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M Mustafa

Publications and source records attributed to M Mustafa.

At least 55 records · Page 3Linked to original sources
PubMed1997

High IL-6 and low IL-10 in the central nervous system are associated with protracted relapsing EAE in DA rats.

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that serves as a model for multiple sclerosis (MS). The mechanisms behind differences in clinical course of EAE in different rat strains have not been defined. We induced acute EAE in Lewis rats and protracted relapsing EAE (PR-EAE) in DA rats and examined mRNA expression of IL-1 beta, IL-6, IL-10, IL-12, and TNF-beta in brain tissue sections, cerebrospinal fluid (CSF) cells, and lymph node cells. IL-1 beta, IL-12 and TNF-beta mRNA expression in brain tissue sections appeared early and peaked at the height of clinical signs in both acute and PR-EAE, consistent with a disease-promoting role for these cytokines. High levels of IL-6 mRNA-expressing cells were present in CNS and lymph node cells in PR-EAE, while almost absent in acute EAE. In contrast, IL-10 was very low in PR-EAE but strongly expressed in acute EAE, in particular during clinical recovery. Regulatory changes of IL-6 and IL-10 both systemically and within the CNS, but with temporal differences between compartments, seem pivotal for development of PR-EAE in DA rats. These findings could have relevance for pathogenesis and treatment of MS.

Animals↗
PubMed1996

Spontaneous, extra-dural haematoma causing spinal cord compression.

We describe a patient with acute compression of the spinal cord by a spontaneous extra-dural haematoma. This rare condition is often misdiagnosed. We believe that an urgent MRI scan is indicated in patients presenting with progressive neurological deficit following spinal trauma. This allows the diagnosis of extra-dural haematoma to be made rapidly and for prompt decompression of the cord.

Aged↗
PubMed1995

Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells.

The potential role of certain important immunoregulatory and effector cytokines in autoimmune neuroinflammation have been studied. We have examined the expression of mRNA, with in situ hybridization, of interferon gamma (IFN-gamma), interleukin 4 (IL-4) and transforming growth factor beta (TGF-beta) both in sections of spinal cords and the antigen-induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63-88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In spinal cords, the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the spinal cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4. Such cells may act in the initiation and promotion of the disease. Later, in the recovery phase, MBP 63-88 induced lymphoid cells to TGF-beta production. Thus, an autoantigen-specific production of TGF-beta occurred during EAE and hypothetically such a mechanism may serve to downregulate aggressive autoimmunity systemically.

Amino Acid Sequence↗
PubMed1995

Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta.

The kinetics of mRNA expression in the central nervous system (CNS) for a series of putatively disease-promoting and disease-limiting cytokines during the course of experimental autoimmune encephalomyelitis (EAE) in Lewis rats were studied. Cytokine mRNA-expressing cells were detected in cryosections of spinal cords using in situ hybridization technique with synthetic oligonucleotide probes. Three stages of cytokine mRNA expression could be distinguished: (i) interleukin (IL)-12, tumor necrosis factor (TNF)-beta (= lymphotoxin-alpha) and cytolysin appeared early and before onset of clinical signs of EAE; (ii) TNF-alpha peaked at height of clinical signs of EAE; (iii) IL-10 appeared increasingly at and after clinical recovery. The early expression of IL-12 prior to the expression of interferon-gamma (IFN-gamma) mRNA shown previously is consistent with a role of IL-12 in promoting proliferation and activation of T helper 1 (Th1) type cells producing IFN-gamma. The TNF-beta mRNA expression prior to onset of clinical signs favours a role for this cytokine in disease initiation. A pathogenic effector role of TNF-alpha was suggested from these observations that TNF-alpha mRNA expression roughly paralleled the clinical signs of EAE. This may be the case also for cytolysin. IL-10-expressing cells gradually increased to high levels in the recovery phase of EAE, consistent with a function in down-regulating the CNS inflammation. From these data we conclude that there is an ordered appearance of putative disease-promoting and -limiting cytokines in the CNS during acute monophasic EAE.

