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Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 235 records · Page 13Linked to original sources

The utility of Nitroderm TTS in angina pectoris: long-term treatment after switching from long-acting oral isosorbide dinitrate.

Long-acting oral isosorbide dinitrate (ISDN) was replaced by Nitroderm TTS, and the utility of this drug in long-term treatment was assessed in 69 patients with angina pectoris. The frequency of attacks (p < 0.001) and the consumption of sublingual nitrate tablets (p < 0.01) were found to be significantly lower at 2 weeks to 6 months than in the observation period in patients who experienced attacks or received sublingual tablets during the observation period. On the other hand, no significant time-lapse changes from the observation period were noted in patients who experienced no attacks or received no sublingual tablets during the observation period. The symptoms of adverse effects were mild. The improvement rates (improved) of subjective symptoms and electrocardiogram (ECG) in Group A were about 50% after 6 months. On the other hand, the improvement rates (not aggravated) of subjective symptoms and ECG in Group B were more than 90%. Nitroderm TTS is considered a useful plaster preparation which can be used for sufficiently extended periods of time because its efficacy was as high as, or higher than, that of oral ISDN when this drug was administered over a long period of time after a switch from long-acting oral ISDN in angina pectoris patients.

Administration, Cutaneous↗

Allelotype study of esophageal carcinoma.

To investigate genetic features of esophageal cancer, we have examined 93 squamous cell carcinomas of the esophagus for loss of heterozygosity (LOH), using 41 restriction fragment length polymorphism (RFLP) markers representing all autosomal chromosomes. Allelic losses at frequencies of at least 30% were observed at loci on chromosomal arms 3p (35%), 3q (30%), 5q (36%), 9p (57%), 9q (60%), 10p (33%), 13q (43%), 17p (62%), 17q (46%), 18q (38%), 19q (32%), and 21q (37%). These results suggest that several putative tumor suppressor genes, in addition to the cyclin D and TP53 genes that are sometimes mutated in esophageal carcinomas, may be associated with development and/or progression of esophageal cancer. By a comparison of LOH on each chromosomal arm with clinicopathological parameters, we have found a significant correlation between LOH on 19q and regional lymph node metastases. Interestingly, the frequency of LOH on 17q was significantly higher in tumors in female patients (12 of 14 cases) than in those in male patients (20 of 56 cases) (P = 0.0009 by Fisher's exact test). Furthermore, we examined for mutations of the APC gene on chromosome arm 5q. Screening of nearly one third of the APC coding region, including the MCR (mutation cluster region), revealed no alterations. Therefore, although allelic loss at the APC locus is frequent in squamous cell carcinomas of the esophagus, it is likely that a gene on 5q other than APC is involved in esophageal tumorigenesis.

Alleles↗

Establishment and characterization of synovial cell clones with integrated human T-cell leukemia virus type-I.

Human T cell leukemia virus type-I (HTLV-I)-integrated synovial cell clones (SCCs) were established from four HTLV-I-infected patients with chronic proliferative arthropathy. Extracted DNAs of these SCCs were examined for the existence of HTLV-I proviral DNA. Electron microscopic analysis and immunohistochemical staining were also performed to examine the nature of the HTLV-I integrated SCCs. SCCs derived from all four patients consisted of either HTLV-I integrated or nonintegrated cells. HTLV-I integrated SCCs also produced viral messenger RNA which was detected by reverse transcriptase-polymerase chain reaction as well as viral protein which was detected by immunohistochemical staining. Phenotypically, these SCCs containing HTLV-I proviral DNA were shown to be all cell types as observed by electron microscopic analysis and immunohistochemical analysis. Moreover, expression of HTLV-I glycoprotein was greater in SCCs with a monocyte marker. These findings suggest that SCCs harboring HTLV-I have an important role in synovial hyperplasia.

Aged↗

Pantropic retroviral vector-mediated gene transfer, integration, and expression in cultured newt limb cells.

