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S Umemoto

Publications and source records attributed to S Umemoto.

At least 37 records · Page 2Linked to original sources
PubMed1996

Autoimmune response in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice.

BACKGROUND: Autoimmune mechanisms have been implicated in the pathogenesis of chronic ongoing myocarditis. To investigate this relation, we used an A/J mouse model inoculated with coxsackievirus B3 and determined whether myocarditis would be transferred to normal hearts that were heterotopically transplanted. METHODS AND RESULTS: Inbred 3-week-old A/J mice were inoculated intraperitoneally with coxsackievirus B3 (Nancy strain; 2 x 10(4) plaque-forming units) and housed for > 60 days. The presence of the viral genome in the myocardium was determined by the polymerase chain reaction with primers specific for the 5' end of the coxsackievirus B3 genome performed at 40, 50, or 60 days after inoculation. Normal A/J mouse hearts were transplanted into the same strain of mice without myocarditis (group A) and into mice with chronic ongoing myocarditis (group B). The hearts were evaluated histologically 2 weeks after transplantation. Conventional histological examination of infiltrated T cells and macrophages was performed, and the expression of intercellular adhesion molecule-1, major histocompatibility complex (MHC) class I antigen, and MHC class II antigen was evaluated by immunoenzymatic staining. The concentrations of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor (TNF-alpha) in the grafts were measured with an ELISA. The viral RNA genomes were not detected in the mice with chronic ongoing myocarditis, but their transplanted hearts did show myocarditis. In the hearts with induced myocarditis, infiltrated mononuclear cells consisted of CD4+ T cells, CD8+ T cells (CD4+ cell number > CD8+ cell number), and macrophages. Intercellular adhesion molecule-1, MHC class I antigen, and MHC class II antigen were expressed in the vascular endothelial cells and myocardial cells in and around the infiltrated lesions. The concentrations of IL-1 alpha and TNF-alpha in group B were significantly higher than those in group A (group A versus group B: IL-1 alpha, 125 +/- 35 versus 180 +/- 34 pg/mL; TNF-alpha, 45 +/- 15 versus 96 +/- 40 pg/mL; P < .05). CONCLUSIONS: Results suggest that an autoimmune response may play a key role in the progression of chronic ongoing myocarditis.

Animals↗
PubMed1996

Immobilization stress induces c-fos and c-jun immediate early genes expression in the heart.

Emotional stress is considered to be one of the etiological factors in ischemic heart disease (IHD) and sudden cardiac death (SCD), mechanisms of which are poorly understood. Immediate early genes (IEGs), such as c-fos and c-jun are used as tools for detection of cellular activation. Male Wistar rats were exposed to acute immobilization (IMO). IMO stress for 30 min induced c-fos and c-jun mRNAs expression in the myocardium and the smooth muscle layer of the coronary arteries. IMO stress for 2 h also induced Fos and Jun like-immunoreactivities in the same regions. Distribution of IEG mRNAs and their protein products in the myocardium was not uniform but rather localized. These data provided histological evidence for an early cellular event in the stress response whose consequences could result in activation of tissues in the myocardium and coronary arterial smooth muscle cells which play a role in the pathophysiological changes in IHD and SCD.

Animals↗
PubMed1996

Comparative effects of type 1 angiotensin II-receptor blockade with angiotensin-converting-enzyme inhibitor on left ventricular distensibility and collagen metabolism in spontaneously hypertensive rats.

We compared the cardiac effects of the selective angiotensin II type 1 (AT1)-receptor blockade, FK-739, with an angiotensin-converting-enzyme (ACE) inhibitor, enalapril, on left ventricular (LV) distensibility and collagen metabolism in spontaneously hypertensive rats (SHRs). We treated 14-week-old SHRs with FK-739 (30 mg/kg/day) or enalapril (10 mg/kg/day) for 6 weeks. Both FK-739 and enalapril induced a significant decrease in blood pressure (p < 0.001) and regression of LV hypertrophy (p < 0.001) compared with vehicle, with no differences between the treated groups. Furthermore, FK-739 caused a greater decrease in LV collagen content than did enalapril (FK-739-treated group, 3.06 +/- 0.11 mg/g; enalapril-treated group, 3.47 +/- 0.05 mg/g; p = 0.015) with no change in collagen phenotypes. Hearts taken from rats treated with FK-739 also showed greater LV distensibility than those taken from enalapril-treated rats (FK-739-treated group vs. enalapril-treated group at > or = 15 mm Hg, p < 0.001). These results suggest that, compared with ACE inhibition, AT1-receptor blockade may have additional effects on LV distensibility and collagen metabolism in the regression of LV hypertrophy induced by pressure overload.

