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Biomedical subjects

N Malik

Publications and source records attributed to N Malik.

At least 55 records · Page 3Linked to original sources
PubMed1996

Activation of human monocytes through CD40 induces matrix metalloproteinases.

The activation of monocytes/macrophages to secrete pro-inflammatory cytokines and matrix metalloproteinases (MMPs) is critically important in the development of chronic inflammatory diseases. However, the consequence of interactions between activated T cells and monocytes in these inflammatory processes is not well understood. In this study we have investigated the induction of MMPs in human monocytes by activated T cells. We show that fixed cells and the cell membranes from a T cell line, BMS-2, that expresses high levels of the CD40 ligand gp39 (also called TRAP, TBAM, or CD40L) stimulate both the expression of mRNA and the production of MMPs by human monocytic cells. Activation of monocytes by the human T cells could be significantly inhibited by a F(ab')2 fragment of a neutralizing Ab specific for human gp39, but not by an Ab that recognizes murine gp39. Furthermore, recombinant soluble gp39 (sgp39) alone induced marked increases in the levels of a 92-kDa metalloproteinase (gelatinase) in both the human monocytic cell line, THP-1, and peripheral human monocytes, and induction was blocked by the anti-human gp39 Ab. Pretreatment with IFN-gamma significantly enhanced gp39 induction of MMPs in THP-1 cells but not in peripheral monocytes. Up-regulation of mRNA for the 92-kDa MMP by gp39 could be detected within 6 h of stimulation and was maximal 24 h after treatment. MMP enzymatic activity was detectable in the culture medium 12 to 18 h following stimulation of the cells and remained high through 48 h. These results suggest the interaction of T cells with monocytes/macrophages via the gp39-CD40 counter receptors may be significant in development or maintenance of chronic inflammatory lesions.

CD40 Antigens↗
PubMed1996

Clinical amnionitis and endometritis in patients with premature rupture of membranes: endocervical prostaglandin E2 gel versus oxytocin for induction of labor.

OBJECTIVE: To compare the rates of clinical amnionitis and endometritis in patients with premature rupture of membranes (PROM), using endocervical prostaglandin E2 (PGE2) gel for induction of labor versus immediate oxytocin induction of labor. METHODS: We randomized 118 patients to receive either endocervical 0.5 mg of PGE2 gel (study group) or immediate oxytocin induction of labor (control group). If labor was not established in the group receiving PGE2 gel in 24 hours, intravenous oxytocin was given in incremental doses. The rates of clinical amnionitis and endometritis in the two groups were analyzed. Also compared were hours of labor, duration of rupture of membranes and number of vaginal examinations. Student t test, chi 2, or Wilcoxon rank-sum test were used for statistical analysis, as appropriate. P < .05 was considered significant. RESULTS: The rates of clinical amnionitis were 5.3% in the PGE2 group and 8% in the control group. Endometritis developed in 1.7% of PGE2 patients and 3.2% of controls. These differences in maternal infection rates were not statistically significant. The two groups were comparable with respect to age, parity, and antepartum group B streptococcal colonization. No significant differences in hours of labor, duration of ruptured membranes, or vaginal examinations were observed. Neonatal outcome data (mean birth weight, Apgar scores at 1 and 5 minutes, Apgar score less than 7 at 5 minutes) were not statistically significant. CONCLUSION: Endocervical placement of 0.5 mg of PGE2 gel does not increase the incidence of clinical amnionitis and endometritis in patients with PROM at term when compared with immediate induction of labor with oxytocin.

Administration, Topical↗
PubMed1996

Surgical management of lymphangiomas in adults.

Lymphangiomas are uncommon benign congenital tumours. Most occur in the head and neck region and the vast majority present before the age of two. This paper describes the presentation and management of four cases presenting after puberty and involving the parotid gland. The cases are unusual in that all were intimately associated with the facial nerve and in an older population. The value of selective neck dissection and facial nerve exposure as an approach to these lesions is discussed.

Adolescent↗
PubMed1996

Mild CF in a delta F508/R347H compound heterozygote woman: does the manifestation of this genotype differ in the two sexes?

A woman with unusually mild cystic fibrosis (CF) and normal sweat chloride levels is reported to have delta F508 deletion on one CF chromosome and the rare mutation R347H on the other, the first known female with this mutation. Of the other eight cases with R347H mutation mentioned in the literature, all five patients whose age and sex were given in the reports were men and had congenital bilateral absence of vas deferens (CBAVD). Considering these data, it is not unrealistic to assume that R347H associates more frequently than other CF mutations with CBAVD, which would mean that the clinical significance of this mutation might differ in males and females.

Adult↗
PubMed1996

Polyarteritis nodosa--a few unusual findings.

OBJECTIVE: To report the clinical spectrum of polyarteritis nodosa (PAN) from North India and highlight some unusual findings. DESIGN: Retrospective study. SETTING: Hospital based. SUBJECTS: Eight children with PAN. INTERVENTION: Treatment with prednisolone and cyclophosphamide. RESULTS: One child had spontaneous remission while another started deteriorating rapidly in spite of treatment and died within 2 weeks. Six children went into remission-of these one died, two were lost to follow-up and the remaining three are on regular follow-up for periods ranging from 3-5 years. CONCLUSIONS: Prednisolone and cyclophosphamide can significantly improve the outcome in childhood PAN.

