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Biomedical subjects

M Segawa

Publications and source records attributed to M Segawa.

At least 73 records · Page 4Linked to original sources
PubMed1995

GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal fluctuation.

We previously reported four different mutations in the coding region of GTP cyclohydrolase I (GCH-I) gene in patients with hereditary progressive dystonia with marked diurnal fluctuation (HPD). We found two independent new mutations (leucine 79 proline and a deletion in exon 4) in patients with HPD. We also found four families of HPD without any mutations in the coding region of GCH-I gene.

Base Sequence↗
PubMed1995

The gene for hereditary progressive dystonia with marked diurnal fluctuation maps to chromosome 14q.

Hereditary progressive dystonia with marked diurnal fluctuation (HPD) is a childhood-onset, postural dystonia that is characterized by marked diurnal fluctuation and a dramatic response to levodopa. Recently, the gene for dopa-responsive dystonia (DRD), an autosomal dominant dystonia showing similarly marked response to levodopa, has been mapped to chromosome 14q. Since HPD and DRD share many clinical characteristics, we have analyzed microsatellite polymorphisms in the region of the DRD locus and obtained a maximal lod score of 2.0 at D14S52 without obligate recombination events in the affected individuals. The results strongly suggest that HPD and DRD are to be caused by mutations in the same gene on the long arm of chromosome 14.

Chromosome Mapping↗
PubMed1995

Determination of salivary cortisol by ELISA and its application to the assessment of the circadian rhythm in children.

In 35 young children, circadian rhythms of salivary cortisol levels were determined by ELISA using a commercially available kit with a minor modification. The concentration of labeled cortisol in the serum kit was reduced in order to measure cortisol in 10 microliters of saliva. Intra- and interassay coefficients of variation for salivary cortisol ranged from 2.4 to 9.9 and 3.2 to 8.9%, respectively. Recovery of salivary cortisol was 82.9-107.0%. There was a highly significant correlation between cortisol levels in saliva and serum in adults (r = 0.857). Salivary cortisol levels ranged from 0.01 to 2.252 micrograms/100 ml and showed significant diurnal variation in the children. Our ELISA is a precise, simple, noninvasive and useful method for clinical practice and study in infants and children.

Adult↗
PubMed1995

Solution conformation of mu-selective dermorphin and delta-selective deltorphin-I in phospholipid micelles, studied by NMR spectroscopy and molecular dynamics simulations.

Complete proton resonance assignments of the naturally occurring mu-selective dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) and delta-selective deltorphin-I (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) were carried out by two-dimensional 1H-NMR techniques to investigate the conformational features in the membrane-mimetic micelles of perdeuterated dodecylphosphocholine. Fifty possible three-dimensional structures for respective peptides were generated by means of distance geometry calculations, all of which satisfy the proton-proton distances derived from NOE measurements within the allowable range, and 25 of them were subjected to the molecular dynamics simulations for 10 ps, in which the NOE distances were included as the energetic constraints. Although conformers simulated for dermorphin showed relatively large conformational variations because of the limited NOE data, most of them were characterized as an entirely folded structure bent at the Gly4 residue, where each of the N- and C-terminal tetrapeptides took an extended conformation. On the other hand, most conformations of deltorphin-I showed the common feature that the N-terminal Tyr-D-Ala-Phe-Asp and C-terminal Val-Val-Gly-NH2 sequences took respective folded conformations, and these were almost at right angles on the border of the Asp-Val sequence. These conformational characteristics are discussed in terms of the possible relationship with the mu/delta-opioid receptor selectivity.

Amino Acid Sequence↗
PubMed1995

[Aging of aorta and atherosclerosis--role of nonenzymatic glycation of collagen].

In order to clarify the role of the nonenzymatic glycation of the collagen matrix in aging of the aorta and atherogenesis, we studied the relation between ketoamine or advanced glycation end-products (AGEs) and the solubility of collagen in human skin and aorta. AGEs were measured as a collagen-linked fluorescence (excitation wavelength: 370 nm. emission wavelength: 440 nm). There was a positive correlation between the level of AGEs and subjects' age in skin and aortic media. Collagen became more insoluble with increase in the amount of ketoamine and AGEs. Collagen was more resistant to pepsin digestion in atherosclerotic intima than in other tissues including aortic media, lesion-free intima and skin. Diabetic rats showed an accumulation of collagen in aortic media at 28 weeks after an injection of streptozotocin. Moreover, they increased the percentage of insoluble collagen to total collagen and the amount of AGEs binding to insoluble collagen in aortic media. In contrast, the amount of ketoamine of insoluble collagen was increased in diabetic rats at 16 weeks as compared to control. There was no difference in DNA contents of cultured smooth muscle cells between glycolaldehyde-modified and non-modified matrices. However, the activity of type I collagenase (inactive form) of smooth muscle cells decreased on glycolaldehyde-modified type I collagen as compared to that on non-modified collagen. These results suggest that AGEs contribute to the accumulation of collagen in atherosclerotic lesions and aged aorta through the insolubility of collagen and the inhibition of collagenase activity of smooth muscle cells.

