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S Harada

Publications and source records attributed to S Harada.

At least 793 records · Page 44Linked to original sources
PubMedDate not supplied

Basis of aldehyde dehydrogenase deficiency in Orientals: immunochemical studies.

While most Caucasians have two main isozymes of liver aldehyde dehydrogenase, in about 50% of Orientals the ALDH I isozyme is missing. This isozyme, which has a faster electrophoretic mobility, is predominantly present in mitochondria and has a relatively low Km for acetaldehyde. The inherent deficiency of ALDH I is responsible for the impaired acetaldehyde oxidation leading to facial flushing and other cardiovascular symptoms of alcohol sensitivity commonly observed in Japanese and Chinese. Antibodies raised against apparently homogeneous liver ALDH I and ALDH II isozymes did not show an immunological similarity between the two isozymes which do not share common subunits. While erythrocyte ALDH II is also immunologically distinct from hepatic ALDH I, it showed an immunological similarity with hepatic ALDH II. On isoelectric focusing in agarose gel followed by immunoelectrophoresis, at least 4 components with an anti-ALDH I antibody were detected in extracts from Caucasian and Oriental livers. In Japanese livers deficient in ALDH I activity, the prominent ALDH component was missing. Apparently, more than one gene is responsible for the synthesis of ALDH isozymes reacting with an antibody against ALDH I. A deletion in one of the genes may be responsible for the loss of ALDH I enzyme activity and altered antigenic properties. However, at this stage, a point mutation in a structural gene coding for ALDH I resulting in a defective protein with altered electrophoretic and enzymatic properties is not ruled out.

Aldehyde Dehydrogenase↗
PubMedDate not supplied

Population genetic and family studies on aldehyde dehydrogenase deficiency and alcohol sensitivity.

Population genetic studies on the prevalence of aldehyde dehydrogenase isozyme I (ALDH I) deficiency in various Caucasian, Oriental, African, and American Indian subjects were carried out using hair roots as peripheral source of the enzyme activity. While a very high percentage of Orientals with Mongoloid origin were found deficient in ALDH I activity, no deficiency was detected in Caucasian and African populations. Native American Indians showed a relatively low incidence of ALDH I deficiency. A genetic model based on the phenotype determination using antisera against purified human liver ALDH I is proposed. Pedigree analysis of Japanese families suggests an autosomal codominant mode of inheritance.

Aldehyde Dehydrogenase↗
PubMedDate not supplied

Aldehyde dehydrogenase polymorphism and alcohol metabolism in alcoholics.

Significant differences in the incidence of aldehyde dehydrogenase isozyme I deficiency were observed between healthy controls and alcoholics in Japan. Only about 5% of alcoholics were found deficient as compared to about 42% in the normal healthy population. Blood acetaldehyde level after alcohol drinking was also found significantly higher in deficient subjects than in individuals without deficiency. Among alcoholics, deficient subjects showed relatively less elevated blood acetaldehyde levels. When two districts in Japan were compared, per capita alcohol consumption correlated with the frequency of isozyme deficiency. Higher percentage of aldehyde dehydrogenase isozyme deficiency was associated with lower per capita alcohol consumption. Thus, individuals deficient in aldehyde dehydrogenase isozyme may consume less alcohol.

Acetaldehyde↗
PubMedDate not supplied

Quantitative and qualitative biochemical parameters for alcohol abuse.

Blood from alcoholics, non-alcoholic patients and healthy controls were analyzed for various biochemical markers. Follow-up measurements were made during about 3 months of abstention. While a gradual increase in aldehyde dehydrogenase activity (ALDH) in red cell was noted in alcoholic patients serum alpha 1-acid glycoprotein (AAG) values returned to normal range within 8 weeks during abstinence. An additional minor band for alpha 1-antitrypsin (AAT) was observed after isoelectric focusing of sera from alcoholics; this band disappeared after 3 weeks of abstinence. However, no such unusual AAT band was found in non-alcoholic patients with liver disorders.

