Association of Changes in Neck Circumference with Cardiometabolic Risk in Postmenopausal Healthy Women.

AIM: Although neck circumference (NC) is thought to predict obesity-related metabolic abnormality, its causal role in cardiometabolic risk is unclear. The aim of this study was to clarify the impact of changes in NC on cardiometabolic risk in healthy postmenopausal women through a community-based longitudinal study. METHODS: From a local community in Japan, 63 generally healthy postmenopausal women were recruited. All participants received an assessment of obesity-related anthropometric markers, biochemical parameters, and hemodynamic measures and were followed on average for 3 years. RESULTS: At baseline analysis, larger NC was positively associated with atherosclerosis-related markers, brachial-ankle pulse wave velocity (baPWV) and blood pressure, as well as some lipid parameters. After the follow-up period, change in NC was associated with changes in body mass index (BMI), body fat percentage, and waist circumference (WC). Interestingly, significant correlations of change in NC with changes in baPWV and blood pressure were observed, whereas changes in WC and BMI were only associated with changes in low-density lipoprotein cholesterol and/or total cholesterol. In multivariate linear regression analysis, change in NC was significantly associated with changes in baPWV and systolic blood pressure, independent of changes in BMI, WC, and biochemical parameters. In addition, an increase in NC was associated with a 2.69-fold increased odds ratio of accelerated baPWV. CONCLUSIONS: Change in NC was independently associated with changes in atherosclerosis-related markers. These observations suggest that NC is an important predictor of the risk of developing obesity-related atherosclerosis in healthy postmenopausal women.

Neck circumference has possibility as a predictor for metabolic syndrome in postmenopausal women.

Subcutaneous fat depots play an important role in regulating metabolic profile in Japanese postmenopausal women. We investigated the possibility of neck circumference (NC) as a surrogate marker for metabolic disease risk estimates in Japanese postmenopausal women. We examined the association of NC with several markers of insulin resistance, lipid metabolism and atherosclerosis in 64 healthy postmenopausal women aged 63.6 ± 7.1 years in community-based samples in Japan. As a result, NC was significantly associated with indices of whole body obesity and visceral fat accumulation, such as body mass index (BMI) and Waist circumference (WC). In the analysis of biomarkers for insulin resistance, NC was positively correlated to HbA1c, homeostasis model assessment ratio (HOMA-R) and leptin. In addition, an increase in triglycerides (TG) and a decrease in HDL-cholesterol (HDL-C) were also associated with NC. Interestingly, NC was also associated with atherosclerosis-related indices. The measurement of NC is an easy, inexpensive and reproducible method for assessment of obesity, and a possible predictor to identify the risk for future metabolic diseases in Japanese postmenopausal women.

Thermographic study on the preservability of heat effects of footbath with salt.

Infrared thermography provides a non-invasive and dynamic measure of heat. The thermal preservability effects of a salt footbath were evaluated by the infrared thermography technique. The subjects were 23 healthy college students. Feet were soaked for 10 min in a 40-42 degrees C normal footbath. Room temperature was set at 26.5-28 degrees C. At the same time on another day within 3 days of the normal footbath experiment, the same feet were soaked for 10 min in a 40-42 degrees C salt footbath. We measured blood pressure, heart rate and temperatures of the feet, second toes, hands and middle fingers, just before and after immersion and at 10-min intervals thereafter. Mean blood pressure changes showed no difference between the normal and the salt footbath. Mean heart rate changes were higher during the normal footbath than at 0, 15 and 20 min during the salt footbath, respectively (p < 0.05). Mean thermal preservability of the feet tended to be lower after the normal footbath than at 20 and 30 min, respectively, after the salt footbath, but these differences did not reach a statistical significance. Mean thermal preservability of the hands and middle fingers was significantly lower after the normal footbath than at 20 and 30 min, respectively, after the salt footbath (p < 0.05). The results suggest that stimulation by a salt footbath affects surface skin temperature, and that stimulation aimed at increasing skin thermal preservability shows a significant difference between normal and salt footbaths.

Changes in bone mineral density and metabolism in women: evaluation of bodily characteristics, bone metabolic markers and bone mineral density.

