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Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 199 records · Page 11Linked to original sources
PubMed1997

Rapidly progressive interstitial lung disease associated with dermatomyositis responding to intravenous cyclophosphamide pulse therapy.

Interstitial lung disease, especially the rapidly progressive type, carries a grave prognosis when associated with polymyositis (PM)/dermatomyositis (DM). We describe a case of rapidly progressive interstitial lung disease associated with DM. Pathological findings included bronchiolitis obliterans organizing pneumonia (BOOP) pattern in the right upper lung lobe and interstitial fibrosis with microscopic honeycomb lesions in the right lower lung lobe. The patient's respiratory distress was severe and persistent, and oral intubation with mechanical ventilation was transitionally introduced. The respiratory distress condition responded to intravenous cyclophosphamide pulse therapy.

Autoimmune Diseases↗
PubMed1997

SLE and Sjögren's syndrome associated with unilateral moyamoya vessels in cerebral arteries.

Moyamoya disease is a rare clinical entity, diagnosed by cerebral angiography and characterized by occlusion of the internal carotid artery system and the development of collateral arteries. A 30-year-old woman with systemic lupus erythematosus and Sjögren's syndrome recurrently presented transient right homonymous hemianopsia. Cerebral angiography showed occlusion of the left posterior cerebral artery associated with the development of collateral circulation ("moyamoya vessels"). In a young adult, as in this case, the unilaterality of the lesion and the presentation of transient ischemic attacks rather than subarachnoid hemorrhage are rare features for Moyamoya disease. Antiphospholipid syndrome was absent.

Adult↗
PubMed1997

Effect of chronic administration of alcoholic beverages and seasoning containing alcohol on hepatic ethanol metabolism in mice.

Five-week-old male mice, C3H/HeNCrj (C3H/He), were given a 5% (v/v) ethanol solution, commercial alcoholic beverages (Japanese sake (sake) or red wine) or a Japanese seasoning (mirin [containing ethanol and a large amount of glucose]) ad libitum for 45 d, and were then examined for changes in the hepatic enzymes related to ethanol metabolism 2 h after oral administration of 5 g of ethanol/kg body weight. The specific activity of aniline hydroxylase (ANH) in the hepatic microsome increased significantly in all groups chronically administered ethanol solution, sake, red wine or mirin, and the greatest increase was in the hepatic microsome of mirin-administered mice. The cytochrome P-450 (CYP) 2E1 increased in the hepatic microsome of the mice administered ethanol solution, red wine or mirin where accompanied by high ANH activity. The immunoreactive band for CYP1A1 showed high specificity in the microsome of mice given sake, red wine or mirin. It was assumed that CYP1A1 was induced by unknown component(s) other than ethanol in these solutions. In the cytosolic fraction, following the chronic administration of sake and mirin, the total aldehyde dehydrogenase (A1DH) activity with high-Km decreased significantly. In the mitochondrial fraction, the activity of high-Km A1DH increased significantly in the mirin-administered mice which drank a large amount of ethanol, whereas that in the red wine-administered group tended to decrease. These results indicate that the enzyme activities related to the oxidation of both ethanol and acetaldehyde in the cytosolic, mitochondrial and microsomal fractions of the liver were affected by either the action of ethanol or its interaction with other constituents of sake, red wine and mirin.

Alcohol Dehydrogenase↗
PubMed1997

[Thymic cyst resembling a bronchogenic cyst].

Bronchogenic cysts are common cystic lesions in the mediastinum. Most are located in the middle or posterior ares of the mediastinum, especially around the carina. We encountered a patient with a mass in the superior and anterior areas of the mediastinum, where bronchogenic cysts are not usually found. The mass was therefore, thought to be a thymic cyst. The cyst was located just behind the sternum and in front of the left brachio-cephalic vein, and was 5.5 x 3.5 x 1.2 cm. It originated in the upper and median part of the thymus, and was not attached to the respiratory tract. Histological examination showed ciliacted epithelium and a layer of smooth muscle in the wall of the cyst. The cyst contained viscid, yellowish, turbid fluid. Preoperative computed tomography and magnetic resonance imaging showed findings characteristic of bronchogenic cysts, except for the location. We know of no previous reported case of a thymic cyst resembling a bronchogenic cyst.