Angiotensin Receptor Antagonists↗
PubMed1996

Echographical assessment of the early stage of experimental atherosclerosis of the descending aorta in rabbits.

To assess the early stage of atherosclerosis of the thoracic descending aorta, we evaluated morphological atheromatous lesions (atherosis) and the stiffness parameter of the artery (beta; sclerosis) in 24 male rabbits using echography. Male Japanese white rabbits weighing 2.5-3.0 kg were fed a diet containing 1% cholesterol for 7 (n = 8) or 14 weeks (n = 8). Rabbits fed a normal diet were used as controls (n = 8). Atheromatous lesions were evaluated with intravascular ultrasound (IVUS: Aloka, 20 MHz, 6F). We also calculated beta using M-mode echography (7.5 or 10 MHz) and direct aortic pressure measurement. Thickening of the intima-media complex was clearly observed with IVUS in the 14-week group but was not detected in the others. Histologically, only a thin layer of foamy cells on the intima (thickness < 20 microns) was observed in the 7-week group. The value of beta was significantly increased in both the 7-week (4.7 +/- 2.2) and 14-week groups (4.5 +/- 0.8) compared with controls (1.7 +/- 0.9, both p < 0.01). These results suggest that the development of atherosis might be preceded by vascular sclerosis during the early stage of atherosclerosis when the serum cholesterol level is high: at a time when the thin layer of foamy cells could not be detected by conventional IVUS.

Animals↗
PubMed1996

A case of acute eosinophilic pneumonia. Evidence for hypersensitivity-like pulmonary reaction.

We examined an 86-year-old man with acute respiratory failure. A chest roentgenogram showed diffuse reticular shadows. Transbronchial biopsy revealed thickening of the alveolar septa accompanied by moderate eosinophil infiltration. After admission to the hospital, the patient's symptoms immediately improved without any medication. Clinical course and pathologic findings suggested acute eosinophilic pneumonia caused by a hypersensitivity reaction.

Acute Disease↗
PubMed1994

Differential regulation of IEGs in the rat PVH in single and repeated stress models.

Various kinds of stressors induce immediate early genes (IEGs) in discrete brain regions. We recently reported the reduced response of Fos expression in the hypothalamic paraventricular nucleus (PVH) when rats are repeatedly exposed to immobilization (IMO) stress. In this study, using in situ hybridization histochemistry, we further extended the research to other IEGs, and the results showed that prior exposure to IMO for 6 days suppressed the induction of fosB, junB and NGFI-B, but NGFI-A, mRNAs in response to a challenge IMO on day 7, suggesting that repeated stress has different effects on the transcription of NGFI-A and the other IEGs, in the PVH.

Animals↗
PubMed1994

Repeated stress reduces the subsequent stress-induced expression of Fos in rat brain.

Repeated stress is known to potentiate the CNS response to subsequent stress. Various stressful stimuli can induce Fos expression in discrete regions of the brain, such as the lateral septum, the hypothalamic paraventricular nucleus and the locus coeruleus. We investigated by immunohistochemistry the effect of the stress of repeated immobilization on Fos expression in those regions of the brain in adult male rats. Six daily immobilizations suppressed the expression of Fos in all regions when immobilization was subsequently applied, suggesting that Fos does not play a major role in potentiating the stress response under repeated stressed conditions.

Animals↗
PubMed1994

Differential expression of fos family and jun family mRNAs in the rat hypothalamo-pituitary-adrenal axis after immobilization stress.

We aimed to clarify the regulatory mechanism of the hypothalamo-pituitary-adrenal axis that plays key roles in initiating stress responses, as well as the roles of immediate early genes in this process. We investigated the stress-induced activation of fos and jun family proto-oncogenes by means of in situ hybridization histochemistry. Immobilization stress induced c-fos and jun B mRNAs in the parvocellular region of the hypothalamic paraventricular nucleus, the anterior and intermediate lobes of pituitary, and in the adrenal gland after 7 min of immobilization, although no c-fos or jun B mRNAs were detected in these and other organs in control rats. The levels of these mRNAs peaked after 30-60 min of immobilization, then declined. A low level of fos B mRNA appeared at 15-30 min and peaked after 60-90 min. On the contrary, c-jun and jun D mRNAs were constitutively expressed in the paraventricular nucleus and adrenal cortex. These findings indicate that the members of the fos and jun family proto-oncogenes play different roles in the transcriptional regulation of genes involved in the hypothalamo-pituitary-adrenal axis, and that monitoring immediate early genes is a useful method for following stress-induced cellular responses in the neuro-endocrine system.

