Biomedical subjects

A Koul

Publications and source records attributed to A Koul.

At least 19 recordsLinked to original sources

PubMed2006

Inhibition of early and late phase allergic reactions by Euphorbia hirta L.

A 95% ethanol extract from whole aerial parts of Euphorbia hirta (EH A001) showed antihistaminic, antiinflammatory and immunosuppressive properties in various animal models. EH A001 inhibited rat peritoneal mast cell degranulation triggered by compound 48/80. It significantly inhibited dextran-induced rat paw edema. EH A001 prevented eosinophil accumulation and eosinophil peroxidase activity and reduced the protein content in bronchoalveolar lavage fluid (BALF) in a 'mild' model of asthma. Moreover, the CD4/CD8 ratio in peripheral blood was suppressed. EH A001 attenuated the release of interleukin-4 (IL-4) and augmented interferon-gamma (IFN-gamma) in ovalbumin-sensitized mouse splenocytes. The results were compared with the effects of known compounds, ketotifen, cetirizine and cyclophosphamide. These findings demonstrated that Euphorbia hirta possessed significant activity to prevent early and late phase allergic reactions.

Animals↗

PubMed2001

Effect of alpha-tocopherol on pulmonary antioxidant defence system and lipid peroxidation in cigarette smoke inhaling mice.

BACKGROUND: Free radicals generated in biological systems by cigarette smoke (CS) inhalation can cause oxidative stress in tissues, resulting in lipid peroxidation (LPO). In view of the antioxidant properties of alpha-tocopherol (AT), in the present study, effects of AT on antioxidant defence system and LPO were investigated in mice inhaling CS for different time intervals. RESULTS: Male Balb/c mice were fed orally with AT (5 I.U./Kg.b.wt.) and /or exposed to CS for 2, 4, 6 or 8 weeks. No effect was observed on body growth, diet consumption, water intake and lung weight due to AT and /or CS treatment in any of the groups as compared to their control counterparts. After two weeks of treatment, no change in LPO, reduced glutathione (GSH) levels and antioxidant enzymes were observed except for glutathione reductase (GR) which increased in all the treated groups. A significant increase in pulmonary LPO levels was observed in mice exposed to CS inhalation for 4, 6 or 8 weeks. There was a gradual increase in the LPO levels as the extent of CS inhalation increased from 4 to 8 weeks. However, the extent of increase in LPO levels due to CS exposure for 4, 6 or 8 weeks in the mice treated with AT was comparatively less. A significant decrease in the GSH levels was also observed in all the animals exposed to CS for 4, 6 or 8 weeks. There was a significant increase in the activities of catalase, glutathione peroxidase (GSH-Px) and GR observed in all the groups exposed to CS for 4,6 or 8 weeks. The increase in above antioxidant enzymes seems to be insufficient to combat the oxidative stress posed by CS inhalation. There was a marked decrease observed in the LPO levels in the animals treated with AT alone for 4, 6, or 8 weeks, when compared to their control counterparts. However, the supplementation of AT for 4, 6 or 8 weeks demonstrated a significant increase in GSH levels. CONCLUSION: It appears from our studies that AT exhibits its antioxidant role either directly by scavenging the oxidative species or indirectly by modulating the GSH levels.

Animals↗

PubMed2001

Two BRCA1-positive epithelial ovarian tumors with metastases to the central nervous system: a case report.

BACKGROUND: Cerebral metastasis secondary to ovarian cancer is a rare phenomenon. While no clear relationship to known prognostic factors is found, others suggest this as a biologically diverse behavior of ovarian cancer. CASES: In a pilot study, 37 invasive epithelial ovarian cancer samples were analyzed to detect the frequency of BRCA1/BRCA2 mutations in the south of Sweden (results published). A retrospective follow-up revealed that 2 of these (2/37; 5.4%) patients developed central nervous system metastases during the course of their disease. Both patients had advanced surgical stage disease at the time of diagnosis, with histopathological serous type tumors that were negative for estrogen and progesterone receptors. One of these patients carried a germline BRCA1 mutation, whereas a somatic BRCA1 mutation was identified in the other patient. CONCLUSIONS: To the best of our knowledge the molecular genetic profile of these tumors is not found in the literature and it is suggested that such analyses could provide some insight for a better understanding of this rare phenomenon.

Adult↗

PubMed2001

No BRCA1 germline mutation in a family with uterine papillary serous carcinoma: a case report.

