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Biomedical subjects

N Mishima

Publications and source records attributed to N Mishima.

At least 37 records · Page 2Linked to original sources

Plasma-free and sulfoconjugated MHPG in major depressive disorders: differences between responders to treatment and nonresponders.

The plasma levels of free and sulfoconjugated forms of 3-methoxy-4-hydroxyphenylglycol (MHPG) were examined before and after treatment in 16 patients with unipolar major depressive disorders without melancholia. The patients were treated with intravenous administration of clomipramine for 4 weeks. Seven depressive disorder patients who showed marked improvement (the improvement group) revealed significant reduction in their plasma sulfoconjugated MHPG levels. In 6 depressive disorder patients who showed no improvement (the no-improvement group), the plasma sulfoconjugated MHPG levels showed no significant change after treatment. The remaining 3 patients, who showed ambiguous change after treatment, were excluded from the analysis. Levels of plasma-free MHPG showed significant change after treatment in neither the improvement group nor in the no-improvement group. It is suggested that levels of plasma sulfoconjugated MHPG may serve as an indicator of brain noradrenergic activity.

Adolescent↗

Backtransplantation of chick cardiac neural crest cells cultured in LIF rescues heart development.

The cardiac neural crest is essential for normal development of the cardiovascular system. Cardiac neural crest cells are derived from the neural folds located between the mid-otic placodes and the caudal limit of somite 3. These crest cells can differentiate into a variety of mesenchymal cell types that support cardiovascular development, in addition to neurogenic cells. When cultured, many express alpha-smooth muscle actin or neurofilaments and lose their undifferentiated neural crest phenotype as shown by a decrease in HNK-1 reactivity. We wanted to determine whether cultured cardiac neural crest cells maintained the potency to support normal heart development when backtransplanted into embryos lacking their native cardiac neural crest. Under usual circumstances removal of the cardiac neural crest results in 80-100% incidence of persistent truncus arteriosus. The present study reports a system in which cardiac neural folds are cultured for 3 days and the cells backtransplanted into chick embryos after laser-induced ablation of the intrinsic cardiac neural folds. Rescue of heart development was improved 50% when cultured cells were backtransplanted and almost 200% when the backtransplanted cells had been cultured in leukemia inhibitory factor (LIF). To determine whether the cultured cells are capable of following normal migratory routes, cultured homospecific cardiac neural crest cells were tagged with DiI. Initially, fluorescent cells were found concentrated around the neural tube. By the second day following backtransplantation, the cells had migrated to the circumpharyngeal crest, populated the pharyngeal arches and aortic arch arteries, and were in the region of the cardiac outflow tract. By the third day, the labeled cells had dispersed, but could be found around the neural tube, esophagus, cardiac outflow tract, and within the dorsal root ganglia. Interestingly, a cranial migration to the periphery of the eyes was also noted. With the exception of the cranial migration to the eyes, cultured and backtransplanted cardiac neural crest cells followed normal migratory pathways to the cardiac outflow tract. LIF is used for the in vitro maintenance of the pluripotential phenotype of embryonic stem cells. In an effort to understand why LIF improves the ability of cultured neural crest cells to support normal heart development, we have examined the relationship of neural crest expression of HNK-1 antigen, alpha-smooth muscle actin, and neurofilament protein in neural crest cells cultured in LIF. LIF treatment resulted in an expanded period of expression of HNK-1 antigen, associated with a decrease in expression of alpha-smooth muscle actin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The 32.6 kb Indian delta beta-thalassaemia deletion ends in a 3.4 kb L1 element downstream of the beta-globin gene.

