Evidence on major gene control of cortical index in pedigree data from Middle Dalmatia,Croatia

It was recently reported that the inheritance of the metacarpal cortical index (CI) in the Chuvashian population can be described in terms of a major gene (MG) model. By applying transmission probability tests, the hypothesis was accepted that not only baseline level of CI but also its sex‐specific dependence on age were under control of the same putative large‐effect gene. Using a pedigree sample from the population of the islands of Middle Dalmatia, Croatia (847 observed individuals in 278 pedigrees), data are presented to support the above findings. The following hypotheses were accepted: (i) inheritance of baseline CI in the Croatian population can be attributed to the effect of a MG responsible for about 42% of the variation; (ii) the same MG takes part in the control of the dependence of CI on age, particularly the age at onset of involutive bone changes (inflection point), and of the rate of decrease in CI with age (slope coefficient). Issues related to the assortative mating effect on CI and the determination of the most parsimonious model are discussed. Am. J. Hum. Biol. 13:398–408, 2001. © 2001 Wiley‐Liss, Inc.     

Atypical Ph negative chronic myeloid leukaemia presenting as sudden profound deafness.

A patient with atypical Ph negative chronic myeloid leukaemia presented with the sudden onset of profound deafness. He survived only eight months. Detailed histological investigation performed at necropsy showed loss of ganglion cells and afferent nerve fibres in the cochlea and vestibule associated with extensive fibrosis and new bone formation in the labyrinthine spaces. Both leucophoresis and high dose chemotherapy capable of rapid cytoreduction are recommended in patients with chronic myeloid leukaemia with profound hearing loss, as conventional chemotherapy is rarely followed by recovery.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

Acculturation and psychosocial stress show differential relationships to insulin resistance (HOMA) and body fat distribution in two groups of blacks living in the US Virgin Islands

The objective of this study was to determine whether acculturation and psychosocial stress exert differential effects on body fat distribution and insulin resistance among native-born African Americans and African-Caribbean immigrants living in the US Virgin Islands (USVI). Data collected from a non-diabetic sample of 183 USVI-born African Americans and 296 African-Caribbean immigrants age > 20 on the island of St. Croix, USVI were studied. Information on demographic characteristics, acculturation and psychosocial stress was collected by questionnaire. Anthropometric measurements were taken, and serum glucose and insulin were measured from fasting blood samples. Insulin resistance was estimated by the homeostasis model assessment (HOMA) method. The results showed that in multivariate regression analyses, controlling for age, education, gender, BMI, waist circumference, family history of diabetes, smoking and alcohol consumption, acculturation was independently related to logarithm of HOMA (InHOMA) scores among USVI-born African Americans, but not among African-Caribbean immigrants. In contrast, among USVI-born African Americans psychosocial stress was not significantly related to InHOMA, while among African-Caribbean immigrants psychosocial stress was independently related to InHOMA in models that included BMI, but not in those which included waist circumference. This study suggests that acculturation and psychosocial stress may have a differential effect on body fat distribution and insulin resistance among native-born and immigrant blacks living in the US Virgin Islands.     

Signalling during hypoxia in human T lymphocytes – critical role of the src protein tyrosine kinase p56Lck in the O2 sensitivity of Kv1.3 channels

T lymphocytes encounter hypoxia when they migrate to pathological sites such as tumours and wounds. The inability of T cells to provide an efficient defence at these sites can in part be explained by the hypoxic environment. Kv1.3 channels, important components of the T cell activation process are inhibited by hypoxia and their inhibition accounts for a hypoxia-induced decrease in T cell proliferation. Although Kv1.3 channels play a key role in T cell O₂ sensing, the signalling mechanisms mediating their response to hypoxia are still not understood. In this study, we show that the src-protein tyrosine kinase p56Lck (Lck) is required for Kv1.3 channel response to hypoxia. Pre-exposure to the src inhibitor PP2 abolished the hypoxia-induced inhibition of Kv1.3 channels in primary human T lymphocytes. Moreover, Kv1.3 channel sensitivity to hypoxia was lost in Lck-deficient Jurkat T cells. Further studies with recombinant Kv1.3 channels showed that Kv1.3 channels lack intrinsic O₂ sensitivity, but delivery of Lck into the cells and transfection of a constitutively active Lck (Y505FLck) restored their sensitivity to hypoxia. Although Lck is necessary for the Kv1.3 channel response to hypoxia, it does not directly inhibit Kv1.3 channels. Indeed, under normal oxygen tension, delivery of active Lck into L929 cells and overexpression of Y505FLck did not decrease recombinant Kv1.3 currents. On the contrary, activation of endogenous src kinases increased wild-type Kv1.3 currents in T lymphocytes. Our findings indicate that Lck is required for the acute response to hypoxia of human T lymphocytes as it is necessary to confer O₂ sensitivity on Kv1.3 channels.     

