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Biomedical subjects

A Haque

Publications and source records attributed to A Haque.

At least 55 records · Page 3Linked to original sources

Infection of mice by a Toxoplasma gondii isolate from an AIDS patient: virulence and activation of hosts' immune responses are independent of parasite genotype.

Virulence of a Toxoplasma gondii isolate from an AIDS patient (designated as PTN) was compared with that of PLK, a variant of P-strain. Virulence was assessed in term of host survival upon inoculation in different strains of mice. All C57BL/6 mice died of acute toxoplasmosis by 7-10 days following intraperitoneal infection with 1 x 105 tachyzoites of PTN and 40% of BALB/c died on day 23 of infection, whereas 100% CBA/J infected with the same dose of PTN survived, as did outbred Swiss Webster mice. All C57BL/6, BALB/c, CBA/J, or Swiss Webster died of acute toxoplasmosis by 3-9 days postinfection upon inoculation with same dose of tachyzoites of the PLK strain. Further studies in CBA/J mice demonstrated that mice infected with PTN elicited a significantly higher lymphoproliferative response to crosslinked anti-CD3 mAb or Con A than PLK infected mice, and augmented production of TNFalpha, lower levels of nitrite and a higher number of NK cells. Genetical analysis indicated that both PLK and PTN strains of T. gondii are from type ll. Interestingly, being of the same genotype, the later showed less virulence upon inoculation in mice and had greater capacity to activate host immune system than the PLK strain.

AIDS-Related Opportunistic Infections↗

Transformed migraine is a cause of chronic daily headaches.

Chronic daily headaches (CDH) consist of episodes of head pain occurring daily; more than 15 days each month; often associated with a history of migraine, with or without aura; or with a history of tension-type headaches occurring alone or both occurring together. Chronic daily headaches are frequently associated with rebound headaches after ergotamine, barbiturate, caffeine, and analgesic abuse. We previously reported that migraineurs with typical intermittent headaches exhibited excessive cerebral cortical vasodilation after oral acetazolamide which usually precipitated and reproduced their typical headaches. In the present study, cerebral vasodilator responses were tested by measuring changes in local cerebral blood flow (Delta LCBF) utilizing xenon-contrasted CT scanning, before and after oral administration of 14.3 mg/kg of acetazolamide, in 11 patients with CDH. The results were compared with 12 age-matched typical migraineurs, with and without aura, who had a history of migraine attacks occurring at intervals of 1 month or longer. Global and subcortical gray and white matter Delta LCBFs were quantitated and compared between both groups. After acetazolamide, Delta LCBF increased in cortical gray matter by 11.8% among patients with CDH and by 16.7% among migraineurs, with no significant differences between groups. Typical migraine attacks were provoked by acetazolamide in 9 patients (82%) with CDH and in 11 (92%) migraineurs with intermittent headaches. These observations are taken as evidence that at least 82% of patients with CDH have transformed migraine as judged by the provocation by acetazolamide of typical migraine attacks associated with excessive Delta LCBF increases. Serotonin agonists should be considered in the treatment of CDH to avoid ergotamine, caffeine, barbiturate, and analgesic abuse.

Acetazolamide↗

Alteration of intracellular calcium flux and impairment of nuclear factor-AT translocation in T cells during acute Toxoplasma gondii infection in mice.

Down-regulation of host immune response to Toxoplasma gondii is associated with the expression of specific cytokines, in particular IL-10, and the induction of CD4+ T cell anergy. In the present study we report that the expression of both CD4 and CD2 antigen is down-regulated during the acute phase of infection. A decrease in the expression of CD2 was apparent during the acute phase of T. gondii infection in three genetically distinct strains of mice, CBA/J, C57BL/6, and BALB/c. The lymphoproliferative response induced by cross-linked anti-CD3 mAb or by Con A was markedly depressed. This suppressed response was associated with a reduction in the influx of Ca2+. We have examined whether lymphocytes from T. gondii mice maintain NF-AT transcription factors in the nucleus where they participate in the Ca2+-dependent induction of genes required for lymphocyte activation and proliferation. Immunofluorescence with confocal microscopy using an Ab to NF-ATc demonstrates a decrease in translocation of NF-ATc in T lymphocytes from acutely infected mice. Together, these results suggest that the defect in T cell expansion that occurs during acute murine toxoplasmosis is related to reduced activity of NF-AT, a calcium-dependent transcription factor required for T cell proliferation.

Acute Disease↗

Formation of ring-shaped structures on erythrocyte membranes after treatment with botulinolysin, a thiol-activated hemolysin from Clostridium botulinum.

