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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 217 records · Page 12Linked to original sources

The optic nerve in children with craniosynostosis. A pre and post surgical evaluation.

Optic nerve (ON) damage especially from papilloedema can be prevented with timely detection. The detailed ocular and radiographic status of 33 unoperated craniosynostosis (CS) was documented prospectively; the ON was also assessed by flash VER and A-scan echography for ON thickness. Fluorescein angiography (FA) was done for all suspected and early papilloedemas. ON involvement diagnosed in 10/33 showed highly significant correlations with multiple suture synostoses (p = 0.004) and exorbitism (p < 0.001). VER latency was increased in all 5 ON atrophies; and also in 1/5 papilloedemas without atrophic changes, urgent surgery in which reversed VER changes, and vision later improved from 6/60 to 6/9. FA was valuable for confirming the clinical diagnosis of the earliest papilloedemas; the FA also returned to normal with immediate therapy along with reversal of the clinical picture. ON echography especially helped in monitoring regression of disc oedema. Ours seems the first report especially in CS where a critical follow-up of all above parameters in 21 operated/33 could objectively establish the role of each investigation in conjunction with careful clinical monitoring especially of the ON head. Such comprehensive evaluation should help reduce the blindness often seen in such children.

Adolescent

Accessory limb attached to the back.

The authors report on a newborn with an accessory malformed leg attached to the back. The limb was associated with a teratomatous mass adjacent to its attachment site. The embryology and nomenclature of this malformation is discussed briefly.

Back

Male-induced implantation failure (the Bruce effect) in mice: protective effect of familiar males on implantation.

Housing newly inseminated female mice in contact with a familiar male (a male that had cohabited with the female for 24 h during the pericopulatory period, but not the coital partner) depressed the implantation failure (the Bruce effect) induced by exposure to alien males. This is comparable to the protective effect of stud males on implantation in alien male-exposed females. The findings imply that exposure to a male (stud or any other) during the pericopulatory period enables the female to memorize the male-originating olfactory cues, and that this memory formation is not contingent upon mating. Reexposure to the male-originating olfactory cues induces a luteotrophic effect in the newly inseminated female, which accounts for the protective effect of the stud/familiar male on implantation in the alien male-exposed female. The male-originating olfactory cues that provide the protective effect on implantation act through contact. The findings also lend support to the view that the female mouse is capable of identifying a male as an individual through olfactory cues perceived during the pericopulatory period.

Animals

Visceral leishmaniasis in the acquired immunodeficiency syndrome: report of two cases.

Core biopsies of the bone marrow are indispensable in the evaluation of fever of unknown etiology in human immunodeficiency virus-positive patients. We report two patients in whom visceral leishmaniasis was diagnosed based on the typical morphology, staining characteristics, and ultrastructure of the organisms.

AIDS-Related Opportunistic Infections

Characterization of a monoclonal antibody against latex protein associated with latex allergy.

Several hybridomas were produced against antigens extracted from the latex sap of Hevea brasiliensis. One of the monoclonal antibodies (LA-E3) reacted with antigens demonstrating binding to patient sera on crossed enzyme immunoelectrophoresis. This monoclonal antibody reacted with 2 of 10 glove extracts studied and with both Malaysian and Indian latex plant extracts. The antigens purified with monoclonal antibody affinity chromatography demonstrated specific IgE in the sera of patients with latex allergy as determined by ELISA. This monoclonal antibody can thus be utilized to obtain reliable antigens useful in the diagnosis of latex sensitivity, although additional antigens will likely be necessary to enhance sensitivity and specificity.

Adolescent

Postnatal ontogeny of GABAA and benzodiazepine receptors in individual layers of rat visual cortex and the effect of visual deprivation.

