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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 505 records · Page 28Linked to original sources
PubMed1997

Metabolism of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, by intestinal microorganisms.

PURPOSE: We evaluated the effect of luminal bacterial metabolism on intestinal absorption of azetirelin in rats. In vitro characteristics of bacterial metabolism of azetirelin were also investigated with the goal of overcoming the low stability of the peptidic drug against luminal microorganisms. METHODS: Plasma azetirelin levels after oral administration to antibiotic-pretreated rats was examined. In vitro incubation experiments with bacterial suspensions were also performed to clarify the location of azetirelin breakdown activity as well as the effects of oxygen, pH, and various protease inhibitors on drug metabolism. RESULTS: Plasma azetirelin levels were sustained after oral administration to antibiotic-treated rats. Incubation with rat luminal contents demonstrated that azetirelin was metabolized by anacrobic bacteria, which are predominant in the distal intestine. Fecal suspensions from rats, dogs, and humans showed comparable metabolic activity. Azetirelin breakdown in the bacterial suspension was pH-dependent and was inhibited in the presence of bacitracin or puromycin. CONCLUSIONS: Bacterial metabolism influences the degree of absorption of azetirelin in the distal intestine. Control of the luminal pH environment may be a practical method for improving the stability of azetirelin against intestinal microorganisms.

Animals↗
PubMed1997

Interstitial pneumonia in patients receiving granulocyte colony-stimulating factor during chemotherapy: survey in Japan 1991-96.

Twenty cases of interstitial pneumonia secondary to treatment with granulocyte colony-stimulating factor (G-CSF) were reviewed. Their interstitial pneumonia had the following features: (a) it occurred predominantly in patients aged 60 years or older; (b) it was prevalent among patients with haematological malignancies, particularly non-Hodgkin's lymphoma; (c) in all patients G-CSF was given after anti-cancer agents with potential to affect the lungs; (d) at the onset, many patients had symptoms such as dyspnoea and fever; and (e) the leucocyte (neutrophil) count as well as lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels were usually higher than normal at the onset. These findings indicate that, when G-CSF is used in combination with pneumotoxic anti-cancer agents, respiratory function should be monitored before and during treatment. If the leucocyte (or neutrophil) count and/or LDH and CRP increase suddenly in association with dyspnoea and fever during administration of G-CSF, interstitial pneumonia should be suspected. Accordingly, a chest radiograph and pulmonary functional tests should be performed promptly. If a diagnosis of interstitial pneumonia is made, steroid pulse therapy should be commenced immediately.

Adult↗
PubMed1997

Malignant histiocytosis-like B-cell lymphoma, a distinct pathologic variant of intravascular lymphomatosis: a report of five cases and review of the literature.

Malignant histiocytosis (MH)-like B-cell lymphoma (BCL) is a neoplastic proliferation of large B cells clinically characterized by fever, hepatosplenomegaly, haemophagocytosis and abnormal laboratory data, without lymphadenopathy or skin lesions. Interestingly, most cases have been reported in Asian patients, and it is unclear whether MH-like BCL is biologically distinct from conventional large B-cell lymphomas. We report five Japanese patients with MH-like BCL. Biopsied specimens of bone marrow, liver and/or spleen showed infiltration of neoplastic B cells accompanied by haemophagocytosing histiocytes. Lymphoma cells were positive for CD19, CD20 and HLA-DR surface antigens, and negative for CD5 and CD10. In four cases elevated serum levels of interleukin (IL)-6 and the soluble IL-2 receptor isoform were noted, but not IL-1beta, IL-2 or tumour necrosis factor-alpha. Autopsies of two cases were pathologically diagnosed as intravascular lymphomatosis (IVL). Based on these observations, the current and nine previous cases reported as MH-like BCL in Japan were re-evaluated. They appear to form a peculiar variant of IVL, characterized by bone marrow involvement at presentation, haemophagocytic syndrome, and a rapidly aggressive clinical course, but rarely neurological complications or skin lesions. This variant may merit separate consideration because of the problems posed in the initial diagnosis and therapeutic approaches.

