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Biomedical subjects

M Fukuzawa

Publications and source records attributed to M Fukuzawa.

At least 73 records · Page 4Linked to original sources
PubMed1998

Thirty-eight years experience of malignant hepatic tumors in infants and childhood.

A description is given of therapeutic experiences with 39 cases of malignant liver tumors in infancy and childhood during the past 38 years. Of these patients, 9 not undergoing hepatic resection all died, while 18 (60%) of 30 patients treated by hepatic resection survived. When only patients with hepatoblastoma are considered, 14 of 24 patients are alive, although 3 of them had local recurrence and had lung metastasis. Among patients with other types of liver tumor, those with hepatocellular carcinomas (2 cases) and vascular neoplasms all died in a short period of time, whereas 2 with yolk sac tumor and one with metabolic pancreatic tumor are alive despite of tumor recurrence. In summary, the results of surgical treatment of malignant liver tumors in infancy and childhood, which formerly were poor, have been improved remarkably, which we owe mainly to: 1) advances in diagnostic imaging techniques (e.g., angiography, ultrasonography, CT and MRI) permitting early diagnosis, localization of tumor, visualization of the coursing of major vessels (particularly, hepatic artery & vein) and more accurate definition of resectability, 2) technical improvement of hepatic resection and 3) progress of chemotherapy mainly with cisplatin and adriamycin.

Adolescent↗
PubMed1998

Basic studies on N''-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid for the dissolution of calcified gallstones.

A novel calcium-chelating agent, N"-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid (UDCA-DTTA), was synthesized to study its ability to dissolve calcified gallstones. The chelating activity of the compound was demonstrated by dissolving calcium carbonate in vitro at a high dissolution rate. In the presence of the agent, sliced human gallstone with a composition of more than 50% calcium bilirubinate was thoroughly dissolved, indicating that calcium bilirubinate was dissolved from the gallstone. The ability to dissolve calcium was comparable to that of EDTA. However, the laminar structure of the sliced gallstone did not disappear in the presence of EDTA, whereas the structure disappeared in the presence of UDCA-DTTA. All these results indicate that UDCA-DTTA is an interesting compound as a parent substance for developing a prodrug for an oral or intravenous agent to dissolve calcium-containing gallstones.

Administration, Oral↗
PubMed1998

[Influence of nitric oxide synthetase inhibitor on the blood pressure action of clonidine in rats].

We are investigating the influence of NO synthetase inhibitor on the clonidine-induced cardiovascular actions in urethane-anesthetized rats. The systemic blood pressure was measured from right femoral artery, heart rate from the pressure pulse under inhalation of O2. Nw-nitro-L-arginine-methylester (L-NAME, 5 mg/kg), NO synthetase inhibitor, administered intravenously increased blood pressure slightly, although decreased heart rate. The responses to L-NAME were stable about 10 min after the injection. Clonidine (5 mg/kg) administered intravenously indicated the transient increase blood pressure and following continuous decrease of blood pressure. The early transient hypertension of clonidine was potentiated by pretreatment with L-NAME and later continuous hypotension was markedly inhibited. While, the early transient hypertension of clonidine was inhibited by pretreatment with L-arginine and later continuous hypotension was potentiated. The hypertension and tachycardia of intravenous tyramine was enhanced by L-NAME. Clonidine administered into the cerebroventricle did not indicate the early transient hypertension, though produced the later continuous hypotension. These results suggest that L-NAME modifies the cardiovascular responses to clonidine and NO may participate in the modulation.

Animals↗
PubMed1998

Purification and characterization of triacylglycerol lipase from Aspergillus oryzae.

