Biomedical subjects
Publications and source records attributed to T Ando.
Irradiation of ultrasound accelerated the rate of the photochemical disappearance of 4,4'-dihalogenated benzils in 1,4-dioxane in the order of halogen = I, Br > Cl > F. 4,4'-dimethoxy and unsubstituted benzils did not show acceleration. Possible mechanisms of the acceleration are discussed.
We investigated the protective mechanism of a protein-bound polysaccharide, PSK, against lethal infection with Candida albicans (C. albicans) in mice. (1) In BALB/c mice inoculated intravenously with C. albicans, the intraperitoneal (ip) administration of PSK increased survival rates and prolonged the survival period depending on the time of administration, the dosage, and the size of fungal inoculum; the maximal effect was obtained when PSK 250 mg/kg was ip administered to mice 24 h before inoculation of 1 x 10(6) C. albicans (30 days survivors showed 60% and the mean survival period of mice with fatal infection increased 209%). (2) The protective effect of PSK was significantly decreased in mice treated with cyclophosphamide or carrageenan, or in mice treated previously with anti-tumor necrosis factor-alpha (TNF-alpha) antibody. (3) The administration of PSK significantly enhanced the expression of TNF-alpha gene in spleen and increased leukocyte functions from 6 h to 1 day after inoculation. (4) When the PSK fraction subjected to hydrolysis with beta1-3 glucanase or hydrazine was used instead of PSK, the anti-fungal activities were significantly decreased. These findings suggested that the protective effect of PSK on lethal C. albicans infection in mice was mainly produced via TNF-alpha functions, and that beta 1-3 glucan and protein moiety in PSK molecule were involved in the expression of the activities.
Given the complexity of the fracture healing process and the involvement of a multitude of cells, we hypothesize that a very large number of genes would be transcriptionally regulated during the repair process. To identify genes that play a role during bone regeneration in cellular events, such as proliferation, migration, adhesion, and differentiation, we employed differential display and compared mRNA populations isolated from postfracture (PF) day 3 calluses to those of intact (contralateral) rat femurs. One such gene whose expression was upregulated at PF day 3 is identified as the osteoblastic lineage marker, E11 antigen. E11 is a cell membrane protein localized predominantly on osteoblasts and osteocytes. In this study we show that E11 mRNA expression is consistently upregulated during fracture repair, with elevated levels (tenfold) seen as early as PF day 3. These high levels of expression were maintained throughout all of the early stages of repair examined (PF day 3-21 calluses) and paralleled those of another osteoblastic marker, osteopontin. Similarly, high protein levels were detected throughout the reparative phase of the callus, particularly in osteoblasts, preosteocytes, and osteocytes, localized within the newly made osteoid. No labeling was detected in fibroblasts, proliferating chondrocytes, or hypertrophic chondrocytes, consistent with previous results. Taken together, these results suggest that the E11 antigen is indeed a suitable marker for both osteoblasts and osteocytes and that it plays a significant role in osteogenesis.
Explore the source record for details and available documents.
All stereoisomers of three diepoxyalkenes derived from (3Z,6Z,9Z)-trienes with a C21, C19, or C18 straight chain, lymantriid sex pheromones and their candidates, were synthesized by MCPBA oxidation of optically active epoxyalkadienes. Their chromatographic behaviors were examined with GC and LC equipped with achiral and chiral columns. Detailed inspection of the mass spectra of these epoxides indicated the following diagnostic ions for determining the chemical structures: m/z 128, 167, M-87 and M-85 for (Z)-cis-3,4-cis-6,7-diepoxy-9-enes; m/z 111, M-125 and M-69 for (Z)-cis-6,7-cis-9,10-diepoxy-3-enes; and m/z M-125 and M-139 for (Z)-cis-3,4-cis-9,10-diepoxy-6-enes. Mass chromatographic analysis that monitored these fragment ions revealed the existence of a new pheromonal compound with a C21 chain in an extract from virgin females of a lymantriid species, Perina nuda F. The three diepoxyalkenes were converted into the corresponding DMDS adducts, which showed characteristic ions from fragmentation between the two thiomethyl groups, reflecting the position of an original double bond.
