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Biomedical subjects

M Kumar

Publications and source records attributed to M Kumar.

At least 91 records · Page 5Linked to original sources

An alternative approach to bandage contact lenses.

PURPOSE: Therapeutic bandage contact lenses have been used in the management of a variety of corneal and anterior segment disorders. However, clinical experience with the therapeutic use of disposable contact lenses is limited. The present study was designed to evaluate the efficacy of disposable contact lenses as bandage lenses in anterior segment disorders. METHODS: We fit 45 patients who had various corneal and anterior segment disorders with disposable contact lenses (42% etafilcon A and 58% water content). We used this lens as a healing and surgical adjunct and for structural support and symptomatic relief. Patients were followed for a minimum period of 3 months. Therapeutic efficacy and complications were evaluated. RESULTS: Eighty-two percent of patients were fit successfully. Ninety-one percent of the successfully fit patients were therapeutic successes. Disposable lenses were found to be very useful in the management of epithelial abnormalities and as surgical adjuncts. Dry eye was the most frequent cause of contact lens associated therapeutic failure. Complications included contact lens deposits, lens loss, and corneal neovascularization. CONCLUSIONS: The use of disposable lenses was most effective in conditions requiring short-term lens use where one to two lens applications were sufficient to allow healing, making disposable lenses a very convenient and cost-effective alternative to conventional therapeutic bandage contact lenses. For reasons of cost, disposable lenses were not a viable alternative in conditions requiring therapeutic lens use for long periods of time.

Adult↗

Infective and traumatic aneurysms.

Traumatic intracranial aneurysms are rare lesions but should be considered in penetrating head injury, particularly in cases of low-velocity gunshot wounds or stab wounds to the head. Because most of these aneurysms are false aneurysms, treatment may require excision or trapping procedures.

Anti-Bacterial Agents↗

Mechanism of carbon monoxide oxidation by the carbon monoxide dehydrogenase/acetyl-CoA synthase from Clostridium thermoaceticum: kinetic characterization of the intermediates.

Carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) from Clostridium thermoaceticum catalyzes (i) the synthesis of acetyl-CoA from a methylated corrinoid protein, CO, and coenzyme A and (ii) the oxidation of CO to CO2. CO oxidation occurs at a Ni- and FeS-containing center known as cluster C. Electrons are transferred from cluster C to a separate metal center, cluster B, to external acceptors like ferredoxin. In the work described here, we performed reductive titrations of CODH/ACS with CO and sodium dithionite and monitored the reaction by electron paramagnetic resonance (EPR) spectroscopy. We also performed pre-steady-state kinetic studies by rapid freeze-quench EPR spectroscopy (FQ-EPR) and stopped-flow kinetics. Redox titrations of CODH/ACS revealed the existence of a UV-visible and EPR-silent electron acceptor denoted center S that does not appear to be associated with any of the other metal centers in the protein. Our results support the previous proposals [Anderson, M. E., & Lindahl, P. A. (1994) Biochemistry 33, 8702-8711; Anderson, M. E., & Lindahl, P. A. (1996) Biochemistry 35, 8371-8380] that the Cred2 form of cluster C is two electrons more reduced than the Cred1 form. The combined results from titrations and pre-steady-state studies were used to formulate a mechanism for CO oxidation, composed of the following steps: (i) CO binding to the [Cred1,Box, Xox] state to yield a Cred1-CO complex; (ii) two-electron reduction of Cred1 to Cred2 concerted with CO2 release; (iii) binding of a second CO molecule to the [Cred2,Box,Xox] state to form a Cred2-CO complex; (iv) electron transfer from Cred2-CO to cluster B to form [Cred2,Bred,Xred] with concerted release of the second CO2. Step iii competes with internal electron transfer from Cred2 to Box and Xox. At high CO concentrations, step iii is favored, whereas at low concentrations, only one CO molecule per turnover binds and undergoes oxidation. Closure of the catalytic cycle involves electron transfer from reduced enzyme to an electron acceptor protein, like ferredoxin. Xox is a yet-uncharacterized electron acceptor that may be an intermediate in the reduction of center S. The Cred2 state appears to be the predominant state of cluster C during steady-state turnover. The rate-determining step for the first half-reaction is step iv, while during steady-state turnover, it appears to be electron transfer to external electron acceptors.

