PubMed Health⌕ Search

Biomedical subjects

M Ahluwalia

Publications and source records attributed to M Ahluwalia.

15 recordsLinked to original sources
PubMed2004

Dental caries, oral hygiene, and oral clearance in children with craniofacial disorders.

The reason that children with cleft palates tend to have a greater prevalence of tooth decay than normal children is unclear. We hypothesized that children with cleft palates would have increased oral clearance times for foods and, consequently, higher levels of caries and caries-associated micro-organisms than control children. Children aged 6-16 yrs, with (n = 81) or without (n = 61) cleft palates, were studied. Children with cleft palates had DMFT and dmft scores greater (p < 0.01) than those of the control group. The number of caries-associated organisms was greater in the saliva of the cleft palate children (all p < 0.001). The oral hygiene, plaque and gingival index scores were greater (p < 0.0001), oral clearance was longer (p < 0.01), and levels of sucrose and starch-derived saccharides higher (p < 0.01) in the cleft palate group. However, salivary concentrations of organic acids were lower in the children with craniofacial disorders, probably reflecting the altered physiology of the more mature dental biofilm. The longer oral clearance times of foods and the consequent generation of fermentable sugars from starches may contribute to the higher caries prevalence observed in children with cleft palates.

Adolescent↗
PubMed2002

The influence of the Pro12Ala mutation of the PPAR-gamma receptor gene on metabolic and clinical characteristics in treatment-naïve patients with type 2 diabetes.

Peroxisome proliferator activated receptor-gamma is an important factor in adipocyte differentiation and energy metabolism and is thus a candidate gene for obesity, insulin resistance and dyslipidaemia. We therefore assessed the associations between the most common variant of the PPAR-gamma, the Pro12Ala (P12A) substitution in the PPAR-gamma 2 gene, with BMI, blood pressure, fasting plasma glucose, HbA1c, total cholesterol, LDL and HDL cholesterol and plasma triglyceride in 183 treatment-naïve patients with type 2 diabetes (T2D). The P12A allele associated with lower fasting plasma glucose but had no influence on HbA1c or BMI. In obese patients (BMI > 29 kg/m2), the P12A substitution associated with elevated total and non-HDL cholesterol levels.

Adult↗
PubMed2001

Isolation and characterisation of an anticryptococcal protein in human cerebrospinal fluid.

An earlier study reported that human cerebrospinal fluid (CSF) has fungistatic activity for Cryptococcus neoformans. The present study reports that molecular sieve fractionation of concentrated CSF yielded three protein peaks, one of which (p2) had anticryptococcal activity. On a DEAE-Sephacel anion-exchange column the active molecular sieve peak (p2) gave two peaks that contained anticryptococcal activity. The first (DEAE-1) eluted with 0.1 M NaCl and the second (DEAE-2) eluted with 0.2 M NaCl in buffer. Fungistatic activity of DEAE-1 was reversed by FeCl3. Moreover, FeCl3 reversed inhibition of C. neoformans growth by CSF. In contrast, activity of DEAE-2 was not reversed by FeCl3, indicating that inhibition was produced by an iron-independent mechanism. Immunoblot assays showed that transferrin was present in DEAE-1 but not in DEAE-2, whereas albumin was present in DEAE-2 but not in DEAE-1. On NuPAGE, DEAE-1 protein migrated as a single band corresponding to transferrin and DEAE-2 protein gave a single band corresponding to albumin. In control experiments, human serum albumin subjected to the same isolation protocol acquired anticryptococcal activity similar to that of DEAE-2. Therefore, CSF albumin (DEAE-2) activity was associated with the isolation protocol. These data indicate that transferrin, present in or isolated from CSF, sequesters trace amounts of ferric iron, inhibits growth of C. neoformans and acts as an innate defence mechanism.

Cerebrospinal Fluid↗
PubMed2000

Characterization of an anticryptococcal protein isolated from human serum.

Human serum at low concentrations inhibits the growth of Cryptococcus neoformans in vitro. Fractionation of serum yielded a purified inhibitory protein with a molecular mass of approximately 81.8 kDa, a pI of approximately 6.2, and an amino acid sequence that matched that of human transferrin. The inhibitory activity and that of apotransferrin and 5% human serum were reversed by 10 microM freshly prepared FeCl(3).

Antifungal Agents↗
PubMed1990

An alkaline pH-activated Cl(-)-anion exchanger regulates pH homeostasis in fibroblasts.