Aged↗
PubMed1997

Decreased pulmonary perfusion in hypersensitivity pneumonitis caused by Shiitake mushroom spores.

Hypersensitivity pneumonitis is an occupational hazard of mushroom workers. We describe a patient with severe hypersensitivity pneumonitis caused by spores of the Shiitake mushroom (Lentinus edodes) who showed a marked decrease in pulmonary perfusion, as demonstrated by pulmonary scintigraphy. This patient was treated successfully with prednisolone. These results suggest that pulmonary vasculitis may be associated with patients with hypersensitivity pneumonitis, and that steroid therapy may be clinically useful in treatment.

Alveolitis, Extrinsic Allergic↗
PubMed1997

Preferential localization of human CD5+ B cells in the peritoneal cavity.

In a transgenic mouse model of autoimmune haemolytic anaemia, CD5+ B lymphocytes localized in the peritoneal cavity are shown to play an important role in the onset of autoimmune disease. The authors have examined whether CD5+ B cells are present in the peritoneal cavity of 12 human individuals with non-invasive gastrointestinal tumours and found that in humans CD5+ B cells preferentially lodge in the peritoneal cavity as compared to the peripheral blood and spleen while the numbers of the peritoneal B lymphocytes in humans are much lower than in mice and vary widely between individuals.

Animals↗
PubMed1997

Limb allografts in rats treated with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies.

This study examined whether administration of anti-ICAM-1 mAb (monoclonal antibody) and anti-LFA-1 mAb were effective for inhibition of the acute rejection reaction in a rat-limb allograft model. The grafts were carried out using major histocompatibility complex mismatch pairs of rats: ACI rats as the donors and Lewis rats as the recipients. The subjects were of species with completely different major histocompatibility complexes. The average length of survival in this combination was 4.7 +/- 0.6 days. When anti-ICAM-1, anti-LFA-1 mAb, or a combination of both were administered intraperitoneally at 1 mg/kg body weight daily for 7 days after the graft, the mean survival times were 4.3 +/- 0.6, 4.7 +/- 0.6, or 4.7 +/- 0.6 days, respectively. The agents were found to exercise no beneficial effects for transplants. Transplants were then carried out with a single intramuscular administration of FK506 at 3mg/kg body weight on the day of the operation to observe the effect of this adjunct therapy. The mean survival time averaged 16.0 +/- 5.5 days with FK506 alone. Administration of anti-ICAM-1, anti-LFA-1, and both antibodies together with FK506 resulted in mean survival times of 15.4 +/- 3.0, 25.0 +/- 5.8 and 13.2 +/- 5.8 days, respectively. Thus, a significant prolongation of survival time was observed when the combination of anti-LFA-1 mAb and FK506 was used. In contrast, anti-ICAM-1 mAb and FK506 or both mAb and FK506 showed no beneficial effects.

Animals↗
PubMed1997

Fasudil (HA1077), an intracellular calcium antagonist, improves neurological deficits and tissue potassium loss in focal cerebral ischemia in gerbils.

The effects of an intracellular calcium antagonist fasudil (HA 1077) on protein synthesis, ion derangement, brain edema, and the neurological signs associated with focal cerebral ischemia, were investigated via a nine-hour occlusion of the left common carotid artery (CCA) in Mongolian gerbils. Protein synthesis was evaluated by the amount of incorporation of [14C]methionine into the tissue. Intravenous infusion of fasudil hydrochloride (1 mg kg-1) just after CCA ligation was effective in reducing neurological deficits six and nine hours after CCA ligation, as well as loss of tissue potassium. However, fasudil did not ameliorate the brain edema or the accumulation of sodium in the tissue. On the other hand, fasudil improved the uptake of [14C]methionine, but not its incorporation into the tissue. The improved uptake of tracer into the tissue may indicate the facilitation of collateral blood flow by fasudil. These results suggest that fasudil may mitigate ischemic damage in the penumbral zone, possibly by ameliorating collateral blood flow and preventing calcium-related cell damage.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Blood flow velocity of middle cerebral artery during prolonged anesthesia with halothane, isoflurane, and sevoflurane in humans.

