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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 1,009 records · Page 56Linked to original sources
PubMed1995

Neurobehavioral, neurochemical and electrophysiological studies in 6-hydroxydopamine lesioned and neural transplanted rats.

Unilateral injection of 6-hydroxydopamine (6-OHDA) into the caudate nucleus of rat caused degeneration of dopaminergic terminals, evidenced by significant (P < 0.05) elevation of spontaneous and drug-induced motor behaviour, enhanced DA receptor binding and significant increase in the neuronal firing rate of caudate neurons, suggesting supersensitivity of dopaminergic receptors. Eight weeks following the transplantation of embryonic cell suspensions from caudate at the lesioned site, a significant restoration of the enhanced 3H spiperone binding and neuronal activity of caudate neurons was observed in comparison with lesioned rats. These results clearly demonstrate that transplanted embryonic neuronal tissue at the lesioned site is capable of restoring the neuronal deficits caused by 6-OHDA as evidenced by significant amelioration in neurochemical, behavioral and electrophysiological alterations.

Action Potentials↗
PubMed1995

Small changes in cationic substituents of diphenylfuran derivatives have major effects on the binding affinity and the binding mode with RNA helical duplexes.

The interactions of dicationic, 2-4, and tetracationic, 5-7, diphenylfuran analogs of 1 (furamidine) with RNA have been analyzed by thermal melting, spectroscopic, viscometric, kinetic and molecular-modeling techniques. The results of these studies indicate that most of the furan derivatives bind to RNA duplexes by intercalation in contrast to their minor-groove binding mode in AT sequences of DNA, but similar to their binding mode in GC rich regions of DNA. The highest affinity for RNA is found for an imidazoline dication, 2. With some substituents which inhibit formation of a strong intercalation complex, the results suggest a non-intercalative type of binding occurs. The non-intercalative binding probably occurs through a complex with the furan derivative bound in the narrow, deep major groove of A-form RNA helices.

Amidines↗
PubMed1995

Quantitation of the protein content of diphtheria and tetanus toxoids by the Biuret method during production of combined vaccines.

The protein content of 15 batches of diphtheria toxoid and 12 batches of tetanus toxoid was measured by Biuret method and was compared to the values obtained by the Kjeldahl method. Statistical analysis did not show any difference between the two methods. The Biuret method, is specific, easy to carry out and takes less time for protein estimation of purified toxoids during production of combined vaccines.

Chemistry Techniques, Analytical↗
PubMed1995

Probability assessment of conformational ensembles: sugar repuckering in a DNA duplex in solution.

Conformational flexibility of molecules in solution implies that different conformers contribute to the NMR signal. This may lead to internal inconsistencies in the 2D NOE-derived interproton distance restraints and to conflict with scalar coupling-based torsion angle restraints. Such inconsistencies have been revealed and analyzed for the DNA octamer GTATAATG.CATATTAC, containing the Pribnow box consensus sequence. A number of subsets of distance restraints were constructed and used in the restrained Monte Carlo refinement of different double-helical conformers. The probabilities of conformers were then calculated by a quadratic programming algorithm, minimizing a relaxation rate-base residual index. The calculated distribution of conformers agrees with the experimental NOE data as an ensemble better than any single structure. A comparison with the results of this procedure, which we term PARSE (Probability Assessment via Relaxation rates of a Structural Ensemble), to an alternative method to generate solution ensembles showed, however, that the detailed multi-conformational description of solution DNA structure remains ambiguous at this stage. Nevertheless, some ensemble properties can be deduced with confidence, the most prominent being a distribution of sugar puckers with minor populations in the N-region and major populations in the S-region. Importantly, such a distribution is in accord with the analysis of independent experimental data--deoxyribose proton-proton scalar coupling constants.

Algorithms↗
PubMed1995

Functional bladder neck obstruction: a rare cause of renal failure.