Aldehyde Oxidoreductases↗

Expression of lacZ reporter gene under the control of the polyhedrin promoter of Spodoptera litura nuclear polyhedrosis virus.

Promoter function of the putative polyhedrin-encoding gene (polh) of Spodoptera litura nuclear polyhedrosis virus (S1MNPV) was determined by transferring it to the Autographa californica nuclear polyhedrosis virus (AcMNPV) through the AcNPV polh based vector, pVL1393. Three transfer vectors pCBT2, pCBT3 and pCBT4 were constructed by substituting the promoter and the neighbouring sequences of AcNPV in pVL1393 by that of S1NPV. The Escherichia coli lacZ gene was placed downstream from the S1NPV polh promoter in the hybrid transfer vector (pCBT) constructs. Co-transfection of Spodoptera frugiperda cells (Sf9) with each of the pCBTlacZ vector and wild-type AcNPV DNAs led to synthesis of beta-galactosidase (beta Gal). The plaque-purified recombinant viruses (S1AcNPV.lacZ) expressing lacZ under the polh promoter of S1NPV are stable. The highest beta Gal activity was obtained with S1AcNPV4.lacZ. Production of beta Gal with recombinant virus, S1AcNPV3.lacZ in which S1NPV polh promoter is in the reverse orientation in the AcNPV genome, is 83% of that produced by S1AcNPV4.lacZ. These results indicate that the S1NPV polh promoter is active in the genetic environment of AcNPV; the polh of S1NPV is phylogenetically related to AcNPV like other baculoviruses.

Animals↗

Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts.

Antisense RNA may regulate the expression of a number of eukaryotic genes, but little is known about its prevalence or mechanism of action. We have used a model system in which antisense control can be studied both genetically and biochemically. Late in polyoma virus infection, early-strand mRNA levels are down-regulated by nuclear antisense RNA from the late strand. Analysis of early-strand transcripts isolated late in infection revealed extensive base modifications. In many transcripts almost half of the adenosines were altered to inosines or guanosines. These results suggest modification of RNA duplexes by double-stranded RNA adenosine deaminase or a related enzyme. Probes that detect only modified RNAs revealed that these molecules are not highly unstable, but accumulate within the nucleus and are thus inert for gene expression. Antisense-induced modifications can account for most or all of the observed regulation, with the lowered levels of early-strand RNAs commonly observed late in infection resulting from the fact that many transcripts are invisible to standard hybridization probes. This work suggests that similar antisense-mediated control mechanisms may also operate under physiological conditions in uninfected eukaryotic cells, and leads to the proposal that there is a novel pool of nuclear RNAs that cannot be seen with many molecular probes heretofore used.

3T3 Cells↗

Novel gene delivery to liver cells using engineered virosomes.

We have demonstrated for the first time that the reconstituted Sendai viral envelopes containing only the fusion protein (F-virosomes) are efficient vehicles for the delivery of foreign genes specifically into human hepatoblastoma cells (HepG2) in culture. The membrane fusion-mediated entry of CAT (chloramphenicol acetyl transferase) gene into the cells was confirmed and the amount delivered to various subcellular fractions was quantitated. The dose dependence and kinetics of expression of biologically active CAT protein in HepG2 cells was measured. The CAT expression level in F-virosome-mediated delivery was significantly higher than that of Lipofectin or liganded proteo-liposome-mediated gene transfer. This kind of targeted delivery by means of membrane fusion induced by viral envelope glycoprotein may have wide applications to various gene transfer strategies both in vitro and in vivo.