Triacylglycerol lipase (L3) was purified from Aspergillus oryzae RIB128 by ammonium sulfate fractionation, acetone precipitation, anion-exchange chromatography, and gel filtration. The purified enzyme was formed from a glycoprotein and a monomeric protein with molecular masses of 25 and 29 kDa, by SDS-PAGE and gel filtration, respectively. The optimum pH at 40 degrees C was 5.5 and the optimum temperature at pH 5.5 was 40 degrees C. The enzyme was stable between a pH range of 4.0-7.5 at 30 degrees C for 24 h, and at up to 30 degrees C at pH 5.5 for 1 h. Heavy metal ions, detergents, DFP, and DEP strongly inhibited the enzyme activity. The lipase hydrolyzed not only triacylglycerols but also monoacylglycerols and diacylglycerols. The enzyme had higher specificity toward triacylglycerols of middle-chain saturated fatty acids than short-chain or long-chain fatty acids. The enzyme had 1,3-positional specificity. The N-terminal amino acid sequence of the enzyme was not significantly similar to that of other lipases with published sequences.

Amino Acid Sequence↗
PubMed1998

[Immunohistochemical study of p53, p27 and PCNA expression in esophageal cancer].

We evaluated the clinical significance of p53, p27 and PCNA expressions in esophageal squamous cell carcinomas. Operative specimens obtained from 70 patients with esophageal squamous cell carcinomas were investigated by staining with antibodies against p53, p27 and PCNA. The correlations among p53, p27 and PCNA expression, clinicopathologic factors and prognosis were studied. The expression of p53 was observed in 55.7%, and it did not correlate to histologic classification, growth pattern, and lymphatic invasion. The expression of p27 was observed in 48.6%, and it correlated to lymph node metastasis. The PCNA positive index (PCNA-PI) was high in the p27 negative cases. The p53 positive and p27 negative group revealed the worst survival rate among groups. Therefore, the p27 positive case, often associated with well differentiated carcinoma, tends to have a slower tumor-growth rate and better prognosis. It is suggested that immunohistochemical assessment on the p53 and p27 expressions would be useful to the recognize the malignant potential and differentiation of squamous cell carcinoma of the esophagus.

Aged↗
PubMed1997

SH2 signaling in a lower eukaryote: a STAT protein that regulates stalk cell differentiation in dictyostelium.

The TTGA-binding factor is a transcriptional regulator activated by DIF, the chlorinated hexaphenone that induces prestalk cell differentiation in Dictyostelium. The same activity also functions as a repressor, controlling stalk cell differentiation. We show that the TTGA-binding factor is a STAT protein. Like the metazoan STATs, it functions via the reciprocal interaction of a phosphotyrosine residue on one molecule with an SH2 domain on a dimerizing partner. Furthermore, it will bind specifically to a mammalian interferon-stimulated response element. In Saccharomyces cerevisiae, where the entire genomic sequence is known, SH2 domains have not been identified. It would seem, therefore, that SH2 signaling pathways arose very early in the evolution of multicellular organisms, perhaps to facilitate intercellular comunication.

Animals↗
PubMed1997

Effect of long-term treatment with complete Freund's adjuvant on KK-Ay mouse, a model of non-insulin-dependent diabetes mellitus.

Nonspecific stimulation with immunoadjuvants significantly improves glucose tolerance in animal models for non-insulin-dependent diabetes mellitus (NIDDM). In this study, we observed the effect of long-term treatment with complete Freund's adjuvant (CFA) on serum factors and histology of various organs in KK-Ay mice with NIDDM. The mice were injected with CFA weekly or every 2 weeks for 12 weeks. Glucose tolerance was significantly improved in the CFA-treated mice throughout the experiment. At the end of the experiment, hypertriglyceridemia was significantly reduced, but serum total protein, glutamic pyruvic transaminase, creatinine, and nonfasting insulin levels were not changed by the treatment. Fatty change of the liver and index of glomerular lesions of the kidney were significantly inhibited in the CFA-treated mice, whereas the pancreatic islet morphology remained unchanged. No toxic effect was observed by the CFA treatment. These results imply that the novel treatment with CFA could control NIDDM and inhibit the development of diabetic glomerular lesions in KK-Ay mice.

Animals↗
PubMed1997

Factors influencing the outcome of liver transplantation for biliary atresia.