Bronchogenic Cyst↗
PubMed1997

Transient rise in serum cytokines during coronary artery bypass graft surgery.

In order to examine the specificity of cytokine production during coronary artery bypass graft (CABG) surgery, we serially measured serum levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF), in twenty patients between 52 and 80 years of age, during surgery and 2 days afterwards. Serum MCP-1, as well as IL-8 and IL-6, increased significantly during the surgery (P < 0.05), while IL-1 beta and TNF did not. MCP-1, IL-8 and IL-6 concentrations were not different in the sera of three patients tested at three different sites, i.e., the hepatic vein, pulmonary artery and radial artery. They increased in parallel in each patient, although the actual timing of the increase relative to the surgical step varied among individuals. In complicated patients, MCP-1, IL-8 and IL-6 showed higher peaks and persisted longer than in patients without complications. The universal and simultaneous appearance of MCP-1, IL-8 and IL-6 could indicate that these three cytokines may be stimulated by a yet undiscovered stimulus (or stimuli) which occurs systemically despite the independent pathways of production.

Aged↗
PubMed1997

[A case of schwannoma arising in the brachial plexus with intrathoracic extension].

A case of benign schwannoma originating from the lowest trunk of the left brachial plexus with intrathoracic extension was reported. Intrathoracic growth of a schwannoma of the brachial plexus has been reported in only 3 cases in the literature. The patient was a 53-year-old man and he was first found to have an abnormal shadow at the left lung apex on the chest roentogenogram. We performed a thoracotomy through the left third intercostal space with an axillary skin incision and removed the tumor completely. There was no neurological problem postoperatively

Brachial Plexus↗
PubMed1997

The complement-activating protease P100 is expressed by hepatocytes and is induced by IL-6 in vitro and during the acute phase reaction in vivo.

Ra reactive factor, a lectin present in the sera of a wide variety of vertebrates, is composed of mannan-binding proteins and a serine protease termed P100, which is known to activate complement. Using differential mRNA display technology to study the "activation"-dependent gene expression of hepatic stellate cells (HSC), we partially cloned a cDNA encoding the rat homolog of P100, which displayed 94% and 88% homology to mouse and human P100 cDNA, respectively. In the rat P100, specific transcripts 5.4, 4.0, and 3.3 kb in size were detected in major amounts in normal liver, but were absent or near the detection limit in other organs. Among the different liver cell populations studied during primary culture, P100-specific transcripts of 4.0 kb were prominent in HSC and present in hepatocytes and hepatoma cells, whereas Kupffer cells and sinusoidal endothelial cells were P100-negative. In addition to 4.0-kb mRNA, freshly isolated hepatocytes also contained transcripts of 5.4 and 3.3 kb, which were down-regulated during primary culture. In situ hybridization of normal liver tissue confirmed the in vitro data in that P100 was expressed by hepatocytes and nonparenchymal liver cells, which probably represent HSC. In vitro P100 steady-state mRNA levels of hepatocytes were stimulated by IL-6 and/or dexamethasone. During the acute phase reaction induced by turpentine injection, P100 steady-state mRNA levels were up-regulated in rat liver. The data demonstrate that: (a) the liver is the primary site for P100 expression in the rat; (b) HSC and hepatocytes appear to represent the cellular sources; and (c) P100 steady-state mRNA levels are up-regulated by the acute phase mediators IL-6 and dexamethasone in vitro and during the acute phase reaction in vivo, suggesting that P100 represents a novel, positive acute-phase gene in the rat.

Acute-Phase Reaction↗
PubMed1997

[Flutropium bromide was effective in relieving symptoms of lymphangioleiomyomatosis--a case report].

