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Biomedical subjects

T Musha

Publications and source records attributed to T Musha.

At least 19 recordsLinked to original sources
PubMed2001

Inhibition of erythropoietin signalling destroys xenografts of ovarian and uterine cancers in nude mice.

We have recently shown that malignant tumours from the ovary and uterus expressed erythropoietin (Epo) and its receptor (EpoR), and that deprivation of Epo signal in tumour blocks induced death of malignant cells and capillary endothelial cells in vitro (Yasuda et al, submitted). These in vitro results prompted us to examine the effect of Epo-signal withdrawal on tumours in vivo. RT-PCR analysis demonstrated the expression of mRNAs for Epo and EpoR in the transplants of uterine and ovarian tumours in nude mice. Then we injected locally anti-Epo antibody or soluble form of EpoR into the transplants. At 12 h, 1, 7 or 14 days after the injection, all transplants were resected and examined macro- and microscopically. Tumour size was reduced in Epo signal-deprived transplants. Immunohistochemical examinations revealed destruction of Epo-responding malignant and capillary endothelial cells through apoptotic death. The degree of tumour regression correlated well with the dose and frequency of the injections. Control xenografts with saline injection or needle insertion showed well-developed tumour masses. This Epo response pathway will have profound implications for our understanding of the development and progression of malignant tumours and for the use of Epo-signal deprivation as an effective therapy.

Animals↗
PubMed2001

Lipoprotein analysis using agarose gel electrophoresis and differential staining of lipids.

We established a strategy to directly measure cholesterol and triglyceride levels of each lipoprotein fraction using a combination of agarose gel electrophoresis and differential staining. The cholesterol and triglyceride levels determined by electrophoresis correlated significantly with those of ultracentrifugation. The correlation coefficients between these methods were, for cholesterol levels 0.975(very low density lipoproteins, VLDL), 0.986(low density lipoproteins, LDL) and 0.965(high density lipoproteins, HDL) and for triglyceride levels 0.994(VLDL), 0.963(LDL) and 0.959(HDL) respectively. Both intra-and inter-assays showed low values of coefficients of variation (CV) (less than 3.57%). We observed a strong linearity between staining and triglyceride concentration. An increased VLDL-cholesterol was observed in type III subjects, a result which enabled distinction between type III and type IIb or type V lipoproteinemia. The method revealed lipoprotein patterns in some samples otherwise unexpected from their corresponding serum lipid parameters. Analyses of these electrophoretic patterns thus provide an effective technique to classify types of hyperlipidemia defined by the WHO. Furthermore, quantitative measurement of chylomicrons, usually difficult, proved to be achievable, providing an additional analysis of postprandial hyperlipidemia and the exact measurement of LDL-cholesterol after diet. Consequently, we recommend this simple and easy method for clinical evaluation of abnormalities in lipoprotein profiles.

Chylomicrons↗
PubMed2001

Expression of erythropoietin in human female reproductive organs.

Erythropoietin (Epo) is known to be a lineage specific cytokine which regulates the number of circulating erythrocytes. Most of it is produced in the kidney. Recently, Epo has been reported to be synthesized in the normal brain, placenta, and capillary endothelium. We also have found that uterine endometrium expresses Epo signals in an estrogen-dependent manner, and that Epo contributes to angiogenesis in the endometrium in mice. To clarify the functional activity of Epo in human reproductive organs, we examined Epo signaling in these organs by Southern analysis of RT-PCR products and studied the distribution of substances relevant to Epo signal transduction by immunohistochemistry and Western blotting. Epo mRNA is expressed in the normal human cervix, endometrium and ovary, but it is not always detected in the specimens. Immunohistochemical analysis revealed Epo-receptor (EpoR) protein in: a) the endothelium of vessels, in glandular and surface epithelial cells, in decidual cells of the endometrium, and b) in follicles at various stages including oocytes, granulosa, theca interna cells and lutein cells of the ovary. Moreover, co-expression of JAK2 and phosphotyrosine, which reflects tyrosine phosphorylation via JAK2, and co-expression of EpoR and STAT5, which is a transcriptional factor relevant to mitogenic activity, were seen at these Epo-responsive sites. Western blotting analysis of these organs confirmed the immunohistochemical results. These findings imply that female reproductive organs can produce Epo, and that signal transduction of Epo contributes to the cyclic changes in the female reproductive organs.