Animals↗
PubMed1994

The expression of neuropeptides and their mRNAs in the trigeminal mesencephalic nucleus following masseteric nerve transection.

By in situ hybridization and immunohistochemistry, we examined the expression of neuropeptides such as neuropeptide Y (NPY), galanin (Gal), substance P (SP), vasoactive intestinal polypeptide (VIP) and their mRNAs in the rat mesencephalic trigeminal nucleus (Mes5) following masseteric nerve transection. On the side contralateral to the nerve transection, none of the peptides examined were labeled in Mes5 cell bodies. However, on the side ipsilateral to the lesion, NPY, Gal and preprotachykinin (PPT) mRNAs appeared in Mes5 cell bodies. Double labeling for mRNAs by in situ hybridization and retrograde tracer fluoro-gold (FG) revealed that almost all (96-97%) the FG-labeled neurons which were cut expressed NPY and Gal mRNAs, whereas less neurons (87%) expressed PPT mRNA. NPY and Gal-like immunoreactivities were detected in Mes5 cell bodies ipsilateral to the axotomy. The results suggested that these neuropeptides play roles in adaptive processes after peripheral nerve injury in Mes5 neurons as they are thought to do so in dorsal root ganglion neurons.

Animals↗
PubMed1993

In vitro studies of determinants of smooth muscle mechanics.

Smooth muscle contraction is dependent upon phosphorylation of the 20,000 Da light chain subunits of myosin. Whereas the kinetics of the hydrolysis of MgATP by smooth muscle myosin suggest a simple phosphorylation-dependent "on-off" mechanism, the contractile response in smooth muscle tissue is complex. Experiments to unravel this complexity have been performed in vitro using a combination of motility assays and kinetic techniques. Some insight into this complexity is obtained, but the mechanism and the regulation of smooth muscle contraction is still not completely known.

Animals↗
PubMed1993

A case of perianal Paget's disease associated with a sigmoid colon carcinoma.

A case of perianal invasive Paget's disease associated with a sigmoid colon carcinoma is presented. The chief complaint was perianal irritation for a year. Histologic examination yielded a correct diagnosis and abdominosacral resection with wide excision of the cutaneous component was performed. Histology of the resected specimen revealed the Paget's disease to be invasive of the dermis, the sigmoid colon carcinoma to be in Dukes' A stage and the two lesions to be different. The patient has been disease-free for more than 5 years after the operation.

Adenocarcinoma↗
PubMed1993

[Evaluation of radionuclide studies in the 8 patients with Takayasu's arteritis].

We evaluated various radionuclide studies performed in the 8 patients with Takayasu's arteritis over the past six years. Radionuclide angiography was performed in 5 patients to investigate the lesions of the branches of the aortic arch, and it demonstrated abnormalities of the affected arteries in 4 patients. Pulmonary perfusion scan demonstrated single or multiple reduced perfusion sites in all the 5 patients examined, while chest radiographies of these patients did not show any abnormalities in the reduced perfusion sites except one case. Renal scintigraphy revealed reduced renal blood flow in 3 patients. In one of those patients, MRI, CT and DSA studies could not detect any stenotic change in the renal artery. Exercise thallium scan revealed myocardial ischemic changes in 2 patients. One of them had angina pectoris, but another patient did not have any complaints. Of the 6 patients who were examined more than one kind of radionuclide studies, five patients showed abnormalities in more than one study. Ambiguous symptoms at the initial stage and rareness of Takayasu's arteritis may delay diagnosis. Radionuclide studies, which can be performed easily and noninvasively to investigate various organs and to depict multiple vascular involvement, seem to be a useful diagnostic tool of this disease.

Adult↗
PubMed1992

[Neo-adjuvant chemotherapy with tegafur suppository for rectal cancer--evaluation of the antitumor effects, tissue levels of 5-FU and inhibition of thymidylate synthase. Tochigi Colorectal Cancer Study Group].

We evaluated antitumor effect histologically and assayed the tissue levels of 5-fluorouracil (5-FU) and thymidylate synthase (TS) activity using surgical specimens obtained from the patients with rectal cancer, who were given tegafur suppositories prior to surgery. The antitumor effect was evaluated histologically according to classification of the general rules for the gastric cancer study (Japanese Research Society for Gastric Cancer). In 39 patients, 16 tumor specimens revealed no effect (grade-0), 22 tumors grade-1 effect, and one was not evaluable because of the severe inflammatory changes. In 23 of these patients, resected specimens were available for the assay. 5-FU levels in cancer tissues were significantly higher than those in normal tissues, and TS inhibition rates (TSIR) were almost identical, averaging around 20%, in both cancer and normal tissues. Comparing the 5-FU levels and TS activity according to the histological effects (i.e.: 'grade-0' vs 'grade-1'), the 5-FU levels in the tumors achieved grade-1 were significantly higher than in the tumors showed 'grade 0' (p less than 0.01), and TSIR in the former were relatively greater than in the latter (p = 0.053). It is suggested that both tissue levels of 5-FU and TSIR may be useful parameters to predict the anti-tumor effect against rectal cancer after administration of 5-FU and its derivatives.

