Huntington disease-linked locusD4S111 exposed as the α-l-iduronidase gene

-l-Iduronidase (IDUA) has been intensively studied due to its causative role in mucopolysaccharidosis type I (Hurler, Scheie and Hurler/Scheie syndromes). The recent cloning of a human IDUA cDNA has resulted in a reevaluation of the chromosomal location of this gene. Previously assigned to chromosome 22, IDUA now has been localized to 4p16.3, the region of chromosome 4 associated with Huntington's disease (HD). The existence of a battery of cloned DNA, physical map information, and genetic polymorphism data for this region has allowed the rapid fine mapping of IDUA within the terminal cytogenetic band of 4p. IDUA was found to be coincident with D4S111, an anonymous locus displaying a highly informative multiallele DNA polymorphism. This map location, 1.1×10⁶ bp from the telomere, makes IDUA the most distal cloned gene assigned to 4p. However, it falls within a segment of 4p16.3 that has been eliminated from the HD candidate region, excluding a role for IDUA in this disorder.     

Detection of cytomegalovirus infection during a vaccine clinical trial in healthy young women: seroconversion and viral shedding.

BACKGROUND: An antibody method based on absorption of serum with cytomegalovirus (CMV) glycoprotein B (gB) was developed for detection of infection during clinical trials of CMV gB vaccine. Previous study showed that this method detected the antibody response to infection and was negative with vaccine induced immunity. OBJECTIVES: In an ongoing efficacy trial of CMV gB vaccine the ability of the gB-absorbed CMV IgG assay to detect CMV infection was assessed and compared with viral culture results. STUDY DESIGN: Two hundred and ninety two healthy, seronegative young women in a phase II, double-blind, placebo-controlled, clinical trial of recombinant CMV gB vaccine (sanofi pasteur) with MF59 adjuvant (Chiron) were randomized to receive CMV gB vaccine or placebo (1:1) on a 0, 1 and 6 month schedule. Participants were screened every 3 months for CMV infection using the gB-absorbed CMV IgG assay, and a subgroup was also screened for infection with viral cultures. Viral culture (urine, vaginal swab and saliva) was used to confirm CMV infection in all subjects with a positive gB-absorbed CMV IgG result. RESULTS: Evidence of CMV infection (gB-absorbed CMV IgG levels>or=5.0 AU/ml) was found in 23/292 (7.88%) study participants. The gB-absorbed CMV IgG levels of their first positive serum ranged from 15.7 to 251.0 AU/ml with a mean of 77.0 AU/ml and a median of 44.9 AU/ml. Cytomegalovirus was isolated from all 23 of them from culture specimens collected after their first positive gB-absorbed CMV IgG. The time to first CMV positive culture from first positive gB-absorbed CMV IgG ranged from 0 to 12 weeks with a median of 2 weeks. CONCLUSIONS: The gB-absorbed CMV IgG assay detects CMV infection in CMV gB vaccine clinical trials earlier and more rapidly than virus culture and does not reveal whether subjects received CMV gB vaccine or placebo.     

Glucose preferences in wild and domestic guinea pigs

Male wild (Cavia aperea) and domestic (C. porcellus) guinea pigs were tested in two-bottle choice tests for preferences between glucose solutions of different concentrations and de-ionized water. Wild males showed significant preferences for concentrations between 0.025 and 0.4 M glucose while domestic males preferred only the 0.2 M glucose solution to de-ionized water. C. aperea males also consumed significantly greater volumes of liquid per kg body $\text{wt.}{}^{\mathrm{<mtext>3</mtext><mtext>4</mtext>}}$ during the glucose tests than did the C. porcellus males. These comparative results contrast sharply with those obtained by other authors with wild and domestic Norway rats.     

Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Current dietary therapy for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency consists of fasting avoidance, and limiting long-chain fatty acid (LCFA) intake. This study reports the relationship of dietary intake and metabolic control as measured by plasma acylcarnitine and organic acid profiles in 10 children with LCHAD or TFP deficiency followed for 1 year. Subjects consumed an average of 11% of caloric intake as dietary LCFA, 11% as MCT, 12% as protein, and 66% as carbohydrate. Plasma levels of hydroxypalmitoleic acid, hydroxyoleic, and hydroxylinoleic carnitine esters positively correlated with total LCFA intake and negatively correlated with MCT intake suggesting that as dietary intake of LCFA decreases and MCT intake increases, there is a corresponding decrease in plasma hydroxyacylcarnitines. There was no correlation between plasma acylcarnitines and level of carnitine supplementation. Dietary intake of fat-soluble vitamins E and K was deficient. Dietary intake and plasma levels of essential fatty acids, linoleic and linolenic acid, were deficient. On this dietary regimen, the majority of subjects were healthy with no episodes of metabolic decompensation. Our data suggest that an LCHAD or TFP-deficient patient should adhere to a diet providing age-appropriate protein and limited LCFA intake (10% of total energy) while providing 10-20% of energy as MCT and a daily multi-vitamin and mineral (MVM) supplement that includes all of the fat-soluble vitamins. The diet should be supplemented with vegetable oils as part of the 10% total LCFA intake to provide essential fatty acids.     

Effects of racist provocation and social support on cardiovascular reactivity in african american women

It has been speculated that exposure to the chronic stress of racism contributes to the high rates of hypertension among African Americans. Social support may buffer the effects of stress on cardiovascular (CV) health by attenuating stress-induced CV responses that have been linked to hypertension. In this study we investigated the effects of racism and social support on CV reactivity in African American women. Participants showed greater increases in CV and emotional responses while responding and listening to racist provocation. Augmented blood pressure (BP) persisted through recovery following racial stress. Participants receiving no support showed the greatest increases in anger during racist provocation. No significant effects were seen for support on CV reactivity. These results provide some of the first evidence that interactive confrontation with racism elicits significant increases in CV reactivity and emotional distress. Furthermore, individuals receiving less support may be at greater risk for the potentially health-damaging effects of racial stress. These findings may have significant implications for the health of African Americans.     

Post-marketing surveillance of enalapril: experience in 11 710 hypertensive patients in general practice

Post-marketing surveillance in general practice represents an important part of the monitoring of adverse events associated with newly introduced drugs. Such a study of the angiotensin-converting enzyme inhibitor enalapril maleate has been undertaken in 11 710 patients with essential hypertension. Serious adverse events occurred in 1.7% of patients, though most of these were not thought to be related to the treatment. The incidence rates of death (0.09%), stroke (0.11%) and myocardial infarction (0.15%) were compatible with rates predicted from age, sex and blood pressure considerations. Other events reported were hypotension (0.3%), angioneurotic oedema (0.03%), rash (0.5%), taste disturbance (0.2%) and cough (1.0%). The degree of blood pressure reduction attained was similar to that previously reported from pre-marketing development studies, as was the overall nature and frequency of both serious and non-serious adverse events. The most frequently reported event during enalapril therapy was of an improvement in well-being (19.8%).     

A simple and inexpensive metabolic cage for mice

An inexpensive and easily constructed metabolic cage for mice is presented. This apparatus can reliably monitor food and fluid consumption, as well as urine and fecal output, in a relatively non-intrusive manner.     

Peripheral blood neutrophil production of interleukin-1 receptor antagonist and interleukin-1β

Journal of Clinical Immunology - The objective of this study was to characterize interleukin-1 receptor antagonist (IL-1ra) and interleukin-1β (IL-1β) production by human peripheral blood...     

Spectral reconstruction of high energy photon beams for kernel based dose calculations

A kernel-based dose computation method with finite-size pencil beams (FSPBs) requires knowledge of the photon spectrum. Published methods of indirect spectral measurements using transmission measurements through beam attenuators use mathematical fits with a large number of parameters and constraints. In this study, we examine a simple strategy for fitting transmission data that models important physical characteristics of photon beams produced in clinical linear accelerators. The shape of an unattenuated bremsstrahlung spectrum is known, varying linearly from a maximum at zero energy to a value of zero at a maximum energy. This unattenuated spectrum is altered primarily by absorption of low energy photons by the flattening filter, causing the true spectrum to roll off to zero at low photon energies. A fitting equation models this behavior and has these advantages over previous methods: (1) the equation describes the shape of a bremsstrahlung spectrum based on physical expectations; and (2) only three fit parameters are required with a single constraint. Results for 4 MV and 6 MV accelerators for central axis and off-axis beams show good agreement with the maximum, average and modal energies for known spectra. Previously published models, representations of beam fluence (energy fluence, dN/dE), experimental methods, and the fitting process are discussed.