Limb regeneration is a unique developmental phenomenon restricted to certain urodeles in which limb cells dedifferentiate and produce the blastema and then redifferentiate into the tissues that compose the missing part. Genetic modification of the blastema cells would greatly facilitate understanding the programmed gene expression that results in the reconstitution of the limb. To test whether pantropic retroviral vectors pseudotyped with the vesicular stomatitis virus G glycoprotein could mediate gene transfer into blastema cells, we infected a stable newt limb cell line and demonstrated integration and expression of the provirus. Thus, pantropic retroviral vectors offer a new tool for the study of limb regeneration and other developmental phenomena in amphibia.

Animals↗

Inhibition of neovascularization in vivo by gold compounds.

As mononuclear cell infiltration and growth of pannus critically depend on synovial neovascularization in rheumatoid arthritis (RA), inhibition of the synovial blood vessels would have the potential to reduce rheumatoid inflammation. In this investigation, we studied the effect of gold sodium thiomalate (GST) and auranofin (AUR) on neovascularization in vivo by using a micropocket technique. Both GST and AUR suppressed rabbit corneal neovascularization in a dose-dependent fashion. Significant inhibition was observed by 3 mg/kg GST and 1 mg/kg AUR injected intravenously every other day. These injections maintained serum gold concentrations at the level of 2-5 micrograms/ml and less than 2 micrograms/ml in GST- and AUR-injected rabbits, respectively. These are concentrations attained in the serum or synovium of rheumatoid patients treated by gold compounds. Similar inhibition was observed by both intramuscular administration of GST and oral administration of AUR. In contrast, no inhibition was observed when non-steroidal anti-inflammatory drugs (NSAIDs; 20 mg/kg acetylsalicylic acid, 10 mg/kg ibuprofen and 10 mg/kg indomethacin) were injected intravenously on a daily basis. These results suggested that gold compounds have an antiangiogenic effect in vivo. The inhibition of neovascularization by gold compounds suggested that they may suppress rheumatoid synovitis by reducing the number of small blood vessels required for mononuclear cell infiltration and synovial tissue proliferation.

Animals↗

Inhibition of mitogen-induced response of human peripheral blood mononuclear cells by bucillamine, a new antirheumatic sulfhydryl drug.

The mechanism of action of bucillamine, [N-(2-mercapto-2-methylpropionyl)-L-cysteine] (BC), a novel antirheumatic drug that is used in patients with rheumatoid arthritis (RA), was compared with that of D-penicillamine (DP). BC inhibited phytohemagglutinin (PHA)-induced DNA synthesis of peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, and this inhibition occurred both in the presence and absence of copper, whereas DP-induced inhibition required the presence of cupric ions. Significant inhibition of DNA synthesis was observed at a BC concentration of 10 micrograms/ml. The disulfide form of BC, but not DP disulfide, suppressed the proliferation of PBMCs. After preincubation of human peripheral blood T lymphocytes or Møs with BC or DP, these cells were combined and the overall PHA response was estimated. Inhibition of the PHA response was observed following pretreatment of either T lymphocytes or Møs with BC, whereas inhibition was attained only when T lymphocytes were pretreated with DP and copper. As sulfhydryl agents produce hydrogen peroxide in the presence of cupric ions, the effect of catalase on DP- and BC-induced inhibition of PBMC DNA synthesis was examined. Catalase partially reversed the BC-induced inhibition of DNA synthesis of PBMCs, and it restored the inhibition by DP and copper almost to the control level. These results suggest that BC suppresses the function of both T lymphocytes and Møs in the mitogen response of PBMCs, whereas the action of DP is targeted at T lymphocytes.

Anti-Inflammatory Agents, Non-Steroidal↗

Better grading systems for evaluating the degree of lymph node invasion in cancer of the thoracic esophagus.

To evaluate the quality of various grading systems for lymph node invasion in cancer of the thoracic esophagus, the surgical results of 142 patients who underwent systematic lymph node dissection with curative intent were analyzed. The survival probability of patients in the same grade was modeled using a Weibull distribution and the parameters were estimated by the maximum likelihood principle. The quality of each grading system was measured by the Akaike Information Criterion (AIC) of the estimated statistical model, by which the smaller the AIC of a grading system, the smaller the loss of information for predicting outcomes. The AIC of the TNM grading of the International Union Against Cancer, the grading of the Japanese Society for Esophageal Diseases, and the grading designed according to the total number of positive lymph nodes became substantially smaller in that order. The AIC of grading systems variously designed on rather simple criteria were examined with the aim of creating a better grading system. It was concluded that a grading system based on the total number of positive nodes and the state of the paratracheal and/or middle mediastinal node groups was better than the other systems examined.