The purpose of the study was to examine BRCA1 germline mutation and its relationship to BRCA1 expression in two patients, a mother and a daughter, both diagnosed with uterine papillary serous carcinoma (UPSC). DNA was screened for BRCA1 and BRCA2 germline mutations common in the Jewish population (185delAG, 5382insC, and 6174delT) by PCR-based assay and with a protein truncation test (PTT) to detect mutation in exon 11 of BRCA1 and exons 10 and 11 of BRCA2. BRCA1 expression in fixed tumor tissues was assessed by immunocytochemistry (IHC). No germline mutation in either BRCAI or BRCA2 gene was found in the two patients. Both samples showed reduced levels of BRCAI expression. Taken together, these results suggest that undetected or unscreened for germline mutation may be associated with occurrence of this rare tumor type in two members of the same family. Alternatively, an epigenetic mechanism such as BRCA1 promoter hypermethylation may be responsible for reduced expression of BRCA1 in the absence of DNA mutations.

Aged↗

PubMed2000

In vitro resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein is associated with alterations in cytoplasmic membrane fluidity.

Platelet microbicidal proteins (PMPs) are small, cationic peptides which possess potent microbicidal activities against common bloodstream pathogens, such as Staphylococcus aureus. We previously showed that S. aureus strains exhibiting resistance to thrombin-induced PMP (tPMP-1) in vitro have an enhanced capacity to cause human and experimental endocarditis (T. Wu, M. R. Yeaman, and A. S. Bayer, Antimicrob. Agents Chemother. 38:729-732, 1994; A. S. Bayer et al., Antimicrob. Agents Chemother. 42:3169-3172, 1998; V. K. Dhawan et al., Infect. Immun. 65:3293-3299, 1997). However, the mechanisms mediating tPMP-1 resistance in S. aureus are not fully delineated. The S. aureus cell membrane appears to be a principal target for the action of tPMP-1. To gain insight into the basis of tPMP-1 resistance, we compared several parameters of membrane structure and function in three tPMP-1-resistant (tPMP-1(r)) strains and their genetically related, tPMP-1-susceptible (tPMP-1(s)) counterpart strains. The tPMP-1(r) strains were derived by three distinct methods: transposon mutagenesis, serial passage in the presence of tPMP-1 in vitro, or carriage of a naturally occurring multiresistance plasmid (pSK1). All tPMP-1(r) strains were found to possess elevated levels of longer-chain, unsaturated membrane lipids, in comparison to their tPMP-1(s) counterparts. This was reflected in corresponding differences in cell membrane fluidity in the strain pairs, with tPMP-1(r) strains exhibiting significantly higher degrees of fluidity as assessed by fluorescence polarization. These data provide further support for the concept that specific alterations in the cytoplasmic membrane of S. aureus strains are associated with tPMP-1 resistance in vitro.

Amino Acids↗

PubMed2000

Cloning and characterization of secretory tyrosine phosphatases of Mycobacterium tuberculosis.

Two genes with sequence homology to those encoding protein tyrosine phosphatases were cloned from genomic DNA of Mycobacterium tuberculosis H(37)Rv. The calculated molecular masses of these two putative tyrosine phosphatases, designated MPtpA and MPtpB, were 17. 5 and 30 kDa, respectively. MPtpA and MPtpB were expressed as glutathione S-transferase fusion proteins in Escherichia coli. The affinity-purified proteins dephosphorylated the phosphotyrosine residue of myelin basic protein (MBP), but they failed to dephosphorylate serine/threonine residues of MBP. The activity of these phosphatases was inhibited by sodium orthovanadate, a specific inhibitor of tyrosine phosphatases, but not by okadaic acid, an inhibitor of serine/threonine phosphatases. Mutations at the catalytic site motif, cysteine 11 of MPtpA and cysteine 160 of MPtpB, abolished enzyme activity. Southern blot analysis revealed that, while mptpA is present in slow-growing mycobacterial species as well as fast-growing saprophytes, mptpB was restricted to members of the M. tuberculosis complex. These phosphatases were present in both whole-cell lysates and culture filtrates of M. tuberculosis, suggesting that these proteins are secreted into the extracellular medium. Since tyrosine phosphatases are essential for the virulence of several pathogenic bacteria, the restricted distribution of mptpB makes it a good candidate for a virulence gene of M. tuberculosis.

Amino Acid Sequence↗

PubMed2000

Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer.

