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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 577 records · Page 32Linked to original sources
PubMed1996

Anti-red blood cell autoantibody transgenic mice: murine model of autoimmune hemolytic anemia.

We established an anti-red blood cell (RBC) autoantibody transgenic mouse line, in which almost all B cells were deleted in the periphery. A small number of B-1 cells, however, escaped from deletion, survived and expanded in the peritoneal cavity and the gut, because of the absence of RBC. The activation of B-1 cells by enteric bacteria induced autoimmune hemolytic anemia (AIHA). In turn, AIHA was cured by elimination of peritoneal B-1 cells. This Tg mouse line is useful for revealing the generation and activation of B-1 cells, and for clarifying the physiological and pathological roles of B-1 cells.

Anemia, Hemolytic, Autoimmune↗
PubMed1996

Expression of stromelysin 1 in human astrocytoma cell lines.

In a wide variety of tumor types, the expression of stromelysin 1 which is one of the matrix metalloproteinases (MMPs) has been shown to correlate with tumor invasion. However, little is known about the distribution of stromelysin in human brain tumors. We have previously shown that a correlation exists between the type IV collagenases, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 transcripts and in vitro invasiveness among 7 human astrocytoma cell lines. In the present study, we analyzed the expression of stromelysin 1 among the same panel of human astrocytoma cell lines and human fibroblasts by northern blot analyses and in situ hybridization. Northern blot analysis demonstrated that SF-126 and U87 MG expressed high level stromelysin 1 transcripts. Following heat shock stimulation, the stromelysin 1 transcript was up-regulated in U87 MG astrocytoma cells. In situ hybridization analysis showed specific intracytoplasmic localization of mRNA for stromelysin in these astrocytoma cell lines. By casein zymography, we have determined that both SF-126 and U87 MG secreted stromelysin 1 protein. We conclude that stromelysin 1 is expressed by certain human astrocytoma cell lines, and this study confirms the importance of continuing to characterize the proteolytic enzyme profile of these tumors to fully understand the molecular mechanisms involved in astrocytoma invasiveness.

Astrocytoma↗
PubMed1996

Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study.

Cerebral blood flow (CBF), oxygen metabolism (CMRO2), and glucose metabolism (CMRGlc) were measured using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO2 was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is impaired and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy.

Acidosis, Lactic↗
PubMed1996

Quantitative evaluation of neutral amino acid transport in cerebral gliomas using positron emission tomography and fluorine-18 fluorophenylalanine.

To elucidate the mechanism of large neutral amino acid (LNAA) transport in cerebral gliomas and to evaluate the clinical usefulness of positron emission tomography (PET) with fluorine-18 fluorophenylalanine (18F-Phe), we examined 18 patients with cerebral glioma using dynamic PET and 18F-Phe. By employing two-compartment model analysis, the influx rate K1, the efflux rate k2 and the distribution volume (Vd) of 18F-Phe were estimated in tumour tissue and contralateral normal grey matter. 18F-Phe showed increased accumulation in tumour tissue regardless of the grade of malignancy in all patients. The rate of uptake of 18F-Phe in high-grade glioma was significantly higher than in low-grade glioma (P <0.05). However, it was difficult to evaluate the tumour grade only from the 18F-Phe accumulation in individual cases. Values of K1 and Vd were significantly increased in the tumour tissue. The K1 value of the tumour tissue tended to decrease with increasing LNAA concentration in plasma. Therefore, influx of 18F-Phe into tumour tissue is mainly related to the carrier-mediated active transport. It is concluded that PET with 18F-Phe is of clinical value for tumour detection rather than assessment of tumour malignancy.

Amino Acids↗
PubMed1996

Clinical evaluation of irreversible data compression for computed radiography in excretory urography.

Efficient data compression is required for practical daily use of digital images in computed radiography (CR). This study investigated the clinical utility of data compression in excretory urography using the FCR 9000 system (Fuji Photo Film, Tokyo, Japan). Type III data compression technique was used, which can achieve a 20:1 to 25:1 compression ratio. To evaluate the degradation of image quality, we compared paired original and compressed CR images. Although a slight deterioration of image quality was noted in the renal calyx including collecting tubules among various anatomical structures, the difference was not significant. Receiver operating characteristics analysis revealed no significant difference among the original and compressed images. We conclude that compressed CR images using Type III data compression technique in excretory urography appear to be clinically applicable and acceptable.

