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Biomedical subjects

Y Hara

Publications and source records attributed to Y Hara.

At least 127 records · Page 7Linked to original sources

Physiologic decrease of single thenar motor units in the F-response in stroke patients.

OBJECTIVE: To investigate the left-right difference and the reproducibility by the F-wave motor unit number estimation and to compare the motor unit number between the hemiplegic and unaffected side in stroke patients. SETTING: A referral center and institutional practice providing outpatient care. SUBJECTS: Seven healthy volunteers and 15 consecutive stroke patients. DESIGN: Diagnostic statistical test and correlational study. METHOD: Submaximal stimuli were used to evoke a sample of surface motor unit action potentials (S-MUAPs) in the F-waves that are entirely representative of the relative numbers of detected S-MUAPs of different sizes. The average S-MUAP amplitude was calculated from a selected population of F-wave responses for each abductor pollicis brevis (APB) muscle. The motor unit number was calculated by dividing the maximum M-potential negative peak amplitude by the average S-MUAP negative peak amplitude. RESULT: There was no statistical difference between motor unit numbers on either side and between test and retest in this motor unit number estimation method among normal subjects. The motor unit number on the hemiplegic side was significantly lower than on the unaffected side (p < .05, Mann-Whitney test) among stroke patients. CONCLUSION: The motor unit could decrease in the hemiplegic side after a moderate-to-severe hemiplegic stroke and this decrement might be due to the transsynaptic degeneration secondary to an upper motor neuron lesion.

Action Potentials↗

Image-guided microsurgery with the Mehrkoordinaten Manipulator system for cerebral arteriovenous malformations.

Four patients with cerebral arteriovenous malformations (AVMs) underwent image-guided microsurgery with the Mehrkoordinaten Manipulator (MKM) system, which integrates a robotic microscope with a computer workstation. The patients were all male, from 8 to 51 years old (mean = 24), all presenting with intracerebral haemorrhage. The lesion was located in the deep sylvian fissure in one patient, the fronto-parieto-occipital area in one and the trigone in two. Stereotactic computed tomography and magnetic resource imaging of 1-mm slices were taken. The extent of AVM and the draining vein, predetermined with the MKM workstation, could be superimposed on the microscopic view, resulting in minimum scalp incision and craniotomy, as well as allowing for a stereotactic approach to deep-seated lesions. Superimposition of the contour of the lesion was also useful for resecting the lesion, although intraoperative diagnosis of the total resection required intraoperative digital subtraction angiography. In conclusion, image-guided microsurgery with the MKM system can assist minimally invasive and maximally effective microsurgery for cerebral AVMs.

Adolescent↗

CD28 knockout mice as a useful clue to examine the pathogenesis of chronic graft-versus-host reaction.

BACKGROUND: Injection of BALB/c or DBA/2 spleen cells into F1 C57BL/6 (B6) hybrids induces a graft-versus-host reaction (GVHR) of a chronic stimulatory type that results in clinical and pathologic manifestations that resemble the human systemic lupus erythematosus (SLE). The aim of the present study was to examine the role of a major T-cell costimulatory signal receptor, CD28, in the production of autoantibody and the development of an immune complex glomerulonephritis, which are common in SLE pathology. METHODS: For this purpose, CD28-deficient (CD28KO) mice were used for the source of donor lymphocytes. Chronic GVHR was induced by an injection of BALB/c or BALB. CD28KO donor cells into normal BCF1 mice. Serum titers of anti-dsDNA antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) and major histocompatibility complex (MHC) class II antigen expression on B cells were tested by flow cytometry. In addition, depositions of immunoglobulin (Ig) were examined by direct immunofluorescence staining on frozen kidney sections. RESULTS: When (BALB/c x B6)F1 mice were injected with parental BALB/c lymphocytes, serum anti-dsDNA titer was significantly increased in association with nonspecific B-cell activation and IgG deposition in the glomerular basement membrane. In sharp contrast, none of these signs were observed in F1 mice, which were injected with CD28KO spleen cells. CONCLUSION: The CD28-mediated T-cell costimulatory pathway plays a pivotal role in the development of polyclonal B-cell activation, autoantibody production, and an immune complex glomerulonephritis. We propose that CD28KO mice are useful clues in examining the pathogenesis of experimental lupus nephritis.

Animals↗

Analysis of capsid formation of human polyomavirus JC (Tokyo-1 strain) by a eukaryotic expression system: splicing of late RNAs, translation and nuclear transport of major capsid protein VP1, and capsid assembly.