The postnatal development of GABAA and benzodiazepine receptors was studied in the rat visual cortex with [3H]muscimol and [3H]flunitrazepam, respectively. The studies were performed by quantitative receptor autoradiography in the different cortical layers from normally raised rats and from monocularly deprived animals. In all cortical layers of normal rats there was a sharp (approx 3-fold) increase in [3H]muscimol binding from days 1 to 10. Between postnatal days 10 and 20 there was a considerable decrease in GABAA receptors; thereafter this decline continued until adulthood but at a more moderate rate. In all cortical layers, [3H]flunitrazepam binding increased sharply, also from day 1 to 10; at this age the adult values were practically attained. Monocular deprivation, by unilateral eyelid suture at the age of 11 days onwards lead to an increase in [3H]muscimol binding in cortical layers IV-VI. This increase in GABAA receptors was detectable at the age of 25 days onwards. In contrast, monocular deprivation did not alter the density of benzodiazepine receptors in any of the cortical layers, and this lack of effects was regardless of the duration of visual deprivation. The present results suggest that the development of GABAA receptors in the deeper cortical layers, but not that of benzodiazepine receptors, is seemingly regulated by the visual experience at a critical period of brain maturation.

Animals

Co-dominant and reciprocal T-helper cell activity of epitopic sequences and formation of junctional B-cell determinants in synthetic T:B chimeric immunogens.

The identification of defined T-helper (Th) cell determinants, particularly those recognized in the context of several MHC or HLA haplotypes, and their use to provide effective carrier help to short synthetic constructs representing a B-cell epitope have made it feasible to synthesize putatively potent immunogens. However, a number of crucial questions regarding immunogenicity of epitopic sequences need to be addressed before an optimally effective synthetic vaccine can be designed. The present study deals with the hybrid constructs incorporating a known B-cell epitope from the merozoite surface protein-1 (MSP-1) of a human malarial parasite, Plasmodium falciparum, and the promiscuous Th-cell epitope from tetanus toxin or from the circumsporozoite protein of P. falciparum. Here, we provide data which suggest that B- and T-cell determinants present in a hybrid construct could, in fact, provide reciprocal helper activity for antibody production; that antibodies to a Th-cell epitope may not necessarily block its helper function; and that junctional B-cell epitopes may be formed. All this may influence, in an unpredictable manner, the quality of protective immune response sought to be generated using the chimeric immunogens, with important implications for vaccine design.

Amino Acid Sequence

A self-associating hepatitis B surface antigen-derived peptide that is immunogenic in alum.

We previously described an oligomeric synthetic peptide derived from the hepatitis B surface antigen that displayed a limited tendency to form self-associating macromolecular structures in solution. Here it is demonstrated that amino-terminal myristylation of this peptide results in near quantitative aggregation of the oligomeric peptide. The myristylated peptide is highly immunogenic when used in conjunction with alum as adjuvant in both the rabbit and rhesus monkey models. The antibody response generated by peptide also cross-reacted with native antigen and was long-lasting. Collectively the results described in this and previous reports offer an attractive new approach for generating immunogenic peptide mimetics of conformational epitopes that may find application as vaccines.

Alum Compounds

Molecular organization and evolution of mosquito genomes.

Given the importance of mosquitoes as disease vectors, relatively little is known about the molecular organization and evolution of mosquito genomes as compared to other insects such as fruit flies. The advances in recombinant DNA technology and the possibility that mosquito populations could be controlled and genetically manipulated using such technology has stimulated considerable research during the last few years in the areas of genome organization and evolution, genome mapping, endogenous transposable elements, and mapping and characterization of genes conferring susceptibility to different parasites and pathogens. This review summarizes research currently underway in our laboratory and elsewhere in these areas.

Animals

Differential laminar expression of AMPA receptor genes in the developing rat visual cortex using in situ hybridization histochemistry. Effect of visual deprivation.

