Biomedical subjects
Publications and source records attributed to M Kumar.
PURPOSE: To discuss the etiology of an unusual finding of black color in a corneal ulcer. METHODS: Smear examination and culture of the corneal scraping were undertaken. RESULTS: The causative organism was found to be Aspergillus ruger. CONCLUSION: Black color in the corneal ulcer is attributed to Aspergillus niger.
Explore the source record for details and available documents.
Northern blot analysis of cultured endothelial cells derived from rat cerebral resistance vessels demonstrated the presence of c-mas mRNA. This is the first description of mas expression in non-neuronal cells. c-mas message was not detectable in cultured endothelial cells derived from other vascular beds, including rat aorta and mesenteric resistance vessels. Since c-mas has been purported to regulate the proliferation response to angiotensin, the growth properties of all three endothelial cell cultures were examined. The data indicated no differences in either basal or angiotensin-stimulated cell growth among brain, mesenteric or aortic-derived endothelial cells. These data suggest that c-mas is selectively expressed in brain endothelial cells and that this proto-oncogene does not regulate cell proliferation in this cell type.
PURPOSE: To evaluate the role of radiation therapy (RT), chemotherapy (CT), and surgery in the local control of synchronous bilateral Wilms Tumor (WT). METHODS AND MATERIALS: Between 1962 to 1993, 45 children were treated for bilateral WT; 38 patients with synchronous tumors were reviewed. Initial surgery depended on the era of treatment and included unilateral nephrectomy (N)/partial nephrectomy (PN) and contralateral PN in 6, unilateral N/PN alone in 7, and biopsy only in 25. Chemotherapy (CT) consisted of vincristine, actinomycin-D, and adriamycin in 32 and vincristine/ actinomycin-D in 6. Radiation therapy (RT) was given to 32 patients. Treatment included both kidneys in 20, unilateral kidney plus contralateral renal bed in 9, unilateral kidney in 2, and unilateral renal bed in 1. Follow-up was 16 months to 25 years (median: 6.3 years). RESULTS: Local control (LC) has been maintained in 66 out of 76 sites (87%). For Stage I-II disease with initial N/PN, LC was 10 out of 12 with RT and 11 out of 11 without RT; for Stage III with initial N/PN, LC was 8 out of 9 with RT and 1 out of 1 without RT. Initial CT and RT was followed by delayed N/PN for 20 sites; LC was 15 out of 17 in post induction Stage I-II and 1 out of 3 in postinduction Stage III. In 23 sites undergoing biopsy and chemotherapy, LC was 19 out of 20 with RT and 1 out of 3 without RT. Seven of 23 sites had a complete response (CR) after induction CT, and LC was maintained in four out of four with RT and one out of three without RT. Univariate Cox Regression analysis demonstrated that sites receiving two drugs had a statistically significant increase in loco-regional relapse when compared to sites receiving three drugs (p = 0.004). Major morbidities related to multimodality therapy have included renal failure in one patient and small bowel obstruction requiring lysis of adhesions in two patients. CONCLUSIONS: Local control does not seem to be compromised by renal conservation therapy. Local control is excellent in sites treated with radiation therapy in combination with three drug chemotherapy.
The efficiency of membrane fusion between reconstituted Sendai viral envelopes containing only the fusion protein (F-virosomes) and the plasma membrane of mouse teratocarcinoma cells (F9) in culture was assessed using an assay based on the relief of self-quenching of a lipid probe incorporated in the F-virosomes. The potential of F-virosomes was also evaluated for a targeted cytosolic delivery of lysozyme to F9 cells. [125I]Lysozyme entrapped into F-virosomes was taken to examine its fusion-mediated transfer to the F9 cells. Target specificity of the F-virosomes was confirmed by the interaction between the terminal Le(x) moiety (Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc) of F protein and the Le(x) determinant on the membrane of F9 cells. Incubation of the loaded F-virosomes with cells led to fusion-mediated delivery, as inferred from the ability of cells to internalize lysozyme in the presence of azide (a potent inhibitor of endocytosis). These results suggest that carbohydrate-carbohydrate interaction is strong enough for target cell recognition followed by phospholipid bilayer melding induced by fusion glycoprotein of Sendai virus.
Reactive oxygen radicals have been implicated as mediators of anoxic injury in brain, but the cellular source of these radicals is unknown. In the periphery, there is evidence that endothelial cells play a fundamental role in anoxic tissue injury. The objective of the present study was to examine the response of rat brain endothelial cells to anoxia/reoxygenation injury in vitro. The results demonstrate that brain endothelial cells produce hydroxyl radicals and have increased nitric oxide synthase activity after anoxic injury. The increased production of nitric oxide in the cerebral endothelial cells does not appear to be mediated by an increase in either inducible or constitutive nitric oxide synthase. The radical trap alpha-phenyl-tert-butyl nitrone blocked hydroxyl free radical production, but not nitric oxide. These data suggest that the cerebral microcirculation may be an important site of oxygen free radical production in the brain in ischemic stroke.