Damage to erythrocyte membranes by botulinolysin (BLY) was studied by electron microscopy, which revealed ring-shaped structures with inner diameters and widths of approximately 32 and 6.7 nm, respectively. BLY bound to membranes at 0 degrees C, but subsequent treatment with glutaraldehyde prevented ring formation during further incubation at 37 degrees C. Zn2+ ions inhibited ring formation but not binding of BLY to membranes.

Bacterial Toxins↗

Evidence of osteolathyrism among patients suffering from neurolathyrism in Bangladesh.

In a study of 500 patients suffering from neurolathyrism in Bangladesh it was found that 60 (all male) complained of bone pain and showed skeletal deformities suggestive of osteolathyrism. On X-ray examination a failure of fusion in both vertebral and iliac epiphyses was found in two patients. At the age of these patients (30 and 37 years) such failure was considered a clear evidence of osteolathyrism. All 60 patients were accustomed to eating the green parts of Lathyrus sativus, which contain 2-cyanoethyl-isoxazolin-5-one, a compound that chemically and metabolically can produce the osteolathyrogen beta-aminopropionitrile (BAPN), as well as foods made from the seeds of the same plant which contain the neurotoxin 3-N-oxalyl-2,3-diaminopropanoic acid (beta-ODAP).

Adult↗

Botulinolysin, a thiol-activated hemolysin produced by Clostridium botulinum, inhibits endothelium-dependent relaxation of rat aortic ring.

The effects of botulinolysin (Blyn), a thiol-activated hemolysin produced by Clostridium botulinum, on contractility of rat aortic ring were studied in order to clarify an underlying mechanism of vasoconstriction by the toxin observed previously as an increase in perfusion pressure in isolated rat organs. Blyn (30 hemolytic units/ml; HU/ml) itself did not elicit any apparent change in resting tension of the ring. Contractile tension elicited by a high concentration of phenylephrine in endothelium-intact rings increased significantly after treatment with Blyn (30 HU/ml), while phenylephrine-induced contraction of endothelium-denuded rings was not influenced by toxin treatment. In rings with intact endothelium, acetylcholine (ACh)-induced relaxation was significantly inhibited after treatment with Blyn (30, 10, 1 HU/ml). In contrast, relaxation of denuded rings by sodium nitroprusside was not affected by toxin treatment (30 HU/ml). Arginine (10(-4) M) partly reversed the inhibition of ACh-induced relaxation by the toxin (1 HU/ml). Endothelium-dependent relaxation by histamine or adenosine triphosphate was also inhibited by Blyn (1 HU/ml), but the relaxation elicited by calcium ionophore A23187 was not influenced by the toxin. The results indicate that Blyn acts on endothelium and inhibits agonist-induced endothelium-dependent relaxation of blood vessels.

Acetylcholine↗

Direct injection HPLC method for the determination of phenylbutazone and oxyphenylbutazone in serum using a semipermeable surface column.

A direct injection HPLC method has been developed for the determination of phenylbutazone and its active metabolite oxyphenylbutazone in serum using a semipermeable surface (SPS) column. The method is easy to perform and requires 20 microliters of a filtered serum sample. The chromatographic time is less than 13 min using a mobile phase of 15:85 v/v acetonitrile-0.05M phosphate buffer pH 7.5. The method was linear in the range 0.5-20 micrograms ml-1 (r > 0.99, n = 6) with R.S.D. less than 6%. Interday and intraday variability were found to be less than 8.3%. The limit of quantitation and detection were 0.5 and 0.25 microgram ml-1 (s/n > 3), respectively, for both drug and metabolite.

Animals↗

Epidemiological study of lathyrism in northwestern districts of Bangladesh.

Two northwestern districts of Bangladesh with a population of 629,752 were surveyed from June 1991 to March 1993 to detect and follow up lathyrism patients. Out of 2,567 neurological patients, 882 were diagnosed as having lathyrism, giving a prevalence rate of 14.0/10,000. This prevalence was higher among young males: only 12.9% of the patients were female, and only 19.3% of the patients were over 30 years of age at onset of the disease. The average family size was 4.6 members. In the surveyed area, 730 families were evaluated: 622 families had only 1 affected member, and 108 families had 2-8 affected members. Most of the patients were working, while only 4% were not. The majority of the patients had a very low intake of animal protein. A few cases of human T-lymphotropic virus infection and osteolathyrism were found during this study.

Adolescent↗

Inguinal lymph node foreign body granulomas after placement of a silicone rubber (Silflex) implant of the first metatarsophalangeal joint.

