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Biomedical subjects

T Manabe

Publications and source records attributed to T Manabe.

At least 109 records · Page 6Linked to original sources
PubMed1999

Characterization of insulin-like growth factor-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes.

This study was designed to investigate whether insulin-like growth factor-1 (IGF-1) transduces signaling through the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in cardiomyocytes and to assess the upstream signals of serine and tyrosine phosphorylation of STAT family proteins. Primary cultured neonatal rat cardiomyocytes were stimulated with IGF-1 (10(-8) mol/L). JAK1, but not JAK2 or Tyk2, was phosphorylated by IGF-1 as early as 2 minutes and peaked at 5 minutes. IGF-1 induced both tyrosine and serine phosphorylation of STAT1 and STAT3. Tyrosine phosphorylation of STAT1 peaked at 15 minutes and correlated with that of JAK1, whereas that of STAT3 was sustained up to 120 minutes and was dissociated from the activation of JAK1. Tyrosine phosphorylation of STAT3 was unaffected by the preincubation with CV11974 (AT(1) blocker), TAK044 (endothelin-1 receptor blocker), RX435 (anti-gp130 blocking antibody), PD98058, wortmannin, EDTA, or KN62 but was significantly attenuated by BAPTA-AM and chelerythrine. The time course of a gel mobility shift of SIE (sis-inducing element) coincided with the phosphorylation of STAT3. Serine phosphorylation of STAT1 peaked at 30 minutes and that of STAT3 was observed from 5 to 60 minutes. These results indicated that (1) IGF-1 activated JAK1 but not JAK2 or Tyk2 in rat cardiomyocytes; (2) IGF-1 induced both tyrosine and serine phosphorylation of STAT1 and STAT3; and (3) the tyrosine phosphorylation of STAT3 was not caused by JAK1 alone, and protein kinase C and intracellular Ca(2+) were required for phosphorylation.

Animals↗
PubMed1999

Effect of an orally active Th1/Th2 balance modulator, M50367, on IgE production, eosinophilia, and airway hyperresponsiveness in mice.

We have found a novel anti-allergic agent, M50367, which suppresses IgE biosynthesis and eosinophil accumulation in vivo. In this study, we evaluated the ability of M50367 to modulate Th1/Th2 balance in Th2-background BALB/c mice and to inhibit airway hyperresponsiveness in a murine model of atopic asthma. Oral M50367 at 3-30 mg/kg/day exhibited 51 to 73% reduction of IL-4/IL-5 production and 2- to 5-fold augmentation of IFN-gamma production by Ag-stimulated cultured splenocytes of the mice sensitized with DNP-Ascaris. These alterations in Th1/Th2 cytokine production were accompanied by 55-85% suppression of plasma IgE level. Oral M50367 at a dose of 10 mg/kg/day significantly inhibited Ig-independent peritoneal eosinophilia by 54%, which was induced by repeated i.p. injections of Ascaris suum extract. To develop airway hyperresponsiveness caused by allergic airway inflammation, BALB/c mice were sensitized with i.p. OVA injections, followed three times by OVA inhalation. Oral M50367 significantly inhibited the increase in airway reactivity to acetylcholine, together with the elevation of plasma IgE level and pulmonary eosinophilia, which were observed in vehicle-treated mice 1 day after the last inhalation. Moreover, M50367 treatment reduced IL-4 and IL-5 production and tended to enhance IFN-gamma production, not only by cultured splenocytes, but also in bronchoalveolar lavage fluid. These results suggest that M50367 has a modulating ability of Th1/Th2 balance to down-regulate Th2 response in the circulating system as well as at the sites of inflammation, and may be beneficial for the treatment of allergic disorders such as atopic asthma.

Adjuvants, Immunologic↗
PubMed1999

Identification of a novel gene, LDOC1, down-regulated in cancer cell lines.

