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Biomedical subjects

M Murayama

Publications and source records attributed to M Murayama.

At least 91 records · Page 5Linked to original sources

[Assessment of localized hypertrophy in the basal part of the interventricular septum in the elderly].

The basal part of the interventricular septum (IVS) is known to show different hypertrophic features from those observed in the other parts of the left ventricular wall. These are considered to reflect physiological changes that occur with normal aging. However, these changes have not been carefully evaluated, and their clinical significance has not been defined. We assessed these changes echocardiographically. The subjects were patients at least 70 years of age in whom localized hypertrophy in the basal part of the IVS was seen during the whole cardiac cycle on echocardiography. The prevalence was 6.3% among 96 consecutively studied patients. All 6 patients had a history of hypertension. Echocardiographic findings were as follows: 1) the left atrium was mildly or moderately dilated, 2) there was no evidence of either dilatation or narrowing of the left ventricular cavity, 3) the left ventricular wall motion appeared normal and indices of systolic function were within normal limits in all subjects except one who had a history of myocardial infarction, 4) the angle formed by the aorta and the IVS averaged 106.7 degrees (range: 95 to 120 degrees), 5) Doppler examination showed increases in the ratio of the peak flow velocity during atrial systole to the peak flow velocity early in diastole, and 6) prolongation of the deceleration time of the flow velocity early in diastole. The last of these findings suggested left ventricular diastolic dysfunction, but peak flow velocity at the left ventricular outflow tract was normal. There was no evidence of stenosis of the left ventricular outflow tract. Localized hypertrophy in the basal part of the IVS in elderly patients could be a type of cardiac hypertrophy caused by hypertension. On echocardiography, the basal part of the IVS seemed to protrude toward the left ventricular cavity, but there was no evidence of stenosis in the left ventricular outflow tract.

Aged↗

[Outcomes of primary angioplasty in patients aged 85 years old and older who have acute myocardial infarction].

Outcomes of primary angioplasty in 6 elderly patients with acute myocardial infarction who were admitted to the hospital between July of 1994 and June of 1997 were reviewed retrospectively. Emergency coronary angiography was done in 7 of 16 patients (44%) who were at least 85 years old and primary angioplasty was done in 6 patients (38%). Dilatation was successful in all 6 patients. Congestive heart failure occurred in 4 patients and cardiogenic shock occurred in 1 patient, but no patient died during hospitalization. Blood transfusion and surgical resection were done in 1 patient because of a giant hematoma and pseudoaneurysm at the puncture site. Although the creatinine level increased after angioplasty in all 6 patients, dialysis therapy was not needed. All patients were alive and none had angina at follow-up (mean follow-up period = 16.5 months). Primary angioplasty was successful in patients at least 85 years old; both short-term and long-term outcomes were good. Primary angioplasty should be considered to be an effective treatment for acute myocardial infarction in people 85 years old and older.

Aged↗

Clinical characteristics and disease course of alcoholics with inactive aldehyde dehydrogenase-2.

Inactive aldehyde dehydrogenase-2 (ALDH2) is known as a genetic negative risk factor for the development of alcoholism. In alcoholics with inactive ALDH2, unidentified factors that overcome the adverse reactions of high blood acetaldehyde concentration after drinking may increase such persons' susceptibility to alcoholism. Comparison of clinical characteristics, including sociofamilial backgrounds and psychopathologies, failed to show significant differences between alcoholics with inactive ALDH2 (inactive group) and those with active ALDH2 (active group). Examination of the temporal profile of disease development showed that the inactive group experienced each stage or event in the history of drinking and alcoholism 1 to 5 years later in life than the active group; however, not all comparisons reached statistically significant levels. Although preliminary, these results suggest that an inactive ALDH2-mediated delay in the occurrence of alcohol-related problems seems to contribute to the suppression of alcoholism development.

Acetaldehyde↗

Cloning of cDNA and expression of the gene encoding rat presenilin-2.

