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M Mahmoudi

Publications and source records attributed to M Mahmoudi.

35 records · Page 2Linked to original sources
PubMed1999

Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39.

Glucagon-like peptide 1(7-36) amide (GLP-1) is postulated to be the major physiological incretin in humans, but evidence is indirect. We report the first studies examining the physiological role of GLP-1 in the postprandial state in humans using the GLP-1 antagonist exendin 9-39. Exendin 9-39 completely blocked GLP-1-induced glucose-stimulated insulin release from perifused human islets of Langerhans. In healthy fasted volunteers, intravenous infusion of exendin 9-39 at 500 pmol x kg(-1) x min(-1) in the hyperglycemic state abolished the insulinotropic effect of a physiological dose of GLP-1 and fully reversed the glucose-lowering effect of GLP-1. Nine healthy subjects consumed a 150-g oral glucose tolerance test and were infused with 500 pmol x kg(-1) x min(-1) exendin 9-39 or saline. Exendin 9-39 increased the peak postprandial glucose level (exendin 9-39, 8.67 +/- 0.35 vs. saline, 7.67 +/- 0.35 mmol/l, P < or = 0.005) and increased postprandial plasma glucose incremental area under the curve by 35% (exendin 9-39, 152 +/- 19 vs. saline, 113 +/- 16 mmol x min x l(-1), P < or = 0.05). This could be explained as partly secondary to the blockade of glucose-induced suppression of glucagon and maybe also to an increased rate of gastric emptying. Thus, in humans exendin 9-39 acts as an antagonist of GLP-1 both in vitro and in vivo. When infused alone, exendin 9-39 causes a deterioration in postprandial glycemic control, suggesting that GLP-1 may be important for maintenance of normal postprandial glucose homeostasis in humans.

Cytokines↗
PubMed1997

Chronic intermittent ethanol treatment in rats increases GABA(A) receptor alpha4-subunit expression: possible relevance to alcohol dependence.

Chronic administration of ethanol to rats on an intermittent regimen, for 60 repeated intoxicating doses and repeated withdrawal episodes, results in a long-lasting kindling phenomenon. This involves an increasing severity of withdrawal, including a reduced threshold to seizures produced by the GABA(A) antagonist, pentylenetetrazol. We have shown previously that muscimol-evoked 36Cl- efflux and paired-pulse inhibition (involving GABA(A)-mediated recurrent inhibition) were decreased persistently in the CA1 region of hippocampal slices from chronic intermittent ethanol (CIE)-treated rats. We now report elevated levels of mRNA in forebrain for the alpha4 subunit of the GABA(A) receptor (GABAR), considered to be a constituent of pharmacologically and physiologically novel subtypes of GABARs. Using in situ hybridization with digoxigenin-labeled RNA probes, we show that at 2 days withdrawal, 60-dose CIE leads to a significant 30% increase in alpha4 subunit mRNA levels in the dentate gyrus, 46% increase in the CA3, and 26% increase in the CA1 regions. In contrast, there was no significant change in the mRNAs for the alpha5 subunit or glutamic acid decarboxylase 67 in the same regions. This study suggests that GABAR subunit-selective alterations occur after CIE treatment, possibly resulting in the alteration of the subunit composition of GABARs, with presumably altered physiological functions. This plasticity of GABARs may contribute to the increased withdrawal severity, reduced hippocampal inhibition, and increased seizure susceptibility of this animal model of human alcohol dependence.

Animals↗
PubMed1997

V region gene analysis of human IgM hybridoma monoclonal anti-Sm antibodies.

Anti-Sm antibodies although highly specific for systemic lupus erythematosus can only be found in 10-25% of lupus patients and lupus-prone MRL/lpr mice. Molecular studies of these autoantibodies from mice have suggested that the anti-Sm response is Ag driven, its expression is controlled by stochastic events and may originate from the same B cell precursors as anti-DNA antibodies. However, relatively little information regarding the molecular characteristics of anti-Sm antibodies in man has been reported. We studied the V region genes of three IgM hybridoma monoclonal antibodies (BUD 45.12.8, BUD 114.4.11 and BUD 94.91.8) which were selected for Sm reactivity and derived from B cells of a healthy child. Two of these antibodies BUD 45.12.8 and BUD 114.4.11 also-reacted with ssDNA, while the third (BUD 94.91.8) did not. Each of these anti-Sm/ RNP antibodies was encoded by different and predominantly unmutated Ig heavy chain germline genes (BUD 45.12.8 by VH3-23, DXP4 and JH4b; BUD 94.91.8 by VH3-33, D21-9 and JH6b; BUD 114.4.11 by VH1-2, DK1 or DM1 or unknown D and JH4b) and light chain genes (BUD 45.12.8 by Humkv325 and JK2; BUD 94.91.8 by hsiggll150 (lambda IIIb) and J lambda 2/3; BUD 114.4.11 by Humk18 and JK3). Many of these genes are also used by antibodies with other specificities including DNA. The two anti-Sm antibodies which also bound ssDNA shared an overall V region net positive charge, while the third antibody without ssDNA reactivity carried a negative V region net charge. These findings demonstrate that (1) normal individuals have the genetic potential to generate autoantibodies to Sm/RNP; (2) acquisition of Sm/RNP binding is not dependent on somatic mutations and (3) some human B cell clones exhibit specificity for Sm and ssDNA.

