Metabolic cardiovascular disease risk factors and their clustering in subclinical hypothyroidism

Objective A possible association between subclinical hypothyroidism and cardiovascular disease (CVD) has been reported. Monitoring of atomic‐bomb survivors for late effects of radiation exposure at the Radiation Effects Research Foundation has provided the opportunity to examine associations between subclinical hypothyroidism and metabolic CVD risk factors. The objective of the study was to evaluate associations between subclinical hypothyroidism and metabolic CVD risk factors, and a cluster of these factors. Design and participants This was a cross‐sectional study of 3549 subjects (mean age 70 years; 1221 men and 2328 women) between 2000 and 2003 comprising 306 subjects with subclinical hypothyroidism and 3243 control euthyroid subjects in Japan. Measurements We investigated associations between subclinical hypothyroidism and metabolic CVD risk factors such as hypertension, diabetes mellitus, dyslipidaemia and hyperuricaemia, and a cluster of these factors. Results Subclinical hypothyroidism was not significantly associated with either hypertension, diabetes mellitus or hyperuricaemia defined by taking into account the use of medications in both men and women, but in men it was associated with dyslipidaemia (P = 0·02). We observed a significantly increased odds ratio (OR) for the presence of three or more metabolic CVD risk factors in men with subclinical hypothyroidism after adjusting for age, body mass index (BMI), and smoking status [OR: 1·83, 95% confidence interval (CI): 1·13–2·94, P = 0·01]. The significant associations remained after an additional adjustment for atomic‐bomb radiation dose. Conclusions There appears to be a significant increase in a cluster of metabolic CVD risk factors among people with subclinical hypothyroidism.     

Survey of <Emphasis Type="Italic">Ephedra </Emphasis>resources in the Northern Areas of Pakistan and their genetic diversity

More than 400 species of medicinal plants grow in the Northern Areas of Pakistan, including Ephedra plants. To investigate the wild Ephedra plant resources in the area, we surveyed the medicinal plants and collected 71 specimens from 18 collecting sites to analyze their genetic variation. The DNA sequences of the internal transcribed spacers 1 and 2 (ITS 1 and 2) of nuclear ribosomal DNA and a noncoding sequence of chloroplast DNA (trn L/F) were analyzed. This DNA data analysis and external morphological features were used to confirm the species of the specimens, and it was found that E. intermedia was the major species in the area and that E. gerardiana and E. przewalskii were present sporadically. Although it inhabits a relatively small area in comparison with the northwestern Chinese provinces, the DNA sequence of E. intermedia in the Northern Areas of Pakistan was significantly more heterogeneous than the same species grown in those neighboring regions. Most of the E. intermedia specimens contained more than 0.7% ephedrine alkaloids, fulfilling the requirement of the Japanese Pharmacopoeia; thus, the Ephedra plants in the area are a genetic and medicinal resource of great importance.     

Gigantomastia induced by bucillamine

Drug-induced mammary hyperplasias have been reported as rare complications of D-penicillamine and Neothetazone. The authors report the first case of bucillamine-induced giant mammary hyperplasia. Bucillamine is used as an antirheumatic drug that is structurally analogous to D-penicillamine. A 25-year-old woman with rheumatoid arthritis for the past 5 years started to develop gradual enlargement of her breasts 15 months before presentation. She had been on a combined treatment of steroid and lobenzarit disodium for the first 3 years, and then continued with a combined treatment of steroid and bucillamine for the following years until she was found to have pulmonary tuberculosis, at which time the steroid was suspended 10 months before she visited the authors' clinic. An almost total breast reduction was performed; 5 kg of right breast tissue and 7 kg of left breast tissue were excised. Retrospectively, bucillamine was believed to be the cause of the giant hypertrophy because of its structural similarity to D-penicillamine, which was the subject of an abundance of reports of mammary hyperplasia.     

Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2000)

From October 2000 to September 2001, we collected the specimen from 410 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various anti-bacterial agents and antibiotics and patients' characteristics. Of 499 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 493 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 73, Haemophilus infiuenzae 99, Pseudomonas aeruginosa (non-mucoid) 64, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 25, Moraxella subgenus Branhamella catarrhalis 21, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 53.8%. Vancomycin and arbekacin had the most potent activities against MRSA as observed in 1999. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 38.4% being consistent with that in 1999 (34.7%). PRSP accounted for 11.0% of the total, being more than that in 1999 (3.0%). Carbapenems had strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 73 strains at 0.125 microgram/ml. Generally, all drugs had strong activities against H. influenzae with MIC80s of 8 micrograms/ml or less. The drug that had the strongest activity against H. infiuenzae was levofloxacin, which inhibited the growth of 94 of the 99 strains at 0.063 microgram/ml. Tobramycin had a strong activity against P. aeruginosa (both mucoid and non-mucoid) with MIC80 of 1 microgram/ml. The mucoid strain was little isolated (14 strains) but the susceptibilities to all drugs were better than the non-mucoid strain. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and the MIC80S were 2 micrograms/ml or less. Particularly, cefpirome, cefozopran, and levofloxacin had strong bactericidal activities against K. pneumoniae with MIC80s of 0.125 microgram/ml, and cefotiam, second-generation cephems, also had a favorable activity being MIC80 of 0.25 microgram/ml. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or less. The drug having the strongest activity was imipenem and levofloxacin inhibiting all 21 strains at 0.063 microgram/ml. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (44.4%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 38.0% and 31.7% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.3%) and S. pneumoniae (16.1%). In contrast, H. infiuenzae (20.4%) and P. aeruginosa (both mucoid and non-mucoid: 16.7%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were S. pneumoniae (24.3%) and H. infiuenzae (26.7%). The frequency of isolated S. pneumoniae tended to decrease with the increase in the number of administration days while that of isolated H. infiuenzae did not. The frequency of isolated P. aeruginosa tended to increase with the duration of administration. The isolated bacteria were comparable between the patients already treated with penicillins and cephems. In the patients treated with aminoglycosides, macrolides, and quinolones, P. aeruginosa was most frequently isolated (33.3 to 40.0%).     

