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Biomedical subjects

A Yamada

Publications and source records attributed to A Yamada.

At least 253 records · Page 14Linked to original sources

[Correlates and prognosis in relation to intellectual dysfunction in a community-residing elderly population].

To estimate the risk factors for intellectual dysfunction and examine its prognosis in a community-residing (non-institutionalized) elderly population, a randomly selected sample of 1,473 elderly people aged 65 years and over living in S city, Osaka Prefecture, was studied in October 1992, and data were obtained from 1,383, a response rate of 93.9%. A cohort of 1,383 was followed for 42 months and follow-up was completed for 1,300 (94.0%). The main results were as follows: 1) The prevalence of intellectual dysfunction did not differ significantly between sexes, and there was an increasing prevalence of intellectual dysfunction with age in both sexes. The prevalence of severe intellectual dysfunction was found to increase highly at age 85 and over. 2) By univariate analysis, odds ratios for age older than 75 years, low Activities of Daily Living (ADL), urinary and fecal incontinence, and no participation in social activities were significantly higher than 1 in any level of mild, moderate, and severe intellectual dysfunction. In the multivariate analysis using logistic regression, age older than 75 years and urinary and fecal incontinence showed significant higher odds ratios than 1 for severe intellectual dysfunction, and low ADL and treatment for hypertension also showed significant higher odds ratios than 1 for moderate intellectual dysfunction. 3) From analysis using the Kaplan-Meier method, the cumulative survival rates decreased with a decline in intellectual functioning in both age groups of 65-74 and 75 years and older. 4) Application of the Cox proportional hazards model resulted in adjusted hazard ratio for severe intellectual dysfunction of 1.79 (95% confidence interval, 1.02-3.12), controlling for other factors such as sex, age, general health status, incontinence and social activities.

Activities of Daily Living↗

[Preliminary screening for antiviral AIDS drugs. VIII. Report for fiscal year 1995].

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 96 samples of different origin tested, two were shown to inhibit the growth of HIV in vitro. One of the positive samples (plant origin) has hopeful signs, as the ranges of effective doses are wider than those of most of positive samples which had been found by us.

Acquired Immunodeficiency Syndrome↗

The mumps virus SH protein is a membrane protein and not essential for virus growth.

By immunoprecipitation analysis using antisera against oligo peptides synthesized based on the deduced N-terminal and C-terminal amino acid sequences of the SH proteins of the mumps virus, the SH protein was detected in mumps virus-infected cells. The SH protein expressed from cDNA by the vaccinia-T7 expression system was recovered in the membrane fraction. Association of the SH protein with the membrane was resistant to high salt, EDTA, and alkaline treatment but sensitive to detergents. Indirect immunofluorescence experiments showed that the SH protein is involved in the exocytotic pathway. These data indicate that the SH protein is a membrane protein. Treatment of microsomes with TPCK-trypsin suggested that the SH protein is oriented in the membrane with its C-terminal facing the cytoplasm. Furthermore the SH protein was not detected in a particular strain (Enders strain) of mumps virus, indicating that the mumps virus SH protein is not essential for virus replication.

Amino Acid Sequence↗

A monoclonal antibody KIS-1 recognizing a new membrane antigen on human squamous-cell carcinoma.

A KIS-1 monoclonal antibody (MAb) (IgG1, kappa) recognizing a membrane antigen on human squamous-cell carcinomas (SCC) was developed to understand their antigenicity using an esophageal SCC as an immunogen. The KIS-1 MAb recognized a membrane antigen on a majority of esophageal, lung, and oral- cavity SCC by immunofluorescent and by immunohistochemical analyses. In contrast, it showed little reactivity to adenocarcinomas from different organs, and none to keratinocyte cell lines. This MAb showed reactivity to the cells in the basal layer of normal esophageal epithelium adjacent to the esophageal SCC, but none of the other normal tissues, including esophageal epithelium far from the SCC and that from patients with non-malignant disease. The KIS-1 MAb immunoprecipitated a 46-kDa membrane protein of the esophageal SCC in non-reducing and in reducing conditions. It recognized the 46- and the 40-kDa proteins of the esophageal SCC by immunoblot analysis. These results suggest that the KIS-1 MAb recognizes a new membrane antigen preferentially expressed on SCC, and that this antigenicity is shared only by the cells in the basal layer of the esophageal epithelium adjacent to SCC. The KIS-1 MAb may be a new tool for understanding the antigenicity of SCC.

