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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 685 records · Page 38Linked to original sources

Rapid calculation of regional cerebral blood flow and distribution volume using iodine-123-iodoamphetamine and dynamic SPECT.

UNLABELLED: Iodine-123-iodoamphetamine (IMP) is commonly used as a flow tracer for SPECT due to its large first-pass extraction fraction. Significant clearance from the brain, however, causes changes in distribution and underestimation of CBF values when a conventional microsphere model is applied to prolonged data acquisition. We have developed a rapid method to calculate CBF images in which clearance effects are taken into account. METHODS: A dynamic SPECT scan was obtained from five subjects (four patients with cerebral infarctions and one healthy volunteer) following intravenous injection of IMP lasting 1 min. The arterial input function was obtained by frequent blood sampling and measurement of the octanol extraction ratio. The dynamic images were weighted and integrated so that the look-up table procedures yielded values of CBF and distribution volume (Vd) simultaneously. RESULTS: Calculated values for CBF and Vd were consistent with those determined by nonlinear least squares fitting [CBF: Y = 1.03X-0.30 (ml/100 ml/min), r = 0.998, p < 0.001; Vd: Y = 0.99X-0.11 (ml/ml), r = 0.99, p < 0.001] and calculated CBF correlated significantly with CBF measured by PET [Y = 0.85X-0.15 (ml/100 ml/min), r = 0.92, p < 0.001]. CONCLUSION: This technique is valid for estimating CBF.

Amphetamines↗

[Diagnostic and clinical features of clinicopathomorphological--findings in multiple myeloma].

The intramedullary infiltration type, cell morphology and the pathological condition of bone lesion are closely related to diagnostic and clinical features in multiple myeloma. They are important factors to evaluate treatment effects and prognosis and to determine therapeutic strategy. In addition to various clinical parameters to determine prognosis, including M protein level, they should be minutely observed because the obtained findings provide useful basic data for monitoring multiple myeloma. In the future, much progress should be made towards identifying various factors which regulate dynamics of myeloma cell proliferation and bone remodeling.

Bone Marrow↗

[An attempt to prevent psychological distress induced by magnetic resonance imaging: effectiveness of psychological interventions].

A magnetic resonance imaging (MRI) examination has reportedly produced psychological distress such as discomfort, anxiety and fear in a certain number of patients. In an attempt to prevent such distress during an MRI, the authors took the following psychological measures: 1) improved psychological support for patients by MRI technicians; 2) providing sufficient information to patients about the imager and the nature of the examination; 3) reassurance of the safety, with the patient free to terminate the examination at any time; 4) environmental modification to induce relaxation, including recorded music, paintings and live plants in the examination room. We then evaluated the effectiveness of these combined psychological support factors for all MRI patients. A questionnaire on psychological distress experienced during an MRI was filled out by 143 patients (mean age, 49.4 years) and 105 patients (mean age, 48.4 years) prior to and after our psychological measures, respectively, after MRI test in Saiseikai Nakatsu hospital, and comparisons made between these two groups (chi 2 test, p < 0.05). The number of patients experiencing psychological distress during an MRI was significantly decreased (50.5%) after the measures were implemented as compared to the number (64.3%) beforehand. In particular, female, 60 or older patients and patients examined for the first time showed significant decreases in experiencing psychological distress after the measures were implemented. The number of patients who reported distress, tended to decrease. Patients who developed certain symptoms, such as palpitation, also tended to decrease. Patients who reported the "long examination time" as a distress factor and those who developed palpitation during the examination significantly decreased. Our results indicate that these combined psychological measures are efficacious in reducing psychological distress during an MRI, mainly by curtailing the patient's subjective sense of examination time. In addition to an MRI examination, our psychological measures should be applied to other medical examinations which tend to generate undue psychological distress.

Adolescent↗

[A pharyngeal carcinoma after resection of a upper esophageal web].

Dysphagia suddenly progressed in a 69-year-old woman who had a 50-year history of intermittent difficulty in swallowing solid food. A thick circumferential who in the upper esophagus was extensive enough to be the cause of dysphagia. There was another thin semicircular web in the pharynx. Bouginage resulted in only 6-months relief of symptoms, and the same esophageal who was reformed with the same severe symptoms 3 years later. Surgical resection of the esophageal web was performed. Extensive pharyngeal carcinoma was found 4 years after surgery. She died of heart failure during combination therapy of irradiation and chemotherapy.