Adolescent↗
PubMed1996

Sex and age differences in soluble guanylate cyclase activity in human platelets.

Soluble guanylate cyclase is a key enzyme of nitric oxide (NO)-related intracellular signal transduction in platelets. In the present study, we investigated the effects of sex and age on the enzyme activity in human platelets. Soluble guanylate cyclase activity was determined by generation of cyclic GMP in platelet cytosol. No significant differences in the basal activity of soluble guanylate cyclase were observed between in men and women, and between in young and old subjects. However, soluble guanylate cyclase activity in response to sodium nitroprusside, an exogenous NO donor, was higher in young men than in young and old women. Furthermore, the enzyme activity was lower in old than in young men, but there were no differences in female platelets between from young and old subjects. The present data suggest that NO-related signal transduction system in the platelet is affected by sex and age, which, to certain extent, contributes to different sensitivity of human platelets.

Adult↗
PubMed1996

Nitric oxide-dependent soluble guanylate cyclase activity is decreased in platelets from male NIDDM patients.

To elucidate the underlying mechanisms of platelet dysfunction in diabetes mellitus, we examined the activity of soluble guanylate cyclase (sGC), a key enzyme in the nitric oxide (NO)-related signalling pathway, in platelets from NIDDM (non-insulin dependent diabetes mellitus) patients. The sGC activity was determined by measuring the amount of cyclic GMP produced in platelet cytosol. In the first study, we investigated the platelet sGC activity in untreated NIDDM patients without diabetic complications. In the male NIDDM patients, sodium nitroprusside (SNP) caused a significantly lower sGC response than that in age-matched control male subjects, while the enzyme activity of female diabetics did not differ from that in the controls. Secondly, we investigated effects of diabetic-associated factors on the enzyme activity in the male NIDDM patients. There was no difference in the SNP-stimulated sGC activity in platelets from male diabetics between with and without retinopathy. In the male diabetic patients with retinopathy, however, the platelet sGC activity was slightly increased by treatment with insulin. Interestingly, the changes in enzyme activity did not correlate with plasma glycosylated hemoglobin A1c levels in diabetic patients. The impairment of the NO-related signalling pathway may contribute to the platelet dysfunction observed in patients with diabetes mellitus.

Adult↗
PubMed1996

The role of DNA repair on cell killing by charged particles.

It can be noted that it is not simple double strand breaks (dsb) but the non-reparable breaks that are associated with high biological effectiveness in the cell killing effect for high LET radiation. Here, we have examined the effectiveness of fast neutrons and low (initial energy = 12 MeV/u) or high (135 MeV/u) energy charged particles on cell death in 19 mammalian cell lines including radiosensitive mutants. Some of the radiosensitive lines were deficient in DNA dsb repair such as LX830, M10, V3, and L5178Y-S cells and showed lower values of relative biological effectiveness (RBE) for fast neutrons if compared with their parent cell lines. The other lines of human ataxia-telangiectasia fibroblasts, irs 1, irs 2, irs 3 and irs1SF cells, which were also radiosensitive but known as proficient in dsb repair, showed moderated RBEs. Dsb repair deficient mutants showed low RBE values for heavy ions. These experimental findings suggest that the DNA repair system does not play a major role against the attack of high linear energy transfer (LET) radiations. Therefore, we hypothesize that a main cause of cell death induced by high LET radiations is due to non-reparable dsb, which are produced at a higher rate compared to low LET radiations.

Animals↗
PubMed1996

Stimulative effect of epinephrine on glucose production and utilization rates in sheep using a stable isotope.

