Aquaporin 1 regulates GTP-induced rapid gating of water in secretory vesicles

The swelling of secretory vesicles has been implicated in exocytosis, but the underlying mechanism of vesicle swelling remains largely unknown. Zymogen granules (ZGs), the membrane-bound secretory vesicles in exocrine pancreas, swell in response to GTP mediated by a G(alpha)i3 protein. Evidence is presented here that the water channel aquaporin-1 (AQP1) is present in the ZG membrane and participates in rapid GTP-induced vesicular water gating and swelling. Isolated ZGs exhibit low basal water permeability. However, exposure of granules to GTP results in a marked potentiation of water entry. Treatment of ZGs with the known water channel inhibitor Hg2+ is accompanied by a reversible loss in both the basal and GTP-stimulatable water entry and vesicle swelling. Introduction of AQP1-specific antibody raised against the carboxyl-terminal domain of AQP1 blocks GTP-stimulable swelling of vesicles. Our results demonstrate that AQP1 associated at the ZG membrane is involved in basal as well as GTP-induced rapid gating of water in ZGs of the exocrine pancreas.     

Beverage choice among native american and african american urban women

BACKGROUND: Little is known about beverage preference, especially among understudied urban minority populations. Also, most studies do not differentiate between beer and malt liquor or among wine, wine coolers, and fortified wine. This article examines whether ethnicity or drinking frequency are associated with beverage choice, considering six types of alcoholic beverages: beer, wine, spirits, malt liquor, fortified wine, and wine coolers. METHODS: Data were analyzed from Native American (n = 70) and African American (n = 129) urban pregnant women who reported drinking in the 12 months before an index pregnancy. A small comparison group of white women (n = 22) was included. Women were queried about their consumption of each of six beverage types during the 12 months before pregnancy. RESULTS: The alcoholic beverage most often used, adjusted for other beverages consumed, was beer, followed in order by spirits, wine coolers, malt liquor, wine, and fortified wine. The Native American women preferred beer, which accounted for one third of total intake. In contrast, malt liquor and spirits each accounted for approximately a quarter of intake among African Americans. Compared with other drinkers, women who drank daily were significantly more likely to choose the beer and wine products with a higher alcohol content. In general, these bivariate results were borne out by multivariate analyses that controlled for age, marital status, and education. CONCLUSIONS: These findings suggest that when accuracy is desired, alcohol studies focusing on urban African American samples (and, to a lesser degree, Native American respondents) should consider not just beer, wine, and spirits consumption, but also stronger beer products, such as malt liquor; stronger wine products, such as fortified wine; and sweeter products, such as wine coolers.     

Spectral karyotyping and interphase FISH reveal abnormalities not detected by conventional G-banding. Implications for treatment stratification of childhood acute lymphoblastic leukaemia: detailed analysis of 70 cases

Seventy uniformly treated children with acute lymphoblastic leukemia were analysed for chromosomal abnormalities with conventional G-banding, spectral karyotyping (SKY) and interphase fluorescent in situ hybridisation (FISH) using probes to detect MLL, BCR/ABL, TEL/AML1 rearrangements and INK4 locus deletions. Numerical and/or structural changes could be identified in 80% of the patients by the use of molecular cytogenetic techniques, whereas abnormalities could be detected in 60% of the patients using G-banding alone. Altogether, 106 structural aberrations were defined by FISH compared to 34 using G-banding. Seventy-four percent of the patients had numerical aberrations, 54% structural aberrations and 20% had no identified aberrations. Twelve cases had prognostically unfavourable chromosomal aberrations that had not been detected in the G-banded analysis. We identified three novel TEL partner breakpoints on 1q41, 8q24 and 21p12, and a recurrent translocation t(1;12)(p32;p13) was found. In addition, two cases displayed amplification (7-15 copies) of AML1. Our results demonstrate the usefulness of SKY and interphase FISH for the identification of novel chromosome aberrations and cytogenetic abnormalities that provide prognostically important information in childhood ALL.     

Smoking and disease severity in rheumatoid arthritis: Association with polymorphism at the glutathione S‐transferase M1 locus

Objective

To determine whether the relationship between smoking and disease severity in women with rheumatoid arthritis (RA) is associated with polymorphism at the glutathione S‐transferase (GST) M1 locus.

Methods

Genotyping for GSTM1 was carried out using polymerase chain reaction methodology on 164 women with established RA. Smoking history was obtained on each patient. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analyses, with correction for age and disease duration.

Results

Ever having smoked was associated with a worse radiographic and functional outcome than was never having smoked. Both past and current smoking were associated with increased disease severity. Stratification by GSTM1 status revealed that polymorphism at this locus affected the relationship between smoking and disease outcome measures. Patients who lacked the GSTM1 gene and had ever smoked had significantly higher Larsen and HAQ scores than did those who lacked the gene and had never smoked. Radiographic outcome in these patients was worse than that in patients who had the GSTM1 gene and who had smoked. The associations were not affected by correction for socioeconomic status. Rheumatoid factor (RF) production was found to be associated with smoking in only the GSTM1‐null patients.

