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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 811 records · Page 45Linked to original sources

A new anti-platelet drug, E5510, has multiple suppressive sites during receptor-mediated signal transduction in human platelets.

The mode of action of E5510, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid, which has very potent anti-platelet activities, was investigated by examining its effects on the biochemical responses in the process of human platelet activation. In a whole-cell system, E5510 inhibited the increased turnover of inositol phospholipids arising from phospholipase C activation, arachidonic acid release from phospholipids by phospholipase A2, mobilization of intracellular free Ca2+, protein kinase C activation, and thromboxane A2 production. In a cell-free system, E5510 inhibited cyclooxygenase activity and cyclic AMP-dependent phosphodiesterase activity in a dose-dependent manner. An elevation of cyclic AMP in platelets was also observed at a relatively high concentration of E5510. It was suggested that receptor-mediated turnover of inositol phospholipids, intracellular Ca2+ increase, arachidonic acid release from phospholipids and protein kinase C activation might be indirectly inhibited by the increased cyclic AMP level in platelets. Thromboxane A2 production in the whole-cell system was very strongly inhibited by E5510, and the IC50 for this effect was 100 times lower than that of direct inhibition of cyclooxygenase in the cell-free system. It was concluded that although the primary mode of action of E5510 is the inhibition of the cyclooxygenase pathway of positive signal transduction in platelets, E5510 has another mode of action by increasing platelet cyclic AMP, which can act as a negative messenger in platelet signal transduction, and these multiple sites of action synergistically antagonize platelet cellular activation.

Arachidonic Acid↗

Comparative study of P element activity in two natural populations of Drosophila melanogaster.

Population structure concerning P element activity was investigated in two natural Drosophila populations. These populations are very different as far as in the viability spectrum is concerned. In one population, the Raleigh, United States population, genetic loads related to viability have been kept at a fairly high level. In the other population, the Nagasaki, Japan, population, the genetic loads tend to be stable at very low levels. In the Raleigh population it is estimated that on the average 4 copies of intact P elements that possess transposase activity exist in the genome. On the other hand only 0.7 complete copies are estimated to exist in the genome of the Nagasaki population. Heterogeneity in the P element copy number and significant positive linkage disequilibrium among occupied sites were detected in the Raleigh population. Our results, with some evidences which indicate that high mutation rate was caused by the P element, suggests that the large genetic loads in the Raleigh population are caused by the rapid invasion of P element in this population.

Animals↗

[Giant aneurysm of the middle cerebral artery presenting with complex partial seizure. Case report].

A 24-year-old female who had had several attacks of complex partial seizures was admitted after minor head trauma. There was no neurological deficit on admission, but a large oval calcification was incidentally found in the left temporal region on the plain skull film. Computed tomography scan and carotid angiography revealed a giant thrombosed aneurysm which arose from the M2 portion of the left middle cerebral artery. Focal spike discharges were found on the left temporal region on conventional electroencephalography. Left frontotemporal craniotomy and opening of the left sylvian fissure disclosed a giant aneurysm at the M2 portion of the left middle cerebral artery. The neck of the aneurysm was buried in the dome of the aneurysm and the parent artery was curved at an acute angle at the site of the neck. The aneurysm was excised and end-to-end anastomosis of the main stem of the M2 portion was successfully performed. Postoperative course was uneventful and the patient became completely free from seizures. The surgical technique and the possible mechanism of complex partial seizure in this patient are described.

Adult↗

Carcinoma of the esophagus: CT vs MR imaging in determining resectability.

