Search PubMed⌕ Search

Biomedical subjects

H Miki

Publications and source records attributed to H Miki.

At least 163 records · Page 9Linked to original sources
PubMed1996

A neurokinin 1-receptor antagonist improves exercise-induced airway narrowing in asthmatic patients.

Recent reports suggest the involvement of vascular phenomena in exercise-induced asthma. Sensory neuropeptides, such as substance P (SP), which causes airway vascular dilatation and plasma leakage, have been demonstrated to play a role in hyperpnea-induced airway narrowing in animal studies. The purpose of this study was to investigate the importance of tachykinins in exercise-induced airway narrowing in patients with asthma using a selective neurokinin 1-receptor (NK1-receptor) antagonist, FK-888. In a double-blind, placebo-controlled, crossover trial, nine subjects with stable asthma were given FK-888 (2.5 mg) or placebo by inhalation 20 min before each exercise at a level previously demonstrated to cause a fall of at least 40% in specific airway conduction (SGaw). Inhalation of FK-888 had no significant effect on baseline SGaw. While the recovery from exercise-induced airway narrowing was significantly faster after treatment with FK-888 the area under the curve for SGaw during the 50 min after exercise was significantly reduced (p<0.05) and the time taken for the SGaw to recover to within 65% of baseline after exercise was also significantly shorter with FK-888 than the placebo (p<0.05). However, treatment with FK-888 did not significantly attenuate the maximal fall in SGaw. These results suggest that NK1-receptor-mediated mechanisms are involved in the recovery phase of exercise-induced airway narrowing. The possible mechanisms of these phenomena are discussed.

Administration, Inhalation↗
PubMed1996

Photoreceptor apoptosis induced by a single systemic administration of N-methyl-N-nitrosourea in the rat retina.

Retinal degeneration was induced by a single intraperitoneal injection of N-methyl-N-nitrosourea in female Sprague-Dawley albino rats at 50 days of age by two dose regimens, which were observed sequentially at 24, 48, and 72 hours and 7, 21, and 35 days after the treatment. After a dose of 75 mg/kg, methylnitrosourea evoked progressive retinal degeneration in all treated rats whereas a dose of 50 mg/kg was less effective. The 75-mg/kg-treated rats showed selective destruction of the photoreceptor cells by an apoptotic mechanism, as confirmed morphologically and by the terminal dUTP nick end labeling method. Apoptosis had already started at 24 hours after the treatment and was completed by day 7. During the photoreceptor degeneration, proliferation of glial fibrillary acidic protein and vimentin-positive Müller cells as detected by proliferating cell nuclear antigen labeling appeared at 48 hours and was prominent 72 hours after the treatment, and macrophage infiltration within the retina as recognized by ED1 positivity was maximal 7 and 21 days after the treatment. Retinal degeneration was also induced in female Brown-Norway colored rats in a similar dose-dependent manner. Pigment epithelium was discontinuous above Bruch's membrane, and migration of the swollen pigment epithelium toward the inner nuclear layer was seen 7 days after the treatment. Therefore, as also confirmed electron microscopically, the most striking change was the destruction of photoreceptor cells by the apoptotic process, followed by Müller cell proliferation, pigment epithelium migration, and macrophage infiltration for cell debris phagocytosis, resulting in a thin remnant of retina with attenuated inner nuclear cells in direct contact with Bruch's membrane or with the pigment epithelium and/or with the Müller cells 35 days after the treatment.

Animals↗
PubMed1996

Heterogeneous distribution of thyrotrophin receptor messenger ribonucleic acid (TSH-R mRNA) in papillary thyroid carcinomas detected by in situ hybridization.

