No association of vitamin D-binding protein gene polymorphisms in Japanese patients with MS

Vitamin D-binding protein (DBP) is known to function as an immunomodulatory factor, as well as the main carrier of vitamin D. We analyzed the frequencies of two polymorphisms (codon 416 and codon 420) in the DBP gene through a case-control study involving 107 Japanese patients with multiple sclerosis (MS) and 109 healthy controls. None of these polymorphisms showed any association with the occurrence of MS. Furthermore, no association was observed between the DBP polymorphisms and the age at disease onset. These results suggest that DBP does not contribute to the development of MS in Japanese.     

Estrogen receptor gene polymorphism and multiple sclerosis in Japanese patients: interaction with HLA-DRB1*1501 and disease modulation

We investigated PvuII and XbaI polymorphism in the estrogen receptor gene (ERG) and HLA-DRB1*1501 positivity in 116 conventional multiple sclerosis (MS) patients and 101 healthy controls in a Japanese population. Logistic analysis revealed independent associations of [P] allele in the profiles for PvuII (p=0.0005, adjusted odds ratio (aOR)=3.17) and DRB1*1501 (p=0.0089, aOR=2.61) with conventional MS. Synergistic elevated risk of MS due to interaction between the [P] allele and HLA-DRB1*1501 allele was found among female patients (odds ratio=16.0; 95% CI=3.99-63.8, p<0.0001). The [P] allele-positive patients with disease duration of more than 5 years had a significantly higher progression index (PI) of disability (p=0.0230) and a worse ranked MS severity score (p=0.0152) than their non-[P] counterparts.     

An examination of the association between beta2 adrenergic receptor polymorphisms and multiple sclerosis

In multiple sclerosis (MS), beta-adrenergic receptor densities on peripheral blood mononuclear cells are enhanced, while the astrocytes present in plaques lack beta2 adrenergic receptor (beta2AR) expression. This differentially altered expression suggests that beta2ARs may influence the pathogenesis of MS. In the present study, we investigated the association of polymorphisms of the beta2AR gene with the occurrence of MS. Our results showed no significant differences in the distribution of the polymorphisms between MS patients overall and control subjects. Furthermore, no association was observed between the presence of beta2AR gene polymorphisms and clinical characteristics, such as age at disease onset and disease severity. While a trend towards an increase of the Gly allele frequency in codon 16 was observed in the secondary-progressive MS, this result was not significantly different from that observed in relapsing-remitting MS patients or control subjects. Together, our findings suggest that the presence of beta2AR gene polymorphisms may be inconclusive in the susceptibility to MS or in the clinical characteristics of Japanese patients with MS and, therefore, need further studies.     

Effect of Mass Screening for Breast Cancer from the Aspect of Psychosocial Assessment of the Quality of Life

To assess the quality of life (QOL) in patients with breast cancer receiving mass screening, a collaborative matched case-control study was conducted in nine hospitals throughout Japan. A total of 122 patients detected by mass screening (study group) and 226 patients found in out-patient clinics (control group) were assessed psychosocially on the basis of questionnaire information. The incidence of patients with early stage breast cancer was significantly higher in the study group than in the control group ( P <0.05). Chest wall pain was observed in 35.2% of the study group and in 46.5% of the control group ( P <0.05). Although control patients were more optimistic than study group patients, disturbed daily life and anxiety about recurrence were a little more frequent in the former group than in the latter. In particular, shoulder stiffness was frequently seen in the control group ( P <0.05). Early detection and information do not create anxiety in mass screening patients ( P <0.01). We should recommend mass screening to patients to detect early stage breast cancer and provide better QOL.     

Intestinal IgA deposition in Henoch-schönlein purpura with severe gastro-intestinal manifestations

Abstract In patients with Henoch-Schönlein purpura (HSP) presenting with severe gastro-intestinal (GI) symptoms, IgA deposition was studied in endoscopically obtained mucosal biopsies. A total number of 11 patients (male, 7; female, 4) were enrolled in this study; 7 patients underwent upper GI endoscopy and biops 1 underwent sigmoidoscopy and 3 underwent both. Upper GI endoscopy in each patient showed various mucosal changes including redness, petechiae, erosions, and ulcerations, most predominant in the second part of the duodenum. Sigmoidoscopy demonstrated no abnormality in two of four patients. Intestinal deposition of IgA was positive in 7 of 11 patients with HSP. Histological examination showed non-specific inflammation of varying degrees in each patient, but no small vessel vasculitis was observed. IgA deposits were seen in only 2 of 23 control subjects with various GI diseases. Positive rate of IgA deposition per patient was significantly higher in patients with HSP than in controls (P<0.005).Conclusion IgA deposition in the GI tract, as in the skin kidneys, is characteristic of HSP. Intestinal IgA deposition complements the diagnostic criferia of HSP.Presented in part at the 4th Pan-Pacific Congress of Paediatric Gastroenterology and Nutrition, Tokyo, September 1994     