MR imaging and CT were performed prospectively in 35 patients with esophageal carcinoma to determine the resectability of the primary tumors, because at our institution patients with resectable tumors have surgery regardless of the presence of distant metastases. Tumors with evidence of aortic or tracheobronchial invasion on MR or CT were considered to be unresectable. Tracheobronchial invasion was diagnosed when the tumor extended into the lumen of the airway, and aortic invasion was diagnosed when the triangular fat space between the esophagus, aorta, and spine adjacent to the primary tumor was obliterated. Two patients were excluded because of suboptimal MR images produced by motion artifacts. Pathologic proof was obtained from either surgery or autopsy in 31 patients. Of these, six patients (19%) had proved unresectable tumors (three aortic invasion and three tracheobronchial invasion). In all six cases, these features were correctly detected with both MR and CT. One patient had false-positive findings on MR and CT. An indeterminate diagnosis was obtained with MR in three patients and with CT in four patients. These incorrect or indeterminate results were all related to the diagnosis of aortic invasion. No patient had a false-negative result. When indeterminate diagnoses were considered false-positive, sensitivity, specificity, and accuracy for resectability were 100%, 84%, and 87%, respectively, for MR and 100%, 80%, and 84%, respectively, for CT. We conclude that MR and CT have nearly the same accuracy in predicting resectability of tumors in patients with esophageal carcinoma.

Adenocarcinoma↗

Effect of uvulonodular lesions on optokinetic nystagmus and optokinetic after-nystagmus in cats.

To investigate the effect of uvulonodular lesions on horizontal optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN), 6 cats were tested before and after lesions made by ablation under anesthesia. In the 3 cats with only uvular lesion, the initial slow phase velocity and the time constant of OKAN were unchanged. In the remaining three cats whose lesions included not only the uvula but also the nodulus, the time constant of OKAN was markedly prolonged, and the initial OKAN velocity was not affected. The postoperative average time constant of OKAN increased from normal value of 9 s to about 40 s. In contrast, OKN was unchanged in all of the 6 animals. These findings indicate that the nodulus may contribute to the discharge characteristics of the velocity storage integrator.

Animals↗

EOG findings in patients with lesions in cerebellar peduncles.

EOG tests were performed in patients with lesions in either the superior or the middle cerebellar peduncle, because these patients showed cerebellar signs and symptoms and were difficult to distinguish from patients with cerebellar lesions symptomatically. EOGs of these patients showed a predominant decrease of pursuit gains and OKN velocity gains toward the lesioned side, whereas the percent reduction of fixation-suppression of caloric nystagmus decreased predominantly toward the side contralateral to the lesioned side, regardless of whether lesions were located either in the superior or the middle cerebellar peduncle. The present EOGs are best interpreted as a corresponding to a deficit of the neuronal events of the flocculus in the monkey and are solely ascribed to lesions in the cerebellar peduncles, because even well-defined cerebellar lesions on one side showed bilateral impairments of these visually induced eye movements.

Cerebellar Diseases↗

[Silent cerebral infarction in the patients with essential hypertension].

Evidence of old cerebral infarction of magnetic resonance imaging (MRI) is common in acute stroke patients without a prior history of stroke. This experience led us to investigate the incidence of silent cerebral infarction (SCI) in the patients with essential hypertension, as well-known major predisposing factor for stroke. The incidence, number, size and localization of SCI on MRI (MARK-J, 0.1 T) and the prevalence of risk factors for stroke were investigated both in 66 hypertensive patients (WHO stage I or II; 63 +/- 9 (mean +/- S.D.) years old) and in 42 age-matched normotensive patients (61 +/- 9 years old). Risk factors selected were as follows: diabetes mellitus, hypercholesterolemia, daily alcohol intake, cigarette smoking, obesity, cardiac disease (arrhythmia and ischemic heart disease), hyperuricemia and high hematocrit. In hypertensive patients, the relationships between the incidence of SCI and hypertensive damages in major organs were also investigated. SCI was found in 45 out of the 108 subjects studied and a total of 216 SCI lesions were detected. All of the SCI lesions were localized in the subcortical white matter or in the basal ganglia. All SCI lesions were smaller than 3 cm in diameter and 201 lesions (93%) were smaller than 1 cm. The incidence of SCI tended to be higher in hypertensive patients (47%) than that in normotensives (33%) and increased significantly with advancing age in hypertensives from 26.9% in the 50s to 86.7% in the 70s, while no significant increase was noted in normotensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A frameless, armless navigational system for computer-assisted neurosurgery. Technical note.

