Successful correction of severe contracture of the palm using arterialized venous flaps

Severe contracture of the palm causes great difficulty in the performance of the tasks required in daily life. Resurfacing with skin grafts may be sufficient for treating mild and small contractures; but severe and extensive contractures involving the joints, tendons, and neurovascular bundles should be covered with thin flaps. The authors present four cases of successful reconstruction of severe and extensive contractures of the palm using large arterialized venous flaps.     

Association of vitamin D and estrogen receptor gene polymorphism with the effects of longterm hormone replacement therapy on bone mineral density

We longitudinally studied whether vitamin D receptor (VDR) and estrogen receptor (ER) gene polymorphisms in Japanese women influenced the effect of longterm hormone replacement therapy (HRT) on bone mineral density (BMD) in the lumbar spine. The 81 subjects were aged 40 to 64 years (mean ± SEM, 49.5 ± 0.6 years), and had received sequential or continuous HRT regimens, including 0.625mg of conjugated equine estrogen and 2.5 to 5mg of medroxy-progesterone acetate, for at least 3 years. Genomic DNA was extracted from blood cells, and analyzed for restriction fragment length polymorphism, using the restriction endonucleases Taq I, Apa I, and Fok I for VDR, and Pvu II and Xba I for ER. At 1 year, subjects with a Taq I genotype of TT (i.e., site absent) showed a significantly greater increase in BMD with treatment (BMD) than subjects with the Tt genotype (2.6 ± 0.5% vs –0.8 ± 1.4%; P = 0.016). A small difference between genotypes remained at 2 years (3.8 ± 0.6% vs 0.8 ± 1.6%; P = 0.069), but no significant difference between genotypes was seen at 3 years. In multiple regression analyses, BMD at 1 year was significantly affected by VDR-Taq I, Apa I, and ER-Pvu II genotypes and by age at treatment initiation, although at 3 years or more, BMD was significantly affected only by age. These results indicate that Taq I VDR gene polymorphism predicted the effect on lumbar BMD for the first year of HRT in Japanese women, and that the differences in BMD versus the polymorphism disappeared if the treatment was continued for over 2 years.     

Impaired vascular endothelium-dependent relaxation in Henoch-Schönlein purpura

Few reports have focused on vascular endothelial function in children with Henoch-Schönlein purpura (HSP). The purpose of the present study was to assess endothelial function and to follow serial changes from the acute to convalescent phases in children with HSP. Forearm flow-mediated vasodilation was evaluated in 21 patients with HSP, aged 4.0–10.3 years (median 6.2 years), and in 14 control subjects. Vascular dimension, mean velocity, and flow volume were measured by ultrasonography in brachial artery before and after hyperemia, and during incremental infusions of nitroglycerin (0.5, 1.0 g/kg per min). In the controls, significant increases in dimension, mean velocity, and flow volume were observed in reactive hyperemia (P<0.01). In contrast, patients in the acute phase of HSP showed a flow velocity profile indicating a highly resistant forearm circulation, and significantly attenuated responses after hyperemia (P<0.01 vs. control), whereas the responses to nitroglycerin were well preserved. In addition, the impaired hyperemic responses recovered in the convalescent phase, with no significant differences compared with controls. These results clearly suggest that forearm vascular endothelium-dependent relaxation was attenuated in patients with acute HSP.     

Histological analysis of the ligamentum flavum of patients with dialysis-related spondyloarthropathy

Dialysis-related spondyloarthropathy (DRS) is a severe complication of long-term hemodialysis that ultimately leads to functional disability of the upper and lower extremities. Although the cause of this disease is still unknown, it is thought that amyloid deposits are involved. 2-Microglobulin (2M) is a major component of amyloid fibrils, some of which are modified with the advanced glycation end-product (AGE). To clarify the pathophysiology of DRS we histologically examined the ligamentum flavum of the cervical spine in 15 patients with DRS. The mean duration of hemodialysis was 20 years (12–27 years). In addition to the congo red stain for amyloid, 2M and AGE were detected by immunohistochemical methods. Macrophages were stained with CD68 antibody. Amyloid deposits were found in tissues, although the extent of the stained area differed among the patients. Part of the amyloid deposit area was positively immunostained for 2M and AGE. In 10 cases macrophages positive for CD68 infiltrated around the amyloid deposits. Comparing these histological findings with the dialysis duration, more positive staining areas for 2M and AGE were found in the tissue from patients with long-term dialysis. These findings suggest that both 2M and AGE play roles in the pathogenesis of DRS.     

Effects of genetic and nutritional factors on bone mineral density in young adults

To estimate the genetic and dietary factors influencing bone mineral density (BMD) in young adults, a total of 53 healthy volunteers (HV) (age 20.89+/-1.34), from whom informed consent was obtained, answered a questionnaire on dietary factors and had DNA from peripheral blood mononuclear cells analyzed for single nucleotide polymorphisms (SNPs) for vitamin (Vit) D receptor (VDR), estrogen receptor alpha (ERalpha), interleukin 1 receptor antagonist (IL1RA), and apolipoprotein E (ApoE) genes. Daily intakes of Vit C, fiber, soybean and related foods, and green and yellow vegetables showed a correlation with % BMD. In addition, Vit B2 as well as Vit C, and vegetables were identified as important factors for BMD by Stepwise regression analysis. Among the SNPs analyzed, the B+ type of the VDR gene tended to be associated with a lower BMD, and pp type of the ER gene digested by the PvuII enzyme in females indicated a significantly lower BMD than that in males. In addition, these SNPs were also identified by factor analysis to be associated with BMD. These results suggested that a complex array of genetic factors, such as two or more SNPs or SNPs and gender, may be important to BMD.     