Human polyomavirus JC (JCV) can encode the three capsid proteins VP1, VP2, and VP3, downstream of the agnoprotein in the late region. JCV virions are identified in the nucleus of infected cells. In this study, we have elucidated unique features of JCV capsid formation by using a eukaryotic expression system. Structures of JCV polycistronic late RNAs (M1 to M4 and possibly M5 and M6) generated by alternative splicing were determined. VP1 would be synthesized from M2 RNA, and VP2 and VP3 would be synthesized from M1 RNA. The presence of the open reading frame of the agnoprotein or the leader sequence (nucleotides 275 to 409) can decrease the expression level of VP1. VP1 was efficiently transported to the nucleus in the presence of VP2 and VP3 but distributed both in the cytoplasm and in the nucleus in their absence. Mutation analysis indicated that inefficiency in nuclear transport of VP1 is due to the unique structure in the N-terminal sequence, KRKGERK. Within the nucleus, VP1 was localized discretely and identified as speckles in the presence of VP2 and VP3 but distributed diffusely in their absence. These results suggest that VP1 was efficiently transported to the nucleus and localized in the discrete subnuclear regions, possibly with VP2 and VP3. By electron microscopy, recombinant virus particles were identified in the nucleus, and their intranuclear distribution was consistent with distribution of speckles. This system provides a useful model with which to understand JCV capsid formation and the structures and functions of the JCV capsid proteins.

Alternative Splicing↗

Gene dosage affects the cardiac and brain phenotype in nonmuscle myosin II-B-depleted mice.

Complete ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice resulted in cardiac and brain defects that were lethal during embryonic development or on the day of birth. In this paper, we report on the generation of mice with decreased amounts of NMHC-B. First, we generated B(DeltaI)/B(DeltaI) mice by replacing a neural-specific alternative exon with the PGK-Neo cassette. This resulted in decreased amounts of NMHC-B in all tissues, including a decrease of 88% in the heart and 65% in the brain compared with B(+)/B(+) tissues. B(DeltaI)/B(DeltaI) mice developed cardiac myocyte hypertrophy between 7 months and 11 months of age, at which time they reexpressed the cardiac beta-MHC. Serial sections of B(DeltaI)/B(DeltaI) brains showed abnormalities in neural cell migration and adhesion in the ventricular wall. Crossing B(DeltaI)/B(DeltaI) with B(+)/B(-) mice generated B(DeltaI)/B(-) mice, which showed a further decrease of approximately 55% in NMHC-B in the heart and brain compared with B(DeltaI)/B(DeltaI) mice. Five of 8 B(DeltaI)/B(-) mice were born with a membranous ventricular septal defect. Moreover, 5 of 5 B(DeltaI)/B(-) mice developed myocyte hypertrophy by 1 month; B(DeltaI)/B(-) mice also reexpressed the cardiac beta-MHC. More than 60% of B(DeltaI)/B(-) mice developed overt hydrocephalus and showed more severe defects in neural cell migration and adhesion than did B(DeltaI)/B(DeltaI) mice. These data on B(DeltaI)/B(DeltaI) and B(DeltaI)/B(-) mice demonstrate a gene dosage effect of the amount of NMHC-B on the severity and time of onset of the defects in the heart and brain.

Animals↗

Transient U wave inversion during treadmill exercise testing in patients with left anterior descending coronary artery disease.

The transient U wave inversion during exercise is specific for detecting left anterior descending coronary artery (LAD) disease. In a homogeneous patient group restricted to LAD disease, however, the significance of the electrocardiographic finding has not yet been clarified. Thus, clinical characteristics in patients with angiographically documented one-vessel disease of the LAD and exercise-induced U wave inversion were delineated. Symptom-limited treadmill exercise testing was performed in 60 patients (43 men, 17 women; mean age 64 +/- 8 years) with angina pectoris whose culprit lesion was located only in the LAD. U wave polarity and amplitude were determined before, during, and after exercise with the P-Q segment as the isoelectric line. Exercise-induced transient U wave inversion was defined as positive when there was a discrete negative deflection > or = 0.05 mV within the T-P segment. Of all patients, 16 (27%) had exercise-induced U wave inversion. There were no differences in age, male gender, antianginal medication use, and coronary angiographic data between the two patients groups: patients with and without U wave inversion. Heart rate and double product of heart rate and systemic systolic blood pressure at peak exercise were also similar. Prevalence of abnormal exercise-induced S-T segment shift was 94% (15 of 16 patients) and 61% (27 of 44 patients) of patients with and without U wave inversion, respectively. The difference was statistically significant (p = 0.02). Among patients with exercise-induced S-T segment shift, the proportion of patients with S-T segment elevation to all the patients was larger in patients with U wave inversion than in patients without U wave inversion [3 (20%) of 15 patients vs 0 (0%) of 27 patients, p = 0.03)]. In conclusion, the exercise-induced U wave inversion in patients with one-vessel disease of the LAD indicates the severe degree of myocardial ischemia induced in the territory perfused by the LAD. However, the electrocardiographic finding does not appear to have independent significance since it closely correlates with the presence of S-T segment shift.

