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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 361 records · Page 20Linked to original sources
PubMed1997

Thallium-201 single-photon emission tomography in the treatment follow-up of nasopharyngeal carcinoma.

In order to assess the usefulness of thallium-201 single-photon emission tomography (SPET) in the treatment follow-up of nasopharyngeal carcinoma (NPC), a total of 75 201T1 SPET studies were performed in 18 patients with histologically proven NPC. The findings were compared with those of magnetic resonance imaging (MRI) before and after therapy. Four patients received radiotherapy alone while the other 14 received concurrent chemo-radiotherapy. Treatment response was classified as complete (CR) or partial (PR) based on the findings of MRI and 201T1 SPET. Intense 201T1 uptake by the tumour was seen in all 18 patients before treatment. After treatment, MRI showed seven CRs and 11 PRs, whereas 201T1 SPET showed 13 CRs and five PRs. In 12 patients, the results of 201T1 SPET were in agreement with those of MRI. In six patients MRI showed PR but 201T1 showed CR. Follow-up (mean 10.6 months) MRI and 201T1 SPET studies of these six patients revealed that tumour gradually decreased and finally vanished in three patients. This preliminary study indicates that 201T1 SPET has potential in the assessment of early response to treatment of patients with NPC when compared with MRI.

Carcinoma↗
PubMed1997

Detection of variants in the mitochondrial glycerophosphate dehydrogenase gene in Japanese NIDDM patients.

Mitochondrial FAD-linked glycerophosphate dehydrogenase (mGPDH) is thought to be an important factor for glucose sensing in pancreatic beta cells. To evaluate the significance of the mGPDH gene in the development of non-insulin-dependent diabetes mellitus (NIDDM), we set up primers and conditions for polymerase chain reaction (PCR) amplification of the coding exons and flanking regions. Screening of 100 Japanese NIDDM patients for mutations using the PCR-single strand conformation polymorphism (SSCP) method revealed four variants (ACA:Thr243-ACG:Thr243, CAT:His264-CGT:Arg264, GCA:Ala305-GCC:Ala305, GCA:Ala 306-TCA:Ser306). The His264-Arg264 variant was found in 36 patients, while the other variants were found in only one patient each. Neither the genotypic (chi 2 = 3.15, p = 0.21) nor the allelic (chi 2 = 2.27, p = 0.13) frequency of the His264-Arg264 mutation differed between 253 Japanese NIDDM patients and 157 non-diabetic subjects. In addition, in NIDDM patients, neither the treatment modality nor body mass index differed between those with and without this mutation. These results suggest that inherited defects at this locus do not make a major contribution to genetic susceptibility to NIDDM in the Japanese population.

Amino Acid Sequence↗
PubMed1997

Potentially multicentric hepatocellular carcinoma: clinicopathologic characteristics and postoperative prognosis.

When multiple hepatic tumors are present, it is sometimes difficult to distinguish between metastatic and multicentric hepatocellular carcinoma (HCC). To identify the important clinicopathologic features of multicentric HCC, we evaluated the clinical characteristics of patients with multicentric HCC and examined the usefulness of surgical treatment in those patients. A total of 99 patients with multiple HCCs were classified into one of the following two groups according to whether their tumors were multicentric or metastatic: Group MO consisted of 18 patients with tumors thought to have developed synchronously from multicentric origins. Group IM consisted of 64 patients with intrahepatic metastases. In this study 18% of the patients with multiple HCCs were thought to have presented with multicentric tumors. This study revealed that synchronous multicentric HCCs often affected multiple segments of the liver and responded relatively well to partial hepatectomy of individual tumor-affected areas. To appropriately treat potentially multicentric HCC, it is important to understand the histopathologic characteristics of multicentric HCC and diagnose during preoperative and intraoperative ultra-sonography, so surgical treatment may be useful.

Carcinoma, Hepatocellular↗
PubMed1997

Intermittent hepatic arterial infusion of high-dose 5FU on a weekly schedule for liver metastases from colorectal cancer.