We have cloned the rat homologue of the presenilin-2 (PS-2) cDNA. PS-2 is responsible for chromosome 1-linked familial Alzheimer's disease. Sequence analysis predicted that the rat PS-2 encodes a 448 amino acid (aa) protein, and there was a very high degree of amino acid identity between rat and human PS-2 (95%). All the mutated codons in PS-2 and PS-1 in chromosome 1- or 14-linked familial Alzheimer's disease patients were conserved in rat PS-2. The expression of PS-2 was weaker than that of PS-1. The alternatively spliced short form of PS-2 mRNA, which was detected in human tissues was not detected in various rat tissues. During brain development, the expression level of both PS-2 and PS-1 increased but decreased in the adult. No remarkable change was observed in neural differentiation of PC12 cells.

Alternative Splicing↗

Different effects of Alzheimer-associated mutations of presenilin 1 on its processing.

Presenilin 1 (PS 1) shows missense mutations in most early-onset familial Alzheimer's disease (FAD). Transfection of cDNA for wild type PS 1 into rat pheochromocytoma PC12 cells generated a 47 kDa full-size PS 1 protein, which was processed into a 28 kDa N-terminal fragment and a 19 kDa C-terminal fragment. We prepared selected Alzheimer-associated mutations (Gly384Ala, Leu392Val, and Cys410Tyr) of PS 1, which localized after a possible cleavage site. By transient expression in PC12 cells and rat glioma cell line, C6, we examined their influence on the processing of PS 1. Cys410Tyr inhibited proteolytic processing of PS 1, while Gly384Ala and Leu392Val did not. Thus, the Alzheimer related mutations can be divided into two groups in terms of their effect on the proteolytic cleavage of PS 1.

Alzheimer Disease↗

Nontoxic amyloid beta peptide 1-42 suppresses acetylcholine synthesis. Possible role in cholinergic dysfunction in Alzheimer's disease.

We show here that amyloid beta peptide1-42 (Abeta1-42) may play a key role in the pathogenesis of the cholinergic dysfunction seen in Alzheimer's disease (AD), in addition to its putative role in amyloid plaque formation. Abeta1-42 freshly solubilized in water (non-aged Abeta1-42), which was not neurotoxic without preaggregation, suppressed acetylcholine (ACh) synthesis in cholinergic neurons at very low concentrations (10-100 nM), although non-aged Abeta1-40 was ineffective. Non-aged Abeta1-42 impaired pyruvate dehydrogenase (PDH) activity by activating mitochondrial tau protein kinase I/glycogen synthase kinase-3beta, as we have already shown in hippocampal neurons (Hoshi, M., Takashima, A., Noguchi, K., Murayama, M., Sato, M., Kondo, S., Saitoh, Y., Ishiguro, K., Hoshino, T., and Imahori, K. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 2719-2723). Neither choline acetyltransferase activity nor choline metabolism was affected. Therefore, the major cause of reduced ACh synthesis was considered to be an inadequate supply of acetyl-CoA owing to PDH impairment. Soluble Abeta1-42 increases specifically in AD brain (Kuo, Y.-M., Emmerling, M. R., Vigo-Pelfrey, C., Kasunic, T. C., Kirkpatrick, J. B., Murdoch, G. H., Ball, M. J., and Roher, A. E. (1996) J. Biol. Chem. 271, 4077-4081). This increase in soluble Abeta1-42 may disturb cholinergic function, leading to the deterioration of memory and cognitive function that is characteristic of AD.

Acetylcholine↗

Glomerular proliferating cell kinetics in acute post-streptococcal glomerulonephritis (APSGN).

