Biomedical subjects

H Miyazaki

Publications and source records attributed to H Miyazaki.

At least 217 records · Page 12Linked to original sources

PubMed1998

Enhanced in vitro percutaneous penetration of salicylate by ion pair formation with alkylamines.

The apparent octanol/water partition coefficient (APC) of salicylate (SA) increased as the concentration of alkylamine (amyl, hexyl, heptyl, octyl and nonylamine) in aqueous phase increased, presumably through intermolecular ion pair formation between the negatively charged SA moiety and the alkylamine cation. The true partition coefficient (TPC) and the formation constant (Kf) of the ion pair were calculated from the partition data. The skin permeability of SA increased as the APC of SA increased, when 20-fold molar excess of alkylamine was added to the donor compartment. Permeability of ion pairs (PAB) from the aqueous phase to a shed snake skin was estimated from the permeability data assuming 1:1 ion pair. The methylene group contribution to the free energy of transfer of ion pairs from water to the shed snake skin was less than the reported value for nonionized drugs. This suggests that the ion pair is more polar by nature than nonionized molecules, even if ionic characteristics are masked to some extent by ion pair formation.

Amines↗

PubMed1998

[The involvement of cytokines, chemokines and inducible nitric oxide synthase (iNOS) induced by a transient ischemia in neuronal survival/death in rat brain].

Inflammatory/immunological processes underlie the survival/damage of neurons after brain ischemia. In glial cells, cytokines such as IL-1 beta and TNF-alpha are produced following ischemic stresses. On the other hand, it is suggested that NO/iNOS is involved in neuronal apoptosis. We here review the ischemia-induced production of cytokine/iNOS and the neurotrophic/neurotoxic effects. It is not clear whether or not the neuronal death after brain ischemia is apoptosis or necrosis. Under the condition of transient forebrain ischemia, however, we obtained results suggesting apoptosis in the delayed neuronal death of the CA1 pyramidal neurons. The time course and cellular localization of postischemic iNOS expression depend on the properties of the ischemic insult. The iNOS induction is detected primarily in astrocytes after the transient forebrain ischemia when the neuronal apoptosis is observed. We discuss a variety of cytokines with neurotrophic/neurotoxic actions that are produced by ischemia or environmental stresses in glial cells. From the neurotoxicological aspect of the neuro-glial interaction, we also review recent findings on signalling pathways of the iNOS induction in glial cells and the mechanisms of the cytotoxic actions of NO.

Animals↗

PubMed1998

Expression of the mutant (1735T-DEL) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia patients.

Hypophosphatasia (HOPS) is an inherited disorder characterized by defects in skeletal mineralization due to the deficiency of tissue-nonspecific alkaline phosphatase (TNSALP). To date, various mutations in the TNSALP gene have been identified. Especially, a deletion of T at position 1735 (1735T-del) located in exon 12 has been detected in three genetically unrelated Japanese patients, which seems to be one of the hot spots among the causative mutations in Japanese HOPS patients. 1735T-del causes a frame shift downstream from codon 503 (Leu), and consequently the normal termination codon at 508 is eliminated. Since a new inframe termination codon appears at codon 588 in the mutant DNA, the resultant protein is expected to have 80 additional amino acids. Expression of the mutant TNSALP gene using COS-1 cells demonstrated that the protein translated from the mutant 1735T-del had undetectable ALP activity, and its molecule size was larger than normal, as expected. Interestingly, an immunoprecipitation study of patients' sera using antibody against TNSALP revealed an abnormal protein which corresponded in size to the mutated TNSALP expressed by COS-1 cells, suggesting that the abnormal TNSALP is made by HOPS patients. The detection of TNSALP in cells transfected with 1735T-del using an immunofluorescent method exhibited only a faint signal on the cell surface, but an intense intracellular fluorescence after permeabilization.

Alkaline Phosphatase↗

PubMed1998

Hypotensive effects of an angiotensin II type 1 receptor antagonist differ between exercised and sedentary rats aged from 4 to 19 weeks.

