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Biomedical subjects

H Hosoi

Publications and source records attributed to H Hosoi.

At least 19 recordsLinked to original sources
PubMed1999

Malignant rhabdoid-tumor cell line showing neural and smooth-muscle-cell phenotypes.

Malignant rhabdoid tumor (MRT) is a rare and extremely aggressive malignant tumor in childhood. In this study, an MRT cell line, designated KP-MRT-NS, was established from the ascitic fluid taken from an 11-month-old girl, whose tumor had originated from the left kidney. Ultrastructural findings demonstrated the typical aggregation of whorls of intermediate filaments. Chromosome constitution was described as 46, XX, add (10)(q26)[17]/46, idem, dis (1;2)(q22;q31)[3] based on ISCN (1995) and a del (22)(q11.2) was not found in this cell line. The origin of MRT is controversial, various cellular origins having been proposed because of the phenotypic diversity of MRT. Therefore, in this study, to clarify the origin of MRT, the expressions of cytoplasmic proteins including smooth-muscle-specific proteins (alpha-smooth-muscle actin, basic calponin, smooth-muscle-myosin-heavy-chain isoforms of SM1 and SM2) in the primary-MRT tissue and cell line were analyzed. In the primary-tumor tissue, the expressions of neurofilament, vimentin and alpha-smooth-muscle actin were demonstrated by indirect immunofluorescence. In the KP-MRT-NS cell line, the expression of neurofilament, alpha-smooth-muscle actin, basic calponin and smooth-muscle-myosin heavy chain of SM1 and SM2 isoforms was revealed by immunofluorescence, Western blot and/or reverse transcriptase-polymerase chain reaction (RT-PCR). MyoD1 mRNA, determined as a skeletal-muscle-cell lineage marker, was not expressed in the primary-tumor tissue or in the KP-MRT-NS cell line. According to our findings, the MRT cells are of both neural and smooth-muscle cell phenotypes, and support the neural-crest origin of MRT.

Blotting, Western↗
PubMed1999

Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells.

The mammalian target of rapamycin (mTOR) has been shown to link growth factor signaling and posttranscriptional control of translation of proteins that are frequently involved in cell cycle progression. However, the role of this pathway in cell survival has not been demonstrated. Here, we report that rapamycin, a specific inhibitor of mTOR kinase, induces G1 cell cycle arrest and apoptosis in two rhabdomyosarcoma cell lines (Rh1 and Rh30) under conditions of autocrine cell growth. To examine the kinetics of rapamycin action, we next determined the rapamycin sensitivity of rhabdomyosarcoma cells exposed briefly (1 h) or continuously (6 days). Results demonstrate that Rh1 and Rh30 cells were equally sensitive to rapamycin-induced growth arrest and apoptosis under either condition. Apoptosis was detected between 24 and 144 h of exposure to rapamycin. Both cell lines have mutant p53; hence, rapamycin-induced apoptosis appears to be a p53-independent process. To determine whether induction of apoptosis by rapamycin was specifically due to inhibition of mTOR signaling, we engineered Rh1 and Rh30 clones to stably express a mutant form of mTOR that was resistant to rapamycin (Ser2035-->Ile; designated mTOR-rr). Rh1 and Rh30 mTOR-rr clones were highly resistant (>3000-fold) to both growth inhibition and apoptosis induced by rapamycin. These results are the first to indicate that rapamycin-induced apoptosis is mediated by inhibition of mTOR. Exogenous insulin-like growth factor (IGF)-I protected both Rh1 and Rh30 from apoptosis, without reactivating ribosomal p70 S6 kinase (p70S6K) downstream of mTOR. However, in rapamycin-treated cultures, the response to IGF-I differed between the cell lines: Rh1 cells proliferated normally, whereas Rh30 cells remained arrested in G1 phase but viable. Rapamycin is known to inhibit synthesis of specific proteins but did not inhibit synthesis or alter the levels of mTOR. To examine the rate at which the mTOR pathway recovered, the ability of IGF-I to stimulate p70S6K activity was followed in cells treated for 1 h with rapamycin and then allowed to recover in medium containing > or =100-fold excess of FK506 (to prevent rapamycin from rebinding to its cytosolic receptor FKBP-12). Our results indicate that, in Rh1 cells, rapamycin dissociates relatively slowly from FKBP-12, with a t1/2 of approximately 17.5 h. in the presence of FK506, whereas there was no recovery of p70S6K activity in the absence of this competitor. This was of interest because rapamycin was relatively unstable under conditions of cell culture having a biological t1/2 of approximately 9.9 h. These results help to explain why cells are sensitive following short exposures to rapamycin and may be useful in guiding the use of rapamycin analogues that are entering clinical trials as novel antitumor agents.