The Indian delta beta-thalassaemia, with elevated fetal gamma globin gene expression, was previously found to have a large deletion beginning 1 kb 3' of the (A) gamma globin gene at GenBank HUMHBB coordinate 42151, and extending into a new L1 sequence. We have now determined the 3' breakpoint of this deletion, and in doing so we have extended the known beta-globin gene cluster DNA sequence from its end at 73326 to projected GenBank coordinate 79016. These data show that the deletion is 32.6 kb long, terminating 11 kb 3' of the beta-globin gene. This 3' breakpoint is at 74772, within a 3.4 kb partial L1 repeat at 74263-77665; the Black ((A) gamma delta beta)(0)-thalassaemia also terminates in this L1, at 76508. In addition, two Alu sequences were found, at 73692-73816 and 78171-78441. Among the protein-binding DNA sequence motifs 3' to the Indian delta beta-thalassaemia breakpoint, at 76581/76607 there is a TGATAA/ACACCC pair that binds the erythroid-specific GATA-1 and ubiquitous CACCC-box binding proteins. We hypothesize that elevated fetal haemoglobin may be due to an enhancer or enhancers 3' to the deletion breakpoints and may involve the TGATAA/ACACCC pair.

Base Sequence↗

Preliminary results of interstitial 192Ir brachytherapy for malignant gliomas.

Twenty-six patients with recurrent or unremovable malignant gliomas were treated by interstitial brachytherapy with iridium-192 seeds. Stereotactic implantation of the afterloading catheters using the Brown-Roberts-Wells computed tomography (CT)-guided stereotactic system was performed in 24 patients and surgical implantation in two patients with pontine glioma. The response to therapy was measured by serial CT, magnetic resonance imaging, and clinical examination. Tumor regression was seen in 17 patients 1-3 months after implantation. Tumor progression was seen in only three patients. After interstitial brachytherapy, the most commonly observed CT finding was central low density. Median survival time was 18 months after implantation. Autopsies in five patients revealed the delayed effects of radiation injury such as typical vascular changes, microcalcification, and coagulative necrosis in the implant area and tumor recurrence at the periphery. The results suggest that brachytherapy is not curative but prolonged the median survival time by 6 months.

Adult↗

[Analysis of tumor-infiltrating lymphocyte in primary malignant lymphoma of the central nervous system using double immunofluorescence staining method].

Three cases of malignant lymphoma were examined immunohistochemically using anti-Leu monoclonal antibodies (MAB) against B lymphocytes, T lymphocytes subsets, NK cells, IL-2 receptor. In all three cases tumor cells were stained with anti-B cell's MABs, that is they were diagnosed as B cell type of malignant lymphoma. Moderate tumor-infiltrating lymphocytes in the parenchyma or around blood vessels were observed, and majority of these cells were T lymphocytes, demonstrating Leu 2a or Leu 3a + 3b positive phenotypes. IL-2 receptor positive cells also found in the parenchyma of these tumors. T lymphocyte subsets, such as Leu 2a positive cells and Leu 3a + 3b positive cells, were analyzed by means of double immunofluorescence staining method using the combination of Leu 2a and Leu15, or Leu 3a + 3b and Leu 8 MABs. This method demonstrated that most of Leu 2a positive cells were negative for Leu 15 and that the majority of Leu 3a + 3b positive cells were negative for Leu 8. These results suggested that tumor-infiltrating lymphocytes in the malignant lymphoma were mainly activated cytotoxic or helper T cells.

Brain Neoplasms↗

[A study of the dynamics of gallbladder contraction in irritable bowel syndrome].

We examined gallbladder motility function after intramuscular injection of caerulein (0.2 micrograms/kg) to the cases of irritable bowel syndrome (IBS) by using ultrasonography. We measured gallbladder area pre and after caerulein injection (0' 5' 10' 15' 20' 25' 30' 40' 50' 60') and calculated contraction rate of gallbladder in each time. We applied one way analysis of variance among the four groups [diarrhea group (N = 9), alternative group (N = 8), constipation group (N = 8), control group (N = 15)]. Gallbladder contraction rate was low in diarrhea group and high in constipation group (p less than 0.05). And then we classified gallbladder contraction pattern to three groups (hyperkinetic, intermediate, hypokinetic). These three groups correlated bowel habits and biliary knocked pain. Therefore, constipation group showed hyperkinetic tendency and diarrhea group showed hypokinetic tendency (chi 2 analysis: p = 0.004 CMH analysis: p = 0.001). And biliary knocked pain significantly appeared in constipation group and hyperkinetic type of gallbladder (chi 2 analysis: p = 0.026, CMH analysis: p = 0.019). Consequently, it was suggested that bowel habits concerned with abnormality of gallbladder motility function in IBS.