BACKGROUND: It is not clear whether the increase of cerebral blood flow (CBF) produced by volatile anesthetics is maintained during prolonged anesthesia. In a previous study, the authors found that CBF equivalent, an index of flow-metabolism relationship, was stable over 3 h, suggesting no decay over time in CBF for 3 h during volatile anesthesia in humans. However, it may be possible that CBF changes in a parallel fashion to functional metabolic changes. In this study, to estimate the response of CBF to three volatile anesthetics, the authors used transcranial Doppler (TCD) ultrasonography to measure time-averaged mean velocity in the middle cerebral artery (Vmca). METHODS: Twenty-four surgical patients were randomly assigned to three groups to receive halothane, isoflurane, or sevoflurane (eight patients, each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5, 1.0, and 1.5 MAC before surgery and then at 1.5 MAC during surgery, which lasted more than 3 h. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 70 mmHg, using phenylephrine infusion, if necessary. TCD recordings of the Vmca were performed continuously. RESULTS: Vmca at 0.5 MAC of halothane, isoflurane, and sevoflurane was 49 +/- 19, 57 +/- 8, and 48 +/- 13 cm/s, respectively. Halothane significantly (P < 0.01) increased Vmca in a dose-dependent manner (0.5, 1.0, 1.5 MAC), whereas isoflurane and sevoflurane produced no significant dose-related changes. At 1.5 MAC for 3 h, Vmca changed significantly (P < 0.05) for the time trends, but it did not exhibit decay over time with all drugs. During burst suppression, observed electroencephalographically (EEG) on patients during isoflurane and sevoflurane anesthesia, the onset of a burst increased Vmca (approximately 5-30 cm/s), which was maintained for the duration of the burst. CONCLUSIONS: The results indicate that there was no decay in Vmca over time during prolonged (3 h) inhalation of volatile anesthetics at 1.5 MAC in humans. The fluctuation of Vmca during burst suppression on EEG at 1.5 MAC indicates that the flow-metabolism coupling occurred.

Adult↗
PubMed1997

Cyclin and cyclin-dependent kinase expression in human astrocytoma cell lines.

The expression of cyclins (A, B1, D1, D3, E), cyclin-dependent kinases (CDK2(3), CDK4), and the cyclin-dependent kinase inhibitors (CDKIs) p16(INK4A) and p21(CIP1) was studied in 9 malignant human astrocytoma cell lines using northern blot analysis, immunocytochemistry, and immunoblotting to see if their altered expression contributed to astrocytoma proliferation. Steady state cell cycle mRNA expression was analyzed in unsynchronized tumor cells, and cell cycle phase-specific gene expression was analyzed in 3 synchronized cell lines. Analysis of steady state expression revealed increased levels of several different cyclin transcripts and CDKs in a number of astrocytoma cell lines compared with normal human brain tissue or cultured fibroblasts. We confirm previous reports identifying loss of p16(INK4A) in astrocytomas, as a p16(INK4A) transcript was identified in only 2 cell lines and protein in 1 cell line. However, we now show that p21(CIP1) expression was also diminished relative to normal fibroblasts in all astrocytoma cell lines studied regardless of p53 mutation status. Analysis of synchronized astrocytoma cells revealed altered timing of mRNA expression of several cyclins. Immunocytochemistry revealed a generalized increase in immunoreactivity of astrocytoma cells for most cyclins and CDKs compared with human fibroblasts. Immunoblotting also revealed increased expression of cyclin proteins in a number of astrocytoma cell lines. These data suggest that increased expression of cyclins and CDKs, and decreased expression of CDKIs by human astrocytoma cell lines may contribute to their increased proliferative state. In addition, our data show that alterations in cell cycle genes in astrocytomas are not confined to the cyclin D1-CDK4-pRb axis.