By screening for differentially expressed genes in cancer cells, using the RNA differential display (DD) technique, we identified a novel cDNA, LDOC1, that is down-regulated in some cancer cell lines. A Northern blot analysis revealed no expression in pancreatic and gastric cancer cell lines but ubiquitous expression in normal human tissues. This new gene was mapped on chromosome Xq27 and the predicted protein sequence showed no similarity to known sequences in the database except for a leucine zipper-like motif at the N-terminal region and a proline-rich region that shares marked similarity to an SH3-binding domain. In an enhanced green fluorescent protein (EGFP) assay, the EGFP-LDOC1 fusion protein was localized in the nucleus. Although the function of LDOC1 is still unknown, our results suggest that this novel gene codes for a nuclear protein, and down-regulation of LDOC1 may have an important role in the development and/or progression of some cancers.

Amino Acid Sequence↗
PubMed1999

Identification of a novel gene, DAM1, amplified at chromosome 1p13.3-21 region in human breast cancer cell lines.

Screening for differentially expressed genes in cancer cell lines by the RNA differential display (DD) technique identified a novel mRNA that encodes a 26-kDa protein and is up-regulated in MCF-7 and BT-20 breast cancer cells. The predicted amino acid sequence showed 38% homology to Caenorhabditis elegans T12A2.7 protein, indicating that this is a possible human homologue for C. elegans T12A2.7 protein. The mRNA, designated DAM1 (DNA amplified in mammary carcinoma), was mapped at the 1p13.3-21 region, which is frequently altered in human breast cancer. By Southern blot analysis, we confirmed that the up-regulation of this novel gene is associated with gene amplification in MCF-7 (10-fold) and BT-20 (5-fold) cells. Our findings suggest that the DAM1 gene is a novel gene up-regulated by amplification in human breast cancer cell lines.

Amino Acid Sequence↗
PubMed1999

Protein spot recognition on the non-denaturing and denaturing two-dimensional electrophoresis patterns using in situ immunosubtraction via Protein A agarose and antibodies.

Specific proteins in small amounts of human plasma were subtracted from patterns of non-denaturing two-dimensional electrophoresis (non-denaturing 2-DE) by layering a 7 microl aliquot of Protein A agarose-antibody complex on the top of an isoelectric focusing (IEF) gel before the loading of a plasma sample. The Protein A agarose suspension was recovered after non-denaturing IEF and was mixed with 8 M urea-5% 2-mercaptoethanol-1% NP-40 to extract the antibody and the specific plasma protein from Protein A agarose. The extract was then subjected to denaturing two-dimensional electrophoresis (denaturing 2-DE) and the location of the specific polypeptide was determined. The technique can be applied to the extraction and analysis of proteins in small amounts of samples.

Antibodies↗
PubMed1999

Experimental implication of celiac ganglionotropic invasion of pancreatic-cancer cells bearing c-ret proto-oncogene with reference to glial-cell-line-derived neurotrophic factor (GDNF).

Perineural invasion is a prominent clinical feature of pancreatic cancer which causes difficulty in curative resection. In the present study, the human pancreatic cancer cell lines, PaCa-2, AsPC-1, SW1990 and Capan-2, were all found to express abundant c-ret proto-oncogene mRNA and RET protein, a member of the receptor-tyrosine-kinase superfamily, identified as being a receptor for glial-cell-line-derived neurotrophic factor (GDNF). In an invasion assay, the migration of pancreatic cancer cells was markedly induced by co-cultivation with human glioma cells, T98G or A172, capable of producing and secreting GDNF. Anti-GDNF antibody in conditioned media of glioma cells suppressed much of the migratory activity. Checkerboard analysis of the migration showed both chemotactic and chemokinetic activity of GDNF. There was no detectable expression of another GDNF receptor component, a glycosyl-phosphatidylinositol-linked receptor (GFR alpha-1), in pancreatic-cancer cell lines, suggesting that the neural invasion of pancreatic-cancer cells spreads along a concentration gradient of GDNF produced from peripheral ganglions through direct interaction of GDNF with its receptor, the c-ret proto-oncogene product. Immunochemical localization of GDNF in human celiac ganglionic tissue supported this contention.