Animals↗

Argyrophilic nucleolar organizer regions: their value and correlation with clinical prognostic factors in breast carcinoma.

BACKGROUND AND OBJECTIVES: Argyrophilic nucleolar organizer regions (AgNORs) have been recently identified as a marker of proliferative index in various tumors. These were evaluated in 46 patients with primary breast carcinoma and were correlated with clinical prognostic parameters of breast cancer. Ten patients with benign breast tumors served as controls in the study. METHODS: AgNORs were stained in paraffin sections of the tissues using Ploton's silver technique. For each specimen, the number of AgNORs, within the nuclei of 100 tumor cells were calculated. The average number of AgNORs per nucleus was calculated and the results expressed as mean +/- S.D. RESULTS: AgNOR count was significantly higher in breast carcinoma (6.61 +/- 1.75) than in benign breast tumors (1.88 +/- 0.19). Further, the AgNOR count in breast carcinoma showed a statistically significant increase in correlation with the increase in the size of the tumor, stage of the cancer, number of metastatic lymph nodes, and tumor recurrence at various sites. However, the differences in AgNOR count at different lymph node levels and histologic grading were not statistically significant. CONCLUSIONS: These results indicate that breast tumors with a higher AgNOR count, even at the initial stage, have a poor prognosis and require aggressive treatment for better control of the disease. Further, it is suggested that the patients with a benign tumor and more than three AgNORs per nucleus need careful surveillance.

Adult↗

Hydropericardium syndrome (HPS) in India: a preliminary study on the causative agent and control of the disease by inactivated autogenous vaccine.

Hydropericardium syndrome (HPS) in broiler birds of 3 to 6 weeks of age was recorded for the first time in the Haldwani area of Nainital district (UP) in India in November, 1994. The overall mortality in 6 poultry farms was 61.62 per cent. The disease was experimentally transmitted by bacteria free infected liver homogenate extract passed through membrane filters of 0.22 and 0.1 mu APD. The aetiological agent was inactivated by heat treatment at 56 degrees C for one hour and 80 degrees C for 10 min. A precipitin band was demonstrated in agar gel immunodiffusion and counter immunoelectrophoresis using infected liver homogenate extract as antigen and homologous antisera raised in the laboratory. The disease was effectively controlled by formalinised and heat inactivated autogenous vaccine prepared from the infected livers of birds which died of natural infection.

Animals↗

Gossypol-induced hypokalemia and role of exogenous potassium salt supplementation when used as an antispermatogenic agent in male langur monkey.

In our earlier study, we have observed that hypokalemia in langur monkeys, following gossypol acetic acid (GAA) treatment (5 mg dose level) when used as an antispermatogenic agent, and potassium salt supplementation partially maintained body potassium level of the animals. The aims of the present investigation was to confirm further occurrence of hypokalemia in the monkey (comparatively at two higher dose levels) and the role of potassium salt in preventing occurrence of gossypol-induced hypokalemia. Highly purified gossypol acetic acid alone at two dose levels (7.5 and 10 mg/animal/day; oral) and in combination with potassium chloride (0.50 and 0.75 mg/animal/ day; oral) was given for 180 days. Treatment with gossypol alone as well as with the supplementation of potassium salt resulted in severe oligospermia and azoospermia. Animals receiving gossypol alone showed significant potassium deficiency with signs of fatigue at both dose levels. Enhanced potassium loss through urine was found in potassium-deficient animals, whereas animals receiving gossypol acetic acid plus potassium salt showed normal serum potassium with a less significant increase in urine potassium level during treatment phases. Other parameters of the body remained within normal range except gradual and significant elevation in serum transaminases activity. The animals gradually returned to normalcy following 150 and 180 days of termination of the treatment.

Animals↗

Characterization of the polyhedrin gene of Spodoptera litura nuclear polyhedrosis virus.

