A Hodgkin cell-specific antigen is expressed on a subset of auto- and alloactivated T (helper) lymphoblasts

A Hodgkin cell-specific antigen detected by the monoclonal antibody Ki- 1 was found on T helper lymphocytes after activation by autologous and allogeneic stimulator cells. About 50% of lymphoblasts generated by auto- and alloactivation reacted with the antibody. In contrast, only less than 6% of lymphoblasts stimulated with Con-A, phytohemagglutinin (PHA), or protein A, and none of lymphoblasts activated by oxidative mitogenesis, expressed this antigen. Among several permanent cell lines tested, the K562, MOLT-4, HL-60, and EBV transformed B lymphoblastoid cells reacted with the Ki-1 antibody. The results may indicate possible relationships between the autoreactive subset of T lymphocytes and the pathogenesis of Hodgkin's disease.     

Transient lower esophageal sphincter relaxations are no more frequent in patients with gastroesophageal reflux disease than in asymptomatic volunteers

OBJECTIVES: Studies of the relative frequency of transient lower esophageal sphincter relaxations (TLESRs) in patients with gastroesophageal reflux disease and asymptomatic controls have revealed conflicting data. We have therefore studied the frequency of TLESRs and the frequency and mechanisms of acid reflux episodes in patients with gastroesophageal reflux disease and age- and sex-matched asymptomatic controls using standardized criteria. METHODS: Ten patients with symptomatic gastroesophageal reflux disease (four male, aged 50 [30-59] yr) and 10 asymptomatic matched volunteers (four male, aged 50 [32-59] yr) were studied. Esophageal, lower esophageal sphincter, and gastric manometric and esophageal pH readings were recorded for 1 h before and 1 h after a 200-kcal, 150 ml long-chain triglyceride meal. RESULTS: TLESR frequency increased after the meal in both volunteers (median 0 [range = 0-3] to 3 [0-8] per hour,p < 0.01) and patients (1 [0-6] to 2.5 [0-9] per hour, p = 0.08). There was no significant difference in the frequency of TLESRs between volunteers and patients. TLESRs were more likely to be associated with acid reflux in patients (65% vs 37%, p = 0.03), whereas volunteers were more likely to reflux gas or liquid without acid (30% vs 3.0%, p = 0.01). CONCLUSIONS: TLESRs are no more frequent in patients with gastroesophageal reflux disease than age- and sex-matched asymptomatic volunteers. However, when TLESRs occur in patients, they are twice as likely to be associated with acid reflux.     

Genetic influences in gastro-oesophageal reflux disease: a twin study

BACKGROUND: A number of families have been described which include multiple members with symptomatic, endoscopic, or complicated gastro-oesophageal reflux disease (GORD). First degree relatives of patients with GORD are more likely to suffer with GORD symptoms. These observations raise the possibility of a genetic contribution to the aetiology of GORD. AIMS: To determine the relative contribution of genetic factors to GORD by evaluating GORD symptoms in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A total of 4480 unselected twin pairs, identified from a national volunteer twin register, were asked to complete a validated symptom questionnaire. GORD was defined as symptoms of heartburn or acid regurgitation at least weekly during the past year. RESULTS: Replies were obtained from 5032 subjects (56% response rate). A total of 1960 twin pairs were evaluable: 928 MZ pairs (86 male pairs, mean (SD) age 52 (13) (range 19-81) years) and 1032 DZ pairs (71 male pairs, mean age 52 (13) (20-82) years). The prevalence of GORD among both groups of twins was 18%. Casewise concordance rates were significantly higher for MZ than DZ twins (42% v 26%; p<0.001). Multifactorial liability threshold modelling suggests that additive genetic effects combined with unique environmental factors provide the best model for GORD. Heritability estimates suggest that 43% (95% confidence interval 32-55%) of the variance in liability to GORD is due to additive genetic factors. CONCLUSIONS: There is a substantial genetic contribution to the aetiology of GORD.     

Administration of low doses of MK-801 during ethanol withdrawal in the developing rat pup attenuates alcohol's teratogenic effects

BACKGROUND: Alcohol exposure during development can produce severe and long-lasting central nervous system damage and consequent behavioral alterations. Recent evidence suggests that NMDA receptor-mediated excitotoxicity during periods of withdrawal may contribute to this damage. We have demonstrated that blocking the NMDA receptor with MK-801 during alcohol withdrawal can attenuate ethanol's adverse effects on behavioral development in the rat. This study examined the dose dependency of MK-801's ability to mitigate ethanol's teratogenic effects. METHODS: Neonatal rat pups were exposed to 6.0 g/kg of ethanol in a binge-like manner on postnatal day (PD) 6, a period of brain development equivalent to a portion of the human third trimester. Alcohol administration was accomplished with an artificial rearing procedure. Twenty-one hours after ethanol treatment, pups were injected intraperitoneally with one of four doses of MK-801 (0.05, 0.1, 0.5, or 1.0 mg/kg) or saline vehicle. An artificially reared control and a normally reared control group were included. On PD 18-19, activity level was monitored, and on PD 40-42, serial spatial discrimination reversal learning was assessed. RESULTS: Alcohol exposure on PD 6 produced significant increases in activity level and deficits in reversal learning. These alcohol-induced behavioral alterations were significantly attenuated in subjects treated with one of the three lower doses (0.05-0.5 mg/kg) of MK-801 during withdrawal. The performance of ethanol-exposed subjects treated with the high dose of MK-801 (1.0 mg/kg) did not differ from that of the Ethanol Only group. CONCLUSIONS: These data suggest that alterations in NMDA receptor activation during alcohol withdrawal contribute to the neuropathology and consequent behavioral alterations associated with developmental alcohol exposure. These data have important implications for pregnant women and newborns undergoing ethanol withdrawal.     