Aged↗

[Yearly changes and geographical distribution of allergic rhinitis morbidity estimated from records of the national health insurance].

The age-adjusted morbidity of allergic rhinitis (AR) in Ibaraki prefecture in May, estimated from data of national health insurance records, increased remarkably from 1980 to 1992 with varying yearly rates of increase. High AR morbidity years coincided with years of high Japanese cedar and cypress pollen counts, and moreover, an estimate equation of the morbidity using as explanatory variables, year and the yearly total count of pollen, accurately estimated AR morbidity. The AR morbidity varied with the size of the municipality. The AR morbidity of the town group and village group were about 80% and about 60% respectively of the city group in 1992. The map of the AR morbidity of each municipality showed that urbanized districts had higher morbidity than areas with cedar forests, which are supposedly sources of the cedar pollen. Continuous increase of morbidity of districts with much cedar forests terminated in 1986. Since then only the fluctuation of the morbidity corresponding to the pollen count was observed. The ratio of the morbidity of the years with much pollen to that of the years with little pollen was mapped. The map showed good agreement with the map of cedar forests. The results obtained above demonstrate the usefulness of the data of the national health insurance records.

Adolescent↗

Aging effect on neutral amino acid transport at the blood-brain barrier measured with L-[2-18F]-fluorophenylalanine and PET.

UNLABELLED: Neutral amino acids (NAAs) are transported from the blood to the brain using the same carrier system in a competitive fashion. The purpose of this study is to establish a method for evaluating neutral amino acid transport at the blood-brain barrier (BBB) in humans and to examine the aging effect of amino acid transport. METHODS: A dynamic PET study with L-(2-18F)-fluorophenylalanine (18F-Phe) was performed in 14 normal volunteers (age 21-71 yr; mean +/- s.d., age range 48.0 +/- 17.1 yr). By using a two-compartment model analysis and a weighted integration technique, the influx rate constant K1, the efflux rate constant k2 and distribution volume Vd of 18F-Phe were estimated in various brain structures. RESULTS: The value of K1 was inversely correlated with plasma NAA concentration (r = -0.69, p < 0.01). The cerebellum showed the highest value of K1, while the white matter showed the lowest. There was no significant change in K1 during aging. The value of k2 was significantly increased with age. CONCLUSION: No decline of K1 during aging indicated that NAA transport from the blood to the brain is a limiting process of age in amino acid incorporation. Fluorine-18-Phe PET imaging is a feasible method to study NAA transport at the BBB in vivo in humans and can be applied to pathological conditions of the brain.

Adult↗

[Effect of intraperitoneal chemotherapy with implantable reservoir against unresectable gastric cancer].

Intraperitoneal chemotherapy was applied for eight unresectable gastric cancer patients, including two exploratory laparotomy and six gastrojejunostomy. Chemotherapeutic agents were given ip at a dose of 75 mg/body of cisplatin and 150 mg/body etoposide and iv at a dose of 10 mg/body of mitomycin C as well as orally 5-FU. This treatment was repeated three to ten times. An overall response rate against primary lesion was 40%. Six month and 1 year survival rate of this therapy were 87.5% and 75% respectively, while those of control group were 42% and 0%. Median duration of survival was 518 days in this chemotherapy group and 172 days in the control. In this study, intraperitoneal chemotherapy group showed a significant improvement of survival compared to the control. All patients were able to stay home between therapies. This method seemed to be beneficial to the unresectable gastric cancer patients.

Aged↗

[Therapeutic results of non-small cell lung cancer in stage III: combined synchronous irradiation with bronchial artery infusion of CDDP].