Amino Acid Sequence↗
PubMed1995

The role of the immunoglobulin heavy chain in human anti-DNA antibody binding specificity.

OBJECTIVE: To investigate the structural basis for DNA binding of the natural human IgM lambda monoclonal antibody KIM4.6. METHODS: An IgM lambda, non-DNA-reactive variant hybridoma was derived during in vitro subcloning of the anti-DNA antibody KIM4.6. The variable (V)-region heavy (H) and light (L) chain genes expressed by the variant hybridoma were amplified by polymerase chain reaction, cloned, sequenced, and compared with those of the KIM4.6 parent and other DNA-binding and non-DNA-binding antibodies. RESULTS: The VL chain of the variant was identical to that of KIM4.6. In contrast, the VH chain was completely different from the VH chain of the parent but was similar or identical, except in the diversity (D) and joining regions, to the VH chain of the systemic lupus erythematosus (SLE) IgG anti-DNA antibody T14 and SLE IgM nephritogenic anti-DNA antibodies NE-1 and NE-13. CONCLUSION: The expression of the KIM4.6 VL chain is not sufficient for DNA specificity. The VH chain and its D region play a key role in conferring DNA binding of the KIM4.6 anti-DNA antibody.

Amino Acid Sequence↗
PubMed1994

Immunoglobulin V region sequences of two human antiplatelet monoclonal autoantibodies derived from B cells of normal origin.

Autoimmune thrombocytopenia has been attributed to the presence of antiplatelet autoantibodies which mediate platelet destruction. The derivation of these autoantibodies is presently unknown. While normal B cells do not produce these autoantibodies in vivo, it has been demonstrated in vitro by somatic cell hybridization that the B lymphocytes of nonthrombocytopenic individuals have the potential to produce antiplatelet autoantibodies. Antigen specificities of these antibodies are similar to those seen in autoimmune thrombocytopenic purpura and the lupus anticoagulant syndrome. The immunoglobulin V region genes encoding two such human monoclonal antiplatelet antibodies, an anti-GP IIb (STO 171) and an anti-phospholipid antibody (STO 103) derived from tonsillar lymphocytes of a non-thrombocytopenic male, have now been sequenced. These antiplatelet antibodies were found to be encoded by unmutated germline VH and VK genes. The third complementarity determining region (CDR3) of the genes encoding both of these antibodies have unique D regions with evidence of N-nucleotide additions, and the light chain genes show VK-JK junctional diversity. STO 103 is encoded by the VH4 V71-2 germline gene and a truncated JH4 gene. The light chain gene showed closest homology with the VK4 Humk18 gene and JK2 gene. STO 171 showed closest homology with the VH4.18 germline gene and had a complete germline JH6 gene. The light chain of STO 171 is encoded by the VK3 Humkv325 germline gene, which is also used by some rheumatoid factors and cold agglutinins, and a JK4 gene. Although these antibodies were not derived from circulating B cells or found to be actively producing antibody at the time they were harvested, it is possible that naturally occurring antibody producing B cells, similar to those represented here, are recruited for the development of pathogenic autoantibodies in immune thrombocytopenia.

Amino Acid Sequence↗
PubMed1993

Immunoglobulin V region heavy and light chain gene sequences of the lymphoblastoid cell line GM 4672.

GM 4672 is an IgG2 kappa-producing lymphoblastoid cell line derived from a patient with multiple myeloma. It has been used by many laboratories as a fusion partner for the production of human-human hybridoma monoclonal antibodies. GM 4672 immunoglobulin variable region heavy and light chain family usage was originally assigned to VH1 and VK1, respectively. This assignment was based on the positions of [3H]leucine of the heavy and light chain proteins using the Edman degradation method. Using the polymerase chain reaction and variable region leader primers and constant region primers, we report here the immunoglobulin variable region gene sequence expressed by GM 4672. The VH region belongs to the VH4 family and is most homologous with the V71-2 (87.9%), DK1, and JH4 germline genes. The entire heavy chain V region contained 41 mutations in 36 codons and included 11 N nucleotide additions flanking the D region. GM 4672 VK region contained a VK1 gene rearranged with a JK4 gene. The VK germline gene used by GM 4672 light chain was not identified but showed the most homology with Vb' germline gene (87.7%). When compared to Vb' and JK4 genes, there were 37 mutations in 30 codons with evidence of antigen selection as determined by the replacement to silent mutation ratio in the complementarity-determining regions. The high frequency of mutations in the V region genes of GM 4672 is comparable to the sequences of other myeloma proteins.

Amino Acid Sequence↗
PubMed1989

Expression of c-myc and c-Ha-ras oncogenes in human lymphoblastoid cells (Namalva).