Adolescent↗

[A study on the mechanism of microvibration changes in patients with eating disorders].

Microvibration (MV), which is a minute vibration observed on the human body surface, has been used clinically as a simple test for the autonomic nervous system function in psychosomatic medicine. The analogue frequency analysis has shown four different MV types in healthy subjects, depending on a major frequency component of MV. Although N type, a MV type with predominant frequencies being in the alpha band, is most common in healthy subjects, we have found that F type, the predominant frequencies being in the fast frequency (beta) band, is most common in patients with psychosomatic disorders, particularly in those with eating disorders. We have developed a system of digital frequency analyses of MV on a personal computer, in which the Fast Fourier Transform (FFT) and the reverse FFT are employed. In this study, the physiological significance of MV changes was investigated in patients with eating disorders, utilizing frequency analysis methods of the analogue and digital systems. The following results and conclusions were obtained. (1) A multiple regression analysis was performed to clarify the relationship between somatic severity (body weight change) and MV frequency bands by the analogue method in 57 patients with eating disorders. Percent change of body weight (% BW) was used as a target (dependent) variable, and 6 frequency bands of MV energy % were used as explanatory (independent) variables. The alpha 1 (7.5-8.5 Hz) and the beta (13-20 Hz) bands were selected as having a high explanatory power for % BW, with the alpha 1 band being greater than the beta band. This indicated that the reduction of % BW had a higher correlation with the decrease of the alpha 1 band than with the increase of the beta band. (2) The reverse FFT of a MV power spectrum was calculated with the digital method to extract frequency bands that was time-locked with ECG. This revealed that the time-locked oscillations were always found in the alpha band in either normal subjects or patients with eating disorders, regardless of the MV type. This indicated that the ballistocardiographic component of MV is included in the alpha band. (3) Putting all these results together, it is concluded that, in patients with eating disorders, the predominance of the beta band in MV (the F type) is caused by the decrease of the ballistocardiographic component of MV.

Adult↗

[Clinical application of micro-vibration to autonomic function test].

Microvibration (MV) is the minute vibration observed on surface of the human body. MV on the thenar eminence has been used as an autonomic function test, and is one of the important psychophysiological methods in psychosomatic medicine because the measurement of MV is not invasive. Although the mechanism generating MV has not been definitely clarified, there seems to be two major components, a ballistocardiographic one and a muscular one. The analysis of MV focuses on frequency characteristics. To broaden the clinical application of MV measurement, it is necessary to improve the analyzing method and to develop a way for evaluating MV comprehensively by combining it with other examinations.

Autonomic Nervous System↗

[Study on the extent of peritumoral edema in glioma: its correlation with the proliferative potential and tumor-infiltrating mononuclear cells].

The correlation between the extent of peritumoral edema and the proliferative potential or the infiltration of mononuclear cells was studied in 17 gliomas. The peritumoral edema was evaluated on contrast enhanced CT scan as the ratio of the low density area around the tumor to the enhanced high density area. The proliferative potential and the infiltration of mononuclear cells into the tumor were investigated immunohistochemically using monoclonal antibody (MAb) against DNA polymerase alpha and anti-Leu MAb's respectively. There was a significant correlation between the extent of the peritumoral edema and the percentage of DNA polymerase alpha positive cells. The degree of the infiltration of mononuclear cells into the tumor tissue also correlated with the extent of peritumoral edema. In gliomas with high proliferative potential and/or severe infiltration of mononuclear cells, the peritumoral edema may be aggravated by disruption of the blood-brain-barrier and increased vascular permeability.

