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Y Shimokawa

Publications and source records attributed to Y Shimokawa.

At least 19 recordsLinked to original sources
PubMed2001

Serotonin-induced hypercontraction through 5-hydroxytryptamine 1B receptors in atherosclerotic rabbit coronary arteries.

BACKGROUND: Augmented vasoconstriction to serotonin (5-hydroxytryptamine [5-HT]) in atherosclerotic vessels plays a crucial role in the development of myocardial ischemia. We investigated mechanisms for serotonin-evoked hypercontraction in atherosclerotic rabbit coronary arteries. METHODS AND RESULTS: Contractile responses to serotonergic agents of endothelium-denuded coronary arteries from control and Watanabe heritable hyperlipidemic rabbits (WHHL) were examined. WHHL coronary arteries exhibited hypercontraction to 5-HT(1)-receptor agonists; the constrictor threshold concentrations and E:D(50) to serotonin, 5-carboxamidotryptamine, and sumatriptan in WHHL were significantly lower, and the E:(max) in WHHL to these agents were increased 55% to 59% above those of the control. Serotonin-evoked contractions in both groups were inhibited by GR127935 (5-HT(1B/1D) antagonist; 0.1 to 1 nmol/L) and pertussis toxin but not by ketanserin (5-HT(2) antagonist; 0.01 to 1 micromol/L), suggesting that the hypercontraction is most likely mediated by 5-HT(1B/1D) receptors through a pertussis toxin-sensitive pathway. Furthermore, simultaneous measurements of [Ca(2+)](i) and isometric tension of fura-2-loaded arteries revealed that the hypercontraction was concomitant with the augmented elevation of [Ca(2+)](i) in the smooth muscle. The 5-HT(1B) mRNA levels in WHHL coronary arteries increased to 2.5-fold over those in control arteries, whereas neither 5-HT(1D) nor 5-HT(2A) mRNA was detected in either group. CONCLUSIONS: Atherosclerotic rabbit coronary arteries exhibited the enhancement in contraction and Ca(2+) mobilization in response to serotonin. The 5-HT(1B) receptor, which is upregulated by atherosclerosis, most likely mediates the augmenting effects of serotonin.

Animals↗
PubMed2001

Signaling mechanism underlying COX-2 induction by lysophosphatidylcholine.

Lysophosphatidylcholine, a component of oxidized low density lipoprotein, is critical for pathological conditions including atherosclerosis. However, the signaling mechanism of lysophosphatidylcholine remains poorly understood. Here we reported that lysophosphatidylcholine induces phosphorylation of p38 and the transcription factors, CREB and ATF-1 with concomitant up-regulation of cyclooxygenase-2 expression in cultured vascular endothelial cells. Lysophosphatidylcholine induced p38 phosphorylation in a time- and concentration-dependent manner partly via pathway depending on protein tyrosine kinase. Both lysophosphatidylcholine-stimulated phosphorylation of CREB and ATF-1 and lysophosphatidylcholine-increased expression of cyclooxygenase-2 mRNA and protein were effectively inhibited by a combination of SB203580 and PD98059, specific inhibitors of p38 and MEK1, respectively, as well as Ro31-8220 and H89, potent inhibitors of MSK1. These results suggest that both p38 and ERK may function as upstream signaling pathways capable of activating CREB and ATF-1 with subsequent induction of cyclooxygenase-2 expression by lysophosphatidylcholine.

Activating Transcription Factor 1↗
PubMed2001

Functional fragments of ingested lactoferrin are resistant to proteolytic degradation in the gastrointestinal tract of adult rats.