Esophageal Neoplasms↗

Pentoxifylline and intravenous gamma globulin combination therapy for acute Kawasaki disease.

We compared the efficacy of oral administration of pentoxifylline (PTX) and intravenous infusions of gamma globulin (IVGG) combination therapy with that of IVGG in reducing the frequency of coronary-artery lesions (CAL) in children with Kawasaki disease (KD), in a randomized trial. All patients with KD received acetylsalicylic acid (30 mg/kg per day), until the 30th day, after the onset of fever, followed by daily acetylsalicylic acid at a dose of 3-5 mg/kg per day there-after, and intravenous IVGG, 200 mg/kg per day, for 5 consecutive days. In addition, patients randomly assigned to PTX and IVGG combination therapy groups received oral PTX at a dosage of 10 mg/kg per day (low-dose) or 20 mg/kg per day (high-dose), in three divided doses until the 30th day. Patients with KD were all free from CAL prior to treatment. We assessed the presence of CAL by two-dimensional echocardiography which was also done prior to treatment and then twice a week after hospital admission. We detected CAL in 3 of 18 patients (16.7%) in the IVGG therapy group, as compared with 2 of 18 patients (11.1%) in the low-dose PTX and IVGG combination therapy group. There were no significant difference between the two groups. In the next study, we detected CAL in 3 of 21 patients (14.3%) in the IVGG therapy group, as compared with none of 22 patients (0%) in the high-dose PTX and IVGG combination therapy group (chi 2 = 6.4, P < 0.02). No adverse side-effects were observed in 79 patients with KD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

Identification of asynergic but viable myocardium in patients with chronic coronary artery disease by gated blood pool scintigraphy during isosorbide dinitrate and low-dose dobutamine infusion: comparison with thallium-201 scintigraphy with reinjection.

To evaluate the ability of low-dose dobutamine and isosorbite dinitrate (ISDN) gated blood pool scintigraphy (GBPS) and thallium SPECT with reinjection to identify viability in asynergic myocardium, both procedures were performed in 38 consecutive patients with chronic coronary artery disease and left ventricular dysfunction. Twenty-two of the 38 patients with successful revascularization were analyzed. GBPS was performed at the baseline and during continuous infusion of low dose dobutamine (5 micrograms/kg/min) and ISDN (2 micrograms/kg/min). Cine mode GBPS wall motion was scored from normal (0) to dyskinesis (4) semiquantitatively. Forty-seven of 110 segments with severe asynergy at the baseline were analyzed. Viability determined by GBPS was defined as wall motion score improvement by more than 1 grade. Thallium viability was defined as the segment with redistribution or fill in with severe initial perfusion defect. GBPS was 76.7% sensitive and 70.6% specific for predicting post vascularization wall motion improvement (p < 0.005). Of 47 segments with severe asynergy, concordance of judgement was obtained in 40 segments (85.1%), and reversibility was correctly diagnosed in 34 of 40 patients (85.0%), but thallium with reinjection correctly identified tissue viability in 6 of 7 segments with discordance between 2 studies. These data suggest that most cases of reversible asynergy (hibernating myocardium) respond to ISDN and dobutamine, suggesting the possibility of predicting improvement by revascularization, although some underestimation of tissue viability remained to be resolved. Thallium with reinjection is superior to low-dose dobutamine + ISDN GBPS for the assessment of myocardial viability.

Adult↗

Serum levels of p60 soluble tumor necrosis factor receptor during acute Kawasaki disease.