We describe a woman who developed foreign body granulomas 8 years after metatarsophalangeal (MTP) joint silicone rubber implantation for hallux rigidus. She developed overnight swelling and tenderness in the inguinal region on the ipsilateral side. Histological evaluation of the lymph node showed foreign body granulomas. Electron microscopy and dispersion x-ray analysis identified the foreign body material in the inguinal lymph node and fibrous capsule surrounding the implant as silicone. Foreign body granulomas of surrounding tissues and regional lymph nodes are infrequently reported postoperative complications in patients with small joint silicone rubber implants. A fractured or eroded implant surface attributed to wear is usually noted at prosthesis excision. Granulomas in normal or enlarged lymph nodes have been described in both symptomatic and asymptomatic patients, with intact or fractured prostheses. Many related joint and lymph node symptoms resolve with removal of the silicone rubber prosthesis.

Adult↗

In vivo treatment with interleukin 2 reduces parasitemia and restores IFN-gamma gene expression and T-cell proliferation during acute murine malaria.

In this study, we describe the functional alterations in the host immune system that occur following acute infection with Plasmodium yoelii. Further, we have addressed the question whether the transient condition of altered immune responsiveness can be restored by a cytokine therapy. The lymphoproliferative response towards concanavalin A (Con A) or to cross-linked anti-CD3 mAb was significantly diminished in acutely infected mice compared to immune and normal animals. This condition was associated with poor production of IL-2. In vivo treatment with recombinant IL-2 (rIL-2) resulted in marked diminution of parasitemia (from 24% +/- 6% to 8% +/- 3%) in mice during the acute phase of infection. Despite this diminution in parasitemia, 70% of the IL-2 treated mice died by day 17 post infection. In vivo treatment with rIL-2 led to a partial but significant restoration in lymphoproliferative response to TCR-mediated (cross-linked anti-CD3 mAb) or to Con A-induced stimulation in acutely infected mice. The transcripts for IL-4, IL-5, GM-CSF, and TNF-alpha were expressed in the splenocytes from acutely infected mice not treated with rIL-2. mRNAs for IL-2, IFN-gamma, IL-6, IL-10 which were not detected in acutely infected mice could be reversed by administration of rIL-2 in vivo. We suggest that some of the hyporesponsive T-cells in the acute phase of infection have the potential to be reversed, and this reversal is manifested also at the level of cytokine gene expression.

Animals↗

Plasmodium yoelii in mice: differential induction of cytokine gene expression during hyporesponsiveness induction and restimulation.

Acute Plasmodium yoelii murine malaria is associated with a marked depression of splenic T cell responses. The present study was undertaken to address the question if a defect in T cell proliferation results from a relative increase of a non-T cell population in the spleen or real biological changes occurring in T cells of the spleen after infection. When animals were acutely infected, the splenic cells responded poorly to cross-linked anti-CD3 mAb, Con A, and PWM stimulation. At this stage, a very limited array of cytokine was expressed. We failed to detect the transcripts for IL-2R p55, IL-2, IL-6, IL-10, and IFN-gamma in mice with acute P. yoelii malaria irrespective of the number of splenocytes subjected to RT-PCR. In contrast, late in the infection when mice cleared the parasites and became resistant to reinfection, mRNAs for the above cytokines as well as for IL-4, IL-5, GM-CSF, and TNF-alpha were detectable. During this late phase of infection, lymphocytes proliferated vigorously in response to TCR- and T cell mitogen-mediated stimulation. Surprisingly, during an early phase (as early as 3 days postinfection) with low parasitemia, before the establishment of T cell unresponsiveness, a broad array of cytokine expression including IL-2 and IFN-gamma expression as well as marked lymphoproliferative response upon T cell mitogen- and TCR-mediated stimulation was observed. When the expression of cytokine gene in freshly isolated (ex vivo) splenocytes from P. yoelii-infected animals was investigated, a similar pattern of cytokine profile was detected. We devised a methodology in which RNA from an increasing number of splenocytes (ranging from 1 to 16 million) was used to compensate for any difference in the frequency of splenic T cells between immune and acutely infected mice and to augment target molecules which could be measured simultaneously by PCR. The data presented in this study led us to speculate that "anergy" or relative increase of a non-T cell population cannot account solely for the T cell unresponsiveness in the acute phase of infection. We suggest that inactivation or/and ablation of reactive T cells may explain T cell hyporesponsiveness during acute malaria.

Animals↗

Coronary vasoconstriction is the most probable cause of death of rats intoxicated with botulinolysin, a hemolysin produced by Clostridium botulinum.

