Biomedical subjects

M Fukushima

Publications and source records attributed to M Fukushima.

At least 181 records · Page 10Linked to original sources

PubMed1998

Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine.

An enzymatic study was performed to clarify the mechanism of 18 acute deaths in patients who had received the new oral antiviral drug, sorivudine (SRV), during anticancer chemotherapy with 5-fluorouracil (5-FU) prodrugs. Human dihydropyrimidine dehydrogenase (hDPD), playing a key role in the liver as the rate-limiting enzyme in catabolism of 5-FU, was expressed in E. coli, purified and incubated in the presence of NADPH with SRV or (E)-5-(2-bromovinyl)uracil (BVU), a metabolite of SRV produced by human gut flora. hDPD was rapidly and irreversibly inactivated by BVU, but not by SRV. Radioactivity of [14C]BVU was incorporated into hDPD in the presence of NADPH in a manner reciprocal to the enzyme inactivation. In the absence of NADPH, hDPD was not inactivated by BVU, nor radiolabeled with [14C]BVU. Thus, as we demonstrated previously with studies using the rat, the acute deaths were strongly suggested to be attributable to markedly elevated tissue 5-FU levels which were responsible for irreversible inhibition of hDPD by covalent binding of a reduced form of BVU as a suicide inactivator.

Antiviral Agents↗

PubMed1998

A new prognostic factor for colorectal carcinoma, thymidylate synthase, and its therapeutic significance.

BACKGROUND: Expression of thymidylate synthase (TS) has been studied as a mechanism of drug resistance and a prognostic factor for various cancers. METHODS: The relation between TS expression in surgically resected specimens and patient survival was examined in 86 patients with colorectal carcinoma (58 of whom received adjuvant chemotherapy and 28 who did not) who had been followed for 10 years. Immunohistochemical demonstration of the protein was achieved using an anti-TS polyclonal antibody. RESULTS: In the 58 patients who received chemotherapy, the overall 10-year survival rate was 77.8% for patients with TS positive tumors and 89.4% for patients with TS negative tumors (difference not significant). However, in the 28 patients who did not receive chemotherapy, these figures were only 42.9% and 85.7%, respectively (P < 0.05). Multivariate analysis also revealed TS expression to be a significant variable for predicting postoperative survival (P < 0.05). CONCLUSIONS: TS expression can be used as an independent prognostic factor for patients with colorectal carcinoma. Patients with TS positive tumors have a poorer prognosis than those with TS negative lesions and therefore should receive special consideration with regard to chemotherapy.

Antibiotics, Antineoplastic↗

PubMed1998

Lobectomy by video-assisted thoracic surgery for primary lung cancer: experiences based on provisional indications.

A retrospective study on compromised patients who underwent a lobectomy by a standard thoracotomy for stage I non-small cell lung cancer revealed them to show a poor prognosis and quality of life due to their deteriorated physical conditions. Therefore, a lobectomy by video-assisted thoracic surgery (VATS lobectomy) was performed on some of these patients according to the provisional indications based on our retrospective study which indicated that it may be beneficial. Fourteen patients underwent VATS lobectomies (VATS group). Sixteen patients who underwent lobectomy by standard thoracotomy (ST group) were compared with those of the VATS group as historical controls. Although the mean operating time for the VATS group was longer than that for the ST group, there was no significant difference. The mean amount of blood loss for the VATS group was significantly less than that for the ST group. The mean maximal postoperative serum CPK level of the VATS group was slightly less than that of the ST group. A significant difference was observed regarding the changes in performance status both before and after operation between the VATS group and the ST group. We thus considered a VATS lobectomy to be beneficial for aged patients, especially in those with restricted physical conditions.