PURPOSE: We performed phase I and II studies to examine the usefulness of intermittent hepatic arterial infusion of high-dose 5-fluorouracid (5-FU) for patients with liver metastasis from colorectal cancer. METHODS: As the phase I study, 1000, 1250 and 1500 mg/m2 of 5-FU were administered over 5 h by hepatic arterial infusion on a weekly schedule to establish the recommended dose. Based on the results of the phase I study, the phase II study was performed to confirm the efficacy of the recommended dose thus obtained. RESULTS: In the phase I study, the dose-limiting factors of this therapy were gastrointestinal and central nervous system toxicities, and the recommended dose was judged to be 1000 mg/m2. In the phase II study, 1000 mg/m2 of 5-FU was administered over 5 h once a week on an outpatient basis, and this therapy was repeated as long as possible. The response rate was 78% (25/32), with an overall median survival time of 25.8 months (without extrahepatic lesions 25.9 months; with extrahepatic lesions 17.3 months). CONCLUSIONS: (1) Compared with conventional continuous infusion, the advantages of this therapy were that it caused no decrease in the patient's quality of life as a result of being permanently equipped with a pump and it thus enabled more cost-effective use of the pump, (2) The phase II study on 32 patients showed that this therapy caused no serious toxicities, with a response rate of 78% and a survival time of 25.8 months, which exceeded the results with conventional continuous infusion. If the reproducibility of these results is established in further studies involving multicenter collaboration, this therapy will be able to become the standard local chemotherapy for liver metastases from colorectal cancer. (3) Important problems remaining to be solved are improvement of the technical aspects and studies of combined use with systemic chemotherapy. Furthermore, to finally determine the position of this therapy in the treatment system for liver metastasis from colorectal cancer, it is necessary to conduct comparative trials versus systemic chemotherapy, using the survival time as the end-point.

Antimetabolites, Antineoplastic↗
PubMed1997

Pulmonary metal distribution in urban dwellers.

To clarify the factors influencing the concentrations and distribution of metal elements in the lung, we analyzed the following 8 metals in the 5 lung lobes of 17 autopsied urban dwellers by flame or flameless atomic absorption spectrometry: aluminum (Al), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), manganese (Mn), copper (Cu), and Zinc (Zn). The arithmetic mean value (in micrograms of metal per gram of dry weight) calculated for five lobar metal concentrations in each subject ranged from 80 to 681 for Al, from 0.34 to 3.41 for Cd, from 0.41 to 12.7 for Cr, from 0.22 to 1.93 for Ni, from 0.15 to 1.47 for Pb, from 0.64 to 2.36 for Mn, from 2.84 to 7.24 for Cu, and from 40.7 to 77.6 for Zn. The eight metals were classifiable into two groups on the basis of the interindividual and interlobar concentration variations. The first group, consisting of Cu and Zn, was characterized by smaller interindividual variations (co-efficient of variation, CV < 30%) and smaller inter lobar variations (mean CV < 15%). Their levels were not affected significantly by sex, smoking habits, or possible occupational exposure to metal-containing dust. In contrast, the second group, consisting of Al, Cd, Cr, Ni, Pb, and Mn, exhibited larger interindividual variations (CV > 45%) and larger interlobar variations (mean CV > 25%). Concentrations of these metals, except for Cd, tended to be higher in the upper lobes than in the lower lobes. The concentrations of Al and Cr were significantly higher in men than in women. Smoking significantly elevated the levels of Cr, Cd, Ni, and Pb, and the concentrations of Al, Cr, Ni, and Mn were higher in subjects with possible occupational exposure to metal-containing dust than in those without such exposure. However, the interlobar distribution patterns of the metals did not seem to be influenced by sex, smoking habits, or occupational exposure to metal-containing dust.

Adult↗
PubMed1997

Establishment and characterization of spontaneous mesothelioma cell lines derived from F344 rats.

