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Biomedical subjects

M Nakata

Publications and source records attributed to M Nakata.

At least 163 records · Page 9Linked to original sources

Development of an integrated radiotherapy network system.

PURPOSE: To introduce the process of developing an integrated radiotherapy network. METHODS AND MATERIALS: We developed a new radiotherapy treatment-planning system in 1987 that we named the Computer Tomography (CT) simulator. CT images were immediately transported to multiimage monitors and to a planning computer, and treatment planning could be performed with the patient lying on the CT couch. The results of planning were used to guide a laser projector, and radiation fields were projected onto the skin of the patient. Since 1991, an integrated radiotherapy network system has been developed, which consists of a picture archiving and communicating system (PACS), a radiotherapy information database, a CT simulator, and a linear accelerator with a multileaf collimator. RESULTS: Clinical experience has been accumulated in more than 1,000 patients. Based on our 7 years of experience, we have modified several components of our original CT simulator and have developed a second generation CT simulator. A standard protocol has been developed for communication between the CT scanner, treatment planning computer, and radiotherapy apparatus using the Ethernet network. As a result, treatment planning data can be transported to the linear accelerator within 1 min after completion of treatment planning. CONCLUSION: This system enables us to make optimal use of CT information and to devise accurate three-dimensional (3D) treatment-planning programs. Our network also allows for the performance of fully computer-controlled dynamic arc conformal therapy.

Computer Communication Networks↗

A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin.

Collectins are C-type animal lectins with both collagenous and carbohydrate recognition domains and are involved in the first line host defense against pathogens. We report here a novel Ca(2+)-dependent and GlcNAc-binding lectin consisting of subunits of 35 kDa (P35) with a collagen-like sequence. When P35 is isolated from human serum, it forms a homopolymer by means of intermolecular disulfide bonding, as is the case with collectins. P35 cDNA was cloned from a human liver cDNA library, and the deduced amino acid sequence of 313 residues revealed that the mature form of P35 consists mainly of collagen- and fibrinogen-like domains. The latter contained two potential Ca(2+)-binding sites that may be involved in carbohydrate binding. The overall sequence of P35 was highly homologous to porcine ficolins alpha and beta. Northern blots of various human tissues showed that the major product of the 1.3-kilobase-long P35 transcript is expressed in liver. P35 enhanced phagocytosis of Salmonella typhimurium by neutrophils, suggesting an opsonic effect via the collagen region. P35 was found to bind to GlcNAc-conjugated bovine serum albumin, a neoglycoprotein, as well as to neoglycolipids containing complex-type oligosaccharides derived from glycoproteins, suggesting that P35 recognizes GlcNAc residues such as those found in microbial glycoconjugates and complex-type oligosaccharides. Therefore, P35 represents a new type of GlcNAc-binding lectin with structural and functional similarities to collectins involved in innate immunity.

Acetylglucosamine↗

Analysis of neurotrophin-3 expression using the lacZ reporter gene suggests its local mode of neurotrophic activity.

We replaced the mouse neurotrophin-3 gene with the Escherichia coli-derived lacZ gene by means of homologous recombination. The mice with this mutation were useful models for studying the distribution of neurotrophin-3 expression in vivo, because visualization by 5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside (X-Gal) staining was simple and rapid compared with in situ hybridization or immunohistochemistry. Whole-mount staining of mutant embryos at embryonic day 10 revealed that lacZ, a reporter for the neurotrophin-3 gene, was expressed in the mesencephalon, mandibular arch and somites. In the embryos at days 13-17, lacZ was markedly expressed in the peripheral target tissues of sensory and sympathetic neurons. We also found that spinal motor neurons and sensory neurons in trigeminal and dorsal root ganglia express lacZ. Some of these X-Gal staining regions overlapped with the sites expressing trkC, a high-affinity receptor for neurotrophin-3. The distribution of X-Gal staining in heterozygotes and homozygotes was similar to that of neurotrophin-3 messenger RNA detected by in situ hybridization. However, there was less lacZ expression in the dorsal root ganglia of homozygotes than neurotrophin-3 expression in wild-type mice. These results suggest that the neurotrophin-3 produced in the dorsal root ganglia also plays a role in the survival of some of the neurotrophin-3-positive neurons and that the local mode of neurotrophic activity is widely distributed.