Pharmaceutical and food-related applications of lactoferrin, an 80-kDa iron-binding glycoprotein found predominantly in milk, have attracted interest lately, but the process of digestion of lactoferrin has been poorly characterized. The digestive fate of bovine lactoferrin in adult rats after oral administration of a single dose and after dietary supplementation was studied by (125)I-labeling and by surface-enhanced laser desorption/ionization (SELDI) affinity mass spectrometry. The latter method was designed to detect multiple forms of degraded lactoferrin as simple molecular ion peaks corresponding to one of the core regions of lactoferrin, namely, the lactoferricin region (Phe17-Ala42). Radioactive fragments with molecular masses of 42, 36, 33 and 29 kDa were observed at 20, 60 and 180 min postingestion in the contents of the lower small intestine. Rats were given free access to milk enriched with lactoferrin at 482 micromol/L (40 mg/mL). The concentrations of lactoferrin fragments in the contents of the stomach, small intestine and lower small intestine as determined by SELDI affinity mass spectrometry were approximately 200, 20 and 1 micromol/L, respectively. These data indicate that functional fragments of LF such as fragments containing glycosaminoglycan-binding site(s), as well as large fragments with a mass >20 kDa, indeed survive proteolytic degradation in the small intestine of adult rats.

Administration, Oral↗
PubMed2001

New biological function of bovine alpha-lactalbumin: protective effect against ethanol- and stress-induced gastric mucosal injury in rats.

Although several studies have shown that milk protein components have a wide range of biological activities, the potential role of these proteins in the gastrointestinal mucosal defense system is less well elucidated. In this study, we investigated the effect of the major proteins in cow's milk on gastric mucosal injury by using two acute ulcer models in Wistar rats. Gastric mucosal injury was induced by either intragastric 60% ethanol-HCl or water-immersion restraint stress (23 degrees C, 7 h). Each test milk protein was orally administered 30 min before the induction of gastric injury. Among the major milk proteins, alpha-lactalbumin (alpha-LA) is demonstrated to have a marked protective effect against ethanol-induced gastric injury, with the same potency as that of the typical antiulcer agent, Selbex. Whey protein isolate (WPI), which contained 25% alpha-LA, also protected against gastric injury, while casein showed no effect. Comparative studies on the protective effect of the four major components of WPI, beta-lactoglobulin, alpha-LA, bovine serum albumin and gamma-globulins (immunoglobulins), on the basis of their contents in WPI revealed that alpha-LA was responsible for the protective effect of WPI, being about 4-fold more effective than WPI itself. Alpha-LA showed dose-dependent protection against gastric injury induced by stress as well as ethanol. Pretreatment with indomethacin (10 mg/kg body weight, s.c.), which is a potent inhibitor of endogenous prostaglandin synthesis, resulted in a significant reduction in the protective effect of alpha-LA. These results indicate that alpha-LA has marked antiulcer activity as an active component of cow's milk protein, and suggest that alpha-LA intake may serve to protect against gastric mucosal injury, in part through endogenous prostaglandin synthesis.

Animals↗
PubMed2001

[A case of a left atrial primary malignant fibrous histiocytoma].

Primary malignant fibrous histiocytoma (MFH) of the heart is very rere. We report a case of a primary intracardiac MFH. A 50-year-old woman underwent an operation for congestive heart failure due to left atrial (LA) tumor. Cardiac echocardiogram showed the tumor attached to the septal wall and posterior wall of LA. We extendedly resected the tumor with septal and partially posterior wall and reconstructed there with pericardial substitute. Pathological diagnosis was MFH. Although she did well postoperatively, cardiac echocardiogram showed a recurrent tumor in the LA at 10 days after operation. She developed respiratory failure, and chest and abdominal CT demonstrated metabolism to the lung, liver and bladder at post operative 47 days. At 77 days after operation, she expired. The prognosis of MFH is poor despite surgery. We recommend extended surgery, if the LA tumor had wide base attached to the septal or posterior wall.

Echocardiography↗
PubMed2000

[Two cases of hypoxemic acute bronchiolitis due to Mycoplasma pneumoniae].

Two males with acute bronchiolitis due to Mycoplasma (M.) pneumoniae, aged 24 and 39 years were reported. They presented prolonged cough and fever in the early stage of the disease. Chest X-rays of those patients showed diffused nodular shadows. Chest CT scan showed diffused nodular shadows and thickning of bronchovascular marking. Blood-gas analysis indicated hypoxemia without abnormal A-aDO2. We diagnosed two patients as M. pneumoniae infection by antibody assays. The Eosinophil cationic protein (ECP) level and IgE level were high. Eosinophilia and endotoxemia were also observed in two patients. We speculated that the allergic reaction and endotoxemia may be related to hypoxemia and the clinical severity of M. pneumoniae infection.