Apoptosis↗
PubMed1999

Suggestion audiometry for non-organic hearing loss (pseudohypoacusis) in children.

Pertaining to non-organic hearing loss in children, three goals should be attained: detection of this disease, determination of true hearing levels and information about the possible cause. Recently, objective tests have been used principally for children with non-organic hearing loss; however, these lack the simplicity and convenience of traditional audiometry. A new method, which is referred to as suggestion audiometry, since it is suggested to the patient that hearing will be improved as a result of the test procedure, was developed for the purpose of simultaneously achieving the above-stated three goals. The subjects were 20 patients aged 8-16 years suspected of demonstrating non-organic hearing loss and whose apparent hearing loss had been identified by school hearing examinations. Suggestion pure tone audiometry was useful for the detection of non-organic hearing loss and suggestion speech audiometry was valuable for the determination of true hearing levels. The subjects were classified into four groups according to the test results. We discuss causes of the disease based on the classification of the subjects obtained from this test procedure.

Adolescent↗
PubMed1999

Amino acid-dependent control of p70(s6k). Involvement of tRNA aminoacylation in the regulation.

In human T-lymphoblastoid cells, downstream signaling events of mammalian target of rapamycin (mTOR), including the activity of p70(s6k) and phosphorylation of eukaryotic initiation factor 4E-binding protein 1, were dependent on amino acid concentration in the culture media, whereas other growth-related protein kinases were not. Amino acid-induced p70(s6k) activation was completely inhibited by rapamycin but only partially inhibited by wortmannin. Moreover, amino acid concentration similarly affected the p70(s6k) activity, which was dependent on a rapamycin-resistant mutant (S2035I) of mTOR. These data indicate that mTOR is required for amino acid-dependent activation of p70(s6k). The mechanism by which amino acids regulate p70(s6k) activity was further explored: 1) amino acid alcohols, which inhibit aminoacylation of tRNA by their competitive binding to tRNA synthetases, suppressed p70(s6k) activity; 2) suppression of p70(s6k) by amino acid depletion was blocked by cycloheximide or puromycin, which inhibit utilization of aminoacylated tRNA in cells; and 3) in cells having a temperature-sensitive mutant of histidyl tRNA synthetase, p70(s6k) was suppressed by a transition of cells to a nonpermissible temperature, which was partially restored by addition of high concentrations of histidine. These results indicate that suppression of tRNA aminoacylation is able to inhibit p70(s6k) activity. Deacylated tRNA may be a factor negatively regulating p70(s6k).

Amino Acids↗
PubMed1999

Variable-speech-rate audiometry for hearing aid evaluation.

A new hearing aid evaluation method using variable-speech-rate audiometry (VSRA) was developed. VSRA was newly created based on the Japanese speech audiometry authorized by the Japan Audiological Society. The ordinary speech audiometry can not reveal a temporal factor in word discrimination ability of the hearing impaired. Since, with VSRA, we can compare several performance-intensity curves obtained from different speech-rate speech audiometries, the impact on the auditory system of each patient by the fast or slow speech rate could be easily determined. Taking the temporal factor of the auditory systems into consideration by using VSRA, hearing aid evaluation was performed for a master hearing aid with three types of signal processing and fitting for 36 hearing impaired subjects. Then hearing aid evaluation was performed using VSRA for a newly developed portable multi-function digital hearing aid with two types of signal processing and analog hearing aids which had been used by hearing-impaired patients. As a result, VSRA was useful for hearing aid evaluation, in particular, for cases when ordinary normal speech rate audiometry does not provide a significant difference in word discrimination scores. In addition, using VSRA revealed that amplitude compression is more effective for improvement of word discrimination than linear amplification.

Adolescent↗
PubMed1999

Development of adaptive phonetic gestures in children: evidence from vowel devoicing in two different dialects of Japanese.

