[Ash/Grb2--toward the elucidation of its mechanism to produce a variety of signals].
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Animals↗
Biomedical subjects
H Miki
Publications and source records attributed to H Miki.
[A case of an intrapulmonary lymph node indistinguishable from carcinoma of the lung by CT].
A 64-year-old female was referred to our hospital for further examination of a coin lesion, 8 mm in diameter, superimposed on the right ninth posterior rib. CT revealed a nodule, close to the minor fissure, with spiculation, which seemed to be connected with the pulmonary vein. Since the bronchofiberscopic examination revealed no histological diagnosis, the exploratory thoracotomy was performed. The nodule was found to be a 10 x 7 x 5 mm black mass located subpleural at the minor fissure. Histologically, it was recognized as a lymph node with anthracosis and silicotic nodules.
Diagnosis, Differential↗
[Portable home monitoring system in screening for sleep-disordered breathing].
Screening for sleep-disordered breathing is often done in an interview and with a questionnaire. This method is indirect and it appears to underestimate the prevalence of sleep apnea syndrome. Recently, several devices such as the Medilog and Vitalog portable monitoring systems were developed. However, these devices are difficult for patients to operate by themselves, because they include EEG monitoring or measurement of chest and abdominal movement. Therefore, we developed a portable monitoring system that is easier to operate. This system can be used to assess three variables: oronasal airflow, tracheal sound, and electrical activity of the heart. It stores the time of the onset of apnea, apnea duration, and R-R intervals with a built-in microcomputer. Apnea episodes, total apnea time, mean apnea time, and R-R interval are analyzed with a host computer. The sensitivity an specificity of this system are 92.5% and 87.5%, respectively, with an apnea index (AI) of less than 10 episodes/h. Using this device, we found that the prevalence of sleep apnea syndrome among Japanese industrial workers who had an AI of more than 10 episodes was 7.5%. Moreover, from 1984 to 1994 we used this device to monitor 1019 outpatients who complained of sleep disturbances such as snoring, abnormal breathing during sleep, and excessive daytime sleepiness, and found sleep apnea (AI > or = 10) in about 50% of these patients. This monitoring system is useful for screening of outpatients with sleep apnea and for epidemiological studies of sleep apnea. However, it may be necessary to include a non-invasive system for monitoring oxygen saturation in the portable sleep monitor, to detect hypoventilation during sleep.
Adolescent↗
Significant Correlation between the Presence of Type W Collagen in the Duct Wall and the Development of Wide Intraductal Cancerous Extension in Breast Cancer.
To identify the characteristics of cases with an wide intraductal cancerous extension (WICE), we examined the relationship between WICE and type IV collagen distribution, and the relationship between WICE and the content of the proliferation-associated proteins in human breast cancer. The immunohistochemical distribution of type IV collagen and proliferating cell nuclear antigen (PCNA) were investigated in formalin-fixed tissue sections from 21 breast cancer cases. We demonstrated a significant correlation (p=0.014) between the presence of WICE and immunostaining of type IV collagen in the cancerous ducts (ducts occupied by cancer cells) in the central invasive area of breast cancer. However, no correlation was found between the presence of WICE and the PCNA index (percentage of positive cells per 1000 tumor cells). These findings suggest that the lack of the process of the loss of type IV collagen in the duct wall is more important than the nature of the tumor cells in the development of WICE.
Journal Article↗
Association of Ash/Grb-2 with dynamin through the Src homology 3 domain.