Acute allograft glomerulopathy (AAG) characterized by hypercellularity, enlargement of endothelial cells, infiltration of glomeruli by mononuclear cells and webs of PAS-positive material has been reported as an unusual but distinct form of acute rejection in kidney transplant recipients. We present a case of persistent AAG proven by serial biopsies. The patient was 53 years old when she received kidney transplantation from her mother. The immunosuppressants were methylprednisolone, azathioprine and FK506. She developed several acute rejections and received antirejection therapy. The patient transferred to our hospital 15 months after transplantation. Serum creatinine was 2.11 mg/dL. The level of serum creatinine was gradually elevated from 2.11 mg/dL to 3.09 mg/dL. Graft biopsy, performed 16.5 months after transplantation, represented prominent intraglomerular infiltration of mononuclear cells, segmental thickening of glomerular basement membrane (GBM) with double contour, grade 1 tubulitis, marked accumulation of mononuclear cells in peritubular capillaries and margination of mononuclear cells in a small artery. It was diagnosed as acute allograft glomerulopathy (AAG). Intravenous methylprednisolone pulse therapy, discontinuation of FK506 and administration of cyclosporin (CYA) resulted in decrease of serum creatinine. To evaluate histological evolution of AAG we performed two subsequent biopsies over 3 yr. Severe glomerulitis persisted as a prominent feature 8 months later and still existed 53.4 months after transplantation with decreased severity. The extent of GBM reduplication also decreased, but the percentage of glomerular sclerosis increased gradually. Multi-layering of basement membrane of peritubular capillary and interstitial fibrosis also increased. The prominence of infiltration of mononuclear cells in peritubular capillary was unchanged. At the last follow-up, i.e. 71 months after transplantation, her serum creatinine was 1.34 mg/dL. Neither proteinuria nor haematuria was observed. We consider that our immunosuppressive treatment has been successful so far, because the patient is still maintaining stable graft function since the transplantation over 6 yr ago. It is thus suggested that AAG per se probably has no influence on acute aggravation of graft function, but AAG and capillaritis in peritubular capillaries may cause an evolution of chronic allograft nephropathy, resulting in a slowly progressive deterioration of graft function.
Helicobacter pylori, Gram-negative, curved bacteria colonizing the human stomach, possess strain-specific complements of functional restriction-modification (R-M) systems. Restriction-modification systems have been identified in most bacterial species studied and are believed to have evolved to protect the host genome from invasion by foreign DNA. The large number of R-Ms homologous to those in other bacterial species and their strain-specificity suggest that H. pylori may have horizontally acquired these genes. A type IIs restriction-modification system, hpyIIRM, was active in two out of the six H. pylori strains studied. We demonstrate now that in most strains lacking M.HpyII function, there is complete absence of the R-M system. Direct DNA repeats of 80 bp flanking the hpyIIRM system allow its deletion, resulting in an "empty-site" genotype. We show that strains possessing this empty-site genotype and strains with a full but inactive hpyIIRM can reacquire the hpyIIRM cassette and functional activity through natural transformation by DNA from the parental R-M+ strain. Identical isolates divergent for the presence of an active HpyII R-M pose different restriction barriers to transformation by foreign DNA. That H. pylori can lose HpyII R-M function through deletion or mutation, and can horizontally reacquire the hpyIIRM cassette, is, in composite, a novel mechanism for R-M regulation, supporting the general hypothesis that H. pylori populations use mutation and transformation to regulate gene function.
AIM: The aim of this study was to determine the prevalence of anti-liver/kidney microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. METHODS: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/kidney microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. RESULTS: Anti-liver/kidney microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. CONCLUSION: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease.
We evaluated the mortality risk among 306 male alcoholics living in Osaka, Japan, at the time of initial diagnosis between 1972 and 1983, with regard to the cause of death, length of time from diagnosis, and participation in an alcohol abstinence self-help group. By the closing date on 1 March 1992, 110 of the 306 alcoholics had died, yielding an observed-to-expected (O/E) ratio of 4.5 [95% confidence interval (CI) = 3.7-5.4]. The alcoholics had significantly elevated mortality risks from all malignant neoplasms (O/E = 2.1, 95%CI = 1.2-3.3), esophageal cancer (O/E = 8.4, 95%CI = 1.7-24.5), diseases of the circulatory system (O/E = 4.4, 95%CI = 3.0-6.2), liver cirrhosis (O/E = 15.9, 95%CI = 10.2-23.6), diseases of the genitourinary system (O/E = 6.3, 95%CI = 1.3-18.5), and external death (O/E = 10.3, 95%CI = 6.3-15.8). The mortality risk from all causes still remained significantly high beyond the tenth year following initial diagnosis (O/E = 2.6, 95%CI = 1.0-6.2). The mortality risks from liver cirrhosis and external death (such as suicide) were highest within the first year following diagnosis, and were still high beyond the tenth year. A significantly high mortality risk from diseases of the circulatory system was observed between the first and ninth years, and the mortality risk from all malignant neoplasms was significantly elevated beyond 10 years following diagnosis. Alcoholics who did not join a self-help group soon after the initial institutional treatment had different cause-specific and time-specific mortality risks from those who did join a self-help group. These findings show the importance of long-term clinical follow-up of male alcoholics, taking into consideration the cause-specific mortality.
