Biomedical subjects

T Murakami

Publications and source records attributed to T Murakami.

At least 379 records · Page 21Linked to original sources

PubMed1999

Atypical phenotype of charcot-marie-tooth disease type 1A.

Two sisters with a Charcot-Marie-Tooth disease type 1A (CMT1A) duplication, who had an unusual CMT1A clinical phenotype, are described. The 63-year-old proband presented with dysesthesia on the inner side of the right leg. Neurological examination revealed a localized sensory disturbance in the lower extremities and mild weakness in the feet and left hand. Her 61-year-old sister had experienced several episodes of acute paralysis, and neurological examination showed moderate, sensory-dominant polyneuropathy. A reduction of myelinated fibers with many onion-bulb formations were observed in the sural nerve of the proband, and electrophysiological studies showed reduced motor nerve conduction velocities in both sisters. To diagnose CMT1A, we developed a CMT1A duplication test based on detection of CMT1A-specific junction fragments using the long polymerase chain reaction (PCR) method. A 3.3-kb CMT1A-specific junction fragment was detected in both patients, and their neuropathy may therefore have been associated with CMT1A duplication.

Charcot-Marie-Tooth Disease↗

PubMed1999

Fat-suppressed T2-weighted MR imaging of hepatocellular carcinoma and metastases: comparison of conventional spin-echo, fast spin-echo, and echoplanar pulse sequences.

The purpose of our study was to compare the diagnostic accuracy of fat-suppressed T2-weighted magnetic resonance (MR) images obtained with conventional spin-echo (SE), respiratory-triggered fast SE, and breath-hold multishot SE echoplanar (EP) sequences for the detection of hepatocellular carcinoma and metastases. Images obtained with the three sequences in 17 patients (15 with cirrhosis) with 31 hepatocellular carcinomas and 14 patients with 45 metastases were retrospectively analyzed. Image review was conducted on a segment-by-segment basis; in all, 248 liver segments were reviewed separately and independently for detection of solid, malignant lesions. Diagnostic accuracy was evaluated with receiver-operating-characteristic (ROC) curve analysis. Diagnostic accuracy for hepatocellular carcinoma as determined by ROC curve analysis was better by a statistically significant amount for conventional SE (Az = 0.95) images when compared with respiratory-triggered fast SE (Az = 0.83, P < 0.05) and breath-hold multishot SE EP (Az = 0.80, P < 0.05) images. Conventional SE MR sequences should not be replaced with respiratory-triggered fast SE or breath-hold multishot SE EP sequences for T2-weighted MR imaging of patients with hepatocellular carcinoma in cirrhosis, unless sufficient contrast-enhanced dynamic MR imaging is subsequently performed.

Adult↗

PubMed1999

Evaluation of gadobenate dimeglumine in hepatocellular carcinoma: results from phase II and phase III clinical trials in Japan.

To evaluate the clinical efficacy of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging for hepatocellular carcinoma (HCC), we reviewed the results of clinical phase II and III trials in Japan. Gd-BOPTA was administered at a dose of 0.1 mmol/kg to 139 patients who were suspected to have HCC. Dynamic phase images [breath-hold T1-weighted gradient echo (GRE)], spin-echo (SE) images obtained within 10 minutes of injection, and delayed breath-hold GRE images obtained 40-120 minutes after injection were evaluated. All post-contrast images were compared with T1- and T2-weighted pre-contrast images. The contrast efficacy for the dynamic study was classified as ( ) or (++) in 92.1% (128/139), in 43.1% (59/137) with SE within 10 minutes of injection, and in 43.2% (60/139) with breath-hold GRE at delayed phase. The increase in lesion-liver contrast-to-noise ratio was best at the arterial phase of dynamic breath-hold GRE. Liver signal-to-noise ratio showed a mean 52.3% increase in delayed phase. Additional information at delayed phase compared with images acquired within 10 minutes of injection (including the dynamic study) was classified as ( ) or (++) in 28.1% (39/139). With regard to safety, the overall incidence of adverse reactions was 5.0% (7/141) of the patients who were suspected to have HCC, all of whom recovered within 12 hours without any sequelae. No clinically important changes were observed in the blood and urine laboratory tests. It was concluded that Gd-BOPTA was well tolerated and effective in both dynamic study and delayed static imaging for the diagnosis of HCC.