DNA amplification at chromosomal region 20q12-q13, which is common in breast cancer, has recently been described also in ovarian tumors. We studied the amplification of the recently identified candidate oncogenes in this region in 24 sporadic, 3 familial and 4 hereditary ovarian carcinomas, and in 8 ovarian cancer cell lines. High-level amplification of at least one of the five nonsyntenic regions at 20q12-q13.2 was found in 13 sporadic (54%) and in all four hereditary tumors. Typically, two or more distinct amplicons (separated by nonamplified DNA) were found coamplified in various combinations. The regions defined by the AIB1 and PTPN1 genes (at 20q12 and 20q13.1, respectively) were amplified in 25% and 29% of the sporadic tumors, also without simultaneous coamplification of other regions. Amplification of AIB1 (a steroid receptor coactivator gene) was associated with estrogen receptor positivity in sporadic ovarian carcinomas (P = 0.01) and showed a tendency to correlate with poor survival of patients. Of the genes amplified in breast cancer, the BTAK gene was amplified in 21%, the MYBL2 gene in 17%, and the ZNF217 gene in 12.5% of the sporadic tumors. The high frequency of gene amplification at 20q12-q13.2 suggests that the genes amplified therein may play a central role in the pathogenesis of sporadic and hereditary ovarian carcinoma.

Chromosomes, Human, Pair 20↗

PubMed1999

hMLH1, hMSH2 and hMSH6 mutations in hereditary non-polyposis colorectal cancer families from southern Sweden.

We have screened 17 Southern Sweden individuals/families with suspected hereditary non-polyposis colorectal cancer (HNPCC) for mutations in the DNA-mismatch repair genes hMLH1, hMSH2 and hMSH6 using denaturing gradient gel electrophoresis, protein truncation test and direct DNA sequencing. The families were selected on the basis of a family history of HNPCC-related tumors or the occurrence of metachronous colorectal cancer/endometrial cancer at young age in an individual with a weak family history of cancer. Furthermore, we required that tumor tissue from at least one individual in the family had to display microsatellite instability. We identified germ-line mutations in 9 individuals from 8 families. Five families had mutations in hMLH1, 4 of which were splice site mutations, 2 had frameshift mutations in hMSH2 and 1 patient with metachronous endometrial and rectal cancer but with a weak family history of cancer had a nonsense mutation in hMSH6. Our results present novel germ-line DNA-repair gene mutations, one of these in hMSH6, and demonstrate the diversified mutation spectrum in Sweden, where no founder mutation has so far been identified.

Adaptor Proteins, Signal Transducing↗

PubMed1999

A somatic BRCA2 mutation in RER+ endometrial carcinomas that specifically deletes the amino-terminal transactivation domain.

Mismatch repair deficiency and replication errors (RERs) occur in approximately 20% of sporadic endometrial carcinomas. Frameshift mutations in several cancer predisposing genes, especially in their mononucleotide repeats, are seen in RER+ tumors. In a survey of hereditary breast cancer genes in gynecological cancer, we analyzed the entire coding sequence of BRCA1 and BRCA2 in 51 endometrial tumors, of which 12 were RER+. Seven somatic mutations were identified in six (50%) of the RER+ tumors, but none in RER- tumors. A novel base pair deletion at a (T)10 tract in BRCA2 intron 2, causing an in-frame splice deletion of exon 3, was observed in four tumors, one of which contained a second, truncating BRCA2 mutation. Two tumors exhibited frameshift mutations at polyA tracts in BRCA1 and BRCA2 exon 11, both predicted to result in premature translation termination. Whereas most mutations in BRCA1 and BRCA2 are known to affect the more carboxy-terminal regions interacting with RAD51, and the transactivating BRCT domains of BRCA1, this is the first demonstration of a recurrent BRCA2 mutation that specifically deletes the amino-terminal transactivation domain. Moreover, our results suggest that somatic mutations in BRCA2(and to some extent BRCA1) may confer a growth advantage in RER+ endometrial carcinomas.

BRCA1 Protein↗

PubMed1999

Effects of voriconazole on Candida glabrata in vitro.

The effects of voriconazole on the growth, morphology and lipids of Candida glabrata were studied. MIC data showed that voriconazole was up to 32- to 64-fold more active than fluconazole in its ability to inhibit various C. glabrata strains. Voriconazole inhibited the growth of C. glabrata in a dose-dependent fashion. Electron microscope examination showed that voriconazole treatment affected the external and internal morphology of C. glabrata. Treatment of C. glabrata with voriconazole inhibited ergosterol synthesis and led to accumulation of methylated sterols. In contrast, no significant difference in phospholipid composition was observed between treated and untreated cells.

