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Biomedical subjects

H Murakami

Publications and source records attributed to H Murakami.

At least 361 records · Page 20Linked to original sources

Disinfection of removable dentures using ozone.

Over time, removable dentures tend to become unsanitary and emit unpleasant odors, and oral mucosa sometimes becomes inflamed or denture stomatitis is caused by denture plaque. Recently, various cleaning products designed to keep removable dentures sanitary have appeared on the market. It is known that denture plaque is mainly composed of Candida albicans (C. albicans), and that ozone seems to inhibit these micro-organisms. Accordingly, a denture cleaner using ozone bubbles (ozone concentration of about 10 ppm) was considered as clinically appropriate because of its strong disinfecting and deodorizing power, and high biological safeness. The effectiveness of this cleaner against C. albicans was investigated using. Results showed that C. albicans decreased to about 1/10 after 30 min and to 1/10(3) after 60 min.

Candida albicans↗

[Levels of alpha-elastin and of desmosine as indexes of elastase-induced lung injury in rats].

Two markers of elastin degradation, alpha-elastin and desmosine levels, were measured in sera from rats after single tracheal instillations of porcine pancreatic elastase (PPE). Biochemical and pathophysiological changes in the lung were also studied. Male Wistar rats were divided into three groups. The control group received one intratracheal dose of saline (0.3 ml). The PPE 60 group received one intratracheal dose of 60 U of PPE. The PPE 120 group received one intratracheal dose of 120 of PPE. Blood samples were collected 0, 1, 3, 5, 7, 14, 28, and 56 days after the intervention, and levels of alpha-elastin and desmosine were measured by enzyme-linked immunosorbent assay. At the end of the study (day 56), lung volumes and static pressure-volume curves were measured by body pletysmography. Then the rats were killed and the mean linear intercept was measured as defined by Thurlbeck. The serum alpha-elastin level in the PPE 120 group on day 7 was significantly higher (p < 0.05) than those in other groups. Desmosine values on day 1 in the PPE 60 group and on days 1 and 7 in the PPE 120 group were significantly higher (p < 0.05) than those in the control group. Functional and morphometric analyses revealed that the PPE 120 group had more emphysematous changes than the control group (p < 0.01) and more than the PPE 60 group (p < 0.05). These results suggest that levels of alpha-elastin and of desmosine reflect changes that occur in the early stages of lung injury, and that these changes are related to abnormalities found in rat lungs on day 56.

Animals↗

Evaluation of the therapeutic range of whole blood cyclosporin concentration in the treatment of psoriasis.

Cyclosporin (CyA) trough levels in whole blood in 17 patients receiving CyA for the treatment of severe psoriasis were measured by fluorescence polarization immunoassay (FPIA) employing a specific monoclonal antibody. Clinical success was defined as a PASI score reduction greater than or equal to 75% (group A), partial success by a PASI score reduction of 60%-74% (group B), and insufficient efficacy by a PASI score reduction of less than 60% (group C). Nine of the 17 patients given CyA (53%) exhibited an improvement rate of > or = 75% in the PASI score within 8 weeks of the initiation of treatment. At 8 weeks of treatment the values for the daily dose and whole blood trough CyA concentration were both significantly higher in group A than in group C, daily dose (3.6 +/- 1.0 vs. 2.3 +/- 0.4 mg/kg/day, respectively) and whole blood concentration (141.3 +/- 46.0 vs. 79.7 +/- 19.0 ng/ml). Throughout the study period, during an average observation period of 30 weeks, 13 of the 17 patients (76%) achieved a reduction rate of > or = 75% in the PASI score. In these 13 patients in whom psoriasis lesions cleared satisfactorily the values for the mean daily CyA dose, and whole blood trough levels were 2.4 mg/kg/day and 94.8 ng/ml, respectively. The improvement rate was significantly higher when the CyA trough level was above, rather than below, 100-140 ng/ml within the first 8 weeks, although a lower CyA dose and/or whole blood level was effective in maintaining the reduced PASI score in the subsequent phase. The most important side-effect was mild hypertension in 7 of the 17 patients (41%), however, the onset of hypertension in these patients varied from 30-100 days after the initiation of treatment. Antihypertensive drug therapy and/or dose reduction resulted in a significant decrease, from 166 +/- 17/100 +/- 7-140 +/- 6/84 +/- 10 mmHg, of the CyA-induced hypertension. The relationship between the time course of the duration of improved PASI score and the whole blood concentration of CyA was observed, which suggests that the changes in drug effects were correlated with changes in whole blood levels. During the study period we experienced recurrences in 2 patients after the tapering or withdrawal of CyA treatment. In these 2 patients the relapse may have been due, in part, to the sharp decrease in whole blood concentration secondary to partial noncompliance. Measurement of whole blood CyA trough level is the only method for assessing the patient's noncompliance. Contrary to previous reports we confirmed that the measurement of CyA concentration in whole blood was useful for monitoring the effects in patients with psoriasis.

