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Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 631 records · Page 35Linked to original sources

A mutated ARO4 gene for feedback-resistant DAHP synthase which causes both o-fluoro-DL-phenylalanine resistance and beta-phenethyl-alcohol overproduction in Saccharomyces cerevisiae.

o-Fluoro-DL-phenylalanine (OFP)-resistant mutants which overproduce beta-phenethyl-alcohol were isolated from a laboratory strain of Saccharomyces cerevisiae. Cells of one of the mutants accumulated tyrosine and phenylalanine 1.5-3 fold more than did wild-type cells. Its 3-deoxy-D-arabino-hepturosonate-7-phosphate (DAHP) synthase (EC 4.1.2.15), encoded by ARO4, was free from feedback inhibition by tyrosine. Genetic analysis revealed that the mutation was controlled by a single dominant gene, ARO4-OFP, encoding feedback-resistant DAHP synthase by tyrosine, and that this gene caused both the OFP resistance and beta-phenethyl-alcohol overproduction. This was supported by molecular genetic studies using cloned ARO4 both from the wild-type and its mutant strain.

3-Deoxy-7-Phosphoheptulonate Synthase↗

Ultrasound examination of caesarean section scars during pregnancy.

Two hundred and sixteen transverse caesarean section scars were examined sonographically near term by a conventional method (175 scars) and a new method (41 scars). The new method consisted of obtaining a transabdominal longitudinal scan by the conventional method and also by a 3M conductor, a transabdominal frontal scan to give a surface view of the scar, and transperineal and transvaginal longitudinal scans. The new method was used from 16 weeks of gestation onwards. Of 41 scars scanned by the new method, 31 showed good healing, being more than 2 mm in thickness throughout; 10 scars showed poor healing with a thickness of less than 2 mm and loss of continuity. Of 31 patients with good healing, 8 delivered vaginally and the remaining 23 patients had repeat caesarean sections for other obstetric indications. All patients with ultrasound evidence of poor healing had repeat caesarean sections. At operation the thickness of the lower uterine segment was measured with ophthalmic calipers. There were 4 false negative results (4/83: 4.8%) and 1 false positive result (1/43: 2.3%) with conventional ultrasound and no false positives or false negatives with the new method.

Adult↗

Intracellular mechanisms involved in basement membrane induced blood vessel differentiation in vitro.

The extracellular matrix, particularly basement membranes, plays an important role in angiogenesis (blood vessel formation). Previous work has demonstrated that a basement membranelike substrate (Matrigel) induces human umbilical vein endothelial cells to rapidly form vessel-like tubes (Kubota, et al., 1988; Grant et al., 1989b); however, the precise mechanism of tube formation is unclear. Using this in vitro model, we have investigated morphologic changes occurring during tube formation and the cytoskeletal and protein synthesis requirements of this process. Electron microscopy showed that endothelial cells attach to the Matrigel surface, align, and form cylindrical structures that contain a lumen and polarized cytoplasmic organelles. The cytoskeleton is reorganized into bundles of actin filaments oriented along the axis of the tubes and is located at the periphery of the cells. The addition of colchicine or cytochalasin D blocked tube formation, indicating that both microfilaments and microtubules are involved in this process. Cycloheximide blocked tube formation by 100%, indicating that the process also required protein synthesis. In particular, collagen synthesis seems to be required for tube formation because cis-hydroxyproline inhibited tube formation, whereas either the presence of ascorbic acid or the addition of exogenous collagen IV to the Matrigel increased tube formation. Our results indicate that endothelial cell attachment to Matrigel induces the reorganization of the cytoskeleton and elicits the synthesis of specific proteins required for the differentiated phenotype of the cells.

Ascorbic Acid↗

Therapeutic efficacy of interferon on HCV-RNA in chronic hepatitis C.

The efficacy of interferon therapy for chronic hepatitis C were evaluated by the changes of serum RNA of the hepatitis C virus (HCV) by the polymerase chain reaction. Before the treatment, HCV-RNA was detected in all of the 17 patients. 5 patients given IFN for 4 weeks, 12 cases given IFN by the 2 weeks/on 2 weeks off schedule (4 cases given 4 cycles and 8 given 6 cycles). Immediately after the treatment ended, the HCV-RNA was not detected in 12 (71%) cases. Five cases were persistently positive for HCV-RNA and showed continuously abnormal level of ALT. In 7 of 12 cases who became negative for HCV-RNA just after the treatment ended, HCV-RNA was detected again at first and 12th month after therapy. The ALT level were continuously abnormal in 4 of these 7 cases during and after the treatment, and became normal transiently in the other 3. In the 5 cases who became persistently negative (at least 1 year), ALT level decreased to normal or near-normal during follow up for more than one year. According to our results, we classified the therapeutic efficacy of IFN therapy for chronic hepatitis C. Type I response is complete response. In this type, HCV-RNA became negative persistently and ALT became normal or near-normal for at least 12 months after therapy. Type II is partial response. In this type, HCV-RNA became negative transiently and ALT level was transiently normal or poor. Type III is ineffective. In this type, HCV-RNA did not become negative and the effect for ALT was poor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bidirectional morphological changes induced by dexamethasone in Morris hepatoma cell lines McA-RH7777 and McA-RH8994: independence of fibronectin and its receptor.