Aged↗

A 25-year-old patient with low cardiac risk factors having a combination of variant angina and severe coronary arterial lesions--a case report.

A 25-year-old man with low cardiac risks underwent coronary arteriography because of chest pain at rest. His only risk factors for coronary artery disease was smoking. Both right and left coronary arteries were ectatic and the left anterior descending artery was obstructed. In the acetylcholine provocation test, the left circumflex coronary artery showed severe constriction. Thus, this patient was diagnosed as having a combination of variant angina and occlusive coronary artery disease.

Adult↗

Coronary spastic angina induced by anticholinesterase medication for myasthenia gravis--a case report.

Myasthenia gravis (MG) is characterized by weakness of skeletal muscles because of a decrease in the number of available acetylcholine receptors at neuromuscular junctions. Anticholinesterase medication is widely used to treat MG, but muscarinic side effects sometimes appear and limit the drug usage. To their knowledge, the authors present the first case of coronary spastic angina quite possibly induced by anticholinesterase medication to treat MG. The appearance of coronary spastic angina in the present case is likely mediated through the increase of acethylcholine by anticholinesterase medication.

Aged↗

Stable prostaglandin I1 analog SM-10906 modulates productions of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 in mouse macrophages.

The present study investigated the effects of stable agonist for prostaglandin (PG) I2 receptor with PGI1 skeleton, SM-10906, on pro-inflammatory cytokine production by mouse peritoneal macrophages (PEMs) in comparison with PGE1 and PGI2. In mouse PEMs, SM-10906 and PGE1 slightly enhanced interleukin (IL)-6 secretion, but had no effects on tumor necrosis factor-alpha (TNF-alpha) or IL-1 production. SM-10906 concentration-dependently inhibited TNF-alpha, IL-1 and IL-6 releases from lipopolysaccharide-activated mouse PEMs, as with PGE1, PGI2 and cAMP analog. Additionally, SM-10906, PGE1 and PGI2 caused concentration-dependent accumulation of cAMP contents in mouse PEMs. It is concluded that PGI1 analog SM-10906 exerts anti-inflammatory effects on stimulated mouse PEMs by increasing in cAMP levels, as with E-series of PG.

Alprostadil↗

Hydroxylation of nitrated naphthalenes with KO2/crown ether.

Superoxide radical anion (O2*-), generated by KO2/crown ether, is effective for hydroxylation of nitronaphthalenes. When mono- and di-nitronaphthalenes are treated with KO2/crown ehter, hydroxylation results at the electron-deficient site caused by the electron withdrawing effect of the substituted nitro group. Kinetic experiments suggest that the hydroxylation proceeds by two different mechanisms dependent on the first one-electron reduction potential of nitronaphthalenes.

Ethers, Cyclic↗

Apical hypertrophic cardiomyopathy associated with life-threatening paroxysmal atrial flutter with a slow ventricular response: a case report.

A 58-year-old male patient had apical hypertrophic cardiomyopathy (HCM) associated with a life-threatening tachycardia due to atrial flutter. Following palpitation and dyspnea for 2-3 h, he became unconscious because of circulatory catastrophe, but was fully resuscitated. An electrocardiogram recorded just before the loss of consciousness revealed atrial flutter at a rate of 260 beats/min with a 2:1 ventricular response. He was diagnosed as having apical HCM based on the echocardiographic and left ventriculographic findings. Atrial stimulation at a rate of 150 pacings/min for 1 min caused a marked drop in systemic systolic blood pressure from 170 to 120 mmHg. The patient was treated with 150 mg of cibenzoline per day to prevent supraventricular tachyarrhythmias and to improve left ventricular diastolic function. At the time of the recent follow-up at 2 and a half years, he felt quite well.

Atrial Flutter↗

Effect of beta-blocker on left ventricular function and natriuretic peptides in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitor.