OBJECTIVE: TSH suppression therapy has been reported to be effective in some cases of papillary carcinoma of the thyroid. However, there has been little information regarding the status of expression of TSH-R mRNA in papillary carcinomas. Therefore, we examined the expression of TSH receptor (TSH-R) mRNA in thyroid tumours by in situ hybridization. DESIGN: Surgically resected thyroid tumour specimens were used. The expression level of TSH-R mRNA was detected by in situ hybridization, and the difference between tumours and their adjacent normal thyroid tissues was assessed. PATIENTS: Tumours and adjacent normal thyroid tissues were obtained from nine patients with differentiated papillary carcinomas and eight with adenomas. MEASUREMENTS: We performed in situ hybridization on frozen sections of thyroid tissues. Digoxigenin-labelled oligonucleotide was used to hybridize and to detect TSH-R mRNA. We counted positively stained cells and non-stained cells in each section, calculated the positivity of stained cells and assessed the distribution of positively stained cells. RESULTS: In normal thyroid tissue, the positivity was 95.3 +/- 2.3% (mean +/- SD) and the distribution of TSH-R mRNA was homogeneous. In adenoma, positivity was 93.5 +/- 4.4%. In most cases of adenoma, the distribution was homogeneous. In papillary carcinoma, the expression level of TSH-R mRNA was significantly lower and the positivity was 81.9 +/- 12.6%. Furthermore, in five cases of papillary carcinoma, the distribution was heterogeneous; four of these cases were stage 3, while the remaining case was stage 1. Three of the four cases with a homogeneous distribution were stage 1, while one case was stage 3. CONCLUSIONS: The heterogeneity of TSH-R mRNA distribution suggests the effect of TSH on carcinoma cells may be variable. Furthermore, papillary carcinomas of advanced clinical stage showed a tendency to low expression and heterogeneous distribution of TSH-R mRNA.

Adenoma↗
PubMed1996

Oncogenicity studies of the new serotonin (5-HT)3-receptor antagonist ramosetron in mice and rats.

Oncogenicity studies of ramosetron ((R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazol e hydrochloride, CAS 132907-72-3, YM060), a new compound having serotonin (5-HT)3 receptor antagonist activity, were carried out in male and female mice and rats. Six groups (two control and four treated) of B6C3F1 mice and F344 rats were given YM060, dissolved in distilled water, once daily by oral intubation at doses of 0, 1, 10, 30 and 100 mg/kg/d. Toxicokinetics indicated that sufficient exposure of the animals to the test material was achieved during the oncogenicity studies. Cmax and AUC of YM060 at 100 mg/kg/d were in the range of 3-5 micrograms/ml and 8 micrograms.h/ml in mice, 1-5 micrograms/ml and 7-16 micrograms.h/ml in rats, respectively. The administration of YM060 resulted in a slightly increased mortality rate among female rats treated with 30 or 100 mg/kg/d, particularly during the Weeks 38-87. Body weights of the high-dosed male and female rats during the Weeks 36 to 96 were significantly decreased when compared to controls. An approximately 30% suppression of body weight gain was recorded during Weeks 36-96 for both male and female rats, and 15% suppression of body weight gain was recorded during Weeks 0-104 for male mice. There was no evidence of a treatment-related effect on the incidence of any tumor or tumor type, and there were no non-neoplastic findings considered to be related to the administration of YM060. All microscopic changes seen in mice and rats were of the usual type commonly occurring in untreated aged B6C3F1 mice and F344 rats. In conclusion, there was no evidence of an oncogenic effect of YM060 in mice and rats.

Animals↗
PubMed1995

Nitric oxide as a retrograde messenger in the nucleus tractus solitarii of rats during hypoxia.