Animals↗
PubMed1994

Protective influences on experimental autoimmune encephalomyelitis by MHC class I and class II alleles.

Experimental autoimmune encephalomyelitis (EAE) is influenced by polymorphism of the MHC. We have previously found that Lewis rats with certain MHC haplotypes are susceptible to disease induced with the myelin basic protein (MBP) peptide 63-88, whereas Lewis rats with other MHC haplotypes are resistant. Interestingly, rats with the MHC u haplotype develop an immune response to the MBP 63-88, but do not get EAE. In this study we have used intra-MHC recombinant rat strains to compare the influences of the MHC u with the a haplotype. We discovered the following: 1) The class II region of the MHC a haplotype permits EAE and a Th1 type of immune response as measured by IFN-gamma production after in vitro challenge of in vivo-primed T cells with MBP 63-88. 2) The class II region of the u haplotype is associated with a disease-protective immune response characterized by production of not only IFN-gamma, but also of IL-4 mRNA expression by the MBP 63-88-activated cells. 3) The class I region upstream of the class II region of the u haplotype is associated with a disease-protective effect and the expression of mRNA for TGF-beta after MBP 63-88-induced activation. Thus, such a TGF-beta response occurs in all strains expressing the class I Au allele. Treatment with Abs to CD8+ cells abrogates peptide-induced TGF-beta mRNA expression, and aggravates disease in strains with the class I Au allele.

Alleles↗
PubMed1994

The immediate outcome of ventilation for pulmonary diseases.

Fifty-eight patients were ventilated for acute respiratory failure complicating respiratory diseases between 1985 to 1990. There were 19 cases of chronic obstructive airway disease (COAD), 17 cases of asthma, 16 cases of pneumonia and 6 cases with other diagnoses. Overall, 40% of patients survived and were discharged from the ward. Patients with pneumonia had the lowest survival rate (25%) whilst the survival rates for asthma and COAD were 47% and 42% respectively. Increasing age had an inverse relationship to survival rate (r = 0.96, p < 0.05) but the duration of ventilation did not correlate with survival. Patients who were electively ventilated before respiratory arrest had a better chance of survival (57%) compared with only 18% survival rate in patients who were ventilated as an emergency (x2 = 4.47, p < 0.05). Patients who developed other organ failure had higher mortality (71%) than those who did not (22%; x2 = 2.14, p < 0.05). We conclude that patients younger than 50 years of age, who were electively ventilated and without other organ failure had a better immediate survival after assisted ventilation.

Adult↗
PubMed1993

The major histocompatibility complex influences myelin basic protein 63-88-induced T cell cytokine profile and experimental autoimmune encephalomyelitis.

Polymorphism of the major histocompatibility complex (MHC) influences susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP) in rats. Current concepts relate such influences to the capacity of class II molecules to present relevant peptides to autoreactive T cells. We have here analyzed the MHC influence on the immune response and the development of EAE after immunization with the immunodominant peptide MBP-63-88. Analysis of MHC-congenic LEWIS strains showed that RT1a, RT1c and RT1(1) haplotypes are permissive for disease induction, whereas RT1d and RT1u are resistant. All EAE responding strains showed peptide-specific proliferation and interferon (IFN)-gamma secretion, but no early significant tendency to express interleukin (IL-4) or transforming growth factor (TGF)-beta mRNA in lymphocytes in response to the MBP 63-88, 7 days post immunization (p.i.). Later, 14 days p.i., peptide-specific induction of IL-4 and TGF-beta occurred in RT1(1) rats. Among the EAE non-responders strains, only the RT1u rats showed an immune response to MBP 63-88. This response, however, was qualitatively different from the immune response in the EAE-susceptible strains. Thus, there was no proliferation and only moderate IFN-gamma production in response to peptide, but in contrast, a significant and early peptide-induced IL-4 and TGF-beta response was observed. The data suggest that the MHC-associated susceptibility to EAE is partly related to the ability to mount a TH1-like immune response while the MHC-associated EAE resistance may either be related to MBP peptide non-responsiveness or to peptide recognition and induction of a qualitatively different and disease down-regulatory immune response.