Blotting, Southern↗
PubMed1999

Approximating dipoles from human EEG activity: the effect of dipole source configuration on dipolarity using single dipole models.

Dipolarity is the goodness-of-fit of the observed potential distribution with one calculated using specific assumptions about the source of the electrical potential distribution. We used computer simulations to examine the effect of different distributions of sources on their resulting dipolarity values. Electric dipoles were placed in a head-shaped model with uniform conductivity using four different dipole configurations (randomly oriented dipoles, a uniform dipole disk layer, a dipole disk layer with uniformly distributed holes, or one with randomly oriented dipoles). The best-fitting single dipole for each configuration was calculated and the dipolarity was computed as the mean squared error of the electrical potential distributions generated by the actual dipole configuration and by the best-fitting single dipole. The simulations show that: 1) a smooth dipole layer with or without holes gives dipolarities above 99.5% even when extended over areas as large as 1256 mm2; 2) randomly oriented dipoles under a smooth dipole layer also give dipolarities above 99.5%; and 3) randomly oriented and distributed dipoles, even if contained in a small portion of the total area, give dipolarities below 93.0%. These simulations show that inhomogeneity (holes) within a dipole disk layer per se do not lower dipolarity; rather, it is the random orientation and distribution of these dipoles which lowers dipolarity. Furthermore, dipolarity is not lowered by such randomly oriented and distributed dipoles when they are beneath a dipole disk layer.

Brain↗
PubMed1999

Cortical atrophy in Alzheimer's disease unmasks electrically silent sulci and lowers EEG dipolarity.

Alzheimer's disease (AD) patients show lower dipolarity (goodness-of-fit) for dipole localizations of alpha or other dominant electroencephalography (EEG) frequency components in the occipital cortex. In the present study, we performed computer simulations to discover which of distributions of dipole activity lower dipolarity in a manner similar to that seen in severe AD. Dipolarity was estimated from simulations of various electric dipole generator configurations within the occipital cortex under conditions of widened cortical sulci (a severely demented AD case) or no sulcal widening (a normal subject). The cortical and scalp surfaces, derived from the subjects' MRI's, were assumed to be uniformly electrically conducting. Randomly placed, nonoverlapping lesions ranging from 1 to 4 mm2 per lesion were used in both the normal and AD models to simulate the electrical effect of neuropathological AD lesions. In both models, dipolarity decreased as total lesion size increased. However, the AD model showed lower dipolarity than the normal model for both individual lesion sizes and for larger total lesion sizes. The larger decline in dipolarity in the AD model appears to be due to sulcal widening which unmasks the effect of lesions buried within sulci. These simulations identify a possible mechanism explaining why sulcally-located neuropathological changes plus progressive cortical atrophy in AD brains (and presumably other cortical disorders producing atrophy) alter EEG patterns and dipolarity differently from normal cortex damaged by similar lesions.

Adult↗
PubMed1999

Three-shell head model constructed from scalp geometry for electroencephalogram dipole localization.

One of the most sophisticated methods of dipole localization from (electroencephalograms) is based on a multi-compartment head model, which consists of the scalp, skull, cerebrospinal fluid (CSF) and brain cortex. The CSF layer in normal subjects is thin and can be ignored in dipole localization to good approximation. This multi-shell model is called the SSB (scalp-skull-brain) head model. The SSB head model is constructed from magnetic resonance imaging (MRI) or X-ray computed tomography slices of the head. These image slices, however, are not easy to obtain. The present paper presents a simple method for constructing the SSB head model only from the geometrical shape of the scalp, which is easily measured with a three-dimensional digitizer. We have derived a relationship between the head structure and the geometry of the head from statistical analysis of MRI slices of 12 normal subjects. The average estimation errors of the outer and inner boundaries of the skull were 1.2 and 2.2 mm, respectively. The head model thus estimated is called the sSSB (statistical SSB) model.