The subjects of this study were 306 male alcoholics who lived in Osaka, Japan, and who were initially diagnosed with alcoholism at a psychiatric institution between 1972 and 1983. Follow-up studies were done on three occasions: 1 March 1985 (Time 1), 1 November 1988 (Time 2) and 1 March 1992 (Time 3). We followed up 232 (75.8%) of the 306 male alcoholics. By the end of the study period 110 (35.9%) of the subjects were deceased. Regarding cross-sectional sobriety status, from Time 1 to Time 3 the complete abstinence rate changed from 16.0 to 18.6%, excessive drinking rate was from 13.1 to 9.8%, and controlled drinking rate was from 6.9 to 9.8%. The longitudinal sobriety status of 122 living patients during the 5 years before the close of this study were: rate of stable abstinence, 28.7%; unstable abstinence, 21.3%; controlled drinking, 12.3%; and relapse 37.7%. Such variables as being without public assistance at the time of the initial diagnosis of alcoholism and attending a self-help group soon after the initial treatment were associated with stable abstinence. Age (20-39 years) and receiving outpatient treatment at the time of the initial treatment also emerged as predictors of survival. However, those variables, except attending a self-help group soon after the initial treatment, might merely indicate severity of alcoholism. For improving treatment results, it may be most important to provide a treatment environment within the residential area so that alcoholics may receive treatment at an early stage of alcoholism and attend a self-help group.
BACKGROUND: Endoscopic ablation with cyanoacrylate glue may achieve gastric variceal obliteration. A prospective evaluation of its therapeutic effects on bleeding gastric varices was conducted, focusing on endoscopic features. METHODS: Thirty-seven patients with bleeding gastric varices underwent endoscopic ablation with cyanoacrylate. RESULTS: Patients with localized-type gastric varices (n = 14) had a better clinical course in terms of recurrent bleeding, variceal eradication, and survival than those with diffuse-type gastric varices (n = 23) after endoscopic ablation with cyanoacrylate. These clinical effects were related to the vascular anatomy of the gastric varices as determined by varicography and 3-dimensional CT. Type 1 vascular anatomy (one varicose vessel without noticeable ramifications) was much more common (86%) in localized-type gastric varices, whereas type 2 vascular anatomy (multiple varicose vessels with complex connecting ramifications) was found almost exclusively (91%) in diffuse-type gastric varices. CONCLUSIONS: Endoscopic ablation with cyanoacrylate is an effective and safe procedure for patients with bleeding gastric varices. Determination of variceal anatomy may be useful for improving treatment strategies for such patients.
BACKGROUND: Although ãlpha-chemokines, such as interleukin (IL)-8 and epithelial neutrophil-activating peptide 78, are implicated in the pathogenesis of inflammatory bowel disease (IBD), little information is currently available on the expression and cellular source of growth-related gene product-alpha (GROalpha) and its functional relationship to other ãlpha-chemokines in the intestinal mucosa of patients with IBD. METHODS: The contents of IL-8 and GROalpha in organ cultures, the expression of IL-8 and GROalpha mRNA, and the modulatory effects of inflammatory mediators on IL-8 and GROalpha-producing cells were examined using colonic mucosal tissues. In vitro stimulatory effects of IL-8 and GROalpha on neutrophils were investigated in terms of chemotactic migration and superoxide anion generation. RESULTS: The contents of IL-8 and GROalpha in organ cultures were elevated in patients with IBD, especially in those with active ulcerative colitis (UC). Both IL-8 and GROalpha contents increased according to an increase in histological disease activity in patients with UC, but not in those with Crohn disease. In contrast, no significant correlation was found between the contents of these alpha-chemokines and clinical disease activity. In situ hybridization detected increased expression of IL-8 and GROalpha mRNA in macrophages, pericrypt myofibroblasts, and the epithelium of tissue specimens with active lesions of IBD. The secretion of IL-8 and GROalpha from macrophages and myofibroblasts obtained from control patients was upregulated by inflammatory cytokines and bacterial products. The concentrations of recombinant (r)-IL-8, which covered the levels of activity detected in individual organ cultures or cell cultures of fractionated mucosal cells, could induce chemotactic migration and superoxide anion generation in neutrophils in vitro, and r-GROalpha had synergistic effects on r-IL-8-induced neutrophil activation. CONCLUSIONS: A coordinate upregulation of IL-8 and GROalpha may be involved in the tissue injury in patients with IBD through their stimulatory effects on neutrophils.
