Allopregnanolone produces hyperphagia by reducing neophobia without altering food palatability.

The neurosteroid allopregnanolone may increase feeding by altering food palatability; however, it may also increase feeding by reducing anxiety (neophobia). Moreover, it is unclear whether this induced hyperphagia is selective to safe, palatable foods only. Male rats were injected with allopregnanolone 20 min prior to behavioral testing. The taste reactivity test was used to examine possible shifts in the palatability of a 0.3 M sucrose solution. A lickometer was used to monitor intake and licking of either a sucrose or sucrose-quinine solution. Sucrose palatability was not enhanced; however, allopregnanolone significantly increased sucrose intake and licking on Test Day 1 when the solution was novel, but not on Test Day 2 when the solution was familiar. Sucrose-quinine intake was not enhanced. Allopregnanolone-induced hyperphagia is not a result of altered sucrose palatability, but rather reflects a reduction in the neophobia elicited by a novel solution; an effect that further seems to be selective to safe, palatable foods.     

GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.

Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n=38 benign, n=27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (P<0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (P<0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.     

Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.     

Socioeconomic deprivation, ethnicity, and stroke mortality in Greater London and south east England.

OBJECTIVE AND SETTING: To examine geographical variation in stroke mortality in Greater London compared with the surrounding South East Region of England. DESIGN: Cross sectional, ecological analysis based on electoral wards. SUBJECTS: Resident population aged 45 years or more. MAIN OUTCOME MEASURE: Age specific stroke mortality rates in five age bands, 1986-92. MAIN OUTCOME MEASURE: Age specific stroke mortality rates in five age bands, 1986-92. MAIN RESULTS: In the 45-54 years age band, stroke mortality rate ratios (95% confidence intervals) relative to the surrounding south east were 2.09 (1.81, 2.4) for Inner London and 1.31 (1.15, 1.5) for Outer London for men and 1.64 (1.4, 1.93) and 1.13 (0.98, 1.31) respectively for women. This gradient diminished and reversed with increasing age. In the 85+ age band, rate ratios were 0.82 (0.76, 0.89) for Inner London and 0.89 (0.84, 0.94) for Outer London for men and 0.8 (0.75, 0.85) and 0.88 (0.84, 0.92) respectively for women. Carstairs deprivation index and the percentages of Afro-Caribbean men and women and Irish born men were significantly and positively correlated with stroke mortality at the ward level. The Carstairs effect diminished with increasing age. Adjustment for these variables diminished or abolished the higher stroke mortality risks in London for younger people but had little effect on the lower risks for older Londoners. CONCLUSIONS: Higher rates of stroke mortality among middle aged adults in Greater London, compared with the surrounding South East Region, are associated with socioeconomic deprivation and ethnicity. These factors do not explain the relatively lower stroke mortality among older Londoners.     

Association of a 70-kDa tyrosine phosphoprotein with the CD16:ζ:γ complex expressed in human natural killer cells

The CD16: ζ: γ receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fcγ domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of ζ and γ are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the ζ subunit and the phospholipase C γ-1 and γ-2 isoforms. Here we show that CD 16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16:ζ:γ receptor complex, results in the tyrosine phosphorylation of a 70 kDa ζ-associated protein (pp70). Similarly, a 70-kDa ζ-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa ζ-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16:ζ:γ complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.     

Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

A comparison of two pancreatin microsphere preparations in cystic fibrosis.

OBJECTIVES: to compare the efficacy and tolerance of Creon and Pancrease in children and young adults with cystic fibrosis. METHODS: a double blind, crossover study of two pH sensitive microsphere preparations of pancreatin (Creon, Pancrease), given in equivalent lipase dosage to 27 children with cystic fibrosis, was conducted. RESULTS: at similar lipase activity no significant difference was found in the following: coefficient of fat absorption (CFA), coefficient of nitrogen absorption (CNA), weight gain, mean adequate daily intake for energy, and subjective symptoms. Three children who had a CFA less than 70% while receiving Pancrease all improved on Creon. No children had a CFA less than 70% while receiving Creon. A significant reduction in the number of capsules required daily to achieve similar control was possible when changing from Pancrease (mean 25/day) to Creon (mean 15/day). Seventy percent of patients preferred Creon and this was likely to be related to a perceived reduction in abdominal pain and stool frequency, and need for less capsules per day. CONCLUSION: Creon and Pancrease are equally effective at doses providing equal lipase activity, however, the reduced number of capsules, fewer symptoms, and possible improvement of more severe steatorrhoea result in an increased patient preference for Creon.     

Stereotaxic needle localization and biopsy of occult breast lesions: first year's experience.

During a 12-month period 115 patients with abnormal mammograms had stereotaxic needle localization and biopsy of nonpalpable breast lesions. The procedure was performed on a Fischer Mammotest II machine (Fischer Imaging; Denver, CO) and the biopsies were taken with a #18 gauge Bard biopsy needle using a Bard biopty gun (distributed by Bard Urological; Covington, GA; manufactured by Radiplast; Uppsala, Sweden). Mammographic lesions were suspicious matrix densities (85), clustered microcalcifications (22), or a combination of both (8). The pathologist recommended open biopsy in 16 per cent (18/115) of the patients. Pathology on the 18 open biopsies revealed that 11 (9 matrix densities and 2 calcifications) were carcinomas and true positives, whereas the other 7 (all matrix densities) were benign mastopathies and false positives. Further analysis of the pathologic data showed that there were three possible diagnoses from the needle biopsies on the patients that later went to open biopsy: cancer (6), very suspicious lesion (9), and slightly suspicious lesion without atypical hyperplasia (3). All 6 cancers were confirmed by open biopsy; about half (5/9) of the very suspicious lesions were cancer and none (0/3) of the slightly suspicious lesions were cancer. More cases, followed by open biopsy, are needed to refine the selection procedure for open biopsy and careful follow-up of the patients who did not have open biopsy will also be needed to determine the false negative rate. Excellent patient acceptance was found and the test was easy to perform in the office without serious complications. Furthermore, the test was cost effective because it avoided open biopsy in 97 patients.     

Community nutrition education for people with coronary heart disease—who attends?

Abstract: A qualitative food-frequency questionnaire was administered by mail to a representative sample of 137 people previously diagnosed with possible or definite myocardial infarct. Seventy-eight per cent of subjects returned a completed questionnaire and were subsequently invited to attend local tastings of foods with the National Heart Foundation Tick of Approval. These tastings were organised and promoted with the active involvement of the local branch of the Australian Cardiac Association. The purpose of this study was to measure voluntary participation by people with coronary heart disease in community nutrition education and to identify any self-selection bias with respect to eating habits among the participants. A dietary risk score, which was the proportion of all food choices that were high in fat, was calculated from the data. Eighteen per cent of subjects who answered also participated in the food tastings; there was a statistically significant association between membership of the Australian Cardiac Association and being a participant. Participants had a significantly lower risk score (P < 0.01) after adjustment for age, sex and membership of the association. The results suggest that voluntary participation by people with heart disease in community nutrition education is low and that there is a self-selection bias, with those at highest dietary risk being least likely to attend. The use of existing community networks to recruit participants is also discussed.