Adult↗
PubMed1999

Forward and inverse problems of EEG dipole localization.

Mathematical procedures are discussed in detail of numerical solutions for obtaining scalp potentials from the electric sources. The finite-element method for an inhomogeneous volume conductor, the boundary-element method for a compartment model, and their hybrid for more general cases are discussed. Construction of the head model and typical estimation of electric conductivity of the compartment model is described, which can reduce errors in estimated dipole location caused by incorrect head geometry. The concept of reciprocity is explained, which is applied to understanding a relation between the electrode configuration and its sensitivity for various source conditions. Typical techniques for solving the inverse problem are reviewed for discrete source models. Methods of estimating accuracy of the dipole location in the presence of noise are discussed, together with some numerical examples. The dipolarity is a goodness-of-fit of the dipole approximation, and lowering of the dipolarity is related to inhomogeneous neuronal activity in the cortex. Finally, a criterion of determining the optimal number of model parameters is given in terms of AIC (Akaike Information Criterion), which is applied to decide the most probable number of equivalent dipoles.

Brain↗
PubMed1998

Antibody to thrombin receptor inhibits neointimal smooth muscle cell accumulation without causing inhibition of platelet aggregation or altering hemostatic parameters after angioplasty in rat.

An antibody was raised in rabbits against SFFLRNPSEDTFEQF peptide, which is an NH2-terminal peptide of the thrombin-cleaved rat thrombin receptor. In vitro, the antibody inhibited rat smooth muscle cell proliferation but had no effect on rat platelet aggregation or clotting time. These data indicate that the antibody is a specific blocker of the thrombin receptor-signaling pathway in rat smooth muscle cells but does not work as a blocker in rat platelets, suggesting the existence of a second thrombin receptor in the platelets. Using an in vivo balloon catheter-induced injury model in rats, we examined the effect of the anti-rat thrombin receptor IgG on intimal smooth muscle cell accumulation 2 weeks after angioplasty. Analysis of the ratio of intimal to medial cross-sectional areas showed that injection of immune IgG resulted in 43.7% and 53.1% reduction (P<0.01) of neointimal smooth muscle cell accumulation compared with saline and nonimmune IgG treatment, respectively. Moreover, the injection of immune IgG caused a significant decrease of thrombin receptor mRNA expression and also 40.5% and 43.0% decreases (P<0.01) of the proliferating cell nuclear antigen (PCNA) index in the intima compared with the PCNA index after saline and nonimmune IgG treatment, respectively. The suppression of the PCNA index was also observed in the immune IgG-treated group at an early stage after angioplasty. These results suggest that thrombin receptor activation is involved in the proliferation and accumulation of neointimal smooth muscle cells induced by balloon injury.

Angioplasty↗
PubMed1998

Clinical usefulness of the dipole tracing method for localizing interictal spikes in partial epilepsy.

PURPOSE: To clarify the clinical usefulness of the dipole tracing method in evaluation of interictal EEG spikes in patients with partial epilepsy. METHODS: Eight patients with partial epilepsy were studied. We compared the generator source of interictal spikes detected by the dipole tracing method with the results of magnetic resonance imaging (MRI), interictal/ictal measurement of cerebral blood flow (CBF) by single photon emission computed tomography (SPECT), interictal measurement of glucose metabolism by positron emission tomography (PET) and invasive electrocorticogram (ECoG). RESULTS: In 5 patients with mesial temporal lobe epilepsy (TLE), including 3 patients who underwent standard temporal lobectomy, the dipole tracing method showed results consistent with those of other examinations and better correlation with ECoG than with other noninvasive examinations. In a patient with mesial TLE who had defects in the skull due to previous surgery, the dipoles were located more laterally than expected. In a patient with frontal lobe epilepsy (FLE) who was finally proved to have an epileptogenic area in the lateral frontal area, the spike dipoles were identified in the medial side of the frontal lobe. CONCLUSIONS: The dipole tracing method used in the present study is useful for localizing epileptogenic areas in patients with mesial TLE. However, in patients with partial skull defects and in those with FLE, the reliability of this method is still in accuracy of the lobe level.