The rates of the production and utilization of blood glucose were measured during intravenous epinephrine infusion (2.0 nmol kg-1 min-1 for 1 hr) in sheep. An isotope dilution method with an infusion of [U-13C]glucose and nonsteady-state equations were used for the determination of blood glucose kinetics. Heart rate and concentrations of blood glucose, plasma free fatty acids, and lactate increased (P < 0.01), whereas plasma insulin concentrations tended to decrease (P < 0.06) during epinephrine infusion. The blood glucose turnover rate was 1.9 +/- 0.1 mg kg-1 min-1 before epinephrine infusion. The rate of blood glucose production increased (P < 0.01) to 6.4 +/- 0.5 mg kg-1 min-1 at 20 min after the initiation of epinephrine infusion. The blood glucose utilization rate increased (P < 0.05) gradually and reached 4.1 +/- 1.2 mg kg-1 min-1 at 60 min after the initiation of epinephrine infusion. These results suggest that in sheep, epinephrine stimulates the rates of both the production and the utilization of blood glucose and that hyperglycemia induced by epinephrine infusion is mainly due to a rapid enhancement in the rate of the production of blood glucose.

Animals↗
PubMed1996

Function of type II phospholipase A2 in dopamine secretion by rat neuronal PC12 cells.

When rat pheochromocytoma PC12 cells, which had differentiated into neuron-like cells following culture with nerve growth factor, were activated with glutamate, approximately 40% of their type II phospholipase A2 (PLA2) was released into the extracellular medium. Glutamate-stimulated secretion of dopamine from PC12 cells was suppressed by type II PLA2 inhibitors. Exogenous type II PLA2 added alone directly elicited release of dopamine from PC12 cells. Thus released type II PLA2 may be involved in the regulation of neurotransmitter exocytosis by PC12 cells.

Animals↗
PubMed1996

Tumor-specific accumulation of 125I-labeled mouse-human chimeric anti-CEA antibody in a xenografted human cancer model demonstrated by whole-body autoradiography and immunostaining.

Whole-body autoradiography (WBAR) was used to study the biodistribution of 125I-labeled mouse-human chimeric antibody (Ch F11-39) to carcinoembryonic antigen (CEA) in athymic nude mice bearing the CEA-producing MKN-45 human gastric carcinoma xenografts. Significantly high uptake of 125I-Ch F11-39 in the tumors obtained by tissue-counting technique was confirmed by WBAR of mice of 12, 24, 48, and 96 h postinjection of 125I-Ch F11-39. When compared with histochemical or immunohistochemical staining results of the tumor tissue sections, imaging profiles of 125I-Ch F11-39 obtained by WBARs were topographically correlated with histopathological findings of tissues and immunohistochemical localization of CEA in the tumor tissues, indicating that the accumulation of 125I-Ch F11-39 at the tumor site is based on its specificity for CEA. These results demonstrate that this chimeric antibody may serve as a potential useful diagnostic and/or therapeutic reagent for human CEA-producing cancers.

Animals↗
PubMed1996

Use of a food composition database to estimate daily dietary intake of nutrient or trace elements in Japan, with reference to its limitation.

Daily dietary intake of 28 trace elements (Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Ga, Ge, Li, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Si, Sn, Sr, Ti, Tl, V and Zn) were estimated from the food intake records (collected by the 24-h total food duplicate method), taking advantage of recently published trace element composition tables for foods in Japan. Because the number of food items listed in the tables was not sufficient, the calculation was made with not all foods recorded, and the results should be taken as semi-quantitative. The estimated intake was high (i.e. > 1 mg/day as a median) for Al, Cu, Mg, Mn, Si, Sr and Zn, medium (i.e. 2-985 micrograms/day) for As, B, Ba, Be, Cr, Ge, Mo, Ni, Sb, Sc, Se, Sn and Ti, and low (i.e. < 1 microgram/day) for Cd, Co, Li, Pb and V. Comparison of the present estimates with the reported values in the literature on 15 elements showed that close agreements were observed in the cases of 10 elements (i.e. Al, B, Cr, Cu, Mg, Mn, Mo, Ni, Se and Zn) for which the present estimates are above 1 microgram/day, whereas the discrepancies were significant for four elements (i.e. Cd, Co, Pb and V) with < 1 microgram/day intake. When the expected dietary uptake was compared with that by respiration in the cases of the 16 elements for which the atmospheric concentration data in Japan are available, the uptake was exclusively attributable to the dietary route for all 16 elements with the possible exception of vanadium.

Adult↗
PubMed1996

Correlation between MIB-1 staining index and the immunoreactivity of p53 protein in recurrent and non-recurrent meningiomas.