To evaluate the role of tumor necrosis factor alpha (TNF-alpha) during acute Kawasaki disease, we measured p60 soluble tumor necrosis factor receptor (sT-NF-R) shedding into the circulation in 48 patients with acute Kawasaki disease, all of whom received intravenous infusions of gamma-globulin. Of the 48 patients, 5 had coronary artery lesions. Serum concentrations of p60 sTNF-R and TNF-alpha were measured by a sandwich enzyme immunoassay. Patients with Kawasaki disease had increased serum levels of p60 sTNF-R. We found a positive correlation between serum levels of p60 sTNF-R and levels of TNF alpha during acute Kawasaki disease. Moreover, patients with coronary artery lesions had higher levels of sTNF-R than did those without coronary artery lesions. Our findings indicate that p60 sTNF-R levels in serum may be useful for determining the severity of vascular damage during acute Kawasaki disease, and that patients with Kawasaki disease and high sTNF-R levels seem to be susceptible to coronary artery lesions even if they receive therapy with intravenous infusions of gamma-globulin.

Acute Disease↗

Developmental change in activity of red cell porphobilinogen deaminase and its electrophoretic variant in the Japanese population.

The activity of porphobilinogen deaminase (PBGD), an enzyme whose partial deficiency is associated with acute intermittent porphyria (AIP), changes during development. Little is known about the postnatal change of PBGD activity and the prevalence of its electrophoretic variant in the Japanese population. The activity of PBGD was measured fluorometrically in 194 infants aged 0-12 months, while isoelectric focusing of PBGD was performed in 400 healthy Japanese adults aged 20-45 years and 30 children with various hematological disorders aged 1-15 years. The PBGD level was 1.9 times higher in the neonates than in the adults, decreased abruptly during the first month of life, and reached the adult level at the age of 9 months. None of the 400 healthy Japanese adults and the 30 children with hematological disorders showed any electrophoretic variant. These results suggest that there is no need to consider any polymorphism in the gene dose study of PBGD and that the biochemical screening of AIP is applicable to since the late infancy.

Adult↗

A sibship with recurrent Kawasaki disease and coronary artery lesion.

Although epidemiologic studies of Kawasaki disease suggest an infectious etiology, the cause of this mysterious disease remains unclear. We describe the occurrence of five episodes of Kawasaki disease over a six-year period in three siblings. Two of the three children experienced recurrent Kawasaki disease and developed coronary artery lesions, which included giant coronary artery aneurysms in the youngest child. The non-contemporaneous occurrence of the disease in these three children emphasizes the importance of a genetic basis and/or environmental factors in the etiology of Kawasaki disease.

Child, Preschool↗

Surgical treatment of ossification of the posterior longitudinal ligament in the thoracic spine.

Thoracic ossification of the posterior longitudinal ligament (OPLL) is a rare entity causing thoracic myelopathy. Its surgical decompression is still challenging. Three patients admitted with progressive myelopathy due to thoracic OPLL are described. A transthoracic anterolateral approach was used in the first and second cases, in which OPLL was located at the T3-T4 and T5-T6 and at the T7-T8 levels, respectively. In the third case, a transsternal approach was adopted for OPLL at the T1-T2 level. The OPLL, including dural ossification, was removed by microsurgical techniques as extensively as possible. Myelopathy in all three cases became relieved or stable postoperatively. Operative procedures are described in detail. From the viewpoint of surgical anatomy, the selection of operative approach depends on the level of the OPLL. The authors emphasize that a transthoracic anterolateral approach is the treatment of choice for extensive anterior pathology such as OPLL involving more than two thoracic bodies below the T4. A transsternal approach can provide excellent access to a lesion at the upper three thoracic bodies.

Aged↗

Microsurgical anatomy of the lower cervical spine and cord.