To investigate the time sequence of glomerular cell proliferation in acute human glomerulonephritis, renal biopsy tissues were examined from 15 acute post-streptococcal glomerulonephritis (APSGN) patients (who were biopsied 1-31 days after onset), using an immunoperoxidase technique with monoclonal antibodies against proliferating cell nuclear antigen (PCNA) and various cell surface markers. Few, if any, PCNA+ cells were observed in normal glomeruli, but many cells were positive for PCNA in the acute phase of APSGN. Glomerular PCNA+ cells were observed either within glomerular tufts, or lining Bowman's capsule (parietal epithelial cells); the number of positive cells tended to decrease exponentially as the disease duration increased (r = -0.91, P < 0.0001). PCNA+ cells within glomerular tufts were further identified by double immunostaining. PCNA was not found in PMN or T cells, but a small proportion of macrophages were PCNA+. Most of the remaining PCNA+ cells were resident glomerular cells; the proportion of PCNA+ endothelial cells (CD31+) was over 80 per cent in the early phase, but as the disease continued the proportion of mesangial cells (alpha-smooth muscle actin+) increased to about half of the total PCNA+ cells within the tuft. These data indicate that the hypercellular glomeruli in APSGN are due not only to immune cell infiltration, but also to resident glomerular cell proliferation, probably induced by locally produced growth factors.

Acute Disease↗

Erythrocyte magnesium and prostaglandin dynamics in chronic sleep deprivation.

BACKGROUND AND HYPOTHESIS: The mechanism of sudden cardiac death occurring in patients with chronic fatigue is controversial. This study was designed to define a hypothesis that coronary arterial spasm and thrombus formation can occur during chronic fatigue. METHODS: For evaluating the feasibility of coronary arterial spasm, erythrocyte magnesium (Mg) was measured. Blood coagulability was evaluated by the change of prostaglandin concentration. Subjects included 16 healthy male volunteers (mean age 21.6 +/- 2.5 years). Test conditions were as follows: (A) control state: a day following a night of good sleep; (B) temporary sleep deprivation: a day preceded by < 3 h of sleep; (C) chronic sleep deprivation: a day preceded by a month during which sleep lasted < 60% of that in condition (A) above. The erythrocyte Mg concentration was measured by the atomic absorption method. The plasma concentration of thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in eight subjects by radioimmunoassay method. RESULTS: (1) Mean erythrocyte Mg concentration was significantly less in chronic sleep deprivation (1.1 +/- 0.4 mg/dl) than in the control state (1.8 +/- 0.4 mg/dl, p < 0.01) or in temporary sleep deprivation (1.6 +/- 0.4, p < 0.01). (2) The level of thromboxane B2 was significantly higher during chronic sleep deprivation than under control conditions (104.4 +/- 78.0 vs. 20.4 +/- 9.0 pg/ml, p < 0.05). (3) There were no significant intergroup differences in 6-keto-prostaglandin F1 alpha level. CONCLUSION: These findings could support the hypothesis that coronary arterial spasm and thrombus formation occur in chronic sleep deprivation.

6-Ketoprostaglandin F1 alpha↗

Suppression of mouse contact hypersensitivity after treatment with antibodies to leukocyte function-associated antigen-1 and intracellular adhesion molecules-1.

We investigated the effects of the antibodies against the adhesion molecules leucocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) on mouse allergic contact hypersensitivity. Mice were injected intraperitoneally with both antibodies before sensitization by an epicutaneous application of dinitrofluorobenzene (DNFB). Simultaneous administration of the antibodies induced suppression of ear swelling in the effector phase of contact hypersensitivity. To show the effect of antibodies in vitro, lymph node cells (LNC) of mice treated with antibodies or with phosphate-buffered saline (PBS) were cultured in the presence of dinitrobenzene sulphonic sodium salts (DNBS), and the production of interleukin-2, interleukin-4 and interleukin-10 in the culture supernatants was measured using an enzyme-linked immunosorbent assay (ELISA). It was found that the production of interleukin-2 in the cells of mice treated with the antibodies was significantly lower than in the cells of PBS-treated mice. On the other hand, no difference was noted in the production of interleukin-4 or interleukin-10. Our results indicate that in vivo simultaneous administration of antibodies to cell adhesion molecules before hapten sensitization induces the suppression of contact hypersensitivity in mice and that the suppression may be due to the inhibition of the production of interleukin-2.