Antifungal Agents↗

PubMed1998

Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans.

The Candida albicans PLB1 gene was cloned using a polymerase chain reaction-based approach relying on degenerate oligonucleotide primers designed according to the amino acid sequences of two peptide fragments obtained from a purified candidal enzyme displaying phospholipase activity (Mirbod, F., Banno, Y., Ghannoum, M. A., Ibrahim, A. S., Nakashima, S., Yasuo, K., Cole, G. T., and Nozawa, Y. (1995) Biochim. Biophys. Acta 1257, 181-188). Sequence analysis of a 6.7-kilobase pair EcoRI-ClaI genomic clone revealed a single open reading frame of 1818 base pairs that predicts for a pre-protein of 605 residues. Comparison of the putative candidal phospholipase with those of other proteins in data base revealed significant homology to known fungal phospholipase Bs from Saccharomyces cerevisiae (45%), Penicillium notatum (42%), Torulaspora delbrueckii (48%), and Schizosaccharomyces pombe (38%). Thus, we have cloned the gene encoding a C. albicans phospholipase B homolog. This gene, designated caPLB1, was mapped to chromosome 6. Disruption experiments revealed that the caplb1 null mutant is viable and displays no obvious phenotype. However, the virulence of strains deleted for caPLB1, as assessed in a murine model for hematogenously disseminated candidiasis, was significantly attenuated compared with the isogenic wild-type parental strain. Although deletion of caPLB1 did not produce any detectable effects on candidal adherence to human endothelial or epithelial cells, the ability of the caplb1 null mutant to penetrate host cells was dramatically reduced. Thus, phospholipase B may well contribute to the pathogenicity of C. albicans by abetting the fungus in damaging and traversing host cell membranes, processes which likely increase the rapidity of disseminated infection.

Amino Acid Sequence↗

PubMed1998

Lobular carcinoma in situ with microinvasion.

Six patients with lobular carcinoma in situ with microinvasion were described in this report. Lobular carcinoma in situ is not known to progress to microinvasive disease. Although this feature is rare, the current under standing that lobular carcinoma in situ is a marker needs to be revised.

Adult↗

PubMed1997

Identification of TP53 gene mutations in uterine corpus cancer with short follow-up.

The involvement of the TP53 tumor suppressor gene in uterine corpus cancer was investigated by single-stranded conformation polymorphism and sequence analysis of its exons 4 to 10. Mutations were found in 12 (18.5%) of 65 cases. Ten of these 12 were single-base substitutions (8 missense and 2 nonsense mutations), whereas 2 were frame-shifting mutations. TP53 gene mutations correlated significantly with advanced surgical stage of disease (P = 0.006) and unfavorable tumor histology types (P = 0.003), whereas the association to myometrial wall invasion did not reach statistical significance (P = 0.054). TP53 gene mutations also correlated significantly with allelic loss at TP53 locus (P = 0.024), absence of estrogen (P = 0.045) and progesterone receptors (P = 0.001), DNA nondiploidy (P = 0.002), and high S-phase fraction values (P = 0.002). Our results suggest that inactivation of the TP53 checkpoint function is associated with disease transition into a stage of rapid progression and spread.

Aged↗

PubMed1997

Comparison of histologic diagnosis between stereotactic core needle biopsy and open surgical biopsy.

BACKGROUND: This study correlates the histologic findings of stereotactic core needle biopsy (SCNB) with open surgical biopsy (OSB) and identifies which lesions can be treated definitively based only on the SCNB histology. METHODS: Women who underwent SCNB between July 1, 1993, and January 1, 1969, were identified by retrospective chart review. Mammographic (MGM) lesions found by SCNB to be ductal or lobular hyperplasia with atypia, or carcinoma underwent OSB. When the histologic findings by SCNB were inconsistent with the MGM findings, the lesion also underwent OSB. RESULTS: 799 women underwent SCNB with 96 (12%) of these going on to OSB. MGM findings in the 92 who presented without a palpable mass included microcalcifications (MCS) in 39, mass in 47, MCS and mass in 7, and tissue distortion in 3. One hundred one breast lesions biopsied first by SCNB, then by OSB were correlated histologically. Sensitivity of SCNB is 89%, with a specificity of 94%. Eight-four women (88%) were able to have definitive treatment at time of OSB because of prior SCNB, and 703/799 (88%) of women were spared OSB entirely. CONCLUSION: SCNB accurately identifies benign breast histology and invasive cancers in women with MGM abnormalities, a distinct advantage over fine needle aspiration cytology. SCNB does not reliably identify women with DCIS and invasion. All women with SCNB diagnosis of ductal or lobular atypia should also undergo OSB.