The hypotensive effects of an angiotensin II type 1 receptor antagonist TCV-116 were accelerated by swimming training in the early period of chronic administration in young rats. In the latter period, however, a severe decrease in blood pressure that appeared during long-term administration of TCV-116 was prevented by swimming training. Therefore exercise may contribute to the stabilization of blood pressure in young rats treated with TCV-116.

Angiotensin Receptor Antagonists↗

PubMed1998

[72 cases of the auditory ossicle malformations but with normal findings in the tympanic membrane].

We evaluated 66 patients (72 ears) with auditory ossicle malformations, but with normal findings in the tympanic membrane, who underwent ossicular reconstruction and stapes surgery at our department between 1984 and 1997. There were 27 men (30 ears) and 39 women (42 ears). Classification of pathologic condition based on surgical findings showed separation of the incus-stapes joint in 43%, fixation of the malleus or incus in 16%, fixation of the stapes footplate in 26%, in incidence of fixation of the auditory oosicles that is higher than that previously reported. In 33% of the patients, conductive hearing loss or mixed hearing loss similar to that observed on the affected side was also present on the contralateral side. Abnormalities in the arrangement of the facial nerves were noted in 4%, inner ear malformation in 1%, and congenital cholesteatoma in 3%. Auditory ossicle reconstruction was performed by the modified type III method in 57% and by the modified type IV method in 37% of the cases. During stapes surgery, 86% underwent small-fenestra stapedectomy. Improvement in hearing after the operation was observed in 90% of the cases and the improvement was relatively high compared with tympanoplasty for chronic otitis media.

Adolescent↗

PubMed1998

[The influence of sleep breathing disorder on growth hormone secretion in children with tonsil hypertrophy].

INTRODUCTION: Recently it has been revealed that Obstructive Sleep Apnea Syndrome has an influence on the endocrine system, especially to the secretion of growth hormone (GH). It was previously reported that secretion of GH has a circadian rhythm along with a correlation with slow wave sleep. Normally in a pediatric patient, after 90 min of sleep the brain wave shows patterns of deep sleep, and a matching peak in GH secretion is observed. We have studied the effect of GH secretion in sleep breathing disorder of pediatric patients by observing the pre- and post-operative difference in GH secretion in children with tonsillar hypertrophy who had tonsillectomies. MATERIAL AND METHODS: Ten pediatric patients who complained of sleep apnea or hypopnea, and were highly suspected of having sleep breathing disorders due to tonsil hypertrophy and underwent surgery were chosen. Pre and post-operative blood somatomedin C and urinary growth hormone levels were measured. In 6 of the 10 patients blood GH levels were measured after overnight collection of blood every 30 min through a catheter placed in the vein. METHOD OF ANALYSIS: Integral blood GH calculated from GH levels of the blood samples taken every 30 min was used to express the efficacy of GH secretion during sleep, and was compared with blood somatomedin C and urinary GH levels. Pre- and post-operative somatomedin C and urinary GH measurements were compared. RESULT: 1) In 6 of the 10 patients, there was a positive correlation with integral GH and urinary GH, and no correlation with integral GH or somatomedin C. 2) Post-operatively, 7 of the 10 patients had increased urinary GH levels, 1 showed no change and 2 had decreased levels. There was a significant increase in the mean urinary GH levels from 18.6 +/- 16.1 pg/ml pre-operatively to 35.8 +/- 19.6 pg/ml post-operatively (P < 0.05). 3) Eight of the 10 patients had a post-operative increase in somatomedin C levels, 1 showed no change and the other patient had a decreased level. There was a significant increase in mean somatomedin C levels from 175.9 +/- 124.8 ng/ml pre-operatively to 226.6 +/- 134.3 ng/ml post-operatively (P < 0.01). CASE: An 8-year-old-boy was diagnosed as having habitual tonsillitis and suspected sleep breathing disorder, and was admitted to our hospital for a tonsillectomy. Apnea and hypopnea were observed during sleep in the hospital. After receiving his parents' consent, GH secretion was evaluated before and after the tonsillectomy. Integrated GH measurements, somatomedin C and urinary GH increased significantly after the operation. CONCLUSION: In this study, the improvement of sleep breathing disorder by surgery was associated with a positive effect to the GH secretion. GH secretion is important for growth of a child. Wen the cause of sleep breathing disorder is evident in the upper airway system, active treatment and cure by surgery is advised. Measurement of urinary GH in the morning is useful and simple for evaluating the ability to secrete GH.

