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Biomedical subjects

T Tsutsumi

Publications and source records attributed to T Tsutsumi.

At least 19 recordsLinked to original sources

Hepatocyte growth factor down-regulates the alpha-fetoprotein gene expression in PLC/PRF/5 human hepatoma cells.

Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes; however, in certain human hepatoma cell lines, the growth is inhibited by HGF. In the present study, the effect of HGF on the alpha-fetoprotein (AFP) gene expression was analyzed in PLC/PRF/5 human hepatoma cells. HGF did not inhibit cell proliferation, but dose-dependently suppressed AFP secretion at the concentrations of 10 ng/ml or less. By Northern blot analysis, the levels of AFP mRNA were suppressed by HGF, whereas the levels of beta-actin mRNA used as a control did not show any significant changes. In the transient chloramphenicol acetyltransferase plasmid transfection assays, the AFP promoter activity was repressed by HGF, in contrast, the AFP enhancer activity was not affected by HGF. These results suggest that the AFP gene expression is down-regulated by HGF through the suppression of its promoter activity in human hepatoma cells.

Animals

Transbilayer movement and metabolic fate of ether-linked phosphatidic acid (1-O-Octadecyl-2-acetyl-sn-glycerol 3-phosphate) in guinea pig peritoneal polymorphonuclear leukocytes.

1-O-Octadecyl-2-acetyl-sn-glycerol 3-phosphate (octadecylacetyl-GP) and its deacetylation product were used as a model of phosphatidic acid and its lyso derivatives, respectively. The binding, transbilayer movement, and intermembranous transport, which should be related to its metabolism in guinea pig peritoneal polymorphonuclear leukocytes, were studied. The albumin extraction procedure (Tokumura, A., Tsutsumi, T., Yoshida, J., and Tsukatani, H. (1990) Biochim. Biophys. Acta 1044, 91-100) was used for studying the transbilayer movement of [3H]octadecylacetyl-GP. The binding, translocation, and metabolism of octadecylacetylglycerol, a dephosphorylated product of octadecylacetyl-GP, in polymorphonuclear leukocytes were also investigated for comparison. The translocation of octadecylacetyl-GP was dependent on temperature, but not on its concentration (in the range of 1-100 nM). The rate of translocation of octadecylacetyl-GP was much slower than that of octadecylacetylglycerol. Treatment of polymorphonuclear leukocytes with N-ethylmaleimide did not affect the translocation of octadecylacetyl-GP. These results suggest that the transbilayer movement of octadecylacetyl-GP is driven by a diffusion process, not by a carrier protein. From these findings, the process of translocation of octadecylacetyl-GP is concluded to be a rate-limiting step in its metabolic conversion to triglyceride, phosphatidylethanolamine, and phosphatidylcholine.

Acetylation

Interaction of interferon-alpha with interleukin-1 beta or tumor necrosis factor-alpha on hepatitis B virus enhancer activity.

The interaction of IFN-alpha with IL-1 beta or TNF-alpha on hepatitis B surface antigen (HBsAg) expression was analysed in hepatitis B virus (HBV)-DNA integrated PLC/PRF/5 and non-integrated HuH-7 human hepatoma cells. Secretion of HBsAg in PLC/PRF/5 cells was reduced by IFN-alpha, IL-1 beta or TNF-alpha, and synergistically depressed when IFN-alpha was used in combination with IL-1 beta or TNF-alpha. By Northern blot analysis, the levels of HBsAg mRNA were suppressed by IFN-alpha in combination with IL-1 beta or TNF-alpha. In the chloramphenicol acetyltransferase plasmid transfection assay, IFN-alpha in combination with IL-1 beta or TNF-alpha caused a much greater suppression of HBV enhancer activity than IFN-alpha, IL-1 beta or TNF-alpha alone in both hepatoma cells. These findings suggest that the interaction of IFN-alpha with IL-1 beta or TNF-alpha synergistically represses HBV enhancer activity, resulting in depressed expression of HBsAg.

Carcinoma, Hepatocellular

Inhibitory effect of prostaglandin delta 12-PGJ2 on cell proliferation and alpha-fetoprotein expression in HuH-7 human hepatoma cells.