Conclusion

Our data suggest that disease outcome in female RA patients with a history of smoking is significantly worse than in those who have never smoked. Smoking was associated with the most severe disease in patients who carried the GSTM1‐null polymorphism. This association may be due in part to a relationship between the GSTM1 polymorphism and RF production in smokers.

     

The role of primary prophylactic factor replacement therapy in children with severe factor X deficiency

Severe factor X (FX) deficiency is one of the severest inherited coagulation disorders. Clinical manifestations include umbilical cord, mucosal, joint and central nervous system bleeding. Four Irish children with severe FX deficiency presented with umbilical cord bleeding. One developed an intraperitoneal haemorrhage and another an intracranial bleed. Prophylaxis, using intermediate purity Factor IX concentrate, was commenced within the first month of life, necessitating the insertion of central venous access devices in two of the children. All children have normal joint function, suggesting that prophylaxis commenced early in life reduces the incidence of arthropathy and improves quality of life.     

Aggression on inpatient units: Clinical characteristics and consequences

Aggression and violence are widespread in UK Mental Health Trusts, and are accompanied by negative psychological and physiological consequences for both staff and other patients. Patients who are younger, male, and have a history of substance use and psychosis diagnoses are more likely to display aggression; however, patient factors are not solely responsible for violence, and there are complex circumstances that lead to aggression. Indeed, patient–staff interactions lead to a sizeable portion of aggression and violence on inpatient units, thus they cannot be viewed without considering other forms of conflict and containment that occur before, during, and after the aggressive incident. For this reason, we examined sequences of aggressive incidents in conjunction with other conflict and containment methods used to explore whether there were particular profiles to aggressive incidents. In the present study, 522 adult psychiatric inpatients from 84 acute wards were recruited, and there were 1422 incidents of aggression (verbal, physical against objects, and physical). Cluster analysis revealed that aggressive incident sequences could be classified into four separate groups: solo aggression, aggression–rule breaking, aggression–medication, and aggression–containment. Contrary to our expectations, we did not find physical aggression dominant in the aggression–containment cluster, and while verbal aggression occurred primarily in solo aggression, physical aggression also occurred here. This indicates that the management of aggression is variable, and although some patient factors are linked with different clusters, these do not entirely explain the variation.     

Reducing the risk of HIV transmission among men who have sex with men: A feasibility study of the motivational interviewing counseling method

HIV prevalence among Chinese men who have sex with men has rapidly increased in recent years. In this randomized, controlled study, we tested the feasibility and efficacy of motivational interviewing to reduce high‐risk sexual behaviors among this population in Changsha, China. Eighty men who have sex with men were randomly assigned to either the intervention group, in which participants received a three‐session motivational interviewing intervention over 4 weeks, or the control group, in which participants received usual counseling from peer educators. High‐risk behavior indicators and HIV knowledge level were evaluated at baseline and 3 months after the intervention. Motivational interviewing significantly improved consistent anal condom use. However, there was no significant change in consistent condom use for oral sex or in the number of sexual partners over time. HIV knowledge scores improved equally in both groups. This study demonstrated that an intervention using motivational interviewing is feasible and results in increased condom use during anal sex for Chinese men who have sex with men. However, further work must be done to increase the use of condoms during oral sexual encounters.     

Iodine metabolism in the red-spotted newt studied with radioactive tracer and by radioimmunoassay

Thyroidal function in the red-spotted newt was assessed both in ¹²⁵I tracer studies and in the measurement of glandular and circulating thyroxine (T₄) and triiodothyronine (T₃) by radioimmunoassay (RIA). Thyroidal uptake of ¹²⁵I was low, being 0.6% at 2 days and 3.6% at 14 days following injection of the tracer. A significant fraction of the injected dose continued to circulate as inorganic iodide at 7 and 14 days following injection, indicating a low rate of renal clearance for iodine. [¹²⁵I]T₄ represented only 6.2% of thyroidal ¹²⁵I at 2 days post-injection, but this figure had increased to 14% by 14 days, suggesting a slow but significant synthesis of hormone. By RIA the T₄ content in thyroids of animals freshly collected in the field was 3.42 ± 0.16 ug/mg protein, a level comparable to that found in beef thyroids. In contrast T₃ stores in the thyroid of the newt were only 9.1 ± 1.2 ng/mg protein. Although no [¹²⁵I]T₄ was detected in the serum of animals for as long as 21 days after injection, circulating thyroid hormones were detected by RIA at levels of 3.0 ± 0.3 ng T4hn1 and 0.28–0.72 ng T₃/ml in freshly collected animals. The data suggest that T₄ in the serum may arise mainly from peripheral deiodination of T₄. Large amounts of an iodoprotein with electrophoretic properties of thyroglobulin were found in the serum of newts. This protein contained 5% of the serum ¹²⁵I at 2 days postinjection and accounted for 30% of the serum radioactivity at 14 days. In captive newts, serum T₄ levels were three times greater and glandular T₄ levels approximately two times lower than those of freshly collected animals, suggesting that the newt thyroid responds to the stresses of captivity by accelerated release of thyroid hormone.