Astrocytoma↗
PubMed1997

Incidence of hypocomplementemia in elementary and junior high school children with urinary abnormalities.

Abnormalities were detected in 2669 of 326,257 elementary and junior high school children (169,856 males and 156,401 females) who were screened at school for urinary abnormalities. Serum complement (C3) level was measured in all 2669 children having urinary abnormalities (811 males, 1856 females). Three had a serum C3 level that was more than three standard deviations below the mean value. Type I membranoproliferative glomerulonephritis (MPGN) was diagnosed on histological examination in one of these three children, while the other two did not undergo renal biopsy because they had serum C3 levels of 40 and 44 mg/dL, respectively, and because their urinary abnormalities were transient. It was considered that there is not much significance in testing the serum complement in the urine screening done at school and the cost/benefit ratio is low. The results appeared to reflect the frequency of persistent hypocomplementemic MPGN in Japan in recent years.

Adolescent↗
PubMed1997

[Antibacterial sensitivity, phage group and coagulase type of Staphylococcus aureus isolated from bullous impetigo].

Bullous Impetigo caused mainly by S. aureus is seen in high incidence in children. Three decades ago CEMs were much more effective for bullous impetigo than today. Recently, the causative S. aureus obtained resistance against not only PCs but multiple antibacterial drugs except a few agents. Therefore the therapy for the disease has become difficult, especially the first choice effective antibacterial drugs for general use. Sensitivity of antibacterial drugs against S. auresu isolated from skin lesions, including some MRSA was studied in 113 patients with bullous impetigo. The agents with high sensitivity against all strains were VCM (100%), MINO (100%), CLDM (96.5%), FMOX (96.3%) and against 39 MRSA strains were VCM (100%), MINO (100%), OFLX (92.3%), CLDM (87.2%) and FOM (82.1%). Clinically available antibacterial drugs for children are MINO granules and FOM drysyrup. Phage group and coagulase type of the S. aureus were simultaneously examined to elucidate which strains were causative or secondary infectious agents of the bullous impetigo.

Adult↗
PubMed1997

Time dependent alterations of serum matrix metalloproteinase-1 and metalloproteinase-1 tissue inhibitor after successful reperfusion of acute myocardial infarction.

OBJECTIVE: To test the hypothesis that changes in serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase-1 (TIMP-1) after acute myocardial infarction reflect extracellular matrix remodelling and the infarct healing process. PATIENTS: 13 consecutive patients with their first acute myocardial infarction who underwent successful reperfusion. METHODS: Blood was sampled on the day of admission, and on days 2, 3, 4, 5, 7, 14, and 28. Serum MMP-1 and TIMP-1 were measured by one step sandwich enzyme immunoassay. Left ventricular volume indices were determined by left ventriculography performed four weeks after the infarct. RESULTS: Serum concentrations of both MMP-1 and TIMP-1 changed over time. The average serum MMP-1 was more than 1 SD below the mean control values during the initial four days, increased thereafter, reaching a peak concentration around day 14, and then returned to the middle control range. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum MMP-1 on day 5, when it began to rise, and for the magnitude of rise in MMP-1 on day 5 compared to admission. Serum TIMP-1 at admission was more than 1 SD below the mean control value, and increased gradually thereafter, reaching a peak on around day 14. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum TIMP-1 on days 5 and 7, and for the magnitude of rise in TIMP-1 on days 5 and 7 compared to admission. CONCLUSIONS: Both MMP-1 and TIMP-1 showed significant time dependent alteration after acute myocardial infarction. Thus MMP-1 and TIMP-1 may provide useful information in evaluating the healing process as it affects left ventricular remodelling after acute myocardial infarction.

Adult↗
PubMed1997

Solitary cystic dilatation of the intrahepatic bile duct.