Alkalinization of the cytoplasm in human fibroblasts activates Cl- efflux. The pathway of Cl- efflux is inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or by removal of Cl- from the extracellular medium, but it is insensitive to the Cl(-)-cation cotransport inhibitor bumetanide. These data indicate that the alkali-stimulated Cl- pathway is a Cl(-)-anion exchanger. One function of this pathway appears to involve intracellular pH homeostasis. Thus, after alkalinization of the cytoplasm, recovery of the pH to basal levels is impaired by DIDS or by removal of HCO3- from the extracellular medium, but it is unaffected by the Na(+)-H+ exchange inhibitor amiloride. Reports from a number of laboratories, including our own, have described a biphasic efflux of Cl- in which kinetics suggested the presence of two subcellular Cl- compartments. The data presented in this study provide a mechanism to explain this kinetic behavior. The biphasic Cl- efflux kinetics are the result of a transient alkalinization of the cytoplasm associated with a change in PCO2 as cells are transferred from the incubator to the bench top for the efflux assay.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1990

Histamine receptors in human fibroblasts: inositol phosphates, Ca2+, and cell growth.

Histamine stimulated inositol phosphate formation by human skin fibroblasts. The effect of histamine was reduced but still readily apparent in the absence of extracellular Ca2+. Histamine caused a transient increase in intracellular free Ca2+ as detected by indo-1 and fura-2 fluorescence studies on cell populations and on individual cells. Similar increases were observed in the absence of extracellular Ca2+, indicating that the effect was primarily due to mobilization of Ca2+ from intracellular stores, presumably by inositol trisphosphate (IP3). The effects of histamine on phosphoinositide metabolism and intracellular Ca2+ were inhibited by pretreatment of the cells with phorbol esters, suggesting that the histamine receptor in fibroblasts is subject to feedback regulation by protein kinase C. Histamine inhibited the incorporation of [3H]-thymidine into DNA. The effects of histamine on inositol phosphate formation, intracellular Ca2+, and thymidine incorporation were blocked by the H1 receptor antagonist mepyramine. Our results indicate that human skin fibroblasts have H1 receptors coupled to the formation of inositol phosphates and mobilization of intracellular Ca2+. We suggest that this H1 receptor also mediates a block of the cell cycle and that histamine may play a physiological role in the regulation of fibroblast proliferation.

Aminopyridines↗
PubMed1988

Glutathione and enzymes related to free radical metabolism in liver of rats fed a choline-devoid low-methionine diet.

Fischer F-344 male rats, fed a choline-devoid diet that leads to a highly reproducible sequence of biochemical and biological changes with an ultimate development of hepatocellular carcinoma, show elevated levels of glutathione in the liver at 3, 6 and 8 days. Several enzymes related to the metabolism of free radicals, including superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and DT-diaphorase show neither increased nor decreased activity as measured between 12 h and 8 days on the diet. Thus, of several known cellular components related to the possible scavenger of free radicals in the liver, only glutathione responded to the feeding of the CD diet. It is tentatively concluded that a decrease in the levels of possible scavengers for free radicals is not a major basis for the nuclear and mitochondrial lipid peroxidation seen early in rats fed a choline-devoid diet.

Animals↗
PubMed1988

Regulation of conductive Cl- transport in human fibroblasts.

Under normal growth conditions, approximately 20% of the efflux of Cl- from human fibroblasts occurs via an electrically conductive pathway or Cl- channel. This basal Cl- conductance is insensitive to the Cl- -anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and to the Cl- -cation cotransport inhibitor bumetanide. Exposure of the cells to dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) for 15 min increases the electrically conductive component of Cl- efflux by approximately 20%. Unlike the basal Cl- conductance, the cAMP-activated channel is DIDS sensitive, indicating that cAMP activates a different Cl- pathway from the one responsible for the basal Cl- conductance. Elevation of intracellular Ca2+ by addition of the ionophore A23187 also stimulates Cl- efflux via a DIDS inhibitable, electrically conductive Cl- pathway. That the cAMP- and Ca2+-stimulated pathways are different is suggested by the observation that simultaneous exposure of cells to optimal levels of dibutyryl cAMP and A23187 results in an increased Cl- efflux equal to the sum of the two factors acting independently. Prostaglandin E1, a known activator of adenylate cyclase, also elevates the levels of intracellular free Ca2+ in these cells and concomitantly activates both the cAMP- and the Ca2+-stimulated Cl- channels. Although regulated, Cl- channels are known to function in the modulation of nerve and muscle excitability, their role in fibroblast function is not clear.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1983

Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogenesis.