Wild type p53 protein has been shown by recent investigations to be involved in the negative regulation of cell proliferation, whereas aberrant p53 protein has lost this negative regulation of cell growth. Wild type p53 protein, which has a very short half-life, has generally been considered to be undetectable using immunohistochemical methods; however, according to a recent report, wild type p53 protein may accumulate in the nuclei because of a defective ubiquitin pathway. Aberrant p53 protein has a longer half-life, and thus is visible using immunohistochemical methods. In this study, both the proliferative potential represented by the MIB-1 staining index (SI) and the immunoreactivity of p53 protein in 51 intracranial meningiomas were studied applying immunohistochemical staining methods to archival paraffin sections. The correlation among MIB-1 SI, p53 immunoreactivity, histopathologic findings and the clinical course of the meningiomas was also analyzed retrospectively. Although it is not possible with available reagents to distinguish between aberrant p53 protein and wild type p53 protein, statistical analyses show that p53 protein was immunostained both in meningiomas with high MIB-1 SI and in recurrent meningiomas. This demonstrates the close relationship among p53 immunoreactivity, MIB-1 SI, and recurrence; therefore, the presence of p53 protein by immunohistochemical examination may suggest the proliferative activity of meningioma and is capable of serving as a predictor of future recurrence.

Antibodies, Monoclonal↗
PubMed1996

CD28 co-stimulatory signals induce IL-2 receptor expression on antigen-stimulated virgin T cells by an IL-2-independent mechanism.

Intravenous sensitization of C57BL/6 (B6) mice with class II H-2-disparate B6-C-H-2bm12(bm12) resting B cells induced anti-bm12 CD4+ T cell tolerance as shown by hyporesponsiveness in the anti-bm12 mixed lymphocyte reaction (MLR). The present study investigated the mechanism(s) of the failure of bm12 B cells to stimulate the proliferation of B6 anti-bm12 CD4+ T cells. While stimulation in vitro to B6 splenic T cells with bm12 antigen-presenting cells (APC) induced IL-2 mRNA expression and IL-2 production, T cells stimulated with bm12 B cells expressed much less IL-2 mRNA and secreted very low but detectable levels of IL-2. Moreover, the T cells stimulated with the bm12 B cells did not proliferate and this was not corrected by the addition of rIL-2 responsiveness. Further, whereas IL-2 receptor (IL-2R) alpha chain expression was significantly induced on B6 T cells stimulated with bm12 APC; stimulation with bm12 B cells did not induce IL-2R expression over background levels. However, virgin T cells stimulated with both bm12 B cells and anti-CD28 mAb proliferated and displayed a dramatic increase in IL-2 production as well as IL-2R expression to levels commensurate with those resulting from bm12 B cells plus anti-CD28 mAb even in the presence of sufficient amounts of anti-IL-2 mAb for neutralizing produced IL-2; while levels of IL-2R were significantly lower compared to those induced in the absence of anti-IL-2 mAb, increased frequencies of IL-2R+ cells were comparable. Conversely, IL-2R was not induced by bm12 B cell stimulation in the presence of IL-2. Moreover, IL-2R expression and proliferation induced by stimulation with bm12 APC was inhibited by CTLA-4-Ig, a soluble recombinant fusion protein capable of blocking the CD28 co-stimulatory signals not only stimulate IL-2 production but also induce IL-2R expression by an IL-2-independent mechanism.

Abatacept↗
PubMed1996

Molecular cloning and characterization of guinea pig Fc gamma RIII: expression but not function is independent of the gamma chain of Fc epsilon RI.