Role of hypomagnesemia in chronic cyclosporine nephropathy

BACKGROUND: Hypomagnesemia is a common finding of cyclosporine (CsA)-treated patients and has been proposed as both a cause and a consequence of CsA-induced nephrotoxicity. This experiment was conducted to elucidate the role of hypomagnesemia in the pathogenesis of chronic CsA nephropathy. METHODS: CsA (15 mg/kg/day subcutaneously) was administered to rats maintained on a low-sodium diet for 1, 2, and 4 weeks, and the effects of magnesium (Mg) supplementation on renal function, renal histology, and renal gene expression profile of fibrogenic molecules and vasoconstrictors was examined. RESULTS: CsA elicited hypomagnesemia and induced a progressive decline in glomerular filtration. At 28 day, renal tubular atrophy and cortical striped interstitial fibrosis were evident with CsA treatment. Dietary supplementation of Mg ameliorated CsA-induced hypomagnesemia and almost completely abolished CsA-induced chronic fibrotic lesions. Neither CsA nor Mg supplementation affected blood pressure. Renal cortical mRNA of transforming growth factor beta, plasminogen activator inhibitor (PAI)-1, and extracellular matrix started to increase at 14 days and elevated further at 28 days. In contrast, the increase in mRNA of tissue inhibitor of matrix metalloproteinase-1 and renin was evident early at 7 days and reached peak at 14 days. These mRNA increases, except that of renin, were almost abolished when hypomagnesemia was corrected. Magnesium supplementation also improved glomerular dysfunction, at least in part, through inhibition of up-regulated mRNA of endothelin-1. CONCLUSION: CsA-induced hypomagnesemia contributes to chronic renal fibrotic lesions seen during CsA treatment through up-regulation of fibrogenic molecules, most notably early activation of tissue inhibitor of matrix metalloproteinase-1 expression.     

Inhibition of growth of human tumor cells in nude mice by a metalloproteinase inhibitor

The effects of a new metalloproteinase inhibitor, BEI6627B [L-N-(N-hydroxy-2-isobutylsuccinynamoyl)-seryl-L-valine, MW: 375.2] isolated from microbial cultures, on human tumor cell growth in nude mice were investigated. BE16627B inhibited metalloproteinases in enzyme assays, as well as gelatinolysis and collagenolysis in cell cultures. BE16627B at 100 μg/ml showed no apparent cytotoxicity to human tumor cells in culture and its LD₅₀ in mice was more than 1,000 mg/kg (i.p.). The effects of BE16627B on the in vivo growth of 1 human tumor cell lines were examined: HT1080 fibrosarcoma, which overproduces metalloproteinases, and HCT116 colon carcinoma, which barely secretes metalloproteinases. When BE16627B was administered to mice at 2 mg/mouse/day by an osmotic pump implanted s.c. for 3 weeks from 1 week after i.v. inoculation of HT1080 cells, the number and size of nodules of HT1080 cells on the lung surface were reduced to 24.3 and 46.4%, respectively, of those of controls, and the increase in lung weight due to tumor-cell growth was inhibited 85.5% without body-weight loss. Moreover, BE16627B inhibited 71.2% of the growth of HT1080 cells inoculated s.c. into mice under the same conditions, but did not significantly inhibit the s.c. growth of HCT116 human colon-carcinoma cells. Thus, BE16627B inhibited metalloproteinase-dependent human tumor-cell growth as well as lung colonization without showing cytotoxicity in nude mice.     

Psychiatric disorders among patients undergoing hemodialysis therapy

We examined the incidence rates of psychiatric disorders in end-stage renal failure patients on hemodialysis (HD) based on 4-year long-term follow-up. Among various psychiatric disorders, the frequency of three psychiatric disorders, dementia, delirium, and major depression, was relatively high. One-year incidence rate of whole psychiatric disorders was 10.6% (7.1% in non-aged and 13.7% in aged). One-year incidence rate of dementia in aged patients was 4.2% (dementia of the Alzheimer's disease, 0.5%; multi-infarct dementia, 3.7%). One-year incidence rate of multi-infarct dementia in aged HD patients was 7.4 times as large as that in the elderly general populations, suggesting that aged HD patients tend to exhibit multi-infarct dementia. The high incidence rate may be closely related to advanced arteriosclerosis and other medical conditions. Psychiatric management is required for ESRD patients with three major psychiatric disorders, dementia, delirium, and major depression, in particular for aged patients with multi-infarct dementia who has received long-term HD therapy.