BACKGROUND/PURPOSE: This study examined the factors present before liver transplantation (LTx) influencing the outcome in 14 patients who had biliary atresia (BA) who underwent LTx. RESULTS: Nine patients survived (Group A), whereas five died primarily of infection (Group B). Rate of the attempted multiple hepatic portoenterostomy (HPE) and existence of intestinal stoma was significantly higher in Group B than in Group A. Pre-LTx parameters showed significant difference between the two groups as follows: total bilirubin, 15.9 +/- 7.9 versus 29.1 +/- 14.5 mg/dL (P = .0446); gamma-glutamyl transpeptidase, 170.0 +/- 97.6 versus 65.2 +/- 38.8 IU/L (P = .0425); the body weight deviation score, 0.17 +/- 0.88 SD versus -1.46 +/- 0.30 SD (P = .0029); total cholesterol, 129.4 +/- 33.5 versus 52.2 +/- 20.4 mg/dL (P = .0008) in Group A versus Group B. Total cholesterol level and body weight for age remained within normal range until the advanced stage and rapidly decreased according to deterioration of the general condition before LTx. CONCLUSIONS: From these results, avoidance of multiple HPE and closure of stoma before LTx may be preferable. LTx should be performed before failure to thrive or hypocholesterolemia develops.

Analysis of Variance↗
PubMed1997

Immunohistochemical assessment of the MIB-1 Labeling Index in human hepatoblastoma and its prognostic relevance.

BACKGROUND/PURPOSE: The MIB-1 monoclonal antibody has been raised against recombinant parts of the Ki-67 antigen, which is a cell cycle-related nuclear protein that is elevated in late G1 and S phases. The aim of the study was to analyze the expression pattern of MIB-1 in hepatoblastoma and to assess whether it provides any prognostic information in clinical practice. METHODS: Sections from formalin-fixed paraffin embedded tissues were collected from 18 patients who had hepatoblastoma and stained with MIB-1 antibody according to streptavidinbiotin method. A percentage score of positively stained nuclei, MIB-1 Labeling Index (LI), was determined and correlated with clinical variables. MIB-1 LI ranged from 0% to 39.5% with a mean value of 13.5%. Among them in 14 patients, who received preoperative chemotherapy, the authors analyzed the result of MIB-1 staining. RESULTS: Although there were no significant correlations between MIB-1 LI and age, sex, or histological type, a statistically significant correlation was found between clinical stage and MIB-1 LI. Mean MIB-1 LI was lower in patients with stage I and II than in those with stages III and IV (P < .05). Metastatic lesions showed higher MIB-1 LI than primary lesions, indicating that metastatic tumor cells have an increased rate of cellular proliferation. Kaplan Meier survival curve showed that patients with MIB-1 higher than 10% (n = 3) had a worse survival rate than those with lower than 10% MIB-1 LI (n = 11), whereas there was no significant difference because of the limited number of cases. Because high MIB-1 LI was correlated with clinical stage and poor survival rate, MIB-1 LI may be considered an important prognostic factor in hepatoblastoma. CONCLUSION: Although further studies, including larger series of patients, are required, the authors consider MIB-1 immunostaining an easy method to assess proliferative activity that provides useful prognostic information in hepatoblastoma.

Antibodies, Monoclonal↗
PubMed1997

Mutation analysis of p53 gene in childhood malignant solid tumors.

Alterations of the p53 gene have been extensively investigated in a wide variety of human malignancies. However, data on childhood malignant solid tumors are still limited. Mutations of the p53 gene on exons 5 through 8 were examined in 82 childhood malignant solid tumors by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method, and the nature of these mutations was confirmed by direct sequencing. The 82 tumors examined included neuroblastomas (n = 44), Wilms' tumors in = 13), hepatoblastomas (n = 11), rhabdomyosarcomas (n = 10), extraosseus Ewing sarcomas (n = 2), undifferentiated sarcoma of the liver (n = 1), and fibrosarcoma (n = 1). Two sarcoma samples were identified as having point mutations. One was a rhabdomyosarcoma with a missense mutation at codon 273, substituting histidine (His) for arginine (Arg). Another was an undifferentiated sarcoma of the liver with a missense mutation at codon 245, substituting serine (Ser) for glycine (Gly). No mutations were detected among neuroblastomas, Wilms' tumors, or hepatoblastomas. The two sarcomas with mutations were localized tumors. Both patients who had these tumors are disease free for 8 and 5 years after treatment, respectively. The overall incidence of p53 mutations was low (2.4%, 2 of 82). However, the incidence, when calculated for sarcomas, was higher at 14.3% (2 of 14). These data indicate that p53 mutations are generally uncommon in childhood malignant solid tumors examined. However, in some childhood sarcomas, p53 mutations appear to have a causative role in the development of these tumors.