Animals↗

A unique case of squamous cell carcinoma showing adenocarcinomatous features with focal apocrine differentiation.

We report an 85-year-old man with squamous cell carcinoma on the right pinna. Two years after the excision of the lesion, metastatic foci were found extending from the right retromandibular to the mastoid region and into the parapharyngeal space. Histopathologically, the primary tumor showed interconnecting nests of atypical cells invading into the dermis from multiple epidermal and infundibular foci. The tumor had both squamous and glandular differentiation. A peculiar finding was the presence of decapitation secretion in the glandular foci. To our knowledge, definite apocrine differentiation in squamous cell carcinoma has not previously been reported.

Adenocarcinoma↗

Effects of alkaloids from Aconitum yesoense var. macroyesoense on cutaneous blood flow in mice.

Nine alkaloid constituents in the root of Aconitum yesoense var. macroyesoense, as well as three acetylated derivatives, were examined for their peripheral vaso-activities by measuring laser-flowmetrically the cutaneous blood flow in the hind foot of mice after intravenous administration. The major constitutive delcosine (1), 14-acetyldelcosine (2) and lucidusculine (3), respectively, had little or very mild vaso-activity. Kobusine (4) and pseudokobusine (5) and three minor constituents, luciculine (6), 1-acetylluciculine (7) and dehydroluciculine (8), together exhibited a rapid increase in blood flow reaching a peak with a magnitude almost equal to that produced by hydralazine, when administered intravenously at the same dosage level of 20 mg/kg. Among them, 4 was characterized by successive reversal of the increase to a decrease in blood flow, while 7 produced a flow with a more delayed peak time. Dehydrolucidusculine (9) exhibited a transient decrease in blood flow prior to occurrence of the increase, as did papaverine. Consequently, it is assumed that the alkaloids, especially those of the C20-diterpenoid type, in the root of this Aconitum plant have peripherally vaso-dilating activities to varying degrees in mice, probably due to their direct action on the cutaneous microvasculature in a similar fashion to that shown by hydralazine. The laser blood flowmetric method would be useful as an in vivo means of qualitative as well as quantitative screening of chemically modified derivatives of peripherally vasoactive agents in mice.

Alkaloids↗

A case of primary malignant fibrous histiocytoma of the heart with a left-to-right atrial shunt.

A previously healthy 64-year-old woman attended our hospital with chest pain, facial edema, and general fatigue. A chest radiograph revealed cardiomegaly, small bilateral pleural effusions, and hilar congestion--findings that improved after early therapy with furosemide and methyldigoxin. A chest radiograph recorded 7 years earlier had revealed no dilation of cardiac shadow. There were no findings suggesting atrial septal defect (ASD) or valvular heart disease. Echocardiography revealed a tumor-like mass adhering to the posterior wall of the left atrium. Color-flow Doppler echocardiography revealed a left-to-right shunt at the atrial level. The Qp/Qs ratio as measured by cardiac catheterization was 2.0. Coronary angiography revealed abnormal dilated arteries from the atrioventricular nodal branch and several feeding arteries from the left circumflex branch. We hypothesized that the left-to-right shunt could be due to the tumor, which extended to the rim of the patent foramen ovale, or to the very small, previously unrecognized, ASD. This patient died 6 months after her first admission and an autopsy was performed. Light microscopic examination of the tumor revealed spindle-shaped fibroblast-like cells arranged in a storiform or fascicular pattern. The immunohistochemical findings were consistent with malignant fibrous histiocytoma (MFH). In the literature, left-to-right shunt at the atrial level has not been reported in patients with cardiac MFH.

Echocardiography↗

Influence of exercise on QT dispersion in ischemic heart disease.