The polyhedrin gene (polh) of a characteristically distinct Spodoptera litura nuclear polyhedrosis virus isolate (SIMNPV) is identified in the HindIII-F fragment of the viral DNA. The nucleotide sequence of the 1057 base pair (bp) region of this fragment contains an open reading frame (ORF) without any intervening sequence for coding a polypeptide of 246 amino acids. Analysis of the nucleotide sequence and deduced amino acid sequence indicate that this has more than 70% sequence identity to known polyhedrins. The coding region is preceded by an AT rich region containing the conserved late promoter motif TAAG. The upstream promoter and coding regions of this polh gene are more similar to polh of the NPVs of Spodoptera frugiperda (Sf), Spodoptera exigua (Se) and Panolis flamea (Pf).

Amino Acid Sequence↗

The effect of selected classical music and spontaneous imagery on plasma beta-endorphin.

This study explored the effect of music and imagery on plasma beta-endorphin in 78 undergraduates. Subjects screened for relevant psychological and health criteria were assigned to music imaging, silent imaging, music listening, and control conditions. Subjects donated 15 ml of blood prior to and following the 2-hr intervention period. There were no group differences in potential confounding variables. Split-plot factorial analysis controlling for individual differences in pretest level of beta-endorphin revealed that those in the music imaging group experienced a significant pre-post decline in beta-endorphin, while no other group demonstrated any significant pre-post difference. These data suggest that music imaging may lower peripheral beta-endorphin levels in healthy subjects. Further exploration of the effects of music and imagery interventions on physiology and health may be warranted.

Analysis of Variance↗

Cognitive-behavioral stress management decreases dysphoric mood and herpes simplex virus-type 2 antibody titers in symptomatic HIV-seropositive gay men.

This study tested the effects of a 10-week group cognitive-behavioral stress management (CBSM) intervention on mood and immunologic parameters in HIV-seropositive gay men whose disease had progressed to a symptomatic stage. Men were randomized to either CBSM or a modified waiting-list control group. The CBSM intervention significantly decreased self-reported dysphoria, anxiety, and total distress. Individuals who practiced relaxation more consistently had significantly greater drops in dysphoria. The intervention also decreased herpes simplex virus-Type 2 (HSV-2) immunoglobulin G antibody titers. The control group showed no significant changes in either mood or antibody titers. Individual difference analyses revealed that decreases in dysphoria significantly predicted lower HSV-2 antibody titers by the end of the 10-week period. Neither group displayed changes in HSV-Type 1 antibody titers or in CD4+ or CD8+ cell numbers.

Adult↗

Effects of guided imagery and music (GIM) therapy on mood and cortisol in healthy adults.

Healthy adults (N = 28) participated in a randomized trial of Bonny Method of Guided Imagery and Music (GIM; a depth approach to music psychotherapy) sessions on mood and cortisol. Participants in both GIM and wait-list control conditions completed the Profile of Mood States (POMS) and donated 15 cc of blood before and after the 13-week intervention period and again at a 6-week follow-up. Split-plot factorial and post hoc analyses demonstrated that after 6 biweekly sessions GIM participants reported significant decreases between pre- and postsession depression, fatigue, and total mood disturbance and had significant decreases in cortisol level by follow-up. Pretest to follow-up decrease in cortisol was significantly associated with decrease in mood disturbance. A short series of GIM sessions may positively affect mood and reduce cortisol levels in healthy adults. Such changes in hormonal regulation may have health implications for chronically stressed people.

Adult↗

Toxicity associated with high-dose cytosine arabinoside and total body irradiation as conditioning for allogeneic bone marrow transplantation.