The postnatal development of laminar pattern of AMPA receptor mRNA subtypes GluR-A through to GluR-D (flip variants) in the visual cortex of both normally raised and monocularly deprived rats (one eyelid sutured at the age of 11 days) was studied using in situ hybridization histochemistry and computer-assisted image analysis. The AMPA receptors GluR-A through to GluR-D transcripts exhibit a differential laminar expression pattern in the developing rat visual cortex. At birth the levels of GluR-A transcripts are lower by about 50% in each visual cortical layer as compared to the adult values. In contrast, GluR-B to GluR-D mRNAs are expressed in all cases at higher levels at birth than in the adult brain. Unilateral eyelid closure at postnatal day 11 for several periods of time resulted in both transient and permanent changes in the laminar development of GluR-A through to GluR-C transcripts but hardly affected the GluR-D mRNA subtype. The distinct laminar developmental pattern of AMPA receptor mRNAs in rat visual cortex as well as the differential effects of visual deprivation suggest specific roles of AMPA receptor subtypes during the early postnatal maturation of visual function.

Animals

Reversible dementias.

With so many conditions that can manifest in dementia, the question arises as to how extensive an evaluation need be done on the individual patient presenting with dementia. Thorough physical, neurologic, and psychiatric examinations are the cornerstones of the work-up, with special attention paid to the history, use of medications, and mental status of the patient. Laboratory tests recommended by the National Institutes of Health Consensus Conference on Differential Diagnosis of Dementing Diseases include a complete blood count, electrolyte and metabolic screen, thyroid panel, vitamin B12 and folate levels, syphilis serology, urinalysis, chest radiograph and electrocardiogram, and head CT scan. These evaluations are sufficient to diagnose the majority of treatable dementias. Other evaluations including magnetic resonance imaging, electroencephalography, cerebrospinal fluid examination, cerebral blood flow and metabolism measures (rate of cerebral blood flow, single photon emission computed tomography, and positron-emission tomography), and brain biopsy all can be of additional assistance in diagnosing the cause of the dementia when justified by the clinical setting. When the appropriate diagnosis is made, therapy is directed at the primary disorder. Successful treatment of the primary condition may result in stabilization or partial or complete reversal of the cognitive disturbance. In some instances, judicious pharmacologic management of the accompanying behavioral disturbance may be required.

Avitaminosis

Transforming growth factor beta increases the expression of HIV-1 gene in transfected human mesangial cells.

Human immunodeficiency virus type 1 (HIV) infection is often complicated by focal glomerulosclerosis (FGS) and other renal lesions collectively termed HIV associated nephropathy (HIVAN). FGS is characterized by glomerular mesangial expansion and increased synthesis of matrix components. The molecular pathogenic mechanisms associated with the development of HIV associated nephropathy are unknown. Experimental animal models suggest a role for cytokines and growth factors, particularly transforming growth factor beta (TGF-beta), in the pathogenesis of glomerulosclerosis. Patients with AIDS have elevated plasma and tissue levels of TGF-beta. We carried out experiments to determine whether primary human mesangial cells (HMC) in culture can be transfected with HIV-1 genes. HMC were transfected with a chloramphenicol acetyl transferase (CAT) reporter construct containing HIV-1 acetyl transferase (CAT) reporter construct containing HIV-1 LTR sequences. Our results show successful transfection of HMC with HIV-1 LTR gene. HMC transfected with LTR gene are responsive to the HIV-1 regulatory gene product Tat. To study whether TGF-beta can modulate the expression of HIV-1 LTR gene in HMC, HMC transfected with an HIV-1 LTR CAT plasmid were treated with TGF-beta and other growth factors two hours before harvest. TGF-beta specifically increased the expression of the HIV-1 gene in HMC in a dose dependent manner. We further studied whether up-regulation of HIV-1 LTR expression in HMC was mediated by the effect of TGF-beta on the interaction of transcription factors to their binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line

Distribution and relevance of insulin-like growth factor-I receptor in metanephric development.