Three mesothelioma cell lines (MeET-4, MeET-5, and MeET-6) established from ascitic fluid of F344 rats with spontaneous abdominal mesothelioma have been maintained through at least 60 passages on the DMEM with 10% FBS. Two of original tumours consisted of epithelioid cells growing in a papillary pattern, while one (original tumour of MeET-5) had sarcomatous areas composed of spindle-shaped tumour cells. The cell line originating from MeET-5 showed a constantly beiphasic growth pattern during the repetitive subcloning, while the other two lines retained a monophasic growth pattern. Although the growth pattern was different, the tumour cells in all three lines were positive for vimentin and keratin and ultrastructurally showed an abundant distribution of glycogen granules in the cytoplasm and numerous long microvilli on all surface. The modal chromosome number of cell lines varied from 41 to 71, and abnormal chromosomes were frequently seen. All cell lines established formed colonies on semi-solid medium and could be successfully transplanted, growing tumour masses in syngeneic rats and thus indicating their malignant nature. Cell lines grew even on a medium with a low concentration of FBS. The evidence suggests that they may produce growth factors that enable them to survive unfavourable medium conditions.

Abdominal Neoplasms↗
PubMed1997

Heterogeneity of mast cells in mastocytosis and inhibitory effect of ketotifen and ranitidine on indolent systemic mastocytosis.

BACKGROUND: Mastocytosis is a disorder of mast cell proliferation that occurs in both cutaneous and systemic forms. The most frequent site is the skin. OBJECTIVE: The mast cell subtype of two patients with mastocytosis was investigated. METHODS: Immunohistochemical studies were performed on the skin or gastric mucosa or both of the two patients. Blood and urine levels of various mediators were measured for one patient. RESULTS: Mast cells containing tryptase and chymase were the only type seen in the skin lesions of an 11-month-old boy with urticaria pigmentosa. Mast cells containing tryptase were predominant in lesions of the skin and gastric mucosa of a 41-year-old man with indolent systemic mastocytosis. However, mast cells containing tryptase and chymase were predominant in the nonlesional and the normal skin of this patient. Tryptase-positive cells were more numerous in lesional skin than nonlesional skin and normal skin. Elevated blood and urine levels of various mediators were decreased by means of combination therapy with ketotifen and ranitidine. CONCLUSION: In indolent systemic mastocytosis, mast cell dynamics involve only cells containing tryptase. Release of mediators from mast cells may be inhibited by means of combination therapy with histamine H1 and H2 receptor antagonists.

Adult↗
PubMed1997

Infection of human cells by an endogenous retrovirus of pigs.

The possible use of pig organs and tissues as xenografts in humans is actively being considered in biomedical research. We therefore examined whether pig endogenous retrovirus (PERV) genomes can be infectiously transmitted to human cells in culture. Two pig kidney cell lines spontaneously produce C-type retrovirus particles. Cell-free retrovirus produced by the PK-15 kidney cell line (PERV-PK) infected pig, mink and human kidney 293 cell lines and co-cultivation of X-irradiated PK-15 cells with human cells resulted in a broader range of human cell infection, including human diploid fibroblasts and B- and T-cell lines. Kidney, heart and spleen tissue obtained from domestic pigs contained multiple copies of integrated PERV genomes and expressed viral RNA. Upon passage in human cells PERV-PK could rescue a Moloney retroviral vector and acquired resistance to lysis by human complement.

Amino Acid Sequence↗
PubMed1997

Hypoxia-induced catecholamine release and intracellular Ca2+ increase via suppression of K+ channels in cultured rat adrenal chromaffin cells.

Hypoxia (5% O2) enhanced catecholamine release in cultured rat adrenal chromaffin cells. Also, the intracellular free Ca2+ concentration ([Ca2+]i) increased within 3 min in approximately 50% of the chromaffin cells under hypoxic stimulation. The increase depended on the presence of extracellular Ca2+. Nifedipine and omega-conotoxin decreased the population of the cells that showed the hypoxia-induced [Ca2+]i increase, showing that the Ca2+ influx was attributable to L- and N-type voltage-dependent Ca2+ channels. The membrane potential was depolarized during the perfusion with the hypoxic solution and returned to the basal level following the change to the normoxic solution (20% O2). Membrane resistance increased twofold under the hypoxic condition. The current-voltage relationship showed a hypoxia-induced decrease in the outward K+ current. Among the K+ channel openers tested, cromakalim and levcromakalim, both of which interact with ATP-sensitive K+ channels, inhibited the hypoxia-induced [Ca2+]i increase and catecholamine release. The inhibitory effects of cromakalim and levcromakalim were reversed by glibenclamide and tolbutamide, potent blockers of ATP-sensitive K+ channels. These results suggest that some fractions of adrenal chromaffin cells are reactive to hypoxia and that K+ channels sensitive to cromakalim and glibenclamide might have a crucial role in hypoxia-induced responses. Adrenal chromaffin cells could thus be a useful model for the study of oxygen-sensing mechanisms.