Cyclosporine↗

Lung cancer-reacting human recombinant antibody AE6F4: potential usefulness in the sputum cytodiagnosis.

Human monoclonal antibody (hMAb) AE6F4 has been shown to be potentially useful for immunocytological detection of lung cancer cells in sputum. By recombinant DNA technology, IgM type hMAb AE6F4 was switched to lgG. The IgG mimic recombinant AE6F4 antibody expression plasmid was assembled using the antibody heavy chain gene, which ligated the gene encoding VH and CH1(mu) domains of hMAb AE6F4 heavy chain to the gene encoding CH2(gamma 1) and CH3(gamma 1) domains of human IgG heavy chain, and the antibody light chain gene of hMAb AE6F4. The recombinant antibody expressed by baby hamster kidney (BHK)-21 cells showed molecular size equivalence to IgG, and consisted of human mu-gamma hybrid heavy and kappa light chains. The immunological specificity of the recombinant antibody was the same as that of hMAb AE6F4 by immunoblotting analysis to the 14-3-3 protein, the putative antigen of hMAb AE6F4, and by immunohistochemical and immunocytological analyses using tissue sections and sputa of lung cancer patients. The transfected BHK-21 cells produced the recombinant antibody persistently and the productivity was greater than 20 times that by human-human hybridoma producing hMAb AE6F4.

14-3-3 Proteins↗

[Up-regulation of NGF, trkA, Fas, down-regulation of bcl-2, and induction of apoptosis by propentofylline in human glioma cell lines].

Propentofylline (PPF) has been reported to stimulate the synthesis/secretion of nerve growth factor (NGF) by cultured mouse astroglial cells. In the present study, we examined whether PPF stimulates NGF synthesis in human glioma cell lines, the same as in mouse astroglial cells, and if so, whether NGF has a biological effect on glioma cells. After administration of PPF into the glioma cell lines, we investigated morphological changes and gene and protein expression of NGF, trkA, Fas and bcl-2 by using GFAP staining. Western blotting, and RT-PCR. Glioma cells showed definite morphological changes, including expansion of astrocytic processes, cytoplasmic enlargement and increases in GFAP staining. Interestingly, apoptosis was identified by DNA ladder formation in each of the cell lines. The mRNA and protein expression of NGF, trkA and Fas increased, but expression of bcl-2 decreased. These findings suggest that PPF works as a transcriptional modulator and induces apoptosis in glioma cells.

Animals↗

Leukemic transformation in three patients with polycythemia vera. Analysis of the clinicopathological features and N-ras gene mutation.

Thirty-three patients were diagnosed as having polycythemia vera (PV) from 1973 to 1993 in our institution. Of these patients, three who had been treated with alkylating agents, progressed to acute non-lymphocytic leukemia (ANLL). Their physical findings and the laboratory data were similar to those patients who did not become leukemic. To investigate the association with leukemic evolution, we examined N-ras oncogene activation in those patients who progressed to acute leukemia. Point mutations in codons 12 and 13 were not always detected, suggesting that the N-ras gene did not influence occurrence of ANLL in our patients.

Adult↗

The protective effect of low power He-Ne laser against erythrocytic damage caused by artificial heart-lung machines.