The relationship of bone mineral density (BMD) and bone metabolic markers in women is an interesting field of research. In this study, we aimed to clarify the relationship of body weight, bone metabolic markers and BMD. The subjects were 72 women. The levels of serum bone-specific alkaline phosphatase (BAP), serum type I collagen-cross-linked peptide (s-NTx) and urinary deoxypyridinoline (u-DPD) were measured. The associations between dependent variables (BMD changes/1 or 4 years in the lumbar spine and femoral neck) and explanatory variables (body weight changes/1 or 4 years, the levels of BAP, s-NTx, u-DPD) were evaluated using multiple regression analysis. Changes in the lumbar spine BMD were significantly correlated with changes in height over a year, and those of the femoral neck were significantly correlated with changes in weight over a year. Changes in the lumbar spine BMD over 4 years were significantly correlated with age, BAP and the changes of weight over 4 years. Changes in the femoral neck BMD over 4 years were significantly correlated with the changes in weight for 4 years. These results suggest that BMD changes of different bones correlate with different explanatory variables and that, to predict BMD changes from bone metabolic markers in women, it is necessary to measure BAP levels.

Alcohol-induced persistent mild cognitive impairment with successful withdrawal from alcohol dependence--a case report.

An 81-year-old man diagnosed with alcohol-induced persistent mild cognitive impairment consulted our clinic presenting with gait disturbance. Between the ages of 20 and 53 years, his alcohol consumption was 1.8 liters of alcoholic sake per day. However, from the age of 53 years onward, his consumption decreased to 360 ml per day. The patient had alcoholic neuropathy, mild cognitive impairment, and alcoholic cerebellar disorder. His score on the revised version of Hasegawa's Dementia Scale (HDS-R) was 22 and his clinical dementia rating (CDR) was 0.5. His score on the Japanese version of the Mini-Mental State Examination (MMSE) was 22. These scores indicated mild cognitive impairment (MCI). He had delusions and confabulations, without impairment of date and place orientation. Magnetic resonance imaging (MRI) demonstrated enlarged ventricles, sulcal widening, and brain atrophy. He was provided with medication and counseling to treat his alcohol abuse. He accepted our treatment and is presently doing well after 1 year 2 months of treatment.

New dopamine agonist pramipexole improves parkinsonism and depression in Parkinson's disease.

Previous studies have shown that pramipexole might have the potential to improve depressive symptoms in patients with Parkinson's disease. To provide more evidence, in five Japanese patients at Hoehn & Yahr stage 1-3 we evaluated the Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Montgomery Asberg Depression Rating Scale (MADRS) at our hospital. After the pramipexole treatment, each total score of UPDRS, HAMD and MADRS significantly decreased compared with that before the treatment. Our data indicate that pramipexole improves depressive symptoms in patients with Parkinson's disease.

Kinetics of blood glucose in mice carrying hemizygous Pax6.

The genotype-phenotype relationship was examined experimentally for the Pax6(Sey-4H) mutant, which carries deletion of its chromosome 2 middle region hemizygously. The genotyping has indicated that this deleted segment is between 102.6 and 109.2 Mb from the centromere. The glucose-6-phosphatase gene followed by the glucagon and carboxyl ester lipase genes were mapped adjacent to the deleted region. Phenotyping indicates that the Pax6(Sey-4H) mutant is more susceptible to diabetes. The glucose tolerance test showed that the mutants were less capable of reducing their level of blood glucose to the standard level than the normal sibs. The insulin-loading test revealed their inability to elevate their blood glucose levels up to normal levels. The time it took for the onset of diabetes induced by streptozotocin was shorter in the mutants than in normal sibs. Both the haploinsufficiency of the genes in the hemizygous segment of chromosome 2 and the quantitative imbalance of the whole genome could contribute the development of this phenotype in the mutant.

Upregulation of c-myc gene accompanied by PU.1 deficiency in radiation-induced acute myeloid leukemia in mice.