Adult↗

PubMed1995

Status of membrane lipids and amino acid transport in morphological mutants of Candida albicans.

The phospholipid composition of various morphological mutants of Candida albicans revealed a complete absence of phosphatidylinositol (PI) from plasma membranes of those cells which completely lacked mycelial growth. No other phospholipid was found to be specific to morphogenesis. The plasma membrane fractions isolated from mutants were more rigid than its wild type as was evident from their unsaturation index and fluorescence polarization measurements. The enhanced membrane rigidity of mutant cells was noted regardless whether the cells could grow only as mycelia or in their budding forms. Although some amino acids are considered to affect the morphological transition of C. albicans, this was not reflected in the transport activities of L-proline, L-alanine, L-lysine and L-glutamic acid.

Amino Acids↗

PubMed1995

High membrane fluidity is related to NaCl stress in Candida membranefaciens.

The effect of hypersaline stress on the lipid composition of the salt-tolerant yeast Candida membranefaciens was studied. Fatty acid analyses of the plasma membrane showed a growth phase- and dose-dependent increase in the level of linolenic acid (C18:3) in 1.35 M NaCl-stressed cells. Palmitoleic acid (C16:1) was completely undetectable at all phases of the life cycle. Changes in the levels of other fatty acids were insignificant. The degree of unsaturation of fatty acids in the plasma membranes was higher in presence of 1.35 M NaCl. The fluorescence polarisation value of DPH (1,6-diphenyl- 1,3,5-hexatriene) in the spheroplasts of the stressed cells was lower as compared to the control cells, indicating the fact that a higher membrane fluidity favours osmotic adaptation against NaCl stress. Among different phospholipids, levels of Phosphatidylinositol and Phosphatidylethanolamine were elevated in the salt-adapted cells as compared to their controls. The levels of Phosphatidylcholine and cardiolipin did not change significantly in response to hypersaline stress. The study points out that hypersalinity signals affect the lipid composition which in turn affects the membrane fluidity of C. membranefaciens.

Candida↗

PubMed1993

Effects of ranitidine alone and in combination with chlorpheniramine on histamine-induced wheal and flare and psychomotor performance.

Some reports suggest that addition of an H2 antagonist increases the efficacy of H1 antagonist but the influence on the side effect profile of antihistamines are largely unknown. The effects of ranitidine, chlorpheniramine, their combination and placebo on histamine induced wheal and flare, psychomotor performance and subjective symptoms were studied in 6 healthy male volunteers in a double blind randomized and cross-over (Latin square) study. Ranitidine significantly reduced the histamine induced wheal at 4 hrs (P < 0.05). Chlorpheniramine and the combination significantly reduced both histamine induced wheal and flare at 2 hrs and at 4 hrs (P < 0.05). Addition of ranitidine reduced the feeling of sleepiness produced by chlorpheniramine, though other subjective symptoms were not affected. None of the treatment schedules produced any consistent change in the psychomotor performance of the volunteers.

Adult↗

PubMed1990

Differential effects of fat deficiency on hepatic and pulmonary drug metabolizing enzymes in rat and mouse.

In the present study, we have evaluated the effect of dietary fat deprivation on the carcinogen/drug metabolizing enzymes in rats and mice. In rats, hepatic AHH, Cyt.P-450 Cyt.b5 and Cyt.c-reductase were significantly decreased due to fat deficiency, whereas in lungs, AHH and Cyt.c-reductase were decreased without any change in Cyt.P-450 level. In mice, feeding of fat-free diet did not cause any alteration in hepatic AHH and Cyt.P-450, but the levels of Cyt.b5 and Cyt.c-reductase were significantly reduced. In contrast to liver, Cyt.P-450 and Cyt.b5 were increased in lungs. Activity of UDPGT was lowered both in liver and lungs of rats whereas GST and GSH were increased in liver only. In mice, a decrease in UDPGT and appreciable increases in GST and GSH in liver were observed. However, in lungs, UDPGT activity was enhanced by feeding fat-free diet. These observations suggest that mice and rats respond differentially to the depletion of fat in the diet.

Animals↗