Aged↗

PubMed1998

Organotin compounds in water, sediment, and biological samples from the port of osaka, japan

Butyltin (Bts) and phenyltin compounds (Pts) were measured in water, sediment, plankton, and mussels collected from eight stations in the harbor area of the Port of Osaka in 1996, and were compared with those of Otsuchi Bay. The levels of tributyltin (TBT) compounds in all samples from the Port of Osaka were slightly high in marinas and mooring areas of small and medium-hull vessels. Of total Bts, the ratio of TBT was under 50% in water and was dominant in sediment, plankton, and mussels. Triphenyltin (TPT) compounds in water were not detected. TPT was present at lower levels than TBT in sediment, plankton, and mussels. Of total Pts, monophenyltin (MPT) compounds and diphenyltin (DPT) compounds represented a high proportion in sediment, while TPT was dominant in plankton and mussels. The concentrations of TBT in water from the Port of Osaka were lower than those from Otsuchi Bay, however TBT concentrations in sediment, plankton, and mussels from the Port of Osaka were higher than those from Otsuchi Bay. The difference of TBT concentration among stations in the Port of Osaka was slight. In contrast, the levels of TBT in Otsuchi Bay were markedly higher at a station near the shipyard. Though TPT in water from the Port of Osaka was not detected, trace amounts of TPT was found in seawater from Otsuchi Bay. The levels and detected frequencies of TPT in sediment, plankton, and mussels from the Port of Osaka were lower than in those from Otsuchi Bay. The partition coefficients of Bts to sediment, plankton, and mussels from the Port of Osaka were higher than those of dibutyltin (DBT) compounds and MBT and those of TBT to plankton and mussels were higher than those in sediment. The partition coefficients of TBT to sediment and biological samples from the Port of Osaka were higher level than those in Otsuchi Bay.

Journal Article↗

PubMed1998

Fusion variations of pancreatic ducts in patients with anomalous arrangement of pancreaticobiliary ductal system.

Fusion variations of the pancreatic ducts were studied to elucidate the significance of such variations. We classified structural fusion anomalies of the main and accessory pancreatic ducts on endoscopic retrograde cholangio-pancreatography (ERCP) in 37 patients with anomalous arrangement of the pancreaticobiliary ductal system (AAPB). The fusion variations of the pancreatic ducts were classified into five types: common, ansa pancreatica, branch fusion, looped, and separated. These fusion variations, except for common type, were found in 68% of the 37 patients with AAPB on ERCP. Fusion variations of the pancreatic ducts were very frequent (93%) in the 30 patients with congenital cystic dilatation of the common bile duct (CCD). The branch confluence fashion, in which the terminal bile duct communicated with a pancreatic duct branch, was found only in patients with cystic dilatation cyst of the CCD, and it appeared that cystic dilatation cyst of CCD might differ from spindle or cylindrical cyst originating from embryonic formation of an anomalous confluence. It was also suggested that in patients with fusion variations of the pancreatic ducts, the flow of pancreatic juice might be disordered, leading to the development of acute pancreatitis or pancreatic dysfunction. Consequently, it appears to be necessary to carefully examine patients with AAPB for the presence or absence of any fusion variations of the pancreatic ducts and to observe such patients with long-term monitoring by ERCP, and computed temography, and with pancreatic function tests.

Adult↗

PubMed1998

Thoracoscopic enucleation of a submucosal bronchogenic cyst of the esophagus: report of two cases.

Thoracoscopic enucleation of a bronchogenic cyst of the esophagus was successfully performed in two cases. The first patient was a 26-year-old female complaining of dysphagia and retrosternal discomfort. The second patient was a 56-year-old female complaining of retrosternal discomfort. A close examination revealed a cystic lesion compressing the esophagus in both cases. Three trocars were employed under general anesthesia. Thoracoscopy offering excellent visualization allowed us to perform a precise anatomical dissection between the muscle layer and the mucosa. Both patients recovered uneventfully and the symptoms disappeared postoperatively. Thoracoscopic surgery is thus considered to be beneficial for the treatment of a benign esophageal tumor because of the small chest wall entry, which might positively contribute to a favorable postoperative course.

Adult↗

PubMed1998

Facilitation of HIV-1 isolation from patients by neuraminidase.