Amino Acid Sequence↗

Novel designed enediynes: molecular design, chemical synthesis, mode of cycloaromatization and guanine-specific DNA cleavage.

The molecular design and chemical synthesis of novel enediyne molecules related to the neocarzinostatin chromophore (1), and their chemical and DNA cleaving properties are described. The 10-membered enediyne triols 16-18 were effectively synthesized from xylitol (10) in a short step, and found to be quite stable when handled at room temperature. The representative and acylated enediyne 16 was cycloaromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in cyclohexa-1,4-diene-benzene to give the benzenoid product 21 through a radical pathway. On the other hand, the enediyne 16 was cycloaromatized by diethylamine in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer to afford another benzenoid product 22 as a diethylamine adduct through a polar pathway. Furthermore, the enediynes 16-18 were found to exhibit guanine-specific DNA cleavage under weakly basic conditions with no additive.

Alkynes↗

Clinical manifestations of hypertrophic cardiomyopathy with mutations in the cardiac beta-myosin heavy chain gene or cardiac troponin T gene.

Introduction of molecular genetics has improved our understanding of HCM substantially, but has simultaneously raised further important questions. Studies on HCM are revealing a more complex picture than might have been expected on clinical grounds. Further extensive studies are warranted to elucidate the pathogenesis and pathophysiology of HCM, and to establish therapeutic strategies to cure or prevent the development of the disease.

Adult↗

Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy.

To investigate the possible role of the superoxide radical and its scavenging system in the human endometrium, the immunohistochemical distribution of superoxide dismutase (SOD), activities of SOD and lipid peroxide concentrations were studied in the human endometrium throughout the menstrual cycle and in early pregnancy. The endometrial epithelium showed a positive immunostaining for Cu, Zn-SOD and Mn-SOD throughout the entire menstrual cycle and in early pregnancy. In the stroma, weak immunostaining for Cu,Zn-SOD and moderate immunostaining for Mn-SOD were observed in the predecidual cells in the late secretory phase. Decidual cells in early pregnancy showed strong immunostaining for Cu,Zn-SOD and Mn-SOD. Total SOD activity in the endometrium increased from early proliferative phase to mid-late proliferative phase and further increased in the mid-secretory phase, and decreased in the late secretory phase. The total SOD activity in the endometrium of of early pregnancy was the same level as that in the mid-secretory phase. Cu,Zn-SOD and Mn-SOD activities changed in a similar manner to total SOD activity throughout the menstrual cycle and in early pregnancy. Lipid peroxide concentration in the endometrium increased from early proliferative phase to mid-late proliferative phase and further increased in the late secretory phase. However, lipid peroxide concentration in the endometrium of early pregnancy was the same as that in the mid-secretory phase. These results suggested that the superoxide radical and its scavenging system may play an important role in the regulation of human endometrial function.

Adult↗

Prognostic factors and a predictive model of follicular lymphoma: a 25-year study at a single institution in Japan.

The incidence of follicular lymphoma in Japan is far lower than that in western countries, and no large-scale clinicopathologic studies on this neoplasm have been conducted in Japan. We reviewed histopathological specimens from 118 of 135 patients who had been diagnosed as having follicular lymphoma between 1968 and 1993. Prognostic factors influencing survival were analyzed using univariate and multivariate analyses. Factors that were independently significant upon multivariate analysis were incorporated into a predictive model. Ninety-three patients (78.8%) had a confirmed diagnosis of follicular lymphoma. Twenty-one of the remaining 25 patients were categorized as having other lymphoma subtypes, and four patients showed indefinite findings or those suggesting diseases other than lymphoma. Major characteristics of the 93 patients with follicular lymphoma were a median age of 53 years (20-85); 59 males (63%) and 34 females (37%); small cleaved cell type in 33 (35%), mixed cell type in 41 (44%) and large cell type in 19 (20%); stage I/II in 41 (44%) and stage III/IV in 50 (54%). Overall survival was 71% at 5 years, 58% at 10 years, and 43% at 15 years with a median survival of 13.3 years. Multivariate analysis revealed that two variables, age (>60) (P=0.001) and the serum LDH level (>1 x normal value) (P=0.026), were unfavorably significant prognostic factors influencing survival. The predictive model using these two variables identified three risk groups with estimated five-year survival rates of 88.5%, 56.8%, and 31.5%. Age and serum LDH were significant predictors of survival in Japanese patients with follicular lymphoma. Our predictive model may provide a basis for future therapeutic trials against follicular lymphoma in Japan.