Tritiated-thymidine uptake in mixed leucocyte cultures: effect of specific activity and exposure time

The degree of in vitro transformation of lymphocytes to blast cells can be estimated by measuring the uptake of radioactive precursors into DNA. We have used ³H-thymidine uptake to quantitate blastogenesis in mixed leucocyte cultures. In experiments designed to standardize this procedure, the kinetics of thymidine uptake were studied by adding 4 μCi of ³H-thymidine of varying specific activities to 5-day mixed cultures. With high specific activity (0·194 μg total thymidine/culture), the rate of uptake was constant for only about 6 hr, then declined. There was no further cellular uptake between 8 and 24 hr, even though the total radioactivity of the supernatant medium did not diminish appreciably. This decreasing rate of uptake was at least partly the result of thymidine degradation to thymine and dihydrothymine by cellular enzymes. It is also possible that eventual radiation damage to blast cell nuclei may have retarded DNA synthesis when ³H-thymidine specific activity was high. With decreasing specific activity (up to 19·4 μg thymidine/culture), the rate of uptake became more nearly linear throughout 24 hr exposure to the isotope. The possible effects of thymidine degradation and radiation damage should be considered when measuring radioactive thymidine uptake in vitro, and short labelling times should be used whenever feasible.     

The immune-dependence of schistosomicidal chemotherapy: relative lack of efficacy of an antimonial in Schistosoma mansoni-infected mice deprived of their T-cells and the demonstration of drug-antiserum synergy.

When T-cell deprived CBA mice, infected with Schistosoma mansoni, were treated orally with potassium antimony tartrate, the reduction in size of their worm burdens was less than in similarly treated, immunologically-intact animals. The defect in deprived mice could be restored by the administration of serum obtained from S. mansoni-infected normal mice simultaneously with the drug, but by a different route. A serum component, probably immunoglobulin, obtained from rabbits which had been injected with an extract from S. mansoni adult worms was also found to act synergystically with the antimonial in the chemotherapeutic eradication of S. mansoni worms from immunologically intact mice.     

Physician assistant education in the United States.

As physician assistant (PA) programs developed in the 1960s, curriculum models emerged around the central themes of physician-dependent practice and competency-based education. By 2007, there were 136 accredited programs in the United States, with 108 (79%) offering a master-degree curriculum. PA program preclinical and clinical curricula are typically evenly divided in length, and the typical U.S. PA program has a full-time attendance curriculum of 26.5 continuous months. In academic year 2005-2006, the typical PA student was a 27-year-old white woman with a 3.4 overall grade point average and 29 months of prior health care experience who matriculated with a baccalaureate degree into a master-degree PA program. In the 2005 application cycle, the number of applicants per available seat was 2.25 for both allopathic medical schools and PA programs. The transition to a predominately master-degree curriculum resulted in new challenges for PA faculty development, and the number of PA educators with terminal academic degrees continues to lag behind the educational needs of training programs. The topic of PA specialty training and recognition remains controversial. Although the PA profession has prospered since inception, concerns exist regarding workforce issues such as the appropriate balance of autonomy and supervision, role delineation, and the continuing trend toward specialization. The omission or inaccurate classification of PAs within U.S. health care access and workforce literature projects an incomplete picture, and it is important to consider the contributions PAs have made and will continue to make in addressing the nation's health care needs.