High vowels between voiceless consonants are often devoiced in many languages, as well as in many dialects of Japanese. This phenomenon can be hypothesized to be a consequence of the adaptive organization of the laryngeal gestures to various conditions, including dialectal requirements. If this theory is correct, it may be possible to predict developmental changes in vowel devoicing based on the developmental improvement in the dialect-specific organization of the laryngeal gestures. To test this expectation, the developmental properties of vowel devoicing were investigated for 72 children of 4 and 5 years of age, and 37 adults in two dialects of Japanese. One was the Osaka dialect, with a low devoicing rate, and the other the Tokyo dialect, with a high devoicing rate. In the Tokyo dialect, the devoicing rate of children significantly increased and reached an adultlike level by the age of 5 years, whereas it remained low irrespective of age in Osaka. The vowel devoicing of 5-year-old children exhibited the same characteristics as that of the adults of their respective dialect. These results suggest that children growing up with the Tokyo dialect acquire the articulatory gestures which do not inhibit vowel devoicing by the age of 5 years, whereas children growing up with the Osaka dialect acquire those which inhibit the devoicing of vowels by the same age. The results fit in well with the predictions of the gestural account of vowel devoicing. It is also suggested that learning dialect-specific adaptive strategies to coordinate voicing and devoicing gestures as required to attain an adultlike vowel devoicing pattern is a long process: By the age of 5 years children have completed enough of this process to become members of their dialectal community.

Adaptation, Psychological↗
PubMed1998

Task-dependent laterality for cue decoding during spoken language processing.

The task-dependent laterality of the auditory cortices was investigated by measuring the magnetic fields elicited by three forms of a Japanese verb, which differed in terms of prosodic and phonetic cues. Significant task-dependent magnetic fields were found in both hemispheres during a prosody-related task, but only in the left during a phoneme-related task. The latency was similar to the mismatch negatively which reflects the neural activity of automatic cue decoding. These results suggest that task-dependent schemata are activated at least partially in parallel with automatic cue-decoding processes such that those in the left hemisphere process linguistic information irrespective of acoustic cues whereas those in the right hemisphere process prosodic information.

Adult↗
PubMed1998

Malignancies of human thyroid tumors and dynamic magnetic resonance imaging (MRI).

Time intensity curves for gadolinium-diethylene triaminepentacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI), namely dynamic MRI, were determined for thyroid diseases and compared with findings of histopathologic examination. Time intensity curves for solid lesions were determined, excluding cases with secondary changes such as calcification, hemorrhage, necrosis and fibrosis. Three different patterns of time intensity curves were observed: rapid washout, delayed washout and no change. In our previous study, malignant grades of thyroid tumors were estimated immunohistochemically by epidermal growth factor receptor (EGFR) antibody. In most of malignant diseases and a few benign diseases that had marked cell proliferative activity with staining EGFR strongly, the time intensity curve displayed a delayed washout pattern, in which intensity was above 1/2-maximal value within 10 min after injection Gd-DTPA. Almost all benign diseases and a few well differentiated carcinomas displayed a rapid washout pastern, in which intensity was decreased to lower than 1/2 of peak grade within 10 min following injection and showed staining EGFR weakly. Benign diseases showing no change of time intensity curve, did not almost show aEGFR positive cell. These findings suggested that the time intensity curve obtained from dynamic MRI might indicate differentiated grades and cell proliferating activity of thyroid tumors.

Contrast Media↗
PubMed1998

Long-term observation after soft posterior meatal wall reconstruction in ears with cholesteatoma.

We performed tympanoplasty with reconstruction of the soft posterior meatal wall for the prevention of post-operative retraction pocket formation. Our method is characterized by the reconstruction of the soft posterior meatal wall, non-obliteration with permanent or temporary materials, including Gelfoam, no use of a Palva flap and the use of fibrin glue for attaching the fascia to the posterior meatal skin. None of the patients experienced post-operative narrow-neck retraction pocket formation, and whenever aeration of the middle ear was disturbed, a balloon-like retraction was observed. Not all the posterior meatal walls retracted. The final position of the posterior meatal wall varied among the subjects. No serious cavity or hearing problems have occurred since surgery. Due to the strong possibility of post-operative retraction pocket formation in cases with a large balloon-like retraction, we rejected adopting the canal wall up technique or hard posterior meatal wall reconstruction.

Cholesteatoma, Middle Ear↗
PubMed1998

Studies on the mechanism of resistance to rapamycin in human cancer cells.