We studied the protective effects of low power He-Ne laser irradiation on erythrocytes against the damage caused by experimental artificial heart-lung machines. The erythrocyte suspension in a closed circuit was perfused with a roller pump. One of two circuits was used for laser treatment and the other for control. The laser group demonstrated significantly higher erythrocyte deformability and erythrocyte ATP levels, and lower free hemoglobin and lipid peroxide levels. A laser output power of 8.5 mW was most effective in protecting the erythrocytes. A further morphological finding using a scanning electron microscope showed fewer echinocytes and more discocytes in the laser group. This finding was consistent with the results of physiological and biochemical tests. Low power He-Ne laser irradiation was shown to protect human erythrocytes from the damage caused by an experimental artificial heart-lung machine, raising the possibility of the clinical application of low power He-Ne laser treatment during extracorporeal circulation in cardiovascular surgery.

Erythrocytes, Abnormal↗

[Idiopathic intracranial hypotension associated with decreased blood concentration of vitamin A].

We report a case of idiopathic intracranial hypotension, a clinically rare syndrome. A 28-year-old woman was admitted with orthostatic headaches associated with nausea secondary to intracranial hypotension. Lumbar puncture yielded an opening pressure of 4 cmH2O in the lateral recumbent position, and the spinal fluid protein concentration was 56 mg/dl. There was no history of lumbar puncture or clear history of head trauma before the onset of symptoms. Spinal and cranial MRI showed no evidence of CSF leakage, and there was diffuse meningeal enhancement following gadolinium infusion. Cranial MRI showed no evidence of brain displacement due to low CSF pressure, such as tonsillar herniation. Radioisotope cisternography (RIC) showed rapid accumulation of isotope within the bladder and early disappearance of radioactivity from the head. About 2 months later the headaches resolved spontaneously, and repeated lumbar puncture yielded opening pressure elevation to 10.5 cmH2O with a decrease in protein concentration to 28 mg/dl. The abnormal MRI and RIC findings had become normal. On the other hand, the patient had a low blood concentration of vitamin A, which is thought to play some role in the production of CSF. The results of RIC suggested that the patient may have become symptomatic because of undetectable CSF leakage or hyperabsorption, but diminished production of CSF due to lower blood vitamin A concentrations may also have been a factor predisposing to this syndrome.

Adult↗

GABA rho1 receptor: inhibition by protein kinase C activators.

The effects of protein kinase C (PKC) activators on gamma-aminoburyric acid (GABA) rho 1 receptor function were studied in rho 1 -expressing Xenopus oocytes. The PKC activator phorbol 12-myristate 13-acetate (PMA) but not the inactive analog phorbol 12-mono-myristate inhibited the GABA-gated chloride currents. Mezerein, a non-phorbol ester type PKC activator, also inhibited the rho 1 responses, but 8-chlorophenylthio-cyclic AMP, a protein kinase A activator, had no effect. The effect of PMA was significantly reduced by a PKC inhibitor, staurosporine. These results suggest that GABA rho 1 receptor function can be regulated by PKC-mediated phosphorylation events.

Alkaloids↗

Distinct signal transduction through the tyrosine-containing domains of the granulocyte colony-stimulating factor receptor.

The receptor for granulocyte colony-stimulating factor (G-CSFR) is a hemopoietic growth factor receptor, which mediates proliferation and differentiation signals. The cytoplasmic region of G-CSFR carries four tyrosine residues in its C-terminal half. We constructed mutant receptors in which each tyrosine residue of G-CSFR was mutated to phenylalanine. Two mutant receptors (Tyr703 and Tyr728) neither transduced the growth-inhibitory signal nor induced the neutrophil-specific myeloperoxidase (MPO) gene. The Tyr703 mutant did not induce morphological changes in cells, whereas transformants expressing the Tyr728 mutant adhered to plates with a macrophage-like morphology upon G-CSF stimulation. Mutation of the most distal tyrosine residue (Tyr763) abolished the ability of G-CSFR to stimulate the tyrosine phosphorylation of a cellular protein with an M(r) of 54 kDa. These results indicated that the regions around the three tyrosine residues of G-CSFR play essential and distinct roles in signal transduction.

Animals↗

Impaired tumor phenotypes in class II major histocompatibility complex antigen-inducible cells originated from human lung adenocarcinoma.