1. We examined the role of nitric oxide (NO) in respiratory regulation in the nucleus tractus solitarii (NTS), where L-glutamate release associated with peripheral chemoreceptor activation modulates the hypoxic ventilatory response. 2. Experiments were performed in unanaesthetized freely moving rats. First, the effects on the hypoxic ventilatory response of sodium nitroprusside (SNP, a NO donor) or NG-monomethyl-L-arginine (L-NMMA, a NO synthase inhibitor), microinjected into the NTS, were investigated. Second, using in vivo microdialysis, changes in extracellular L-glutamate during hypoxia were examined in the presence of L-NMMA. Third, the effect of L-NMMA on ventilatory augmentation by exogenous L-glutamate was examined. Furthermore, we measured extracellular L-citrulline concentration changes during hypoxia in the NTS to assess NO formation indirectly and also examined the effect of MK-801 (an NMDA receptor antagonist) on L-citrulline levels during hypoxia. 3. SNP increased ventilation during both normoxia and hypoxia. L-NMMA did not alter ventilation or L-glutamate levels during normoxia but significantly attenuated the hypoxic ventilatory response and the increase in L-glutamate during hypoxia. The inhibition by L-NMMA was blocked by L-arginine. The ventilatory augmentation by exogenous L-glutamate was attenuated by L-NMMA. L-Citrulline increased during hypoxia, and this increase was inhibited by MK-801. 4. We provide the first in vivo evidence that, in the NTS, NO works as a retrograde messenger in an L-glutamate-releasing positive feedback system contributing to the augmentation of ventilation during hypoxia.

Animals↗
PubMed1995

Splicing isoforms of rat Ash/Grb2. Isolation and characterization of the cDNA and genomic DNA clones and implications for the physiological roles of the isoforms.

We obtained three types of cDNA clones homologous to Ash/Grb2(Ash-l) cDNA from rats. One of these clones, Ash-psi, was an unusual transcribed gene having 93% identity in the nucleotide sequence to Ash-l. The other two clones, Ash-m and -s, had nucleotide sequences identical with Ash-l cDNA in the amino-terminal region. The coding sequence of Ash-m cDNA is 42 nucleotides shorter than that of Ash-l cDNA. The defective region of Ash-m cDNA encodes 14 amino acid residues (157 to 170 of Ash-l), which comprise the most conserved region of the second SH3 domain. On the other hand, the coding sequence of Ash-s terminated at the end of the first SH3 domain due to a stop codon at the boundary of the sequence, thereby differing from Ash-l cDNA. Cloning of the genomic DNA of the Ash-l-encoding gene, determination of the gene organization, and nucleotide sequencing revealed that the two isoforms, as well as Ash-l, are generated from a single gene by unusual alternative splicings. The gene spans more than 16 kilobases and contains 6 exons and 5 introns. Ash-m and Ash-s mRNAs were detected in various tissues by reverse-transcribed polymerase chain reaction. Ash-m physically associated with dynamin, but the association with Sos was less effective than that of Ash-l in rat pheochromocytoma PC12 cell lysates, irrespective of treatment with nerve growth factor. In contrast, Ash-s formed a complex with dynamin and Sos in cell lysates. Moreover, the newly formed carboxyl-terminal SH3 of Ash-m by splicing bound different proteins from those bound to the carboxyl-terminal SH3 domain of Ash-l, suggesting that Ash-m generates different signals. Microinjection of Ash-m or Ash-s into Balb/c 3T3 cells inhibited DNA synthesis induced by platelet-derived growth factor. These results show that these isoforms act as dominant negative regulators of mitogenic signals by Ash-l.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Immunohistochemical features of the human retina and retinoblastoma.

The immunohistochemical features of 24 retinoblastoma specimens from 22 patients, 15 with unilateral and 7 with bilateral disease, were examined by the labelled streptavidin biotin (LSAB) method and compared with those of specimens from the remaining morphologically normal retina. In the normal retina, S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin were detected in astrocytes and/or Müller cells. Neurofilament protein was seen in axons of the ganglion cells, synaptophysin was present in both plexiform layers, bcl-2 oncoprotein was seen in ganglion cells and bipolar cells, and neuron-specific enolase (NSE) was detected in ganglion cells, bipolar cells and photoreceptor cells and in their cell processes. While retinoblastoma (Rb) protein expression was noted in ganglion cells, bipolar cells, and some photoreceptor cells, p53 protein was not expressed at all. In all retinoblastomas, strong NSE expression and weak bcl-2 expression was observed in almost all tumour cells and synaptophysin was localized in rosette-forming cells, while tumour cells were devoid of S-100, GFAP, vimentin and neurofilament protein. These findings support the view that retinoblastomas are composed of neuron-committed cells. In addition, no Rb protein expression was detected in retinoblastomas, whereas p53 expression was found in 18 cases (75%).