To evaluate whether or not beta-blockers can improve the condition of patients with heart failure treated with a combination of diuretics, digitalis and angiotensin-converting enzyme inhibitor (ACEI), 52 patients with chronic heart failure who have been treated with ACEI for more than 6 months were enrolled. They were divided into 2 groups: 26 patients continued the same therapy another 6 months or more (group A), and 26 patients were given oral metoprolol for 6 months or more, in addition to the ACEI (group B). Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured. The left ventricular dimensions at end-diastole and end-systole were significantly decreased and fractional shortening was significantly increased in group B after 6 months' treatment with the beta-blocker, but these parameters remained unchanged in group A. Plasma levels of both ANP and BNP were significantly decreased in group B, but remained unchanged in group A. These results indicate that concomitant beta-blocker therapy can improve left ventricular function and attenuate plasma ANP and BNP levels in patients with chronic heart failure treated with ACEI.

Adrenergic beta-Antagonists↗

[A case of unresectable gallbladder cancer responding to combination therapy with hyperthermia and local chemotherapy].

A 78-year-old woman was admitted to our hospital for the control of gallbladder cancer. A peritoneal metastasis, diagnosed as unresectable cancer, was detected during surgery in a previous hospital, and a biliary stent was introduced and gastrojejunostomy was performed. In our hospital she was treated weekly with local chemotherapy (PFL; cisplatin 2.5-5 mg/body ia, fluorouracil 300 mg/body ia, and calcium folinate 30 mg/body ia, via the common hepatic arterial port) at the time of hyperthermia. Hyperthermia was performed with a Thermox 500 (HEH-500 C) at the power of 500 watts for 45-60 minutes. To enhance the hyperthermia effect, mitomycin C 2-4 mg/body ia via the common hepatic arterial port and 500 ml of 7.5% glucose infusion were given. As a result of the combination therapy, the volume of the whole tumor was reduced to 60.9% on computed tomography, and diagnosed as PR. The serum level of CA19-9 decreased from 3,000 U/ml to 300 U/ml. The patient continued to receive the therapy for 1 year, and is now well. Therefore, we conclude that combination therapy with hyperthermia and local chemotherapy seems beneficial in managing unresectable advanced gallbladder cancer, especially for the elderly.

Aged↗

[Successful treatment of a patient with recurrent ovarian clear cell adenocarcinoma under combination chemotherapy of 5-FU (civ) and low-dose CDDP (i.v.)].

Resistance to conventional chemotherapy including CDDP is the most important therapeutic problem in ovarian cancer. The combination chemotherapy of 5-FU (civ) and low-dose CDDP (i.v.) was applied to a patient with recurrent ovarian clear cell adenocarcinoma (stage IIa), which is often more resistant to systemic chemotherapy than other ovarian adenocarcinomas and is a poor prognostic factor. The patient underwent cytoreductive surgery. Then, 5-FU 375 mg/m2/day civ (days 1-5, 8-12, 15-19, 22-26) and CDDP 3.75 mg/m2/day i.v. (days 1-5, 8-12, 15-19, 22-26) were administered. After four courses of this treatment, there is no sign of recurrence. This result indicates that the combination of 5-FU and CDDP is useful in the treatment of recurrent ovarian cancers.

Adenocarcinoma, Clear Cell↗

[Evaluation of clinical utility of 123I-MIBG scintigraphy in localization of tumors of sympathetic and adrenomedullary origin--a report of multicenter phase III clinical trials].

Phase III clinical study was performed to evaluate clinical utility of 123I-MIBG in the localization of tumors in 48 patients with tumors of sympathetic and adrenomedullary origin, diagnosed or strongly suspected. Sixteen patients had pheochromocytoma, 23 had neuroblastoma, 7 had medullary carcinoma of the thyroid, and 2 had Sipple syndrome. In 3 out of 48 patients, 123I-MIBG scintigraphy was performed twice. The clinical utility of 123I-MIBG was evaluated in 50 cases. Out of 140 lesions, 123I-MIBG scintigraphy demonstrated 51 true positive, 79 true negative, 1 false positive, and 2 false negative. Seven lesions were not evaluable. Sensitivity was 96.2%, Specificity was 98.8%, and Accuracy was 97.7%. An acquisition between 4 hrs and a day after injection was adequate for tumor detection. Neither adverse reactions nor abnormal laboratory findings were noted in relation to 123I-MIBG injections. Our study indicates that 123I-MIBG is a safe and useful radiotracer for visualization and localization of tumors of sympathetic and adrenomedullary origin.

3-Iodobenzylguanidine↗

[Natriuresis and blood pressure in patients with chronic renal failure following L-arginine infusion].