Acute Disease↗
PubMed2000

[Autoimmune thrombocytopenia and erythroid hypoplasia associated with hepatitis A].

A 53-year-old woman developed fever and fatigue after eating raw oysters, and consulted a local clinic. She exhibited liver dysfunction and jaundice, and was therefore referred and admitted to our hospital. Hepatitis A was diagnosed based on virus markers, and palliative therapy was administered. After admission, the increased levels of transaminases and lactic acid dehydrogenase (LDH) normalized rapidly. However, marked thrombocytopenia was observed, and steroid pulse therapy was administered. Thereafter, idiopathic anemia developed, and a bone marrow puncture was performed. Bone marrow smears showed marked depletion of cells of the erythroblastic and megakaryocytic series. Parvovirus B19 infection was ruled out, and an additional steroid was administered. However, the patient's anemia and thrombocytopenia persisted. She suffered a prolonged period of cholestasis and died of acute renal failure. At autopsy, the bone marrow revealed severe erythroblastopenia. A diagnosis of thrombocytopenia due to an autoimmune mechanism was made on the basis of elevated levels of platelet-associated immunoglobulin G (PAIgG) and immune complex. Furthermore, the advanced anemia was complicated by concurrent hemolysis. This case may provide information useful for clarifying the pathogenesis of hematopoietic disorders complicated by hepatitis.

Female↗
PubMed1999

[Two cases of suspected Bartonella henselae infection from a dog].

A 55-year-old male was admitted to our hospital because of fever and left submaxillary, right axillary, and left inguinal lymphadenopathy. A presumptive diagnosis of rickettsiosis was made and treatment with oral doxycycline was started. Lymphadenopathy was partialy resolved after antibiotics treatment. Ablation of the left inguinal node was done and histopathological examination showed non-Hodgkin's lymphoma. Lymphadenopathy was resolved by chemotherapy. The second patient, a 40-year-old male, developed a tender submandibular node. Excisional biopsy of the node was performed to eliminate lymphoma. Histopathological examination revealed granulomatous lymphadenitis with follicular hyperplasia. The patients had no history of cat contact, but owned a dog. Diagnosis of both cases was confirmed by the detection of IgG antibodies to Bartonella henselae with an enzyme immunoassay. Our findings suggest that dogs are implicated in B. henselae infection and can serve as a reservoir of the organism as well as cats. In the abscence of other bacterial and especially after exposure to dogs, B. henselae should be included as possible cause of lymphadenopathy.

Adult↗
PubMed1999

[Lactoferrin].

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Adult↗
PubMed1997

Structures of the sugar chains of recombinant macrophage colony-stimulating factor produced in Chinese hamster ovary cells.

The structures of the N- and O-linked sugar chains of recombinant human macrophage colony-stimulating factor (rhM-CSF) from Chinese hamster ovary (CHO) cells were studied. rhM-CSF is a homodimeric glycoprotein. Sugar composition analysis revealed that rhM-CSF contained 4.1 mol N-acetylgalactosamine, 10.3 mol N-acetylglucosamine, 5.0 mol mannose, 10.0 mol galactose, 1.4 mol fucose, and 11.8 mol sialic acid per mol of the monomer. The N- and O-linked sugar chains liberated by hydrazinolysis were N-acetylated, and the reducing-end sugar residues were tagged with 2-aminopyridine. The pyridylamino (PA-) sugar chains thus obtained were purified by HPLC. The structures of the PA-sugar chains were analyzed by a combination of reversed-phase and size-fractionation HPLC, and exoglycosidase digestions, from which the structures of the rhM-CSF sugar chains were estimated to be as follows: monosialo biantennary sugar chain (9 mol%), monosialo fucosylbiantennary sugar chain (10 mol%), disialo biantennary sugar chain (30 mol%), disialo fucosylbiantennary sugar chain (28 mol%), disialo triantennary sugar chain (7 mol%), trisialo triantennary sugar chain (11 mol%), and trisialo fucosyltriantennary sugar chain (5 mol%) for the N-linked sugar chains, and asialo (27 mol%), monosialo (51 mol%), and disialo (22 mol%) Galbeta1-3GalNAc for the O-linked sugar chains. Sialic acid residues were linked to the N-linked sugar chains through an alpha2-3 linkage.