Biomarkers↗

PubMed1998

[Expression and anti-metastatic potential of nm 23/NDP kinase in human head and neck cancer cells].

The nm23, encoding a protein identical to nucleoside diphosphate (NDP) kinase, is thought to be a candidate metastasis suppressor gene. Low expression of nm23 at the protein or/and mRNA levels was associated with metastatic potential of several types of rodent and human tumors. Expression and anti-metastatic action of nm23/NDP kinase gene products of human head and neck cancer (squamous cell carcinoma) cell lines were investigated. Among six cell lines examined, only those which showed metastatic potential exhibited reduced levels of nm23-H2 protein with no apparent change in nm23-H1 protein levels as compared with non-metastatic cells. When either nm23-H1 or nm23-H2 cDNA was transfected into a high metastatic cell line, only cell clones expressing higher levels of nm23-H2 protein above control levels displayed a reduced number of lung foci in an experimental metastasis assay. The data suggested that nm23-H2 gene product possesses the metastasis suppressor activity in human head and neck cancer cells.

Animals↗

PubMed1998

Proliferative properties of human umbilical cord blood megakaryocyte progenitor cells to human thrombopoietin.

We evaluated the effects of human thrombopoietin (TPO) alone, or in combination with other several hematopoietic factors, on megakaryocyte colony growth from human umbilical cord blood CD34+ cells in serum-depleted agar cultures. The addition of TPO alone had a concentration-dependent effect on the number of pure megakaryocyte colonies and of megakaryocytes per colony (colony size). The maximally stimulating concentration of TPO generated a greater number of megakaryocyte colonies and larger megakaryocyte colony size compared with the stimulation observed with an optimal concentration of human interleukin-3 (IL-3) or stem cell factor (SCF). At the high concentration of TPO that yielded the maximum colony numbers, a substantial proportion of megakaryocyte colonies contained 100 or more cells per colony. The combination of TPO plus SCF resulted in a synergistic enhancement of both the number and size of megakaryocyte colonies. Among the combinations of TPO plus other cytokines tested, IL-3 plus TPO had a modest effect on megakaryocyte colony numbers. The generation of megakaryocyte colonies from subpopulations of CD34+ cells was further examined. The addition of TPO alone induced a greater number of megakaryocyte colonies from CD34+CD41+ cells compared with CD34+CD41- cells, and TPO plus IL-3 exerted a synergistic effect on the number of megakaryocyte colonies only from CD34+CD41- cells. In contrast to the effects on colony numbers, TPO induced larger megakaryocyte colony sizes from CD34+CD41- cells, compared with CD34+CD41+ cells. In the case of HLA-DR expression, TPO and IL-3, administered singly or in combination, induced similar megakaryocyte colony numbers and sizes from CD34+DR+ and CD34+DR- subpopulations. Ploidy analysis revealed that the majority of megakaryocytes generated from cord blood CD34+ cells in serum-free liquid cultures containing TPO displayed 2N and 4N values, suggesting that they were immature. These results indicate that, compared with IL-3 and SCF, TPO has more potent proliferative effect on human cord blood megakaryocyte progenitors, leading to greater numbers of megakaryocyte progenitors triggered for both growth and cell division, and synergizes with SCF to enhance megakaryocyte colony growth.

Antigens, CD34↗

PubMed1998

[Traumatic intracerebral pneumocephalus communicating with two different paranasal sinuses: a case report].

We report a case of a 17-year-old male who had hit the front of his head in a traffic accident. CT scan revealed contusional hemorrhage and pneumocephalus of the left frontal lobe 10 hours after the accident. A month later he complained of rhinorrhea and CT scan revealed intracerebral pneumocephalus. One day he complained of headache and began to vomit after he sneezed. CT scan revealed that the pneumocephalus had become worse and air had spread throughout the subarachnoid space. Bone CT scan revealed the air communicated from the frontal sinus to the intracerebral air cavity. 3D-CT scan revealed bone defect in the roof of the ethmoid sinus. The intraoperative findings revealed that the intracerebral air cavity communicated with the frontal sinus and ethmoid sinus. Though the brain which dropped into the paranasal sinus, adhered to the dura mater around the bone defect, a part of the brain had come off from the dura mater around the frontal sinus. We suspected that the intracerebral air cavity communicated with the frontal sinus initially. When the air cavity communicated with the ethmoid sinus secondarily, intracranial pressure abated and air came into the subarachnoid space from the frontal sinus.

