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R K Kumar

Publications and source records attributed to R K Kumar.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dimeric S100A8 in human neutrophils is diminished after phagocytosis.

S100A8 is a major cytoplasmic protein of neutrophils and monocytes/macrophages and has been associated with myeloid cell differentiation and activation. Little is known about its functions or mechanisms of release from neutrophils. We have developed a monoclonal antibody to murine S100A8, which cross-reacts with human S100A8. This antibody, which recognizes the homodimeric form of the protein, detects its expression specifically in human neutrophils and is reactive in formalin-fixed, paraffin-embedded tissues. Using this antibody as well as a commercially available antibody to human S100A8, we show that phagocytic activation of neutrophils, in vivo in acute appendicitis and in vitro following phagocytosis of opsonized zymosan, is characterized by loss of cytoplasmic immunoreactivity for S100A8. In vitro, phagocytosis is associated with rapid diminution of immunostaining without loss of viability. Loss of immunoreactivity for S100A8 may serve as a marker of localized neutrophil activation in tissues.

Acute Disease↗
PubMed2001

Urinary tract infections in children. Tips for a family physician.

BACKGROUND: Urinary tract infections in children are the second most common bacterial infection requiring medical attention. Despite this, precise definition and management of urinary tract infection in children can be quite evasive for the unwary family physician. OBJECTIVE: This article provides a few tips for the busy family practitioner to help manage this problem. DISCUSSION: Much debate still abounds in relation to this issue. However, untreated urinary tract infections in childhood can result in unacceptable morbidity in adulthood. Hence aggressive management of urinary tract infections in children and identifying children 'at risk' remains our top priority.

Child↗
PubMed2000

Expression patterns of E-cadherin, involucrin, and connexin gap junction proteins in the lining epithelia of inflamed gingiva.

The structural integrity and functional differentiation of the lining epithelium were studied in relation to inflammatory changes associated with destructive periodontitis. In the different regions of lining epithelia from clinically healthy gingiva and periodontitis, comparisons were made of the expression patterns of E-cadherin, which is critical in intercellular adhesion; of proteins associated with gap junction communication channels; and of involucrin, which is a key marker of differentiation in stratified epithelia. Filamentous actin (F-actin), which is important in cell structural integrity, attachment, and migration, was also examined. Semiquantitative immunohistochemical analysis revealed that in both clinically healthy gingiva and lesions of advanced periodontitis, expression patterns of E-cadherin, involucrin, and connexins 26 and 43 were similar, with a statistically significant reduction in staining intensity from the external oral epithelium, through the gingival sulcus, to the junctional epithelium or pocket epithelium, respectively. Furthermore, there was a striking reduction in staining for E-cadherin, involucrin, and both connexins in the pathological lining epithelium of the periodontal pocket. These changes were associated with marked alterations of filamentous actin expression, collectively indicating profound perturbation of the epithelial structure. The data reported support the concept that the ability of the pathological lining epithelium to function as an effective barrier against the ingress of microbial products into the tissues is severely compromised.

Actins↗
PubMed2000

Bronchial asthma: recent advances.

Asthma is one of the oldest diseases about which there are lots of myths in most parts of the world. The exact cause of this global disease still eludes scientists. The recent knowledge about the pathogenesis of the disease, led to rationalise the medications into different groups. Parallel to the increasing incidence of this disease, is the knowledge about the trigger factors and steps to reduce their exposure. Childhood asthma is a lot different from asthma in adults, as many children won't be able to use the inhalers like adults and most children will not be able to do lung function tests until they are about 6 years of age. Unlike for any other diseases, research has helped year after year in developing new strategies for management of asthma. Starting from definition of the disease to inventing newer medications, management of asthma has revolutionised in the last few years and has also accounted for the decreasing mortality in many countries. This article tries to give an overview of bronchial asthma in children including recent advances and possible future developments.

Asthma↗
PubMed2000

Vascular remodelling in chronic inflammatory periodontal disease.

