18%), 2.04 (32.43%) and 0.23 x 10(9) (6.44%) cells respectively. Therefore CD 34 positivity may be a better indicator of total yield, loss during manipulation and reinfusion of hemopoietic progenitor cells in bone marrow transplantation.

Antigens, CD34↗
PubMed1994

Estrogen receptor mutations in tamoxifen-resistant breast cancer.

Clinical resistance to antiestrogens like tamoxifen is a major problem in the treatment of hormone-dependent breast cancers. Since the estrogen receptor plays a central role in mediating the effects of estrogens and antiestrogens, we hypothesized that mutations in the estrogen receptor could be one mechanism by which breast tumors evolve from a hormone-dependent to a hormone-independent phenotype. The eight exons of the estrogen receptor complementary DNA from 20 tamoxifen-resistant and 20 tamoxifen-sensitive tumors were screened by Single Strand Conformation Polymorphism (SSCP), and the variant conformers were sequenced to identify the nucleotide changes. A 42-base pair replacement was found in exon 6 of a tamoxifen-resistant tumor. A single base pair deletion in exon 6 of a tamoxifen-resistant metastatic tumor but not in the primary tumor was detected in another case. If translated, both these mutations could generate truncated receptors with an intact DNA-binding domain and a defective hormone-binding domain that could constitutively activate transcription of previously estrogen-responsive genes. The remaining 18 of 20 tamoxifen-resistant tumors did not contain mutations in any of the 8 exons of the estrogen receptor complementary DNA. These results suggest that mutations in the estrogen receptor occur at a low frequency and do not account for most estrogen-independent, tamoxifen-resistant breast tumors.

Amino Acid Sequence↗
PubMed1994

Detection of psychiatric morbidity in gynecology patients by two brief screening methods.

Psychiatric morbidity was studied in 100 women attending gynecological outpatient and inpatient set-ups using two brief screening instruments: the General Health Questionnaire, 12 items, and the Present State Examination, ten short questions. Psychiatric morbidity was detected in 36% and was found to be higher in women with uterine prolapse and infections but not in those with menstrual irregularities (p < 0.001). The commonest psychiatric symptoms detected in this population were worrying (50%), aches and pains (51%), depression (50%) and disturbances of biological function (51%). The commonest diagnoses were neurotic depression (70%) and adjustment disorders (23%). The screening instruments used were found to be simple, sensitive, specific, with high identification indices and easy to administer.

Adult↗