Animals↗
PubMed1997

Contralateral external carotid-middle cerebral artery bypass for carotid artery resection.

Resection of the common carotid or internal carotid artery is occasionally unavoidable in cases of advanced head and neck carcinoma with carotid artery involvement. To prevent the consequent decrease in cerebral perfusion, we have developed a contralateral external carotid-middle cerebral artery bypass grafting technique. From 1990 through 1995, six patients with advanced head and neck cancer involving the carotid artery underwent total tumor resection combined with vascular reconstruction using the contralateral external carotid- middle cerebral artery bypass grafting. No bypass-related complications occurred in any patient postoperatively. Cerebral hemodynamics after surgery indicated that this bypass graft worked steadily over a long term and supplied sufficient volume of blood to the cerebral cortex on the opposite side in every case.

Adult↗
PubMed1997

The comparative study of anti-double stranded DNA antibody levels measured by radioimmunoassay and enzyme-linked immunosorbent assay in systemic lupus erythematosus.

Anti-double stranded (ds) DNA antibody is an autoantibody specific for systemic lupus erythematosus (SLE). For the measurement of this antibody, radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA) is widely used in Japan. We studied the correlation of anti-dsDNA levels in 158 sera from 53 SLE patients between RIA and ELISA. The correlation coefficient between anti-dsDNA antibody levels measured by RIA and ELISA was 0.736 (p < 0.001). The concordance rate of sera with both ELISA/RIA-positive or both ELISA/RIA-negative results was 82.3% (130/158 sera). Twenty sera (12.7%) of 14 patients were ELISA-positive but RIA-positive, and 8 sera (5.0%) of 6 patients were ELISA-negative but RIA-positive. Our results suggest that both methods may be equally reliable for the detection of anti-dsDNA antibodies and that ELISA may be more sensitive than RIA. ELISA may be preferable because of its simplicity and convenience of the measurement procedure. The correlation coefficient between anti-ssDNA levels measured by ELISA and anti-dsDNA levels measured by RIA was 0.322 (p < 0.01), and the correlation coefficient between anti-ssDNA and anti-dsDNA antibody levels measured by ELISA was slightly higher, 0.515 (p < 0.001). These results may reflect the predominance of anti-DNA antibodies reactive with both ss and dsDNA in SLE sera. Since the clinical significance of anti-ssDNA antibodies remains unclear, further analysis of accumulated cases is required.

Antibodies, Antinuclear↗
PubMed1997

Rapid, sensitive and specific diagnosis of Bordetella pertussis using the polymerase chain reaction.

Use of a repetitive DNA sequence of Bordetella pertussis allowed successful detection of the organism by the polymerase chain reaction (PCR). The method was highly sensitive, being able to detect B. pertussis in specimens containing only a few cells. It was also highly specific, with no amplification of specimens containing other organisms, for example Haemophilus influenzae or Neisseria, being observed. A diagnosis could be made within 1 day. The PCR assay was also evaluated in clinical specimens. Among 47 nasopharyngeal specimens obtained from 24 patients with laboratory-confirmed pertussis, 27 were positive by PCR and 19 by culture. In particular, all three bronchial aspirates from one patient with pertussis were positive by PCR, but only one showed positive on culture. Eleven specimens from parapertussis patients and 65 specimens from patients without pertussis tested negative. It was concluded that this newly developed PCR method for the diagnosis of pertussis was more rapid and sensitive than the usual culture method. Polymerase chain reaction could have a major impact on the treatment and control of this infection and would be a useful tool for studying the pathogenesis of B. pertussis infection.