The present series consisted of 55 patients with non-small cell lung cancer in stage III who underwent radiotherapy from 1986-1989. They were divided into two groups: 35 patients with combined concurrent bronchial artery infusion (BAI) of CDDP (50 mg) and unevenly fractionated radiotherapy (combined group) and 20 with evenly fractionated irradiation (radiation group). The combined therapy was expected to achieve higher local control of disease. The rationale for the combined regime was based on the effects of CDDP, which causes cytostasis following intra-arterial infusion, and increased radiosensitivity from unevenly fractionated irradiation just after BAI. The radiotherapy group was considered a control in this study. The results of the combined group were limited to no CR, PR in 33 patients and NC in two with a period of 30 +/- 13 days for 50% reduction of tumor, superior to the radiation group. There was no difference between the two groups in the rate of local recurrence (combined group: 63%). The combined group showed 28 months of MST in cause-specific survival, a significant difference. Survival rates were 71% at one year, 27% at three years, and 15% at five years, including three survivors without recurrence. Stage III a patients in the combined group showed a better outcome than stage III b patients in the same group, and stage III a patients in the radiation group. Although radiation pneumonitis as a fatal side effect was noted in one patient of the combined group, the combined therapy presented here seemed to improve the prognosis of locally advanced lung cancer if properly indicated.

Aged↗

Carbon-11-methionine PET evaluation of intracerebral hematoma: distinguishing neoplastic from non-neoplastic hematoma.

UNLABELLED: We evaluated whether PET with L-methyl-11C-methionine (11C-methionine) was clinically useful in distinguishing neoplastic from non-neoplastic intracerebral hematoma. METHODS: We examined eight patients with neoplastic (n = 4) or non-neoplastic (n = 4) intracerebral hematomas between 5 and 68 days after the bleeding episode using PET with 11C-methionine (Met-PET). RESULTS: Carbon-11-methionine accumulated in the area surrounding the hematoma in both groups, except in one patient with an acute hypertensive hematoma. Between 22 and 45 days after the ictus, non-neoplastic hematomas showed increased 11C-methionine accumulation largely in accordance with the contrast-enhanced areas on CT or MR images; whereas between 14 and 68 days after bleeding, neoplastic hematomas showed increased 11C-methionine accumulation that extended beyond the contrast-enhanced areas on CT or MR images. The intensity of 11C-methionine accumulation in tumor tissue was greater than that in non-neoplastic hematomas. CONCLUSION: Preliminary results suggest that Met-PET can distinguish neoplastic from non-neoplastic hematomas on the basis of differences in lesion extent compared with CT or MR findings.

Adult↗

[Effect of inhaled vancomycin hydrochloride on elimination of methicillin-resistant Staphylococcus aureus].

Vancomycin hydrochloride (VCM) is one of the most useful drugs in treating methicillin-resistant Staphylococcus aureus (MRSA) infections. Intravenous administration of the drug is, however, not appropriate in patients with impaired renal or liver function. Thus, we studied the effect of inhaled VCM on MRSA. Fifty-one patients with MRSA in their sputum (35 men and 16 women 21, in the "infected" group and 30 in the "colonized" group, mean age 76.4 years) were studied. MRSA was eliminated in 84.3% of the patients (43 of 51 patients), and the average time required for elimination was 14.7 days. MRSA colonization or infection recurred in 46.5% of the patients (20 of 43 patients), and the duration from elimination until recurrence of MRSA averaged 28 days. Eight patients in whom MRSA was not eliminated by inhaled VCM were not clinically distinguishable from other patients, but their performance status was worse. Two hours after VCM was inhaled, serum VCM concentrations were unmeasurable in 7 patients. The VCM level in sputum peaked at 262.5 micrograms/g just after inhalation, and then gradually decreased. No side effects of this treatment were observed. These results suggest that inhaled VCM can be used to eliminate MRSA.

Administration, Inhalation↗

A novel biological aspect of ovarian oxytocin: gene expression of oxytocin and oxytocin receptor in cumulus/luteal cells and the effect of oxytocin on embryogenesis in fertilized oocytes.

Recently, several authors have reported the existence of oxytocin (OT) in mammalian granulosa-luteal cells after ovulation. The purpose of this study was to examine the evidence for gene expression and localization of OT and OT receptor (OTR) in the cumulus cells surrounding the oocytes. Cumulus cells with mature oocytes were obtained from experimental and clinical in vitro fertilization-embryo transfer (IVF-ET) programs. OT and OTR gene expression was analyzed with reverse transcriptase-polymerase chain reaction (RT-PCR) and RT-PCR/single strand conformation polymorphism (SSCP). OT gene expression was detected in mouse and human cumulus cells. The results of RT-PCR/SSCP showed that the structure of OT mRNA in cumulus cells was similar to that in the hypothalamus. Furthermore, OTR gene expression was clearly demonstrated in human cumulus cells, and a weak positive signal was observed in human oocytes. Immunocytochemical staining of OTR was clearly detected in human cumulus cells. The rate of mouse blastocyst development was significantly higher in the group cultured with OT than that without OT. These results are the first observations of simultaneous OT and OTR gene expression in cumulus cells, suggesting that ovarian OT might have some physiological role in the early stage of embryo development.