Adult↗

PubMed1999

Mutations in nonstructural protein 5A gene and response to interferon in hepatitis C virus genotype 2 infection.

An association has been reported between mutations in the amino acid residues 2209-2248 of the nonstructural protein 5A (NS5A) gene (interferon-sensitivity determining region [ISDR]) and interferon efficacy in hepatitis C virus (HCV)-1b infection. This relationship was analyzed in chronic HCV-2 infection. Forty patients with HCV-2a and 35 with HCV-2b were treated with interferon alfa for 6 months with a total dose of 468 to 860 million units. Pretreatment NS5A sequences were determined by direct sequencing. A higher complete and sustained response rate was observed in HCV-2a than in HCV-2b (70% vs. 34%; P =.003). Serum HCV-RNA levels were lower in complete responders than nonresponders in HCV-2a (P =.049) and HCV-2b (P =. 02). The number of amino acid mutations was greater in complete responders than nonresponders in NS5A2193-2228 (the region corresponding to the ISDR of HCV-1b) alone (P =.049), or NS5A2163-2228 consisting of NS5A2193-2228 plus its upstream region (P =.02) in HCV-2a, but not in HCV-2b. A significant inverse correlation was observed between serum HCV-RNA levels and the number of amino acid mutations in NS5A2193-2228 (P =.003) or NS5A2163-2228 (P =.005) in HCV-2a. With multivariate analysis, the number of substitutions in NS5A was an independent predictor for complete response in HCV-2a (odds ratio: 6.4; P =.03). Interferon efficacy is associated with amino acid variations in the NS5A protein in HCV-2a infection.

Adult↗

PubMed1999

Presymptomatic detection and treatment of Japanese carriers of the multiple endocrine neoplasia type 2A gene.

DNA extracted from the peripheral blood leukocytes of 36 members of five families with multiple endocrine neoplasia (MEN) type 2A was analyzed for mutations of exons 10, 11, 13, 14, and 16 of the RET proto-oncogene by nonisotopic polymerase chain reaction-single-strand conformation polymorphism analysis and automated DNA sequencing. Germline mutations were found in all 9 of the affected individuals and in 6 of the 27 individuals of unknown status. A 70-year-old man who had been completely asymptomatic before genetic diagnosis underwent left adrenalectomy and total thyroidectomy, and was found to have pheochromocytoma and multifocal micromedullary thyroid carcinoma (MTC). A 32-year-old man and a 15-year-old boy, with elevated calcitonin levels detected by the C-cell-stimulation test, but no evident thyroid tumor, underwent total thyroidectomy. Histopathological diagnosis revealed multiple micro MTCs. A 7-year-old girl without evidence of a thyroid tumor or an elevated calcitonin level is being followed up. The remaining two subjects with an evident thyroid tumor and elevated calcitonin levels refused surgery. These results suggest that genetic screening for MEN type 2 afflicted family members can facilitate the presymptomatic detection of gene carriers. Thus, we must carefully evaluate whether immediate prophylactic total thyroidectomy is indicated for gene carriers of MEN 2A without an evident thyroid tumor or elevated calcitonin levels.

Adolescent↗

PubMed1999

Early detection of the no-reflow phenomenon in reperfused acute myocardial infarction using technetium-99m tetrofosmin imaging.