Child↗
PubMed1995

Submental stimulation and supraglottic resistance during mouth breathing.

We studied submental stimulation on supraglottic resistance (Rsg) in 5 normals and 6 patients with obstructive sleep apnea. We then examined the most effective sites of stimulation in the submental regions, and the relationships between Rsg and stimulation frequency and voltage in the supine position. Inspiratory and expiratory Rsg's were obtained as the slope of the linear portion of the pressure-flow relation determined at zero flow. Before stimulation, inspiratory and expiratory Rsg's were 0.76 +/- 0.06 (means +/- SE) and 0.61 +/- 0.02 cmH2O.L-1.sec, respectively, in normals, and 1.04 +/- 0.20 and 0.92 +/- 0.29 cmH2O.L-1.sec, respectively, in patients. Stimulation in the proximal half submental region with surface electrodes 1 cm apart decreased inspiratory and expiratory Rsg's in patients, and inspiratory Rsg in normals. Inspiratory Rsg measured in this submental region showed a stimulation frequency-and voltage-dependency in both groups, but expiratory Rsg did not. These findings suggest that submental stimulation in the proximal half region widens the supraglottic airway during mouth breathing and probably involves the upper airway muscles.

Adult↗
PubMed1995

Familial hyperparathyroidism associated with jaw fibroma: case report and literature review.

A 53-year-old female suffering from renal stones and hypercalcaemia was diagnosed as having primary hyperparathyroidism caused by hyperplasia of the parathyroid glands. She underwent total parathyroidectomy and implantation of parathyroid tissue. After one year, she underwent surgery for a jaw tumour. The pathological findings indicated it to be a cementifying fibroma. Jackson et al. (1990) reported the familial association of hyperparathyroidism with jaw tumours, and they suggested that this condition represents a new clinical syndrome. We believe that our case belongs to this syndrome.

Female↗
PubMed1995

Role of hypoxia on increased blood pressure in patients with obstructive sleep apnoea.

BACKGROUND: Cyclical changes in systemic blood pressure occur during apnoeic episodes in patients with obstructive sleep apnoea (OSA). Although several factors including arterial hypoxaemia, intrathoracic pressure changes, and disruption of sleep architecture have been reported to be responsible for these changes in blood pressure, the relative importance of each factor remains unclear. This study assessed the role of hypoxaemia on the increase in blood pressure during apnoeic episodes. METHODS: The blood pressure in apnoeic episodes during sleep and the blood pressure response to isocapnic intermittent hypoxia whilst awake were measured in 10 men with OSA. While asleep the blood pressure was measured non-invasively using a Finapres blood pressure monitor with polysomnography. The response of the blood pressure to hypoxia whilst awake was also measured while the subjects intermittently breathed a hypoxic (5% or 7% oxygen) gas mixture. Each hypoxic gas exposure was continued until a nadir arterial oxygen saturation (nSaO2) of less than 75% was reached, or for a period of 100 seconds. The exposure was repeated five times in succession with five interposed breaths of room air in each run. RESULTS: The mean (SD) increase in blood pressure (delta MBP) during apnoeic episodes was 42.1 (17.3) mm Hg during rapid eye movement (REM) sleep and 31.9 (12.5) mm Hg during non-REM sleep. The delta MBP during apnoeic episodes showed a correlation with the decrease of nSaO2 (delta SaO2) (r2 = 0.30). The change in blood pressure in response to intermittent hypoxia whilst awake was cyclical and qualitatively similar to that during apnoeic episodes. Averaged delta MBP at an SaO2 of 7% and 5% oxygen was 12.6 (5.7) and 13.4 (3.6) mm Hg, respectively, whereas the averaged delta MBP at the same delta SaO2 during apnoeic episodes was 38.4 (15.5) and 45.2 (20.5) mm Hg, respectively. CONCLUSIONS: The blood pressure response to desaturation whilst awake was about one third of that during apnoeic episodes. These results suggest that factors other than hypoxia may play an important part in raising the blood pressure during obstructive sleep apnoea.