Ash/Grb-2 is an adaptor protein composed only of Src homology (SH) 2 and SH3 domains that is considered to be essential for Ras activation. To clarify the downstream of Ash signaling, we investigated Ash-bound proteins. Ash-glutathione S-transferase (GST) fusion proteins were used to affinity-purify proteins bound to Ash. We found 180-, 150-, 100-, and 70-kDa proteins bound to GST-Ash, among which the 100 kDa protein was found to be dynamin by amino acid sequencing and Western blot with anti-dynamin antibody. Next, the in vitro and in vivo associations between Ash and dynamin were examined using PC12 cells. Dynamin in PC12 cell lysates bound to GST-Ash independent of NGF treatment. Also, Ash and dynamin co-precipitated when cell lysates of PC12 were immunoprecipitated with anti-Ash antibody or anti-dynamin antibody. Using various GST-Ash constructs, we studied the importance of the individual domains in binding and found that the SH3 domain is necessary for binding. This binding was inhibited by a synthetic peptide (GPPQVPSRPNRC, amino acids 827-838 in dynamin). These data show that Ash SH3 domains bind to the proline-rich region of dynamin. Considering the function of dynamin in membrane trafficking, Ash may regulate endocytosis in addition to Ras activation.
Adaptor Proteins, Signal Transducing↗
Kinetic properties of Ash/Grb2-interacting GDP/GTP exchange protein.
Ash/Grb2 is a protein having one SH2 domain flanked by two SH3 domains and is implicated to serve as an adaptor protein which links the EGF receptor to mammalian Sos (mSos), a GDP/GTP exchange protein for Ras. We isolated here several Ash-interacting proteins from bovine brain cytosol by use of glutathione-S-transferase-Ash-linked agarose column chromatography. The Ash-interacting proteins stimulated the GDP/GTP exchange reaction of Ki-Ras and Ha-Ras but not that of other small GTP-binding proteins including at least Rap1, RhoA, Rac1, and Rab3A. The Ash-interacting proteins were much more active on the post-translationally lipid-modified form of Ki-Ras than on the unmodified form. At least one of them was identified as mSos by Western blot analysis using a specific anti-mSos antibody.
Adaptor Proteins, Signal Transducing↗
Primary poorly differentiated adenocarcinoma of the middle ear.
Adenocarcinoma of the middle ear is seldom encountered in clinical practice. In the past 20 years, nearly 20 cases of primary adenocarcinoma of the middle ear have been reported, and most cases of these tumors have been described without histologic presentation. To our knowledge, only one case of adenocarcinoma originating in the postoperative middle ear has been reported. We describe a case of primary poorly differentiated adenocarcinoma in the middle ear which was surgically treated for chronic otitis media 50 years ago. Planning diagnostic and therapeutic procedures in connection with middle ear tumors is also discussed.
Adenosarcoma↗
Effects of submental stimulation for several consecutive nights in patients with obstructive sleep apnoea.
BACKGROUND: It has previously been reported that short term submental stimulation can reduce the frequency of apnoea and improve sleep architecture in patients with obstructive sleep apnoea. The effects of submental stimulation during consecutive nights on apnoea or on daytime sleepiness have not, however, been studied. METHODS: Patients with obstructive sleep apnoea were studied by polysomnography on a control night, for five consecutive nights of submental stimulation, and on three following nights (n = 8). A multiple sleep latency test (MSLT) (n = 8) and measurement of the upper airway resistance (n = 5) were performed during the day after the polysomnographic study, on the control night, and on the fifth stimulation night. In an additional five patients with obstructive sleep apnoea, matched for age, sex, and weight, the effects of two nights of stimulation were examined for comparison. Submental stimulation began when an apnoea lasted for five seconds and stopped with the resumption of breathing as detected by oronasal flow. RESULTS: The apnoea index, the number of times per hour that SaO2 dropped below 85% (SaO2 < 85%/hour), and the total apnoea duration expressed as a percentage of total sleep time during stimulation nights decreased to approximately 50% of the corresponding values on the control night. This improvement persisted for at least two nights after the five consecutive stimulation nights, but not after the two consecutive stimulation nights. Sleep architecture and MSLT following the stimulation nights improved but upper airway resistance did not change. CONCLUSIONS: Submental stimulation for five consecutive nights in patients with obstructive sleep apnoea improved the breathing disturbance, sleep quality, and daytime sleepiness. The effect lasted for the following two nights, but did not completely abolish the sleep disordered breathing.