Evaluation of myocardial perfusion in the early stage of acute myocardial infarction (MI) is clinically important for adjunctive therapies to minimize infarct size. To determine the role of early scintigraphic detection of impaired myocardial reperfusion after primary coronary angioplasty (PTCA) in patients with acute MI, semiquantitative technetium-99m tetrofosmin single-photon emission tomographic (SPET) imaging was performed before primary PTCA (before; area at risk), 60 min after PTCA (after) and at 1 month (1 M; final infarct) in 35 patients with acute MI. The left ventricle was divided into 13 segments and the defect score was calculated as the sum of the perfusion defect of each segment, from 3 (complete defect) to 0 (normal perfusion). A significant myocardial perfusion change after PTCA was defined as a change in the defect score (before minus after PTCA) of >/=4. The echocardiographic asynergic score was defined as the number of asynergic (severe hypokinetic or akinetic) segments corresponding to the analogous segments on SPET images, and recovery of wall motion was calculated as absolute change in the asynergic score (before PTCA minus 1 M). Among the 35 patients, 15 (43%) had a change in the defect score of <4 (no reflow: group 1) while 20 had a change in the defect score of >/=4 (reflow: group 2). There were no significant differences between the two groups with respect to the time between admission to PTCA, revascularization time, collateral grade or Thrombolysis in Myocardial Infarction (TIMI) flow grade before PTCA. Despite the lack of a difference in area at risk between the two groups (group 1 = 12.8+/-4.3 and group 2 = 15.1+/-4.7), final infarct size in group 1 was significantly larger compared with that in group 2 (8.1+/-4.3 vs 4.9+/-3.0, P<0.001). Recovery of wall motion was significantly smaller in group 1 than in group 2 (4.3+/-1.7 to 3.5+/-1.5 vs 4. 1+/-2.1 to 1.6+/-1.6, P<0.001). In conclusion, a small change (<4) in defect score (scintigraphic no-reflow phenomenon) after primary PTCA indicates persisting impaired myocardial perfusion or irreversible cellular damage just after PTCA which is associated with poor recovery of wall motion, as compared with that observed in cases of reflow (>/=4 in defect score).

Aged↗

PubMed1999

MR imaging of non-squamous vaginal tumors.

We reviewed the MR images and pathologic findings of five cases of primary vaginal neoplasms of non-squamous origin. Histologic types consisted one case each of adenocarcinoma, adenosarcoma, melanoma, lymphoma, and neurilemoma. Magnetic resonance imaging was found useful for evaluating the type and the extension of vaginal tumors.

Adult↗

PubMed1999

Quantitative analysis of three-dimensional complexity and connectivity changes in trabecular microarchitecture in relation to aging, menopause, and inflammation.

There are several types of bone loss besides that associated with normal aging, eg, that associated with the menopause, and that associated with chronic inflammation, and these are considered to be caused by different mechanisms. The microarchitecture that results from these different bone-loss mechanisms would not be the same. The purpose of this study was to investigate differences in the three-dimensional trabecular microarchitecture in various types of osteopenia, using microcomputed tomography (Micro-CT). Thirty-five Fisher 344 rats were divided into five groups (control, young, senile, ovariectomized [OVX], and inflammation-mediated osteopenia [IMO]) and distal femoral metaphysis was scanned by Micro-CT to nondestructively acquire a 3-D CT stack consisting of 50 consecutive slices at a spatial resolution of 26 microm. The volume of interest, consisting of the secondary spongiosa, was prepared to analyze the 3-D trabecular microarchitecture. A parametric analysis was carried out using bone volume fractions, fractal dimensions, and the first Betti number in order to quantitatively express the mass, complexity, and connectivity of the trabecular microarchitecture. Complexity tended to decrease with age, and decreased significantly in estrogen deficiency-induced and inflammation-mediated osteopenia. Connectivity did not appear to change with aging, but was significantly decreased in estrogen deficiency-induced and inflammation-mediated osteopenia. There was no significant difference between the OVX and the IMO groups.

Age Factors↗

PubMed1999

Septal branch right ventricular fistula: a complication in coronary artery snaring.

We report a septal branch right ventricular fistula complicated after coronary snaring in coronary artery bypass surgery without aortic cross-clamping. The tip of the needle of the snaring suture is made blunt in order to decrease the risk of mechanical injury, but trauma to the septal branch is possible. This rare complication of snaring should be taken into consideration in performing aortic nonclamping coronary artery bypass surgery.

Aged↗

PubMed1999

A new friction tester of the flexor tendon.