Two Morris hepatoma-derived cell lines, McA-RH7777 (7777) and McA-RH8994 (8994), exhibit different alterations in morphology upon exposure to glucocorticoid. After treatment with synthetic glucocorticoid dexamethasone (DEX), 7777 cells show increased adhesiveness and more flattened shape, while DEX-treated 8994 cells show decreased adhesiveness to substratum and exhibit a marked increase of round and detached cells. Since fibronectin has been thought to play an important role in cell adhesiveness to substratum in hepatoma cell culture, we have also compared the effects of DEX on the biosynthesis of fibronectin (FN) and the functional level of FN receptor in 7777 and 8994 cells. Northern blot analysis and immunofluorescent studies showed that 7777 cells have a high basal expression level of FN synthesis and that DEX treatment induces FN expression two- to threefold with establishment of an extensive fibrillar FN network around the cells. On the other hand, 8994 cells were shown to express little FN and no apparent FN was localized on nonstimulated 8994 cells. However, DEX-treatment drastically increased FN expression in 8994 cells to the level of more than that of DEX-treated 7777 cells and induced a detectable level of cell-associated FN around DEX-treated 8994 cells, which appears to be contradictory to the decreased adhesiveness to the substratum in DEX-treated 8994 cells. Cell attachment assays using FN-coated plates demonstrated that DEX does not exhibit significant effects on the attachment of either 7777 or 8994 cells to FN-coated dishes. Our results suggest that decrease of adhesiveness to the substratum and increase of round detached cells in DEX-treated 8994 cells are independent of changes in the FN expression and the function of FN receptor.

Animals↗

Cerebrotendinous xanthomatosis: clinical and biochemical evaluation of eight patients and review of the literature.

We present the clinical and laboratory findings of 8 patients with cerebrotendinous xanthomatosis. The clinical features consisted of a combination of bilateral Achilles tendon xanthomas, cataracts, low intelligence, pyramidal signs, cerebellar signs, convulsions, peripheral neuropathy, foot deformity, cardiovascular disease or atherosclerosis, EEG abnormality, and increased CSF protein. Increased cholesterol was present in the serum, CSF and red cell membrane of all 8 patients. The bile of one patient with late age onset of the disease showed an attenuated production of bile acids and bile alcohols. Three of the 7 had obstruction and/or marked narrowing of the coronary arteries. Data on 136 patients reported throughout the world are reviewed.

Achilles Tendon↗

Characterization of CS-045, a new oral antidiabetic agent, II. Effects on glycemic control and pancreatic islet structure at a late stage of the diabetic syndrome in C57BL/KsJ-db/db mice.

Antidiabetic effects of CS-045 were evaluated in 5-month-old C57BL/KsJ-db/db mice (db/db). CS-045 administered for 3 weeks to diabetic db/db mice as a 0.2% food admixture improved hyperglycemia (855 +/- 25 v 298 +/- 62 mg/dL, P less than .01) and glucose intolerance, and lowered plasma triglyceride (299.6 +/- 28.7 v 76.3 +/- 20.7 mg/dL, P less than .01) and free fatty acid (FFA) levels (1.16 +/- 0.14 v 0.57 +/- 0.07 mEq/L, P less than .01). Food intake was not changed, while a small but significant increase in body weight was observed in CS-045-treated mice. Plasma insulin levels gradually increased after 5 days of CS-045 treatment, and a nonsignificant increase was observed in plasma insulin levels after 3 weeks (1.85 +/- 0.50 v 4.54 +/- 1.47 mg/mL). In contrast, the plasma glucagon levels decreased after 3 weeks of CS-045 treatment. Histological examination by aldehyde-fucshin staining demonstrated that pancreatic beta cells in CS-045-treated db/db mice were heavily regranulated, whereas most of the beta cells were extensively degranulated in nontreated db/db mice. The heavily regranulated state of beta cells was also compatible with an increase in pancreatic insulin content in CS-045-treated db/db mice. Electron microscopic analysis showed a well-developed endoplasmic reticulum and the accumulation of much amorphous structural material in the intracisternal space of beta cells from CS-045-treated db/db mice, which were suggestive of an increase in insulin synthesis. Moreover, CS-045 treatment decreased exocrine-containing islets, which was associated with the islets' degeneration process. Immunohistochemical staining of islets showed that CS-045 treatment normalized the distribution pattern of endocrine cells in the islets of db/db mice, reflected by a predominantly peripheral location of alpha and delta cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Identification of (23S)-5 alpha-cholestane-3 alpha,7 alpha,12 alpha,23,25-pentol in urine of patients with cerebrotendinous xanthomatosis.

