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Biomedical subjects

M Kumar

Publications and source records attributed to M Kumar.

At least 37 records · Page 2Linked to original sources

No difference exists in the alteration of circadian rhythm between patients with and without intensive care unit psychosis.

OBJECTIVE: To determine if a difference exists in the circadian rhythm entrainment between patients with and without intensive care unit (ICU) psychosis. DESIGN: Retrospective chart reviews from 149 consecutive patients admitted to our ICU during the period of January 1993 to August 1993. Twelve patients with a history of mental illness or alcohol or substance abuse were excluded from the study. SETTING: A 20-bed surgical ICU at a large teaching hospital. PATIENTS: Patients who remained in the ICU for a minimum of 2 days after undergoing thoracic or vascular operations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hourly temperature and urine output were ascertained from the patient records. The time of temperature and urine output nadir was used as a marker of circadian rhythm. Of the 137 patients included in the study, 17 (12.4%) developed ICU psychosis as defined by standard criteria. The time of temperature nadir was randomly distributed around the clock for each group. Cosinar rhythmometry analysis of temperature data showed a lack of circadian rhythm entrainment in most patients up to the third postoperative day. No statistically significant difference exists in the deviation of such impairment between the groups. CONCLUSION: Either patients who develop ICU psychosis have an increased sensitivity to an alteration of their circadian rhythm, or ICU psychosis develops independent of circadian rhythm abnormalities.

Adaptation, Physiological

Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

Brain

Hematopoietic growth factors for the treatment of aplastic anemia.

The use of hematopoietic growth factors, although well established for the management of chemotherapy-induced neutropenia, remains controversial for the treatment of aplastic anemia and inherited bone marrow failure syndromes. The most commonly used factors are granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, and erythropoietin. Newer growth factors such as stem cell factor, thrombopoietin, Flt3 ligand, and interleukins have shown promising results in the laboratory, and some have been used in clinical trials. This article reviews the clinical use of old and new hematopoietic growth factors in acquired and inherited bone marrow failure, and discusses emerging concerns about long term toxicity of these factors.

Anemia, Aplastic

A bereavement support group intervention is longitudinally associated with salutary effects on the CD4 cell count and number of physician visits.

A randomized, controlled, clinical trial was conducted to examine the impact of a semistructured, 10-week, once weekly, 90-min/session bereavement support group intervention on immunological, neuroendocrine, and clinical health status in human immunodeficiency virus type 1-seropositive (HIV-1+) and HIV-1-seronegative (HIV-1-) homosexual men, compared to a standard of care control condition. A total of 119 homosexual men (74 HIV-1+ and 45 HIV-1-) were assessed at baseline, 10 weeks, and 6 months follow-up. At the 6-month follow-up assessment, the intervention groups exhibited significant beneficial effects compared to controls on changes in CD4 cell, total T-lymphocyte, and total lymphocyte counts, when baseline levels, antiretroviral medication use, CDC stage of disease, and other potentially confounding factors were accounted for. There was no statistically significant effect on the CD4/CD8 ratio or on the CD8 cell count. The effect on CD4 cell count was associated with group attendance and with changes in plasma cortisol level. Plasma cortisol levels decreased significantly among intervention subjects, compared to controls. A significantly reduced number of health care visits over the 6-month follow-up period among the intervention subjects supported the clinical relevance of the immunological changes observed for both HIV-1+ and HIV-1- individuals. These results indicate that behavioral interventions may have salutary immunological and clinical health effects following bereavement among HIV-1-infected individuals. The effect in HIV-1- individuals suggests that this bereavement support group intervention might have similar salutary effects in the general population. Potential effects of such interventions on clinical HIV disease progression are of interest and should be studied.

Adult

Antisense RNA: function and fate of duplex RNA in cells of higher eukaryotes.

There is ample evidence that cells of higher eukaryotes express double-stranded RNA molecules (dsRNAs) either naturally or as the result of viral infection or aberrant, bidirectional transcriptional readthrough. These duplex molecules can exist in either the cytoplasmic or nuclear compartments. Cells have evolved distinct ways of responding to dsRNAs, depending on the nature and location of the duplexes. Since dsRNA molecules are not thought to exist naturally within the cytoplasm, dsRNA in this compartment is most often associated with viral infections. Cells have evolved defensive strategies against such molecules, primarily involving the interferon response pathway. Nuclear dsRNA, however, does not induce interferons and may play an important posttranscriptional regulatory role. Nuclear dsRNA appears to be the substrate for enzymes which deaminate adenosine residues to inosine residues within the polynucleotide structure, resulting in partial or full unwinding. Extensively modified RNAs are either rapidly degraded or retained within the nucleus, whereas transcripts with few modifications may be transported to the cytoplasm, where they serve to produce altered proteins. This review summarizes our current knowledge about the function and fate of dsRNA in cells of higher eukaryotes and its potential manipulation as a research and therapeutic tool.

Animals

Cerebral perfusion imaging in asymptomatic carotid artery occlusion following gun shot.

Recognition of brain injury in asymptomatic carotid artery injuries with conventional methods can be difficult. We present a case of angiographically proven asymptomatic left internal carotid artery occlusion with normal CT after a gunshot wound. The SPECT brain perfusion imaging showed mild generalized supratentorial hypoperfusion of the bilateral cerebral cortices on the left side and severe left temporal lobe hypoperfusion.

Adult

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