Cell Movement↗
PubMed1999

Differential inhibition by ferrous ions of [3H]MK-801 binding to native N-methyl-D-aspartate channel in neonatal and adult rat brains.

In vitro addition or pretreatment with >/=1 microM ferrous chloride markedly inhibited in a concentration-dependent manner [3H]dizocilpine (MK-801) binding to an open ion channel associated with the N-methyl-D-aspartate (NMDA) receptor in rat brain synaptic membranes. The addition of NMDA agonists invariably attenuated the inhibition of [3H]MK-801 binding in hippocampal synaptic membranes previously treated with ferrous chloride, without significantly affecting that in cerebellar synaptic membranes. In the absence of spermidine, ferrous chloride was more potent in inhibiting binding in the cerebral cortex and hippocampus in adult rats than in those in rats at 3 days after birth, while in the striatum [3H]MK-801 binding was 10 times more sensitive to inhibition by added ferrous chloride in neonatal rats than in adult rats. Addition of spermidine significantly attenuated the potency of ferrous chloride to inhibit binding in the cerebral cortex of adult rats, with facilitation of the inhibition in newborn rats. Moreover, spermidine significantly reduced the inhibitory potency of ferrous chloride in neonatal rat striatum, without markedly affecting that in adult rat striatum. These results suggest that ferrous ions may interfere with opening processes of the native NMDA channel through molecular mechanisms peculiar to neuronal development in a manner associated with the polyamine recognition domain.

Animals↗
PubMed1999

Capillary electrophoresis of proteins for proteomic studies.

Analyses of proteins in complex mixtures such as cell lyzates are presently performed mainly by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. For structural analysis, each protein in a spot is digested with proteases and the fragment peptides are subjected to Edman sequencing and/or mass spectrometry. These works aim at the total analysis of proteins in a complex mixture and reconstruction of their cooperative functions. Genomic studies are now being combined with these proteomic studies. This review article focuses on the application of capillary electrophoresis aiming at the total analysis of complex protein systems or structural analysis of each separated protein. From this viewpoint, articles on capillary zone electrophoresis, capillary isoelectric focusing, and sieving SDS capillary electrophoresis are reviewed. Since these techniques of capillary electrophoresis have been thoroughly reviewed previously, papers published in 1997 and 1998 are mainly covered.

Electrophoresis, Capillary↗
PubMed1999

Separation of human cerebrospinal fluid proteins by capillary isoelectric focusing in the absence of denaturing agents.

Conditions of capillary isoelectric focusing (CIEF) to separate human cerebrospinal fluid (CSF) proteins were examined referring to those which we have established for the separation of human plasma/serum proteins. Since the average protein concentration in CSF is about 1/200 of plasma and the salt concentration is at almost the same level as plasma, desalting of CSF samples with minimum dilution was a prerequisite for CIEF analysis of CSF proteins. We constructed an apparatus to dialyze CSF at the level of 20-30 microL, this volume being sufficient for 3-4 repeated analyses of the CSF sample. To trace the process of dialysis, a simple device to measure the conductivity of the dialyzate was also constructed. Most of the CIEF conditions for plasma protein analysis could be applied for CSF protein analysis. However, the addition of N,N,N',N'-tetramethylethylenediamine (TEMED) at a suitable concentration was necessary to improve the resolution of basic proteins (IgG region), since some CSF patterns showed peaks of basic proteins which are not obvious in the serum of the same patient. About 70 peaks and shoulders of CSF proteins could be detected by the established CIEF technique. The results of CIEF analysis of CSF samples suggested that the technique will be useful as a survey method to detect specific proteins in CSF, which might relate to disorders in the central nervous system.