Amino Acid Sequence↗
PubMed1993

Immunopharmacologic modulation of experimental allergic encephalomyelitis: low-dose cyclosporin-A treatment causes disease relapse and increased systemic T and B cell-mediated myelin-directed autoimmunity.

Therapies with immunosuppressive drugs in autoimmune experimental diseases often down-regulate disease but sometimes may lead to paradoxical disease exacerbation. To elucidate possible mechanisms behind such phenomena the effects were studied of mitoxantrone (Mx) and cyclosporin A (CsA) given at high and low doses on clinical course, and on autoreactive T- and B-cell responses in actively induced experimental allergic encephalomyelitis (EAE) in Lewis rats. Treatment with Mx and high dose CsA abrogated EAE and decreased dramatically the measured immune responses compared to vehicle-treated control EAE rats. Low-dose CsA treatment caused a disease relapse 20-30 days post immunization (p.i.). This relapse was accompanied by increased numbers of cells spontaneously producing IFN-gamma in the CNS and regional lymph nodes. Furthermore, anti-myelin and anti-MBP secreting cells were increased as were numbers of primed T cells that produced IFN-gamma in response to myelin antigens. It was concluded that these aspects of the myelin autoreactive immune response correlated well with clinical disease and are useful in evaluating immunotherapeutic intervention. Low-dose CsA treatment may interfere with systemic down-regulatory mechanisms acting on both T- and B-cell myelin-directed autoimmunity.

Animals↗
PubMed1992

Interaction of monocrotophos and its novel thion analogues with microsomal cytochrome P-450: in vivo and in vitro studies in rat.

The binding of monocrotophos (MCP) and its two thion analogues (coded as RPR-II and RPR-V) to rat hepatic microsomal cytochrome P-450 (HMC) were investigated in vitro by difference spectroscopy. These three organophosphorus insecticides were found to bind stoichiometrically to HMC with very high affinity (Ks 34-50 microM). RPR-V showed the highest binding affinity followed by RPR-II and MCP. Association of these compounds with HMC occurred within 2 min of addition in the cuvette and therefore, appeared to be tight binding ligands of cytochrome P-450. In vivo studies at equitoxic doses of the three compounds 24 h after oral treatment in rats revealed that they all caused reduction in MC content in liver, lung, kidney and brain, as against induction in cardiac and splenic cytochrome P-450. These in vivo results suggest organ specificity in modulating the microsomal cytochrome P-450 (MC) content of hepatic and extra-hepatic tissues by the three compounds. Apparently, their binding affinity with HMC is strongly correlated with their LD50 value and has a substantial co-relationship with the cytochrome P-450 level in the liver.

Animals↗
PubMed1991

A comparative study of blood changes and brain acetylcholinesterase inhibition by monocrotophos and its analogues in rats.

The effects of monocrotophos and its newly synthesized analogues, RPR-II and RPR-V, on hematology and blood chemistry 24 hr post-treatment were studied in rats given doses of 0.96, 1.23, and 3.0 mg/kg po, respectively. It was found that monocrotophos caused a significant increase in the mean WBC count. RPR-V, a significant decrease in hematocrit and RBC count, whereas RPR-II did not alter any hematological parameter. The activities of membrane-bound enzymes in serum were not significantly changed by all three compounds except for a statistically significant increase of 38% in SGOT activity by RPR-II. Only monocrotophos caused a significant inhibition of the brain acetylcholinesterase activity. In vitro studies with partially purified preparations of rat brain cholinesterase revealed that monocrotophos was the most potent anticholinesterase agent, followed by RPR-II and RPR-V. All three compounds caused inhibition of rat brain cholinesterase by decreasing the Vmax and increasing the Km values, indicating a mixed type of inhibition. The two analogues appeared to be less neurotoxic than monocrotophos.

Acetylcholinesterase↗
PubMed1991

Inhibition of the release of endothelium-derived relaxing factor in vitro and in vivo by dipeptides containing NG-nitro-L-arginine.