Child↗
PubMed1995

Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells.

Oncostatin M (OSM) is a 28-kD glycoprotein recently identified as a growth factor for human multiple myeloma cells. It belongs to a family of distantly related cytokines that includes interleukin 6, ciliary neurotrophic factor, leukemia-inhibitory factor, and interleukin 11. These cytokines initiate signaling by inducing either homodimerization of gp130 or heterodimerization of gp130 with leukemia-inhibitory factor receptor beta components. Such dimerization in turn activates receptor-associated tyrosine kinases. In the present study using U266B1 human multiple myeloma cells, we show that OSM induces tyrosine phosphorylation and activation of JAK2, but not JAK1 or Tyk2, kinases. The results also demonstrate that OSM induces direct interaction of JAK2 kinase with Grb2, an SH2/SH3 domain containing adaptor protein. The SH2 domain of Grb2 is directly associated with tyrosine-phosphorylated JAK2. Furthermore, the presence of Sos in the JAK2-Grb2 complex suggests a role for Ras in OSM-transduced signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Autocrine/paracrine induction of tissue inhibitor of metalloproteinase-1 in Chinese hamster ovary cells by oncostatin M.

Chinese hamster ovary (CHO) cells expressing recombinant human oncostatin M (rOM) were found to secrete high levels of a 28-kDa protein. Sequence analysis of the protein suggested that it was hamster tissue inhibitor of metalloproteinase-1 (TIMP-1). In this study, we show that induction of TIMP-1 mRNA and protein by CHO cells is due to rOM action in an autocrine/paracrine mode. TIMP-1 expression in rOM-producing CHO cells increased concomitantly with methotrexate-induced rOM amplification. TIMP-1 upregulation was not caused by either transfection of nonspecific DNA nor was it a direct effect of treatment of the cells with methotrexate. These results suggest that oncostatin M is a potent inducer of TIMP-1 and that its receptor-mediated expression is conserved across species.

Animals↗
PubMed1995

Developmental abnormalities in mice transgenic for bovine oncostatin M.

Oncostatin M belongs to the subfamily of hematopoietin cytokines that binds a receptor complex containing gp130. To date, only the human form of oncostatin M has been identified, and its evolutionary conservation is unresolved. We have isolated a bovine gene whose open reading frame encodes a precursor protein that is 58% identical to human oncostatin M. A comparison of the bovine and human amino acid sequences predicts significant similarity, including the four-alpha-helical-bundle structure and the placement of disulfide bridges. As with the human protein, bovine oncostatin M binds specific receptors on human H2981 cells and inhibits the proliferation of human A375 tumor cells and mouse M1 leukemia cells. To identify activities regulated in vivo, we injected bovine oncostatin M fusion genes containing various tissue-specific promoters into mouse embryos. The frequencies of transgenic mice were reduced significantly, suggesting that overexpression of the bovine cytokine is detrimental to normal mouse development. In addition to deaths associated with expression in neurons and keratinized epithelia, bovine oncostatin M caused abnormalities in bone growth and spermatogenesis, stimulated fibrosis surrounding islets in the pancreas, and disrupted normal lymphoid tissue development. This work establishes the existence of a nonprimate oncostatin M gene and provides the first demonstration that this cytokine can function in a pleiotropic manner in vivo. Information regarding bovine oncostatin M may help characterize the structure and function of this cytokine in other vertebrate species.

Amino Acid Sequence↗
PubMed1994

Cloning, expression, and tissue distribution of the rat homolog of the bovine alpha 1C-adrenergic receptor provide evidence for its classification as the alpha 1A subtype.

Three alpha 1-adrenergic receptors (ARs) have been cloned, i.e., the alpha 1B-, alpha 1C-, and alpha 1D-ARs. Compared with the alpha 1B subtype, the alpha 1A subtype in tissue is described as being insensitive to chloroethylclonidine and sensitive to SZL-49 and having a 10-100-fold higher affinity for a number of agonists and antagonists. The alpha 1A subtype is also expressed in a variety of rat tissues (as assessed by pharmacology), with greatest abundance in the cerebral cortex, hippocampus, vas deferens, and submaxillary gland. The cloned bovine alpha 1C-AR, though having an alpha 1A-AR pharmacology, was first reported as not being expressed in any rat tissue (as determined by Northern analysis) and was therefore designated as a new subtype. We report the cloning, expression, and characterization of the rat homolog of the bovine alpha 1C-AR. Using a human alpha 1C-AR probe obtained by polymerase chain reaction screening of a neuroblastoma cell line (SK-N-MC), both exon 1 and exon 2 of the rat alpha 1C-AR gene were cloned from a rat genomic library. These two exons were spliced together and cloned into the expression vector pMT2'. Transfection into COS-1 cells and analysis of the ligand-binding profile of the expressed protein receptor using 125I-HEAT revealed a 10-100-fold higher affinity for the alpha 1-AR antagonists 5-methylurapidil, (+)-niguldipine, WB-4101, and phentolamine and the agonists oxymetazoline and methoxamine, compared with the alpha 1B-AR. This ligand-binding profile is similar to that for endogenously expressed tissue alpha 1A-ARs. In addition, the rat alpha 1C-AR was the least sensitive of the three cloned subtypes to the alkylating effects of chloroethylclonidine but was the most sensitive to the alkylating prazosin analog SZL-49, properties also observed for the tissue alpha 1A subtype. Furthermore, by three different techniques, i.e., RNase protection assays, reverse transcription-polymerase chain reaction Northern blotting, and in situ hybridization histochemistry, the rat alpha 1C-AR mRNA was localized to alpha 1A-AR-rich tissues, such as rat vas deferens, hippocampus, aorta, and submaxillary gland. Taken together, these data suggest that this receptor may actually represent the alpha 1A subtype.