OBJECTIVE: High-dose radiation exposure induces acute myeloid leukemia (AML) in C3H mice, most of which have a frequent hemizygous deletion around the D2Mit15 marker on chromosome 2. This region includes PU.1, a critical candidate gene for initiation of leukemogenesis. To identify novel cooperative genes with PU.1, relevant to radiation-induced leukemogenesis, we analyzed the copy number alterations of tumor-related gene loci by array CGH, and their expressions in primary and transplanted AMLs. MATERIALS AND METHODS: For the induction of AMLs, C3H/He Nrs mice were exposed to 3 Gy of x-rays or gamma-rays. The genomic alterations of 35 primary AMLs and 34 transplanted AMLs obtained from the recipient mice transplanted the primary AMLs were analyzed by array CGH. According to the genomic alterations and mutations of the 235th arginine of PU.1 allele, we classified the radiogenic AMLs into three types such as Chr2(del) PU.1(del/R235-) AML, Chr2(del) PU.1(del/R235+) AML and Chr2(intact) PU.1(R235+/R235+) AML, to compare the expression levels of 8 tumor-related genes quantitatively by real-time polymerase chain reaction and cell-surface antigen expression. Results. In addition to well-known loss of PU.1 with hemizygous deletion of chromosome 2, novel genomic alterations such as partial gain of chromosome 6 were recurrently detected in AMLs. In this study, we found similarity between cell-surface antigen expressions of bone marrows and those of spleens in AML mice and significantly higher expressions of c-myc and PU.1 expression, especially in the PU.1-deficient (Chr2(del) PU.1(del/R235-)) AML and Chr2(del) PU.1(del/R235+) compared to Chr2(intact) PU.1(R235+/R235+) AMLs. CONCLUSION: The new finding on upregulation of c-myc and PU.1 in both and hemizygous PU.1-deficient AMLs and different genomic alterations detected by array CGH suggests that the molecular mechanism for development of radiation-induced AML should be different among three types of AML.

Intestinal tumorigenicity of mice carrying hemizygous Pax6, Pax6(Sey-4H).

The genotype-phenotype relationship in mice was examined experimentally using one of the small eye mutants, Pax6(Sey-4H), which deletes the chromosome 2 middle region, hemizygously. The genotyping indicated that the deleted region starts at a site 102.60 Mb from the centromere and has a length of 6.51 Mb, in which 12 known and 27 novel genes are located. Expecting the development of myeloid leukemia, gamma-irradiation was performed to female mutants at the age of 10 weeks. The mutants did not develop myeloid leukemia during the observation period of 18 months. Instead, they developed tumors in the alimentary tract spontaneously (56.0%). The tumor latency was shortened by the radiation exposure, but the tumor incidence of the gamma-irradiated group (62.5%) was as high as that of spontaneously developing tumors. Intraductal proliferation of the epithelium of the Wirsung duct was observed in the gamma-irradiated mutants (18.8%). Considering the results of the Pax6(Sey-4H) mutant together with those of another small eye mutant, Pax6(Sey-3H), the anomaly and the tumorigenicity of the intestinal tract were closely related to the hemizygosity of the 3.2 Mb segment of chromosome 2, where both mutants show a common deletion.

Comparison of the effectiveness of high and low LET radiations for the proportion of survivals with liver tumors at every age in (C57BL/6N x C3H/HeN) F1 mice.

To investigate the late effects of neutrons at the energy below 1 MeV on the liver carcinogenesis as a function of age, one-week old mice were exposed to 1.0 Gy monoenergetic neutrons (0.317, 0.525 and 1.026 MeV) or 137Cs gamma rays. Survival and carcinogenesis were examined by 18 months of age. Following radiation, tumor incidences in liver, Harderian gland, lung, ovary and pituitary gland were compared. The proportion of the lifespan with liver tumors exposed to neutrons to that exposed to gamma rays was calculated as a function of age. Survival rates among the three groups exposed to neutrons of different energies were not significantly different from one another but shorter than those treated with gamma rays for both sexes. With regard to liver tumor incidence evaluated at 18 months of age, the effectiveness of neutrons to gamma rays was 2.54 for females, and 2.08 for males by the factor. Levels of estrogen in the serum were similar between mice bearing liver tumors and those devoid of tumors. In conclusion, all three energies of neutrons induced similar effectiveness with respect to liver carcinogenicity. Proportions of the lifespan with liver tumors of neutron-exposed to gamma-exposed were shorter in females than males along with ages over 12 months. To obtain this factor at every age contributed for the evaluation of the biological effectiveness of radiations with the parameter of tumor incidence and latency simultaneously.

Effect of monoenergetic neutron irradiation on the postnatal development of the cochlea in C3H/HeN mice.

