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Biomedical subjects

M A Majid

Publications and source records attributed to M A Majid.

9 recordsLinked to original sources

Characterization of ATP receptor which mediates norepinephrine release in PC12 cells.

PC12 cells, a rat pheochromocytoma cell line, has been reported to release norepinephrine in response to extracellular ATP in the presence of extracellular Ca2+. The potency order of ATP analogues was adenosine 5'-O-(3-thiotriphosphate) greater than ATP greater than adenosine 5'-O-(1-thiotriphosphate) = 2-methylthioadenosine 5'-triphosphate (MeSATP) greater than 2'- and 3'-O-(4-benzoyl-benzoyl)ATP (BzATP) greater than ADP greater than 5-adenylylimidodiphosphate. Adenosine 5'-O-(2-thiodiphosphate), beta, gamma-methyleneadenosine 5'-triphosphate, AMP and adenosine were inactive. The ATP action in the absence of extracellular Ca2+, suggests a small but appreciable contribution of intracellular Ca2+ mobilization, for norepinephrine release. However, for some ATP derivatives, like BzATP, almost no contribution of the phospholipase C-Ca2+ pathway is suggested, based on their low activity in inositol phosphates production. To identify the ATP-receptor protein, PC12 cell membranes were photoaffinity-labeled with [32P]BzATP. SDS-PAGE analysis showed that a 53-kDa protein labeling was inhibited by ATP and its derivatives, as well as by P2-antagonists, suramin and reactive blue 2, which inhibit the nucleotide-induced norepinephrine release. The inhibitory activity of the nucleotides was, in parallel with their potency, to induce norepinephrine release. Despite their inability to release norepinephrine, GTP and GTP gamma S inhibited the BzATP labeling, suggesting the participation of a putative G protein in the ATP-receptor-mediated actions. We suggest that the 53-kDa protein on the PC12 cell surface is an ATP receptor, which mediates the norepinephrine release, depending, mainly, on extracellular Ca2+ gating.

Adenosine Triphosphate

Change of intracellular calcium of neural cells induced by extracellular ATP.

Exposure of various neural cells to ATP increased intracellular Ca2+ and the production of inositol trisphosphate. The Ca2+ responses were also observed in the absence of extracellular Ca2+, suggesting that a part of Ca2+ mobilization took place from cytosolic storage. Since adenosine had no effect on intracellular Ca2+ increment, ATP appears to act through a P2-purinergic receptor. Islet-activating protein or pertussis toxin pretreatment hardly influenced the increase in intracellular Ca2+ and inositol trisphosphate production induced by ATP, suggesting that IAP-sensitive GTP-binding proteins do not play a practical role in this reaction.

Adenosine

Evaluation of two intravenous rehydration solutions in cholera and non-cholera diarrhoea.

A clinical trial was carried out with 126 male patients over 2 years of age suffering from diarrhoea requiring intravenous rehydration, 80 of the patients suffering from cholera and 46 from non-cholera diarrhoea. A new "diarrhoea treatment solution" (DTS) containing sodium at a concentration of 118 mmol/litre and glucose at 44 mmol/litre was compared with the usual Dacca intravenous solution (DS) which has a sodium concentration of 133 mmol/litre and contains no glucose. The other constituents and their concentrations were the same in both solutions. All the patients responded well clinically and made an uneventful recovery. Oral water intake measured during the first 24 h was higher in the group receiving the DS. This group also excreted a significantly higher quantity of sodium in the urine. A significant fall in the level of blood glucose from the admission values occurred in both the groups; the fall was relatively less in the DTS group, this solution containing 44 mmol of glucose per litre. Further work is required to find the optimum concentration of glucose in the solution for infants and young children.

Child

Hemolytic-uremic syndrome after shigellosis. Relation to endotoxemia and circulating immune complexes.

To investigate three possible causes of the acute hemolysis in the hemolytic-uremic syndrome, we studied prospectively 207 children and 34 adults with shigellosis in Bangladesh. Nineteen children showed acute hemolytic anemia, a leukemoid reaction, thrombocytopenia and oliguria; nine other had, in addition, a serum urea nitrogen level of over 100 mg per diciliter. Eight of the nine had pseudomembranous colitis, and six of the nine died. The frequency of bacteremia was similar in all grades of shigellosis. Circulating immune complexes were found in 10 of 20 patients with uncomplicated shigellosis and in four of six with severe hemolytic-uremic syndrome. Limulus assay for endotoxemia was positive in nine of 18 patients with hemolysis (50 per cent) and three of 61 with uncomplicated shigellosis (5 per cent) (P less than 0.001). These data support the hypothesis that severe colitis in shigellosis is associated with circulating endotoxin from the colon producing coagulopathy, renal microangiopathy and hemolytic anemia.

Adolescent

Effects of doxycycline in actively purging cholera patients: a double-blind clinical trial.