Animals↗

The effect of hepatitis B virus X gene expression on response to growth inhibition by transforming growth factor-beta 1.

Hepatitis B virus X protein (HBx protein), which seems to be involved in hepatocarcinogenesis, was studied for its effect on cell growth regulation. We examined the response to growth inhibition of transforming growth factor beta 1 (TGF-beta 1) in HBx gene-introduced cells. HBx gene in pRc/CMV was transfected to mink lung epithelial cells (Mv1Lu cells) and a stable transformant was obtained. The inhibition rates of [3H] thymidine incorporation by addition of TGF-beta 1 (0.08 ng/ml) to parent cells and pRc/CMV-transfected cells were 34% and 26%, respectively. However, the inhibition rates in the HBx gene-transfected cells were 3-8%. The amount of TGF-beta type II receptor on the surface of HBx gene-transfected cells was about half of that on the parent or pRc/CMV-transfected cells. Our results indicated that expression of HBx gene reduces the response to growth inhibition by TGF-beta 1.

Animals↗

Expression of heparin-binding EGF-like growth factor in rat liver injured by carbon tetrachloride or D-galactosamine.

We reported recently that heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF family, is a new hepatotrophic factor for the regeneration of rat liver after partial hepatectomy. The current study examined changes in the amount of HB-EGF mRNA in liver injured by hepatotoxins. The level of HB-EGF mRNA was very low in normal rat liver, but increased markedly in the liver of rats injured by CCl4, showing two peaks, the first at 6 h and the second at 36 h. Western blot analysis showed that HB-EGF protein in the liver of CCl4-treated rats (at 6 h) was increased about 3.4-fold above normal. The level of HB-EGF mRNA also increased markedly in the liver of rats treated with D-galactosamine, showing a major peak at 18 h, and a smaller one at 6 h. These results indicate that HB-EGF may play a role in the regeneration of the liver following hepatotoxic injury.

Animals↗

Secondary contour reconstruction of maxillectomy defects with a bone graft vascularized by flowthrough from radial vascular system.

We describe post-total maxillectomy secondary facial contour reconstruction using an osteocutaneous scapular flap nourished by flow-through vascularization from the radial vascular system. Scar contracture caused by either total or partial maxillectomy for maxillary cancer was completely released with exposure of the edge of the zygomatic arch, orbital floor, and nasal bone. The scapular skin flap was placed into the mucosal defect, and the orbital floor and zygomatic prominence were reconstructed with the scapular bone. The flap nutrient vessels were anastomosed to radial vessels and cephalic vein grafts. Two representative cases are illustrated to demonstrate the application and advantage of this operative method.

Anastomosis, Surgical↗

Comparison of end-to-end and end-to-side venous anastomosis in free-tissue transfer following resection of head and neck tumors.

A comparative study was conducted of the results of venous end-to-end and end-to-side anastomosis in 948 clinical cases of microvascular free-tissue transfers for head and neck reconstruction following tumor resection. End-to-side anastomosis to the internal jugular vein was achieved uneventfully in the present series, while a variety of recipient veins was used for end-to-end anastomosis. The incidence of thrombosis was 1.8% (15/835) in the end-to-end anastomosis group and 2.7% (3/113) in end-to-side venous anastomosis. No statistical difference was observed between the two groups. One may hesitate to perform end-to-side anastomosis because of unfamiliarity, concern over technical difficulty, and unreliability. As a result of our statistical analysis, we are convinced that end-to-side anastomosis directly to the internal jugular vein, whenever available, is the preferred procedure in microvascular free-tissue transfers for reconstruction of the head and neck following tumor resection.