We previously reported that infectivities of human and other non-human lentiviruses including human immunodeficiency virus type 1 (HIV-1) are activated by desialylation of the virion surface [H. Hu et al., J Virol 70: 7,462-7,470 (1996)]. The present study was designed to determine whether neuraminidase (NA) is useful for isolation of HIV-1 from patients. Peripheral blood mononuclear cells (PBMC) or CD4+ cells isolated from the PBMC of infected individuals were cocultured with PBMC or CD4+ cells from uninfected healthy donors, and the efficiency and frequency of virus isolation in the presence of NA were compared with those by a routine conventional procedure. In a total of 41 isolation trials from 28 individuals, the presence of NA markedly increased the frequency of isolation. Furthermore, both the day when virus was first detected and the day when the virus titer was the highest in the cultures were significantly earlier in the presence of NA than in the absence of NA. The deduced amino acid sequences of the V2 and V3 regions of gp120 were identical or very similar between the isolates obtained in the presence or absence of NA, suggesting that both isolation procedures selected a similar population. NA was thus found to facilitate HIV-1 isolation and its use is recommended particularly when isolation is negative by the conventional procedures.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Baicalin, an inhibitor of HIV-1 production in vitro.

The flavonoid baicalin markedly inhibits replication of human immunodeficiency virus type 1 (HIV-1) in a concentration-dependent manner in normal peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA) in vitro. The effect was more pronounced when the cells were pretreated with baicalin. Furthermore, baicalin inhibits HIV-1 replication in PHA-stimulated PBMC from asymptomatic HIV-1-seropositive carriers. The 50% inhibitory concentration for HIV-1 replication was approximately 0.5 microg/ml. At the concentration of 2 microg/ml of baicalin, copy numbers of HIV-1 proviral DNA were approximately 50 times less than in untreated controls. In a cell-free infection system, baicalin inhibited the activity of HIV-1 reverse transcriptase (RT), but not the activity of human DNA polymerases alpha and gamma (DNA polymerase beta was slightly inhibited), suggesting that the anti-HIV-1 effect of baicalin may at least partly be due to inhibition of HIV-1 RT.

Anti-HIV Agents↗

PubMed1998

Contamination of butyltin and phenyltin compounds in the marine environment of Otsuchi Bay, Japan.

Butyltin (BT) and phenyltin (PT) compounds were measured in seawater, sediment, and biological samples collected from coastal areas of Otsuchi Bay, Japan. Tributyltin (TBT) compounds in seawater, sediment, plankton, mussels, scallops and fish were in the range of 0.008-0.074 microg liter(-1), 0.01-0.64 mg (kg dry wt)(-1), 0.24-9.8 mg (kg dry wt)(-1), 0.04-0.18 mg (kg wet wt)(-1), 0.10-0.13 mg (kg wet wt)(-1) and 0.01-0.02 mg (kg wet wt)(-1), respectively. Trace amount of PTs were found in seawater. The highest concentrations of TBT and triphenyltin (TPT) were found near a shipyard. Triorganotin compounds were more dominant than their metabolites. A positive correlation was observed between the concentrations of TBT and TPT in the mussels. Concentrations of TBT and TPT in mussels were high in the upper intertidal zone, and decreased toward the water.

Journal Article↗

PubMed1998

Diagnosis of measles viral pneumonia in a patient with Hodgkin's disease by reverse transcription-polymerase chain reaction of serum.

We report a case of fatal measles viral pneumonia in a patient with Hodgkin's disease who had no rash. The measles viral cDNA was detected in autopsy tissue from the lung by reverse transcription-polymerase chain reaction. This method was then applied successfully to stored serum. The diagnosis of measles viral pneumonia may be improved by the application of RT-PCR using peripheral blood. Sequence analysis of amplified cDNA suggested the virus infecting this patient was a recent strain, predominantly isolated after 1980. The fatal outcome may have been due to a lack of immune response to the newer strain.