Hypertension in a Brazilian Urban Slum Population

Low- and middle-income countries account for the majority of hypertension disease burden. However, little is known about the distribution of this illness within subpopulations of these countries, particularly among those who live in urban informal settlements. A cross-sectional hypertension survey was conducted in 2003 among 5649 adult residents of a slum settlement in the city of Salvador, Brazil. Hypertension was defined as either an elevated arterial systolic (≥140 mmHg) or diastolic (≥90 mmHg) blood pressure. Sex-specific multivariable models of systolic blood pressure were constructed to identify factors associated with elevated blood pressure. The prevalence of hypertension in the population 18 years and older was 21 % (1162/5649). Men had 1.2 times the risk of hypertension compared with women (95 % confidence intervals (CI), 1.05, 1.36). Increasing age and lack of any schooling, particularly for women, were also significantly associated with elevated blood pressure (p < 0.05). There was also a direct association between men who were black and an elevated blood pressure. Among those who were hypertensive, 65.5 % were aware of their condition, and only 36.3 % of those aware were actively using anti-hypertensive medications. Men were less likely to be aware of their diagnosis or to use medications (p < 0.01 for both) than women. The prevalence of hypertension in this slum community was lower than reported frequencies in the non-slum population of Brazil and Salvador, yet both disease awareness and treatment frequency were low. Further research on hypertension and other chronic non-communicable diseases in slum populations is urgently needed to guide prevention and treatment efforts in this growing population.     

The effect of hyperthyroidism and hypothyroidism on alpha 1- and alpha 2-adrenergic responsiveness in rat aortic smooth muscle

We report the role of thyroid hormones on in vitro responsiveness of rat aortic smooth muscle to alpha-adrenergic stimulation. Four groups of rats: hypothyroid, hyperthyroid, thyroxine (0.1 mg/kg) treated hypothyroid and controls were employed. Response of alpha 1- and alpha 2-adrenoceptors was evoked with 6 incremental doses (10(-9) to 10(-4) M) of preferential alpha 1-agonist, phenylephrine and alpha 2-agonist, clonidine respectively. alpha 1-Adrenoceptors were also evoked by phenylephrine after blockade of alpha 2-adrenoceptors with 10(-7) M yohimbine. Similarly, alpha 2-adrenoceptors were stimulated with clonidine after blocking alpha 1-adrenoceptors with selective antagonists prazosin (10(-7) M). Aortic responsiveness to alpha-agonist norepinephrine was compared between the aortae of hypothyroid and euthyroid rats after blockade of alpha 2-adrenoceptors with 10(-4) M corynanthine. We report that in hypothyroid aortae, alpha 1-adrenergic response was significantly decreased, the dose response curve shifted to the right and the maximal response was 30% less than the normal; alpha 2-adrenergic response was completely inhibited in hypothyroid state; also, IP injections of 0.1 mg/kg thyroxine twice in 48 h to thyroidectomized rats reversed the effects of hypothyroidism on both alpha 1- and alpha 2-adrenergic response. Hyperthyroidism did not alter alpha 1- and alpha 2-adrenergic response. These results signify the role of thyroid hormones in the regulation of alpha-adrenergic response in rat aortae.     

Differential antibody recognition of FC27-like Plasmodium falciparum merozoite surface protein MSP2 antigens which lack 12 amino acid repeats

Three alleles of the FC27-type allelic family of the MSP2 gene of the malaria parasite Plasmodium falciparum have been sequenced from parasites from the field (The Gambia and Tanzania). These alleles lack the 12 amino acid repeat units which are usual in this family of MSP2 alleles. We have investigated the recognition by sera from an endemic area (The Gambia) of three recombinant MSP2 proteins that have 5, 1 and no copies of this repeat region. Antibody recognition of these recombinant proteins varied according to the number of repeats present. High titre antibody levels were seen with most sera using the recombinant protein with 5 × 12-mer repeats, whereas only low responses were measured using proteins containing 1 or no 12-mer repeats. Several sera entirely failed to recognise the protein which lacked 12-mer repeats. The data suggest that variation in the number of tandem repeat sequences could allow the parasite to avoid high avidity antibody binding and this may allow escape from immune recognition.