Child↗
PubMed1997

Expression of endothelial constitutive nitric oxide synthase mRNA in gastrointestinal mucosa and its downregulation by endotoxin.

Endothelial nitric oxide exerts local vasodilatory actions in the gastrointestinal (GI) microvasculature and is proposed to play a role in enteric vasomotor regulation. The aims of this study were to characterize the tissue distribution of mRNA for endothelial nitric oxide synthase (NOS-III) and to examine its response to endotoxin challenge in vivo. We demonstrate the expression of NOS-III mRNA and protein in mucosa throughout the gastrointestinal tract and show for the first time that NOS-III mRNA expression in the GI mucosa was down-regulated in the rats treated with endotoxin. The ubiquitous expression of NOS-III mRNA in digestive tissues is consistent with the proposed role of NOS-III in the physiology of the gastrointestinal tract. The decreased NOS-III mRNA, in parallel to induction of inducible NOS (NOS-II) mRNA, may contribute to the impaired endothelium-dependent relaxation and damaged mucosal integrity during sepsis.

Animals↗
PubMed1997

Beneficial effects of growth hormone combined with parenteral nutrition in the management of inflammatory bowel disease: an experimental study.

BACKGROUND: Growth hormone (GH) improves net protein anabolism and stimulates wound healing. Although GH is also known to exert the trophic effect on the intestinal tract, its role in the healing of intestinal ulceration is not known. The aim of this study was to evaluate the effects of exogenous GH coinfused with parenteral nutrition (PN) in an experimental model of inflammatory bowel disease in rats. METHODS: All rats underwent central venous cannulation and were randomized to two groups after induction of small intestinal ulceration with indomethacin. Both groups received the same PN formula. In addition, the GH group (n = 10) received subcutaneous injections of human GH at a dose of 1.0 IU/kg daily for 4 days, whereas the control group (n = 10) received injections of normal saline solution. Nitrogen balance, macroscopic inflammation score, intestinal myeloperoxidase activity, DNA content, and mucosal permeability were determined for each rat. Insulin-like growth factor-I (IGF-I) mRNA was detected by reverse transcription and polymerase chain reaction. RESULTS: Administration of GH significantly improved the cumulative nitrogen balance, ameliorated the gross inflammation score, and decreased intestinal myeloperoxidase activity. Similarly, intestinal permeability was significantly decreased in the GH group as compared with the control group. GH treatment resulted in increased plasma concentration of IGF-I and IGF-I mRNA expressions in both the liver and the small intestine compared with those in the control group. CONCLUSIONS: Exogenous GH plays an important role in accelerating intestinal healing in an experimental model of small bowel ulceration in rats. The mechanisms may include the stimulated IGF-I production, which thereafter augments intestinal epithelial cell growth.

Animals↗
PubMed1997

Angiotensin converting enzyme inhibitors suppress production of tumor necrosis factor-alpha in vitro and in vivo.

It has been reported that angiotensin converting enzyme (ACE) inhibitors have beneficial effects on insulin resistance and congestive heart failure, in which elevations of serum tumor necrosis factor-alpha (TNF-alpha) level have been indicated. Therefore, in this study, we examined effect of ACE inhibitors on TNF-alpha production both in vitro and in vivo by using human blood mononuclear cells and mice, respectively. LPS (20 micrograms/ml)-induced in vitro TNF-alpha production, measured by bioassay and enzyme-linked immunosorbent assay, was significantly inhibited with captopril, delapril and cilazapril in a concentration of 10(-3) mol/l. A single, oral administration of captopril, delapril and cilazapril at more than 10-fold doses of common clinical use in man significantly inhibited LPS (2 mg/kg)-induced serum TNF-alpha activity in Balb/c mice. These results indicate that ACE inhibitors such as captopril, delapril and cilazapril have an inhibitory effect on TNF-alpha production not only in vitro as previously reported, but also in vivo, although relatively high concentrations and large doses were required in this study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Inhibitory effect of nicotinamide on in vitro and in vivo production of tumor necrosis factor-alpha.