Rapamycin is a potent cytostatic agent that arrests cells in the G1 phase of the cell cycle. The relationships between cellular sensitivity to rapamycin, drug accumulation, expression of mammalian target of rapamycin (mTOR), and inhibition of growth factor activation of ribosomal p70S6 kinase (p70(S6k)) and dephosphorylation of pH acid stable protein I (eukaryotic initiation factor 4E binding protein) were examined. We show that some cell lines derived from childhood tumors are highly sensitive to growth inhibition by rapamycin, whereas others have high intrinsic resistance (>1000-fold). Accumulation and retention of [14C]rapamycin were similar in sensitive and resistant cells, with all cells examined demonstrating a stable tight binding component. Western analysis showed levels of mTOR were similar in each cell line (<2-fold variation). The activity of p70(S6k), activated downstream of mTOR, was similar in four cell lines (range, 11.75-41. 8 pmol/2 x 10(6) cells/30 min), but activity was equally inhibited in cells that were highly resistant to rapamycin-induced growth arrest. Rapamycin equally inhibited serum-induced phosphorylation of pH acid stable protein I in Rh1 (intrinsically resistant) and sensitive Rh30 cells. In serum-fasted Rh30 and Rh1 cells, the addition of serum rapidly induced c-MYC (protein) levels. Rapamycin blocked induction in Rh30 cells but not in Rh1 cells. Serum-fasted Rh30/rapa10K cells, selected for high level acquired resistance to rapamycin, showed >/=10-fold increased c-MYC compared with Rh30. These results suggest that the ability of rapamycin to inhibit c-MYC induction correlates with intrinsic sensitivity, whereas failure of rapamycin to inhibit induction or overexpression of c-MYC correlates with intrinsic and acquired resistance, respectively.

Adaptor Proteins, Signal Transducing↗
PubMed1998

[A clinical and portal hemodynamic analysis for obliteration of gastric-renal shunt communicated with gastric fundic varices].

To clear the efficacy of treatment for large porto-systemic shunts, changes of liver function and portal hemodynamics after obliteration of gastric-renal shunt (GRS) or gastric-inferior phrenic vein shunt (GIS) communicated with gastric fundic varies in 24 patients treated with balloon-occluded retrograde transvenous obliteration (B-RTO) were studied. 1) The wedged hepatic venous pressure and the hepatic venous pressure gradient were statistically not significant changed after obliteration of GRS or GIS. 2) Serum albumin value was significantly increased (p < 0.005) and ICGR15 was significantly improved (p < 0.005) at one year after treatment in patients that, not only whose GRS or GIS were larger than 10mm in diameter, but also whose superior mesenteric arterial venography before treatment showed hepatofugal flow. 3) At a mean follow-up abdominal angiography of 23.3 months in 20 cases, GRS or GIS was yet obliterated respectively. And more, superior mesenteric arterial venography revealed hepatopetal flow alone in 43% of patients that, whose superior mesenteric arterial venography before treatment showed hepatofugal flow. 4) During a mean follow-up of 32.5 months, gastric fundic varies were not recurrent in all patients, but the other hand, cumulative red color sign positive esophageal varies apparent rates were high (16.7% at before treatment, 38.4% at 2-years, 54.4% at 4-years). According to their hemodynamic characteristics, cumulative red color sign positive esophageal varies apparent rates in patients with another collaterals besides GRS or GIS before treatment (26.7% at before treatment, 61.1% at 2-years, 74.1% at 4-years) were significantly higher (p < 0.05) than those in patients without another collateral except GRS or GIS (0% at 2-years, 16.7% at 4-years). We conclude that, 1) Increment of portal flom and improvement of liver function can be expected by obliteration of GRS or GIS in patients that, whose superior mesenteric venous blood flow into large GRS or GIS. 2) After obliteration of GRS or GIS, the incidence of aggravation of esophageal varies in patients with another collaterals besides GRS or GIS before treatment is high, while that in cases without another collateral is low.

Adult↗
PubMed1997

Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin.

The immunosuppressant rapamycin interferes with G1-phase progression in lymphoid and other cell types by inhibiting the function of the mammalian target of rapamycin (mTOR). mTOR was determined to be a terminal kinase in a signaling pathway that couples mitogenic stimulation to the phosphorylation of the eukaryotic initiation factor (eIF)-4E-binding protein, PHAS-I. The rapamycin-sensitive protein kinase activity of mTOR was required for phosphorylation of PHAS-I in insulin-stimulated human embryonic kidney cells. mTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E. These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Quantitative scintigraphic analysis of 123I-MIBG by polar map in patients with dilated cardiomyopathy.