Periodontitis is a chronic inflammatory disease of the highly vascularised supporting tissues of the teeth. Little is known about the vascular changes in untreated advanced periodontitis. Using confocal immunofluorescence microscopy and morphometry, we defined and quantified vascular remodelling in this lesion. In the connective tissue subjacent to the altered epithelium lining of the periodontal pocket, there was a significant increase in the numerical density of vascular profiles, primarily accounted for by vessels > or = 25 microm in diameter. In addition, vascular basement membranes were thickened and there was accumulation of non-vascular basement membrane remnants. We investigated the distribution of major angiogenic growth factors in periodontitis using immunohistochemistry. Basic fibroblast growth factor, although consistently associated with blood vessels, showed no regional variation in its distribution. In contrast, there was a marked regional variation in the intensity of immunostaining for vascular endothelial growth factor, with significantly reduced staining of the pocket epithelium. The changes in the vascularity of the periodontal connective tissues in untreated advanced periodontitis may be, in part, a consequence of altered expression of angiogenic activity by the epithelium. In turn, this may reflect the epithelial response to microbial flora in the microenvironment of the periodontal pocket.

Adult↗
PubMed2000

Dissociation of inflammatory and epithelial responses in a murine model of chronic asthma.

To study pathogenetic mechanisms in chronic asthma, we employed a novel experimental model that replicates characteristic features of the human disease. Chronic inflammation and epithelial changes, specifically localized to the airways, were induced by repeated exposure of systemically sensitized BALB/c mice to low mass concentrations of aerosolized ovalbumin for 6 weeks. The contribution of Th2 cytokine-driven inflammation to the development of airway lesions and hyperreactivity was assessed in cytokine-deficient mice. In interleukin-5-deficient animals, intraepithelial eosinophils and chronic inflammatory cells in the lamina propria of the airways were markedly decreased; however, these animals developed epithelial hypertrophy and subepithelial fibrosis comparable with that observed in sensitized wild type mice. Airway hyperreactivity to inhaled methacholine did not develop in interleukin-5-deficient mice. In contrast, interleukin-4-deficient mice exhibited no decrease in airway inflammation, but had significantly greater epithelial hypertrophy and subepithelial fibrosis, as well as exaggerated hyperreactivity to methacholine. We conclude that interleukin-5, but not interleukin-4, plays a central role in the development of chronic inflammation of the airways and the induction of airway hyperreactivity. Furthermore, chronic epithelial and fibrotic changes occur independently of interleukin-5 and are not required for the development of airway hyperreactivity. The dissociation between airway wall remodeling and airway hyperreactivity has important implications for therapeutic approaches to chronic asthma.

Animals↗
PubMed2000

Substrate preference profiles of proteases released by allergenic pollens.

BACKGROUND: Pollens are important triggers for allergic asthma and seasonal rhinitis. We have recently reported that proteases released by major allergenic pollens can injure airway epithelial cells in vitro. Disruption of epithelial integrity by proteases released following deposition of pollens on mucosal surfaces could promote sensitization and induce inflammation. OBJECTIVE: To compare protease activities released by allergenic pollens of various genera. METHODS: We used a rapid microassay which quantifies cleavage of dipeptide ester substrates to characterize the substrate preference profiles of serine proteases in diffusates of the pollens of perennial ryegrass (Lolium perenne), Kentucky blue grass (Poa pratensis), Bermuda grass (Cynodon dactylon), Western ragweed (Ambrosia spp.), white birch (Betula spp.) and Sydney golden wattle (Acacia longifolia). RESULTS: Comparison of the profiles revealed notable differences as well as similarities between serine protease activities released by these pollens. Diffusates of Kentucky blue grass pollen exhibited very high substrate preference for arginine and lysine. For other pollens, cleavage of the cysteine substrate was usually the most rapid and was associated with marked preference for leucine and methionine. There was considerable variation between these pollens in the rates of cleavage of the histidine substrate. In addition, we observed high rates of cleavage of arginine and lysine substrates by Acacia pollen diffusate. CONCLUSION: At least two dominant patterns of substrate preference are identifiable in the mixtures of proteases released by hydrated pollens. Purification of the proteases responsible for these patterns of activity will facilitate investigation of their role in airway epithelial injury and allergic disease.