A 32-year-old woman was admitted with persistent dyspnea. Chest roentgenogram showed hyperinflation of the lungs, and diffuse reticular shadows in both lung fields. Chest CT showed diffuse cystic lesions and thickened vasculature. Examinations revealed severe hypoxemia, restrictive and obstructive ventilatory impairments, increased residual volume, and decreased carbon monoxide diffusing capacity. Lymphagioleiomyomatosis was strongly suspected, and a diagnosis confirmed histopathologically by lung biopsies. Inhalation of flutropium bromide was remarkably effective in relieving dyspnea and impaired pulmonary functions. It is suggested that flutropium bromide is beneficial for symptomatic improvement in patients with lymphangioleiomyomatosis.

Administration, Inhalation↗
PubMed1997

Mitochondrial methionyl-tRNA transformylase from bovine liver.

Substrate specificities of mammalian mitochondrial methionyl-tRNA transformylase (MTFmt) toward tRNA substrates were characterized in vitro. The MTFmt is able to formylate E. coli initiator methionyl-tRNA (Met-tRNA(fMet)) as efficiently as mammalian mitochondrial methionyl-tRNA. Furthermore, E. coli elongator methionyl-tRNA (Met-tRNA(mMet)) also serves as a substrate for mt MTF, whereas E. coli MTF rigorously excludes E. coli Met-tRNA(mMet) from formylation reaction. Thus, mammal mt MTF is suggested to have recognition mechanism different from E. coli MTF. To pursue the relationship between protein structure and unexpected substrate specificity of mammalian MTFmt, the nucleotide sequence of MTFmt gene was determined and its amino acids sequence was compared to other MTFs of prokaryotic origin.

Animals↗
PubMed1996

Thromboxane A2 receptor blockade suppresses intercellular adhesion molecule-1 expression by stimulated vascular endothelial cells.

Inhibition of the thromboxane A2-synthesizing enzyme (DP-1904: [+/-]-6-[1-imidazolylmethyl]-5,6,7,8-tetrahydronaphthalene-2-carbo xylic acid hydrochloride hemihydrate) reportedly suppresses intercellular adhesion molecule-1 (ICAM-1) expression on the surface of stimulated vascular endothelial cells (Ishizuka et al., 1994, Eur. J. Pharmacol 262, 113). In the present study, thromboxane A2 receptor antagonists suppressed the expression of ICAM-1 on the surface of human vascular endothelial cells that were stimulated by tumor necrosis factor alpha (TNF alpha), platelet activating factor (PAF), or U46619 (9,11-dideoxy-9 alpha, 11 alpha-epoxymethanoprostaglandin F2 alpha). Augmentation of ICAM-1 expression on human vascular endothelial cells stimulated by U46619 was suppressed by protein kinase C inhibitors. Thromboxane A2 receptor antagonist suppressed U46619 stimulation of protein kinase C activity of a cell membrane fraction. These results indicate that in human vascular endothelial cells, thromboxane A2, the production and secretion of which is stimulated by TNF alpha or PAF, binds to the thromboxane A2 receptors on cell membranes and augments ICAM-1 expression on the cell surfaces mainly through protein kinase C.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Pathomechanism of pain-related behavior produced by allografts of intervertebral disc in the rat.