9-deoxy-delta 9,delta 12-13,14-dihydro-prostaglandin D2 (delta 12-PGJ2) is a potent inhibitor of proliferation of tumor cells. In the present study, the effect of delta 12-PGJ2 on the alpha-fetoprotein(AFP) and the albumin gene expression was analyzed in HuH-7 human hepatoma cells. delta 12-PGJ2 inhibited the cell growth and reduced the medium AFP concentrations dose-dependently. To determine whether this decline of AFP depends only on the relative decrease in cell numbers by delta 12-PGJ2, or is in part, due to the decrease in the cellular AFP synthesis by delta 12-PGJ2, Northern blot analysis was performed in this study. By Northern blotting, it was shown that delta 12-PGJ2 caused a marked reduction in the levels of the AFP mRNA and the albumin mRNA. In contrast, the level of the beta-actin mRNA was not changed by delta 12-PGJ2. In the transient chloramphnicol acetyltransferase plasmid transfection experiments, delta 12-PGJ2 did not suppress the AFP enhancer activity, which possibly regulates both the AFP and the albumin gene expression in HuH-7 hepatoma cells, but resulted in the selective repression of the AFP and the albumin promoter activity. These results suggest that delta 12-PGJ2 suppresses not only cell growth but also expression of the AFP gene and the albumin gene at the transcriptional level in human hepatoma cells.

Albumins

Antagonism of ceruletide, a cholecystokinin analog, to the neurochemical effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine and MK-801, on regional dopaminergic neurons in the rat brain.

In the present study, we investigated the effects of ceruletide (CL), a cholecystokinin analog, on the neurochemical response to non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine (PCP) and MK-801, of the dopaminergic neuron systems in the discrete regions of the rat brain. Systemically administered PCP (7.5 mg/kg, i.p.) or MK-801 (1.0 mg/kg, i.p.) produced significant increases in the tissue contents of dopamine metabolite, homovanillic acid (HVA), in the prefrontal cortex, the nucleus accumbens and the olfactory tubercle but not in the nucleus caudatus putamen after 60 min. The effects of NMDA receptor antagonists in the nucleus accumbens and the prefrontal cortex were partially antagonized by pretreatment with CL (80 and 400 micrograms/kg, i.p., at 60 min prior to the drugs). While CL alone decreased the dopaminergic metabolism only in the nigrostriatal pathways in naive rats, the present results indicated that CL also attenuates the activities of the meso-limbic and meso-cortical dopaminergic neuron systems when these are enhanced by either PCP or MK-801.

3,4-Dihydroxyphenylacetic Acid

Follow-up study of camp marathon group psychotherapy for adolescents with emotional disturbances.

Every summer since 1972, the Department of Psychiatry at Fukuoka University has been holding the Camp Marathon Group Psychotherapy (MGP) for adolescents with emotional disturbances. This time we conducted a follow-up survey on 114 camp attendees from 1978 to 1985. Questionnaires were mailed out and we received 56 replies, that is a response rate of 49.1%. The average observation period of the follow-up was 4 years. The results were as follows: Thirty-six cases or 64.3% were making satisfactory progress at the time of the survey. Eight or 14.3% showed no change or showed worsening conditions. Seven or 12.5% cases developed into schizophrenia. Based on these results, we studied roughly what role MGP plays in the therapy of adolescents with emotional disturbances.

Adolescent

[The efficacy and side effects of chemotherapy for primary lung cancer with cisplatin and etoposide].

We treated 34 primary lung cancer patients with chemotherapy of cisplatin and etoposide. There were 2 cases of CR (15%) and 8 cases of PR (61%) out of 13 cases of small cell lung cancer. No case of CR and one case of PR (5%) were obtained out of 21 cases of non-small cell cancer. Side effects were leukopenia, increase of BUN and creatinine, angina pectoris, supraventricular premature contraction, and renal failure. WBC reached nadir on day 15 on average. When we repeated this regimen, we encountered 3 cases of acute myocardial infarction, and it was useful for small cell lung cancer.

Adenocarcinoma

A case of transient elevation of the serum carcinoembryonic antigen and associated with severe malnutrition and low T3, T4 syndrome.

A patient with a transient elevation of the serum carcinoembryonic antigen (CEA) associated with a benign disease was reported. The elevation of CEA was noted in the patient with low T3, T4 syndrome associated with malnutrition due to malabsorption syndrome induced by post-gastrectomy and chronic pancreatitis. Mild liver dysfunction and diabetes mellitus were also noted. The CEA level decreased as T3, T4 level and malnutrition were improved by administration of a massive digestive enzyme preparation. This inverse correlation between the serum CEA and serum T3, T4 levels suggested that high levels of the serum CEA can be found in the patient with malnutrition.

Biomarkers, Tumor

[The usefulness of pleural biopsy in benign or malignant pleurisy].