Chemotherapy, Adjuvant↗
PubMed1991

Intra-abdominal desmoid tumors in familial polyposis coli: a case report of tumor regression by prednisolone therapy.

A case of intra-abdominal desmoid tumors in familial polyposis coli (FPC), which regressed and disappeared by prednisolone treatment, is reported. A 37-year-old Japanese man with abdominal lumps was admitted to our hospital. He had had proctocolectomy two years before because of FPC with rectal cancer. At laparotomy, tumors were present in the abdominal wall, mesentery, and retroperitoneum. Only a small part of the tumors was resected and diagnosed microscopically to be desmoid tumors. With prednisolone administration (20 to 5 mg/day) subjective symptoms were ameliorated and desmoid tumors slowly regressed. Bilateral hydronephrosis continued and resulted in "retroperitoneal fibrosis." To our knowledge, this case is the first well-documented case of retroperitoneal fibrosis in a patient with FPC. The characteristics of the desmoid tumor in familial polyposis coli or in Gardner's syndrome and the methods for its management are discussed.

Abdominal Neoplasms↗
PubMed1990

Characterization of in vitro motility assays using smooth muscle and cytoplasmic myosins.

We have used two in vitro motility assays to study the relative movement of actin and myosin from turkey gizzards (smooth muscle) and human platelets. In the Nitella-based in vitro motility assay, myosin-coated polymer beads move over a fixed substratum of actin bundles derived from dissection of the alga, Nitella, whereas in the sliding actin filament assay fluorescently labeled actin filaments slide over myosin molecules adhered to a glass surface. Both assay systems yielded similar relative velocities using smooth muscle myosin and actin under our standard conditions. We have studied the effects of ATP, ionic strength, magnesium, and tropomyosin on the velocity and found that with the exception of the dependence on MgCl2, the two assays gave very similar results. Calcium over a concentration of pCa 8 to 4 had no effect on the velocity of actin filaments. Phosphorylated smooth muscle myosin propelled filaments of smooth muscle and skeletal muscle actin at the same rate. Phosphorylated smooth muscle and cytoplasmic myosin monomers also moved actin filaments, demonstrating that filament formation is not required for movement.

Actins↗
PubMed1989

Effect of multiple phosphorylations of smooth muscle and cytoplasmic myosins on movement in an in vitro motility assay.

The Nitella-based in vitro motility assay developed by Sheetz and Spudich (Sheetz, M.P., and Spudich, J. A. (1983) Nature 303, 31-35) is a quantitative assay for measuring the velocity of myosin-coated beads over an organized substratum of actin. We have used this assay to analyze the effect of phosphorylation of various sites on the 20,000-Da light chain of smooth muscle and cytoplasmic myosins. Phosphorylation by myosin light chain kinase at serine 19 on the 20,000-Da light chain subunit of smooth muscle myosin from turkey gizzard, bovine trachea and aorta, and of cytoplasmic myosin from human platelets was required for bead movement. The individual phosphorylated myosin-coated beads moved at characteristic rates under the same conditions (turkey gizzard myosin, 0.2 micron/s; aorta or trachea myosin, 0.12 micron/s; and platelet myosin, 0.04 micron/s; in contrast, rabbit skeletal muscle myosin, 2 micron/s). Myosin light chain kinase can also phosphorylate threonine 18 in addition to serine 19, and this phosphorylation resulted in an increase in the actin-activated MgATPase activity (Ikebe, M., and Hartshorne, D.J. (1985) J. Biol. Chem. 260, 10027-10031). Phosphorylation at this site had no effect on the velocity of smooth muscle myosin-coated beads. Protein kinase C (Ca2+/phospholipid-dependent enzyme) can also phosphorylate two to three sites on the 20,000-Da light chain, and this phosphorylation alone did not result in the movement of myosin-coated beads. When myosin that had been previously phosphorylated by myosin light chain kinase at serine 19 was also phosphorylated by protein kinase C, myosin-coated beads moved at the same velocity as beads coated with myosin phosphorylated by myosin light chain kinase alone. Tropomyosin binding to actin also had an activating effect on the actin-activated MgATPase activity through an effect on the Vmax and also resulted in an increase in the velocity of myosin-coated beads.

Actins↗