We have developed a new device to measure the friction force and calculate the friction coefficient between a rabbit flexor tendon, a pulley and a proximal phalanx. The flexor digitorum fibularis tendon of a rabbit was taken intact with the proximal phalanx, and tendon pulleys were attached to both ends of the bone. Both ends of the tendon were clamped to acrylic plates and connected to stainless-steel plates equipped with strain gauges. A pretension of 1.96 N was applied so as not to loosen the tendon. The proximal phalanx was fixed to an acrylic plate on the actuator, which gave 8 mm of transfer to the acrylic plate at a speed of 2 mm/s. The interface between the tendon and the surrounded tissue created the friction force, when the load was applied on the distal pulley. The friction force could be obtained from the difference between the tension of both ends of the tendon, which was measured with strain gauges and sampled with a personal computer. The friction force and the friction coefficient were calculated from the measured force and the applied load. The load and the pre-loading time, which was defined as loading duration before gliding, were varied in order to observe the change of the friction coefficient. The friction coefficient was not affected by the load and increased with the pre-loading time. The value of mu(s) ranged from 0.027 to 0.111 (0.072 +/- 0.023), and that of (mu)d ranged from 0.010 to 0.069 (0.039 +/- 0.014) (pre-loading time was 5 s). Our method will allow for the examination of various surgical treatments and lubricants. Moreover, it can be applied to other tissues of any animals with similar structures to the rabbit's digitorum.

Animals↗

PubMed1999

Human livers with cirrhosis and hepatocellular carcinoma have less mitochondrial DNA deletion than normal human livers.

We measured the populations of mutated mitochondrial DNAs with the 7,436 bp or the 4,977 bp deletion from apparently normal human liver and human livers with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The amount of the mutated mitochondrial DNA was at the same level between normal and chronically hepatitic livers but was significantly lower in human livers with cirrhosis and hepatocellular carcinoma, especially the latter, suggesting that the mutated mitochondrial DNAs may be decreased with the progress of liver disease from chronic hepatitis to cirrhosis and hepatocellular carcinoma. This phenomenon is opposite to that occuring in the ageing process.

Adult↗

PubMed1999

Effects of chronic liver diseases on mitochondrial DNA transcription and replication in human liver.

To evaluate the effects of chronic liver diseases on mitochondrial DNA (mtDNA) transcription and replication, nuclear respiratory factor-1 (NRF-1) mRNA, mitochondrial transcription factor A (mtTFA) mRNA, a RNA component of ribonuclease (RNase) for mitochondrial RNA processing (MRP), mitochondrial cytochrome b mRNA, and mtDNA were measured in normal, chronically viral-hepatitic and cirrhotic human livers. The mRNA levels of the regulatory factors for mitochondrial gene (NRF-1 and mtTFA) and cytochrome b were significantly increased by chronic hepatitis (160, 280, and 175%, respectively) compared with those in normal livers, but were not different between cirrhotic and normal livers. On the other hand, concentrations of mtDNA and RNA component of RNase MRP were not different among normal, chronically hepatitic, and cirrhotic livers. These results suggest that either persistent hepatitis viral infection or repeated cell necrosis and regeneration in chronically hepatitic liver may be associated with increase in mtDNA transcription.

Adult↗

PubMed1999

Changes in islet capillary angioarchitecture coincide with impaired B-cell function but not with insulin resistance in male Otsuka-Long-Evans-Tokushima fatty rats: dimorphism of the diabetic phenotype at an advanced age.