The class II major histocompatibility complex (MHC) antigens play important roles in T cell activation and are thought to be involved in tumor development. Using anti-class II antibodies with interferon gamma (IFN-gamma), we have here selected class II MHC antigen positive cancer cells from the human lung adenocarcinoma cell line A549, which is originally negative (> 95%) for the antigens. A part of the class II antigen-positive cells presented a flat morphology, which was not observed in the parental A549 cells. Class II antigen expression in these flat cells was IFN-gamma inducible; there was a correlation between the inducibility and phenotypic changes. A class II antigen-inducible flat subline restored the ability of contact inhibition and anchorage-dependent growth as well as lost tumorigenicity in athymic mice.

Adenocarcinoma↗

The mode of actions of glyceraldehyde-3-phosphate dehydrogenase identified as an immunoglobulin production stimulating factor.

Immunoglobulin production stimulating factor-II alpha, which enhances immunoglobulin production of human and mouse hybridomas was purified from cell lysate of human Burkitt's lymphoma, Namalwa cells, and identified as glyceraldehyde-3-phosphate dehydrogenase. The enhancement of immunoglobulin production with this enzyme was not linked with its enzymatic activity. The enzyme enhanced immunoglobulin productivity of transcription-suppressed hybridomas, but did not enhance that of translation-suppressed hybridomas. From these results, it is suggested that this enzyme takes part in the post-translational control or the enhancement of translation activity to stimulate immunoglobulin production of hybridomas.

Glyceraldehyde-3-Phosphate Dehydrogenases↗

A kinase from fission yeast responsible for blocking mitosis in S phase.

In virtually all eukaryotes, mitosis starts after the completion of DNA synthesis. This orderly process is ensured by the checkpoint mechanism that blocks the onset of mitosis while DNA is being synthesized or is damaged. In the fission yeast Schizosaccharomyces pombe, this mechanism involves some rad+ and hus+ genes. However, it is not known how the checkpoint system monitors these events. Recently a multicopy suppressor of a temperature-sensitive DNA polymerase-alpha mutant was isolated. This gene, named cds1+ (checking DNA synthesis), encodes a typical protein kinase. Here we report that this protein kinase is a key component of the DNA replication-monitoring S/G2 checkpoint system. Our data suggest that its primary role is to monitor DNA synthesis by interacting with DNA polymerase alpha and send a signal to block the onset of mitosis while DNA synthesis is in progress.

Amino Acid Sequence↗

Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption.

The biological role of phosphatidylinositol (PI)-3 kinase was examined in osteoclast-like multinucleated cells (OCLs) formed in co-cultures of mouse osteoblastic cells and bone marrow cells. The expression of PI-3 kinase in OCLs was confirmed by Western blot analysis. Wortmannin (WT), a specific inhibitor of PI-3 kinase, inhibited PI-3 kinase activity in OCLs both in vitro and in vivo. WT also inhibited pit-forming activity on dentine slices and disrupted a ringed structure of F-actin-containing dots (an actin ring) in OCLs in a dose-dependent manner. The inhibitory profiles of WT for pit and actin ring formation were similar to that for PI-3 kinase activity in OCLs. Electron microscopic analysis revealed that OCLs treated with WT did not form ruffled borders. Instead, numerous electron lucent vacuoles of differing sizes were found throughout the cytoplasm. These results suggest that PI-3 kinase is important in osteoclastic bone resorption.

Actins↗

The role of extrinsic nervous system in jejunal absorption during elevation of intraluminal pressure in anesthetized dogs.

The aim of this study was to investigate the role of the extrinsic nervous system in jejunal absorption under elevated intraluminal pressure of the jejunum. Increase in intraluminal pressure from 0 to 70-100 mmHg decreased net absorption of fluid, Na+ and Cl-, from 7.6 +/- 0.5 to 5.6 +/- 0.3 ml/15 min, 1.1 +/- 0.1 to 0.7 +/- 0.1 mEq/15 min, and 1.2 +/- 0.1 to 0.8 +/- 0.1 mEq/15 min, respectively. To examine the role of the extrinsic nervous system in the depressed net jejunal absorption induced by the increase in intraluminal pressure, jejunal afferent and efferent nerve activities were measured in response to the increase in intraluminal pressure. Both afferent and efferent nerve activities increased to 224 +/- 14 and 236 +/- 18% in response to the increase in intraluminal pressure. In the extrinsic denervated jejunal loop, the responses of net absorption to the elevation of intraluminal pressure were quite different from those in innervated jejunum. That is, in the denervated jejunal loop the elevation of intraluminal pressure converted jejunal absorption to jejunal secretion. These results indicate that elevation of intraluminal pressure elicits the jejuno-jejunal reflex, and this mechanism counteracts jejunal secretion.

