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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 235 records · Page 13Linked to original sources
PubMed2002

Role of red cell selenium in recurrent pregnancy loss.

Selenium is an essential trace mineral required for normal human health and reproduction. In recent years selenium deficiency in humans has been implicated as a risk factor for recurrent pregnancy loss. So far the selenium status in recurrent pregnancy loss (RPL) has been evaluated only in plasma and serum samples showing discrepancies of selenium deficiency as a cause for RPL. The present pilot study from India has evaluated selenium status in red cells (as they are the better indicators of selenium levels) in 20 women with three or more unexplained recurrent pregnancy losses compared to similar number of controls. The mean+/-SD red cell selenium levels in the study group was found to be 119.55+/-32.94 ng/ml (range 55-170 ng/ml), which was significantly lower compared to the control group with a mean+/-SD of 150.85+/-37.63 ng/ml (range 87-225 ng/ml). The difference was statistically significant at the 1% level ( P <0.01). Since selenium supplementation resulted in successful pregnancy outcome in veterinary practice, we conclude that large randomised studies are needed to assess the contribution of selenium in the aetiology of RPL and the potential benefits of its supplementation.

Abortion, Habitual↗
PubMed2002

Disease progression markers during asymptomatic phase of HIV-1 infected children with unimpaired CD4+ cell values: evaluation of repeat CD4+ cell evaluation vs. other immunological parameters.

The availability of a marker that could predict the course of disease progression in HIV-infected individuals would be of considerable relevance during the asymptomatic stage in order to undertake timely prophylactic measures. A prospective study was undertaken in a group of 42 children suffering from thalassemia major with HIV-1 infection to assess the status of immune parameters, such as peripheral CD4+ T lymphocyte (CD4+ cell) percentage, delayed type of hypersensitivity (DTH) response to recall antigens, detection rate and levels of p24 antigen, and levels of beta-2 microglobulin and cytokines in serum. All were assessed at an interval of 2 years during the asymptomatic period, (baseline and follow-up assessments) in relation to the development of AIDS defining illness within a follow-up period of 3 years. No difference could be observed in the mean CD4+ cell percentage at baseline between those who progressed subsequently to develop AIDS within the follow-up period (progressors) and those who did not (non-progressors). However, at the point of follow-up assessment the progressor group showed significantly lower CD4+ cell percentage compared to the non-progressor group (33 +/- 4.9 vs. 22 +/- 5.6; p < 0.05), although in the progressor group there was no correlation of the baseline and follow-up CD4+ cell percentage with the duration of the AIDS-free interval. However, in the progressor group there was a strong negative correlation between the rate of decline in CD4+ cell percentage and subsequent duration of the AIDS-free interval (r = -0.859). Analysis of additional immune parameters at baseline revealed that the progressor group, despite having CD4+ cell values comparable to non-progressors, showed impaired DTH response (number and total induration of positive responses being 2.0 +/- 1.23 and 6.2 +/- 1.4 in the former group vs. 3.2 +/- 0.76 and 12.6 +/- 3.80 in the later group; p < 0.05 for both the parameters), and elevated levels (mg/l) of serum beta-2 microglobulin (2.92 +/- 0.89 vs. 1.38 +/- 0.43; p < 0.05). The serum cytokine profile at baseline in the progressor group showed a T helper type-2 (Th2) dominant pattern, i.e. elevation of interleukin-4 (IL-4) and interleukin-10 (IL-10) levels with decreased levels of interleukin-2 (IL-2) and gamma interferon (gamma-IFN) compared to the non-progressor group that showed a T helper type-1 (Th1) dominant profile, i.e., elevation of IL-1 and gamma-IFN level with decreased levels of IL-4 and IL-10 (p < 0.05 for all four cytokines). The present study points out that rate of decline rather than single point of assessment of CD4+ cell values is a more reliable predictor for disease progression in HIV-1 infected children. In addition, parameters such as DTH response, serum levels of beta-2 microglobulin and serum cytokine profile, may provide valuable predictors of subsequent fall in CD4+ cell value.