To evaluate sympathetic dysfunction of the heart, one of the factors responsible for heart failure in patients with dilated cardiomyopathy (DCM), we performed 123I-metaiodobenzylguanidine (123I-MIBG) myocardial single photon emission tomography (SPET) in 22 cases of DCM. There were significant relationships between severity scores and defect scores for the early and delayed images. When the data acquired by 123I-MIBG myocardial SPET were compared with left ventricular function, the extent score (r = -0.754, P < 0.01) and severity score (r = 0.693, P < 0.01) for the early images were both significantly correlated with left ventricular ejection fraction (LVEF). For the delayed images also, a good correlation was obtained between LVEF and extent score (r = -0.704, P < 0.01) and between LVEF and severity score (r = -0.801, P < 0.01). the washout rate for the entire left ventricle, calculated from the early and delayed images, also correlated with LVEF (r = -0.643, P < 0.01). Since the 123I-MIBG defect on the early images was shown to be significantly related to left ventricular function, a decrease in neuronal uptake at sympathetic nerve endings appears in the main to account for the 123I-MIBG defect on the early images. The regional washout rate was increased compared to that in the control group (P < 0.01). It was particularly high in the inferior wall, suggesting that acceleration of turnover and poor retention in the area of the 123I-MIBG defect on the early images and then the entire left ventricle was strongly associated with the 123I-MIBG defect on the delayed images. Our results suggest that 123I-MIBG myocardial SPET may be useful in determining the severity of DCM.

3-Iodobenzylguanidine↗
PubMed1996

Clinical application of three-dimensional myocardial imaging: evaluation of efficacy of medical treatment on myocardial perfusion.

To investigate the clinical applicability of the three-dimensional (3D) myocardial imaging using a newly developed system (the Application Visualization System-Medical Viewer), thallium-201 myocardial single photon emission computed tomography was performed in 19 patients with previous myocardial infarction before and after treatment with nisoldipine. We have developed a new method for automatically reconstructing 3D imaging for the stereoscopic evaluation of myocardial perfusion. The left ventricular myocardial volume with a radioisotope count > or = 50% of maximum was calculated by using the conventional surface rendering method. With these images, the effect of nisoldipine on myocardial perfusion was assessed and the myocardial volume with a radioisotope count > or = 50% of maximum was compared. In fifteen (88%) of 19 patients, myocardial perfusion increased in the infarct areas after nisoldipine treatment. Nisoldipine significantly increased the myocardial volume with a radioisotope count > or = 50% of maximum from 141 +/- 17 to 153 +/- 18 ml on the stress 3D imagings. These findings indicate that nisoldipine improved myocardial perfusion during exercise. 3D imaging provided stereoscopic assessment of the changes in myocardial perfusion following treatment with nisoldipine and also detected transient enlargement of the left ventricular lumen induced by exercise.

Aged↗
PubMed1996

Estimating myocardial damage and the need for surgery in patients with valvular heart disease by Tl-201 SPECT.

Left ventricular myocardial disorders due to volume overload were investigated by Tl-201 myocardial SPECT (Tl-201 SPECT) in patients with aortic or mitral regurgitation, and its utility for timing cardiac valve replacement was studied. There were significant correlations between Tl-201 scores and electrocardiographic changes and the New York Heart Association classification. There also were favorable correlations between Tl-201 scores and the left ventricular end-diastolic dimension and between Tl-201 scores and left ventricular ejection fraction, and a close relationship between the presence of a left ventricular myocardial disorder and left ventricular diameter. These results suggest that myocardial perfusion abnormalities and left ventricular myocardial disorders may accompany left ventricular dilatation owing to volume overload. After valve replacement, left ventricular end-diastolic dimension normalized, and Tl-201 scores improved slightly, suggesting normalization of myocardial perfusion. When moderate or more severe Tl-201 defects are present on Tl-201 SPECT images, in addition to inverted Tl-201 waves on the electrocardiogram or a left ventricular end-diastolic dimension of 65 mm or more, cardiac valve replacement should be considered.

Aortic Valve Insufficiency↗
PubMed1995

Using biopsy materials to detect mutations in gastrointestinal tumors.

Because endoscopic examinations are a crucial first step in the diagnosis of carcinomas, we have analyzed point mutations of the c-K-ras and p53 genes using biopsied samples. There is no previous report of such an approach, using only biopsied materials. We analyzed point mutations of the c-K-ras and p53 genes using 60 colorectal and 31 gastric tumor biopsy specimens. None of the gastric and seven of the colorectal tumors had mutations of the c-K-ras gene. p53 gene mutations were detected in six gastric carcinomas [two out of 11 intramucosal carcinomas (18.2%) and four out of 11 invasive carcinomas (36.4%)]. Eight of 15 invasive colorectal carcinomas (53.3%) showed point mutations in the p53 gene. Although point mutation frequencies in this study were relatively low when compared with previous reports in which surgical samples were used, our study shows that biopsied specimens are adequate and useful for analysis of gene point mutations.

Adenocarcinoma↗