Adolescent↗

Cytokine messenger RNA expression in the labial salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: To characterize the initiation and progress of localized autoimmune damage in Sjögren's syndrome (SS), an autoimmune disease that is also considered to be a lymphoaggressive disorder, by examining the pattern of cytokine production at the site of autoimmune damage. METHODS: Using a polymerase chain reaction-based method, cytokine messenger RNA (mRNA) expression in the labial salivary glands of 15 patients with SS was investigated. In addition, the infiltrating lymphocytes in the labial salivary glands were examined immunohistochemically. RESULTS: Messenger RNAs of Th1 cytokines, such as interleukin-2 (IL-2) and interferon-gamma, were consistently detected in all patients, while Th2 cytokine mRNAs, such as IL-4 and IL-5, were detected in some cases, in association with strong B cell accumulation in the labial salivary glands. Other cytokine mRNAs produced by a variety of cell types, including IL-10, IL-6, and transforming growth factor beta (TGF beta), were also consistently detected in all patients, while IL-12 mRNA was detected in some of the patients. CONCLUSION: These results suggest that Th1 cytokines, as well as IL-10, IL-6, and TGF beta, are essential in the induction and/or maintenance of SS, while Th2 cytokines are involved in the progression of the disease process, especially local B cell activation.

Adult↗

A distant evolutionary relationship between bacterial sphingomyelinase and mammalian DNase I.

The three-dimensional structure of bacterial sphingomyelinase (SMase) was predicted using a protein fold recognition method; the search of a library of known structures showed that the SMase sequence is highly compatible with the mammalian DNase I structure, which suggested that SMase adopts a structure similar to that of DNase I. The amino acid sequence alignment based on the prediction revealed that, despite the lack of overall sequence similarity (less than 10% identity), those residues of DNase I that are involved in the hydrolysis of the phosphodiester bond, including two histidine residues (His 134 and His 252) of the active center, are conserved in SMase. In addition, a conserved pentapeptide sequence motif was found, which includes two catalytically critical residues, Asp 251 and His 252. A sequence database search showed that the motif is highly specific to mammalian DNase I and bacterial SMase. The functional roles of SMase residues identified by the sequence comparison were consistent with the results from mutant studies. Two Bacillus cereus SMase mutants (H134A and H252A) were constructed by site-directed mutagenesis. They completely abolished their catalytic activity. A model for the SMase-sphingomyelin complex structure was built to investigate how the SMase specifically recognizes its substrate. The model suggested that a set of residues conserved among bacterial SMases, including Trp 28 and Phe 55, might be important in the substrate recognition. The predicted structural similarity and the conservation of the functionally important residues strongly suggest a distant evolutionary relationship between bacterial SMase and mammalian DNase I. These two phosphodiesterases must have acquired the specificity for different substrates in the course of evolution.

Amino Acid Sequence↗

Selective accumulation of anti-histone antibodies in glomeruli of lupus-prone lpr mice.

Immunoglobulins were eluted from glomeruli of 50 lupus-prone, lpr mice and their physicochemical properties and specificity were compared with those in sera pooled from the same mice. Although immunoglobulins in glomeruli had higher isoelectric points than those in sera, there were no appreciable differences in the relative contents of neutral and acidic immunoglobulins between them. The proportion of IgG3 subclass was slightly higher in glomerular than serum immunoglobulins. Both anti-single-stranded and anti double-stranded DNA antibodies were twofold higher in glomerular than serum immunoglobulins, while anti-Sm antibodies were not recovered in glomerular eluate despite their high activity in serum. Antibodies in glomerular eluate reacted most strongly with histones, especially with core histones, while those in sera bound preferentially with histone H1, Sm-B, -B', and -D antigens. Since histones are very basic, they would have a higher affinity for negatively charged glomerular constituents, leading to an in situ formation of immune complexes involving fixed histones and their binding with antibodies for the induction of nephritides. Otherwise, such immune complexes themselves might retain positive charges sufficient for an affinity with the glomerular basement membrane. These results indicate that histone-anti-histone antibody system may play a role in the perpetuation of murine lupus nephritis.

Animals↗

Plasma levels of activated FVII in various diseases.

Plasma activated factor VIIa (FVIIa) levels were measured in various diseases using mutant tissue factor (TF). FVIIa levels in thrombotic patients and patients with idiopathic thrombocytopenic purpura were significantly higher than those in healthy control subjects. The plasma FVIIa levels in thrombotic patients treated with warfarin were similar to those of control subjects. The plasma FVIIa levels in pregnant women and patients with systemic lupus erythematosus, infection or malignancies were high. However, the levels in patients with disseminated intravascular coagulation (DIC) were not significantly increased. DIC patients are in a severe hypercoagulable state, and exhibit severe consumption of coagulation factors. The slightly increased FVIIa level in the DIC patients observed is probably considered to be caused by consumption of coagulation factors. The plasma FVIIa level was poorly correlated with other hemostatic parameters except for protein C in our analysis of all cases. In the analysis of DIC and thrombotic patients treated without warfarin, the plasma FVIIa level was negatively correlated with TF antigen. Plasma FVIIa levels might reflect hypercoagulability in thrombotic diseases, and a normalized FVIIa level in patients with thrombotic diseases should be considered to be associated with DIC.