Adult↗

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↗

Objective method to determine the contribution of the great toe to standing balance and preliminary observations of age-related effects.

The purpose of this study was to examine the relationship between toe pressure and tactile sensitivity in the great toe and to describe two newly developed measurements of postural stability. The subjects of the study were 21 healthy volunteers. The subjects were divided into two age groups, the young group (mean 21.0 +/- 1.6 years, 7 males and 6 females), and the elderly group (mean 71.4 +/- 2.8 years, 4 males and 4 females). The methods and materials used for the first experiment (balance test): The instrument for measuring standing balance was a force plate. Data were analyzed to provide two main variables: 1) body sway index (SI: mm) and 2) toe pressure (%BW/cm2). The subjects were asked to stand in a relaxed posture for 20 s. The variables of body sway were measured in four conditions: normal surface with eyes open or closed, and soft surface with eyes open or closed. Second experiment (tactile sense test): This experiment utilized a new system which was developed for measuring the tactile sensation. The tactile threshold value was measured with the subject seated in a chair, the back supported, and the hips and knees flexed at 90 degrees. The contactor pulled and pushed the toe longitudinally along its axis at a constant velocity of 1 mm/s. There were significant differences between the young and elderly groups in the tactile sense of the great toe (p < .001). No significant difference between age groups was found for postural sway while the subjects stood on the normal surface with eyes open; however, when they stood on the soft surface with their eyes open and closed, the elderly showed significantly more sway (p < 0.01) than the young. Moreover, the maximal great toe pressure in the elderly group was significantly greater than that in the young group. The results suggest that the reduced tactile sense, deprivation of visual information, and toe pressure weakness are all important factors associated with postural instability.

Adult↗

Doppler-velocity waveforms in ductus venosus in normal and small-for-gestational-age fetuses.

OBJECTIVE: To investigate blood-flow patterns in ductus venosus in growth-retarded fetuses. METHODS: Reference ranges of ductus venosus flow velocities were constructed from a cross-sectional study of 179 normal fetuses between 16 to 38 weeks' gestation. and the ductus venosus flow-velocity waveforms in 11 small-for-gestational-age (SGA) fetuses were compared with normal patterns. RESULTS: Of 179 pregnant women who were possible subjects, 175 were employed for the analysis, and ductus venosus flow-velocity waveforms were obtained in 197 out of 211 examinations (success rate = 93.4%). The peak forward velocities during (a) ventricular systoles, (b) the lowest forward velocities during atrial contractions, and (c) the time-averaged velocities all linearly increased as gestational ages increased [respectively: (a) slope, 1.135; constant, 31.720; (b) slope, 1.154; constant, 1.557; (c) slope, 1.240; constant, 19.386]. Peak forward velocities during ventricular systoles and time-averaged velocities in the SGA group did not differ from those of the normal group. Three SGA fetuses with abnormal flow in the umbilical artery showed a marked reduction of the lowest velocities during atrial contractions in the ductus venosus, and two of them showed no forward velocity at all. CONCLUSION: The Doppler-velocity waveforms of ductus venosus showed a marked reduction of the end diastolic flow, especially in SGA fetuses with abnormal umbilical artery flows.

Blood Flow Velocity↗

Tumor necrosis factor-alpha stimulates the production of squamous cell carcinoma antigen in normal squamous cells.