The authors dissected the cervical spine and its surrounding structures from 40 adult cadavers under a surgical microscope. The anterior part of the spine and spinal cord was examined after vertebrectomy. The posterior longitudinal ligament (PLL) consists of two layers; the anterior one is termed the deep layer, and the posterior one is termed the superficial layer. These two layers adhered together loosely. In the lateral portion of the spinal canal, the superficial layer joined the periradicular sheath at the level of the intervertebral disc spaces and joined the dura mater at the level of the vertebral bodies. After the removal of the deep layer, the anterior internal vertebral venous plexus was seen on top of the lateral part of the superficial layer. The venous plexus was embedded between the double-layered PLLs, was not located in the epidural space, and was not seen in the medial part of the PLL. The PLL without venous channels on top of it was about 10 mm in width at the levels of the intervertebral disc and about 5 mm at the levels of the vertebral body. The anterior root exit zone (AREZ) was an elliptical shape; the transverse length of the AREZ was about 2 mm, and the longitudinal length was 10 to 15 mm. The average number of anterior rootlets on the AREZ was 17 to 25 and tended to decrease in the lower cervical spinal cord. The posterior structures were examined after en bloc laminectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of leukotriene D4 on myocardial blood flow and high energy phosphate concentration in anesthetized dogs.

The effects of intracoronary administration of leukotriene D4 (LTD4) on myocardial blood flow (MBF) and myocardial energy metabolism in anesthetized open-chest dogs were examined, and compared with those of coronary ligation. Two series of experiments were conducted. In the first, LTD4 (0-3.0 micrograms/kg) was injected into the left anterior descending coronary artery (LAD) and MBF was measured. While no changes in MBF were observed after 0.5 microgram/kg of LTD4, a significant decrease in MBF in the LAD area was apparent after 1.0 micrograms/kg of LTD4, with a return to baseline values by within 10 min after the injection. With 3.0 micrograms/kg of LTD4, MBF remained decreased up to 15 min after the injection. In the second study, myocardial high energy phosphate concentrations in the LAD area were determined 5 min after LTD4 administration and compared to those after ligation. ATP levels in the 1.0-3.0 micrograms/kg LTD4 groups were significantly less than those in the ligation group, although there were no associated significant differences in MBF values in the LAD area. These results indicate that LTD4 brings about changes in myocardial energy metabolism which are not secondary to reduced blood flow.

Anesthesia↗

Malignant lymphoma presenting as a cardiac tumor.

We report a case of malignant lymphoma whose initial symptoms were heart failure. An echocardiogram showed a large tumor in the right ventricle, and a definitive diagnosis was obtained at autopsy. Of particular interest in our case, the lymphoma was confined to the heart and a mediastinal lymph node, with its greatest bulk being intracardiac. This case is a rare manifestation of malignant lymphoma.

Heart Neoplasms↗

Intracoronary acetylcholine-induced prolongation of the QT interval and Torsade des Pointes in long QT interval syndrome.

A 75-year-old female had syncopal episodes from Torsade des Pointes (TdP). Her electrocardiogram showed a prolonged QT interval which was not associated with electrolyte imbalances or drug therapy. Similar electrocardiographic abnormalities were found in three family members. Electrophysiologic study showed a mildly prolonged effective refractory period of 260-290 msec, but no tachyarrhythmia was induced. Coronary arteriography was normal but intracoronary acetylcholine unexpectedly induced a prolongation of the QT interval and TdP. Direct action of acetylcholine on the ventricular muscle was suggested.

Acetylcholine↗

Beneficial effects of iloprost on acute myocardial ischemia in dogs.

The effects of intravenous administration of iloprost, a prostacyclin analogue, on myocardial energy metabolism and myocardial blood flow (MBF) were examined in anesthetized open-chest dogs subjected to 60 min of myocardial ischemia by coronary ligation. Iloprost administration at levels of 0.1 or 0.2 micrograms/kg/min was started 30 min before the commencement of ischemia and continued throughout the 90 min observation period. Since systolic aortic pressure in the iloprost 0.2 micrograms/kg/min group showed significantly lower values than that in the control group, whereas no clear effect was observed with the lower concentration (0.1 micrograms/kg/min), this latter group was further investigated. This 0.1 microgram/kg/min dose of iloprost lacked influence on MBF in both ischemic and nonischemic areas but did result in a significantly higher value for high energy phosphate contents in the ischemic myocardium. Moreover, myocardial mitochondrial respiratory function in the ischemic area was significantly improved. These results indicate that iloprost brought about preservation of myocardial energy metabolism without alteration of coronary perfusion, suggesting that it may exert a direct cardioprotective effect.

Animals↗