Allergens↗
PubMed2000

Airway inflammation in a murine model of chronic asthma: evidence for a local humoral immune response.

BACKGROUND: Asthma is an acute-on-chronic inflammatory disease of the airways characterized by recruitment of eosinophils into the epithelial layer, chronic inflammation in the lamina propria, as well as variable accumulation of mast cells in the airway wall. The role of local production of allergen-specific immunoglobulins in triggering mast cell-mediated asthmatic inflammation is unknown. METHODS: We used a chronic inhalational exposure model of asthma in ovalbumin-sensitized BALB/c mice to examine the phenotype of immunoglobulin-secreting cells and mast cells in the airway wall. In parallel, we assayed ovalbumin-specific IgG and total IgE in the plasma of these animals. RESULTS: In sensitized mice exposed to aerosolized ovalbumin for 6 weeks, aggregates of chronic inflammatory cells consisted of a majority of plasmacytoid cells, including numerous IgG-synthesizing cells, which were significantly increased in sensitized animals compared to controls. IgA-synthesizing cells were also present, but were not increased in the sensitized exposed mice. Immunoglobulins in the cytoplasm of the plasma cells were demonstrated to be antigen-specific. No IgM-or IgE-synthesizing cells were observed, although levels of total IgE in the plasma were significantly increased. There was no recruitment of mast cells of either the mucosal or the connective tissue phenotype into the lamina propria or the epithelium. CONCLUSION: In this experimental model of chronic asthma, the pattern of inflammation in the airway wall is consistent with development of a local IgG-mediated humoral immune response. However, there is no evidence of local production of IgE or recruitment of mast cells.

Animals↗
PubMed2000

Meningococcal infections and meningitis: what is new?

Meningococcal infection is one of the very few severe bacterial infections, in this era, that still can kill a relatively healthy child within minutes. Fortunately, it is a relatively rare disease. Rural practitioners may see one affected child once every 2-3 years, but once seen they will never forget it. The present article gives some examples of case scenarios along with a brief overview of the problem, with emphasis on early diagnosis, prevention and possible future developments.

Child, Preschool↗
PubMed2000

Triploidy syndrome.

Explore the source record for details and available documents.

Abnormalities, Multiple↗
PubMed2000

Expression of the alphaEbeta7 integrin by mast cells in rheumatoid synovium.

OBJECTIVE: Rheumatoid synovitis is characterized by a mast cell response in which tryptase containing mast cells (MCT) associate with T lymphocyte infiltration, and tryptase and chymase containing mast cells (MCTC) correlate more closely with tissue damage or repair events. We investigated expression of the alphaEbeta7 integrin and its ligand E-cadherin in rheumatoid and normal synovium and compared this expression to synovial mast cell responses. METHODS: Immunohistochemical analysis was used to determine the expression of alphaEbeta7 and E-cadherin in rheumatoid (n = 17) and normal (n = 6) synovium. The density of MCT and MCTC mast cell subsets was compared to the density of alphaEbeta7 positive mast cells. RESULTS: The mean density of alphaEbeta7 positive cells in rheumatoid synovia was 25.2 cells/mm2 (range 0.3-102.9), of which 26.7% (range 0-68.6%) were mast cells. A mean of 11.9% (range 0-30.4%) of rheumatoid synovial mast cells expressed alphaEbeta7 compared to 0% in normal synovium (p < 0.0001). There was a strong correlation between the density of alphaEbeta7 positive cells and the total mast cell density in rheumatoid synovium (r2= 0.74). alphaEbeta7 positive mast cell density correlated significantly with the MCT subset density (r2 = 0.5, p = 0.014), but not with the MCTC subset density. E-cadherin expression was increased in rheumatoid compared with normal synovium, but did not colocalize or correlate with alphaEbeta7 expression. CONCLUSION: These results indicate a role for alphaEbeta7 in the mast cell response that occurs in rheumatoid synovitis, in particular the MCT mast cell subset expansion associated with inflammatory events and interactions with infiltrating lymphocytes.