Alanine Transaminase↗
PubMedDate not supplied

Gustatory information of umami substances in three major taste nerves.

The chorda tympani (CT), glossopharyngeal (GL), and greater superficial petrosal (GSP) nerves, the three major branches of cranial nerves innervating taste buds, respond with considerable differences to various taste stimuli. To examine which nerve is responsible for transmitting umami taste in rats, we conducted electrophysiological and behavioral experiments. In the electrophysiological study, responses to umami substances were compared among these three nerves. The CT and GSP were more responsive to mixtures of monosodium L-glutamate (MSG) and 5'-inosine monophosphate (IMP) than the GL. Synergistic effects by the mixture of MSG and IMP were the most prominent in the CT followed by the GSP, whereas it was negligible in the GL. In the behavioral study, rats with a combined transection of the CT and GSP could not acquire conditioned taste aversions to umami substances. These results suggest that umami taste is conveyed more dominantly via the CT and GSP than the GL in the rat.

Animals↗
PubMedDate not supplied

Binding of a non-beta-lactam antibiotic to penicillin-binding proteins.

In the search for new beta-lactam antibiotics of natural origin, the discoveries of cephamycins and sulfazecins (monobactams) were important turning points in that they accelerated many screening efforts aimed at other new compounds. In our target-directed screening for beta-lactam antibiotics using beta-lactam hypersensitive mutants, we have examined Gram-negative bacteria isolated from natural habitats and have recently reported several types of beta-lactam antibiotics such as cephabacins and formadicins. Here we report a novel antibiotic, lactivicin, found using this system. Although lactivicin has various biological activities commonly observed in beta-lactam antibiotics, it does not possess a beta-lactam ring in its molecule, but has the unique structure of a dicyclic dipeptide.

Anti-Bacterial Agents↗
PubMedDate not supplied

Human T cell leukemia virus-1 antibodies not detected in AIDS.

A collaborative study of sera from men in New York City with AIDS and at risk for AIDS, by investigators in Omaha, Cambridge and Kyoto, has failed to identify antibodies to human T cell leukemia virus I (HTLV-I).

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Detection of antibodies to human T-lymphotropic viruses type I and III in Japanese hemophiliacs.

Sera of 65 hemophiliacs, 85 hemodialysis patients and 304 healthy volunteer blood donors in Japan were tested for antibodies against both HTLV-I and -III by an indirect immunofluorescence and radioimmunoprecipitation assay. The results showed that 10 (15.4%) of the hemophiliacs were anti-HTLV-III positive, while all other subjects were anti-HTLV-III negative. All groups contained subjects positive for anti-HTLV-I. The prevalence of the antibody in the hemophiliacs (17.4%) and hemodialysis patients (9.4%) was significantly high as compared to that of healthy controls (1%).

Adolescent↗
PubMedDate not supplied

Epstein-Barr virus and chronic lymphadenomegaly in male homosexuals with acquired immunodeficiency syndrome (AIDS).

Male homosexuals at risk for developing AIDS frequently exhibit chronic lymphadenomegaly (LAD). They are at high risk for developing malignant B cell lymphomas. A study of Epstein-Barr virus (EBV) revealed marked abnormalities in these patients. One hundred percent of the patients were seropositive. The patients with most severe acquired immune deficiency disorders manifested a decreased number of circulating B cells with EBV receptors and decreased lymphocyte transformation. Patients often showed defective memory T cell cytotoxic responses to autologous EBV infection in vitro. Three of five lymph node specimens contain significant EBV genome copies to suggest a significant etiologic role. In addition, a Burkitt-like lymphoma carried EBV genome. Although all of the men were seropositive for EBV, reactivation patterns were not as common as anticipated. Given the presence of EBV genome in the lymph nodes of the patients who lack anti-early antigen (EA) antibodies indicative of reactivation, we suggest that reliance on serology to indicate EBV involvement is insufficient for assessing the patient. The detection of a t(8;14) transposition in the monoclonal mu kappa Burkitt-like lymphoma containing EBV genome supports the view that cytogenetic transposition is a mechanism in lymphomagenesis.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

The prevalence of mitochondrial gene mutations in childhood diabetes in Japan.