Adult↗
Intracranial aneurysms: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography.
PURPOSE: To assess the accuracy of three-dimensional, Fourier transform, time-of-flight magnetic resonance (MR) angiography in the identification of intracranial aneurysms. MATERIALS AND METHODS: MR angiograms of 126 patients (59 male and 67 female patients, aged 12-77 years) with various intracranial vascular lesions were evaluated. Seventy-eight aneurysms, including 60 less than 5 mm in diameter, in 61 patients were depicted at conventional angiography. Eight projection images, as well as one axial collapsed MR angiogram obtained with a maximum-intensity projection algorithm, were used for evaluation. RESULTS: Sensitivity for the five observers ranged from 58% to 68% (mean, 63%). Higher sensitivity was achieved for anterior communicating and middle cerebral artery aneurysms, while that for internal carotid artery aneurysms was poor. Sensitivities for small and medium aneurysms ranged from 50% to 60% (mean, 56%) and from 77% to 94% (mean, 86%), respectively. CONCLUSION: MR angiography can depict intracranial aneurysms 5 mm or larger with good accuracy but is less useful for the identification of smaller aneurysms.
Algorithms↗
Intracranial vascular stenosis and occlusion: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography.
PURPOSE: To assess the accuracy of three-dimensional, Fourier transform, time-of-flight magnetic resonance (MR) angiography in the detection of intracranial steno-occlusive diseases. MATERIALS AND METHODS: One hundred thirty-one patients (62 male and 69 female patients, aged 6-77 years [mean, 53 years 8 months]) underwent MR and conventional angiography for evaluation of possible intracranial vascular disease. A total of 502 arteries were assessed. Eight projections and a collapsed image postprocessed by means of a maximum-intensity projection algorithm were reviewed by five observers in a blinded manner, with conventional angiography as the standard. RESULTS: A total of 32 steno-occlusive lesions were available for review. Receiver operating characteristic analysis from the pooled data revealed overall sensitivities of 85% and 88% and specificities of 96% and 97% for the internal carotid artery and the middle cerebral artery, respectively. CONCLUSION: MR angiography is useful as the primary diagnostic tool for evaluating suspected intracranial steno-occlusive disease.
Algorithms↗
Prostaglandin E1 abrogates early reductive stress and zone-specific paradoxical oxidative injury in hypoperfused rat liver.
This study was designed to investigate the effects of prostaglandin E1 on reductive stress and the subsequent oxidative cell injury in hypoperfused rat liver. The intralobular heterogeneity of hepatocellular redox state, mitochondrial dysfunction, and intracellular hydroperoxide formation were visually monitored by digital microfluorography of pyridine nucleotide autofluorescence, rhodamine 123, and dichlorofluorescein fluorescence, respectively. Under the 25% low flow perfusion, pyridine nucleotide autofluorescence increased time-dependently and reached a steady state at 10 min among the entire lobules. The decrease in mitochondrial membrane potential was > 20 mV in all portions of the lobules at 60 min. The onset of hydroperoxide formation was observed at 40 min in the marginally oxygenated proximal portion of anoxic pericentral regions and the oxidative impact reached a maximum level at 60 min. Sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazo [1,5-a]-1,3,5-triazine-4-olate monohydrate (BOF 4272), a novel xanthine oxidase inhibitor, suppressed the zone-specific oxidative changes without attenuating the increase in pyridine nucleotide autofluorescence and mitochondrial dysfunction. Pretreatment with prostaglandin E1 not only abrogated an early increase in pyridine nucleotide fluorescence and mitochondrial dysfunction induced by hypoperfusion but also diminished the subsequent midzonal oxidative injury. Since prostaglandin E1 has no oxyradical-scavenging action, the preventive effect of this reagent on the hypoxia-induced oxidative cell injury is attributable to the attenuation of mitochondrial dysfunction. These results suggest that, in low flow hypoxia, early reductive stress plays a key role in the initiation of xanthine oxidase-mediated midzonal oxidative changes, which may lead to subsequent centrilobular necrosis.