Nicotinamide, a pellagra-preventive factor, has multiple functions such as inhibition of poly-ADP-ribose synthetase, inhibition of inducible nitric oxide synthase, free radical scavenging and suppression of major histocompatibility complex class II expression and ICAM-1 expression on endothelial cells. In addition to these, we have found an inhibitory effect of nicotinamide on production of tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo. Lipopolysaccharide (LPS)-induced in vitro TNF-alpha production by human peripheral blood mononuclear cells, measured by enzyme-linked immunosorbent assay (ELISA), was significantly inhibited with more than 1 x 10(-3) mol/l of nicotinamide, while interleukin-1-beta was not inhibited and interleukin-6 was slightly inhibited even with 10(-2) mol/l. Oral administration of nicotinamide with more than 62.5 mg/kg also significantly inhibited LPS-induced serum TNF-alpha production measured by ELISA and bioassay in Balb/c mice. Thus, nicotinamide has an inhibitory effect on TNF-alpha production that may be beneficial to TNF-alpha-mediated diseases.

Animals↗
PubMed1997

cudA: a Dictyostelium gene with pleiotropic effects on cellular differentiation and slug behaviour.

The Dictyostelium cudA gene encodes a nucleoplasmic protein that is essential for normal culmination. There are no functionally characterised homologues in other organisms but there is a related gene of unknown function in Entamoeba histolytica. The cudA gene is expressed by the prestalk cells that constitute the slug tip (the pstA cells), it is not detectably expressed in the band of prestalk cells that lies behind the tip (the pstO cells) but it is expressed in the prespore cells. This unusual pattern of expression suggests a role on both the stalk and spore pathways of differentiation and cudA- mutant cells are indeed defective in both stalk and spore formation. Furthermore, the slugs formed by cudA- cells continue to migrate under environmental conditions where normal slugs culminate immediately. This aspect of their behaviour can be reversed when the cudA gene is selectively expressed in the pstA cells. This shows that processes occurring in the pstA cells regulate entry into culmination.

Animals↗
PubMed1996

Evaluation of patients with advanced neuroblastoma surviving more than 5 years after initiation of an intensive Japanese protocol: a report from the Study Group of Japan for Treatment of Advanced Neuroblastoma.

In January 1985, a single protocol consisting of cyclophosphamide, vincristine, tetrahydropyranyl adriamycin, and cis-platinum for the treatment of advanced neuroblastoma was begun nationwide in Japan and was found to improve clinical results significantly in terms of 2- or 3-year survival rate. Between January 1985 and December 1988, 113 eligible patients (7 infants younger than 12 months of age with stage IVA disease and 106 patients aged 12 months or older with stage III or IV disease) were enrolled and followed up for 5 years or more after initiation of treatment, as of March 1994. In this study, the usefulness of the protocol for the treatment of advanced neuroblastoma was evaluated with survival rates in relation to age, tumor site, stage, and N-myc amplification for patients surviving more than 5 years after initiation of the protocol. Fifty of the 113 patients were alive 5 years or more after initiation of the treatment, 39 without any episodes of disease recurrence. Fourteen (70%) of 20 patients with stage III, 6 (50%) of 12 with stage IVB, and 24 (30%) of 81 with stage IVA disease were alive and disease-free 5 years after initiation of the protocol. Twenty (56%) of 36 patients without N-myc amplification were alive at 5 years after initiation of the protocol. Only one patient who was alive without evidence of the disease at 5 years had recurrence afterward.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.

Acetylcysteine↗