Squamous cell carcinoma (SCC) antigen, a tumor marker of squamous cell carcinoma, is also increased in several nonmalignant skin lesions, e.g. pemphigus. The aim of the present investigation was to determine if tumor necrosis factor-alpha (TNF-alpha), one of the important environmental factors, stimulated the production of SCC antigen in the normal squamous cells. The exposure of normal human epidermal keratinocytes to TNF-alpha (100 IU/ml) for 72 h greatly increased the SCC antigen production. The stimulatory effect of TNF-alpha (1,000 IU/ml) on the production of SCC antigen was also observed in the normal squamous epithelium tissue. These results would be helpful for understanding the increase of SCC antigen in several nonmalignant skin disorders.

Antigens, Neoplasm↗

Chronic L-arginine administration attenuates cardiac hypertrophy in spontaneously hypertensive rats.

Nitric oxide inhibits proliferation and migration of vascular smooth muscle cells and contractility of cardiomyocytes in vitro. In spontaneously hypertensive rats (SHR), evidence suggests intrinsic abnormalities of the L-arginine-nitric oxide axis, such as low cGMP-dependent protein kinase in the heart and abnormal L-arginine metabolism. To investigate the in vivo effect of L-arginine on cardiac hypertrophy, 30 SHR and 30 Wistar-Kyoto rats (WKY) were randomly grouped to receive L-arginine (7.5 g/L in drinking water) or vehicle for 12 weeks. L-Arginine treatment did not affect body weight or arterial pressure in either strain. In vehicle-treated animals, the heart/body weight ratio was significantly higher in SHR than in WKY (P < .01). L-Arginine treatment decreased the heart/body weight ratio in SHR (P < .05) but did not affect it in WKY. Expression of skeletal alpha-actin mRNA, known to be expressed in the hypertrophied myocardium, was attenuated in L-arginine-treated SHR compared with vehicle-treated SHR. Cardiac cGMP content and nitrate/nitrite content were less in SHR than WKY. L-Arginine treatment increased these levels only in SHR, suggesting enhanced nitric oxide production. Thus, chronic L-arginine administration attenuated cardiac hypertrophy independently of blood pressure and increased myocardial content of cGMP and nitrate/nitrite. Our results suggest that abnormality of the cardiac L-arginine-nitric oxide axis may play an important role in the pathogenesis of cardiac hypertrophy in SHR.

Actins↗

A fibrous histiocytoma with a polypoid pattern of growth in a major bronchus.

A 47-year-old man was admitted to our hospital for abrupt onset of hemoptysis and dyspnea. Chest roentgenography revealed a left lower mass shadow with obstruction of the left main bronchus. However, on the third hospital day, he expectorated a coagulum-like substance which resembled bronchial tree, and his symptoms then dramatically subsided. Except for small amounts of bleeding from left B10a, the endobronchus was intact on bronchoscopic examination, and the pathologic diagnosis of the tumor using resected material was fibrous histiocytoma of low-grade malignancy. In addition, given the similarity in histologic findings between the expectorated substance and resected tumor, the expectorated substance was considered to be a part of the tumor which had grown along the endobronchial tree.

Bronchi↗

Analysis of toe pressures under the foot while dynamic standing on one foot in healthy subjects.

Dynamic balance is a crucial element in performing many activities of daily living. The one-leg stance test is a valuable test for balance impairment. The aim of the present study was to assess the relationships between body sway and toe pressure for dynamic balance test of one-leg standing on a perturbation platform. The subjects were 15 volunteers (six males and nine females, age = 21.1 +/- 1.8 years). The instrument used for evaluation of balance was the Balance System, whose software provides information on the subject's stance balance through calculation of two main variables: 1) body sway parameters (cm) and 2) peak pressure (percent of body weight/cm2) under the toes. The Balance System includes actuators which move the foot platform back and forth (+/- 40 mm perturbation at 0.25 Hz) at an average velocity of 20 mm/sec. The subjects were asked to balance on each leg for 20 seconds. The trials were repeated on the opposite foot after 5 minutes of rest. The dynamic postural control induced by low frequency perturbation in the anterior/posterior direction used the ankle strategy. Body sway was more significantly correlated with the peak anterior/posterior sway component than with lateral sway (p < 0.01). The peak pressure value of the great toe was significantly greater (p < 0.01) than the sum of the peak values of the other four toes for both sides. The study indicates the importance of the strength of the toes and somatosensory information from the sole and ankle during the dynamic one-foot standing balance as goals in rehabilitation for poor balance.