UNLABELLED: QT dispersion (QTd: maximum QT interval-minimum QT interval) is associated with severe cardiac arrhythmia and with abnormal ventricular repolarization. We investigated the influence of exercise on QTd in patients with ischemic heart disease. On standard 12-lead electrocardiograms, QTd was measured before and after treadmill exercise in 7 normal subjects, 17 patients with effort angina pectoris (and > or = 75% stenosis on coronary arteriography), and 33 patients with old myocardial infarction. Bazett's formula was used to obtain the corrected QTd (QTcd). The pre-exercise resting QTcd was 45.9 +/- 10.6, 44.3 +/- 15.2, and 74.8 +/- 28.1 msec in the respective groups, being significantly greater in the infarct group (p < 0.05). The QTcd at 5 min after exercise was respectively 49.3 +/- 9.0, 58.8 +/- 19.9, and 75.4 +/- 30.9 msec (p = 0.0347, infarct vs. controls). The difference in QTcd was significant for the angina group before and after physical exercise (p = 0.0003). There was a significant increase of QTcd after exercise in the angina group whether or not the patients were receiving beta-blockers. The infarct patients without beta-blocker therapy showed an increase of QTcd after exercise, while those receiving beta-blockers showed a decrease. The post-exercise difference between these subgroups was significant (p = 0.0351). CONCLUSIONS: QTcd was significantly increased by exercise in the angina group, possibly reflecting impaired repolarization due to ischemia. Inhibition of the increase in QTd by beta-blockers suggested a possible preventive effect on severe arrhythmias due to nonhomogeneous ventricular repolarization.

Adrenergic beta-Antagonists↗

[Successful direct percutaneous transluminal coronary angioplasty in a 91-year-old male with acute myocardial infarction complicating cardiogenic shock].

A 91-year-old male patient was admitted to hospital with acute myocardial infarction complicating cardiogenic shock. An emergency coronary arteriogram showed 99% stenosis at the mid-section of the right coronary artery, and in order to achieve an early recovery direct percutaneous transluminal angioplasty (PTCA) was performed through the brachial artery using a 6 french catheter. The lesion was successfully dilated up to 25% residual stenosis. Hypointention had been sustained during the admission; however, it gradually improved and he was discharged on the 31st hospital day. He has been followed up for 6 months after discharge at the out-patient clinic and has not recurrent ischemic episodes. According to other reports on the use of direct PTCA in the elderly, the postdischarge mortality rate is lower than that with medical therapy or thrombolysis. When cardiogenic shock occurs even in the elderly, direct PTCA should be selected as the first choice of treatment.

Aged↗

[Efficacy of increase of cardiac index during exercise in the chronic phase of various cardiovascular diseases: evaluation by exercise tolerance and brain natriuretic peptide].

Cardiac index is widely used as a parameter of cardiac function for cardiovascular patients, but its value is limited when measured in the resting supine position, because it never demonstrates the maximal cardiac index performance. The incremental increase in cardiac index (delta CI) was evaluated during incremental exercise (delta work rate: delta WR), delta CI/delta WR, in patients with chronic congestive heart failure, and compared to brain natriuretic peptide (BNP), which is known to be increased in patients with chronic left ventricular dysfunction. The subjects were 18 heart failure patients (16 males and 2 females, mean age [+/-SD] 63.8 +/- 8.9 years). Symptom-limited cardiopulmonary exercise test using cycle ergometer was performed. Cardiac index was calculated with the Benchmark Exercise Test device using oxygen uptake, carbon dioxide output and respired flow. Blood samples were taken in the resting state before the exercise test. A positive correlation was obtained between delta CI/delta WR and peak oxygen uptake (peak VO2) (r = 0.71, p < 0.01), and delta CI/delta WR and peak oxygen pulse (r = 0.66, p < 0.01). A negative correlation was obtained between delta CI/delta WR and BNP (r = 0.45) in the resting state. Peak VO2 (20.9 +/- 7.5 vs 13.9 +/- 2.7 ml/min/kg, p < 0.05), peak cardiac index (7.2 +/- 1.7 vs 5.5 +/- 0.9 l/min/m2, p < 0.05), and delta CI/delta WR (20.1 +/- 8.1 vs 12.4 +/- 2.5 ml/m2/W, p < 0.05) were significantly higher in the group with normal BNP (mean [+/-SD] 11.0 +/- 3.2 pg/ml) than in the group with high BNP (40.7 +/- 22.7 pg/ml). Delta CI/delta WR reflects the grade of exercise tolerance and may be useful for evaluating exercise capacity in patients with congestive heart failure.