Accidents, Traffic↗

PubMed1998

[Intratumoral hemorrhage associated with cystic meningioma under observation: a case report].

Cystic meningiomas are not commonly encountered and are said to account for only 1 to 2% of all types of meningioma. There have been several reports on them and most of them were discussed under the aspect of the mechanism of cystic formation. Though few reports present the process of cystic formation, here we were able to present the process of cystic formation with intratumoral hemorrhage. The case was a 56-year-old man who presented with urinary incontinence. MRI revealed a large cystic tumor in the right frontal lobe and he was admitted to another hospital. After 20 days, MRI incidentally revealed hematoma near the intratumoral cyst. Two weeks later, MRI revealed that the hematoma flowed out the cyst and the cavity of the hematoma communicated with the cyst. Angiography showed that the tumor was fed by the left anterior ethmoid artery. After surgical removal of the tumor, histopathological diagnosis was that the tumor was a transitional meningioma and there were no findings of malignancy. Commonly, intratumoral hemorrhage is unusual for a meningioma but we suspect that there are not a few cases in which small hemorrhage occurred without symptoms and the hematoma cavity joined the intratumoral cyst while the cyst grew gradually.

Cerebral Hemorrhage↗

PubMed1998

N-Dealkylation and hydroxylation of ebastine by human liver cytochrome P450.

Ebastine [4'-tert-butyl-4-[4-(diphenylmethoxy)piperidino]butyro phe- none] is a new-generation, nonsedative, H1 antihistamine. The present study was performed to characterize the cytochrome P450 (CYP) isoforms responsible for ebastine N-dealkylation and hydroxylation. Human liver microsomes metabolized ebastine to two major metabolites, i.e. a desbutyrophenone metabolite (des-BP) and hydroxyebastine (M-OH), and the ratio of Vmax values was 3:1. N-Dealkylation yielded des-BP, whereas M-OH, an hydroxylation product, could be further oxidized to the pharmacologically active carebastine. In a panel of 14 human liver microsomal preparations, the rate of dealkylation showed a highly significant correlation with CYP3A-mediated testosterone 6beta-hydroxylation but not with reactions of seven other CYP isoforms. However, there was no correlation between the two pathways for ebastine (dealkylation and hydroxylation). Differential chemical inhibition in liver microsomes, in which dealkylation was more sensitive than hydroxylation, was demonstrated with ketoconazole, troleandomycin, cyclosporin A, and midazolam. Anti-CYP3A antibodies markedly reduced the dealkylation rate (>95%) in liver microsomes but exhibited insignificant effects on hydroxylation (<5%). Among 12 cDNA-expressed human CYP isoforms, which account for up to 70% of the total CYP enzyme content in human liver, CYP3A4 alone metabolized ebastine; the ratio of des-BP to M-OH formation was 12:1. This ratio for metabolism by the pure enzyme was much larger than the ratio (3:1) observed for the microsomal reaction mixture. This change in ratio, which is attributed to a decrease in M-OH formation, indicates that, although ebastine is metabolized to two major metabolites, N-dealkylation to des-BP is mediated by CYP3A, whereas hydroxylation to M-OH appears to be mediated mainly by unidentified enzymes other than CYP3A.

Butyrophenones↗

PubMed1998

[A case of intrapulmonary lymphangioma].