Animals↗

Blockade of the renin-angiotensin system in heart failure in conscious dogs.

OBJECTIVE: To study the different cardiac and renal hemodynamic effects of an angiotensin converting enzyme inhibitor and an angiotensin II receptor antagonist in experimental heart failure in conscious dogs. DESIGN AND METHODS: We compared the effects of the angiotensin converting enzyme inhibitor, captopril, with those of the angiotensin II (Ang II) subtype-1 receptor antagonist, losartan, on hemodynamics and hormonal changes in congestive heart failure by rapid ventricular pacing on conscious dogs. Furthermore, we characterized the Ang II receptors in canine heart, using the canine cardiac membrane fraction in heart failure. RESULTS: Acute intravenous administration of captopril improved the cardiac output by 19% (P < 0.01) but losartan did not, although blockade of the renin-angiotensin system by losartan (1.1 mumol/kg) or captopril (0.69 mumol/kg) induced similar changes in the plasma renin activity, norepinephrine and arginine vasopressin, and a similar decrease in mean arterial pressure (-10 mmHg). Renal blood flow was increased by either losartan or captopril. In the binding study, losartan produced a single displacement curve (IC50 = 0.25 mumol/l), while the Ang II subtype-2 (AT2) receptor antagonist PD123319 did not, indicating that the predominant Ang II receptor is type-1 (AT1) in canine heart. Neither the ratio of AT1 to AT2 receptors nor the receptor density changed with the development of heart failure. CONCLUSIONS: The lack of effect of losartan on cardiac output may be the result of its inability to block non-AT1 receptor-mediated Ang II activities adequately. Captopril may improve cardiac output by means of mechanisms not mediated by Ang II, such as locally increasing bradykinin.

Angiotensin II↗

Novel dual inhibitors of 5-lipoxygenase and thromboxane A2 synthetase: synthesis and structure-activity relationships of 3-pyridylmethyl-substituted 2-amino-6-hydroxybenzothiazole derivatives.

As part of our search for novel antiinflammatory drug candidates, we have designed and synthesized a series of 3-pyridylmethyl-substituted 2-amino-6- hydroxybenzothiazoles. Introduction of a 3-pyridylmethyl group into the 2-amino group (type-A) or the benzene ring (type-B) of 2-amino-6-hydroxybenzothiazoles imparted dual inhibitory activity against the production by glycogen-induced peritoneal cells of rat (in vitro) of leukotriene B4 (LTB4) and thromboxane A2 (TXA2), while not significantly inhibiting that of prostaglandin E2 (PGE2). The observed inhibition of the former two arachidonic acid metabolites was indicated to be the result of a direct action on 5-lipoxygenase and TXA2 synthetase by a cell-free in vitro assay. On the other hand, the inhibitory activities against PGE2 production were for most compounds very weak, indicating that they did not inhibit cyclooxygenase. Structure-activity relationship studies concerning the position of the 3-pyridylmethyl group revealed that type-B compounds generally showed about 10-fold stronger inhibitory activity against TXA2 synthetase than type-A compounds. The position of the 3-pyridylmethyl group played an important role in TXA2 synthetase inhibition. When some of these compounds (8, 13a, 26a (E3040), 26b, 27b, and 28b) were orally administered in the rat TNB/ethanol-induced chronic colitis model (100 mg/kg), the production of both LTB4 and TXB2 in the rat colon was reduced (ex vivo). In addition, one type-B compound, 6-hydroxy-5,7-dimethyl-2-(methylamino)-4-(3-pyridylmethyl)benzothiazole (26a), demonstrated a therapeutic effect at treatments of 100 mg/kg po once daily for 11 days and showed almost comparable activity to sulfasalazine at a dose of 500 mg/kg, the reference drug for inflammatory bowel diseases, in this in vivo model.

Animals↗

Prostaglandin endoperoxide synthase-1 and -2 couple to different transmembrane stimuli to generate prostaglandin D2 in mouse bone marrow-derived mast cells.