A computer-assisted neurosurgical navigational system has been developed which displays intraoperative manipulation on the preoperative computerized tomography (CT) scans or magnetic resonance (MR) images. The system consists of a three-dimensional digitizer, a personal computer, and an image-processing unit. Utilizing recently developed magnetic field modulation technology, the three-dimensional digitizer determines the spatial position and orientation angles of the resin probe, triangle-shaped pointer, or suction tube with a small attached magnetic field sensor. Four fiducial markers on the scalp were used to translate the spatial data of the probe onto the preoperative CT scans or MR images of the patient. With this frameless, armless navigational system, CT or MR-imaging stereotaxy can be applied to conventional open neurosurgery without limiting the operative field or interfering with the surgical procedures.

Adult↗

[Clinical evaluation of serum basic fetoprotein for prostatic cancer--comparative study with PAP, gamma-Sm and PSA].

The clinical significance of serum basic fetoprotein (BFP) in prostatic cancer was investigated together with serum prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PA). Investigated in this study were 40 patients with prostatic cancer, ranging in age from 50 to 85 years (mean age: 69.5 years). According to clinical staging, 3 cases (7.5%) had a stage A disease, 10 cases (25.0%) a stage B disease, 7 cases (17.5%) a stage C disease, and 20 cases (50.0%) a stage D disease. The positive rates for serum BFP, PAP, gamma-Sm, and PSA were 60.0, 45.0, 63.6, and 68.4%, respectively, and these rates increased as the stage advanced. The above results suggest that BFP is the most useful marker of the four for monitoring prostatic cancer. In a combination assay of these four markers, 29 (87.9%) of 33 patients with prostatic cancer could be diagnosed by observing an elevated serum level in one of the markers. This suggests that a combination assay of BFP, PAP, gamma-Sm and PSA in patients with prostatic cancer is useful for diagnosis and monitoring of the disease.

Acid Phosphatase↗

Composition and structure of "group B saponin" in soybean seed.

The composition of "group B saponin" in soybean seed was analyzed by HPLC, and six kinds of "group B saponin," named Ba, Bb, Bb', Bc, Bd and Be according to elution order from HPLC, were detected. Of these saponins, Ba, Bb, Bb' and Bc were identified with soyasaponin V, I, III and II, respectively. Bd and Be were novel saponins possessing soyasapogenol E as the aglycone and the same sugar chain as Ba and Bb, respectively. These saponins were very unstable in the isolated state and had a tendency to form Ba and Bb, respectively. From these results, Bd and Be are presumed to be the precursors of Ba and Bb in soybean seed.

Chromatography, High Pressure Liquid↗

Inhibitory effects of the novel platelet activating factor receptor antagonist, 1-ethyl-2-[N-(2-methoxy)benzoyl-N-[(2R)-2-methoxy-3-(4- octadecylcarbamoyloxy) piperidinocarbonyloxypropyloxy]carbonyl] aminomethyl-pyridinium chloride, in several experimentally induced shock models.

E5880 (1-ethyl-2-[N-(2-methoxy)benzoyl-N-[(2R)-2-methoxy-3-(4- octadecylcarbamoyloxy) piperidinocarbonyloxypropyloxy] carbonyl]aminomethylpyridinium chloride, CAS 128420-61-1) is a novel analog-type antagonist of platelet activating factor (PAF). This paper describes the in vitro PAF antagonistic activity of E5880 and its in vivo effect in various experimentally induced shock models. Inhibition by E5880 of [3H]platelet activating factor (PAF) binding to human platelet PAF receptor was extremely potent; its IC50 value was 0.27 nmol/l, so that it was about 5 times more potent than PAF itself. Its IC50 value in inhibition of washed human platelet aggregation induced by PAF was 0.66 nmol/l. Intravenous treatment with E5880 dose-dependently reversed PAF-induced hypotension in rats and protected mice from lethality caused by PAF. Lipopolysaccharide (LPS)-induced hypotension in rats was inhibited by both pre- and post-treatment with E5880. It was also confirmed that blood PAF level, measured by the GC-NICI-MS method, was increased after LPS challenge in this model. Furthermore, E5880 was extremely effective in preventing passive anaphylactic lethality in mice. Blood PAF level in this model was also increased immediately after antigen challenge, and this was coincident with the time at which signs of shock became apparent. These findings support the concept that PAF is an important mediator in the development of LPS-induced shock and anaphylactic shock, and suggest that E5880, a novel and potent PAF antagonist, may be effective in clinical treatment for shock states.