Retrospective studies of pleural biopsy, cytology and ADA in pleural effusion were performed in 116 patients with pleural effusion between 1980 and 1988. Pleural malignant disease was diagnosed in 25 patients (75.8%) by cytology, in 19 patients (57.6%) by pleural biopsy. Thus, cytology should be performed first in patients with pleurisy. Both of cytologic study and CEA in pleural effusion were negative in 3 cases of squamous cell carcinoma. Tuberculous pleuritis was diagnosed in 24 patients (50.0%) by pleural biopsy, in 5 patients (10.4%) by isolation of Mycobacterium tuberculosis. Both pleural biopsy and adenosine deaminase activity (ADA) were examined in 19 cases of tuberculous pleuritis and ADA was elevated in 16 patients (84.2%). These data suggested that pleural biopsy was useful for diagnosis of pleuritis and the combination of cytology, tumor markers and ADA with biopsy improved diagnostic rates of pleuritis.

Adult

Translocation of exogenous platelet-activating factor and its lyso-compound through plasma membranes is a rate-limiting step for their metabolic conversions into alkylacylglycerophosphocholines in rabbit platelets and guinea-pig leukocytes.

Platelets and leukocytes are known to degrade platelet-activating factor (PAF), a potential mediator of inflammation, to its lyso-derivative (lyso-PAF) and then convert this to 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholines. However, little is known about the mechanism of internalization of PAF and lyso-PAF, which is a prerequisite for their metabolism within the cells. In this work, the internalization of PAF and lyso-PAF by rabbit platelet and guinea-pig leukocyte plasma-membranes were examined by the washing method with bovine serum albumin. The rates of translocation of PAF and lyso-PAF across guinea-pig plasma membranes were significantly higher than those across rabbit platelets. In these cells, the translocation of PAF was found to be accelerated indirectly by activation of PAF receptors by a small portion of added PAF. Results suggest that a temperature-dependent diffusion process is involved in the internalization of these phospholipids. In both rabbit platelets and guinea-pig leukocytes, the translocation of PAF and lyso-PAF through the plasma membranes was shown to be rate-limiting for the metabolic conversion of these compounds to 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine.

Animals

Regional distribution of DNA and RNA in rat brain: a sensitive determination using high-performance liquid chromatography with electrochemical detection.

DNA and RNA contents in 20 brain regions or nuclei of the rat were determined by a highly sensitive method using high-performance liquid chromatography with electrochemical detection. The high DNA and RNA contents were found in the hypothalamic nuclei, especially the median eminence-arcuate nucleus. These results may be available for the preparation of nucleic acids as the regional control.

Amygdala

Behavioral sensitization to beta-phenylethylamine (PEA): enduring modifications of specific dopaminergic neuron systems in the rat.

Repeated daily administration of an endogenous trace amine, beta-phenylethylamine (PEA), produces behavioral sensitization such that the intensity of PEA-induced stereotyped behaviors in rats increases gradually during the treatment, and a challenge injection with PEA reinstates the enhanced stereotypy even long after withdrawal. In the present study, we examined the neurochemical changes in the central dopaminergic neurons systems in the rat for 7 drug-free days after repeated treatment with PEA (50 mg/kg, IP day for 14 or 28 days). During withdrawal, a decrease in steady-state levels of tissue dopamine (DA) and its metabolite, dihydroxyphenylacetic acid (DOPAC), was found in the mesolimbic DA nerve terminal areas of the rat brain receiving repeated PEA treatment. Fifteen minutes after challenge administration of PEA at varying doses from 6.3 to 75 mg/kg, the rats with repeated PEA treatment required smaller doses of PEA challenge than the rats with acute PEA treatment in order to obtain a significant decrease in striatal DOPAC content compared to the saline control in each treatment group. These results imply that the behavioral sensitization to PEA is accompanied by enduring modifications of the specific dopaminergic neuron systems in the rat brain. This suggestion was strongly supported by the results of the study using in vivo intracerebral dialysis, which indicated that 25 mg/kg PEA challenge elicited a remarkable increase in the extracellular DA concentrations in striatal perfusates collected from the PEA-pretreated rats, in accordance with the intensity of stereotyped behaviors. These findings argue that the hyper-responsiveness to PEA of the striatal dopaminergic neuron systems persists long after withdrawal from repeated treatment with PEA.

3,4-Dihydroxyphenylacetic Acid

Computer simulation of supraventricular tachycardia with the Wolff-Parkinson-White syndrome using three-dimensional heart models.