The view that the two isoforms of prostaglandin-endoperoxide synthase (cyclooxygenase), PGHS-1 and PGHS-2, mediate physiologic and inflammatory processes, respectively, implies separate pathways of arachidonic acid metabolism with different benefits to the host. Functional segregation of these steps in endogenous arachidonic acid metabolism in a single cell in response to different stimuli is now demonstrated. When mouse bone marrow-derived mast cells developed in interleukin-3 (IL-3)-containing medium were cultured with c-kit ligand in combination with IL-10 and IL-1 beta, transient expression of PGHS-2 mRNA and protein occurred in a dose- and time-dependent fashion, accompanied by substantial release of prostaglandin D2 (PGD2) into the culture medium from 2 to 10 h. In contrast, induction of PGHS-2 did not mediate an increase in PGD2 generation in response to stimulation with IgE and antigen. After a longer period of culture, from 24 to 48 h, the expression of PGHS-1 increased, as did the increase in IgE/antigen-dependent generation of PGD2. Dexamethasone, which inhibited the induction of PGHS-2 but not PGHS-1, and a PGHS-2-selective inhibitor suppressed cytokine-induced PGD2 generation but not IgE-dependent PGD2 generation. Thus, at a time when both PGHS-1 and PGHS-2 are present in bone marrow-derived mast cells, they function independently by coupling to different stimulus-initiated pathways to PGD2 generation from endogenously derived arachidonic acid.

Animals↗

Molecular mechanisms for B lymphocyte selection: induction and regulation of antigen-receptor-mediated apoptosis of mature B cells in normal mice and their defect in autoimmunity-prone mice.

Apoptosis (programmed cell death) has been suggested to be involved in clonal elimination of self-reactive lymphocytes for the normal function of the immune system. By crosslinking the antigen receptor (surface immunoglobulin; sIg) on the peritoneal B cells of normal mice, we found that strong crosslinking of sIg induces apoptosis of mature B cells, suggesting that interaction with membrane-bound self-antigens may eliminate self-reactive mature B cells by apoptosis. Antigen-receptor-mediated B cell apoptosis is blocked when a signal is transduced via the CD40 molecule on the B cell surface. Because the ligand of CD40 (CD40L) is expressed on activated T helper cells, B cells may escape from apoptosis and are activated when the immune system interacts with foreign antigens, which are normally able to activate T helper cells. Moreover, sIg crosslinking fails to induce apoptosis of both bcl-2-transgenic mice and autoimmune-disease-prone New Zealand mice. In these mice, the defect in sIg-mediated apoptosis of mature B cells may allow generation of self-reactive B cells, resulting in pathogenic consequences.

Animals↗

Dual regulation of cytosolic phospholipase A2 in mast cells after cross-linking of FC epsilon-receptor.

We have reported previously that cultured mast cells (MC) express three discrete phospholipases A2 (PLA2s), one of which corresponds to arachidonoyl-preferential cytosolic PLA2 (cPLA2). In the present study, we investigated the possible role of cPLA2 in eicosanoid synthesis by activating mouse bone marrow-derived mast cells (BMMC) through cross-linking of the high affinity IgE receptor (Fc epsilon RI) with a specific Ag. BMMC released arachidonic acid within 2 min after Fc epsilon RI cross-linking. A rapid, transient phosphorylation of cPLA2 was observed after Fc epsilon RI cross-linking, reaching the maximum within 2 min, and accompanied by an increase of cPLA2 activity in the cell lysate. Exposure of BMMC to the IgE-Ag for longer periods resulted in a time-dependent increase of the cPLA2 protein. The increase was detected within 10 h after stimulation and reached the maximum within 30 h. Dexamethasone inhibited the Ag-stimulated cPLA2 induction significantly. cPLA2 activity in cells stimulated for 24 h was increased significantly, and suppressed in cells treated with dexamethasone. When the cells were exposed to IgE-Ag for 36 h and then challenged with a secondary agonist, thrombin, arachidonate release was augmented significantly in comparison with cells without the Ag pretreatment. Thus, cPLA2 activation in BMMC by short term exposure to the Ag might be regulated by post-Fc epsilon RI modification (phosphorylation) of pre-existing enzyme, whereas that observed after long term exposure might be explained by the increase in cPLA2 protein.

Animals↗