Biomarkers↗
PubMed2002

Mice lacking skeletal muscle actin show reduced muscle strength and growth deficits and die during the neonatal period.

All four of the muscle actins (skeletal, cardiac, vascular, and enteric) in higher vertebrates show distinct expression patterns and display highly conserved amino acid sequences. While it is hypothesized that each of the muscle isoactins is specifically adapted to its respective tissue and that the minor variations among them have developmental and/or physiological relevance, the exact functional and developmental significance of these proteins remains largely unknown. In order to begin to assess these issues, we disrupted the skeletal actin gene by homologous recombination. All mice lacking skeletal actin die in the early neonatal period (day 1 to 9). These null animals appear normal at birth and can breathe, walk, and suckle, but within 4 days, they show a markedly lower body weight than normal littermates and many develop scoliosis. Null mice show a loss of glycogen and reduced brown fat that is consistent with malnutrition leading to death. Newborn skeletal muscles from null mice are similar to those of wild-type mice in size, fiber type, and ultrastructural organization. At birth, both hemizygous and homozygous null animals show an increase in cardiac and vascular actin mRNA in skeletal muscle, with no skeletal actin mRNA present in null mice. Adult hemizygous animals show an increased level of skeletal actin mRNA in hind limb muscle but no overt phenotype. Extensor digitorum longus (EDL) muscle isolated from skeletal-actin-deficient mice at day 2 to 3 showed a marked reduction in force production compared to that of control littermates, and EDL muscle from hemizygous animals displayed an intermediate force generation. Thus, while increases in cardiac and vascular smooth-muscle actin can partially compensate for the lack of skeletal actin in null mice, this is not sufficient to support adequate skeletal muscle growth and/or function.

Actins↗
PubMed2002

Calorimetric studies of diclofenac sodium in aqueous solution of cyclodextrin and water-ethanol mixtures.

The technique of solution calorimetry has been employed to study the interaction between diclofenac sodium and beta-cyclodextrin by determining the enthalpies of solution of the drug in water and in aqueous beta-cyclodextrin solution. Thermodynamic parameters characterizing the binding process such as enthalpy deltaH0, equilibrium constant K, free energy deltaG0 and entropy deltaS0 have been calculated to be 12.00 kJ mol(-1), 1670 dm3 mol(-1), -19.03kJ mol(-1) and 22.98 J K(-1) mol(-1), respectively. Enthalpies of solution of diclofenac sodium have also been determined in water-ethanol mixtures.

Algorithms↗
PubMed2002

Irreducible dorsal radiocarpal fracture dislocation with dissociation of the distal radioulnar joint: a case report.

We report a case of dorsal radiocarpal fracture dislocation with dissociation of the distal radioulnar joint. Closed reduction was unsuccessful due to interposition of the osteochondral fragments and open reduction and fixation was carried out with a satisfactory end result. The advantages of volar approach and use of external fixator in the management of this injury are discussed.

Adult↗
PubMed2002

Results of inguinal canal repair in athletes with sports hernia.

