Nationwide survey on predictive genetic testing for late-onset,incurable neurological diseases in Japan

A nationwide survey was conducted for predictive genetic testing for late-onset, incurable neurological diseases. A questionnaire was sent to 125 university hospitals and national hospitals, and was returned by 69% of them. Of the 86 responding hospitals, 63 had genetic counseling clinics and answered the questions concerning predictive testing. Of these, 46 had experienced clients with an interest in or a request for predictive testing during the period from April 2004 to March 2006. A total of 322 clients were accumulated, the majority of which were interested in myotonic dystrophy (n = 150), followed by spinocerebellar ataxia (n = 86), spinal and bulbar muscular atrophy (n = 40) and Huntington’s disease (n = 31). Most such clients were counseled by medical doctors, who had the “Japanese Board of Medical Genetics, Clinical Geneticist” certification, but others, including neurologists, nurses, clinical psychologists or genetic counselors also contributed, albeit to a lesser extent, to genetic counseling in Japan. Many respondents felt that a multidisciplinary approach by a counseling team consisting of a clinical geneticist, a neurologist, a genetic nurse, a clinical psychologist and a genetic counselor had not yet been established. There will be a great need for educated and trained non-medical doctor staff not only to improve the quality of genetic counseling and psychological support for such clients, but also to conduct the psychosocial research on Japanese clients requesting predictive genetic testing.     

A genomewide linkage analysis of Kawasaki disease: evidence for linkage to chromosome 12

Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. The cause of KD is largely unknown, but its higher incidence in the Asian population and increased risk in patients’ families suggests the existence of underlying genetic factors. To determine the loci of a susceptibility gene for KD, a genomewide linkage analysis with affected sib pairs was performed on 78 family samples collected from all over Japan. Multipoint linkage analysis using MAPMAKER/SIBS 2.0 identified evidence of linkage on 12q24 [maximum lod score (MLS) = 2.69]. Possible linkage (MLS > 1.0) was also found on 4q35, 5q34, 6q27, 7p15, 8q24, 18q23, 19q13, Xp22, and Xq27. This is the first large-scale study of the genetic susceptibility to KD, and our results, combined with the accumulated knowledge of the human genome, could greatly promote research on identification of the molecular pathogenesis of KD.     

Vitamin D receptor polymorphism among rickets children in Mongolia

BACKGROUND: It was reported that 32% of children under five years old in Mongolia had symptoms of rickets. Vitamin D receptor (VDR) gene polymorphism has received attention in relation to bone metabolism. We therefore investigated whether VDR polymorphism is related to high prevalence of rickets in Mongolia and to bone properties in childhood. METHODS: We conducted a case-control study in Ulaanbaatar involving 80 children aged 7-10 years with a history of rickets (cases) and 72 children with no history of rickets (controls). VDR polymorphism was assessed using BsmI, ApaI, and TaqI, and bone properties were determined by measuring age standardized tibial cortical speed of sound (TCSOS). FINDINGS: Each allelic frequency was verified to satisfy the Hardy-Weinberg equilibrium in cases, controls, and the total sample. The VDR polymorphisms among cases (BB 3%, Bb 18%, bb 80%; AA 15%, Aa 38%, aa 47%; and TT 81%, Tt 17%, tt 3%) did not differ significantly from those among controls (BB 1%, Bb 13%, bb 86%; AA 16%, Aa 46%, aa 38%; and TT 86%, Tt 13%, tt 1%). There were no significant differences in TCSOS according to the VDR genotype among either cases or controls. CONCLUSIONS: The VDR polymorphism does not play a major role in the development of rickets in Mongolia and has no effect on TCSOS in childhood.     

Nutrient and food intake in relation to serum leptin concentration among young Japanese women

OBJECTIVE: Little is known about the relation of modifiable dietary factors to circulating leptin concentrations, particularly in young adults and non-Western populations. We examined cross-sectional associations between nutrient and food intake and serum leptin concentration in young Japanese women. METHODS: Subjects were 424 female Japanese dietetic students 18-22 y of age. Intake of macronutrients (protein, total fat; saturated, monounsaturated, and polyunsaturated fatty acids; and carbohydrate), dietary fiber, and 12 food groups was assessed with a validated, self-administered, comprehensive, diet history questionnaire. Fasting blood samples were collected, and serum leptin concentrations were measured by radioimmunoassay. RESULTS: For nutrients, only dietary fiber was a significant determinant of serum leptin concentration. Increasing dietary fiber intake was associated with lower serum leptin concentration independent of potential confounding factors, including body mass index (mean serum leptin concentrations in the lowest and highest quintiles of dietary fiber intake were 8.6 and 7.5 ng/mL, respectively; P for trend = 0.026). Vegetables and pulses were the only foods significantly associated with serum leptin concentration, with higher intakes independently associated with lower concentrations (mean serum leptin concentrations in the lowest and highest quintiles of intake were 8.1 and 7.0 ng/mL, P for trend = 0.007, for vegetables and 8.8 and 7.6 ng/mL, P for trend = 0.019, for pulses, respectively). CONCLUSION: Intake of dietary fiber, vegetables, and pulses showed an independent inverse association with serum leptin concentration in a group of young Japanese women.     