This paper describes the identification of a new bile alcohol possessing the 5 alpha-cholestane structure that was found in the urine of patients with cerebrotendinous xanthomatosis. The urine samples were extracted with reversed-phase resin, treated with beta-glucuronidase, and separated on silica gel and reversed-phase column chromatography. The new bile alcohol isolated was the second component of the urinary bile alcohols and was identified as (23S)-5 alpha-cholestane-3 alpha,7 alpha,12 alpha,23,25-pentol by means of gas-liquid chromatography/mass spectrometry and nuclear magnetic resonance spectroscopic studies.

Brain Diseases↗

Expression of ras oncogene product and EGF receptor in cervical squamous cell carcinomas and its relationship to lymph node involvement.

The expression of ras oncogene product p21 and epidermal growth factor (EGF) receptor was studied immunohistochemically in tissues obtained from 52 patients with squamous cell carcinoma of the uterine cervix. We examined the relationship between p21 and EGF receptor expression and lymph node metastasis in cervical cancer. The data demonstrate that the patients with positive staining for ras p21 in cervical carcinomas have a higher incidence of lymph node metastasis than the patients with negative staining for p21 (P = 0.027). Although the levels of p21 expression in the metastatic sites were reduced compared to those in the primary sites, tumor cells in metastatic lymph nodes also expressed p21. No relationship was found between EGF receptor expression and lymph node metastasis. These results suggest that expression of ras oncogene product may be associated with the biological aggressiveness of cervical carcinomas.

Carcinoma, Squamous Cell↗

Antitumor effects of human recombinant interferon-gamma and tumor necrosis factor on five cervical adenocarcinoma cell lines, in vivo and in vitro.

We examined the antitumor effects of recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) on cervical adenocarcinoma cell lines, in vitro and in vivo. Four of five cell lines showed a high sensitivity to IFN-gamma, in vitro. One of five cell lines showed a remarkable sensitivity to TNF, in vitro. Only one cell line resistant to both IFN and TNF was derived from a well-differentiated adenocarcinoma of endocervical type. Experiments using nude mice bearing transplanted tumors revealed that these cytokines were also effective against tumors in vivo. All these observations suggest that IFN-gamma or TNF can have positive effects in the treatment of patients with adenocarcinoma of the uterine cervix.

Adenocarcinoma↗

Subepicardial microischemia formation induced by epicardial application of endothelin-1.

The effects of endothelin-1 (ET-1), applied topically on the epicardium, on the coronary microcirculation of the beating canine heart were investigated in situ. ET-1 (1, 10, 100, and 1,000 pmol) induced a dose-dependent elevation of the ST segment in the epicardial ECG (n = 5). After application of ET-1 (100 pmol), the beating hearts were rapidly cross-sectioned and freeze-clamped in 120 ms using a specially developed device (n = 6). By NADH fluorescence photography of the cross-sectioned frozen sample, an increased fluorescent area in the subepicardium was clearly observable. The fluorescent dye injected from the left atrium was negative in the NADH fluorescent area. It can be concluded that ET-1, when administered extravascularly, induces severe vasoconstriction and myocardial ischemia in the microcirculation of the beating canine heart.

Administration, Topical↗

[Hafnia alvei septicemia with shock and DIC in an adult with postoperative lung cancer].

In Japan, we experienced the first case of Hafnia alvei septicemia with shock and disseminated intravascular coagulation (DIC) in an adult with postoperative lung cancer. A 63 year-old male, who had been followed up in our department since 1987, was admitted to our hospital with the complaints of fever, hemoptysis and dyspnea on June 25, 1989. After admission, he was treated with sulbactam/cefoperazone 4 g/day intravenously for suspicion of respiratory-tract infection. After antibiotic administration, the fever subsided and the general condition became almost good. The patient experienced fever again after the antibiotic was stopped. For this reason subsequent Clavulanic acid/Amoxicillin, Flomoxef, and Ceftazidime was administered, but was not effective. Therefore septicemia was suspected and blood culture was done. The bacteria isolated from blood culture was identified as Hafnia alvei. Hafnia alvei is a gram-negative organism belonging to the Enterobacteriaceae family and quite rare pathogen in human.

Bacteremia↗

A quantitative histopathological study of right bundle branch block complicating acute anteroseptal myocardial infarction.