We have studied the expression of c-myc and c-Ha-ras oncogenes in this cell line. Daudi lymphoblastoid cells and normal human leukocytes served as a positive and a negative control, respectively. The Northern blot analysis using a c-myc probe revealed a 2.7 kb transcript and two larger transcripts greater than 23 kb. In the Northern blot hybridization using a c-Ha-ras probe, two transcripts with sizes of 1.8 and 6.1 kb were observed. The affinity of the Namalva RNA hybridization to c-myc probe was about 10-fold lower than that in Daudi RNA, whereas no difference in the c-Ha-ras hybridization was observed between the two cell lines. These data indicate that c-myc and c-Ha-ras are expressed in Namalva cells. It is noteworthy to consider that the difference in oncogene expression between Namalva and Daudi cells might be due to the difference in interferon properties between the two cell lines.

Blotting, Northern↗
PubMed1986

Oncogene expression in human hepatoma cells PLC/PRF/5.

The expression of 7 cellular oncogenes in a human hepatoma cell line PLC/PRF/5 was studied using Northern blot analyses. Among the oncogenes tested, c-abl, c-fes, c-fms, c-myc, c-Ha-ras and c-sis were expressed. The oncogene c-Ki-ras was not expressed. The length of the mRNAs expressed was almost consistent with published data. Compared to the oncogene expression in Daudi lymphoma cells, the same kind of oncogenes were expressed in PLC/PRF/5 cells, but the intensity of the signal in each oncogene expression was stronger in Daudi cells than in PLC/PRF/5 cells. Considering the cellular localization and the function of each oncogene, the oncogene survey in hepatoma cells broadens the knowledge of hepatocarcinogenesis and the character of human hepatoma cells.

Carcinoma, Hepatocellular↗
PubMed1986

Antitumor effect of human necrosis factor on human hepatoma cells PLC/PRF/5.

The antitumor activity of natural human tumor necrosis factor (TNF) on a human hepatoma cell line PLC/PRF/5 was studied in vitro. TNF produced by the LuKII human lymphoblastoid cell line showed a cytostatic effect on the hepatoma cells, whereas the growth of non-tumorigenic Chang liver cells was little affected. The combined effects of TNF and interferon-gamma (IFN-gamma) were additive on the PLC/PRF/5 cells as shown by statistical analyses. The same combination showed synergistic effects on a human breast cancer cell line BT-20, which was highly sensitive to TNF. These data may provide some informations concerning the use of TNF in the treatment of hepatoma.

Animals↗
PubMedDate not supplied

Dermatophytoses in Iran.

A total of 12,150 cases of suspected dermatophytoses in different areas of Iran were studied between 1986 and 1991. The age groups most commonly infected were 1-9 and 20-29 years. Clinical diagnosis was confirmed in only 9345 cases by laboratory examination. Of these positive samples, 1633 cases were found to be positive by direct microscopic observation only, 429 by culture only and 7283 by both techniques. Scalp ringworm of children was the most common type of tinea. But according to the rate of infection, tinea corporis, tinea pedis, tinea cruris, tinea manuum, tinea unguium and tinea barbae were the next most prevalent in that order. The frequencies of dermatophytes isolated from patients were as follows: Microsporum canis 19.4%, Trichophyton rubrum 16.5%, Epidermophyton floccosum 14.9%, Trichophyton mentagrophytes var. interdigitale 14.6%, Trichophyton verrucosum 11.5%, Trichophyton mentagrophytes 6%, Trichophyton violaceum 8.7%, Trichophyton schoenleinii 5.5%, Trichophyton tonsurans 1.3%, Trichophyton erinacei 0.8% and Microsporum gallinae 0.2%.

Adolescent↗
PubMedDate not supplied

Iron status and socioeconomic determinants of the quantity and quality of dietary iron in a group of rural Iranian women.

Iron intake and status were investigated in 471 mothers (age range: 16-53 years) from rural areas in Khorramabad, Islamic Republic of Iran. Although average total iron intake was acceptable, only 6.4% of women derived at least 4% of their total intake from animal iron. Average energy and protein intakes were inadequate. Low iron status was seen in 8.2%-28.7%, depending on the parameter used, with 28.3% experiencing iron-deficiency anaemia. Significantly higher animal iron intakes were found in literate or employed women, or those of family size fewer than six people. Increasing employment opportunities, income levels and literacy rates for women will result in better iron intake and status and should receive particular attention in national planning.

Adolescent↗
PubMedDate not supplied

Bromocriptine-induced hypothermia: D-2 receptor involvement.

Bromocriptine (2-16 mg/kg, i.p.) caused a dose-dependent fall in core body temperature of mice. The hypothermic effect of bromocriptine was decreased by pretreatment of the animals with sulpiride, but SCH 23390, methergoline, phenoxybenzamine, propranolol and atropine did not decrease the response. Administration of reserpine plus alpha-methyl-p-tyrosine prior to bromocriptine injection abolished hypothermia in mice. It is concluded that D-2 dopamine receptors may be involved in bromocriptine-induced hypothermia.

Adrenergic alpha-Antagonists↗