Blood Proteins↗
PubMed1999

Florid endocervical glandular hyperplasia with intestinal and pyloric gland metaplasia: worrisome benign mimic of "adenoma malignum".

We describe three cases of florid endocervical glandular hyperplasia with intestinal and pyloric gland metaplasia, which can be a benign mimic of adenoma malignum. In two cases, adenoma malignum was seriously considered preoperatively because of watery vaginal discharge and the results of imaging studies. The three cases shared common histopathological features, i.e., (i) proliferating endocervical glands surrounded by clusters of smaller glands, resembling the pyloric glands of the stomach; (ii) occasional intestinal metaplasia; (iii) bland nuclear features; and (iv) predominantly PAS-positive neutral mucin in the glandular epithelium. In two cases, glands were densely and irregularly arranged in some areas. Immunohistochemistry disclosed that the intracytoplasmic mucin of the metaplastic epithelium was positive for M-GGMC-1 (HIK1083), which reacts with mucin of pyloric glands. Monoclonal CEA was negative in all cases. This pseudoneoplastic benign condition should be recognized by both gynecologists and pathologists, although it might be difficult to establish a definite diagnosis preoperatively even with deep cone biopsy.

Adenoma↗
PubMed1999

Trigeminal ganglioneuroma.

We present the case of an 8-year-old girl with a ganglioneuroma in the left cerebellopontine angle region. The tumor originated from the sensory root of the trigeminal nerve. Histopathologically, it was composed of neoplastic ganglion cells and Schwann cells, leading us to the diagnosis of ganglioneuroma. Intracranial ganglioneuroma is very rare. To our knowledge, this is the first report of a trigeminal ganglioneuroma. The nature and origin of this tumor are discussed and the literature reviewed.

Cerebellopontine Angle↗
PubMed1999

A bidirectional closing aortic dissection from an atherosclerotic distal aortic arch aneurysm: report of a case.

We experienced one rare case of a 76-year-old male with a Stanford type A bidirectional closing aortic dissection from a coexisting atherosclerotic distal arch aneurysm. He showed a cardiac tamponade, and effective pericardial drainage allowed us to conservatively manage the patient. Both an increase in the size of the aneurysm and a recrudescent dissection in the descending aorta were identified 2 months after the onset. A scheduled surgical repair was successful. The coexistence of an acute aortic dissection and an atherosclerotic aneurysm increases the risk of an aortic rupture, particularly at the confluence of the two lesions. Meanwhile, the management of a closing aortic dissection remains controversial because its characteristics still are not well known. We studied not only the pathogenesis but also the management of these two forms of aortic disease and their complex relationships.

Aged↗
PubMed1999

Protective effects of calpain inhibitor for prolonged hypothermic cardiac preservation.

PURPOSE: For successful organ transplantation, it is important to properly preserve the donor organ. This study was carried out to investigate tissue damage generated by the activation of calpain during prolonged hypothermic cardiac preservation using specific antibodies for mu- and m-calpain proenzymes, and to ensure the protective effect of calpain inhibitor 1 (N-acetyl-leucyl-leucyl-norleucinal). METHODS: Excised rat hearts were divided into two groups: in Group I, the heart was arrested and immersed in University of Wisconsin solution with 20 microM of calpain inhibitor 1 (n = 28) and in Group N, the heart was arrested and immersed in University of Wisconsin solution without calpain inhibitor (n = 27). After a 12-hour preservation period at 4 degrees C, the hearts were reperfused on an isolated perfusion apparatus. Separation of the myocardial calpain isozymes was carried out by DEAE cellulose chromatography and both calpain proenzymes were detected by immunoblotting. RESULTS: The cardiac function was more satisfactorily maintained in Group I in comparison with Group N. Remarkable leakage of creatine kinase, glutamic-oxaloacetic transaminase and lactate dehydrogenase was detected in Group N, while it was efficiently suppressed in Group I. During ischemia, mu-calpain proenzyme decreased in Group N (p < 0.01), but there was no significant change in m-calpain. However, during reperfusion, both mu- and m-calpains decreased more in Group N (p < 0.01). CONCLUSION: Activation of calpain proenzymes and a decrease in cardiac function during preservation and reperfusion were demonstrated. The use of calpain inhibitor to protect against tissue damage was suggested as being useful for the prolonged preservation of the heart.