We studied 7 men and 6 women (average age 33 years) who presented in renal failure with obstructive voiding symptoms or retention. Of these patients 11 had a dilated upper tract and 2 had shrunken kidneys. Mean serum creatinine at presentation was 7.0 mg./dl. No abnormality was noted on cysto-panendoscopy, retrograde urethrography and voiding cystourethrography. The patients were initially treated with clean intermittent self-catheterization following 7 to 10 days of indwelling catheterization. The majority of patients had low pressure and low flow rate at initial presentation but high end filling pressure (mean 35.3 cm. water), high voiding pressure (mean 118.9 cm. water), high opening pressure (mean 95.3 cm. water) and low peak flow (mean 5.7 ml. per second) on video pressure flow electromyography. The external sphincter was relaxed during voiding but the bladder neck opened intermittently or inadequately. No proper funneling of the bladder neck was seen. Thus, functional bladder neck obstruction was considered to be responsible for obstructive voiding in these patients. Of the patients 3 void to completion with the help of alpha blockers alone, 5 underwent bladder neck incision and are voiding well, and 5 were practicing clean intermittent self-catheterization at last followup. Serum creatinine returned to near normal in 10 patients. End stage renal failure persisted in 2 patients, 1 of whom underwent renal transplantation and is voiding well but the other died without having undergone renal replacement therapy. In the remaining patient serum creatinine was stable at 3.2 mg./dl. Mean serum creatinine at 6 months of followup was 2.33 mg.%. Bladder neck obstruction is a rare cause of renal failure which can be corrected if treated appropriately.

Adult↗
PubMed1995

Effect of cisplatin administration on the proliferation and differentiation of bone marrow cells of tumour-bearing mice.

In the present study the effect of tumour growth with respect to two tumour systems (Dalton's lymphoma [DL] and P815) on the in vitro, colony-forming ability (CFA) and proliferation of the bone marrow cells (BMC) of C3H/He mice was investigated. The P815-bearing mice showed an enhanced bone marrow colony forming ability in vitro, in response to L929 conditioned medium (L929 CM) used as a source of CSF. On the other hand, DL-bearing mice did not have any significant alteration in this process compared to normal mice. In vivo, administration of cisplatin resulted in a significant rise in the CFA of normal as well as DL- or P815-bearing mice. The tumour-conditioned medium (TCM) and ascitic fluid (AF) of P815 but not of DL, was found to support the in vitro colony formation of BMC obtained from cisplatin-treated or untreated mice. The number of CFU-granulocyte-macrophage was predominantly high in the cultures of BMC incubated with TCM or AF of P815. The TCM and AF of P815 also enhanced the in vitro proliferation of BMC obtained from cisplatin-treated or untreated mice. In vivo, administration of cisplatin in normal mice resulted in enhanced numbers of peritoneal exudate macrophages (PEM) and PBL. Similarly, the number of PEM and PBL was augmented in both the P815- and DL-bearing mice. However, cisplatin administration in the tumour-bearing mice decreased the count of PEM, while the number of leucocytes remain unaffected. This study indicates that the cancer chemotherapeutic drug cisplatin can influence the differentiation of the bone marrow progenitor cells in response to tumour growth in situ.

Animals↗
PubMed1995

Hind III genomic polymorphism of the C3b receptor (CR1) in patients with SLE: low erythrocyte CR1 expression is an acquired phenomenon.

Expression of the human erythrocyte C3b receptor (CR1-CD35) and its Hind III RFLP was studied in a group of 37 patients with SLE, 15 consanguineous relatives of the patients and 48 healthy normal subjects. The CR1 number on erythrocytes was quantitated by ELISA using a mAb to CR1. Serum levels of complement proteins (C3, C4, C3d) and circulating immune complexes (CIC) were estimated simultaneously in controls and relatives. The patients were followed up during the course of the treatment. The CR1/erythrocyte (CR1/E) in patients were found to be significantly low in comparison to controls. The gene frequencies for the alleles H and L (7.4 and 6.9 kb Hind III restriction fragments) in the patients were 0.75 and 0.25, respectively, which did not differ significantly from the controls (0.77 and 0.23 in normal subjects and 0.79 and 0.21 in consanguineous relatives of the patients). However, patients expressed fewer CR1/E within each genotype than their relatives and healthy subjects. CR/E was found to be stable in consecutive samples in controls. In patients, the numbers varied between low and high during the course of the treatment. The variation in the numbers was significantly correlated with C3d and CIC as well as with the severity of the disease. Our results suggest that low levels of CR1 on erythrocytes in SLE patients are required during the course of the disease and that the 6.9 kb restriction fragment does not play a role in causing susceptibility to the disease.

Adolescent↗
PubMed1995

Cloning of mouse c-ros renal cDNA, its role in development and relationship to extracellular matrix glycoproteins.