Aged↗

PubMed1998

Induction of apoptosis, p53 and heme oxygenase-1 by cytotoxic prostaglandin delta12-PGJ2 in transformed endothelial cells.

Delta12-prostaglandin (PG)J2, which has been reported to have potent growth inhibitory activity in various tumor cells, induced apoptosis at 5 microg/ml culture medium in transformed mouse endothelial (F2) cells. Immunoblot analysis using anti-p53 or anti-WAF1 antibodies demonstrated that these two proteins had increased following delta12-PGJ2 treatment in F2 cells. Western blotting analysis using anti-heme oxygenase-1 (heat shock protein (HSP)32) antibody also revealed that delta12-PGJ2 induced HSP32 formation in F2 cells. HSP32 was also induced by heat shock treatment at 43 degrees C for 90 min. In contrast, HSP72 was not induced by heat shock or by delta12-PGJ2 treatment. In agreement with these findings, HSP32 immunofluorescence in the cytoplasm of F2 cells was intensified by delta12-PGJ2 treatment. More intense HSP32 immunoreactivity was similarly observed after heat shock treatment. These results suggest that delta12-PGJ2 caused the apoptotic cell death of F2 cells, which involved a certain process required for p53 or HSP32 induction.

Animals↗

PubMed1998

In vitro study on intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant brain tumors.

We investigated 5-fluoro-2'-deoxyuridine (FdUrd) as a potential agent for intrathecal treatment of malignant brain tumors with meningeal dissemination. We examined the neurotoxicity of FdUrd in vitro using primary cultures of neurons from C57BL/6 mice (ED14). Tumoricidal activity was also studied in four glioma cell lines and one medulloblastoma cell line. In addition, thymidine phosphorylase (TPase) and thymidine kinase (TK), which are key enzymes for FdUrd metabolism, were measured in the cerebrospinal fluid (CSF) of 36 patients with brain tumors. The antitumor activity of FdUrd for murine glioma cells was approximately 20- to 200-fold higher than that of 5-fluorouracil (5-FU). Against human cell lines, it was 3- to 500-fold higher than that of 5-FU. The neurotoxic effect of FdUrd on cultured neurons was far less than that of 5-FU or 5-fluorouridine (FUrd). Cerebrospinal fluid contained no detectable thymidine phosphorylase in most patients with brain tumors. Several studies have indicated that FdUrd is rapidly converted to 5-FU in the presence of thymidine phosphorylase, so that a high dose of FdUrd must be administered to obtain good efficacy. However, a high dose FdUrd frequently cause severe toxicity. In contrast, the data obtained here suggest that no enzymatic conversion of FdUrd to 5-FU should occur in the CSF. In addition, FdUrd has an excellent antitumor activity and minimal neurotoxicity. We therefore conclude that intrathecal FdUrd is a potential therapy for CSF dissemination of malignant brain tumors.

Animals↗

PubMed1998

Developmental changes in the NGF content in the brain of young, growing, low-birth-weight rats.

The NGF content in each region of the brain of four-week-old rats was ranked in the decreasing order of cerebral cortex, hippocampus, cerebellum, midbrain/diencephalon, and pons/medulla oblongata, and the NGF concentration, in the decreasing order of hippocampus, cerebral cortex, cerebellum, midbrain/diencephalon, and pons/medulla oblongata in both AFD and SFD groups. The NGF content and concentration in the cerebral cortex were about the same value at each age between those in the AFD and SFD groups. Those in the hippocampus were a little higher in the SFD group than in the AFD group at the ages of three and four weeks, unlike those in the other regions, where the values for the cerebellum, midbrain/diencephalon and pons/medulla oblongata tended to be somewhat higher in the AFD group than in the SFD group. The NGF concentrations in the hippocampus and cerebral cortex increased with growth: the concentration in the hippocampus at four weeks of age was about 4-fold of that at one week in the AFD group and about 5.7-fold of that at one week in the SFD group; and likewise the concentration in the cerebral cortex at four weeks of age was about 5.3-fold in the AFD group and about 7-fold in the SFD group. The NGF concentrations in the cerebellum decreased, and those in midbrain/diencephalon and pons/medulla oblongata hardly changed with growth in either AFD or SFD group. From these results NGF may have stronger implications for the neuronal growth in the hippocampus compared with those in the lower brain regions of the SFD rats.