Animals↗

[Effect of natural panting frequency and cheek support on the plethysmographic determination of thoracic gas volume in patients with chronic obstructive pulmonary disease].

The authors studied the effects of natural panting frequency (NF) and the cheek support on the plethysmographic measurement of thoracic gas volume (TGV) in 8 normal subjects (non-smokers) and 46 patients with chronic obstructive pulmonary disease (COPD). The patients were divided into 2 groups according to the degree of airway obstruction (group I; specific airway conductance (SGaw) greater than 0.1 (n = 18), group II; SGaw less than 0.1 (n = 28)). TGV was measured with a pressure-type body plethysmograph (BP). NF was 2.00 +/- 0.43 Hz (mean +/- SD) in control subjects, 1.92 +/- 0.78 Hz in group I, and 1.39 +/- 0.59 Hz in group II, respectively, indicating lower NF in the patients with severe airway obstruction. In control subjects and group I, the differences between TGV at NF and at 0.5-1.0 Hz (TGVNF-TGV1.0) were -0.01 +/- 0.07L, and -0.06 +/- 0.16L, respectively, and cheek support did not alter the difference. On the other hand, in group II, the difference was slightly larger than other groups in spite of the lower NF, and this overestimation was abolished by cheek support (0.13 +/- 0.25L-----0.06 +/- 0.27L, p less than 0.05). These results suggest that, in patients with severe airway obstruction, TGVNF may be overestimated even if NF is relatively low. This overestimation may be mainly due to the extrathoracic airway compliance including the cheek.

Adult↗

[Plasma cell tumor of the parieto-occipital bone; a case report].

Plasmacytoma originating in the cranial bone is a rare disease. A report is presented of a case of plasmacytoma originating in the parieto-occipital region. The patient was a 62-year-old male with palpation of a parieto-occipital mass as chief complaint. He showed no neurological deficit. Ig-G in the serum was 2240 mg/dl, and M-protein (n-type) was demonstrated in the serum. Bence-Jones protein was negative and bone marrow was normal. Skull X-ray showed osteolytic change in the parieto-occipital region. CT scan and MRI demonstrated a markedly enhanced mass extending from the epidural to the subcutaneous space at the parieto-occipital region. Common carotid angiography showed remarkable tumor stain flowing from the occipital artery, the superficial temporal artery, and the middle meningeal artery. Following embolization of the bilateral occipital artery, parieto-occipital horse shoe scalp incision was done. The tumor was elastic soft and bled easily around the margin of destroyed bone. Subtotal removal of the tumor was accomplished. The removed surgical specimen of the tumor was found to be plasmacytoma. The patient's postoperative course was favorable and no neurological deficit was found. Laboratory studies revealed a remarkable reduction of Ig-G in the serum to 1170 mg/dl. Six months after the operation, no signs of recurrence were seen on CT scan. Plasmacytoma originating in the cranial bone is so rare that only 18 cases have been reported to date. In these cases, laboratory studies have shown no evidence of anemia, Bence-Jones protein in urine, and abnormality of the bone marrow which are characteristic of multiple myeloma.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

[An evaluation of the attitudes and productivity of public health nurses in mental health service programs for the elderly].