Adenosine↗
PubMed1999

Tall cell variant of papillary thyroid carcinoma with foci of columnar cell component.

We report a case of the tall call variant of papillary thyroid carcinoma with foci of columnar cell component in a 67-year-old Japanese man. Tall cell variant occupied more than 70% of the tumour, and columnar cell component was of two types in representative sections. One showed striking stratification of nuclei with scanty cytoplasm, and the other appeared clear. Characteristic nuclear features of papillary carcinoma were also observed in the area of the tall cell variant. The patient died of the thyroid cancer with aspiration pneumonia 10 years and 6 months after operation. Although autopsy was not performed, metastatic lymph nodes of the neck removed during life also showed papillary carcinoma with both tall cell and columnar cell components. Our case indicates that tall cell and columnar cell variants may coexist in the same tumour although the pathogenesis remains unclear.

Aged↗
PubMed1999

Parasitic nodule of the thyroid in a patient with Graves' disease.

We report a case of a parasitic nodule of the thyroid in a patient with Graves' disease, which mimicked a lymph node metastasis from a primary occult thyroid carcinoma. The patient was a 67-year-old Japanese woman with a past history of subtotal thyroidectomy for Graves' disease, who was referred to our hospital because of a right cervical mass. A lymph node-like lesion measuring 1.5 cm in diameter was palpable, distinct from the remnant of the right thyroid lobe. Thyroid scintigraphy using 123I-Na revealed a hot lesion at the upper lateral portion of the right thyroid lobe, and this was resected. Microscopically, the mass showed thyroid follicles with lymphocytic infiltration and lymphoid follicles. Clear ground glass nuclei, nuclear grooving and intranuclear inclusions were not observed. No morphological evidence of the lymph node was found in the mass by reticulin staining. Parasitic nodules of the thyroid in patients with Graves' disease may mimic a metastatic carcinoma of the thyroid.

Aged↗
PubMed1999

Cannulation of the supraceliac aorta for perfusion in small infants.

Because the usual arterial cannulation was not possible, two small infants successfully underwent cardiovascular operation with an arterial cannula in the supraceliac aorta through the gastrohepatic ligament for cardiopulmonary bypass. Follow-up 2.5 years after operation revealed no morbidity. Cannulation of the supraceliac aorta is unusual but should be considered as a valuable surgical option in special cases such as ours.

Aorta↗
PubMed1999

Serrated adenoma of the colorectum: colonoscopic and histologic features.

BACKGROUND: Serrated adenoma is a recently recognized epithelial neoplasm of the colorectum. The aim of this study is to clarify the colonoscopic features of serrated adenomas. METHODS: The endoscopic findings for 52 serrated adenomas of the colorectum were investigated; these were then divided into three groups according to surface features. The histologic type (tubular, tubulovillous or villous) and the incidence of high-grade dysplasia were compared among the three groups. RESULTS: The surface under chromoscopy showed a hyperplastic pattern in 17 lesions, a cerebriform pattern in 18 lesions and a combined pattern in 17 lesions. The tubular type of serrated adenoma was predominant in the hyperplastic pattern group (94%), whereas the tubulovillous or villous histologic types were frequent in the cerebriform pattern (89%) and combined pattern (82%) groups. High-grade dysplasia was found in 18% of the combined pattern adenomas; the incidence was lower in hyperplastic (6%) or cerebriform pattern (0%) adenomas. CONCLUSIONS: Surface features of serrated adenomas have a close correlation with their histologic type. A combined hyperplastic-cerebriform surface pattern under chromoscopy was seen only in serrated adenomas.

Adenoma↗