Supraventricular tachycardias with the Wolff-Parkinson-White (WPW) syndrome have been successfully simulated using a newly developed simulation system. The heart model, including atria and ventricles, was constructed of about 50,000 discrete elements (model cells) in three dimensions with 1.5-mm spatial resolution. The model cells covered all of the types of cells in the actual heart, including the normal myocardium, special conduction system and abnormal cells, such as the bundle of Kent (accessory pathway) and ectopic pacemaker (premature beat). Different model cells were specified by their electrophysiologic parameters, such as action potential, refractory period, and conduction velocity. The WPW syndrome was simulated by setting an accessory pathway between the right atrium and ventricle. Based on this model a premature atrial beat was introduced, which initialized the tachycardia. By adjusting the parameters, three types of reciprocal supraventricular tachycardia were simulated with the reentry circuits (1) formed anterogradely by the A-V node and retrogradely by the accessory pathway, (2) formed anterogradely by the accessory pathway and retrogradely by the A-V node, and (3) confined within the A-V node. Time relations for initializing and maintaining the tachycardias were evaluated. The simulated ECGs were in good agreement with the clinical findings.

Computer Simulation

Involvement of the cholinergic system in haloperidol-induced release of dopamine from slices of striatum in the rat.

The effects of cholinergic and anticholinergic drugs on spontaneous or haloperidol-induced release of dopamine (DA) were studied in vitro. The slices of striatum were placed in a chamber and continuously superfused with Krebs' solution, containing various concentrations of haloperidol, with or without atropine, d-tubocurarine (d-TC), tetrodotoxin (TTX), physostigmine or carbachol. Haloperidol, enhanced the release of endogenous DA from the slices of striatum at an EC50 value of 25.6 microM. The effect of haloperidol was significantly reduced by atropine (2.5 microM), while it was unaffected by d-TC (10 microM) and TTX (1 microM). In contrast, physostigmine (3.7 microM) significantly increased the haloperidol-induced efflux of DA from the slices of striatum. In addition, acetylcholine (ACh), in the presence of physostigmine or carbachol, enhanced the basal efflux of DA at EC50 values of 2.8 microM and 83 microM, respectively. The effect of ACh on the efflux of DA was antagonized by atropine. These data suggest that haloperidol-induced release of DA is, at least partially, mediated by the activation of muscarinic ACh receptors located in the striatum.

Acetylcholine

[Clinical and bacteriological studies in four cases of pulmonary infection caused by Protomonas extorquens].

A novel bacterium, Protomonas extorquens was isolated from sputum, pleural effusion and ascitis in four cases of pulmonary infection by buffered charcoal yeast extract agar (B-CYE) which was generally used for Legionella spp. Three cases were so-called immunocompromised hosts (2 malignant diseases, 1 renal failure), and they died from underlying diseases. Protomonas extorquens was newly named by Komagata in 1984, which was characterized by production of pink pigment, growth in methanol medium and positive production of oxidase and catalase. This organism is ordinarily isolated from soil and dead leaves. This is the first report for isolation of P. extorquens from clinical specimens in Japan and it seems to have a significant role in immunocompromised hosts.

Adult

[Acute myocardial infarction induced by lung cancer chemotherapy with cisplatin and etoposide].

From June of 1986 to May of 1989, we encountered 78 cases of lung cancer and administered CDDP and etoposide, orally and intravenously. We found 3 cases of acute myocardial infarction (AMI) onset after this chemotherapy regimen. It is important to detect AMI onset as soon as possible. We must take prophylactic procedures for patients with coronary risk factors who have had radiation therapy previously.

Adenocarcinoma

[Diagnostic usefulness of transbronchial aspiration and bronchial lavage for pulmonary tuberculosis].

Fiberoptic bronchoscopy is a well established methods as a useful tool in the diagnosis of pulmonary tuberculosis with smear negative cases. In order to get the early and definite diagnosis of pulmonary tuberculosis, we performed transbronchial aspiration and bronchial lavage by a fiberoptic bronchoscope in 97 patients. All patients (1) were clinically suspected of having active tuberculosis; (2) showed abnormal chest roentgenogram suggesting tuberculosis; (3) showed negative sputum smears of acid-fast bacilli, or had no sputum. The results of the study were summarized as follows: 1) Final diagnosis of study subjects were 90 patients of active pulmonary tuberculosis, and 7 patients of pulmonary atypical mycobacteriosis. 2) Sputum culture of acid-fast bacilli was positive in 22 out of 90 patients with active pulmonary tuberculosis. 3) Smear and culture examination of acid-fast bacilli of transbronchial aspirates were positive in 9 and 28, respectively out of 90 patients. 4) Smear and culture examination of acid-fast bacilli of bronchial lavage were positive in 12 and 39, respectively out of 90 patients. 5) A rapid and definite diagnosis was made in 16 out of 90 patients by transbronchial aspirates or bronchial lavage. 6) Atypical mycobacteria were detected in 7 out of 97 patients by transbronchial aspirates or bronchial lavage. 7) There were no serious complications such as pneumonia and exacerbation of pulmonary tuberculosis. These results suggested that transbronchial aspiration and bronchial lavage were useful procedures for rapid and definite diagnosis of pulmonary tuberculosis.

Adult