The pathophysiology of lethal intoxication by botulinolysin (Blyn) was studied using anesthetized rats and isolated rat organs. Intravenous injection of 10,000 and 1000 hemolytic units (HU) of Blyn killed rats rapidly while 100 HU of the toxin did not. Congestion and edema of lungs were observed at autopsies of the rats killed by intoxication. Hemoglobinemia was obvious in rats injected with 1000 HU of Blyn but not in rats with 10,000 HU. Electrocardiograms of the intoxicated rats showed depression of T waves but not changes characteristic of hyperpotassemia. All the rats injected with the above doses of Blyn showed a rapid fall in arterial blood pressure (BP) immediately after the toxin injection, and BP soon recovered in rats injected with 100 HU, partially and transiently in rats with 1000 HU, and not in rats with 10,000 HU of Blyn. Perfusion of Blyn (1 HU/ml) to isolated rat hearts caused a rapid and marked increase in perfusion pressure and cessation of spontaneous heart beat. Acetylsalicylic acid (10(-3) M) and quinacrine dihydrochloride (10(-5) M) did not essentially influence the effects of Blyn on the isolated hearts, but verapamil (10(-6) M) inhibited at least the initial increase in perfusion pressure elicited by Blyn. Spontaneous contractions of the isolated atria were little influenced by Blyn (60 HU/ml). Perfusion pressures of isolated kidneys, lungs and livers were also increased by Blyn (1 HU/ml). The results indicate that Blyn caused vasoconstriction but had little direct effect on myocardium. Based on the above findings, we conclude that coronary vasoconstriction elicited by direct action of Blyn causes acute cardiac dysfunction leading to systemic hypotension and death of the intoxicated animals.

Animals↗

Inhibitory and excitatory amino acids in cerebrospinal fluid of neurolathyrism patients, a highly prevalent motorneurone disease.

Neurolathyrism is caused by overconsumption of seeds containing 3-N-oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP). Amino acids levels of cerebrospinal fluid (CSF) were studied in 50 patients with neurolathyrism and 12 healthy volunteers. The levels of excitatory amino acids glutamate and aspartate were 281% and 71% respectively of control values. The concentration of inhibitory amino acids glycine and taurine were 277% and 198% respectively of the levels in CSF from control individuals. There was a significant correlation between the level of glycine and the duration of the disease. We also found increased levels of threonine, serine and alanine. In contrast to reports on other motor neurone diseases where an increase of isoleucine was observed we found a significant decrease of isoleucine. The results suggest a disturbance of amino acid metabolism due to excitotoxic damages caused by beta-ODAP, a dietary excitatory amino acid.

Adolescent↗

A Toxoplasma gondii-derived factor(s) stimulates immune downregulation: an in vitro model.

Suppression of the T-cell lymphoproliferative response and downregulation of interleukin 2 (IL-2) production by Toxoplasma gondii has been observed following in vivo infection. In this study, an experimental in vitro murine system was developed to evaluate the kinetics of these responses. Normal splenocytes from uninfected mice were stimulated with either concanavalin A or an anti-CD3 monoclonal antibody and cocultured with Toxoplasma tachyzoites either directly or separated by a transwell. A progressive decline in the lymphoproliferative response was observed as the concentration of parasites in culture increased. Neither heat-killed nor formaldehyde-fixed parasites stimulated this downregulatory response by the splenocytes. A decline in IL-2 production was associated with the decrease in lymphocyte proliferation. The addition of an antibody to IL-10 or heat-inactivated anti-Toxoplasma sera to the culture supernatant partially neutralized the inhibitory effect on lymphocyte proliferation. Cytokine analysis of the responder splenocytes demonstrated a decrease in the message for IL-2 and IL-2 receptor and an increase in IL-10. Together, these observations suggest that during in vitro culture in a murine system, parasite antigens that stimulate the release of a soluble factor(s), such as IL-10, that inhibits proliferation of mitogen-stimulated T cells are expressed.

Animals↗

Study of HTLV-I antibodies in CSF and serum of neurolathyrism patients in Bangladesh.

Neurolathyrism is a form of human spastic paraparesis related to the overconsumption of the legume Lathyrus sativus or grass pea (Khesari in Bangladesh) containing the neurotoxin 3-N-oxalyl-2,3-diaminopropanoic acid (beta-ODAP). The clinical symptoms of neurolathyrism are similar to those of Tropical Spastic Paraparesis. In order to eliminate the proposed causative agent of TSP (HTLV-I) as a potential cause of the symptoms ascribed to neurolathyrism, a total of 444 diagnosed lathyrism patients were screened for HTLV-I antibodies. 50 CSF and 394 serum samples were collected from male (415) and female (29) patients. Only 4 serum samples were found sero-positive for HTLV-I. This agrees with the assumption that overconsumption of beta-ODAP containing Lathyrus seeds, and not HTLV infection, is the causative agent for neurolathyrism.

Adult↗