Hepatocyte ("hyperplastic") nodules induced in the liver by initiation with diethylnitrosamine and selected by dietary 2-acetylaminofluorene plus partial hepatectomy ("resistant hepatocyte model") have a special pattern of biochemical behavior and metabolic activity different than that seen acutely with many xenobiotics including many promoting agents and carcinogens. The nodule cells show a very low uptake of 2-acetylaminofluorene, relative to surrounding and normal liver, low levels of activity in the cytochromes P-450 and aryl hydrocarbon hydroxylase, high levels of activity in gamma-glutamyltransferase, microsomal epoxide hydrolase, soluble glutathione-S-transferase and soluble UDP-glucuronyltransferase (UDP-GT(1)) and elevated levels of glutathione. This metabolic pattern appears to maximize the resistance of the nodules to xenobiotics generally, such as 2-acetylaminofluorene, and thereby may account for the resistant behavior of nodule hepatocytes to the inhibition of cell proliferation and the cytotoxicity by 2-acetylaminofluorene and other carcinogens. The possible importance of this seemingly new metabolic program in carcinogenesis is discussed briefly.

2-Acetylaminofluorene↗
PubMed1983

The rapid induction of liver cell death in rats fed a choline-deficient methionine-low diet.

This study was undertaken to test the hypothesis that the basis for the cell proliferation seen in the livers of rats fed a choline-deficient methionine-low (CMD) diet is regeneration following hepatocyte cell death and necrosis. Exposure of rats to a CMD diet for 2 weeks was found to induce liver cell loss and necrosis as monitored by three different approaches: 1) histologic examination, 2) serum sorbitol dehydrogenase assay, and 3) measurement of the total radioactivity in liver DNA prelabeled during a prior period of regeneration. These observations suggest that the basis for liver cell proliferation in rats fed a CMD diet probably resides in the cell loss and necrosis induced in the liver by the deficient diet.

Animals↗
PubMed1982

Pulmonary functions during peritoneal dialysis.

Lung volumes, flows, flow volume loop, diffusing capacity and closing volume were studied in 7 patients (Group I) before, with 2 liter dialyzate in the peritoneal cavity and after 8 hours of peritoneal dialysis. The functional residual capacity, residual volume and the total lung capacity decreased (P less than 0.01, less than 0.05, and less than 0.05 respectively) with 2 liter dialyzate in the peritoneal cavity and returned to baseline after the dialyzate was removed. Arterial blood gas analysis was performed in another 8 patients (Group II) before, with 2 liter dialyzate in the peritoneal cavity, and after the dialyzate had been drained. No significant difference was observed in PaO2, PaCO2 or pHa during any phase of the study. It is concluded that except for a minor decrease in FRC, RV and TLC, there were no deleterious effects with the use of 2 liter dialyzate volume on gas exchange or pulmonary functions during peritoneal dialysis.

Adult↗
PubMedDate not supplied

Investigation of the Mek-MAP kinase-Rsk pathway in human breast cancer.

BACKGROUND: Mitogenic signaling through the principal growth factor receptor tyrosine kinase (RTK) pathway, i.e. RTK-->Ras-->Raf-->Mek-->MAPK has been implicated in the pathogenesis of human cancer. However, biochemical characterization of this has not been adequately assessed in human cancers. MATERIALS AND METHODS: Using extracts from 23 human breast cancers and control tissue from the same resected specimens, the protein levels, phosphotransferase activities and subcellular locations of the mitogen-activated protein (MAP) kinase isoforms p42 Erk2 and p44 Erk1 were examined, together with their phosphotransferase activities towards myelin basic protein (MBP) and a peptide substrate patterned after the Thr-669 site in the epidermal growth factor receptor (EGFR T669) that is phosphorylated by MAP kinase. RESULTS: Overexpression of both Erk2 and Erk1 isoforms was evident using specific antibodies. A universal activation of MBP and EGFR T669 peptide phosphotransferase activities was also found (up to 3-fold). MonoQ fractionation resolved the bulk of the EGFR T669 peptide phosphorylation from elution of the MAP kinase protein. Erk1 and Erk2 activities determined by specific immunoprecipitation were increased by up to only 2.5-fold in only 50% of tumors overall. Immunohistochemical studies, using a monoclonal antibody specific for Erk2 demonstrated that the cellular distribution of this MAP kinase was similar in both control and tumor tissues, and Erk2 was largely confined to normal and malignant acini, whilst the intensity of staining was actually reduced in the tumor tissue. Mek1 and especially Mek2 protein expression, as well as MAP kinase kinase activity as determined by phosphorylation of kinase-inactive Erk [GST-K71A] were increased in cancer samples. CONCLUSIONS: a) This confirms that MAP kinase activity is increased in human breast cancer. However, the frequency and magnitude of this change is dependent upon the chosen methodology (i.e. crude lysate assays versus specific immunoprecipitation). b) A MAP-kinase-independent source of increased EGFR T669 phosphotransferase activity in tumor extracts has been demonstrated for the first time in human breast cancer. c) By immunohistochemistry, Erk2 protein was actually found to exhibit lower intensity in tumor samples; the increased expression was most likely due to its increased distribution. d) Increased Mek protein expression and activation have been demonstrated for the first time in human breast tumors.

Anion Exchange Resins↗