During embryogenesis, various ligand-receptor interactions take place to modulate the development and growth of various mammalian organs. During these interactions, a critical concentration of a given receptor is needed to elicit a ligand-induced biologic response at a defined gestational stage of the fetus. In this study, the distribution and the relevance of insulin-like growth factor-I receptor (IGF-IR) in metanephric development was investigated. Kidneys were harvested from mouse embryos at days 13 to 19 of fetal gestation, and maintained in a metanephric culture system. Immunofluorescence studies, using anti-IGF-IR, revealed a high expression of IGF-IR at day 13, which declined during the later stages of gestation through neonatal life. To study the relevance of IGF-IR expression in metanephric development, antisense-oligodeoxynucleotide (ODN) experiments were carried out. Antisense-ODN 43 mer probes were synthesized utilizing rat IGF-IR cDNA selected nucleotide sequences which are highly conserved in other mammalian species. Southern blot analyses of various restriction fragments of the rat and mice genomic DNA yielded similar bands when hybridized with the antisense-ODN or rat IGF-IR cDNA, suggesting a high degree of homology in the region of the gene selected for the synthesis of antisense-ODN. Also, the antisense-ODN hybridized with the appropriate murine fetal kidney mRNA species, as ascertained by S1 nuclease protection assay. Inclusion of antisense-ODN in the culture medium resulted in an inhibition of the growth of the kidney, reduction in the population of the nephrons and disorganization of the ureteric bud branches.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Detection of antisense transcripts in transgenic plants by RT-PCR.

A reverse transcriptase-polymerase chain reaction (RT-PCR) where one oligonucleotide primer is end-labelled has been used to analyse expression in transgenic plants carrying antisense gene constructs. Specific detection of both sense and antisense RNA transcripts of the spliceosomal protein gene, U2B'', was achieved using the same pair of oligonucleotide primers. To maintain specificity, a reaction step in which reverse transcriptase was inactivated and RNA digested was found to be essential.

Base Sequence

Perinatal mortality in rural India with special reference to high risk pregnancies.

One-thousand-and-sixty-five pregnant mothers among a rural population of 30,000 in Uttar Pradesh were followed for 1 year. A still birth rate of 26.1 and perinatal mortality rate of 121.1 per thousand births were registered. Early neonatal mortality rate was found to be 97.4 per thousand live births. Twenty per cent of the women were identified with high risk factors. Inadequate or no antenatal care, bad obstetric history, and prolonged labour attributed to 13, 20, and 27 per cent of the risk, respectively, with a respective relative risk of 2.23, 3.1, and 4.09 times. These three factors were found to be the major and significant contributors to high perinatal mortality amongst the 'high risk' group. Selective extension of comprehensive M.C.H. Care to this group using the high risk approach is expected to lower perinatal mortality in rural community where M.C.H. services are far from optimum.

Female

Evidence for involvement of nitric oxide in pretectal analgesia in rat.

The study was undertaken to evaluate the role of nitric oxide (NO) in pretectal (PTN)-induced analgesia in rats. Microinjection of varying concentrations of L-arginine (1 nM to 1 microM) produced a quick, long-lasting and concentration-dependent analgesic response, whereas similar concentrations of D-arginine failed to produce analgesia. Moreover pretreatment with N-nitro-L-arginine methyl ester (L-NAME, 1 microM) significantly prevented L-arginine induced analgesia. Further, pretreatment of animals with methylene blue, a known guanylate cyclase inhibitor also prevented the development of analgesia. Our study suggests that L-arginine caused production of NO, which in turn activates pretectal analgesic system involving cyclic GMP.

Analgesia

Analgesic effect of morphine, clonidine and serotonin microinjected into the PTN of rats.

The study was aimed to delineate the neurotransmitter receptors involved in pretectal analgesic mechanisms by direct microinjection of neurotransmitter agonists and antagonists through chronically implanted cannulae in the pretectal nucleus of rats. Morphine, clonidine and serotonin, at doses of 2.5 and 5.0 micrograms microinjected into the pretectal nucleus, produced a significant and prolonged analgesia as measured by the tail-flick test. The analgesia produced by morphine, clonidine and serotonin is significantly attenuated by pretreatment of the animals with naloxone (1 micrograms), yohimbine (5 micrograms) and methysergide (5-10 micrograms) respectively. The results indicate the possible involvement of opioid, adrenergic and serotonergic mechanisms in pretectal analgesia.

Analgesics