Fibroblast growth factors (FGFs) affect a broad spectrum of developmentally regulated cellular responses involved in the control of growth and differentiation. To identify specific FGF receptor forms involved in these responses, we have characterized FGF receptor transcript expression, and its modulation by FGF-2, as enriched populations of oligodendrocyte progenitors differentiate into mature oligodendrocytes. The data demonstrate that the levels of mRNA expression for FGF high-affinity receptors-1, -2, and -3 are differentially regulated during lineage progression: FGF receptor-1 expression increases with lineage progression, FGF receptor-2 is predominantly expressed by terminally differentiated oligodendrocytes, and FGF receptor-3 reaches a peak level of expression in late progenitors and then declines upon further differentiation; FGF receptor-4 expression was not detected in oligodendrocytes. Distinct patterns of alternatively spliced variants of FGF receptor-1 and -2 transcripts are expressed: the predominant FGF receptor-1 transcripts contain three Ig-like domains (FGF receptor-1 alpha), whereas the FGF receptor-2 transcripts contain two Ig-like domains (FGF receptor-2 beta 2) and this form is up-regulated as oligodendrocytes differentiate. In addition, the expression of these receptors is differentially regulated by the ligand, FGF-2: FGF receptor-1 mRNA expression is up-regulated in early progenitors, and FGF receptor-2 mRNA expression is down-regulated in mature oligodendrocytes. Finally, astrocytes express FGF receptor-1, -2, and -3 transcripts, but at different levels and with different exon utilization (FGF receptor-1 beta, FGF receptor-2 beta 1/beta 2) compared to oligodendrocytes. To our knowledge this is the first report that demonstrates that the mRNA expression of these three FGF receptor types is differentially regulated in primary cells as they differentiate along a lineage from progenitors to terminally differentiated cells. We propose that this pattern of expression provides a molecular basis for the developmentally varying response of cells to a common ligand. For example, according to this hypothesis, in response to FGF-2, FGF receptor-1 transduces signals that stimulate the prolonged proliferation and migration of early progenitors, FGF receptor-3 promotes the proliferation and arrest of differentiation of late progenitors, and FGF receptor-2 transduces signals for terminal differentiation, but not proliferation, in mature oligodendrocytes.
Differentiating cells undergo developmentally regulated changes in cell-cell and cell-matrix adhesion that control migration through microenvironments, proliferation, and differentiation. The diversity of the patterns of expression of heparan sulfate proteoglycans (HSPGs), coupled with their interactions with extracellular matrix, cell adhesion molecules, and growth factors, has emphasized their critical importance in the regulation of these events. Syndecans (1-4), glypican, and cerebroglycan are membrane-associated HSPGs that have been implicated in these events in various tissues and several tumor cell lines. We have examined the developmental expression and FGF-2-mediated regulation of these HSPGs during differentiation within a specific lineage of primary cells, oligodendrocytes (OL). Northern analyses of highly purified, developmentally synchronized populations of OL-lineage cells at three stages of differentiation (early and late progenitors and mature OLs) showed that the expression of individual forms of these syndecans and glypican are developmentally regulated. Specifically, the level of expression of syndecan-2 and -4 and glypican mRNAs increased as the cells differentiated from proliferative late progenitors to postmitotic mature cells. The expression of syndecan-1 and -3 had the inverse developmental pattern. Therefore, these two sets of molecules may have different roles in regulating the onset of terminal differentiation in OLs. The levels of mRNA expression were regulated by FGF-2: in late progenitors, FGF-2 induced a doubling of the mRNA levels of syndecan-2, -3, and -4, while those for syndecan-1 and glypican remained unaffected; in mature OLs, the levels of syndecan-1 mRNA were up-regulated, the levels of syndecan-2 and -4 and glypican were down-regulated. These results suggest that the individual syndecan molecules have distinct functions during the differentiation process and that multiple levels of regulation must exist, leading to a changing repertoire of these molecules during OL lineage progression and myelinogenesis.