Amino Acid Sequence↗
PubMed1993

Pancreatic pseudocyst. A rare complication of polyarteritis nodosa.

An 18-year-old male who developed a pancreatic pseudocyst during the active phase of polyarteritis nodosa is described. Cytotoxic therapy with cyclophosphamide and prednisolone was unable to control the manifestation of this disease, and he required percutaneous drainage of the pseudocyst. The drainage resulted in complete resolution.

Adolescent↗
PubMed1993

Renal mucormycosis: computerized tomographic findings and their diagnostic significance.

Isolated renal involvement by mucormycosis has been reported rarely in immunocompromised individuals. We describe four patients with mucormycosis confined to the kidneys, three of whom did not exhibit any predisposing factors. Only one patient had acute viral hepatitis with fulminant hepatic failure as the preceding disease. Two patients presented with oliguric renal failure of undetermined etiology and investigations revealed bilateral extensive involvement of the kidneys. Computerized tomography showed diffuse enlargement of the kidneys and multiple low-density areas. Treatment included systemic amphotericin B therapy in all four patients and nephrectomy in three patients. Two patients recovered completely. Our experience emphasizes the need for a high index of suspicion and recognition of computed tomographic scan appearances for making a prompt diagnosis. Early surgical intervention and systemic antifungal therapy are necessary for survival in this life-threatening condition.

Adolescent↗
PubMed1993

Intramedullary enterogenous cyst.

A case of intramedullary enterogenous cyst in the thoracic region is reported. Computed tomography findings are highlighted with a brief review of the literature.

Adult↗
PubMed1993

Molecular genetic analysis of Turkish cystic fibrosis patients.

The cystic fibrosis (CF) gene was recently cloned and a three basepair deletion removing phenylalanine 508 from the coding region was identified as the mutation on the majority of cystic fibrosis chromosomes. The frequency of this mutation varies among different geographic locations. In this study we analysed 25 Turkish families and have found the relative frequency of the delta F508 (DF508) mutation to be 20.37%. This is similar to that reported in other Middle Eastern countries and contrasts with the considerably higher frequencies encountered in Northern Europe and North America. Molecular analysis of the two nucleotide binding folds (NBFs) of the cystic fibrosis transmembrane conductance regulator (CFTR) gene with direct sequencing, has also shown that the other defined mutations in these regions of the gene do not occur in the CF patients from the Turkish population. One patient presenting with severe clinical features was determined to be a compound heterozygote for the mutations delta F508/1677delTA.

Alleles↗
PubMed1993

Selection and characterization of a variant of human melanoma cell line, A375 resistant to growth inhibitory effects of oncostatin M (OM): coresistant to interleukin 6 (IL-6).

Human melanoma cell line A375 is extremely sensitive to growth inhibitory effects of oncostatin M (OM). A375 cells resistant to the antiproliferative effect of OM were isolated by exposing OM-sensitive cells to ethyl methane sulfonate (EMS) for 24 h followed by continuous exposure to OM. An A375 subline resistant to OM-induced growth inhibition was selected by a limiting dilution technique and designated 4-1.10". The resistant cells were completely refractory to OM even up to a concentration of 500 ng/ml. Interestingly, the resistant cells were also nonresponsive to the growth inhibitory effects of interleukin-6 (IL-6). Other cytokines such as transforming growth factor beta (TGF-beta), interleukin-1 (IL-1), and tumor necrosis factor alpha and beta (TNF-alpha and TNF-beta) exhibited similar growth inhibitory effects on OM-sensitive or -resistant cells. OM-resistant cells were found to possess approximately 20% of OM receptors with the same affinities as compared to the parental OM-sensitive cells. However, the affinities and number of receptors for IL-6 were the same on both cell types. The OM treatment did not alter the cyclic AMP (cAMP) level of either the parental or the resistant cells. The OM-resistant cell line will be very useful in elucidating the mechanism of OM-elicited growth inhibition.

Antineoplastic Agents↗