To investigate the toxic effect of neutrons at energies of approximately 1MeV on the ear, we exposed 7-day-old mice to 1.0 Gy of monoenergetic neutrons (1.026 MeV) or (137)Cs gamma rays, and assessed subsequent morphological changes in the inner ear by light and scanning electron microscopy. Monoenergetic neutrons, but not gamma rays, caused acute changes in the ear. The epithelium of the greater epithelial ridge in the organ of Corti had disappeared by 72 hr post-irradiation, as a result of epithelial apoptosis observed 6 hr post-irradiation. Radiation could induce apoptotic cell death of the epithelium of the greater epithelial ridge at 3 or 4 days of age. Protruding structures were detected on the surface of the hair cells by 72 hr post-irradiation. The neutron-irradiation also caused the apoptotic cell death of epithelial cells at the nasal conchae, and subsequent acute otitis media continued until 10 weeks of age.

Effects of high linear energy transfer radiation on the cochlea of C3H/He mouse during postnatal developmental course.

To investigate the biological effectiveness of neutrons at energies below 1MeV with regard to ear toxicity, we exposed mice to 1.0 Gy of monoenergetic neutrons (1.026 MeV) or 137Cs gamma rays at 7 days of age, and observed subsequent morphological changes in the inner ear with light and scanning electron microscopes. Monoenergetic neutrons, but not gamma rays, caused acute changes in the ear. The epithelium of the greater epithelial ridge in the organ of Corti showed degeneration around 6 hours and disappeared by 72 hours post-irradiation. The apoptotic cell death of the epithelium of the greater epithelial ridge was inducible by the radiation at 3 or 4 days of age. The hair cells formed the protrusion structures of the surface by 72 hours post-irradiation. Neutron-irradiation also caused acute otitis media until 10 weeks of age.

Spontaneous and radiation-induced leukemogenesis of the mouse small eye mutant, Pax6(Sey3H).

Allelic loss on the chromosome 2 is associated with radiation-induced murine acute myeloid leukemia. However, the gene, which contributes mainly to the leukemogenesis has not yet been identified. Expecting any predisposition to acute myeloid leukemia, we performed a radiation leukemogenensis experiment with Pax6(Sey3H), one of the small eye mutants carrying a congenital hemizygosity of the chromosome 2 middle region. A deletion mapping of Pax6(Sey3H) with 50 STS markers indicated that the deleted segment extended between the 106.00 and 111.47 Mb site from the centromere with a length of 5.47 Mb. In the deleted segment, 6 known and 17 novel genes were located. Pax6(Sey3H) mutants that crossed back into C3H/He did not develop myeloid leukemia spontaneously, but they did when exposed to gamma-rays. The final incidence of myeloid leukemia in mutants (25.8%) was as high as that in normal sibs (21.4%). Survival curves of leukemia-bearing mutants shifted toward the left (p = 0.043 by the Log rank test). F1 hybrids of Pax6(Sey3H) with JF1 were less susceptible to radiation than Pax6(Sey3H) onto C3H/He in regard to survival (p = 0.003 and p < 0.00001 for mutants and normal sibs, respectively, by a test of the difference between two proportions). Congenital deletion of the 5.47 Mb segment at the middle region on chromosome 2 alone did not trigger myeloid stem cells to expand clonally in vivo; however, the deletion shortcut the latency of radiation-induced myeloid leukemia.

The quality of DNA recovered from the archival tissues of atomic bomb survivors is good enough for the single nucleotide polymorphism analysis in spite of the decade-long preservation in formalin.

It is well known that the yield of DNA recovered form tissues preserved in formalin is inversely proportional to the stored duration. How is the quality? We tested the quality of DNA from archival tissues of atomic-bomb survivors stored in formalin for decades with the parameters of gene amplification efficiency by a polymerase chain reaction. All of the DNA extracted from the tissues preserved in formalin for 30 years amplified the 54- and 61-base pairs of the DNA fragments successfully. The direct sequencing of the PCR products confirmed the accurate amplification of the target sequence. A further trial to amplify the longer sequence of 111 base pairs succeeded in 20% of the samples tested. From these results, we propose a new utility of archival samples for the analysis of single nucleotide sequence polymorphism of genes, no matter how long the samples have been preserved in formalin.