To investigate the prevalence of mitochondrial DNA mutations among Japanese children with IDDM as well as in those with NIDDM, a total of 155 patients with IDDM and 30 patients with NIDDM who were younger than 15 years of age at onset were studied for the following mtDNA mutations: 1) the A-->G mutation at position 3243 of mitochondrial leucine transfer RNA (3243 mutation); 2) the G-->A mutation at position 3316 of mitochondrial leucine transfer RNA (3316 mutation), and 3) The T-->C mutation at position 3394 of the mitochondrial NADH dehydrogenase subunit (3394 mutation). None of the 155 IDDM patients had the 3243 mutation. Although two of the 155 IDDM patients had homoplasmy of 3316 and five had 3394 mutations, these frequencies were not significant compared with healthy controls. None of the 30 NIDDM patients had the 3243, 3316 or 3394 mutation. The presence of these mutations even in control subjects suggests that the effect of the 3316 or 3394 mutation on mitochondrial function is relatively mild. It seems that 3316 and 3394 mutations contribute to the manifestation of diabetes together with other genetic and/or environmental factors.

Adolescent↗
PubMedDate not supplied

Erythrocytosis in hypophosphatemic rickets: irreversible complication due to nephrocalcinosis after vitamin D and phosphate therapy.

A patient with hypophosphatemic vitamin D-resistant rickets developed secondary erythrocytosis during treatment with large doses of vitamin D2 and phosphate. Erythrocytosis was accompanied by a fall in circulating plasma volume and appeared to have developed as a consequence of nephrocalcinosis because it occurred after the appearance of nephrocalcinosis following several episodes of hypercalcemia and hyperphosphatemia. Nephrocalcinosis and erythrocytosis did not disappear even after recovery of renal function. Thus, the present observations point to the importance of preventing these irreversible complications that could cause renal failure, erythrocytosis, and thrombotic events during the management of hypophosphatemic vitamin D-resistant rickets.

Adult↗
PubMedDate not supplied

[Granulocyte colony-stimulating factor producing undifferentiated carcinoma of urinary bladder: a case report].

A case of bladder cancer producing granulocyte colony-stimulating factor (G-CSF) is reported. A 94-year-old woman with a progressive, grade 3 undifferentiated carcinoma, showed marked leukocytosis (maximum 29,780/mm3) with an elevated G-CSF (420 pg/ml). Immunohistochemical examination with monoclonal antibody specific for G-CSF revealed positive staining. Further examination for epidermal growth factor receptor (EGF-R) and p53 were both positive and Ki67 index were 40.7%. These data suggested that this tumor had extremely aggressive growing nature, as the biological character is this.

Aged↗
PubMedDate not supplied

Antitumor and immunosuppressive activities of lankacidin-group antibiotics: structure-activity relationships.

The antitumor and immunosuppressive activities of the lankacidin-group antibiotics were studied in mice. Seventeen of 29 newly prepared lankacidin-group antibiotics, including 14-derivatives of lankacidin C, lankacidinol, isolankacidinol, and lankacidinol 14-acetate, possessed considerable antitumor activity against ascites 6C3HED/OG lymphosarcoma. Comparative studies on the antitumor activity of lankacidin C and eight of its derivatives against L1210 leukemia and solid 6C3HED/OG lymphosarcoma demonstrated that replacement of the hydroxyl group at position 8 or 14 of lankacidin C by an acyloxy group potentiated antitumor activity. However, these modifications of lankacidin C resulted in reduction of the immunosuppressive activity.