The relationship between productivity of public health nurses (PHN) employed in mental health programs including home visit service for elderly people with dementia, and their attitudes toward mental health services was studied by surveying PHN at 31 health centers (HC) in Osaka Prefecture. A review of the services provided for 382 clients with dementia visited during a one-year period showed that PHN had provided the following services: home health care education: family education to promote understanding of the disease; management of interpersonal relations in the family; intervention to reduce the burden placed on the family members; medical facility referral; social service resource referral. For each of these PHN-provided services, the service had been provided to more than 60% of the clients. The percentage of clients who had been visited by a PHN accompanying a psychiatrist or a social worker was significantly higher at the 13 HC where PHN attach importance to counseling programs for the elderly, the 8 HC which provide group work services, and the 13 HC which hold case conferences more than six times a year than at other HC. In addition, the service provision rates for many PHN-provided services were significantly higher for these HC than for other HC. Analysis on the basis of whether PHN did or did not attach importance to the counseling program, showed that in either group, clients who had been visited by a PHN accompanying a psychiatrist or a social worker were more likely to have received PHN-provided services than other clients. Furthermore, at HC where PHN actively participated in mental health programs, PHN attitudes toward mental health care were more enthusiastic than at other HC. These results indicate that increased productivity of PHN employed in mental health programs and promotion of a multidisciplinary approach in client services are correlated with each other, and that both factors contribute to improving the quality of home visit services provided by PHN.

Aged↗

[Clinical study of miconazole on deep-seated fungal infections].

An investigation was made on the efficacy and the safety of miconazole (MCZ) in the treatment of deep seated mycosis. The drug was administered through intravenous drip infusion at dose levels of 800 to 2,000 mg/day to 21 cases of confirmed mycosis for which causative organisms was identified and to 32 cases to which other antibiotics considered to be appropriate had been administered at febrile stages but had failed to take effect, hence mycoses were strongly suspected. The overall clinical efficacy rate was 84.3% (43/51). Treatments were "remarkably effective" in 6 cases, "effective" in 37, "not effective" in 8 and "indeterminable" in 2. The efficacy rates were 100% (21/21) in the confirmed mycosis cases and 73.3% (22/30) in the suspected mycosis cases. The mycological efficacies in the cases for which causative strains were identified were: disappeared in 14 (66.7%), decreased in 4 (19%), unchanged in 2 (9.5%) and unknown in 1 (4.8%), thus the overall disappearance ratio was 70% (14/20). Chest X-ray showed the disappearance of shadow in 1 patient and improvements in 14 of 23 patients examined. Adverse reactions were observed in 5 of the 53 cases (9.4%). From these results, MCZ may be considered as a highly useful drug not only in the treatment of deep mycosis but also in cases for which mycosis is strongly suspected.

Adolescent↗

[Hemodynamic and metabolic changes in crossed cerebellar hypoperfusion--similarity to the early stage of olivo-ponto-cerebellar atrophy].

Using positron emission tomography in twenty-four unilateral supratentorial stroke patients, we evaluated regional blood flow, metabolic rate of oxygen, oxygen extraction fraction, and blood volume in the cerebellar cortex and pons. Sixteen patients with a significant cerebellar blood flow asymmetry, which lay beyond the upper ninety-five percent confidence limits defined in eight normal subjects, were selected as the group with crossed cerebellar hypoperfusion. In these patients, cerebellar metabolic rate of oxygen was also significantly decreased in the cerebellar cortex contralateral to the supratentorial stroke, compared with the ipsilateral cerebellar cortex, although to a lesser degree than the cerebellar blood flow. The degrees of cerebellar asymmetry in these two parameters were negatively correlated with the metabolic rate of oxygen in the pons. Oxygen extraction fraction was slightly, but significantly, increased in the cerebellar cortex contralateral to the stroke. In contrast to the ischemic state, cerebellar blood volume was decreased, with no difference in the ratio of cerebellar blood flow to blood volume. These findings suggest 1) interruption of the cortico-ponto-cerebellar tract as the mechanism of crossed cerebellar hypoperfusion and 2) mild elevation in the oxygen extraction fraction in this state, with a mechanism distinct from primary hypoperfusion. We also studied six patients with sporadic olivo-ponto-cerebellar atrophy who were in the incipient stage of the disease with slight cerebellar atrophy on magnetic resonance images. The cerebellar cortex in these patients showed the same hemodynamic and metabolic changes as in crossed cerebellar hypoperfusion, suggesting the cerebellar metabolic depression by transneuronal mechanism in the early stage of olivo-ponto-cerebellar atrophy.

Adult↗