AIMS: To evaluate the role of surgical exploration and repair of the inguinal canal in athletes suspected of having a sports hernia. METHODS: Thirty-five (34 males, 1 female) athletes with a suspected sports hernia underwent surgical exploration and inguinal hernia repair. After six months, all athletes were sent questionnaires to assess any improvement in analogue pain scores, return to sport, recurrence of symptoms and the overall result of surgery. RESULTS: Operative findings revealed a tear in the external oblique aponeurosis with or without a significant posterior bulge (n=20), a lone significant posterior bulge (n=10), a tear in the conjoint tendon with dilated superficial ring (n=3), small direct hernial sac (n=1) and lipoma of the spermatic cord (n=1). Surgery consisted of repair of external oblique tear (when present) and prolene darn or lichtenstein mesh repair of the posterior inguinal canal. Twenty-seven patients replied to the questionnaire giving a response rate of 78%; of these, 25 patients (93%: 95% CI 83-100) had returned to normal athletic activities at pre-injury level. There was a marked improvement in level of pain (median pain level=8 pre-operative vs 2 post-operative, p<0.001). Eleven patients (41%) rated the results as excellent, eleven (41%) as good and five (18%) as fair and none worse. Six patients complained of occasional discomfort related to the scar. Three patients complained of recurrence of their symptoms after 4 to 5 months following strenuous exercise. CONCLUSION: Sports hernia presents with a spectrum of surgical findings. Athletes with sports hernia should be considered for routine hernia repair, as the majority of the patients benefit from surgery. It is important to offer a structured rehabilitation programme to maximise the benefits of surgery.

Adult↗
PubMed2002

Problem of timely diagnosis in anthrax meningitis.

Anthrax continues to remain a problem in parts of India. Meningitis is often a complication encountered among cases with cutaneous anthrax. We have encountered a dozen cases of anthrax meningitis in our hosptal in the past decade. A sudden unexplained rise in cases in the past two years with hundred percent mortality stresses the need for rapid confirmatory diagnosis. Most of the cases admitted with central nervous system involvement had a provisional diagnosis of conditions other than anthrax meningitis. A strong clinical suspicion with a simple Gram stain smear of the CSF will help confirm anthrax meningitis in endemic areas.

Adult↗
PubMed2002

Left atrial myxoma presenting as pseudobulbar palsy.

A case of left atrial (LA) myxoma presenting as pseudobulbar palsy, due to multiple cerebral infarcts, without any cardiac manifestations, is presented. LA myxoma is rare cause of embolization to CNS causing ischemic infarcts. Due to multiple CNS infarcts patient can present with varied clinical picture and pseudobulbar palsy is not a very common presentation. It was a real diagnostic dilemma before LA myxoma was diagnosed on echocardiography.

Adult↗
PubMed2002

Wasp sting induced neurological manifestations.

Wasp stings generally cause local reactions like pain, wheal, flare, edema and swelling, which are generally self-limiting. Multiple stings can lead to vomiting, diarrhea, generalized edema, dyspnea, hypotension, collapse, renal failure or death. Unusually, they may cause serum sickness, vasculitis, neuritis or encephalitis. We report a case of a 40 year old male who developed focal neurological deficit 10 hours following a wasp sting, which was confirmed to be ponto-cerebellar infarction on MRI scan, and recovered within five days.

Adult↗
PubMed2002

Evaluation of analgesic, antipyretic and anti-inflammatory activity of spirobarbitunylphenothiazines in rodents.

Analgesic, antipyretic and anti-inflammatory activities of newly synthesized spirobarbitunylphenothiazines viz 10-[7, 11-Di(4-4' dimethoxphenyl)-3-oxo-9-methylaminoimino-2, 4-diazaspiro [5.5] undecane 1, 5 dione] acetylphenothiazine (test drug A) and 10-[7, 11-Di (N.N-dimethylaminophenyl)-3-oxo-9-methylaminoimino-2, 4-diazaspiro [5, 5] undecane-1, 5 dione] acetylphenothiazine (test drug B) have been screened in Swiss mice and Wistar rats. The peripheral analgesic activity of test drugs A and B was investigated by acetic acid induced writhing test in Swiss mice while the central analgesic action was assessed by hot-wire (tail flick test) of the analgesiometer and tail-clip test in Wistar rats. Antipyretic activity was assessed on Brewer's yeast induced pyrexic model while antiinflammatory activity was seen on carrageenan induced hind paw oedema. Analgesic activity was found to be only of peripheral type as there was reduction of 66% in writhing responses by test drugs A and B in dose of 80 mg/kg in mice. No change in the tail flick responses was observed on analgesiometer or by tail clip by both the test drugs. Reduction of 1.5 to 2.0 degrees C in rectal temperature was observed in pyretic rats by test drugs A and B in dose of 80 mg/kg. 80% reduction in paw volume was noted in 80 mg/kg dose of both the test drugs which was comparable to the anti-inflammatory activity of 300 mg/kg, p.o. of phenylbutazone.