Seventy-three patients with hematological cancers undergoing allogeneic bone marrow transplantation (BMT) were evaluated for event-free survival (EFS) and toxicity. All received 36 g/m2 cytosine arabinoside (HDA) and 1200 cGy fractionated total body irradiation (TBI). We assessed the association of EFS and toxicities with the following risk factors; age, gender, diagnosis, initial relapse risk and patient-donor histocompatibility. The EFS probability is 33% at 800 days post-BMT. Twenty-six patients (36%) died of toxicity within 100 days and 14 (19%) have relapsed. EFS was inversely associated with age (P < 0.0001) and initial relapse risk (P = 0.007). The risk of pulmonary (P = 0.023) and hepatic toxicity (P = 0.011) increased with age. Diagnosis other than acute lymphoblastic leukemia (ALL) was a risk factor (P = 0.015) for graft-versus-host disease (GVHD); and fewer ALL patients died from toxicity (P = 0.014). The probability of sepsis within 100 days post-BMT correlated (P = 0.007) with initial relapse risk. We conclude: (1) the lower EFS and greater pulmonary and hepatic toxicity associated with increasing age indicate a need for less toxic regimens that maintain high antileukemic efficacy for older patients; (2) the high GVHD and sepsis rates seen in certain categories of patients indicate a need for careful definition of eligibility criteria for this still highly toxic treatment.

Adolescent↗

TPO1, a member of a novel protein family, is developmentally regulated in cultured oligodendrocytes.

Although the myelin membrane contains only a small set of major proteins, more sensitive assays indicate the presence of a plethora of uncharacterized proteins. We have used an antibody perturbation approach to reversibly block the differentiation of prooligodendroblasts into myelinating cells, and, in combination with a differential screening procedure, identified novel mRNAs that are activated during this period. One cDNA, TPO1, recognizes a 5.5-kb mRNA that is strongly up-regulated in oligodendrocytes after release of the differentiation block and that is expressed at high levels in brain tissue during active myelination. This cDNA represents at least two mRNAs differing from each other in their 5'-termini. The TPO1 cDNA contains an open reading frame of 1,380 bp, encoding a protein of 51.8 kDa with a predicted pI of 9.1 that contains two regions homologous to nonclassic zinc finger motifs. Subcellular localization studies suggest the enriched presence of TPO1 in spherical structures along the major cytoplasmic processes of oligodendrocytes. TPO1, along with homologues expressed in testis, placenta, and PC12 cells, form a novel family of proteins with multiple hydrophobic domains possibly serving as membrane spanning regions. We postulate that in oligodendrocytes, TPO1 encodes a protein factor involved in myelin biogenesis.

Amino Acid Sequence↗

Endoscopic sclerotherapy for esophageal varices in children with extrahepatic portal venous obstruction: a follow-up study.

BACKGROUND: Results of treatment with endoscopic sclerotherapy for esophageal varices in children extrahepatic portal venous obstruction are limited. METHODS: A prospective study was undertaken of fifty children (mean age, 7.4 +/- 3.8 years; range, 4 months to 14 years) with esophageal variceal bleeding caused by extrahepatic portal venous obstruction (EHPVO) treated by repeated intravariceal endoscopic sclerotherapy (EST) at intervals of 2-3 weeks until eradication (no varices on endoscopy). RESULTS: Eradication of varices was achieved in 44 children (88%) with a mean of eight sessions per child. In six other cases, variceal grade decreased by 50% from the initial grades. Bleeding episodes at presentation were controlled in all of the children with first ET >. Over a mean follow-up period of 19 months (range, 12-36 months), a total of 15 episodes of rebleeding occurred in 13 children (26%) before the third session of EST and all were controlled with EST. Risk of rebleeding in children with eradicated varices (n = 44) significantly decreased from 0.2 episodes per month to nil after eradication. None of the children without eradicated varices had rebleeding. Thus, EST was successful in controlling rebleeding in all of the cases. Recurrence of varices was observed in five children (10%). None of our children either required surgery for EST failure or died. CONCLUSIONS: EST is a safe and effective nonsurgical mode of therapy in controlling esophageal variceal bleeding in children with EHPVO. Significant variceal bleeding did not occur during the relatively short follow-up in this series.

Adolescent↗