Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 235 records · Page 13Linked to original sources

PubMed1999

RhoN, a novel small GTP-binding protein expressed predominantly in neurons and hepatic stellate cells.

A cDNA encoding a novel member of the small molecular weight GTP-binding protein (small G-protein) superfamily was cloned from rat spinal cord. The deduced amino acid sequence was highly homologous with those of so-far-known Rho proteins. Rho proteins were reported to alter many important cellular functions including formation of both actin stress fibers and focal adhesions. RNA blot hybridization and in situ hybridization analyses indicated that the novel small G-protein is expressed specifically in neurons in the brain and spinal cord and also in hepatic stellate cells. Based on the sequence similarity and neuron-specific expression in the brain, this protein was named RhoN. Unlike classical Rho proteins, RhoN was not susceptible to the ADP-ribosylation reaction by C3 botulinum toxin. Accordingly, RhoN seemed to be specifically involved in neuronal and hepatic functions as a C3 toxin-insensitive member of the Rho subfamily. Then, a mouse genomic DNA segment containing the RhoN gene was cloned. The locus was mapped on the mouse chromosome 11C-D. The sequence data showed that the protein-coding sequence for RhoN is divided by 4 introns, and that the defined 5 exons may encode intramolecular domains serving for different functions.

Adenosine Diphosphate Ribose↗

PubMed1999

Peptide 19 in the dorsal root ganglion and the mesencephalic trigeminal tract nucleus of the adult rat.

Peptide 19-immunoreactivity (PEP 19-ir) was examined in the dorsal root ganglion (DRG) and the mesencephalic trigeminal tract nucleus (Mes5) of the adult rat. Thirty-eight percent of DRG cells were immunoreactive (ir) for PEP 19. These neurons were small to large and measured 167-4583 micron2 (mean+/-S.D.=2048+/-913 micron2). Seventy-five percent of DRG cells >2000 micron2 and 15% of those <1000 micron2 exhibited PEP 19-ir. Thirty-six percent of DRG neurons in the range 1000-2000 micron2 showed the ir. In the Mes5, 87% of primary neurons were ir for this peptide. Muscle spindles in the soleus and masseter muscles contained PEP 19-ir spiral axon terminals. Double immunofluorescence methods revealed the co-expression of PEP 19 and calcium binding proteins. Eighty-six percent of parvalbumin-ir neurons exhibited PEP 19-ir. Conversely, 60% of PEP 19-ir neurons showed parvalbumin-ir. The cell size analysis revealed that 55% of PEP 19-ir neurons >600 micron2 showed parvalbumin-ir and that all PEP 19-ir neurons <600 micron2 were devoid of it. Ninety percent of PEP 19-ir DRG neurons showed S100-ir, whereas 60% of S100-ir ones co-expressed PEP 19-ir. In the Mes5, virtually all PEP 19-ir primary neurons exhibited parvalbumin-ir. The co-expression of PEP 19 and S100 could not be observed in the nucleus. The present study indicates that PEP 19-ir neurons which co-express parvalbumin-ir are proprioceptors in the spinal and the trigeminal systems. PEP 19-ir small DRG neurons without S100-ir are probably exteroceptors and may include unmyelinated nociceptors.

Animals↗

PubMed1999

Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes.

Streptozotocin (STZ), a glucose analogue known to induce diabetes in experimental animals, causes DNA strand breaks and subsequent activation of poly(ADPribose) polymerase (Parp). Because Parp uses NAD as a substrate, extensive DNA damage will result in reduction of cellular NAD level. In fact, STZ induces NAD depletion and cell death in isolated pancreatic islets in vitro. Activation of Parp therefore is thought to play an important role in STZ-induced diabetes. In the present study, we established Parp-deficient (Parp-/-) mice by disrupting Parp exon 1 by using the homologous recombination technique. These mice were used to examine the possible involvement of Parp in STZ-induced beta-cell damage in vivo. The wild-type (Parp+/+) mice showed significant increases in blood glucose concentration from 129 mg/dl to 218, 370, 477, and 452 mg/dl on experimental days 1, 7, 21, and 60, respectively, after a single injection of 180 mg STZ/kg body weight. In contrast, the concentration of blood glucose in Parp-/- mice remained normal up to day 7, slightly increased on day 21, but returned to normal levels on day 60. STZ injection caused extensive necrosis in the islets of Parp+/+ mice on day 1, with subsequent progressive islet atrophy and loss of functional beta cells from day 7. In contrast, the extent of islet beta-cell death and dysfunction was markedly less in Parp-/- mice. Our findings clearly implicate Parp activation in islet beta-cell damage and glucose intolerance induced by STZ in vivo.