OBJECTIVE: To study the clinical features of methicillin-resistant Staphylococcus aureus (MRSA) enteritis in our surgical ward. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 16 men and 1 woman who developed MRSA enteritis from January 1995 to October 1999. MAIN OUTCOME MEASURES: Causes and treatments. RESULTS: The underlying diseases were as follows: gastric cancer (n = 13), colorectal cancer (n = 2), recurrent cancer (n = 1) and bowel obstruction following gastrectomy (n = 1). 16 patients were operated on. Two cases were treated with histamine H2 receptor blockers. The mean age of patients was 65 years (range 50-80). In 13 cases MRSA enteritis developed within 6 days of operation. 10 strains of MRSA were isolated from stools, 8 from gastric juice, and 3 from intra-abdominal exudate. 10 patients were treated with vancomycin given through a nasogastric tube and 2 through a nasogastric tube and by drip intravenous infusion. 15 patients survived and 2 died. CONCLUSIONS: Patients who are given broad-spectrum antibiotics and whose gastric secretion is reduced are at high risk of MRSA enteritis. In the surgical ward, early diagnosis, treatment, and isolation are essential for patients with MRSA enteritis.
Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid gland and produces a variety of peptides such as calcitonin (CT) and gastrin-releasing peptide (GRP). Here we measured serum levels of pro-gastrin-releasing peptide (Pro-GRP), a more stable precursor of GRP, in 15 patients with MTC (4 males, 11 females) who did not show any clinical or radiologic signs of small cell lung cancer. Serum Pro-GRP levels were elevated in 80% (12/15) patients. Significant correlation was observed between serum Pro-GRP and CT (r = 0.52) and carcinoembryonic antigen (CEA) (r = 0.56). Serum Pro-GRP levels also correlated with tumor size (r = 0.70). Serum Pro-GRP levels also decreased below the cut-off range in one patient after surgical resection. Our data suggest that Pro-GRP, which is considered to be a specific marker for small cell lung carcinoma, seems to be also helpful and additional marker for the diagnosis and monitoring the response to therapy in patients with MTC in addition to calcitonin as the main tumor marker.
BACKGROUND: Acute hemorrhagic rectal ulcer (AHRU) occurs suddenly with painless, massive, fresh rectal bleeding in elderly, bed-ridden patients who have a serious primary disease. There have been several reports on AHRU in Japan, but in Western countries, there have been none. We examined the clinical characteristics of four cases, and we report on AHRU in Western countries. STUDY: The medical records and endoscopic findings in four patients with AHRU seen during a 3-year period were reviewed. The diagnosis of AHRU was established by clinical symptoms, endoscopic examination, and other methods. RESULTS: All of the patients were elderly and bed-ridden and all had sudden onset of massive, fresh rectal bleeding without pain. Sigmoidoscopic examination of all patients showed a shallow or irregular bleeding ulcer in the lower rectum. In three cases, the clinical course was uneventful. In the other case, massive, fresh rectal bleeding recurred but transanal ligation was effective. CONCLUSIONS: When painless, massive, fresh rectal bleeding occurs in elderly and bed-ridden patients, it is important to carefully examine the lower rectum, as there is a strong possibility of AHRU.
We have screened 200 Japanese workers and 105 Japanese patients with alcoholism for the mutation in the signal peptide of pre-pro-neuropeptide Y resulting in a substitution of proline for leucine at position 7. This polymorphism was reported in the Finnish and Dutch populations recently. None of our subjects displayed the mutation at this site. Therefore, this allele does not play any role in the development of alcoholism in the Japanese population.
Genetic factors have been implicated in playing a significant role in susceptibility to anorexia nervosa (AN). Among many candidate genes for AN, an association with the A allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor has been reported. However, these findings are controversial and all patients studied to date have been Caucasian. This study was designed to determine whether this association is reproducible in Japanese subjects. This case-control study of a cohort of 75 female Japanese AN sufferers and 127 normal female control subjects revealed no significant association between the 5-HT2A promoter polymorphism and AN. Thus, at least for Japanese subjects, the A-allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor gene does not contribute to a predisposition to AN.
Elevated plasma tumor necrosis factor-alpha (TNFalpha) levels and enhanced spontaneous TNFalpha release from peripheral blood mononuclear cells in patients with anorexia nervosa (AN) have been reported. TNFalpha activates the hypothalamic-pituitary-adrenal axis and reduces food intake, which is characteristic of eating disorders. Recently, three novel polymorphisms in the 5'-flanking region of the TNFalpha gene were reported at positions -1031 (T --> C substitution), -863 (C --> A) and -857 (C --> T). Differences in these alleles are reportedly related to altered TNFalpha-transcriptional promoter activity. Therefore, we performed a case-control association analysis to determine whether any of those three polymorphisms in the TNFalpha promoter region were involved in a predisposition to AN. The results of our analysis of a cohort of 79 female Japanese AN sufferers and 127 normal female control subjects provide no support for the hypothesis that -1031T/C, -863 C/A and -857C/T polymorphisms in the TNFalpha gene promoter region influence the susceptibility to AN.