Bacteriological Techniques↗
PubMed1997

Simple, speedy, sensitive, and specific serodiagnosis of pertussis by using a particle agglutination test.

We developed a particle agglutination test (KPA) with poly(gamma-methyl L-glutamate) as the solid particle for measurement of pertussis toxin (PT) antibody. In this study, KPA was assessed as a means of serodiagnosing pertussis, and the results were compared with those of indirect enzyme-linked immunosorbent assay (indirect ELISA) and the microagglutination test. First, four serum samples were collected from each of 21 healthy children: before and 4 weeks after receiving three primary doses of acellular pertussis vaccines and before and 4 weeks after receiving a booster dose. In all 21 vaccinees, a significant rise in PT antibody titers was observed by KPA after each vaccination, and among all 84 serum samples collected, an excellent correlation was demonstrated between the values obtained by indirect ELISA and those obtained by KPA (r = 0.92). Second, paired serum samples were collected at intervals of approximately 2 weeks from 51 patients with culture-confirmed pertussis. A significant increase in titer (fourfold or more) was observed in 39 (76%) patients by KPA, 34 (67%) patients by indirect ELISA, and 23 (45%) patients by the microagglutination test. In acute- and convalescent-phase sera collected from 20 nonpertussis patients, there were no changes in titers by KPA. The KPA procedure was as simple as that of the microagglutination test, and the reaction time was only 2 h (or overnight). In this study, KPA was demonstrated to be a simple, speedy, sensitive, and specific serodiagnostic method for pertussis.

Agglutination Tests↗
PubMed1997

Sensitization of rhabdo-, lenti-, and spumaviruses to human serum by galactosyl(alpha1-3)galactosylation.

Vesicular stomatitis virus, human immunodeficiency virus type 2, and human foamy virus, which were produced by cell lines expressing galactosyl(alpha1-3)galactosyl (alphaGal) sugars, were found to be less stable in human serum than those from alphaGal-negative cells, indicating that galactosyl(alpha1-3)galactosylation sensitizes these viruses as well as mammalian type C oncoviruses (Rother et al., J. Exp. Med. 182:1345-1355, 1995; Takeuchi et al., Nature (London) 379:85-88, 1996) to complement killing via natural anti-alphaGal antibodies. Thus, virus killing mediated by anti-alphaGal antibodies may play a role as a barrier to animal-to-human infection of various enveloped viruses. Virus vectors for human in vivo gene therapy based on the viruses mentioned above should be produced from alphaGal-negative cells.

3T3 Cells↗
PubMed1997

Molecular mechanisms for somatostatin inhibition of c-fos gene expression.

We reported previously that somatostatin inhibits the expression of the immediate early gene c-fos. Accordingly, we characterized the molecular mechanisms by which somatostatin inhibits c-fos gene expression. Because growth factors activate c-fos through a region of its promoter known as the serum response element [SRE; base pairs (bp) -357 to -276] we transfected rat pituitary adenoma cells (GH3) with plasmids containing the SRE or the SRE core fragment (bp -320 to -298) upstream of the luciferase reporter gene. Epidermal growth factor (EGF) stimulated SRE-luciferase activity, and this effect was inhibited by somatostatin and by the analog MK-678. Identical results were obtained with the SRE core plasmid, demonstrating that the sequence between bp -320 and -298 of the c-fos promoter is a somatostatin response element. Because the extracellular signal-regulated protein kinases (ERKs) induce the SRE via phosphorylation of transcription factors such as Elk-1, we examined the effect of somatostatin on ERK phosphorylation and activation. EGF stimulated tyrosine phosphorylation of ERK2, and MK-678 attenuated this effect. In experiments using in-gel kinase assays, MK-678 also inhibited EGF-stimulated ERK activity via a pertussis toxin sensitive pathway, and this effect resulted in inhibition of Elk-1 transcriptional activity. Our data suggest that one mechanism of somatostatin action involves inhibition of ERK activity, Elk-1 phosphorylation and transcriptional activation, and ultimately c-fos gene transcription.

Animals↗
PubMed1997

Molecular mechanisms for the growth factor action of gastrin.