Analgesics↗
PubMed2001

Reversal of GSTP1 CpG island hypermethylation and reactivation of pi-class glutathione S-transferase (GSTP1) expression in human prostate cancer cells by treatment with procainamide.

Among the many somatic genome alterations present in cancer cells, changes in DNA methylation may represent reversible "epigenetic" lesions, rather than irreversible "genetic" alterations. Cancer cell DNA is typically characterized by increases in the methylation of CpG dinucleotides clustered into CpG islands, near the transcriptional regulatory regions of critical genes, and by an overall reduction in CpG dinucleotide methylation. The transcriptional "silencing" of gene expression associated with such CpG island DNA hypermethylation presents an attractive therapeutic target: restoration of "silenced" gene expression may be possible via therapeutic reversal of CpG island hypermethylation. 5-Aza-cytidine (5-aza-C) and 5-aza-deoxycytidine (5-aza-dC), nucleoside analogue inhibitors of DNA methyltransferases, have been widely used in attempts to reverse abnormal DNA hypermethylation in cancer cells and restore "silenced" gene expression. However, clinical utility of the nucleoside analogue DNA methyltransferase inhibitors has been limited somewhat by myelosuppression and other side effects. Many of these side effects are characteristic of nucleoside analogues that are not DNA methyltransferase inhibitors, offering the possibility that nonnucleoside analogue DNA methyltransferase inhibitors might not possess such side effects. Human prostate cancer (PCA) cells characteristically contain hypermethylated CpG island sequences encompassing the transcriptional regulatory region of GSTP1, the gene encoding the pi-class glutathione S-transferase (GSTP1), and fail to express GSTP1 as a consequence of transcriptional "silencing." Inactivation of GSTP1 by CpG island hypermethylation, the most common somatic genome alteration yet reported for human PCAs, occurs early during human prostatic carcinogenesis and results in a loss of GSTP1 "caretaker" function, leaving prostate cells with inadequate defenses against oxidant and electrophile carcinogens. We report here that the drug procainamide, a nonnucleoside inhibitor of DNA methyltransferases, reversed GSTP1 CpG island hypermethylation and restored GSTP1 expression in LNCaP human PCA cells propagated in vitro or in vivo as xenograft tumors in athymic nude mice.

Animals↗
PubMed2001

Type-specific separation of animal cells in aqueous two-phase systems using antibody conjugates with temperature-sensitive polymers.

A new type of aqueous two-phase system (ATPS) has been developed in which a temperature-sensitive polymer, poly-N-isopropylacrylamide [poly (NIPAM)] was used as a ligand carrier for the specific separation of animal cells. Monoclonal antibodies were modified with itaconic anhydride and copolymerized with N-isopropylacrylamide, and the ligand-conjugated carriers were added to the polyethylene glycol 8000-dextran T500 aqueous two-phase systems. The antibody-polymer conjugates were partitioned to the top phase in the absence or presence of 0.15 M NaCl. When ligand-conjugated carriers were used, more than 80% of the cells were specifically partitioned to the top phase in the presence of NaCl up to 0.1 M. The cells were partitioned almost completely to the bottom phase at 0.1 M NaCl or above, when no antibody-conjugate was added in the ATPS. As a model system, CD34-positive human acute myeloid leukemia cells (KG-1) were specifically separated from human T lymphoma cells (Jurkat) by applying anti-CD34 conjugated with poly-N-isopropylacrylamide in the aqueous two-phase system. By the temperature-induced precipitation of the polymer, about 90% of the antibody-polymer conjugates were recovered from the top phase, which gave approximately 75% cell separating efficiency in the next cycle of reuse.