We have isolated two cDNA clones encoding the guinea pig receptor for the Fc portion of IgG2 (Fc gamma 2R) from a guinea pig peritoneal macrophage cDNA library. Analysis of the predicted amino acid sequence of the one cDNA clone indicated that the guinea pig Fc gamma 2R is a type I transmembrane protein and has approximately 72% DNA sequence homology and approximately 57% protein sequence homology with the human Fc gamma RIII. Therefore, we propose that the guinea pig Fc gamma 2R is referred to as guinea pig Fc gamma RIII. The most important finding in this report is that the obtained cDNA directed the cell surface expression of the Fc gamma 2R on COS-7 cells without association with the gamma chain of the high-affinity IgE receptor (Fc epsilon RI gamma) which is required for human and mouse Fc gamma RIII to be expressed on the cell surface. Furthermore, we demonstrated that the endocytosis activity of Fc gamma RIII is dependent upon the association with Fc epsilon RI gamma, suggesting that Fc epsilon RI gamma is involved in the functions of guinea pig Fc gamma RIII. The other clone was found to lack the sequence encoding transmembrane and cytoplasmic domains, suggesting the presence of a soluble form of guinea pig Fc gamma RIII. Northern blot analysis and RT-PCR showed that a transmembrane form of guinea pig Fc gamma RIII was expressed in peritoneal macrophages, but not in neutrophils in spite of the fact that they express Fc gamma 2R, indicating that the Fc gamma 2R on neutrophils is a product of a distinct gene.

Amino Acid Sequence↗
PubMed1996

Preservation of the ration of cerebral blood flow/metabolic rate for oxygen during prolonged anesthesia with isoflurane, sevoflurane, and halothane in humans.

BACKGROUND: In several animal studies, an increase in cerebral blood flow (CBF) produced by volatile anesthetics has been reported to resolve over time during prolonged anesthesia. It is important to investigate whether this time-dependent change of CBF takes place in humans, especially in clinical situations where surgery is ongoing under anesthesia. In this study, to evaluate the effect of prolonged exposure to volatile anesthetics (isoflurane, sevoflurane, and halothane), the CBF equivalent (CBF divided by cerebral metabolic rate for oxygen (CMRO2) was determined every 20 min during anesthesia lasting more than 4h in patients. METHODS: Twenty-four surgical patients were assigned to three groups at random to receive isoflurane, sevoflurane, or halothane (8 patients each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 MAC before surgery and then 1.5 MAC for the 3 h of surgical procedure. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 60 mmHg, using phenylephrine infusion, if necessary. CBF equivalent was calculated every 20 min as the reciprocal of arterial-jugular venous oxygen content difference. RESULTS: CBF equivalent at 0.5 MAC of isoflurane, halothane, and sevoflurane was 21 +/- 4, 20 +/- 3, and 21 +/- 5 ml blood/ml oxygen, respectively. All three examined volatile anesthetics significantly (P<0.01) increased CBF equivalent in a dose-dependent manner (0.5, 1.0, 1.5 MAC). AT 1.5 MAC, the increase of CBF equivalent with all anesthetics was maintained increased with minimal fluctuation for 3 h. The mean value of CBF equivalent at 1.5 MAC in the isoflurane group (45 +/- 8) was significantly (P<0.01) greater than those in the halothane (32 +/- 8) and sevoflurane (31 +/- 8) groups. Electroencephalogram was found to be relatively unchanged during observation periods at 1.5 MAC. CONCLUSIONS: These results demonstrate that CBF/CMRO2 ratio is markedly increased above normal and maintained during prolonged inhalation of volatile anesthetics in humans. It is impossible to determine whether these data indicate a stable CBF or whether CBF and CMRO2 are changing in parallel during the observation period. The unchanging electroencephalographic pattern suggests that the former possibility is more likely and that the increase of CBF produced by volatile anesthetics is maintained over time without decay, which has been reported in several animal studies. It also is suggested that isoflurane possesses greater capability to maintain global CBF relative to CMRO(2) than does halothane or sevoflurane. time.)

Adult↗
PubMed1996

Glomus tumor of the musculotendinous junction of the rotator cuff. A case report.

A rare case of glomus tumor of the rotator cuff is presented. A 35-year-old man had a 20-year history of left shoulder pain. Through physical examination, muscular atrophy in the supraspinatus and infraspinatus muscles and restriction of shoulder motion was seen. Magnetic resonance imaging showed an abnormal oval shadow in the supraspinatus musculotendinous junction, and postcontrast computed tomographic scanning showed a small calcification focus in the tumor. Surgical excision of the tumor and rotator cuff reconstruction using Debeyre's procedure were done. Microscopic examination of the tumor showed a typical glomus tumor. It was difficult to diagnose glomus tumor in this patient before surgical intervention. Retrospective consideration indicated that the history of the present illness, computed tomographic scanning, and magnetic resonance imaging were critical for differential diagnosis.

Adult↗