Aged↗

[Factors affecting exercise capacity after coronary bypass grafting].

In order to determine the contribution of cardiac reserve and the peripheral muscle to exercise capacity in patients after Coronary Artery Bypass Grafting (CABG), 19 patients (18 males, 1 female, mean age 63.3 +/- 7.1 years, mean numbers of grafting 2.5 +/- 0.8) performed exercise tests at 1 week, 3 weeks, and 3 months after CABG. Ventilatory gas was analyzed throughout the testing and anaerobic threshold (AT) and peak oxygen uptake (peak VO2) was determined. During exercise testing, the cardiac index (CI) was measured, and the change in CI during exercise, delta CI = (CI at peak exercise) (CI at rest), was calculated. O2 delivery was derived from the product of CO and the oxygen content of arterial blood at peak exercise. The sectional area of the thigh muscles at the level of 10 cm above the patella was measured using a computed tomography before each test. Average peak VO2 at 1 week after CABG was 867 +/- 171 ml/min and it increased to 1,214 +/- 246 ml/min at 6 months. Average AT did not change from 1 week to 3 weeks, however, it increased significantly from 665 +/- 122 ml/min at 3 weeks to 873 +/- 181 ml/min at 6 months. The muscle area of the thigh increased significantly from 170 +/- 24 cm2 at 3 weeks after CABG to 186 +/- 27 cm2 at 3 months. delta CI showed a tendency to increase from 6.6 +/- 1.2 l/min/m2 at 1 week after CABG to 7.3 +/- 1.3 l/min/m2 at 3 weeks, and also showed a tendency to increase from 3 weeks to 6 months. Peak VO2 and AT correlated to delta CI at 1 weeks and also it correlated significantly to both the muscle area of the thigh and delta CI at 3 weeks, 3 months, and 6 months after CABG. The delta value of peak VO2 from 1 week to 3 weeks showed a significant correlation to those of delta CI and O2 delivery. Moreover, the delta values of peak VO2 and AT from 3 weeks to 3 months showed a correlation to those of delta CI and O2 delivery. These results suggest that both cardiac reserve and peripheral factors contribute to the exercise capacity up to 3 months after CABG, and, in particular, O2 delivery are important to increase exercise capacity.

Cardiac Output↗

[A patient with unilateral atrophy of trigeminal nerve-innervated muscle associated with contralateral glossopharyngeal and vagal neuropathy].

A 23-year-old woman was admitted to our hospital because of the left cheek swelling. On neurological examination, marked muscle atrophy of the right masseter muscle was recognized on chewing. The jaw was not deviated when she opened her mouth. Corneal reflex and the sensation on the face were intact. Curtain phenomenon was observed on the right side. The hypesthesia in the left palatal mucosa was observed. Routine laboratory data including cerebrospinal fluid analysis were normal. EMG from the right masseter muscle was not elicited, but normal in the left masseter muscle. The CT scan showed atrophy and low density areas in the right masseter, temporalis, lateral and medial pterygoid muscles, and hypertrophy in left masseter muscle. The MRI on T1 and T2 images confirmed the above muscle involvement. The etiology of trigeminal motor neuropathy, glossopharyngeal and vagal neuropathy were unknown. Masseter muscle hypertrophy was thought to be work hypertrophy compensated for the contralateral muscular atrophy.

Adult↗