Renal organogenesis ensues following reciprocal interactions between the uninduced metanephric mesenchyme and the ureteric bud. Conceivably, the presence of ligands or growth factors on a given cell type, and expression of receptors, including receptor proto-oncogenes, on the other cell type of different lineage would facilitate such epithelial-mesenchymal interactions. During these interactions, other macromolecules, such as extracellular matrix (ECM) proteins, present at the epithelial-mesenchymal surface, also play a role in the kidney morphogenesis. In this study the proto-oncogene, c-ros, was cloned and sequenced; its role in the metanephric development was examined, and correlated with the changes in the expression of ECM proteins. The mouse c-ros renal cDNA, belonging to phosphotyrosine kinase (PTK) receptor family, had a translation product of 2340 amino acids. The extracellular domain had 32 N-linked glycosylation sites and 30 cysteine residues. The transmembrane segment had a hydrophobicity approaching approximately 3.5. Multiple phosphorylation sites, typical of a PTK catalytic unit, were present in the cytoplasmic domain. The 3' noncoding region did not contain any A(U)nA mRNA instability motifs. The c-ros mRNA was highly expressed on the ureteric bud branches and their tips and on the developing glomeruli. Competitive RT-PCR analyses revealed the c-ros expression was the highest at 13th day of gestation, and it declined to very low levels during the neonatal period. Exposure of metanephric kidneys to c-ros antisense-oligonucleotide, derived from the PTK domain, caused dysmorphogenesis of the kidney and loss of c-ros expression on the ureteric bud branches. Concomitant with the reduced c-ros gene expression, a decreased expression of ECM glycoproteins, in particular the proteoglycans, was observed. These findings suggest that the c-ros plays a role in the metanephric development, and its effects may be modulated by the ECM macromolecules present at the epithelial-mesenchymal interface.

Amino Acid Sequence↗
PubMed1995

Role of body surface cultures in prediction of sepsis in a neonatal intensive care unit.

An analysis of surface cultures of 35 preterm infants of less than 33 weeks gestational age hospitalized in a neonatal intensive care unit was made. The babies had received neither antiseptic nor antibiotic therapy prior to collection of specimens. Surface cultures were collected on the 4th or 5th day of life from 16 skin or mucosal sites. At the onset of a febrile episode within 14 days of collection of surface swabs, a blood culture was done on 31 infants (four did not develop fever) and the results were compared with the surface cultures. Sepsis was diagnosed by positive blood culture in twenty neonates (57.1%). With this frequency of sepsis, the optimum sensitivity, specificity and positive predictive values of surface cultures were 60%, 27% and 60%, respectively. These values did not improve substantially for any anatomic site cultured or for any pathogen recovered. We conclude that surface cultures are of limited value in predicting the aetiology of sepsis in neonates.

Bacteria↗
PubMed1995

Regulation of mesothelial cell mitogenesis by antisense oligonucleotides for the urokinase receptor.

The association of urokinase-type plasminogen activator (uPA) with its receptor (uPAR) influences various biologic functions, including cell migration, angiogenesis, differentiation, and wound healing. Expression of uPAR at the mesothelial surface could, therefore, influence cellular responses in the pleural space. We found that a line of cultured human mesothelial cells (MeT5A) expressed specific and saturable binding sites for uPA that increased on stimulation with PMA. Ligand blotting studies showed that the mesothelial receptor is a 50 kD protein similar to that in other cell lines. Binding of active and intact, but not amino terminal or low molecular weight fragment, uPA to mesothelial cells enhanced DNA synthesis and cell proliferation, and antibodies against either the active site of uPA or uPAR abrogated this effect. We reasoned that regulation of uPAR expression could control uPA-induced mitogenesis and tested this hypothesis with antisense oligonucleotides complementary to uPAR mRNA. Phosphorothioate-modified antisense oligonucleotides inhibited uPA-mediated mesothelial cell proliferation in a concentration-dependent manner. These effects were associated with decreased binding of 125I-uPA and reduced expression of the uPAR gene product. The results indicate that uPAR is involved in signal transduction pathways that control uPA-mediated mesothelial cell proliferation, a process implicated in the pathogenesis of mesothelial inflammation and pleural neoplasia. Antisense oligonucleotides to uPAR suppress mesothelial cell mitogenesis in vitro and offer a potential means of regulating the process in vivo.

Base Sequence↗
PubMed1995

Mutation analysis of the TSC2 gene in an African-American family.