Animals↗
PubMed1997

[CABG performed for LMT orifice stenosis 15 years after AVR in a case of aortitis syndrome].

The case is a 54-year-old female at age 39 years, she underwent aortic valve replacement (AVR) for aortic valve regurgitation (AR) due to aortitis syndrome at a certain hospital. At the 15th year after AVR she was diagnosed with unstable angina due to LMT orifice stenosis and underwent CABG at this hospital. A distal side of anastomosis was performed on the LAD branch seg 6, an artificial vascular patch was placed for the proximal side of anastomosis to prevent inflammation of the aortic wall from spreading to the proximal side of anastomosis. On the postoperative cardiac catheter examination, the graft was found to be patent well. In the case of CABG complicated with aortitis syndrome, stenosis and obstruction of the proximal side of anastomosis long time after surgery pose a problem. However, the method so as to perform a proximal anastomosis by placing an artificial vascular patch on the aortic wall is considered to be one of the useful means which can avoid such a problem.

Angina, Unstable↗
PubMed1996

Serological study of Bartonella henselae in cat scratch disease in Japan.

It has become clear that Bartonella henselae is a common cause of cat scratch disease (CSD). The indirect fluorescence antibody (IFA) test for detection of IgG and IgM antibodies to B. henselae concerning CSD showed that 5 (50%) of 10 patients with CSD had a serum IgG antibody titer of 1:128 or more and that 2 (20%) patients had a serum IgM antibody titer of 1:20 or more. One of 7 asymptomatic members of patients' families (14%) had IgG antibody to B. henselae at a titer of 1:256. IgM antibody to B. henselae was not detected in sera from the patients' families. Both IgG and IgM antibodies to B. henselae were not detected in sera from the healthy control group. These data suggest that B. henselae may be a cause of CSD in Japan.

Adult↗
PubMed1995

Analysis of antitumor properties of effector cells stimulated with a cell wall preparation (WPG) of Bifidobacterium infantis.

Intestinal Bifidobacterium species are thought to be beneficial in animal and human intestines. We studied the mechanisms of Bifidobacteria in antitumor activity using a cell wall preparation (WPG) of B. infantis (Cancer Res., 45, 1300, (1985)). WPG enhanced the in vitro antitumor activities of mouse peritoneal exudate cells elicited with proteose-peptone (P-PEC) and thioglycollate broth (TG-PEC), determined by cytostatic ([3H]thymidine uptake inhibition) and cytolytic ([3H]uridine release) assays. Tumor necrosis factor-alpha (TNF-alpha) and reactive nitrogen intermediates (RNI) play a role in such augmented cytotoxicity, because anti-TNF-alpha antibody almost completely blocked the increased cytolytic activity of P-PEC in the presence of WPG. Moreover, WPG induced RNI in the supernatant of TG-PEC in a dose-dependent manner. The mRNA expression of several cytokines (IL-1 beta, IL-6, IL-10, IFN-alpha and TNF-alpha) was induced in BALB/c mouse peritoneal cells 3 h after an intraperitoneal injection of WPG (3 h WPG-PEC). However, this expression disappeared from 24 h WPG-PEC, except for that of IFN-alpha. IFN-gamma was not induced. Kinetic studies of the tumor neutralizing activities of the WPG-PECs by means of the in vivo Winn assay revealed that the activity emerged at 1.5 h, became maximal at 3 h and disappeared at 24h. These results indicated that Bifidobacterial WPG is a Biological Response Modifier (BRM) with characteristics similar to those of other bacterial BRMs.