The influx of serum albumin to enamel matrix in rat incisors after trauma

The most frequent results of trauma to tooth germs are enamel hypoplasia and enamel hypocalcification. These differing results may be due to the stage of amelogenesis at which trauma occurs. The cellular and biomolecullar events involved in the genesis of these defects are poorly understood. We hypothesized that one factor involved is the possibility that relatively high levels of serum albumin enter the enamel matrix through the damaged enamel organ, and impair mineralization of the matrix. The present study was undertaken to immunohistochemically and autoradiographically localize serum albumin in the enamel organs of rat incisors after trauma was inflicted to the mandibular incisor region of 4-day-old rats. Hemorrhage was seen surrounding the enamel organ and between the detached secretory-stage ameloblasts. One day after trauma, the most intense immunohistochemical (IHC) staining for albumin was localized in the outer layer of the enamel matrix adjacent to the detached secretory-stage ameloblasts. Albumin was also detected autoradiographically in the secretory-stage ameloblasts layer and enamel matrix. These findings indicate that serum albumin can leak between the detached ameloblasts and penetrate the enamel matrix after trauma. Leaked albumin was still present in the matrix during the maturation stage. Leaked albumin in the developing enamel could inhibit crystal growth and result in hypocalcification.     

Engraftment of sorted/expanded human central nervous system stem cells from fetal brain

Direct isolation of human central nervous system stem cells (CNS-SC) based on cell surface markers yields a highly purified stem cell population that can extensively expand in vitro and exhibit multilineage differentiation potential both in vitro and in vivo. The CNS-SC were isolated from fetal brain tissue using the cell surface markers CD133(+), CD34(-), CD45(-), and CD24(-/lo) (CD133(+) cells). Fluorescence-activated cell sorted (FACS) CD133(+) cells continue to expand exponentially as neurospheres while retaining multipotential differentiation capacity for >10 passages. CD133(-), CD34(-), and CD45(-) sorted cells (approximately 95% of total fetal brain tissue) fail to initiate neurospheres. Neurosphere cells transplanted into neonatal immunodeficient NOD-SCID mice proliferated, migrated, and differentiated in a site-specific manner. However, it has been difficult to evaluate human cell engraftment, because many of the available monoclonal antibodies against neural cells (beta-tubulin III and glial fibrillary acidic protein) are not species specific. To trace the progeny of human cells after transplantation, CD133(+)-derived neurosphere cells were transduced with lentiviral vectors containing enhanced green fluorescent protein (eGFP) expressed downstream of the phosphoglycerate kinase promoter. After transduction, GFP(+) cells were enriched by FACS, expanded, and transplanted into the lateral ventricular space of neonatal immunodeficient NOD-SCID brain. The progeny of transplanted cells were detected by either GFP fluorescence or antibody against GFP. GFP(+) cells were present in the subventricular zone-rostral migrating stream, olfactory bulb, and hippocampus as well as nonneurogenic sites, such as cerebellum, cerebral cortex, and striatum. Antibody against GFP revealed that some of the cells displayed differentiating dendrites and processes with neurons or glia cells. Thus, marking human CNS-SC with reporter genes introduced by lentiviral vectors is a useful tool with which to characterize migration and differentiation of human cells in this mouse transplantation model.     

Functional MRI of motor sequence acquisition: effects of learning stage and performance

Neural networks of motor control are well understood and the motor domain therefore lends itself to the study of learning. Neuroimaging of motor learning has demonstrated fronto-parietal, subcortical, and cerebellar involvement. However, there is conflicting evidence on the specific functional contributions of individual regions and their relative importance for early and advanced stages of learning. Using functional MRI (fMRI), we examined hemodynamic effects in seven right-handed men during brief episodes of explicit learning of novel six-digit sequences (experiments 1 and 2) and during prolonged learning of an eight-digit sequence (experiment 3), all performed with the dominant hand. Brief episodes of new learning were predominantly associated with bilateral activations in premotor and supplementary motor areas, superior and inferior parietal cortices, and anterior cerebellum. In experiment 2, which included a control condition matched for complexity of motor execution, we also found unexpectedly strong activation in the bilateral inferior frontal lobes. In experiment 3, analysis of task by learning stage interactions showed greater involvement of the bilateral superior parietal lobes, the right middle frontal gyrus, and the left caudate nucleus during early stages, whereas left occipito-temporal and superior frontal cortex as well as the bilateral parahippocampal region were more activated during late learning stages. Analysis of task by performance interactions (based on each subject's response times and accuracy during each scan) showed effects in bilateral fronto-polar, right hippocampal, and anterior cerebellar regions associated with high levels of performance, as well as inverse effects in bilateral occipito-parietal regions. We conclude that superior parietal and occipital regions are most intensely involved in visually driven explicit digit sequence learning during early stages and low performance, whereas later stages of acquisition and higher levels of performance are characterized by stronger recruitment of prefrontal and mediotemporal regions.