Animals↗

PubMed1999

Electron microscopic demonstration of nick end-labeled DNA fragments during capsaicin-induced apoptosis of trigeminal primary neurons in neonatal rats.

DNA fragmentation was induced in the trigeminal ganglion of newborn rats by subcutaneous capsaicin injection (50 mg/kg). Twenty-four hours later, numerous roundish profiles were intensely labeled by both a DNA polymerase I-mediated nick translation method and a terminal transferase-mediated tailing method. Direct electron microscopic examination of labeled profiles indicated that the labeled profiles were neurons at earlier stages of apoptosis. DNA fragmentation signal was first detected in the nucleoplasm and later spread to the cytoplasm. The cell finally disintegrated forming many small apoptotic bodies. DNA fragmentation signal in the apoptotic bodies was readily labeled by the tailing but not the translation method.

Analysis of Variance↗

PubMed1999

Cloning and characterization of a novel Rab-family gene, Rab36, within the region at 22q11.2 that is homozygously deleted in malignant rhabdoid tumors.

Malignant rhabdoid tumors (MRTs) are rare, pediatric soft-tissue tumors. Homozygous deletions at chromosome 22q11.2 are a recurrent cytogenetic characteristic of MRTs, an indication that this locus may harbor one or more genes conferring tumor-suppressor activity. We constructed a deletion map of the relevant part of 22q11.2 from a panel of seven MRT cell lines, and isolated a novel gene from the center of the region. As it showed a high degree of sequence homology to genes of the Rab family, we designated it Rab36. The protein encoded by Rab36 was localized at the Golgi body. Sequencing of Rab36 cDNAs from three cell lines that retained at least one allele of this gene revealed no nonsense or frameshift mutations. Experiments to induce over-expression of Rab36 by transfection to an MRT cell line similarly failed to justify designation of this gene as a tumor suppressor that would contribute to tumorigenesis by a loss-of-function mechanism.

Amino Acid Sequence↗

PubMed1999

Mitogen-activated protein kinase phosphatase: a negative regulator of the mitogen-activated protein kinase cascade.

Mitogen-activated protein kinases (MAPKs) are activated by various stimuli, such as growth factors, cytokines, or stress, and are considered to be important mediators in intracellular signal transduction networks. The dual-specificity kinases, MAPK kinases (MKKs), which phosphorylate the TXY motif in the catalytic domain of MAPKs, can cause the activation of MAPKs. Recently, a family of dual-specificity phosphatases has been identified, members of which are able to dephosphorylate and inactivate MAPKs. The studies cited in this review have revealed that these MAPK phosphatases might play an important role in various cellular functions by downregulating the MAPK cascade.

Animals↗

PubMed1999

Soluble fas ligand in natural killer cell lymphoma.

We measured serum soluble Fas ligand (sFasL) in a patient with natural killer cell lymphoma, and investigated relationship between sFasL and liver dysfunction. An elevated level of sFasL was decreased after local radiation therapy, and liver function improved. When lymphoma relapsed, liver dysfunction reappeared and the level of sFasL increased parallelly. Lymphoma cells expressed mRNA of FasL. This suggested that this liver dysfunction was induced by some remote effectors, and sFasL was one of candidates of these effectors.

Adult↗

PubMed1999

Control of acetic acid concentration by pH-stat continuous substrate feeding in heterotrophic culture phase of two-stage cultivation of Alcaligenes eutrophus for production of P(3HB) from CO2, H2, and O2 under non-explosive conditions.

A-two stage culture method of hydrogen-oxidizing bacterium, Alcaligenes eutrophus, is used to produce poly-D-3-hydroxybutyrate, P(3HB) from CO2, O2, and H2 without using a very high oxygen transfer rate while maintaining the O2 concentration in gas phase below 6.9 (v/v)% to prevent detonation of the gas mixture. The two-stage method consists of a heterotrophic culture using fructose as carbon source for exponential cell growth and an autotrophic culture for P(3HB) accumulation. We investigated the use of acetic acid as a cheaper carbon source than fructose for the heterotrophic culture in the two-stage method. However, the acetate concentration in the culture system must be maintained at 1.0 g. dm-3 since its inhibitory effect on the cell growth is very strong. Then, high cell density cultivation of A. eutrophus was investigated by pH-stat continuous feeding of acetic acid to control acetate concentration. As a result, acetate concentration was automatically maintained around 1.0 g. dm-3 by using a feed with a composition in CH3COOH/CH3COONH4/KH2PO4 molar ratio of 5:1:0.084. Cell concentration increased to 48.6 g. dm-3 after 21 h of cultivation. The cell mass grown in the fed-batch culture on acetic acid was useful for P(3HB) production from CO2 in the subsequent autotrophic culture stage. Copyright 1999 John Wiley & Sons, Inc.