Improvements in health by consultations using mobile videophones among participants in a community health promotion programme

We conducted a health promotion programme using mobile videophones and examined changes in the participants' health conditions, health practices and their subjective sense of health. The subjects were volunteers (mean age, 59 years) recruited from a community-based health promotion group. A focus group interview was conducted to evaluate the quality of the programme. All subjects expressed concerns about lifestyle-related diseases. The subjects participated in group activities at least twice a month under the supervision of public health professionals. Six of them participated in mobile care in addition to group activities (mobile care group) and the other eight subjects (control group) participated in the regular group activities. Three consecutive health examinations were carried out at intervals of 12 weeks. There were significant reductions in low-density lipoprotein cholesterol (P = 0.01) and health locus of control internal score (P = 0.05) in the mobile care group. The subjects who used mobile phones were highly accepting of the use of the device for further health consultations. There is potential for wider application of mobile videophones in health promotion programmes for people who have concerns about lifestyle-related diseases and are seeking healthier lifestyles.     

Conditional Ror1 knockout reveals crucial involvement in lung adenocarcinoma development and identifies novel HIF-1α regulator

We previously reported that ROR1 is a crucial downstream gene for the TTF-1/NKX2-1 lineage-survival oncogene in lung adenocarcinoma, while others have found altered expression of ROR1 in multiple cancer types. Accumulated evidence therefore indicates ROR1 as an attractive molecular target, though it has yet to be determined whether targeting Ror1 can inhibit tumor development and growth in vivo. To this end, genetically engineered mice carrying homozygously floxed Ror1 alleles and an SP-C promoter–driven human mutant EGFR transgene were generated. Ror1 ablation resulted in marked retardation of tumor development and progression in association with reduced malignant characteristics and significantly better survival. Interestingly, gene set enrichment analysis identified a hypoxia-induced gene set (HALLMARK_HYPOXIA) as most significantly downregulated by Ror1 ablation in vivo, which led to findings showing that ROR1 knockdown diminished HIF-1α expression under normoxia and clearly hampered HIF-1α induction in response to hypoxia in human lung adenocarcinoma cell lines. The present results directly demonstrate the importance of Ror1 for in vivo development and progression of lung adenocarcinoma, and also identify Ror1 as a novel regulator of Hif-1α. Thus, a future study aimed at the development of a novel therapeutic targeting ROR1 for treatment of solid tumors such as seen in lung cancer, which are frequently accompanied with a hypoxic tumor microenvironment, is warranted.     

Case report of intralobar pulmonary sequestration detected by lung cancer screening with low-dose spiral CT

A 52-year-old man underwent lung cancer screening with low-dose spiral computed tomography (CT) in a medical check-up at the Japanese Red Cross Kumamoto Health Care Center. He was asymptomatic. Chest x-ray on a medical check-up showed no abnormal shadows. CT scans revealed a nodule in the right lower lung, suggestive of its connection to the descending thoracic aorta. A diagnosis of pulmonary sequestration was considered. He was transferred to Kumamoto University Hospital for further examination. Contrast enhanced multidetector CT images demonstrated that a nodule in the right lower lobe and an anomalous artery ran from the descending thoracic aorta, flowed through the right lower lobe and returned to the right inferior pulmonary vein. Intralobar pulmonary sequestration was confirmed by contrast enhanced multidetector CT. We report this case of asymptomatic intralobar pulmonary sequestration diagnosed using contrast enhanced multidetector CT.     

(2S,3R) beta-methyl-2',6'-dimethyltyrosine-L-tetrahydroisoquinoline-3-carboxylic acid [(2S,3R)TMT-L-Tic-OH] is a potent,selective delta-opioid receptor antagonist in mouse brain

The constrained opioid peptide (2S,3R)beta-methyl-2',6'-dimethyltyrosine-L-tetrahydroisoquinoline-3-carboxylic acid [(2S,3R)TMT-L-Tic-OH] exhibits high affinity and selectivity for the delta-opioid receptors (). In the present study, we examined the pharmacological properties of (2S,3R)TMT-L-Tic-OH in mouse brain. A 5'-O-(3-[(35)S]thiotriphosphate) ([(35)S]GTP gamma S) binding assay was used to determine the effect of (2S,3R)TMT-L-Tic-OH on G protein activity in vitro, in mouse brain membranes. delta- (SNC80; (+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxy-benzyl]-N,N-diethyl-benzamide) or mu- (DAMGO; [D-Ala(2), Me-Phe(4),Gly(ol)(5)]enkephalin) selective opioid full agonists stimulated [(35)S]GTP gamma S binding in mouse brain membranes 150 +/- 4.5% and 152 +/- 5.7% over the basal level, respectively. (2S,3R)TMT-L-Tic-OH did not influence basal [(35)S]GTP gamma S binding in mouse brain membranes but dose dependently shifted the dose-response curve of SNC80 to the right, with a K(e) value of 3.6 +/- 0.7 nM. In contrast, (2S,3R)TMT-L-Tic-OH had no effect on the dose-response curve of the mu-selective opioid agonist, DAMGO. Warm water (55 degrees C) tail-flick and radiant heat paw-withdrawal tests were used to determine the in vivo nociceptive properties of (2S,3R)TMT-L-Tic-OH in the mouse. Intracerebroventricular injection of (2S,3R)TMT-L-Tic-OH had no significant effect on withdrawal latencies in either nociceptive tests. (2S,3R)TMT-L-Tic-OH (30 nmol/mouse) attenuated deltorphin II- but not DAMGO-mediated antinociception (40 +/- 13 and 100% of maximal possible effect, respectively) when administered intracerebroventricularly 10 min before the agonist. Taken together these results suggest that (2S,3R)TMT-L-Tic-OH is a potent highly selective neutral delta-opioid antagonist in mouse brain.     

Anomalous right lobe of the liver: CT appearance

We report five cases of anomalous right lobe of the liver diagnosed by computed tomography (CT). There were three men and two women, with an average age of 67 years. The right lobe was deformed and decreased in size in all patients. Hypertrophy of the left lobe was present in all patients.