STUDY DESIGN: This study was designed to evaluate whether allografts of intervertebral disc materials produce hyperalgesia in the rat and whether an immune response, pH, or chemicals correlate with the induced hyperalgesia. OBJECTIVE: To elucidate the pathomechanisms of radicular pain secondary to lumbar disc herniation. SUMMARY OF BACKGROUND DATA: It has been reported that a low pH, an autoimmune reaction, or chemical radiculitis is likely responsible for radicular pain associated with lumbar disc herniation. In animal studies, it has been shown that hyperalgesia (an increased sensitivity to painful stimuli) involves activation of phospholipase A2 and nitric oxide synthase. METHODS: Fat, nucleus pulposus, and anulus fibrosus were allografted into the epidural space at L6 in the rat. Withdrawal response thresholds to mechanical stimuli and withdrawal response latencies to thermal stimuli on the tail and pH in the applied tissues were measured after surgery. Interleukin-1, phospholipase A2, and nitric oxide synthase were examined in the applied tissues using immunohistochemistry, nicotineamide adenine dinucleotide phosphate-diaphorase histochemistry, and in situ hybridization. RESULTS: Allografted fat did not produce hyperalgesia. Allografts of nucleus pulposus and nucleus pulposus plus anulus fibrosis showed evidence of mechanical and thermal hyperalgesia, respectively. There were no observed changes in pH over time. Although interleukin-1 was demonstrated in all applied tissues, phospholipase A2 was only observed around the applied nucleus A2 was only observed around the applied nucleus pulposus and nucleus pulposus plus anulus fibrosus. Nitric oxide synthase was only markedly increased around the applied tissues. CONCLUSION: The nucleus pulposus and anulus fibrosus produce different forms of hyperalgesia (mechanical vs. thermal) associated with different and distinct immunohistochemical changes. It is possible that radicular pain of a lumbar disc herniation results from chemicals, such as phospholipase A2 and nitric oxide.

Adipose Tissue↗
PubMed1996

A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation.

By targeting the ATP binding conserved domain in three ATP binding cassette superfamily proteins (P-glycoprotein, multidrug resistance protein, and cystic fibrosis transmembrane regulator), we isolated the cDNA of a new ATP binding cassette superfamily that was specifically enhanced in a cisplatin-resistant human head and neck cancer KB cell line. A human clone homologous to rat canalicular multispecific organic anion transporter (cMOAT) was found and designated human cMOAT. Fluorescence in situ hybridization demonstrated the chromosomal locus of the gene on chromosome 10q24. The human cMOAT cDNA hybridized a 6.5-kb mRNA that was expressed 4- to 6-fold higher by three cisplatin-resistant cell lines derived from various human tumors exhibiting decreased drug accumulation. Human cMOAT may function as a cellular cisplatin transporter.

Adenosine Triphosphate↗
PubMed1996

MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies based on selective mitochondrial accumulation.

MKT-077 (formerly known as FJ-776) is a newly synthesized, highly water-soluble ( > 200 mg/ml) rhodacyanine dye that exhibits significant antitumor activity in a variety of model systems. In culture, MKT-077 inhibits the growth of five human cancer cell lines (colon carcinoma CX-1, breast carcinoma MCF-7, pancreatic carcinoma (CRL 1420, bladder transitional cell carcinoma EJ, and melanoma LOX) but not monkey kidney CV-1, an indicator cell line for normal epithelial cells. In nude mice, MKT-077 inhibits the growth of s.c. implanted human renal carcinoma A498 and human prostate carcinoma DU145 and prolongs the survival of mice bearing i.p. implanted human melanoma LOX (tumor:control = 344%). Subcellular localization indicates that MKT-077 is taken up and retained by mitochondria, and flow cytometric analysis suggests that CX-1 cells take up MKT-077 to a much greater extent than CV-1 cells. Quantitation of MKT-077 uptake by ethanol extraction shows that CX-1 cells accumulate 65-fold more MKT-077 than do CV-1 cells. MKT-077 is the first delocalized lipophilic cation with a favorable pharmacological and toxicological profile in preclinical studies. MKT-077 is now being investigated in Phase I clinical trials.

Animals↗
PubMed1996

Anti-DNA antibody kinetics following selective removal by adsorption using dextran sulphate cellulose columns in patients with systemic lupus erythematosus.

The aim of this study is to determine by mathematical analysis which of two models, the one- or the two-compartment model, more closely approximates the kinetics of anti-dsDNA following immunoadsorption procedures in patients with systemic lupus erythematosus. Titers of anti-dsDNA were measured at specified intervals after apheresis to each model by nonlinear least-squares methods, and Akaike's Information Criterion (AIC) was calculated to determine which model most approximately described the kinetics. The AIC of the two-compartment model was larger than that of the one-compartment model in all 14 SLE patients (P < .001). Therefore, the one-compartment model is thought to be suitable. The generation rate and catabolic rate of anti-dsDNA were obtainable using this model. The anti-dsDNA replenishment curve after an immunoadsorption session was defined by only two parameters: the generation and catabolic rates of anti-dsDNA.