In 51 actively purging cholera patients the efficacy of doxycycline, a long-acting tetracycline, was compared with a placebo and tetracycline hydrochloride. Seventeen patients who were given doxycycline at the recommended dose of 2 mg/kg at the beginning of the study, at 12 h, and at the repeated dose once daily purged a mean volume of 5.1 liters of stool and received an average of 5.7 liters of intravenous fluid. Nineteen patients receiving the placebo purged 10.1 liters of stool and received 9.7 liters of fluid. Fifteen patients given tetracycline hydrochloride at 6-h intervals passed 4.8 liters of stool and received 5.5 liters of fluid. The durations of diarrhea calculated in 8-h periods were 3.5, 8.0, and 4.1 h in the respective groups receiving doxycycline, placebo, and tetracycline. The differences between the doxycycline and placebo treatments and the tetracycline and placebo treatments were statistically significant. Those receiving doxycycline became vibrio-free in about 3 days as compared with 2 days for those receiving tetracycline; the group given the placebo were vibrio positive for the duration of their hospitalization. The results show that in the treatment of cholera the administration of doxycycline once daily has effects equal to those when tetracycline is administered at 6-h intervals. This is a distinct advantage because it decreases the demand on nursing personnel in epidemics. Also, doxycycline may be safely administered in cases of suspected renal failure from prolonged shock in cholera.

Cholera

Epidemiology of organomercury poisoning in Iraq. I. Incidence in a defined area and relationship to the eating of contaminated bread.

A survey was carried out in a defined area in rural Iraq where there had been many cases of organomercury poisoning following the consumption of bread contaminated by mercury, in order to determine the true incidence of the disorder. The results were compared with those obtained from a similar rural area from which few cases had been reported. A questionnaire was used to determine the amount of contaminated bread eaten and the frequency of symptoms; a simple clinical examination was performed and blood and hair samples were collected for estimation of total mercury concentration. Of 700 people over the age of 5 years in the high-exposure area, 66% admitted to having eaten contaminated bread, while none of the 864 persons in the low exposure area had done so. The mean period during which contaminated bread was eaten was 32 days, but some people had eaten it for as long as 3 months. A mean of 121 loaves was eaten, the maximum being 480 loaves. For the mean number of loaves the intake of methylmercury was likely to have been between 80 mg and 250 mg, but the people who had consumed the largest amount of contaminated bread may have ingested up to 1 000 mg of methylmercury over a 3-month period. Of those with signs of alkylmercury poisoning at the time of the survey, 80% had eaten more than 100 loaves, and 53 (71%) out of 75 persons who had eaten more than 200 loaves showed some evidence of poisoning.The incidence rate for poisoning was estimated at 271 per 1 000; this figure includes a mortality rate of 59 per 1 000, 32 per 1 000 cases with severe disability, 41 per 1 000 cases with mild or moderate disability and 138 per 1 000 cases with only subjective evidence of poisoning at the time of the study.

Adolescent

Epidemiology of organomercury poisoning in Iraq. II. Relationship of mercury levels in blood and hair to exposure and to clinical findings.

In the survey described by Al-Mufti et al. (see page 23) blood and hair samples were analysed for total mercury by modified atomic absorption spectrophotometry. The hair samples were divided into 2.5-cm segments and analysed consecutively. The mean blood levels were 34 ng/ml and 7 ng/ml, respectively in those who had and those who had not eaten contaminated bread.Corresponding mean maximum hair mercury values were 136 mug/g and 5 mug/g, respectively. Hair mercury values provided a better discrimination between different categories of exposure than blood mercury values at the time the survey was performed, some months after the end of the outbreak. Those persons who had not eaten contaminated bread but who lived in the area of high exposure had hair mercury values between the values of those who had eaten and those who had not eaten contaminated bread and who lived in the area of low exposure. Sequential estimation of mercury in 2.5-cm segments of hair in women gave information on the period of accumulation of mercury more than 1 year before the time of collection of the samples. It was possible to show an approximate relationship between the maximum hair mercury value and the amount of contaminated bread eaten. The match between the blood mercury level and the severity of poisoning was poor, owing to the length of time that had elapsed between the onset of poisoning and the sampling. With hair mercury, while the group results showed a good relation to the severity of poisoning, in individual cases the match was less good, especially in those persons where an insufficient length of hair was available for analysis. Biological variation in sensitivity to methylmercury was also likely to have been an important factor.

Adolescent

Epidemiology of organomercury poisoning in Iraq. III. Clinical features and their changes with time.

Three categories of mercury poisoning were defined in the survey described by Al-Mufti et al. (see page 23) and the age-specific incidence rates for these are given. Persons with physical signs consistent with a diagnosis of organomercury poisoning were allocated to categories of severe disability or mild/moderate disability. However, the largest category consisted of persons who had symptoms but no readily elicitable physical signs at the time of the survey. These symptoms followed a consistent pattern with paraesthesia involving the lips and/or circumoral region or trunk and difficulty with walking, described as weakness or unsteadiness of the legs, and in some cases repeated falls, forming the most commonly occurring symptom complex. Mean maximum hair mercury levels differentiated this group very clearly from the group with no symptoms of mercury poisoning. Very few people in the area of low exposure complained of such symptoms; where they did occur they were less well related to the time of the outbreak and showed little tendency to improve. Most people reported improvement in their symptoms by the time of the survey, with more improvement in some symptoms than in others. However, it is not known whether those people with symptoms only at the time of the survey had had at an earlier stage mild signs which had cleared. It was thought unlikely that further substantial improvement would occur in those persons with disability at the time of the survey.

Adolescent