Adult↗

[Electrophysiological evaluation of the demented state and the nootropic effect of TA-0910 by "automated fluctuation analysis" of the high-frequency EEG--relation between neuropsychological test results and Lorentzian parameters].

This study was performed to evaluate the demented state and the nootropic effect of TA-0910 by "Automated Fluctuation Analysis" of the human high-frequency EEG. Correlations between Lorentzian parameters S1 and S2 and the results of neuropsychological tests was investigated. The subjects of this study were 12 demented patients, four males and eight females, aged 57 to 80 years. After obtaining their informed consent a daily dose of 10 mg or 20 mg of TA-0910 was assigned to these subjects one by one. The Kana Hiroi test for pre-frontal lobe function and the Mini Mental State (MMS) test for function of the posterior part of brain were administered before and after the medication period. Particular attention was paid to the consciousness level of the subjects during EEG recording, and EEGs were stored on magnet tape. Statistical analysis was performed by Student's t-test. Improvement in the MMS score from 16.4 +/- 6.2 (mean +/- S.D.) before treatment with TA-0910 to 24.3 +/- 5.7 after treatment was significant (p < 0.001), and a tendency toward dose-dependency was noted. The changes in the traditional EEG did not coincide with these findings but Lorentzian parameters S1 and S2 and the results of the neuropsychological tests correlated well. All of the subjects failed the Kana Hiroi test both before and after the medication period, and in keeping with this finding, the normal frontal dominant pattern of the S1 topographical display was not detected. Furthermore, not only was the elevation of the S2 value significant but the correlation with the MMS scores was also significant, especially in the posterior and right half of the brain. These findings strongly suggest that 1) "Automated Fluctuation Analysis" is very useful not only for evaluating the demented state but for evaluating nootropics as well and 2) TA-0910 activation of subcortical structures, especially A-10, appears to be the mechanism to action.

Aged↗

[A successfully operated case of tuberous sclerosis presenting with intractable epilepsy].

A 20-year-old male patient with tuberous sclerosis was admitted to our hospital complaining of intractable epilepsy. He had been suffering from frequent seizures despite anticonvulsant treatment since the age of 1 year. CT scan and magnetic resonance images showed multiple calcified lesions at the paraventricle and temporal lobe on both sides. Electroencephalogram showed left temporal lobe dominant spike waves. After deep electrodes were inserted into the left amygdala and hippocampus and subdural electrodes were placed on the left temporal cortex, clinical seizures were monitored by video and EEG. The primary focus was found in the amygdala. Left temporal lobectomy was carried out through the cranio-orbital zygomatic approach. Postoperatively, the patient has been seizure-free for one year. Despite multiple intracerebral lesions in tuberous sclerosis, resection of the primary epileptogenic focus is needed to solve the seizure problem if the focus is localized.

Adult↗

Pancreatic secretory trypsin inhibitor gene is highly expressed in the liver of adult-onset type II citrullinemia.

Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS is deficient specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there are no apparent abnormalities in the amount, translational activity, and nucleotide sequence of hepatic ASS mRNA. Recent results of homozygosity testing indicate that the primary defect of type II citrullinemia is not within the ASS gene locus. In this present work, to understand the pathogenesis and pathophysiology of type II citrullinemia, we have characterized the alterations of gene expression in the liver of type II patients using the recently developed mRNA differential display method. Some cDNA bands expressed differently in type II citrullinemia patients and control were selected, cloned, and sequenced. Nucleotide sequence analysis and homology searching revealed an interesting clone which has 99% homology with the human pancreatic secretory trypsin inhibitor (hPSTI). Northern blot and RT-PCR analyses showed that the expression of hPSTI mRNA increased significantly in the liver of all type II patients tested. Furthermore, the concentration of hPSTI protein was found to be higher in the liver of type II citrullinemia than in control. These results suggest that hPSTI may be related to the primary defect of type II citrullinemia and may be useful as a diagnostic marker, although the detailed mechanism of the high expression of hPSTI mRNA in type II liver is not yet known.

Amino Acid Metabolism, Inborn Errors↗