Brain Edema↗

Serum pepsinogen I concentrations in peptic ulcer patients in relation to ulcer location and stage.

To investigate the relation of the serum group I pepsinogen (PG I) concentration to the location of gastric ulcers and chronicity of peptic ulcers, ulcer patients (n = 322) were compared with endoscopically normal subjects (n = 174). The mean PG I concentration was significantly higher in male control subjects (n = 90) than in female control subjects (n = 84). In male patients with ulcers in the duodenum (n = 69), antrum (n = 34), or angulus portion (the lower third of the body; n = 83), the mean serum PG I concentration was significantly higher than in the control subjects but in patients with an ulcer in the upper body (n = 49) it was similar to control values. Men with active or healing ulcers (n = 149) showed a significantly higher serum PG I concentration than those with scarred lesions (n = 86) when the abnormality was located in either the upper body or in the angulus portion. For female patients (n = 87), the results were similar. These results suggest that serum PG I concentrations reflect the stages of activity of peptic ulcer.

Adult↗

[Immunohistochemical study for choroid plexus papillomas and ependymomas].

An immunohistochemical study of glial fibrillary acidic protein (GFAP), S-100 protein, cytokeratin (CKER), epithelial membrane antigen (EMA), and transthyretin (TTR) was carried out on 11 cases of choroid plexus papilloma (CPP) and 19 of ependymoma, using the peroxidase antiperoxidase technique. Among the 11 cases of CPP, all 11 were positive for CKER, EMA, and TTR, 10 for S-100 protein, and five for GFAP. Most of the GFAP-positive papilloma cells were simultaneously positive for CKER. However, these GFAP-positive cells were negative for TTR. Among the 19 cases of ependymoma, 16 were positive for GFAP, 17 for S-100 protein, three for CKER, eight for EMA, but none for TTR. Some GFAP-positive cells were also stained for CKER. However, TTR was not found in any of the ependymal cells. These findings suggested that CPP cells which show ependymal or glial differentiation lost the ability to synthesize TTR which is known to be synthesized in the epithelial cells of the choroid plexus. The more GFAP-positive cells present in a CPP, fewer TTR-positive cells are present. Though CPPs are usually easily distinguishable from ependymomas, occasional doubt arises concerning the differential diagnosis between CPP and papillary ependymoma. TTR can be a very useful diagnostic marker of CPP.

Adult↗

G gamma and A gamma globin genes are identical from -471 of the promoter midway through gamma IVSII in a Benin beta s haplotype associated with elevated fetal hemoglobin.

In seven kindreds in which sickle cell (SS) patients had elevated (greater than 12%) fetal hemoglobin (Hb F), Milner and colleagues reported that a determinant for elevated Hb F and elevated F cells was linked to the beta s gene. Independently, the Senegal (SEN) beta s haplotype has been found in association with elevated Hb F in SS and beta-thalassemia patients. We have used the kindreds of Milner and colleagues to characterize further the association of haplotype and gamma gene DNA sequence variation with Hb F expression. For the largest kindred, Wi, all four SS had high (greater than 14%) Hb F and both SEN and Benin (BEN) haplotypes. Two AS cases carrying SEN had low Hb F and low F cells, while three AS and one CS carrying BEN had elevated Hb F and elevated F cells; only one AS carrying BEN had low Hb F and low F cells. In order to look for genetic alterations that could account for the elevated Hb F of kindred Wi, we sequenced both the G gamma and A gamma genes of the Wi BEN haplotype. The data showed largely identical G gamma and A gamma genes which may have been generated by two gene conversions: the A gamma promoter was like that of G gamma 3' to -471, while the G gamma IVSII was like that of A gamma in its 5' half. In addition, three new mutations were found in gamma IVSII.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Sickle Cell↗

[Basal ganglia germinoma treated with interstitial brachytherapy; case report].