1. We have shown that dipeptides containing NG-nitro-L-arginine (NO2Arg) inhibit the biosynthesis of endothelium-derived relaxing factor (EDRF) in vitro and in vivo. 2. In anaesthetized rats, intravenous administration at 1-30 mg kg-1 of the methyl ester of NO2Arg, NO2-Arg-L-phenylalanine (NO2Arg-Phe), L-alanyl-NO2Arg (Ala-NO2Arg) or NO2Arg-L-arginine (NO2Arg-Arg) produced dose-related increases in mean arterial blood pressure (MABP) which were unaffected by D-arginine (D-Arg; 20 mg kg-1 min-1 for 15 min), but prevented by co-infusions of L-arginine (L-Arg; 20 mg kg-1 min-1 for 15 min) or by their parent dipeptides. 3. NO2Arg methyl ester, NO2Arg-Phe methyl ester or Ala-NO2Arg methyl ester (10 mg kg-1, i.v.) also inhibited the reduction in MABP caused by the endothelium-dependent vasodilator, acetylcholine (30 micrograms kg-1 min-1 for 3 min), but not those induced by glycerly trinitrate (20 micrograms kg-1 min-1 for 3 min) or iloprost (6 micrograms kg-1 min-1 for 3 min) which act directly on the vascular smooth muscle. 4. Moreover, NO2Arg methyl ester, NO2Arg-Phe methyl ester or NO2Arg-Arg methyl ester (100 microM) inhibited the acetylcholine-induced relaxation of rabbit aortic strips, and NO2Arg-Phe methyl ester (30 microM) blocked the stimulated (bradykinin, 30 pmol) release of EDRF from bovine aortic endothelial cells grown on microcarrier beads. 5. In endothelial cells grown in L-Arg-deficient medium, L-Arg-containing dipeptides such as L-Arg-LPhe, L-Ala-L-Arg or L-Arg-L-Arg increased both the basal and stimulated release of EDRF. Moreover, the L-Arg containing dipeptides, but not their NO2Arg analogues, were rapidly cleaved by these cells. 6. Thus, dipeptides containing NO2Arg can directly interfere with the biosynthesis of EDRF in vitro and in vivo. Moreover, the potentiation of EDRF release from endothelial cells deprived of L-Arg by dipeptides containing L-Arg suggests that such peptides may serve as an additional or alternative substrate for the biosynthesis of EDRF.

Amino Acid Sequence↗
PubMed1991

Effect of dimethoate on hepatic cytochrome P-450 and glutathione S-transferase activity in pigeon and rat.

Effect of acute exposure (24 hr) to different oral doses of dimethoate on hepatic microsomal cytochrome P-450 (Cyt. P-450) content and cytosolic glutathione S-transferase (GST) activity were determined in pigeon and rat to ascertain difference in the metabolic response as a measure of species selective toxicity. Dimethoate at five different doses caused a statistically significant decrease in Cyt. P-450 content both in pigeon and rat. However, reduction in GST activity was significant at three doses in pigeon and at high dose in rat. Thus, a different quantum of hepatic Cyt. P-450 decrease and a differed response of GST activity against dimethoate exposure in pigeon and rat may be one of the possible causes for relatively higher toxicity of dimethoate in birds.

Animals↗
PubMed1990

Hepatic and extra hepatic glutathione depletion and glutathione-S-transferase inhibition by monocrotophos and its two thiol analogues.

Effect of monocrotophos (MCP) and its thiol analogues (coded as RPR-2 and RPR-5) on hepatic and extra-hepatic glutathione (GSH) depletion and glutathione-S-transferase (GST) inhibition was studied at 0.96, 1.23 and 3.0 mg/kg respectively 24 h after medication in rats. All the three compounds caused tissue specific depletion of GSH from hepatic and extra-hepatic tissues. Cytosolic GST activity was significantly inhibited in all the tissues, MCP being the most potent inhibitor. Both in vitro and in vivo data indicate that hepatic GST inhibiting potential of the three compounds lies in the order MCP greater than RPR-5 greater than RPR-2. In vitro effect of 3 compounds on GSH activation kinetics of GST demonstrate competitive inhibition by MCP and non-competitive inhibition by the two analogues. However, CDNB activation kinetics of the enzymes revealed mixed inhibition by all 3 compounds. The present study suggests that monocrotophos and its thiol analogues may bring about physiological upsets by altering GSH and GST dependent events in different tissues of exposed organisms.