Animals↗
PubMed1994

[Two cases of advanced breast cancer effectively treated with chemoendocrine therapy and radiotherapy].

We reported 2 cases of breast cancer with lymph node metastasis treated with CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and medroxyprogesterone acetate (MPA). Case 1 was stage IV [T4b, N3 M1 (lung)] and case 2 was stage IIIa (T1, N2, M0). The two cases responded well to CAF and MPA therapy in local and systemic lesions, and then underwent radiotherapy and lymph node resection without mastectomy. After these treatments, both cases were thought to be disease-free. Major side effects were allopecia, obesity, and leukopenia. These results suggest that combination chemoendotherapy, radiotherapy, and surgery can be utilized for most patients with moderately advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A new monoclonal antibody, PM-2K, specifically recognizes tissue macrophages but not blood monocytes.

A new monoclonal antibody, PM-2K, was raised against 24-h cultured human peritoneal macrophages. Immunohistochemically, PM-2K recognized most tissue macrophages in lymphoreticular organs such as the thymus, spleen, lymph node, and tonsil. Kupffer cells of the liver, alveolar macrophages, and macrophages in the interstitial tissue of the kidney, pancreas, and many other organs were also positively labelled. On the other hand, PM-2K failed to recognize blood monocytes, freshly isolated peritoneal macrophages, microglial cells, osteoclasts, and dendritic cells such as Langerhans cells, interdigitating cells, and follicular dendritic cells. In various pathological conditions, PM-2K labelled a wide variety of proliferating macrophages. Reaction products of PM-2K were observed by immunoelectron microscopy on the cytoplasmic membrane of cultured peritoneal macrophages. The molecular weight of the antigen recognized by PM-2K was determined to be 150 kD by Western blotting. As no cells other than macrophages were reactive with PM-2K, this antibody is considered to be very useful not only in the investigation of macrophage differentiation and maturation, but also in the diagnosis of various proliferative disorders of macrophages.

Animals↗
PubMed1991

Hepatocellular carcinoma presenting with pyrexia and leukocytosis: report of five cases.

In the past 26 years we have encountered five patients with primary liver malignancy clinically characterized by high remittent fever and leukocytosis mimicking liver abscess. Two patients underwent exploratory laparotomy, and drainage was carried out in another. The clinical courses went rapidly downhill. The liver was cirrhotic in two patients. The interior of the main mass was almost totally necrotic in four cases. Histologically, the malignant cells in the main portion resembled sarcoma, but in some areas cells appeared epithelial with eosinophilic cytoplasm and were in a trabecular arrangement, except for one case not subjected to autopsy in which histological study was inadequate because of extensive necrosis. It seems that these neoplasms were very poorly differentiated hepatocellular carcinomas rather than combinations of sarcoma and hepatocellular carcinoma. These patients, therefore, may represent a distinct clinicopathological type of hepatocellular carcinoma that is very rare in Japan but perhaps more common in South Africa, where similar cases have been clinically described in larger numbers.

Adult↗
PubMed1990

Influence of captopril on urinary excretion of furosemide in hypertensive subjects.

Influence of captopril on urinary excretion of furosemide was examined in a placebo-controlled, crossover design. Furosemide (20 mg) was injected intravenously in eight hypertensive subjects with pretreatment with captopril (25 mg) or matching placebo. Urine samples for furosemide and sodium were collected during the following intervals: -60-0, 0-60, 60-120, and 120-180 minutes after furosemide. Blood samples for plasma renin activity (PRA) and angiotensin II (AII) were obtained, and blood pressure was measured at -60, 0, 60, 120, and 180 minutes after furosemide. No significant difference was observed in urinary excretion of furosemide, volume or sodium between these trials. Although PRA increased following furosemide with captopril, as predicted plasma AII did not increase. Blood pressure significantly decreased following the combined therapy, but not furosemide alone. These data indicate that the urinary excretion of furosemide and its subsequent diuretic effects are not influenced by captopril.

Adult↗