We report an extremely rare case of intrapulmonary lymphangioma. A 41-year-old woman was admitted to our hospital for complete medical evaluation of a pulmonary nodule on chest X-ray, which was found during an annual check-up. Chest radiograph showed a well-circumscribed spherical mass adjacent to the right border of the heart in the right lower lung field. Although a cystic tumor of the lung was suspected based on computed tomogram and magnetic resonance imaging findings, a histologic diagnosis could not be made on transbronchial biopsy. In addition, the nodule had increased in size compared with a chest X-ray taken 1 year previously. Enucleation was performed. Histological examination revealed numerous cysts with thin walls lined by a single layer of cells in which immunoreactivity to von Willebrand factor was weakly positive. Intrapulmonary lymphangioma was subsequently diagnosed.

Adult↗

PubMed1998

[5-fluorouracil and low-dose leucovorin as surgical adjuvant therapy from viewpoint of long-term outcome].

Biochemical modulation of 5-FU by leucovorin (LV) has been demonstrated to increase the therapeutic effect compared to single agent 5-FU in the treatment of patients (pts) with advanced colorectal cancer. The purpose of this study was to determine the effectiveness of the 5-FU + LV combination as adjuvant therapy following surgery in pts with Dukes' B, C colon cancer. Pts were entered in a stratified clinical trial comparing two different combination chemotherapeutic regimens to single agent 5-FU, given orally as a control. This report summarized the result of treatment in 61 pts who were 5-FU oral alone and 32 pts who were 5-FU (375 mg/m2) and low-dose LV (20 mg/m2) intravenously for 5 days with 5-FU oral intake. 5-FU with LV regimen was associated with an improved survival compared with the single agent 5-FU oral intake (p < 0.05). 5-FU with LV regimen resulted in less recurrence in liver and lung compared with single-agent 5-FU oral intake.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

[Intracellular signaling pathways of angiotensin II receptor type 1 involved in the development of cardiovascular diseases].

Angiotensin II (AII) receptor type 1 (AT1), a G-protein-coupled receptor, is involved in the development of cardiovascular diseases such as hypertensin, cardiac hypertrophy, and atherosclerosis. Recent reports indicate that tyrosine phosphorylation of multiple intracellular molecules is responsible for most of these AII actions mediated by AT1, similar to receptor tyrosine kinase signaling pathways. AII activates MAPK by tyrosine phosphorylating the EGF receptor by the mechanism called transactivation with subsequent Ras activation in vascular smooth muscle and cardiac fibroblast cells. In contrast, AT1 leads to MAPK activation through PKC in cardiac myocytes. In addition to these signals, JAK/STAT pathways, which mediate cytokine actions, are also important for several AII functions through AT1.

Animals↗

PubMed1998

[Correlation between pyrimidine nucleoside phosphorylase (PyNPase)/platelet-derived endothelial cell growth factor and histological prognostic factor, and influences of 5'-deoxy-5-fluorouridine (5'-DFUR) administration on PyNPase levels. 5'-DFUR Joint Research Group in the Osaka Area for Gastric Cancer].

PURPOSE: Pyrimidine nucleoside phosphorylase (PyNPase), among which thymidine phosphorylase (dThdPase) exists mainly in human tumor tissues, is an enzyme to convert 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil. Recently, it was reported that dThdPase was identical to platelet-derived endothelial cell growth factor, angiogenetic factor. Therefore, we expect that there is possibility of dThdPase being a prognostic factor. METHODS: We investigated for a possible correlation between PyNPase activities in tumor tissues and prognostic factors of histological findings, examined the influences of preoperative oral 5'-DFUR administration to PyNPase levels and investigated for a correlation between HPLC methods and ELISA methods in patients with gastric cancer. RESULTS: Higher levels of PyNPase were observed in patients with advanced t,n,v, and ly factors. PyNPase levels decreased by 5'-DFUR in patients with differentiated cases. A high correlation was found between HPLC and ELISA methods. CONCLUSION: This study suggests that we must investigate possibility of PyNPase being a prognostic factor in more detail.

Antineoplastic Agents↗

PubMed1998

[Multilocular chronic intracerebral hematoma due to metastatic brain tumor: a case report].