Alprostadil↗
Oxygen consumption of respiratory muscles in patients with COPD.
We measured the oxygen consumption (VO2) of respiratory muscles in 8 COPD patients and 12 age-matched healthy subjects using a closed circuit device which allows a continuous increase in external dead space and is equipped with a 9-L Collins spirometer. Furthermore, we measured simultaneously mouth occlusion pressure at 0.1 s of inspiration (P0.1), minute ventilation (VE), and other ventilatory parameters during the measurement of total VO2 (VO2 tot). We found that the logarithm of VO2tot (logVO2tot) had a good correlation with VE in both groups. The mean slope of the regression line of logVO2tot and VE (delta logVO2tot/delta VE) of COPD patients was significantly higher than that of normal subjects (p < 0.001). However, the mean Y-intercept (metabolic VO2[VO2met]) of the regression lines did not differ between the two groups. The P0.1 in COPD patients was higher than that in normal subjects at the corresponding dead space loading. However, the VE did not differ between the two groups except for at rest and the first 1 min after dead space loading. These results suggest that the VO2 of respiratory muscles in patients with COPD is higher at given ventilation compared with that in age-matched normal subjects and that this increased VO2 partly may be due to an augmented ventilatory drive.
Aged↗
[Bronchial asthma and desaturation--assessment by pulse oximetry].
In the first study, we used pulse oximetry to continuously measure SpO2 and pulse rate in inpatients with paroxysmal attacks of acute asthma. Desaturation and increases in pulse rate occurred during coughing, urination, defecation, eating, and sleeping. Desaturation was most severe and frequent when peak expiratory flow was in the red zone. When it was in the yellow zone or blue zone, desaturation was less severe and less frequent. In the second study, outpatients experiencing exacerbations of chronic asthma and inpatients experiencing acute asthmatic attacks inhaled of a beta 2-stimulant via an ultrasonic nebulizer and were monitored with pulse oximetry. In the former, SpO2 either did not change or increased, but in the latter SpO2 decreased markedly when patients were in the red zone. Therefore, when patients inhale a bronchodilator during an acute asthmatic attack they should be carefully monitored with pulse oximetry. In the third study, pulse oximetry was used to measure saturation in outpatients who were suspected of having hyperresponsive airways and had undergone an airway hyperresponsiveness test with an Astograph. Almost all of those who had desaturation of more than 4% from were markedly hyperresponsive. The degree of desaturation and the percent change in respiratory resistance were significantly correlated. In conclusion, pulse oximetry can be useful in the short-term and long-term management of asthma tic patients.
Adolescent↗
[Histopathological study of trabecular meshwork after trabeculotomy in monkeys].
Trabeculotomy is a commonly indicated surgical procedure for primary open angle glaucoma and congenital glaucoma. In order to clarify the mechanisms of lowering the intraocular pressure (IOP) following the intervention, we performed this procedure in monkey eyes, and did postoperative histopathological examinations using light microscopy, and scanning and transmission electronmicroscopy for trabecular mesh work specimens incised at various time intervals up to one year after operation. Immediately after the operation, a direct communication was seen between the Schlemm's canal and the anterior chamber. Subsequently, the repairing process of trabecular tissue occurred initially in the corneoscleral and endothelial meshwork and finally in the uveal meshwork. At one year after operation the chamber angle was almost completely repaired by newly-formed trabecular tissue which was identical to the normal trabecular tissue. There was no direct communication between the Schlemm's canal and anterior chamber at that time. These results suggest that the decreased resistance for the aqueous outflow might be caused by direct communication between the Schlemm's canal and anterior chamber at an early postoperative stage, and the repairing process of the endothelial meshwork increases the resistance of aqueous outflow.