Nitric oxide (NO) is known to be generated from L-arginine and may regulate glomerular filtration, tubular sodium reabsorption, and renin secretion. Impairment of renal function might influence NO production secondary to endothelial dysfunction, decreased NO synthesis and increased activity of arginine analogues inhibiting NO synthase. In this study, we evaluated the effect of L-arginine on the blood pressure and urinary sodium excretion in patients with chronic renal failure. A 300-ml dose of 10% L-arginine solution was administered intravenously over 30 min and blood pressure was monitored every 10 min under basal conditions and for 120 min after infusion. The patients were divided into two groups based on the reduction in mean blood pressure (dMBP) following infusion, namely non-responders (dMBP < 10 mmHg) and responders (dMBP > 10 mmHg). Urine and blood samples were collected to determine electrolytes, urinary NO2 + NO3 by the Griess method, urinary cGMP, plasma renin activity (PRA), and the plasma aldosterone concentration (PAC). L-arginine significantly decreased MBP in 8 patients and caused no significant change in 10 patients. Urinary sodium excretion and the NO2 + NO3 level were significantly increased following L-arginine infusion and the increment of fractional excretion of sodium was higher in responders. However, there were no significant changes in PRA, PAC, and cGMP. Our findings suggest that a vasodilator effect of NO induced by L-arginine loading may, at least in part, be associated with increased renal sodium excretion in patients with chronic renal failure.

Adult↗

Doxorubicin-induced late cardiotoxicity: delayed impairment of Ca2+-handling mechanisms in the sarcoplasmic reticulum in the rat.

Doxorubicin treatment causes delayed development of cardiotoxicity. Whether the doxorubicin-induced impairment of cardiac functions reverses or progresses with time after the cessation of the treatment was examined. The rats were injected with doxorubicin (2.5 mg/kg, i.v., once a week for 3 weeks) and sacrificed at 1 (1W), 13 (13W), or 18 (18W) weeks after the final doxorubicin administration. The time to peak of twitch contraction observed at 2-Hz stimulation was not altered in left atrial or ventricular muscle preparations isolated from 1W rats, but it was prolonged in those from 13W and 18W rats. The reduction of the magnitude of postrest contraction and the alteration of force-frequency relationships in left atrial muscle preparations in 1W rats were not significant, but were intensified in the 13W and 18W groups. Alterations in the postrest contraction and the force-frequency relationships in ventricular muscle preparations isolated from doxorubicin-treated rat hearts were weaker, but the pattern of alteration was similar to that observed in left atrial muscle preparations. Caffeine-induced contraction observed in skinned fibers that were isolated from the 1W rats was not altered, but it was reduced in the 18W rats. The Ca2+ sensitivity of contractile proteins was not altered in doxorubicin-treated rat hearts in any of the groups. The K(d) values estimated from a [3H]ryanodine binding study were not altered, but the B(max) values were significantly lower in the 13W and 18W groups than those observed in control rats. These results suggest that the dysfunction of the sarcoplasmic reticulum progresses after the completion of doxorubicin treatment and contributes to the doxorubicin-induced late cardiotoxicity.

Animals↗

[A case of recurrent breast cancer with carcinoma erysipeloides responding to sequential therapy with docetaxel (TXT) and doxifluridine (5'-DFUR) accompanied by leucovorin (LV)].

A left radical mastectomy was performed on a 53-year-old woman, diagnosed with left inflammatory breast cancer, after local arterial chemotherapy with cyclophosphamide (CPA), doxorubicin and 5-fluorouracil (5-FU). Adjuvant therapy was added with irradiation and ECF. Four months after the operation, a red eruption was detected on the left upper chest wall. The lesion was diagnosed by skin biopsy as a recurrent breast cancer with carcinoma erysipeloides. Tumor marker levels suggested the recurrent cancer was ECF resistant, so we changed the chemotherapy regime to a single dose of TXT. Although tumor marker levels and the skin eruptions improved at the beginning of the therapy, pleuritis carcinomatosa was found. We changed the regime again to a continuous dose of 5'-DFUR and LV for day 1 to 7. With this regime the clinical symptoms improved, and 2 courses of this modified FL therapy were carried out. After the therapy, the tumor seemed resistant to this modified FL therapy. Therefore, we tried a sequential therapy with TXT and the modified FL, which induced an improvement in clinical symptoms. Two years later, the patient died from the breast cancer. Therefore, we conclude that the sequential therapy may be beneficial in managing untreatable carcinoma erysipeloides of recurrent breast cancer.

Antineoplastic Agents, Phytogenic↗