Animals↗

PubMed1998

A longitudinal analysis of alteration in lecithin-cholesterol acyltransferase and paraoxonase activities following laparoscopic cholecystectomy relative to other parameters of HDL function and the acute phase response.

The composition of high-density lipoprotein (HDL) changes during inflammation; however, potential changes of HDL function during inflammation and the effects of acute phase proteins that are either on the HDL particles or in the serum have not been clarified. The concentrations of C-reactive protein (CRP), serum amyloid A protein (apoSAA) isoforms, lipids and apolipoproteins, and the activities of lecithin-cholesterol acyltransferase (LCAT) and paraoxonase (PON) were measured before and after laparoscopic cholecystectomy, in 12 patients with cholecystolithiasis to clarify the function of acute-phase HDL and the relationship between acute-phase proteins and HDL functions. Both acute-phase apoSAA (A-apoSAA) and CRP increased, reached their maximum levels 3-6 days after the operation, and then returned to preoperative levels after 2 weeks. In contrast, apolipoproteins and LCAT decreased reciprocally, reached their minimum levels 3-6 days after the operation, and returned to preoperative levels after 2 weeks. However, PON decreased 3-6 days after the operation, and remained low even after 2 weeks. At the nadir the mean activities of LCAT and PON were 56 and 76% of the preoperative levels, respectively. HDL-cholesterol or constitutive apoSAA did not change significantly. LCAT has been reported to be involved in reverse-cholesterol transport and PON to be preventive for lipid peroxidation of low-density lipoprotein in vitro. Thus, during the acute phase of inflammation, HDL may be altered to an atherogenic state due to a decrease in LCAT and PON activities. Therefore, this longitudinal analysis was carried out to determine whether HDL function is modified in a single episode of inflammation and thus may contribute to the occurrence of atherosclerotic disease in patients with chronic or recurrent acute inflammation.

Acute-Phase Reaction↗

PubMed1998

The characterization of cell death induced by 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl) cytosine (ECyd) in FM3A cells.

The characterization of cell death induced by 1-(3-C-ethynyl-beta-D- ribopentofuranosyl) cytosine (ECyd), a potent inhibitor of RNA synthesis, was performed using mouse mammary tumor FM3A cells in vitro. Accompanied with the cell death induced by ECyd (3.0 muM) -treatment, about 100-200 kbp-sized and internucleosomal DNA fragmentation were observed by orthogonal-field-alternation gel electrophoresis (OFAGE) and conventional gel electrophoresis, respectively. Protease inhibitors, carbobenzoxy-L-aspart-1-yl[(2,6-dichlorobenzyl)oxy]methane (Z-Asp-CH2-DCB), N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) and N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), effectively blocked the cell death, suggesting that the proteases inhibited by Z-Asp-CH2-DCB, TLCK or TPCK were involved in the process of cell death.

Animals↗

PubMed1998

Anticancer activity and toxicity of S-1, an oral combination of tegafur and two biochemical modulators, compared with continuous i.v. infusion of 5-fluorouracil.