Autoimmune Diseases↗

Comparison of direct negative chronotropic and positive inotropic effects of sematilide to those of E-4031 and MS-551 and the reverse frequency-dependent prolongation of cardiac refractoriness of sematilide.

Direct cardiac effects of sematilide, a new class III antiarrhythmic drug, were compared with those of E-4031 and MS-551 in canine isolated blood-perfused heart preparations. Doses of sematilide, E-4031, and MS-551 causing a 10% decrease in the spontaneous sinoatrial beating rate were 58 +/- 15, 9 +/- 5, and 84 +/- 10 micrograms (n = 5); those causing a 10% increase in developed tension of the papillary muscle were 485 +/- 49, 17 +/- 2, and 267 +/- 50 micrograms (n = 6); and those causing a 10% prolongation of effective refractory period (ERP) of the atrioventricular node were 68 +/- 10, 11 +/- 2, and 53 +/- 15 micrograms (n = 5), respectively. There were few effects on atrio-His or His-ventricular intervals. Also, in in situ open-chest dog hearts, the percent increases in ERP of the atrioventricular conduction system caused by 1 mg/kg of sematilide were 21 +/- 3, 16 +/- 2 and 9 +/- 1% at cycle lengths of 800, 600, and 400 ms, respectively (p < 0.01; n = 8). These results indicate that (a) sematilide, as well as E-4031 and MS-551, has direct negative chronotropic and positive inotropic effects and prolongs cardiac refractoriness without affecting conduction velocities; (b) quantitatively, the cardiac effects of sematilide were almost identical to those of MS-551 and five to ten times less potent than those of E-4031; (c) and prolongation of ERP of the atrioventricular conduction system by sematilide occurred in a reverse frequency-dependent manner.

Animals↗

Long-term acceptance of major histocompatibility complex-mismatched cardiac allograft induced by a low dose of CTLA4IgM plus FK506.

The immunosuppressant FK506 prolongs allograft survival. However, at therapeutic doses it has significant side effects. A fusion protein consisting of the extracellular portion of CTLA4 and the Fc portion of human IgG (CTLA4IgG) also prolongs allograft survival, but large doses of CTLA4IgG are required for the induction of cardiac allograft acceptance. Therefore, we constructed a pentameric form of a new CTLA4 fusion protein, CTLA4IgM. We tested whether low doses of CTLA4IgG or CTLA4IgM in combination with subtherapeutic doses of FK506 can prolong allograft survival in a synergistic fashion. C57BL/6 (H-2b) neonatal hearts were transplanted to CBA/J (H-2b) mice in a heterotopic, nonvascularized cardiac allograft model. The findings demonstrate that a combination of low doses of FK506 plus a pentameric form of CTLA4Ig, CTLA4IgM, leads to significant graft survival, while a combination of FK506 plus CTLA4IgG does not.

Abatacept↗

Isolation and characterization of mumps virus strains in a mumps outbreak with a high incidence of aseptic meningitis.

In 1993, mumps with a high incidence of aseptic meningitis became prevalent in Akita prefecture, Japan. Three mumps virus isolates obtained from the nonvaccine-associated cases lacked the BamHI restriction cleavage site of the P gene, like the Urabe strain (Yamada, A. et al, Vaccine 8: 553-557). However, four additional nucleotide substitutions were found in the determined region of 157 bp. Fourteen of 19 cases from which mumps virus showing the Urabe-like RFLP profile was detected were complicated with symptomatic meningitis, whereas there were only four cases of meningitis among 23 individuals infected with the wild type showing no Urabe-like RFLP profile (non-"Urabe-like" wild-type). The incidence of meningitis was over 70% among patients infected with the "Urabe-like" wild-type virus. The "Urabe-like" wild-type. disappeared after February 1994 in the epidemic area and was replaced by the non-"Urabe-like" wild-type. Patients infected with the "Urabe-like" wild-type lived in a closed colony, in which there were two instances of transmission between siblings. Thus this outbreak was transient and narrowly localized.

Base Sequence↗