Adolescent↗
PubMed1998

Urinary and salivary stress hormone levels while performing arithmetic calculation in a noisy environment.

The effects of environmental conditions on stress responses to mental work, were examined by measuring urinary catecholamine and cortisol excretion and salivary cortisol concentrations before, during and after an arithmetic calculation task under 90 dB(A) white noise and quiet conditions. Adrenaline excretion increased similarly during the task under both environmental conditions. The salivary cortisol level was significantly higher than the pre-task level during the task with noise, but not under quiet, conditions. The subjects reported that they felt more irritable when performing the task with noise, than under quiet conditions. The results suggest that environmental conditions may affect on the pattern of hormonal response to mental work, which may be related to psychological states of the subjects.

Adult↗
PubMed1998

[Assessment of enlarged left atrium with 99mTc-tetrofosmin SPECT and echocardiography].

This study was performed to clarify the possibility of visualization and quantification with 99mTc-tetrofosmin (Tf) myocardial scintigraphy in cases with a large atrium demonstrated by trans-thoracic echocardiography (TTE). Myocardial SPECT was evaluated in 4 patients with mitral stenosis and 15 patients with mitral regurgitation. Left atrium was identified in 12 out of 19 cases from an antero-posterior projection. The Tf uptake ratio of the left atrium, which was defined as the ratio of ROI count of the left atrium divided by the ROI count of the left ventricle, showed a good correlation with the left atrial area obtained by both trans-thoracic and trans-esophageal echocardiography (r = 0.88 and 0.91, respectively), These data suggest that Tf myocardial SPECT is a useful method of evaluating left atrial enlargement.

Aged↗
PubMed1995

Conductivity ratios of the scalp-skull-brain head model in estimating equivalent dipole sources in human brain.

The dipole tracing (DT) method estimates the position and vector dipole moment of an equivalent current dipole by minimizing the mean squared error of the dipole potentials at the surface electrode positions. In the scalp-skull-brain/DT (SSB/DT) method, which we have developed, the head model consists of three compartments of uniform conductors corresponding to the scalp, skull and brain. The accuracy of the calculations are mainly dependent on the ratios of the conductivities of the three compartments. The best result was obtained with the conductivity ratios of 1:1/80:1 for the scalp, skull and brain compartments, respectively.

Brain↗
PubMed1995

[The accuracy of computed tomography and magnetic resonance imaging in evaluating the extent of endometrial carcinoma].

The present study was designed to determine the accuracy of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in evaluating the extent of the tumor in 36 patients with endometrial carcinoma. The CT and MRI findings were compared with the microscopic pathologic characteristics in all cases. Linear regression analysis for measurements of residual normal myometrium revealed significant positive correlations (p < 0.001) between MRI (r = 0.861) and CT (r = 0.826) findings and pathologic evaluation. Thirty-six patients were divided into two groups according to our previous CT and MRI criteria: the superficial myometrial invasion group and advanced tumor group. In MRI findings, higher incidences of deep (> or = 1/2) myometrial invasion (p < 0.001), vessel permeation (p < 0.05) and cervical involvement (p < 0.05) were observed in the advanced group. In CT findings, deep myometrial invasion (p < 0.001) was observed in the advanced group. The incidence of extrauterine extension of the tumor did not differ significantly between CT and MRI findings. The accuracy figures for cervical involvement evaluated by CT and MRI were 83% and 86%, respectively. In four of 6 patients, in whom an intact Junctional zone (j-zone) was detected by MRI, the tumor was localized in the endometrium. The remaining 2 patients had only superficial myometrial invasion histologically. In all 16 patients, in whom the j-zone was interrupted in MRI findings, myometrial invasion was confirmed pathologically.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrial Neoplasms↗
PubMed1994

Location of electric current sources in the human brain estimated by the dipole tracing method of the scalp-skull-brain (SSB) head model.