The Otsuka-Long-Evans-Tokushima fatty (OLETF) rat is a genetic model of spontaneous development of non-insulin-dependent diabetes mellitus (NIDDM) established as an inbred strain after 20 generations of selective breeding. Although they are thought to be genetically homogeneous, they show a dimorphism regarding the diabetic phenotype at an advanced age, with one remaining obese and modestly diabetic while the other becomes lean and overtly diabetic. To clarify the causes for this divergence, we examined the physical, biochemical, and histopathological features in rats at 50 weeks of age, including an analysis of islet angioarchitecture. Sixty-one of 85 male OLETF rats lost weight, while the remainder remained obese. Mean nonfasting plasma glucose in the lean group was 21.8+/-4.6 mmol/L, significantly higher versus the obese group (10.5+/-1.4 mmol/L) and the age-matched control Long-Evans-Tokushima-Otsuka (LETO) group (7.1+/-0.6 mmol/L). Morphological studies of the pancreas from the lean group showed enlarged multilobulated fibrotic islets with a paucity of B cells, whereas islets from the obese group appeared slightly enlarged and showed a relative abundance of B cells. The fine capillaries that form a network in the islets were extremely sparse in the lean group, resulting in a defective glomerular-like configuration, whereas those from the obese group were dense, forming a nearly typical glomerular-like configuration. Increased plasma insulin responses to oral and intravenous (i.v.) glucose and i.v. glucagon loads were nearly absent in the lean group, while they were evident in the obese group, although to a lesser extent compared with the LETO group. Mean insulin secretory output from the perfused pancreas in response to 11.1 mmol/L glucose in the lean group (3.5+/-2.2 pmol/20 min) was significantly lower versus the obese group (8.8+/-6.5 pmol/20 min) and LETO group (22.0+/-10.8 pmol/20 min). Similarly, pancreatic insulin content was significantly lower in the lean group (9.3+/-6.1 microg) versus the others (26.1+/-17.3 microg for obese and 41.1+/-24.8 microg for LETO). In vivo insulin-stimulated glucose uptake measured by a euglycemic clamp technique was significantly higher in the lean group compared with the obese group. These results demonstrate that the dimorphism regarding the diabetic phenotype in male OLETF rats at 50 weeks of age was due to differences in the number of islet B cells, which could be the result of a variation in the capacity for B-cell proliferation among male OLETF rats.

Aging↗

PubMed1999

Interaction between purinoceptor subtypes on hippocampal serotonergic transmission using in vivo microdialysis.

The effects of purinoceptor subtypes on hippocampal extracellular serotonin levels were determined by using in vivo microdialysis. Perfusion with adenosine-5'-triphosphate (ATP) for 20 min produced concentration-dependent changes in hippocampal extracellular serotonin levels, which consisted of an initial rise phase, with levels increasing to 309% of control with 100 microM ATP, followed by a later rebound reduction phase, with levels decreasing to 6% of control. The P2X1-7 active P2 purinoceptor agonist, 2-methylthioATP (2-MeSATP: 100 microM) increased the extracellular serotonin level drastically (638%), while the P2X1,3 active P2 purinoceptor agonist, alpha, beta-methylene-L-ATP (alpha, beta-meATP: 100 microM) produced a small increase (132%) in the serotonin level. The P2X1,2,3,5,7 active P2 purinoceptor antagonist, suramin (100 microM), reduced the basal serotonin level (86%) and the ATP-evoked initial rise phase (from 309 to 254%) without affecting the late reduction phase. The adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT: 50 microM) potentiated the rising phase (167%) and abolished the subsequent ATP-evoked reduction phase. Perfusion with CPT and an adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX: 10 microM), reduced the ATP-evoked initial rise (to 181%) and abolished the late reduction phases of serotonin release. These results indicate that ATP-evoked hippocampal serotonin release is composed of an initial rise phase and a later reduction phase. The ATP-evoked initial rise phase might be produced by an activation of P2X purinoceptor function, whereas the late reduction phase was modulated by the activation of adenosine A1 receptor function by adenosine, metabolized from ATP in the synaptic cleft.

Adenosine Triphosphate↗

PubMed1999

Structure and function of type I and II macrophage scavenger receptors.

Type I and II macrophage scavenger receptors are implicated in the pathologic deposition of cholesterol during the atherogenesis. There is a charged collagen structure of type I and II receptors identified as a ligand binding domain, which can recognize a wide range of negatively charged macromolecules including oxidized LDL as well as damaged or apoptotic cells and pathogenic micro-organisms. After binding these ligands can be either internalized by endocytosis, phagocytosis, or remain at cell surface and mediate the adhesion. Under physiological condition, scavenger receptors serve to scavenge or clean up cellular debris and other related materials, as well as playing a role in the hosts defence. In pathological condition, they mediate the recruitment, activation and transformation of macrophages and other cells, which may be related to the development of atherosclerosis and to disorders caused by the accumulation of denatured materials, such as Alzheimer's disease.

Alzheimer Disease↗

PubMed1999

Biphasic effects of zonisamide on serotonergic system in rat hippocampus.

