Favorable Impact of Growth Hormone Treatment on Cholesterol Levels in Turner Syndrome

Background: Patients with Turner syndrome (TS) are prone to having metabolic abnormalities, such as obesity, dyslipidemia, hypertension, hyperinsulinemia and type 2 diabetes mellitus, resulting in increased risks of developing atherosclerotic diseases. Objective: To determine the effect of growth hormone (GH) therapy on serum cholesterol levels in prepubertal girls with TS enrolled in the Turner syndrome Research Collaboration (TRC) in Japan. Patients and methods: Eighty-one girls with TS were enrolled in the TRC, and their total cholesterol (TC) levels before GH therapy were compared with reported levels of healthy school-aged Japanese girls. TC levels after 1, 2 and 3 yr of GH treatment were available for 28 of the 81 patients with TS. GH was administered by daily subcutaneous injections, 6 or 7 times/wk, with a weekly dose of 0.35 mg/kg body weight. Results: Baseline TC levels revealed an age-related increase in TS that was in contrast to healthy girls showing unchanged levels. During GH therapy, TC decreased significantly after 1 yr of GH treatment and remained low thereafter. Conclusions: Girls with untreated TS showed an age-related increase in TC that was a striking contrast to healthy girls, who showed unchanged levels. GH therapy in girls with TS brought about a favorable change in TC that indicates the beneficial impact of GH on atherogenic risk.     

Improvement in peripheral blood T cell subset imbalance in a house with an elimination system for various allergens

We analyzed the change of peripheral blood T cell subsets after moving into a house with a Healthy Air system (HAS) elimination system for various allergens, e.g. pollens, house dusts, etc. The 20 subjects were divided into an allergic group (13 subjects) and control group (7 subjects). We measured complete blood counts (CBC), white blood cell differentiation (DIFF), CD4/CD8 ratio, Th1/Th2 ratio, and percentage of CD4+CD25+T-cells and regulatory T-cells in peripheral blood, and these data were compared before and 3 and 6 months after moving into the HAS house. There was no significant difference in CBC, DIFF, CD4/CD8 ratio, and Th1/Th2 ratio before and after the move. The mean levels and 95% confidence interval of CD4+CD25+T-cells in the allergic group were as follows: before, 16.66% (12.99-20.34%); at 3 months, 13.86% (10.49-17.22%); and at 6 months, 12.66% (9.28-16.05%), respectively. Those in the control group were as follows: before, 13.60% (5.27-21.93%); at 3 months, 12.51%(5.41-19.61%); and at 6 months, 11.77% (3.93-19.61%), respectively. CD4+CD25+T-cells were significantly decreased at 6 months after the move compared to before the move in the allergic group (p < 0.01). However, there was no significant difference between before and after the move in the control group. The mean levels of regulatory T-cells were not different between before and after the move in both groups. The mean level of CD4+CD25+T-cells in subjects that had improved allergic condition was significantly decreased at 6 months after the move compared to before the move (p < 0.05). These results suggest that decreases in allergens in the home environment may affect lymphocyte subsets.     

Short sleep duration and poor sleep quality increase the risk of diabetes in Japanese workers with no family history of diabetes

OBJECTIVE

To investigate whether a difference in the risk for diabetes exists in Japanese workers with regard to sleep duration/quality and the presence or absence of a family history of diabetes (FHD).

RESEARCH DESIGN AND METHODS

The researchers conducted a prospective, occupational-based study of local government employees in Sapporo, Japan. Between April 2003 and March 2004, 3,570 nondiabetic participants, aged 35–55 years, underwent annual health checkups and completed a self-administered questionnaire that included information on sleep duration/quality and FHD at baseline. Having diabetes was defined as taking medication for diabetes or a fasting plasma glucose level of ≥126 mg/dL at follow-up (2007–2008).