Using a realistic, 3-shell head model including the scalp (S), skull (S) and brain (B) with conductivity ratios of 1:1/80:1, respectively, the electrical activity in the human brain recorded by conventional electroencephalography was approximated by 1 or 2 equivalent current dipoles. The dipole locations and vector moments were estimated by minimizing the squared difference between the potentials actually recorded from the scalp and those theoretically calculated from the equivalent dipoles. The validity of this dipole tracing method (the DT of the SSB head model) was tested in patients with focal epileptic seizures undergoing presurgical evaluation with intracranial subdural strip electrodes. Weak currents were passed through 1 or 2 pairs of subdural electrodes to create artificial dipoles. The dipole estimations correctly distinguished between single and double generator sources, but there were certain dislocations of the calculated dipoles. The average error of dislocation was found to be 8.5 mm for the 1-dipole model. That for the 2-dipole model was 6 mm for one of the components and 18 mm for the other. It was concluded that the DT method of the SSB head model can be a valuable clinical tool in 3-dimensional localization of focal epileptic discharges in the human brain.

Brain↗
PubMed1994

Localization of dipole by boundary element method in three dimensional reconstructed monkey brain.

The boundary element method was applied to 3-dimensionally reconstructed monkey brain to localize a current source generator (dipole) of somatosensory evoked potentials (SEPs) recorded from epidural electrodes under assumption that a brain is electrically homogeneous and is bounded by a high resistant substance (skull). Absolute mean deviation of estimated dipoles from actual dipoles artificially generated by electrical stimulation at known coordinates in the brain were within 1-3 mm. The estimated dipole computed from SEPs by right median nerve stimulation at latency of P10-N10 waves was located in area 3b of the somatosensory hand area in monkey. Our data suggest that this technique of locating dipoles by the boundary element method applied to a reconstructed brain allows accurate determination of the 3-dimensional coordinates of a dipole.

Algorithms↗
PubMed1994

Growth site localization of Rho1 small GTP-binding protein and its involvement in bud formation in Saccharomyces cerevisiae.

The Rho small GTP-binding protein family regulates various actomyosin-dependent cell functions, such as cell morphology, locomotion, cytokinesis, membrane ruffling, and smooth muscle contraction. In the yeast Saccharomyces cerevisiae, there is a homologue of mammalian RhoA, RHO1, which is essential for vegetative growth of yeast cells. To explore the function of the RHO1 gene, we isolated a recessive temperature-sensitive mutation of RHO1, rho1-104. The rho1-104 mutation caused amino acid substitutions of Asp 72 to Asn and Cys 164 to Tyr of Rho1p. Strains bearing the rho1-104 mutation accumulated tiny- or small-budded cells in which cortical actin patches were clustered to buds at the restrictive temperature. Cell lysis and cell death were also seen with the rho1-104 mutant. Indirect immunofluorescence microscopic study demonstrated that Rho1p was concentrated to the periphery of the cells where cortical actin patches were clustered, including the site of bud emergence, the tip of the growing buds, and the mother-bud neck region of cells prior to cytokinesis. Indirect immunofluorescence study with cells overexpressing RHO1 suggested that the Rho1p-binding site was saturable. A mutant Rho1p with an amino acid substitution at the lipid modification site remained in the cytoplasm. These results suggest that Rho1 small GTP-binding protein binds to a specific site at the growth region of cells, where Rho1p exerts its function in controlling cell growth.

Actins↗