Maintenance of serum immunoglobulin G antibodies to Epstein-Barr virus (EBV) nuclear antigen 2 in healthy individuals from different age groups in a Japanese population with a high childhood incidence of asymptomatic primary EBV infection

Immunoglobulin G (IgG) antibodies to Epstein-Barr virus (EBV) nuclear antigens 2 and 1 (EBNA-2 and EBNA-1, respectively) were studied using sera from healthy individuals of a population with a high incidence of asymptomatic primary EBV infections during infancy or childhood in Japan. Two CHO-K1 cell lines expressing EBNA-2 and EBNA-1 were used for anticomplement and indirect immunofluorescence assays. The positivity rate for EBNA-2 IgG rose in the 1- to 2-year age group, increased and remained at a plateau ( approximately 45%) between 3 and 29 years of age (3- to 4-, 5- to 9-, 10- to 14-, and 15- to 29-year age groups), and then reached 98% by age 40 (>/== 40-year age group). Both seropositivity for EBNA-1 and seropositivity for EBNAs in Raji cells (EBNA/Raji) were detected in the 1- to 2-year age group, remained high, and finally reached 100% by age 40. The geometric mean titer (GMT) of EBNA-2 IgG reached a plateau in the 5- to 9- and 10- to 14-year-old groups and remained elevated in the older age groups (15 to 29 and >/== 40 years). The GMT of EBNA-1 IgGs increased to a plateau in the 1- to 2-year-old group and remained unchanged in the older age groups. The GMT of EBNA/Raji IgGs also reached a plateau in the 1- to 2-year-old group, remained level throughout the 3- to 14-year age groups, and decreased in the 15- to 29-year-olds. EBNA-2 IgGs emerged earlier than EBNA-1 IgGs in 8 of 10 patients with infectious mononucleosis, who were between 1 and 27 years old, and declined with time in three of eight cases. These results suggest that EBNA-2 IgG antibodies evoked in young children by asymptomatic primary EBV infections remain elevated throughout life, probably because of reactivation of latent and/or exogenous EBV superinfection.     

Association of early endosomal autoantigen 1 with macropinocytosis in EGF-stimulated A431 cells

Association of early endosomal autoantigen 1 (EEA1) with macropinosomes was examined in EGF-stimulated A431 cells by dual labeling with immunofluorescence of anti-EEA1 and FITC-dextran (FDx), a fluid-phase endocytic marker. Addition of EGF to A431 cells drastically enhanced macropinosome formation. Newly formed macropinosomes labeled with 5-min pulse of FDx were located at the cell periphery and labeled weakly for EEA1. After a 5-min chase, these macropinosomes aggregated and frequently fused with each other. Immunofluorescence showed that EEA1 appeared on the membrane of FDx-labeled macropinosomes at that time, suggesting that EEA1 functioned in homotypic macropinosome fusion. With longer chase (30-60 min), macropinosomes decreased in number and size, indicating that FDx was largely exocytosed via recycling compartments. A small amount of FDx-labeled macropinosomes remained in the perinuclear region even at 60 min after pulse labeling. They were EEA1-positive but negative for cathepsin D, a lysosomal enzyme. This indicates that macropinosomes do not mature to late endosomes or fuse with lysosomes. Instead, EEA1 continuously mediates homotypic fusion as long as the macropinosomes persist.     

Development of realistic high-resolution whole-body voxel models of Japanese adult males and females of average height and weight, and application of models to radio-frequency electromagnetic-field dosimetry

With advances in computer performance, the use of high-resolution voxel models of the entire human body has become more frequent in numerical dosimetries of electromagnetic waves. Using magnetic resonance imaging, we have developed realistic high-resolution whole-body voxel models for Japanese adult males and females of average height and weight. The developed models consist of cubic voxels of 2 mm on each side; the models are segmented into 51 anatomic regions. The adult female model is the first of its kind in the world and both are the first Asian voxel models (representing average Japanese) that enable numerical evaluation of electromagnetic dosimetry at high frequencies of up to 3 GHz. In this paper, we will also describe the basic SAR characteristics of the developed models for the VHF/UHF bands, calculated using the finite-difference time-domain method.     

Diversity of the muscarinic and nicotinic responses of subfornical organ neurons in rat slice preparations

Recently we found that subfornical organ (SFO) neurons were activated through nicotinic receptors as well as muscarinc. In this study, the preferential responses of single SFO neurons to both muscarine and nicotine were examined by using rat slice preparations, and current and voltage clamp recordings. When the amplitudes of the depolarizations and inward currents by muscarine and nicotine in single SFO neurons were compared, some neurons showed a higher sensitivity to muscarine than to nicotine while others showed vice versa. These data indicate that acetylcholine activates SFO neurons preferentially through either muscarinic or nicotinic receptors and suggest a diversity of cholinergic responses in the SFO.