Adolescent↗
PubMed1996

High-avidity anti-DNA antibody removal from the serum of systemic lupus erythematosus patients by adsorption using dextran sulfate cellulose columns.

The purpose of this study is to determine whether immunoadsorption treatment using a dextran sulfate (DS) column can remove high-avidity anti-double-stranded DNA (anti-dsDNA) antibody from the blood of patients with systemic lupus erythematosus (SLE). Before and after each immunoadsorption therapy routine, titers of the high-avidity anti-dsDNA antibody of 11 SLE patients were measured by using a newly developed assay kit to exclusively detect high avidity anti-DNA antibody. Patients with active SLE showed significantly higher titers of high-avidity antibody than did those with inactive SLE, and their titers were significantly reduced by immunoadsorption procedures. Removal of high-avidity antibodies in vitro was also confirmed by mixing patients' sera and DS gel. Immunoadsorption therapy using DS columns is effective in the removal of high-avidity anti-dsDNA antibodies that are closely associated with pathogenicity in SLE.

Adult↗
PubMed1996

Anti-dsDNA antibody kinetics during in vivo apheresis in systemic lupus erythematosus patients and in an in vitro apheresis model.

Levels of anti-dsDNA measured just after an immunoadsorption procedure in systemic lupus erythematosus (SLE) patients are sometimes paradoxically larger than those measured just before the procedure. A 1:100 in vitro single-compartment immunoadsorption system model was devised to determine which of two models, one- or two-compartment, more closely approximates the kinetics of anti-dsDNA during apheresis procedures. Ten SLE patients were employed in this study. A total of 4,100 ml of plasma was passed through the dextran sulfate cellulose columns during one clinical apheresis session. In eight of ten patients, the log of RIA-measured anti-dsDNA titers decreased linearly as treated plasma volume increased, in both the clinical procedure and the experimental model. The mean adsorption efficacy in the clinical apheresis procedure and in the in vitro model was 0.37 and 0.27, respectively. However, in one patient the RIA-measured level of anti-dsDNA increased during the apheresis procedure; this phenomenon was mirrored in the model (definitely a single pool model). In contrast, the level of anti-dsDNA, as measured by ELISA, decreased in accordance with the increase of treated plasma volume in both the clinical and the in vitro apheresis procedures. Therefore, an increased titer of anti-dsDNA as measured by RIA immediately following clinical apheresis cannot be accounted for exclusively by an inflow of antibodies from a secondary (extravascular) pool into the circulating plasma. In short, a one-compartment model is applicable and an explanation must be sought elsewhere.

Adult↗
PubMed1996

Clinicopathologic features associated with long-term survival in node-negative breast cancer patients.

This study was undertaken to assess blood vessel invasion (BVI) and other histologic features to determine the best method of histologic prognosis in node-negative breast cancer patients. The prognostic significance of the clinico-pathological findings was evaluated in 70 patients with node-negative breast cancer among 135 patients operated on between 1971 and 1981. The prognostic factors investigated included BVI, peritumor lymphatic invasion, clinical tumor size, nuclear grade, histological grade, mitotic grade, and tumor necrosis. BVI was detected by factor VIII-related antigen and elastica van Gieson staining. BVI-negative patients had a 20-year cumulative survival of 93.7%, versus 74.7% for BVI-positive patients (P = 0.0294). The clinical tumor size also correlated well with prognosis (P < 0.001). However, the other histologic features did not correlate with a poor prognosis. Moreover, we retrospectively examined the effect of postoperative chemotherapy for patients with BVI and T3, and the prognosis of those given chemotherapy seemed to be better than that of those who were not. Tumors measuring more than 51 mm and BVI may thus represent adverse prognostic factors in node-negative breast cancer patients.

Adult↗