A 31 year old man was hospitalised with general fatigue and epigastric pain. Abdominal ultrasonography, computed tomography, and magnetic resonance imaging showed a cystic lesion in the left lobe of the liver. Endoscopic retrograde cholangio-pancreatography and percutaneous trans-hepatic cholangiography revealed a localised dilatation of the intrahepatic bile duct without any obstruction. However, a large mass of mucinous material was noted in the saccular intrahepatic duct and the common bile duct. There was no evidence of a choledochal cyst, anomalous pancreaticobiliary ductal union, or congenital cystic change of the kidneys. A possible diagnosis of mucinous cystic neoplasm of the intrahepatic bile duct was made and a left hepatectomy performed. Cholangiography of the resected specimen showed a non-obstructive solitary cystic dilatation of the left hepatic duct. Histologically, the dilated duct was lined with columnar biliary epithelium without any papillary proliferation and/or atypia. Neither malignancy nor hepatic fibrosis was observed; the term "solitary cystic dilatation of the intrahepatic bile duct" perhaps is more descriptive and the concept easier to understand.

Adult↗
PubMed1997

Role of kinin and renal ANG II blockade in acute effects of ACE inhibitors in low-renin hypertension.

In conscious deoxycorticosterone acetate (DOCA) salt-hypertensive dogs, the angiotensin-converting enzyme (ACE) inhibitors captopril and imidaprilat significantly decreased mean arterial pressure (MAP) and significantly increased urine flow rate, effective renal plasma flow (ERPF), glomerular filtration rate, and urinary sodium excretion. However, the angiotensin type 1 (AT1) receptor antagonist losartan caused a significant increase only in urinary sodium excretion without significant changes in MAP, urine flow rate, ERPF, and glomerular filtration rate. Simultaneous infusion of a bradykinin receptor antagonist inhibited the ACE inhibitor-induced reduction in MAP and increase in ERPF. DOCA salt treatment markedly suppressed plasma angiotensin II (ANG II) concentration (P < 0.001), although it decreased renal ANG II content only slightly (P < 0.05). Comparison of the expression of renal AT1 receptor mRNA in control kidneys with that in DOCA salt-hypertensive kidneys revealed no significant change. These results suggest that, in low-renin hypertension, inhibition of the relatively maintained ANG II production in the kidney participates in the natriuretic action of ACE inhibitors. However, hypotensive and other renal effects are mainly due to the action of bradykinin.

Angiotensin II↗
PubMed1997

Spontaneous polyploidization results in apoptosis in a Meth-A tumor cell line.

Cultured Meth-A cells always include a small fraction of large cells, which had a DNA content above 4c (polyploid cells). The process from the formation to the disintegration of polyploid Meth-A cells was measured by means of time-lapse videography. Polyploid Meth-A cells arose spontaneously from normal cells (polyploidization), then died by apoptosis. The fraction of polyploid cells gradually increased in seven day-exponential cultures with a low concentration of demecolcine, which is a specific inhibitor of cell division. The results revealed that the polyploid Meth-A cells are generated from normal cells by failing cell division and that they die by apoptosis.

Apoptosis↗
PubMed1997

Different manner of DNA synthesis in polyploidizations of meth-A and B16F10 cell lines.

Polyploidization of Meth-A and B16-F10 cells by demecolcine was examined using flow cytometry (FCM). In the presence of demecolcine, both cell lines were polyploidized to more than 16c DNA content. A marked difference was observed in the durations of S phase of polyploidy. The S-phase duration of Meth-A cells was doubly increased with ploidy, but that of B16F10 cells remained constant. When the rate of DNA synthesis in the polyploidizing cells was examined through the BrdU-uptake experiments, it was confirmed that the level of DNA-synthesis rate was constant in Meth-A cells but increased in B16F10 cells. The cellular content of c-Myc protein in polyploidized cells was also examined using anti-c-Myc monoclonal antibody. The c-Myc level of Meth-A cells was constant regardless of the ploidy but that of B16F10 cells increased with ploidy. Thus, the c-Myc content seems to be related to the duration of S phase in polyploidy.

Animals↗