Anesthetics↗

All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group.

We conducted a multicenter trial of treatment with all-trans retinoic acid (ATRA) for newly diagnosed acute promyelocytic leukemia (APL) in the AML-92 study and compared it with our previous study with standard intensive chemotherapy, the AML-89 study, in the view of complete remission (CR) rate, incidence of early death, and event-free survival (EFS). Patients were scheduled to receive oral ATRA 45 mg/m2 daily until CR. If patients had leukocyte counts above 3 x 10(9)/L at the start of therapy, they received daunorubicine (DNR) 40 mg/m2 for 3 days and behenoyl cytosine arabinoside (BHAC) 200 mg/m2 for 5 days in addition to ATRA. During the ATRA therapy, if patients showed myeloblast plus promyelocyte counts higher than 1 x 10(9)/L in the peripheral blood, they received additional DNR and BHAC in the same schedule, as well. A total of 110 patients were entered into the study. Median age was 43 years (range, 16 to 74). Twenty-eight (26%) of 109 patients (one died before the start of therapy) received ATRA alone. Ninety-seven patients (89%) achieved CR; 48 of 49 (98%) aged less than 40 years, 44 of 52 (84%) aged between 40 and 69, and 5 of 8 (63%) aged above 70 achieved CR, respectively; 25 of 28 (89%) with ATRA alone, 46 of 51 (90%) with ATRA plus initial chemotherapy and 26 of 30 (87%) with ATRA plus later chemotherapy attained CR, respectively. Nine (8%) patients died within 28 days after the start of therapy. In contrast, 44 of 62 patients (71%) attained CR, and 13 (21%) died within 28 days in the AML-89 study with the combination of DNR, BHAC, 6-mercaptopurine and prednisolone. Seven developed retinoic acid syndrome and one died of it in the present study. Other toxicities associated with this drug included cheilitis, desquamation, muscle pain, and hypertriglyceridemia. Predicted 23 months EFS for all ATRA-treated patients and disease-free survival (DFS) in the CR cases were 75% and 81%, respectively, in a median follow-up period of 21 months. Compared to the AML-89 study, there was a highly significant difference in remission rate (P = .004), EFS (P = .0007), and also early mortality rate (P = .02). Present results demonstrated that ATRA with or without chemotherapy gives a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL.

Adolescent↗

Anti-neutrophil antibody attenuates the severity of acute lung injury in rats with experimental acute pancreatitis.

OBJECTIVE: To examine the role of activated neutrophils in microvascular injury after severe acute pancreatitis. We used the polyclonal anti-rat neutrophil antibody (PoAb) to deplete peripheral neutrophil counts and the anti-rat monoclonal antibody (MoAb) CD18 to block neutrophil adherence functions. DESIGN: Prospective, controlled trial. SETTING: Laboratory. PARTICIPANTS: Anesthetized male Wistar breeder rats, in which necrotizing pancreatitis was induced by injecting necrotizing agents into the pancreatic duct. INTERVENTIONS: Treatment groups received an infusion of PoAb, 8 mL/kg, before induction of pancreatitis or MoAb CD18, 2 mg/kg, after induction of pancreatitis. Control animals received 2 mL of rabbit serum or 1 mL of saline solution. MAIN OUTCOME MEASURES: Survival rate, white blood cell count, levels of serum amylase and lipase, myeloperoxidase activity in the lung, lipid peroxide levels in the pancreas, and results of histological studies. RESULTS: The survival rate of rats treated either with PoAb before or MoAb CD18 after induction of sepsis improved significantly (P < .01). Histologically and according to the levels of neutrophil myeloperoxidase in their lungs, rats treated with the antibodies 24 hours after inducing pancreatitis improved significantly (P < .05). Moreover, the serum lipase concentrations and lipid peroxide levels in the pancreas of these rats decreased significantly (P < .05). CONCLUSIONS: Both the depletion of peripheral neutrophils by PoAb and blocking of neutrophil adherence functions by MoAb CD18 may help to prevent acute lung injury caused by severe acute pancreatitis in this model.

Acute Disease↗