Administration, Oral↗
PubMed1990

Haematological and hepatotoxic effects of isoprocarb in chicken.

The haematological and hepatotoxic effects were studied after oral administration of Isoprocarb at 75, 112.5 and 150 mg kg-1 daily for 21 days in male and female chicken Gallus gallus domesticus (White Leghorns). The toxic effects as observed 10 or 21 days after medication include a statistically significant reduction in haemoglobin (Hb) content, haematocrit (Ht), protein and serum glutamate pyruvate transaminase (SGPT), and an increase in glucose, serum glutamate oxaloacetate transaminase (SGOT) and serum acid phosphatase (SAP) activities of male and female chicken. The changes in other haematological parameters were generally insignificant, except for one or two doses in RBC, WBC, mean corpuscular haemoglobin concentration (MCHC) and chloride. A significant inhibition of RBC acetylcholinesterase was noticed after 21 days of dosing only at the high dose (150 mg kg-1) in hens. The decrease in food intake and body weights of males and females indicated the overt signs of toxicity. In addition to haematological alterations, the results suggest both hepatotoxic and stress effects and pinpoint that these early biochemical changes induced by Isoprocarb may be predictive of pesticide toxicity.

Animals↗
PubMed1989

Prevalence of hepatitis B surface antigen (HBsAg) among prostitutes at Dhaka.

One hundred prostitutes were studied with an aim to acquire more insight on the role of sexual transmission of HBsAg and to detect carrier state among them. All subjects were interviewed and their serum samples were tested for HBsAg by reverse passive haemagglutination method (RPHA). Eleven (11%) of the prostitutes were found to be positive for HBsAg. Their mean age was 19.3 +/- 4.9 years. The mean duration in the profession was 2.5 +/- 1.6 years. Mean number of clients for each woman per 24 hours was 10.7 +/- 1.2. Most of the prostitutes (84%) were lacking knowledge about spread and contact of the disease.

Adolescent↗
PubMed1989

Prevalence of hepatitis B surface antigen (HBsAg) among parenteral drug abusers at Dhaka.

One hundred parenteral drug abusers were studied with an aim to detect HBsAg in their sera and to know carrier state among them. All subjects, were interviewed and their serum samples were tested for HBsAg by reverse passive haem-agglutination method (RPHA). Eight percent of the drug addicts were found to be positive for HBsAg. The mean age of addicts was 23.65 +/- 5.06 years. Ninety two percent were educated (above class VIII) and 59 percent were students. Forty three percent were influenced by friends to develop this habit and 34 percent became addicted out of frustration. Forty four percent addicts were using disposable syringes and needles and 32 percent were sharing their syringes and needles among themselves. Nineteen percent addicts had past history of jaundice. Fifty seven percent had extra-marital sexual life and 64 percent were lacking in knowledge of spread, or contraction of disease by their habits.

Adolescent↗
PubMed1988

Species differences in brain acetylcholinesterase and neuropathic target esterase response to monocrotophos.

The species differences in the neurotoxic and delayed neurotoxic potential of monocrotophos (MCP) were assessed by determining the in vitro inhibition of brain Acetylcholinesterase (AChE) and Neuropathic target esterase (NTE) in rat, mice, chicken and pigeon. Based on I50 values, chicken brain AChE was found to be most sensitive to inhibition by MCP followed by rat whereas mice and pigeon were almost equally sensitive to AChE inhibition by MCP. The data on NTE inhibition by MCP in all the four species indicate the non-delayed neurotoxic nature of MCP. The results show that although there are many common features of the brain AChE and NTE of the four non-target organisms studied, certain species characteristics exist in their inhibition responses to MCP.

Acetylcholinesterase↗