Acrylamides↗
PubMed2001

Terminal-repeat retrotransposons in miniature (TRIM) are involved in restructuring plant genomes.

A new group of long terminal repeats (LTR) retrotransposons, termed terminal-repeat retrotransposons in miniature (TRIM), are described that are present in both monocotyledonous and dicotyledonous plant. TRIM elements have terminal direct repeat sequences between approximately 100 and 250 bp in length that encompass an internal domain of approximately 100-300 bp. The internal domain contains primer binding site and polypurine tract motifs but lacks the coding domains required for mobility. Thus TRIM elements are not capable of autonomous transposition and probably require the help of mobility-related proteins encoded by other retrotransposons. The structural organization of TRIM elements suggests an evolutionary relationship to either LTR retrotransposons or retroviruses. The past mobility of TRIM elements is indicated by the presence of flanking 5-bp direct repeats found typically at LTR retrotransposon insertion sites, the high degree of sequence conservation between elements from different genomic locations, and the identification of related to empty sites (RESites). TRIM elements seem to be involved actively in the restructuring of plant genomes, affecting the promoter, coding region and intron-exon structure of genes. In solanaceous species and maize, TRIM elements provided target sites for further retrotransposon insertions. In Arabidopsis, evidence is provided that the TRIM element also can be involved in the transduction of host genes.

Amino Acid Sequence↗
PubMed2001

Rate acceleration and subsequent retardation of Diels-Alder reactions in LiClO4-diethyl ether: an experimental investigation.

The experimental kinetic data for several Diels-Alder reactions show why a 5 M LiClO(4)-diethyl ether (LPDE) solution offers maximum enhancement of reaction rates, endo/exo ratios, and yields. These reactions, if carried out in LPDE solutions of concentrations higher than 5 M, show a substantial decrease in these kinetic parameters. This decrease is attributed to the very high viscosity of LPDE solutions near saturation, though this interpretation is not consistent when considered in terms of sizes of the diene and dienophile. The monoetherates, dietherates, and higher other clusters in LPDE solutions and their relationship with the Lewis acid catalysis by Li+ offer a more plausible explanation of both the enhancement and the decrease of the rate of Diels-Alder reactions in this medium.

Journal Article↗
PubMed2001

Both the environment and somatic mutations govern the aggregation pathway of pathogenic immunoglobulin light chain.

Deposition of monoclonal immunoglobulin light chain (LC) aggregates in tissues is the hallmark of a class of fatal diseases with no effective treatment. In the most prevalent diseases two different types of LC aggregates are observed: fibrillar deposits in LC amyloidosis (AL) and granular aggregates in LC deposition disease (LCDD). The mechanisms by which a given LC forms either type of aggregate are not understood. Although some LCs are more aggregation-prone than others, this does not appear to be due to specific sequence determinants, but more likely from global properties that can be introduced by multiple somatic mutations. Moreover, a single LC isotype can sometimes form both fibrillar and granular aggregates within the same patient. To better understand how the different aggregation pathways arise, we developed a series of in vitro assays to analyze the formation of distinct aggregate types. The recombinant kappa IV LC (SMA) assembles into fibrils when agitated. We now show that SMA can also form granular aggregates upon exposure to copper, and that this aggregation can occur not only in vitro, but also in cells. A constellation of somatic mutations, consisting of His89/His94/Gln96, is sufficient to confer sensitivity to copper on wild-type kappa IV proteins. The formation of both types of aggregates is inhibited by synthetic peptides derived from the LC variable domain. However, the peptide that inhibits fibrillar aggregation is different from the peptide that inhibits copper-induced aggregation. Thus, distinct molecular surfaces of the LC underly each type of aggregate. We conclude that both the intrinsic properties of the sequence and extrinsic conditions govern the aggregation pathway of a LC.

Amino Acid Sequence↗