Animals↗
PubMedDate not supplied

D-penicillamine cooperates with copper sulfate to enhance the surface expression of functional Fas antigen in rheumatoid synovial fibroblasts via the generation of hydrogen peroxide.

OBJECTIVE: D-penicillamine (DP) has been shown to cooperate with copper ion to inhibit cell growth in a variety of cell types. To determine whether this inhibitory action is involved in Fas-mediated apoptosis, we examined the effect of DP and copper sulfate on the expression and function of Fas antigen in rheumatoid synovial fibroblasts (RSFs). METHODS: The expression of Fas antigen on the cell surface was determined by flow cytometric analysis. Western blot analysis was performed to examine the protein expressions of Fas and Fas-ligand In addition, the amounts of apoptotic cells were determined by 4', 6-diamidino-2'-phenylindol dihydrochloride (DAPI) and propidium iodide (PI) staining. RESULTS: Although DP and copper sulfate alone did not affect the surface expression of Fas antigen on RSFs, both in combination augmented the Fas expression in dose- and time-dependent manners. The enhanced expression of Fas antigen on their surface was also observed in interleukin-1alpha (IL-1alpha) and/or tumor necrosis factor a (TNFalpha) stimulated RSFs. On the other hand, the combination of DP and copper sulfate did not increase the amounts of cellular Fas protein, as determined by Western blot analysis. To determine whether the induced Fas antigen is functional, we examined the effect of DP and copper sulfate on Fas-mediated apoptosis, using an agonistic anti-Fas antibody. The treatment of this antibody induced the apoptosis in untreated RSFs, as determined by DAPI staining. The combination of DP and copper sulfate further enhanced the Fas-mediated apoptosis. The enhanced apoptosis and cell surface expression of Fas was completely prevented by catalase, indicating that hydrogen peroxide may be involved in these effects of DP and copper sulfate. The protein expression of Fas-ligand, a natural ligand for Fas antigen, in RSFs. was expressed in untreated RSFs. However, the protein levels were not modulated by DP and copper sulfate. CONCLUSIONS: Our data demonstrated that DP cooperated with copper sulfate to enhance the cells surface expression of functional Fas antigen in RSFs. In addition, Fas-ligand was expressed in the RSFs. These findings suggested that DP might regress rheumatoid synovial hyperplasia via Fas-mediated apoptosis.

Antirheumatic Agents↗
PubMedDate not supplied

Cooperative induction of 15-lipoxygenase in rheumatoid synovial cells by IL-4 and proinflammatory cytokines.

OBJECTIVE: To clarify the role of interleukin-4 (IL-4) in the expression of 15-lipoxygenase (15-LOX), whose metabolities are known to suppress the inflammatory reaction, in freshly prepared rheumatoid synovial cells. METHODS: Adherent synovial cells were prepared by enzymatic digestion of synovia obtained from patients with rheumatoid arthritis (RA). Protein expression of 15-LOX was determined by Western blot analysis. The messenger RNAs of 15-LOX were determined by reverse transcription and the polymerase chain reaction (RT-PCR). RESULTS: Freshly prepared rheumatoid synovial cells did not express 15-LOX at either the mRNA or protein levels. IL-4 induced the protein expression of 15-LOX after 24 hours of culture. Although interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha), major inflammatory cytokines in rheumatoid synovia, did not induce the expression of 15-LOX, IL-4 and these inflammatory cytokines synergistically enhanced the protein expression of 15-LOX. The synergistic effect was also observed at the level of mRNA. CONCLUSIONS: We demonstrate that IL-4 cooperated with the inflammatory cytokines IL-1 alpha and TNF alpha to enhance the expression of 15-LOX in rheumatoid synovial cells. Since 15-LOX metabolites have potent anti-inflammatory actions, our data suggest that IL-4 might downregulate rheumatoid inflammation via the induction of 15-LOX and its metabolites.

Alprostadil↗