Tuberous sclerosis complex is an autosomal dominant disorder with loci on chromosome 9q34 (TSC1) and chromosome 16p13.3 (TSC2). The TSC2 gene has been isolated. To date, only a small number of intragenic deletional and point mutations have been detected, almost exclusively in sporadic (no family history) cases. With the exception of a single parent/offspring pair, there have been no published reports of mutations in extended multigenerational chromosome 16-linked TSC2 families. For our TSC studies we ascertained and sampled a four-generation African-American TSC family that shows a high likelihood for linkage to chromosome 16 (z=1.53). Using single-strand conformation polymorphism analysis we identified a 4590/4591delC mutation in exon 34. The 4590/4591delC causes a frameshift mutation resulting in the creation of a premature stop codon. In addition, we have detected a 542del4 polymorphism in the two partially overlapping polyadenylation signals in exon 40 that segregates in the family. The polymorphism has been detected in six of 72 African-American control chromosomes examined, and has not been detected in 80 Caucasian control chromosomes examined.

Amino Acid Sequence↗
PubMed1995

Profile of HLA-B27-related 'unclassifiable' seronegative spondyloarthropathy in females and its comparison with the profile in males.

Unclassifiable seronegative spondyloarthropathy (SSA) syndrome is primarily considered to be an affliction of males. In this report from northern India, 25 HLA-B27 antigen positive females with this condition are described and compared with 39 HLA-B27-positive males with the same disease. All these patients presented with typical features of spondyloarthropathy such as predominantly lower limb synovitis, enthesopathy and inflammatory spinal pain. The onset was insidious in 56% of the females and in 64% of the males. The mean age of onset as also the mean duration of symptoms prior to diagnosis were significantly higher in females (26.2 vs 19.4 yr and 8 vs 2 yr, respectively). A mono- or oligo-arthritis was seen in 52% of the females and in 53% of the males, but the average number of joints involved was less in females (4.8 vs 7.7). Lower limb joints alone were involved in 56% of the females and 49% of the males, with the knees, ankles and hips being most commonly involved, often asymmetrically. The mean degree of symmetry was significantly lower in females (62 vs 76). Ninety-two per cent of females and 74% of males had inflammatory spinal pain. Radiographic sacroiliitis was demonstrable in 56% females and 74% males. It is concluded that 'unclassifiable' SSA syndrome is not infrequent in females but is diagnosed late. Fewer joints tend to be involved and there is greater tendency towards asymmetry in females.

Adolescent↗
PubMed1995

Adult onset Still's disease in northern India: comparison with juvenile onset Still's disease.

The present study compared the clinical and laboratory picture, the disease course and outcome in 31 patients having adult onset Still's disease (AOSD) with 23 patients having juvenile onset Still's disease (JOSD). The median age at disease onset was 20 and 7 yr for AOSD and JOSD patients, respectively. On analysing and comparing our data on these two groups, no significant differences emerged except that adults had a significantly lower time interval from disease onset to remission as compared to juveniles. Upon comparison of data on our AOSD patients with that published from abroad, rash, adenopathy and sore throat were less frequent. No clinical or laboratory variables were found to predict the subsequent disease course and outcome in either group. The functional outcome was good in about 70% of both groups and mortality was low. It is concluded that the clinical picture and outcome in AOSD is similar to that of JOSD.

Adult↗
PubMed1995

Does mixed connective tissue disease exist in India?

One thousand consecutive patients with systemic connective tissue diseases were screened clinically and serologically to determine the existence of mixed connective tissue disease (MCTD) in the Indian population. After completion only three patients could be diagnosed as having MCTD using the standard diagnostic criteria. The results of this study point to MCTD existing but it appears to be a rare entity in the Indian population.

Antibodies, Antinuclear↗
PubMed1995

Behçet's disease in India: a clinical, immunological, immunogenetic and outcome study.

The clinical and laboratory profile of 58 consecutive patients satisfying the ISG 1990 criteria for the diagnosis of Behçet's disease was analysed. It appears that Behçet's disease in India is predominantly 'mucocutaneous' and 'arthritic'; 'ocular' and 'neuro' Behçet's being uncommon. In comparison to published literature, the onset of disease in this part of the world is significantly delayed. The pathergy test is rarely positive. There is no significant difference in clinical presentation and laboratory investigations between children and adults with this disease; also, no sex difference was observed. A combination of oral steroids and colchicine gives good relief in most cases. Preliminary observations seem to reflect no definite association of any known class I antigen to disease in this part of the world. A detailed study on immunogenetics is underway.

Adult↗