A case of primary intracranial germinoma in the left basal ganglia treated with interstitial brachytherapy was reported. A 15-year-old boy was referred to our hospital for evaluation of right hemiparesis. A CT scan showed a slightly hyperdense mass with multiple cystic low density in the left basal ganglia. The mass was heterogeneously enhanced after intravenous administration of contrast material. T1 weighted image showed a slightly hyperintense mass with cystic components and the mass was heterogeneously enhanced with Gd-DTPA. T2 weighted MR image showed a mixed intensity mass and peritumoral edema. Stereotactic needle biopsy and implantation of 3 catheters for interstitial brachytherapy were performed simultaneously using BRW CT guided stereotactic apparatus. After the histological diagnosis was confirmed to be two cell pattern germinoma, 9 iridium-192 seeds were inserted into the catheters and maintained for 10 days to give 35Gy of irradiation at the tumor periphery. Subsequent CT scans showed marked tumor regression and the clinical symptoms were improved. Germinoma originating in the basal ganglia is rare and hard to diagnose previous to biopsy. Histological confirmation is essential before initiation of treatment because germinoma is commonly thought to be radiosensitive tumor. The interstitial brachytherapy enables selective irradiation of the tumor and actually causes no complications such as bone marrow suppression or cerebral atrophy. The neuroradiological findings, especially of CT scan and MRI, were presented and the strategy for treatment of germinoma in basal ganglia was discussed.

Adolescent↗

Immunohistochemical demonstration of DNA polymerase alpha in human brain-tumor cells.

The proliferative capacity of brain-tumor cells was analyzed in vitro and in situ using monoclonal antibody (MAb) against deoxyribonucleic acid (DNA) polymerase alpha. For the in vitro studies, two cultured human glioma cell lines were investigated using MAb against DNA polymerase alpha, the MAb Ki-67, a serum against proliferating cell nuclear antigen (PCNA/cyclin), bromodeoxyuridine (BUdR), and an anti-BUdR MAb. During exponential growth of the cells, the percentage of polymerase alpha-positive cells (the "polymerase alpha score") ranged from 72.0% to 77.1%, the Ki-67-positive cells (the "Ki-67 score") ranged from 43.4% to 59.4%, the PCNA/cyclin-positive cells from 30.9% to 41.4%, and the BUdR labeling index from 28.6% to 39.3%. For the in situ studies, tissue from 60 human brain tumors and from two normal human brains was investigated and the polymerase alpha scores and Ki-67 scores were compared. In normal brain tissue, no immunostaining was found by either method. In brain tumors, both the polymerase alpha scores and the Ki-67 scores correlated with the histological grade of malignancy. Polymerase alpha scores were generally higher than Ki-67 scores in the same specimen, especially in malignant brain tumors. These findings suggest that immunostaining of DNA polymerase alpha is a convenient and important new method by which to estimate the cellular proliferation rate of brain tumors. Polymerase alpha scores may be closer to the growth fraction of the individual tumor than the MAb Ki-67 or other scores.

Antibodies, Monoclonal↗

[Interstitial brachytherapy for malignant gliomas using the Brown-Roberts-Wells (BRW) stereotactic system].