The aim of the present study was to evaluate whether necrosis of the right bundle branch is responsible for development of right bundle branch block in acute myocardial infarction. Twenty patients with acute anteroseptal myocardial infarction were studied--10 with right bundle branch block (group A) and 10 without (group B)--to evaluate by serial sectioning the pathological extent of myocardial infarction surrounding the right bundle branch and also that of right bundle branch necrosis. Myocardial infarction reached the right bundle branch more than 8 mm above the moderator band in all of group A, whereas myocardial infarction reached the right bundle branch less than 3 mm above the moderator band in only three patients in group B. Nine hearts in group A showed significant necrosis of the right bundle branch. In group B and in one case with transient right bundle branch block no necrosis was found. The occurrence of right bundle branch block was almost entirely explained by necrosis of the right bundle branch, but transient right bundle branch block did develop without necrosis of the right bundle branch.

Aged↗

Histamine H1-receptor-mediated keratan sulfate production in rabbit chondrocytes: involvement of protein kinase C.

We investigated the characteristics of the histamine H1-receptor in cultured rabbit chondrocytes. Scatchard analysis of [3H]pyrilamine, an H1-antagonist, binding to the chondrocytes revealed a single class of binding sites with KD and Bmax values of 90 +/- 12 nM and 56 +/- 11 fmol/10(4) cells, respectively. H1-agonists stimulated the production of keratan sulfate in a dose-dependent manner. Stimulation of keratan sulfate production was inhibited by pyrilamine. Protein kinase C inhibitors (sphingosine and H-7) also had inhibitory effects. Phorbol 12,13-dibutyrate, a direct activator of protein kinase C, activated the production. When protein kinase C in the chondrocytes was down-regulated by preincubation with phorbol ester, the effect of the H1-agonist on keratan sulfate production was abolished. These results indicate that the histamine H1-receptor on chondrocytes mediates the accumulation of keratan sulfate production and that protein kinase C is involved in these events.

Animals↗

Enzyme labeling in steroid enzyme immunoassays. Comparison of the p-nitrophenyl ester and N-succinimidyl ester methods.

Enzyme labeling of steroids by the p-nitrophenyl ester method was investigated in comparison with the N-succinimidyl ester method. The active ester of a testosterone or 11-deoxycortisol derivative was treated with beta-galactosidase and horseradish peroxidase to give labeled antigens. Various molar ratios of steroid to enzyme and pH conditions were tested. Satisfactory immunoreactivities with an anti-steroid antibody in each enzyme immunoassay system were obtained with the labeled antigens prepared at pH 8.5 by the use of molar ratios higher than 30. The enzyme labeling method should be useful in the case of polar steroids or drugs, since the p-nitrophenyl ester is relatively stable when compared with the N-succinimidyl ester.

Esters↗

Personality of healthy young adults with sleep paralysis.

Sleep paralysis occurs in normal persons. This phenomenon had been studied psychoanalytically or in terms of the deviation of the victims' personality. This present study aimed to assess the personalities of such persons by using the MMPI and the Maudsley Personality Inventory. The subjects showed a slightly higher mean T score on the MMPI Paranoia Scale than those who did not have this experience. Although this personality difference might be related to the occurrence of the phenomenon, this difference is probably too small to take a major role. It is unlikely that the subjects developed paranoic behavior through their experiences of sleep paralysis, since their experiences were very few. Some of the subjects might have only overestimated their behavior and experiences concerning delusions and hallucinations, with the result that their Paranoia scores were higher and perhaps their kanashibari experiences exaggerated.

Adolescent↗

Cell toxicity, hemolytic action and clastogenic activity of asbestos and its substitutes.

The cell toxicity, hemolytic and clastogenic activity were examined in various kinds of asbestos and some asbestos substitutes with reference to the their mineralogical and physicochemical characteristics. There were thirty-five fibrous and non-fibrous samples including UICC chrysotile, size-selected samples of UICC chrysotile, chrysotile altered by heating and grinding, Yamabe (Japan) chrysotile with long and short fibers, Coalinga (U.S. A.) chrysotile with short fibers, UICC crocidolite, amosite, and 19 non-asbestos samples such as, glass fibers, calcium silicates, sepiolites and some clay minerals. The cell toxicity and the hemolytic and clastogenic activity of asbestos were the strongest for chrysotile among all of the asbestos samples tested, and their strengths varied with fiber length and with the conditions of grinding and heating. These cellular effects of Yamabe chrysotile with long fibers and size-selected UICC chrysotile with long fibers were stronger than those of chrysotile of the same origin but with short fibers. These effects were weaker in chrysotile altered by heating and grinding. Among the asbestos substitutes, the cell toxicity, hemolytic and clastogenic activities of thin glass fibers were more marked than those of thick glass fibers. The four types of sepiolite were strongly hemolytic, but their cell toxicity and clastogenicity varied according to their grade of crystallinity and/or fiber size. These effects of calcium silicates and some clay minerals were generally low but varied with mineral species. In general, the cell toxicity, hemolytic and clastogenic activities of the asbestos substitutes tested here were mild compared with those of asbestos.

Animals↗