Journal Article↗

PubMed1999

Pharmacokinetics of 9alpha-fluoromedroxyprogesterone acetate in rats: comparison with medroxyprogesterone acetate.

Medroxyprogesterone acetate (MPA) is widely used in endocrine therapy for breast cancer and other diseases. Recently, it has been demonstrated that 9alpha-fluoromedroxyprogesterone acetate (FMPA) also has anti-tumour activity in chemical-induced rat mammary tumour and its activity is greater than that of MPA. In the present study, the physico-chemical properties of FMPA and MPA and their pharmacokinetics in female rats were investigated. Partition coefficients (log P) of FMPA and MPA were 3.1 and 3.8, respectively, while the solubilities of FMPA and MPA in phosphate buffer saline were 3.8 and 1.1 microg/mL, respectively. When the two agents were intravenously or orally administered into female rats, there was no significant difference between their plasma concentrations. However, unmetabolized drug excreted into urine accounted for 4.7 and 0.7% of the intravenous dose of FMPA and MPA, respectively. The free fraction of FMPA in rat plasma was approximately four times that of MPA. Assuming the well-stirred model, hepatic intrinsic clearances of FMPA and MPA were estimated to be 64 and 293 L/h per kg, respectively. In addition, the free fraction of FMPA in blood is estimated to be higher than that of MPA, which may explain the higher anti-tumour activity.

Administration, Oral↗

PubMed1999

Aortic stump tailoring with GRF glue and a felt strip.

We describe herein a new technique of aortic stump tailoring for aortic dissection. This method involves the application of gelatine-resorcin-formalin (GRF) glue and a felt strip, with manipulation using the balloon of an endotracheal tube. The conjoined wall consists of three layers, but it is completed like a single layer. This procedure facilitates anastomosis to the graft in the next step.

Aortic Dissection↗

PubMed1999

Aortic valve replacement after retrosternal gastric tube reconstruction for esophageal cancer.

A 59-year-old man with a history of the thoraco-abdominal esophagus resection with retrosternal gastric tube reconstruction for esophageal cancer complicated by anastomosis leakage and purulent pericarditis was admitted for aortic regurgitation due to infective endocarditis. Floppy vegetation and worsening cardiac failure indicated aortic valve replacement. In a median sternotomy approach, the thickest adhesion between the cervical esophagus and posterior surface of the manubrium sternae was freed using an ultrasonic osteotome. Severe adhesions in the pericardium due to purulent pericarditis were found. Median sternotomy enabled minimal exposure of the aortic root, upper right atrium, and right superior pulmonary vein for instituting extracorporeal circulation and replacing the aortic valve. The patient's postoperative course was uneventful. For cardiac surgery in patients with a retrosternal gastric tube, left anterior or right thoracotomy may be considered to avoid gastric tube injury. Median sternotomy, however, is an alternative enabling safe heart exposure, and the ultrasonic osteotome was very useful in incising the sternum without injuring the cervical esophagus, which had no serosa.

Aortic Valve↗

PubMed1999

AVP-induced mitogenic responses of Chinese hamster ovary cells expressing human V1A or V1B receptors.

Arginine vasopressin (AVP) induces cell proliferation and hypertrophy; however, the human receptor subtype and the intracellular signaling pathways responsible for this mitogenic activity remain unclear. Experiments were conducted to determine which AVP receptor is linked to mitogen-activated protein (MAP) kinase activation and the mitogenic effect seen in Chinese hamster ovary (CHO) cells expressing human V1A or V1B receptors. Adding AVP to CHO cells transfected with human V1A or V1B cDNA significantly and concentration-dependently induced activation of MAP kinase and increased DNA synthesis, as measured by [3H]thymidine incorporation. These effects were inhibited by AVP receptor antagonists and the potency order of antagonists in vitro was similar to that observed in radioligand binding assays. These results suggest that AVP induces the MAP kinase cascade leading to cell proliferation through either human V1A or V1B receptors, and that these cloned, expressed AVP receptors may prove an invaluable tool for probing the physiologic and pathophysiologic effects of AVP.