Eleven patients harboring recurrent or deep-seated malignant gliomas were treated by interstitial brachytherapy with 192Ir seed assembly, between June 1987 and September 1989. Implantations for the afterloaded catheter were performed using the Brown-Roberts-Wells (BRW) CT guided stereotactic system. The number of seeds and the distribution of the implants were chosen in such a way that the minimum tumor dose of 30-50Gy could be delivered to the surface or 1cm beyond the rim of the contrast enhancement. The radioactive sources were held in the afterloaded catheters that were removed after the desired dose had been delivered. Response to therapy was measured by serial CT scans and clinical examination. Tumor regressions were seen by CT scans made 2 or 3 months after implantation. One tumor showed complete regression (CR), four showed partial response (PR), one showed minor response (MR) and 5 showed no change (NC). Overall response rate was 54%. Six patients died 3 to 18 months following implantation, and five are still alive 7 to 27 months after implantation. No complications such as infection or hemorrhage were observed during the treatment. A patient harboring large (6.5cm in diameter) recurrent glioblastoma in the rt. parietal robe required a craniotomy due to the mass growing for one and half month after implantation, and radiation necrosis of the entire tumor mass was documented. The technique of stereotactic interstitial implantation was clinically well tolerated and easily reproducible and our preliminary results seemed encouraging. Technical improvement to achieve an adequate isodose distribution to cover the tumor volume might lead to improved survival rates.

Adolescent↗

Type A behavior pattern in Japanese employees: cross-cultural comparison of major factors in Jenkins Activity Survey (JAS) responses.

The responses to the Japanese edition of the Jenkins Activity Survey (JAS) (Form C) were analyzed in 1682 male employees of a Japanese enterprise to investigate the characteristics of the Type A behavior pattern (TABP) in Japan. When the occupational level was controlled, the mean values of the Type A score were found to be quite similar to those of the Western Collaborative Group Study (WCGS), although those of factor H scores were considerably lower than those of the WCGS. Additionally, the results of a factor analysis conducted on the responses to JAS questions showed that the factor structure of the responses was basically equal to that found in the WCGS. In contrast to factor J of the WCGS, however, Japanese factor J did not comprise the items which signaled rises in positions or incomes in recent years. The results of this study indicate that the JAS is able to measure the TABP in Japan, at least concerning its three component factors. Furthermore, they suggest that the TAPB is not necessarily reinforced in Japanese occupational environments.

Coronary Disease↗

The DNA deletion in an Indian delta beta-thalassaemia begins one kilobase from the A gamma globin gene and ends in an L1 repetitive sequence.

High fetal haemoglobin levels of 5-15% are present in adult heterozygotes for delta beta-thalassaemia as the result of large deletions of DNA. We have cloned DNA spanning the deletion breakpoint for a new Indian delta beta-thalassaemia associated with mild anaemia. The 5' breakpoint is at 42151 of GenBank file HUMHBB, which is about 1 kb 3' of the A gamma globin gene poly A site at 41003. On the 3' side of the breakpoint, the sequence is homologous to L1 (KpnI) repetitive DNA located 3.6-10 kb 3' of the beta-globin gene: Indian delta beta-thalassaemia DNA is 74% homologous to the inverted complement of HUMHBB from 69849 to 70020, followed by a region 78% homologous to the direct sequence of HUMHBB from 70534 to 71010. The precise location of the 3' endpoint of this deletion has not been determined, but it is within L1 sequences located more than 10 kb 3' of the beta-globin gene.

Base Sequence↗

[Effect of zinc iontophoresis on sealing of dentinal tubules by a new handy electolytic applicator].

The authors devised a new handy apparatus for iontophoresis in order to prevent pulp irritation caused by tooth reduction. This study was intended to observe the ability of the device. 8% zinc chloride solution was iontophoresed in the dentin of extracted human and bovine teeth by the device. Then, the dye and microbial invasion tests were carried out to investigate how effectively it could seal the dentinal tubules. The following conclusions were drawn: 1. By the zinc iontophoresis, the zinc briefly penetrated into the deep portion of the dentin. 2. The zinc iontophoresis by using the new device showed enough ability to decrease the coloring and bacterial invasion into the dentin, although all of the dentinal tubules were not sealed. 3. The tensile strengths of an adhesive luting resin 'Panavia EX' to the bovine dentin decreased significantly by the zinc iontophoresis. This phenomenon could be partly due to the lack of resin tag formation into the dentinal tubules.

Animals↗