We have previously observed that gastrin has a cholecystokinin B (CCK-B) receptor-mediated growth-promoting effect on the AR42J rat pancreatic acinar cell line and that this effect is paralleled by induction of expression of the early response gene c-fos. We undertook these experiments to elucidate the mechanism for induction of c-fos and the linkage of this action to the trophic effects of gastrin. Gastrin (0.1-10 nM) dose dependently induced luciferase activity in AR42J cells transfected with a construct consisting of a luciferase reporter gene coupled to the serum response element (SRE) of the c-fos promoter. This effect was blocked by the specific CCK-B receptor antagonist D2 but not by the specific CCK-A receptor antagonist L-364,718 or by pertussis toxin, indicating that gastrin targets the SRE via specific CCK-B receptors through a mechanism independent of Gi. Inhibition of protein kinase C (PKC) either by prolonged (24 h) exposure of the cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (100 nM) or by incubation with the selective inhibitor GF-109203X (3.5 microM) resulted in an 80% reduction in luciferase activity. Similar results were observed in the presence of the specific extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor PD-98059 (50 microM). We measured ERK2 activity in AR42J cells via in-gel kinase assays and observed that gastrin (1 pM-100 nM) induced ERK2 enzyme activity in a dose-dependent manner. Addition of GF-109203X and PD-98059, either alone or in combination, produced, respectively, partial and total inhibition of gastrin-induced ERK2 activity. Gastrin induction of ERK2 activity also resulted in a threefold increase in the transcriptional activity of Elk-1, a factor known to bind to the c-fos SRE and to be phosphorylated and activated by ERK2. PD-98059 blocked the growth-promoting effect of gastrin on the AR42J cells, demonstrating that this effect depends on activation of MEK. Our data lead us to conclude that the trophic actions of gastrin are mediated by ERK2-induced c-fos gene expression via PKC-dependent and -independent pathways.

Animals↗
PubMed1997

Functional role of extracellular signal-regulated protein kinases in gastric acid secretion.

Epidermal growth factor (EGF) has acute inhibitory and chronic stimulatory effects on gastric acid secretion. Because a cascade of intracellular events culminating in the activation of a family of serine-threonine protein kinases called extracellular signal-regulated protein kinases (ERKs) is known to mediate the actions of EGF, we undertook studies to explore the functional role of the ERKs in gastric acid secretion. ERK2 was immunoprecipitated from cell lysates of highly purified (> 95%) gastric canine parietal cells, and its activity was quantified using in-gel kinase assays. Of the primary gastric secretagogues, carbachol was the most potent inducer of ERK2 activity. Gastrin and EGF had weaker stimulatory effects, whereas no induction was noted in response to histamine. The effect of carbachol appeared to be independent of Ca2+ signaling. PD-98059, a selective inhibitor of the upstream ERK activator mitogen-activated protein kinase/ERK kinase, dose-dependently inhibited both carbachol- and EGF-stimulated ERK2 activity, with a maximal effect observed between 50 and 100 microM. ERKs activation is required for induction of the early gene c-fos via phosphorylation of the transcription factor Elk-1 which binds to the c-fos serum response element (SRE). Carbachol stimulated a two- to threefold induction of luciferase activity in cultured parietal cells transfected with either a SRE-luciferase reporter plasmid or with a chimeric GAL4-ElkC expression vector and the 5 x GAL-luciferase reporter plasmid. To examine the significance of ERK activation in gastric acid secretion, we tested the effect of PD-98059 on carbachol-stimulated uptake of 14C-labeled aminopyrine (AP). Acute inhibition of the ERKs by PD-98059 led to a small increase in AP uptake and a complete reversal of the acute inhibitory effect of EGF on AP uptake induced by either carbachol or histamine. In contrast, exposure of the cells to PD-98059 for 16 h led to a reversal of the chronic stimulatory effect of EGF on AP uptake induced by carbachol. Our data led us to conclude that carbachol induces a cascade of events in parietal cells that results in ERK activation. Although the acute effect of the ERKs on gastric acid secretion appears to be inhibitory, the activation of transcription factors and of early gene expression could be responsible for its chronic stimulatory effects.

Aminopyrine↗