RESULTS

A total of 121 (3.4%) new cases of diabetes were reported. In multivariate logistic regression models of workers without an FHD, and after adjustment for potential confounding factors, the odds ratio (95% CI) for developing diabetes was 5.37 (1.38–20.91) in those with a sleep duration of ≤5 h compared with those with a sleep duration of >7 h. Other risk factors were awakening during the night (5.03 [1.43–17.64]), self-perceived insufficient sleep duration (6.76 [2.09–21.87]), and unsatisfactory overall quality of sleep (3.71 [1.37–10.07]). In subjects with an FHD, these associations were either absent or weaker.

CONCLUSIONS

The current study shows that poor sleep is associated with a higher risk of developing diabetes in workers without an FHD. Promoting healthy sleeping habits may be effective for preventing the development of diabetes in people without an FHD.Modern society encourages late-night activities, such as watching television, using the computer or Internet, round-the-clock entertainment, as well as demanding shift work or night work that further promotes such activities. According to a survey by the National Sleep Foundation (2010), approximately one-fourth of participants stated that their current work schedule prevented them from getting enough sleep (1). One study reported that the average sleep duration for Finnish people had decreased by ~18 min during a period of 33 years (1972–2005), whereas sleep complaints, such as difficulty in falling asleep or awakening during the night, had increased, especially among the employed middle-aged population (2). According to a 2006 survey of Japanese adults on “Time Use and Leisure Activities,” average sleep duration was the shortest it has been for the past two decades (3). Furthermore, another report showed that one-fifth of Japanese adults habitually used alcohol or medicine to help them fall asleep (4).It has been reported that poor sleep is associated with higher HbA_1c levels in subjects with type 2 diabetes (5,6). Some prospective studies have reported that extreme sleep duration (7–10) and poor sleep quality, such as difficulty in sleep initiation (11–13) and sleep maintenance (12,14,15), are associated with a higher risk of impaired glucose tolerance or developing type 2 diabetes. However, those at greatest risk of developing diabetes from poor sleep remains to be elucidated. A recent meta-analysis indicated that no significant difference existed between men and women with regard to sleep duration/quality and diabetes, with the exception of short sleep duration in women (16). One multiethnic cohort study found that the risk in non-Hispanic whites and Hispanics differed from that in African Americans (10). However, the sleep-diabetes association in Asians is controversial, with few published studies (12,13).Type 2 diabetes is well known as a disease involving a complex combination of genetic, environmental, and behavioral factors. In 2004, the U.S. Centers for Disease Control and Prevention developed Family Healthware, a family history screening tool, to prevent common chronic diseases, including diabetes. They subsequently reported that a family history of diabetes (FHD) was associated with a two- to sixfold risk of developing diabetes compared with no FHD. Three academic centers now are trying to determine whether personalized prevention messages tailored to familial risk will motivate people at risk to change their lifestyles or screening behavior (17). FHD is considered to be an indicator for intervention to prevent the development of diabetes in a high-risk population. However, it is not clear whether the sleep-diabetes association also should be an indicator for intervention. Furthermore, whether people without an FHD have any specific risks for developing diabetes according to their daily lifestyle has not been ascertained. The aim of this article was to investigate whether a difference in risk for diabetes exists in Japanese workers with regard to sleep duration/quality and the presence or absence of an FHD.     

Skin potential response in letter recognition task as an alternative communication channel for individuals with severe motor disability.

OBJECTIVES: Skin potential responses (SPRs) to target and non-target stimuli in letter recognition tasks were studied to evaluate their potential as communication channels for individuals with severe motor disability. METHODS: SPRs were recorded from the palm or sole of 5 subjects with cerebral palsy and 6 healthy subjects. Subjects discriminated target letters from non-target ones in a random sequence of single letters. In Task 1, subjects made a behavioral response upon presentation of the target. In Task 2, the target letters were presented as "go" or "nogo" signals. RESULTS: For target letters, irrespective of behavioral requirements ("go" or "nogo"), skin potential waves frequently occurred with latency consistent with the sympathetic skin response (SSR) latency, and were regarded as SPRs evoked by target stimuli. In Task 1, the occurrence rate of the SPR was 47% for target, and 4% for non-target stimuli. In Task 2, the SPR occurred in 34% of "go" target, 29% of "nogo" target, and 2% of non-target stimuli. CONCLUSIONS: SPRs with SSR latency are potentially useful in controlling signals of communication tools for individuals with severe motor disability.     

Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: A prospective cohort study

Only a subset of cervical precursor lesions progress to cervical cancer and because of the lack of the predictive markers, it cannot be ascertained which lesions will progress or not. To estimate the risk of disease progression associated with human papillomavirus (HPV) genotypes, we followed 570 Japanese women with cytological LSIL (low‐grade squamous intraepithelial lesion) and histological CIN (cervical intraepithelial neoplasia) grade 1–2 lesions (479 CIN 1; 91 CIN 2) at 3 to 4 month intervals for a mean follow‐up period of 39.1 months. At entry, we detected HPV DNA in cervical samples by polymerase chain reaction‐based methodology. Over the period of follow‐up period, 46 lesions progressed to CIN 3 while 362 regressed to normal cytology. Women with multiple HPV infections were more likely to have persistent lesions (hazard ratio [HR] for regression, 0.65; 95% confidence interval [CI], 0.42–1.02; p = 0.07); however, multiple infections did not increase the risk of progression (HR for progression, 1.04; 95% CI, 0.37–2.94; p = 0.94). After adjusting for CIN grade and women's age, HRs for progression to CIN 3 (vs. women with low‐risk types or negative for HPV DNA) varied markedly by HPV genotype: type 16 (11.1, 95% CI: 1.39–88.3); 18 (14.1, 0.65–306); 31 (24.7, 2.51–243); 33 (20.3, 1.78–231); 35 (13.7, 0.75–251); 52 (11.6, 1.45–93.3); 58 (8.85, 1.01–77.6); other high‐risk types (4.04, 0.47–34.7). HPV 45 was not detected in our study subjects. The cumulative probability of CIN 3 within 5 years was 20.5% for HPV 16, 18, 31, 33, 35, 52 and 58; 6.0% for other high‐risk types; 1.7% for low‐risk types (p = 0.0001). In conclusion, type‐specific HPV testing for women with LSIL/CIN 1–2 lesions is useful for identifying populations at increased or decreased risk of disease progression.     

Hepatomas with activating Ctnnb1 mutations in 'Ctnnb1-deficient' livers: a tricky aspect of a conditional knockout mouse model

Conditional knockout mice, based on the Cre-loxP system, are a widely used model for examining organ-specific gene functions. To date, efficient hepatocyte-specific knockout has been reported in many different models, but little attention has been paid to the long-term stability of the recombination efficiency. In the present study, we characterized Alb-Cre;Ctnnb1flox/flox 'hepatocyte-specific Ctnnb1 knockout' mice of different ages to test whether efficient recombination is maintained over time. At 2 months of age, the knockout mouse livers achieved efficient deletions of β-catenin in hepatocytes. However, as the mice aged, the reappearance and expansion of β-catenin-expressing hepatocytes were observed. In 1-year-old mice, a significant proportion of the pericentral hepatocytes in the knockout mouse livers were replaced with β-catenin-positive hepatocytes, whereas the periportal hepatocytes mostly remained β-catenin-negative. Furthermore, most of the 1-year-old mice spontaneously developed hepatocellular adenomas and carcinomas that were positive for β-catenin and overexpressed glutamine synthetase and Slc1a2, both of which are hallmarks of active β-catenin signaling. Sequencing analysis revealed that the Ctnnb1 alleles were not inactivated but had activating mutations in these tumors. The present study suggests that recombination efficiency should be carefully examined when hepatocyte-specific knockout mice of different ages are analyzed. In addition, illegitimate deletion mutations should be recognized as potential adverse effects of the Cre-loxP system.