To study the mechanisms of antiepileptic action of zonisamide (ZNS), we determined the effects of ZNS on extracellular, total levels and re-uptake activity of serotonin (5-HT) in rat striatum and hippocampus. After acute administrations, plasma ZNS concentrations associated with anticonvulsive action (effective concentrations) increased the total levels of 5-HT, its metabolise (5-hydroxyindoleacetic acid: 5-HIAA) and precursor (5-hydroxytryptophan: 5-HTP). After chronic administration of ZNS, effective plasma concentrations also increased the extracellular and total levels of 5-HT, 5-HIAA, and 5-HTP. On the other hand, after both acute and chronic administrations of ZNS, a supra-effective ZNS concentration either decreased or did not affect the total levels of these substances. Therefore, the stimulatory effects of ZNS on the 5-HT system were reduced by an increase in ZNS concentration to supra-effective concentrations. ZNS concentrations of 30-1000 microM did not affect hippocampal 5HT re uptake activity in vitro. These results suggest that ZNS has biphasic effects on the 5-HT system, in that effective concentrations of ZNS enhance and supra-effective concentrations of ZNS reduce the function of the 5-HT system. These biphasic effects of ZNS on the 5-HT system may be involved in the mechanisms of action of the antiepileptic and psychotropic effects, and side effects of ZNS.

5-Hydroxytryptophan↗

PubMed1999

Effects of zonisamide on K+ and Ca2+ evoked release of monoamine as well as K+ evoked intracellular Ca2+ mobilization in rat hippocampus.

To clarify the effects of zonisamide (ZNS) on neurotransmission and intracellular Ca2+ mobilization, both Ca2+ and K+ evoked hippocampal releases of dopamine (DA) and serotonin (5-HT) were determined by in vivo microdialysis, and K+ (25 and 50 mM) evoked elevation of intracellular Ca2+ level was determined by fluorescence microscopy in vitro. Therapeutic concentrations of ZNS had different effects on Ca2+ and K+ evoked release of monoamine. ZNS stimulated Ca2+ evoked monoamine release, while ZNS inhibited K+ evoked monoamine release. ZNS inhibited K+ evoked elevation of hippocampal intracellular Ca2+ levels in a concentration dependent manner. These results suggest that ZNS inhibits the depolarization induced by neuronal excitation, whereas ZNS might enhance the N-type Ca2+ channel activity or N-type Ca2+ channel related exocytosis mechanisms.

Animals↗

PubMed1999

Structure-related inhibitory activity of oleanolic acid glycosides on gastric emptying in mice.

We examined the effects of various oleanolic acid oligoglycosides obtained from traditional herbs on gastric emptying in non-nutrient meal- or nutrient meal-loaded mice. Test samples were given orally to fasted mice 0.5 h before loading of test meals. Oleanolic acid 3-O-monodesmosides [oleanolic acid 3-O-glucuronide (3, 12.5-50 mg/kg), momordin Ic (4, 25 and 50 mg/kg), momordin I (6, 12.5-50 mg/kg), and 28-O-deglucosyl-chikusetsusaponins IV (8, 12.5-50 mg/kg) and V (10, 50 mg/kg)] were found to show inhibitory effects on gastric emptying in 1.5% CMC-Na test meal-loaded mice. 4, 6, and 8 also inhibited gastric emptying in mice given 40% glucose test meal, milk test meal, and 60% ethanol test meal. 3 inhibited gastric emptying in mice given milk test meal or 60% ethanol test meal, but lacked significant inhibition in 40% glucose test meal-loaded mice. 10 (50 mg/kg) also slightly inhibited gastric emptying in milk test meal-loaded mice, but lacked the significant inhibition in mice given 40% glucose or 60% ethanol test meal. Whereas oleanolic acid 3,28-0-bisdesmosides [momordin IIc (5), chikusetsusaponins IV (7) and V (9)], oleanolic acid 28-O-monodesmoside [compound O (2)], and their common aglycon [oleanolic acid (1)] showed no such effects at dose of 50 mg/kg. 28-O-Deglucosyl-chikusetsusaponin V (10) showed a little inhibition in these experiments. These results indicate that both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 28-ester glucoside moiety and 2'-O-beta-D-glucopyranoside moiety reduce the activity.

Animals↗