The sympathetic responses in left heart valvular disease may depend on the ventricular load conditions. We proposed to evaluate this possibility by comparing the effects of left ventricular pressure (LVP) and volume (LVV) overload on beta-adrenoceptor density and ligand binding affinity in lymphocytes and in the four myocardial chambers in rheumatic heart valvular patients. Receptor activity was determined by radioligand binding using [125I]iodocyanopindolol. In the lymphocytes (n = 45), the beta-adrenoceptor density was reduced by 88% (P < 0.001) in LVP patients (n = 15) and 79% (P < 0.001) in LVV patients (n = 30) compared with 23 controls. In the myocardium, the receptor density of the LVP (n = 12) was attenuated by 55% (P < 0.05) in the left ventricle, 42% in the right ventricle, 13% in the left atrium, and 37% in the right atrium, while in LVV patients (n = 22) it decreased by 73% (P < 0.01) in the left ventricle, 62% (P < 0.05) in the right ventricle, 30% in the left atrium, and 34% in the right atrium compared with 15 controls. Thus, the reduction in density was greatest in lymphocytes and least in the atria in both groups. The decrease in ventricular density of the LVV group was similar to the reduction in the lymphocytes and two-fold higher than in the atrial density. These alterations were significantly greater for the LVV than for the LVP group. The Kd for the myocardial receptor binding to [125I]iodocyanopindolol was not significantly influenced in either group, but was lower in the lymphocytes. These findings suggest that in patients with left heart valvular disease, there is a significant attenuation in both peripheral and myocardial beta-adrenoceptor density. The decrease in receptor density is significantly greater in the left ventricular volume overload than in the left ventricular pressure overload patients.
We have investigated the possibility that the various left ventricular load conditions may exert different effects on the sympathetic function by comparing the influence of volume (VOL) and pressure (POL) overload on platelet alpha-adrenoceptor activity, plasma catecholamines and cAMP in 44 patients with rheumatic heart valvular disease. Receptor activity was determined by radioligand binding methods, catecholamines by HPLC using an electrochemical detector, and cAMP by radioimmunoassay. The mean alpha-adrenoceptor density (Bmax) of the control group (n = 29) was 4.71 +/- 0.41 fmol per 10(7) platelets and the corresponding dissociation constant (Kd) was 2.47 +/- 0.15 nM. In VOL patients, the density was elevated by 70% (P < 0.0001), but it remained unchanged in the POL patients. In contrast to the Bmax, the Kd of the VOL group was not changed, and it increased by 34% (P < 0.01) in the POL group. Norepinephrine was elevated by 91% (P < 0.05) in POL, and epinephrine increased by 65% (P < 0.05) in POL and 71% (P < 0.05) in VOL. These results suggest that the sympathetic nervous system responds to left ventricular volume overload by increasing alpha-adrenoceptor density with no apparent change in receptor affinity toward [3H]-yohimbine binding, and to left ventricular pressure overload by decreasing their binding affinity without a parallel decrease in receptor density. The increase in receptor density in VOL is accompanied by an increase in plasma epinephrine, and the decrease in binding affinity in POL is associated with increased plasma norepinephrine and epinephrine levels.
OBJECTIVES: Cardiopulmonary bypass has been shown to cause hypoperfusion of certain vascular beds leading to multiple system organ failure. It has been reported that the gut may be an important trigger. The underlying mechanism is not fully known, but vascular changes, particularly those due to cooling, could play a role. METHODS: We examined the effect of cooling (28 degrees C) and subsequent rewarming (37 degrees C) on the vascular reactivity of the rabbit mesenteric artery and abdominal aorta to a range of vasoactive substances using an in vitro organ bath apparatus. Cumulative concentration-responses of the agonists (noradrenaline, histamine, dopamine and potassium chloride) were examined at 37 degrees C, then repeated at 28 degrees C and then subsequently repeated after rewarming to 37 degrees C. RESULTS: All agonists were capable of inducing a constrictor response on the mesenteric artery and abdominal aorta. The results represent means +/- SEM. There was an increase in potency of noradrenaline at the lower temperature [from 5.6 +/- 0.1 (37 degrees C) to 6.0 +/- 0.1 (28 degrees C); Bonferroni-corrected P < 0.05; n = 10], which returned to normal [5.6 +/- 0.1 (37 degrees C)] following rewarming in the mesenteric artery. In contrast, there was a decrease in potency of noradrenaline in the aorta on cooling [6.5 +/- 0.1 (37 degrees C) to 6.2 +/- 0.1 (28 degrees C); Bonferroni-corrected P < 0.05; n = 8]. Neither histamine or dopamine showed any difference in potency at 28 degrees C or at 37 degrees C following rewarming in the mesenteric artery or aorta. There was no difference in the efficacy of the response of the mesenteric artery to noradrenaline as indicated by the maximum responses. However, the response to the highest dose of dopamine was increased on rewarming to 37 degrees C compared to control responses at 37 degrees C before cooling in the aorta [7.23 +/- 1.48 g vs 3.6 +/- 0.6 g; Bonferroni-corrected P < 0.05; n = 14]. Histamine contractions were attenuated at 28 degrees C and following rewarming to 37 degrees C in the mesenteric artery [5.5 +/- 0.5 g (37 degrees C) vs 2.2 +/- 0.2 g (28 degrees C); Bonferroni-corrected P < 0.05; n = 18], [5.5 +/- 0.5 g (37 degrees C) vs 2.32 +/- 0.5 g (37 degrees C rewarming); Bonferroni-corrected P < 0.05; n = 18]. CONCLUSIONS: We conclude that cooling elicits a heterogeneous responsiveness of the rabbit mesenteric artery and abdominal aorta to noradrenaline and dopamine which could have important implications for blood flow to mesenteric vascular beds during hypothermic cardiopulmonary bypass.