Arthritis, Rheumatoid↗
PubMed1999

Comparison of outcome when hypoplastic left heart syndrome and transposition of the great arteries are diagnosed prenatally versus when diagnosis of these two conditions is made only postnatally.

We sought to determine the impact of prenatal diagnosis on the perioperative outcome of newborns with hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). All neonates with HLHS or TGA encountered at Children's Hospital, Boston, Massachusetts, from January 1988 to May 1996 were identified and outcomes documented. Birth characteristics, preoperative, operative, and postoperative variables of term newborns with a prenatal diagnosis of HLHS or TGA who underwent a Norwood operation (n = 27) or arterial switch operation (n = 14), respectively, were compared with newborns with a postnatal diagnosis of HLHS (n = 47) or TGA (n = 28) who had undergone surgery. Of 217 neonates with HLHS and 422 with TGA, 39 and 16, respectively, had a prenatal diagnosis. The preoperative mortality among neonates aggressively managed did not differ between the prenatal and postnatal diagnosis groups for either HLHS or TGA (p >0.05). Neonates with a prenatal diagnosis who underwent surgery had objective indicators of lower severity of illness preoperatively, including a higher lowest recorded pH (p = 0.03), lower maximum blood urea nitrogen (p = 0.002), and creatinine (p = 0.03) among newborns with HLHS, and a tendency toward higher minimum of partial pressure of arterial oxygen in the TGA group (p = 0.06). Prenatal diagnosis was not associated with an improved postoperative course or operative mortality (p <0.05) within a diagnostic group. Thus, a prenatal diagnosis improves the preoperative condition of neonates with HLHS and TGA, but may not significantly improve preoperative mortality or early postoperative outcome among neonates managed at a tertiary care center.

Humans↗
PubMed1999

Neonatal cerebral infarction: an under recognised/unreconised cause of neonatal seizures?

Neonatal cerebral infarction or neonatal stroke is a well recognised cause of neonatal seizures. The awareness of its existence among healthcare workers is low and it is not even mentioned as a cause of neonatal seizures in most books. Many of the affected neonates are well, without any evidence of neurological disturbances between seizures. Awareness of its existence among healthcare workers is critical for the diagnosis of this problem. Early diagnosis can lead to early intervention, which may mean a better prognosis for these children.

Cerebral Infarction↗
PubMed1999

Cisapride and caesarean section: their role in babies with gastroschisis.

OBJECTIVE: The objective of this study was to compare the neonatal postoperative course and morbidity for patients with gastroschisis who received cisapride with those who did not receive cisapride. STUDY DESIGN: Data were obtained by review of the medical records of all the patients with gastroschisis who were admitted to Sydney Children's Hospital between January 1984 and December 1995. Data were compared between 15 babies who received cisapride with 27 who did not. The mode of delivery and outcome of babies in whom gastroschisis was diagnosed antenatally was compared with those who were diagnosed at birth. RESULTS: Duration to the commencement of feeds, attainment of full feeds and the length of hospital stay were not statistically different between these two groups, with or without cisapride (p = > or = 0.1). There were more elective Caesarean sections in the antenatally diagnosed group compared to those detected at birth and the outcome of these two groups showed no statistically significant difference. CONCLUSIONS: Our study identified no benefit from cisapride therapy in babies with gastroschisis and also there was no benefit from elective Caesarean section for babies with antenatal diagnosis of gastroschisis.

Australia↗