Animals↗

PubMed1999

Cardiac tamponade originating from primary gastric signet ring cell carcinoma.

A 45-year-old man with dry cough and dyspnea was referred by a medical practitioner for evaluation of heart failure on February 10, 1996. Chest X-ray revealed increased cardiothoracic ratio, and ultrasonographic echocardiography disclosed massive pericardial effusion with right ventricular collapse. Cardiac tamponade was diagnosed and pericardiocentesis was performed. Ten days after admission, the pleural effusion had become more pronounced, and thoracocentesis was performed. Carcinoembryonic antigen level was elevated in both the pericardial and pleural effusion, and cytology implicated adenocarcinoma, which suggested malignant effusion. Endoscopic study disclosed gastric cancer in the posterior wall of the upper body, and the histopathological diagnosis was signet-ring cell carcinoma. The patient died of respiratory failure on May 2, 1996, and autopsy was performed. The final diagnosis was gastric cancer with pulmonary lymphangitis, pericarditis, and pleuritis carcinomatosa, accompanied by enlargement of mediastinal and paraaortic lymph nodes. Interestingly, the primary signet-ring cell carcinoma of the stomach was situated mostly in the mucosa. Deep in the submucosal region, there was prominent invasion of the intralymphatic vessels, without direct destruction of the mucosa muscularis.

Carcinoma, Signet Ring Cell↗

PubMed1999

Long-term evaluation of treatment for functional tricuspid regurgitation with regurgitant volume: characteristic differences based on primary cardiac lesion.

OBJECTIVES: The aim of this study was to characterize differences in the long-term effects of treatment for functional tricuspid regurgitation based on the primary cardiac lesion. METHODS: Ninety-six patients with valvular heart disease and 32 patients with atrial septal defects associated with tricuspid regurgitation were studied. The tricuspid annular diameter was associated with evidence of right heart failure. In valvular heart disease, a Kay annuloplasty was performed in 33 patients with a tricuspid annular diameter of >/=40 mm to 44 mm, a modified De Vega annuloplasty in 12 patients with a tricuspid annular diameter of >/=45 mm to 49 mm, and a modified De Vega annuloplasty, annuloplasty using a Carpentier ring, or tricuspid valve replacement in each of 4 patients with a tricuspid annular diameter of >/=50 mm. In atrial septal defects, a Kay annuloplasty was performed in 11 patients with a tricuspid annular diameter of >/=45 mm to 49 mm, and a modified De Vega annuloplasty was performed in 5 patients with a tricuspid annular diameter of >/=50 mm. A mean follow-up period was 79 months after operation. RESULTS: In the patients with a tricuspid annular diameter of <50 mm, the hemodynamic and clinical findings and tricuspid regurgitation remarkably improved. In the patients with valvular heart disease with a tricuspid annular diameter of >/=50 mm, however, the right heart parameters also showed improvement but less so when compared with those patients with a tricuspid annular diameter of <50 mm. In addition, 4 patients undergoing a modified De Vega annuloplasty have had a gradual increase in tricuspid regurgitation and clinical manifestations late after the operation. In contrast, all 5 patients with atrial septal defects with a tricuspid annular diameter of >/=50 mm have shown remarkable improvement, similar to those with a tricuspid annular diameter of <50 mm. Preoperative analyses revealed that the right heart function in atrial septal defects had not deteriorated to the same extent as in valvular heart disease. CONCLUSION: In the patients with a severely dilated tricuspid anulus (>/=50 mm), the postoperative change of tricuspid regurgitation differed between those patients with valvular heart disease and atrial septal defects.

Cardiac Output, Low↗

PubMed1999

Chiral separation and quantitation of pentazocine enantiomers in pharmaceuticals by capillary zone electrophoresis using maltodextrins.