Adult↗
PubMed1995

Solitary pulmonary nodule: preliminary study of evaluation with incremental dynamic CT.

PURPOSE: To use incremental dynamic computed tomography (CT) to evaluate solitary pulmonary nodules (SPNs). MATERIALS AND METHODS: Thirty-two adult patients with SPNs less than 3 cm in diameter had 18 primary lung cancers, 10 tuberculomas, and four hamartomas. The CT numbers of the inner area of the nodule were calculated before and 30 seconds, 2 minutes, and 5 minutes after administration of contrast material. RESULTS: All lung cancers and one of four hamartomas showed significantly greater enhancement (P < .0001) than benign SPNs, which did not show enhancement (except for one hamartoma). All lung cancers and one of four hamartomas showed complete enhancement, one hamartoma showed peripheral enhancement, two hamartomas and eight of 10 tuberculomas showed capsular enhancement, and two tuberculomas showed no enhancement. CONCLUSION: Maximum attenuation of 20-60 HU appears to be a good predictor of malignancy.

Adult↗
PubMed1995

Small peripheral lung carcinoma evaluated with incremental dynamic CT: radiologic-pathologic correlation.

PURPOSE: To correlate incremental dynamic computed tomographic (CT) and pathologic findings in peripheral lung cancer. MATERIALS AND METHODS: Lung lesions smaller than 3 cm in diameter were evaluated in 18 patients. CT values of the inner area of the nodule at plain CT and at 30 seconds, 2 minutes, and 5 minutes after administration of nonionic contrast material were calculated with incremental dynamic CT. Maximum attenuation was compared with pathologic type of lung carcinoma and with number of vessels and distribution of elastic fibers in the pathologic specimen. RESULTS: Enhancement of all lesions was statistically significant (P < .0001). Maximum attenuation of lung carcinomas correlated positively with number of small vessels (diameter, 0.02-0.10 mm) (r = .77). Distribution of elastic fibers in the tumoral interstitium correlated with maximum attenuation (P = .04 between grades 1 and 3) and with number of small vessels (P = .01 between grades 1-3; P = .008 between grades 1 and 3). CONCLUSION: Enhancement characteristics of lung carcinomas reflect the number of small tumoral vessels and the distribution of elastic fibers in the tumoral interstitium.

Adenocarcinoma↗
PubMed1995

Spontaneous oscillations of intracellular calcium in single bovine parathyroid cells may be associated with the inhibition of parathyroid hormone secretion.

PTH secretion is tightly regulated by extracellular calcium ([Ca2+]e) and in turn regulates calcium homeostasis through its action on target tissues. We investigated the mechanism and physiological significance of intracellular calcium ([Ca2+]i) levels in relation to the secretion of PTH in single bovine parathyroid cells. [Ca2+]i was recorded using digital imaging microscopy, and secretion of PTH was correlated in the same cell using the reverse hemolytic plaque assay. In individual parathyroid cells, oscillations of [Ca2+]i were present in response to specific stimuli. Like secretory activity, response to [Ca2+]e concentrations was heterogeneous. Oscillations of [Ca2+]i occurred spontaneously in 22% of cells at inhibitory concentrations of [Ca2+]e. Oscillations were present only in high [Ca2+]e (> or = 1.8 mM) and not noted at lower concentrations of [Ca2+]e. The interval and amplitude of [Ca2+]i oscillations were 42 +/- 2 sec, and 20 +/- 1 nM (mean +/- SE), respectively. Oscillations were rapidly abolished when [Ca2+]e was removed by EGTA, and this effect was reversible. Addition of Mg2+ or polycationic antibiotics such as neomycin resulted in an [Ca2+]i spike, but oscillations were absent. Lanthanum, which blocks Ca2+ influx through calcium channels in various cells, rarely caused oscillations even in the presence of high concentrations of [Ca2+]e. To test the role of cAMP in [Ca2+]i oscillations, we added the beta-agonist isoproterenol. The addition of isoproterenol, however, did not cause oscillations. The number of cells that released PTH was significantly lower in cells with oscillations compared with cells without oscillations. We suggest that spontaneous [Ca2+]i oscillations are due to the influx of [Ca2+]e through ion channels rather than release from [Ca2+]i stores and may be a specific intracellular signal associated with inhibition of PTH secretion.