Animals↗
[A case of subacute stroke with high uptake of 99mTc-HMPAO in the reperfused infarct corresponding to low perfusion area].
We reported a case of subacute stroke which showed high uptake of 99mTc-d,l-hexamethylpropyleneamine oxime (HMPAO) in the reperfused infarct corresponding to slightly decreased perfusion by 133Xe inhalation CBF measurement. In the chronic stage, both SPECT images of 99mTc-HMPAO and 133Xe showed low perfusion in the affected lesion. It was, therefore, considered that the high uptake of 99mTc-HMPAO had represented luxury perfusion. In the subacute stage of stroke, high uptake of 99mTc-HMPAO may imply luxury perfusion but not always hyperperfusion. It is suggested that the fractional fixation of 99mTc-HMPAO temporarily change in the affected lesion and it is essential to take into consideration the clinical stage for the interpretation of SPECT images.
Acute Disease↗
[Two cases of thyroid cancer resected with trachea].
We described two patients of thyroid cancer with tracheal invasion. A 54-aged female visited our hospital with complaint of the neck pain. Echography showed a tumor in the right lobe of the thyroid. In operation the thyroid tumor invaded the trachea and right recurrent nerve. A 24-aged male visited our hospital with complaint of a mass of the left side neck. Echography showed a tumor in the left lobe of the thyroid. In operation the thyroid tumor invaded the trachea, lymph node and left recurrent nerve. In these two cases we could find thyroid tumors invaded into the trachea by echography. We re-evaluated the utility of echography.
Adult↗
Combined analysis of flow cytometry and morphometry of ovarian granulosa cell tumor.
BACKGROUND: It is difficult to determine the prognosis of granulosa cell tumors (GCT) at the time of diagnosis. METHODS: The nuclear DNA content of 17 patients with ovarian GCT was investigated by flow cytometry using paraffin-embedded tissue. Nuclear area (NA), nuclear perimeter (NP), and nuclear shape factor (NSF) were measured by an image analyzer using hematoxylin- and-eosin-stained sections. RESULTS: The follow-up period of the patients ranged from 2 months to 11 years. Thirteen tumors were diploid or near diploid, whereas one was tetraploid, and three were aneuploid. Two tumors had varying degrees of DNA content heterogeneity. Crude survival of the patients with an euploid tumor (13 diploid, 1 tetraploid) was more favorable than that of the patients with an aneuploid tumor. Patients with S-phase fraction (SPF) greater than 10% or DNA content heterogeneity experienced disease recurrence or metastasis. A significant difference was observed in NA and NP between those with and without metastasis. CONCLUSIONS: Our results indicate that DNA aneuploidy, large SPF, DNA content heterogeneity, and large NA and NP are adverse prognostic factors in GCT. Thus, flow cytometric and morphometric measurement may provide a rapid and valuable method to predict the biologic behavior of GCT.
Adult↗
Immunohistochemical study of estrogen receptors and the responsiveness to estrogen in papillary thyroid carcinoma.
BACKGROUND: Epidemiologic data suggested that the differentiated thyroid carcinoma was affected by sex hormones, especially estrogen. METHODS: The authors have immunohistochemically studied estrogen receptors (ER) in papillary thyroid carcinoma in women. Two anti-ER monoclonal antibodies, D5 and H222, were used. The authors then investigated the responsiveness to estrogen of thyroid neoplasms using primary culture of surgically resected thyroid tissues. The proliferative activity of cultured cells was measured by the bromodeoxyuridine (BrdU) labeling index (LI). RESULTS: Twenty-six percent of the specimens (18/70) showed positive staining with D5, but only 5.6% of the specimens (2/36) showed positive staining with H222. The BrdU LI of ER-positive papillary thyroid carcinoma increased with the addition of estradiol. CONCLUSIONS: These findings indicate that estrogen may affect the proliferation of ER-positive papillary thyroid carcinoma.
Adolescent↗