The chiral separation of pentazocine was achieved by capillary electrophoresis using oligosaccharides. Enantiomers were separated on 100 mM Tris/H3PO4 buffer (pH 2.5) with 5% maltodextrin as a chiral selector, and migration behavior was monitored at 200 nm. Under these conditions, (-)- and (+)-pentazocine and dextromethorphan (internal standard) migrated within 9 min, and the resolution of pentazocine enantiomers was 2.54. Linear calibration curves were obtained in the range 5-50 microg/ml(-1) for each enantiomer. The detection limit of pentazocine enantiomers was 29 pg, and the recoveries of(-)- and (+)-pentazocine were 98.9 (R.S.D., 3.4%) and 101.4% (R.S.D., 4.3%) with 10 microg/ml(-1), respectively.

Analgesics, Opioid↗

PubMed1999

A morphological and morphometric study of the peripheral process of the human vestibular nerve following posterior cranial fossa neurectomy.

Three vestibular nerve specimens removed at transmeatal neurectomy were studied in order to understand better retrograde degeneration and regeneration after vestibular neurectomy in the posterior cranial fossa. In two cases this procedure followed retrolabyrinthine retrosigmoid posterior fossa vestibular neurectomy. The subjects, three patients with Menière's disease, were compared with one another and two autopsy controls with no known otological problem. The specimens were obtained at the distal end of the internal auditory canal and transversely sectioned. Many collapsed Schwann cell basement membranes were observed. The ratio of small-diameter nerve fibres increased significantly after neurectomy. Onion bulb formation around myelinated nerve fibres with small diameters and Schwann cell proliferation around the soma of vestibular ganglion cells reflected remyelination. We conclude that peripheral processes of vestibular nerve fibres can undergo retrograde degeneration and subsequent regeneration after transection of the central process.

Aged↗

PubMed1999

Suppression of parathyroid hormone-related protein messenger RNA expression by medroxyprogesterone acetate in breast cancer tissues.

The level of parathyroid hormone-related protein (PTHrP) expressed in breast cancer tissue is closely related to the incidence of bone metastasis. We examined the PTHrP mRNA expression in breast cancer tissues by coamplification polymerase chain reaction (PCR) in mole ratio to internal standard beta-actin mRNA. The PTHrP expression was higher in premenopausal patients than in postmenopausal patients (P < 0.05). More pronounced difference by menopause found in estrogen receptor (ER) positive groups (P < 0.001) indicated that the PTHrP expression in breast cancer tissue is hormonally regulated and might be altered by endocrine agents. To clarify the changes of PTHrP expression by endocrine therapy of breast cancer, we measured PTHrP expression in the breast cancer tissue incubated for 24 h with 1 x 10(-8) M of estradiol (E2), 1 x 10(-6) M of tamoxifen (TAM) and 1 x 10(-5) M of medroxyprogesterone acetate (MPA). The PTHrP expression was decreased significantly by MPA (P < 0.005), while E2 and TAM did not change the PTHrP expression. Progesterone receptor (PgR) mRNA expression was also examined to confirm that the breast cancer tissue responds to E2 and TAM. The results were well compatible with the better therapeutic effect of MPA reported for the treatment of breast cancer with bone metastases. As a potential candidate for the receptor that mediates the suppressive effect of MPA, androgen receptor (AR) is suggested most probable. Present results also demonstrated that the clinical response of individual tumors is closely associated with the early in vitro changes of gene expression detected in the cancer specimen.

Antineoplastic Agents, Hormonal↗

PubMed1999

Levels of soluble FasL and FasL gene expression during the development of graft-versus-host disease in DLT-treated patients.

Three patients with different clinical symptoms of graft-versus-host disease (GVHD) who had received donor lymphocyte transfusion (DLT) for the treatment of relapsed leukaemia after an allogeneic bone marrow transplantation (BMT) from HLA-matched sibling donors were analysed for the presence of soluble FasL (sFasL) in the sera and for the expression of the Fas ligand (FasL) gene in the peripheral blood mononuclear cells (PBMNC). Two patients who demonstrated liver damage with increased levels of serum bilirubin showed significantly increased levels of serum sFasL. The increase in the sFasL level was observed prior to the increase in the bilirubin during the clinical courses of both patients. The high dose of methyl predonisolone administered to one of these patients greatly reduced the levels of sFasL in the serum. The bilirubin levels were also reduced thereafter. The third patient (without liver damage) did not show any increase in the serum sFasL level. The expression of the FasL gene in the PBMNC of these three patients was examined. All three patients showed increased levels of the FasL gene expression during their clinical courses. However, only one patient showed a parallel alteration of FasL gene expression with sFasL in the serum. These cases provide evidence that the Fas/FasL system is closely associated with human GVHD, especially in the development of liver GVHD.

Adult↗