Animals↗
PubMed1995

Effect of specific binding of high density lipoprotein to eel hepatocytes on their secretion of lipoprotein.

Specific binding of eel serum high-density lipoprotein (HDL) to eel hepatocytes was demonstrated by using a synthesized fluorescent lipophilic dye. HDL binding was inhibited by the addition of unlabeled HDL. The binding of HDL to the hepatocytes was saturated at concentrations over 100 micrograms HDL protein/ml and Kd value was 20 micrograms HDL protein/ml. A fluorescent photomicrograph of the cultured eel hepatocytes which were incubated with the dye showed the bright, circumferential plasma membranes stained with the dye. 125I-HDL was incorporated into the acid insoluble- and soluble-fractions of the cultured hepatocytes during incubation at 28 degrees C for 1 h. There are three remarkable characteristics of the effect of HDL on the cultured hepatocytes. One is that the addition of HDL to the hepatocytes induced the efflux of cholesterol, triacylglycerol, and phospholipid from the hepatocytes. The second characteristic is that the efflux of the intracellular lipids was carried out with very-low-density-like or chylomicron-like lipoprotein secreted by the hepatocytes. The third characteristic is that HDL specifically stimulated the synthesis of the lipoprotein and had no effect on the synthesis of intracellular proteins and the secreted proteins except for the lipoprotein.

Anguilla↗
PubMed1995

Sonographic findings in muscle strain injury: clinical and MR imaging correlation.

Both sonography and magnetic resonance imaging were performed in 57 patients with clinically suspected strain injury in lower extremity muscles. Sonography demonstrated normal findings in nine patients (16%), hyperechoic infiltration in 31 patients (54%), mass in nine patients (16%), and compound lesions of infiltration and mass in eight patients (14%). Clinically grade 2 lesions ranged from small infiltration to large compound lesions on both sonography and magnetic resonance imaging. Hyperechoic infiltration was not demonstrated on T1-weighted magnetic resonance images and with less than 50% cross-sectional muscle involvement. The mass and compound lesions were ascertained to be moderate or severe injury because the masses of the lesions had obvious hemorrhage or hematoma on magnetic resonance images.

Adolescent↗
PubMed1995

[Neoadjuvant chemotherapy and chemoradiotherapy in the treatment of esophageal cancer].

Adjuvant therapy following surgery has been mainstream in surgical adjuvant therapy for the patients with esophageal cancer in Japan. In western countries, neoadjuvant therapy has become popular in which surgery is performed depending on the effects of preoperative treatment. Neoadjuvant chemotherapy offers the advantage of downstaging the primary tumor and enhancing resectability and the potential advantage of assessing the response to preoperative chemotherapy directly in the primary tumor. Disadvantages include possible emergence of chemotherapy-resistant tumor cells, as well as the delay in achieving effective local tumor control and postoperative morbidity. In the phase II studies, most regimens have included CDDP/5-FU. Pathological CR rates have been less than 10% and median survival terms from eight to 28 months. The rationale for the concurrent use of chemotherapy and radiotherapy is to combine an agent that has an effect upon systemic micrometastases with a modality that enhances local tumor control. In addition, a number of chemotherapeutic agents have radiosensitizing effects. The majority of trials have employed CDDP/5-FU combined with RT for a total dose of 30 Gy. Pathological CR rates were from 20 to 40% and median survival terms from 12 to 29 months. Neither neoadjuvant chemotherapy nor chemoradiotherapy increased operative morbidity mortality, and there was a statistically significant increase in survival in complete responders. However, though the early and median survival was improved, the cure rate was not. Both therapies remain investigational.

Aged↗