Explore the source record for details and available documents.
BACKGROUND: Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. METHODS: Infants < or = 1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m2/dose given either twice daily or three times per day) was administered for 6 months. RESULTS: Twelve (46%) of the 26 infants developed neutropenia (< 1000 cells/mm3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. CONCLUSIONS: Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.
Explore the source record for details and available documents.
Portal hypertensive gastropathy and duodenopathy are distinct clinical and endoscopic entities. Data on factors influencing the development of these lesions are still emerging. Data on portal hypertensive duodenopathy are scarce. We prospectively studied 230 patients with liver cirrhosis and oesophageal varices attending the liver clinic of the Sanjay Gandhi Post Graduate Institute of Medical Sciences. One hundred and forty-two patients had no history of upper gastrointestinal bleeding, while the remainder had bled in the past. Endoscopic appearances were recorded before starting patients on a sclerotherapy programme. Forty-four patients were re-evaluated after variceal eradication. The frequency of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) was 61 and 14%, respectively. Mild PHG was present in 85% and was severe in the rest. Portal hypertensive duodenopathy was mild in 50%, while in the other half it was severe. There was no relationship of PHG and PHD to: (i) a history of upper gastrointestinal bleed; (ii) size of oesophageal varices; (iii) aetiology of liver cirrhosis; or (iv) liver function status as assessed by Child Pugh's scores (P = NS for all). The prevalence of PHG was higher in those patients with oesophagogastric varices (74 of 107; 69%) compared with patients with oesophageal varices alone (68 of 123; 55%; P < 0.05). However, no such increase in frequency of PHD was noted in patients with oesophagogastric varices. Sclerotherapy increased the frequency of PHG. Twenty-four patients had PHG before starting sclerotherapy, while it was noted in 33 patients 1-3 months after variceal eradication (P < 0.05). In contrast, there was no increase in the prevalence of portal hypertensive duodenopathy after sclerotherapy (P = NS). There was no correlation between endoscopic and histological changes of PHG and PHD. In conclusion, PHG is quite frequent in patients with cirrhosis and its frequency increases with the presence of oesophagogastric varices and after sclerotherapy. However, the frequency of PHD is low and is not affected by the factors studied.
Seventy-nine human immunodeficiency virus type 1 (HIV-1)-seropositive homosexual men participating in a longitudinal study of HIV-1 infection were assessed twice, 6 months apart, to investigate associations between bereavement and cellular immune function. Subjects were assessed by using a theory-driven model comprising life stressors, social support and coping style, and control variables. Natural killer cell cytotoxicity was decreased among the bereaved at both times. Lymphocyte proliferative response to phytohemagglutinin was decreased among the bereaved at the second time point but not at the first. These functional immune decrements are associated with increased neuroendocrine responses of the sympathetic adrenomeduallary system as well as the limbic-hypothalamic-pituitary-adrenal axis. Implications for differential neuroendocrine responses over time are discussed. Active coping style was independently and positively related to both immune measures. The results imply that a bereavement support group intervention merits investigation for an effect on immunological measures and clinical progression of HIV-1 infection as well as grief resolution.
We have isolated a homolog of the cell division gene ftsZ from the extremely halophilic archaebacterium Halobacterium salinarium. The predicted protein of 39 kDa is divergent relative to eubacterial homologs, with 32% identity to Escherichia coli FtsZ. No other eubacterial cell division gene homologs were found adjacent to H. salinarium ftsZ. Expression of the ftsZ gene region in H. salinarium induced significant morphological changes leading to the loss of rod shape. Phylogenetic analysis demonstrated that the H. salinarium FtsZ protein is more related to tubulins than are the FtsZ proteins of eubacteria, supporting the hypothesis that FtsZ may have evolved into eukaryotic tubulin.
Explore the source record for details and available documents.