Chronic intracerebral hematoma is a fairly rare clinical entity. We report a case of a 76-year-old man who presented with left hemiparesis on admission. CT scan revealed a hematoma in the right basal ganglia. Under observation, the hyperdense lesion on CT scan changed to isodense 2 weeks after admission and then changed to low density 4 weeks after the first scan. These findings suggested hypertensive intracerebral hemorrhage but, 3 months after admission, hemiparesis grew worse and the appearance of the lesion changed from low density to isodensity again. When the patient presented disturbance of consciousness, CT scan revealed a new hemorrhage from the capsule of the hematoma and the new hematoma markedly expanded 2 weeks later. The contents of the hematoma was old uncoagulated hematoma resembling chronic subdural hematoma and drainage was carried out under local anesthesia. The patient died because of respiratory failure and autopsy was performed. Histopathologically cancer cells were shown in the hematoma cavity and the capsule of the hematoma was composed of two layers: a collagenous layer on the inside and a granulation layer with neovascular system on the outside. As the neovascular system existed on the outside of the capsule, the rebleeding occurred outside the capsule and the second hematoma appeared beside the initial one. We suspected that the initial bleeding occurred in the tumor tissue and the rebleeding occurred in the granulation layer of the capsule.

Adenocarcinoma↗

PubMed1998

Involvement of angiotensin II receptor subtypes during testicular development in rats.

Expression of testicular angiotensin II (AT2) receptors in Sprague-Dawley rats at various stages of development (1 and 5 days, 2, 3, 4 and 7 weeks postnatal) were studied by in vitro autoradiography and Northern blot analysis. The receptors were labelled with 125I-[Sar1, Ile8]AT2 and differentiated into two subtypes according to their susceptibility to AT1 (losartan, 5 microM) or AT2 (PD123319, 5 microM) antagonist. Total AT2 receptor binding in the testis was highest at 1 day of age (8.12 +/- 0.35 fmol/mg protein, mean +/- secEM, n = 8) and decreased gradually thereafter (5 days: 6.9 +/- 0.41, 2 weeks: 2.85 +/- 0.10, 3 weeks: 1.64 +/- 0.19, 4 weeks: 0.76 +/- 0.09, 6 weeks: 0.77 +/- 0.09 fmol/mg protein, n = 8-11). AT2 receptor binding was strikingly abundant in 1-day-old rat testis (6.98 +/- 0.34 fmol/mg protein), while considerably less AT1 receptor binding (1.46 +/- 0.19 fmol/mg protein) was observed. The relative amounts of each subtype did not change for the first 3 weeks but the 4-week-old rat testis contained almost exclusively AT1 receptors (0.63 +/- 0.05 fmol/mg protein). Northern blot analysis showed that mRNA expression of both AT1 and AT2 types decreased with age. Microscopic emulsion autoradiography was undertaken to clarify the localization of binding. At 10 days of age, both AT1 and AT2 receptors were present in the interstitial area, whereas seminiferous tubules contained mainly AT2 receptors. At 7 weeks of age, no significant binding was observed in the seminiferous tubule and the interstitial area contained AT1 receptors exclusively. These results demonstrate expression of AT2 receptors in the rapidly growing testis and suggest that change in the levels of AT2 receptor subtypes may be relevant to development and/or growth of the testis.

Angiotensin II↗

PubMed1998

[Study of the validity of ADL assessment by Minsei-iin of bed ridden elderly cared for at home].

We studied the validity of assessment of activities of daily living (ADL) by minsei-iins of the bed ridden elderly cared for at home. The cases, 66 male and 128 female elderly in a county of Gunma Prefecture, had been registered by minsei-iins (non-professional district welfare commissioners) as bed ridden cared for at home. Minsei-iins interviewed the case and the caregiver at home, asking them about the term of care, the levels of independence in their daily living, and seven items of ADL. Out of the 194 cases registered, PTs or OTs interviewed 136 cases, 42 male and 94 female, and calculated the Barthel index score. The Quantification method of the first type was applied to the data to predict the Barthel index score. The independent variables were five items of ADL assessed by the minsei-iins. The relation was close between the assessment of all items of ADL by the minsei-iins and the Barthel index calculated by the PTs or OTs. The Quantification method of the first type revealed that bathing, excreting and walking contributed most to the measured Barthel index. The multiple correlation coefficient was 0.687. There were three cases who scored 100 in the Barthel index.

Activities of Daily Living↗