S-1 is an oral combined form of 1 M tegafur [a prodrug of 5-fluorouracil (5-FU)], 0.4 M 5-chloro-2,4-dihydroxypyridine (a reversible inhibitor of dihydropyrimidine dehydrogenase) and 1 M potassium oxonate (an inhibitor of orotate phosphoribosyltransferase). S-1 has been shown to exert a potent antitumor effect with low gastrointestinal toxicity in experimental tumor models. We have therefore compared the antitumor effect of oral S-1 with that of continuous infusion of 5-FU in rats bearing transplants of human and murine tumors. Almost complete inhibition of the tumor growth was obtained on 7 day schedules in Yoshida sarcoma-bearing rats by consecutive administration of 30 mg/kg/day of oral S-1 and 40 mg/kg/day infusion of 5-FU. However, a significant difference between the incidence of toxicities of S-1 and 5-FU, including body weight loss and diarrhea, was noted. The rats given the 5-FU infusion had marked weight loss and severe diarrhea, while those given oral S-1 had neither. Although about 50% inhibition of the tumor growth was attained with 15 mg/kg/day of oral S-1 and 30 mg/kg/day infusion of 5-FU in nude rats with xenografted human colon cancer (KM12C), the rate of body weight loss in the 5-FU-treated group was distinctly higher than in the S-1-treated group. The ratio of the 5-fluoronucleotide concentrations in gastrointestinal tissue to that in the tumor was lower in the S-1-treated rats than in the 5-FU-treated rats. In conclusion, the results suggest that oral S-1 might be more effective in the treatment of cancer patients than continuous infusion of 5-FU, from the standpoint of antitumor potency and toxicity.

Administration, Oral↗

PubMed1998

Relationship between protein levels and gene expression of dihydropyrimidine dehydrogenase in human tumor cells during growth in culture and in nude mice.

Protein levels and gene expression of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme for degradation of 5-fluorouracil, were studied in two human tumor cell lines (fibrosarcoma HT-1080 and pancreatic carcinoma MIAPaCa-2) in various growth phases of the cultured cells and of tumor xenografts implanted into nude mice. DPD catalytic activity and DPD protein content in cytosolic preparations were determined by means of radioenzymatic assay and western blot analysis, respectively. Relative DPD mRNA expression was determined by using a semi-quantitative reverse transcription-polymerase chain reaction in which glyceraldehyde-3-phosphate dehydrogenase mRNA was used as an internal standard. DPD activity and protein content in cultures of both cell lines increased in proportion to cell density (DPD activities ranged from undetectable to 84 pmol/min/mg protein in the HT-1080 cells and from undetectable to 335 pmol/min/mg protein in the MIAPaCa-2 cells). DPD mRNA levels, on the other hand, tended to decrease slightly during cell growth. DPD activity and protein content in HT-1080 tumor xenografts increased during growth in proportion to tumor weight (DPD activities ranged from 7 to 131 pmol/min/mg protein), but DPD mRNA levels did not correlate with tumor weight. DPD activity and protein content in MIAPaCa-2 tumor xenografts did not change much, and seemed to have already plateaued, since the tumors were small (weighing about 30 mg). These findings suggest that DPD protein expression during tumor growth is controlled at the post-transcriptional level.

Animals↗

PubMed1998

Cross-cultural comparison of attitudes and opinions on fluorides and fluoridation between Australia and Japan.

This paper reports on two studies exploring similarities and contrasts in knowledge, attitudes and opinions on fluorides and fluoridation of two culturally different population groups. The first study compares the attitudes and opinions of parents of primary (elementary) schoolchildren in Melbourne, Australia, and Yokohama, Japan, and the second study compares the attitudes and opinions of dentists drawn from the same geographic areas. A self-administered questionnaire collected data on 517 parents and 629 dentists. The questionnaires were of similar design and content for both parents and dentists. They included a series of knowledge and attitudinal statements on preventive dentistry and use of fluorides. Attitudinal responses were measured on a 5-point agree-disagree Likert scale. Data were analyzed using both bivariate and multivariate techniques. Australian parents appeared better informed on the benefits of water fluoridation and held more favorable opinions on fluorides and fluoridation than their Japanese counterparts. Similarly, Australian dentists held more positive attitudes toward the use of fluorides and fluoridation than their Japanese peers. Cultural norms and experiences appear to shape parental attitudes, whereas the focus of dental education and dental practice on restorative treatments in Japan appears to be a substantial influence on the attitudes and opinions held by Japanese dentists.

Adolescent↗