Adult↗
PubMed1995

Norepinephrine stimulates the expression of fibroblast growth factor 2 in rat brown adipocyte primary culture.

To elucidate the role of norepinephrine (NE) in the hyperplasia of brown adipose tissue (BAT), we investigated the effects of NE on the expression of fibroblast growth factor-2 (FGF-2) in rat brown adipocyte primary culture and on capillary growth in an in vitro angiogenesis model in which microvascular fragments and brown adipocyte precursor cells isolated from rat BAT were grown in coculture. NE significantly increased the number of brown adipocyte precursor cells. The NE effect on cell proliferation was greatly inhibited by anti-FGF-2-specific antibody. Likewise,NE considerably increased the levels of FGF-2 mRNA and the antigen in brown adipocyte primary culture. The ability of NE to stimulate the expression of FGF-2 mRNA was blocked by actinomycin D or was inhibited partly by propranolol. Moreover, NE considerably increased the in vitro capillary growth and the level of FGF-2 antigen in the coculture. These results suggest that NE is a crucial factor to mediate FGF-2 production, in part via the beta-adrenergic receptor, in rat brown adipocytes and to stimulate the cell proliferation and capillary growth in BAT by an autocrine/paracrine mechanism.

Adipocytes↗
PubMed1995

[Pathophysiologies of dystonia and myoclonus--consideration from the standpoint of treatment].

Pathophysiologies of disorders with dystonia or myoclonus were studied by evaluating the effects of treatment. Naturally, the main lesion of the dystonia responding to levodopa is in the nigrostriatal dopamine neuron. The target of stereotaxic operations is ventrolateral palladium for postural dystonia and the nucleus ventralis oralis posterior (Vop) thalamus for action dystonia. Torsion dystonia with lesion in the striatum and/or the pallidum causes axial torsion, it may be postural through the descending pathway and action through Vop. Stereotaxic operations on these pathways have shown to be effective. Focal dystonia is a reflection of abnormal co-activation of cortical motor neurons, occurring in a particular voluntary movement. Botulinus toxin injected into the affected muscle should be effective. Of myoclonus with epilepsy, cortical reflex myoclonus or cortical induced reticular myoclonus responds to valproic acid. However, no antiepileptic drugs are effective on those with primary brainstem lesion. Reticular reflex myoclonus due to asphyxia responds to ventralis intermedius thalamotomy. Idiopathic myoclonus associated with dystonia is particular because it responds to ventrolateral thalamotomy. Myoclonus except for idiopathic myoclonus with dystonia is associated with atonic NREM suggesting dysfunction of the dorsal raphe serotonergic neuron or the brainstem nucleus reticularis gigantocellularis, the causative neuron for experimental uremic myoclonus. Treatment for these neurons is necessary.

Age of Onset↗
PubMed1994

Surgical results of performing R4 gastrectomy for gastric cancer located in the upper third of the stomach.

Because gastric cancers located in the upper third of the stomach are difficult to detect at an early stage, the surgical results remain poor. We performed R4 gastrectomy as a radical procedure for 25 patients, involving complete resection of the latero-aortic and interaorticovenous lymph modes above and below the left renal vein, in combination with the ordinary R2 or R3 gastrectomy (the R4 group). These patients were compared with 156 others who underwent R2 gastrectomy alone (the R2 group). There were no significant differences in operation time, blood loss, or the incidence of complications between the two groups; however, when the survival rates of the patients with tumors invading beyond the subserosa were compared, the 5-year survival rate was found to be significantly higher in the R4 group than in the R2 group. Furthermore, in patients with para-aortic nodal involvement, a significant survival advantage was observed in the R4 group, as compared with the R2 group. These results suggest that the R4 gastrectomy is a rational approach for patients with advanced gastric cancer located in the upper third of the stomach.

Female↗
PubMed1994

Induction of oesophageal and forestomach carcinomas in rats by reflux of duodenal contents.

A study was designed to determine whether oesophageal carcinomas can be induced through reflux of duodenal contents. Male Wistar rats weighing 230-250 g were divided into three groups according to the surgical procedure performed: (1) the duodenal contents were directed into the forestomach through a stoma (duodeno-forestomach reflux); (2) the duodenal contents were regurgitated into the forestomach through the glandular stomach (duodeno-glandular-forestomach reflux); and (3) a sham operation was performed as a control. Animals were fed standard CRF-1 solid food and tap water that was not exposed to carcinogens and were sacrificed 50 weeks post-operatively. While no neoplasia was observed in any of the 32 control rats, 4/11 (36%) with duodeno-forestomach reflux and 3/18 (17%) animals with duodeno-glandular-forestomach reflux developed carcinomas in the lower oesophagus and forestomach. The incidence in each group was significantly higher than in the controls (P < 0.01 and P < 0.05 respectively). Six of the seven lesions consisted of squamous cell carcinomas, and one was a mucinous adenocarcinoma. Oesophageal columnar epithelial metaplasia was observed in two (18%) of the animals with duodeno-forestomach reflux. Carcinomas were always surrounded by chronic inflammatory changes, including regenerative thickening, basal cell hyperplasia and dysplasia. Additional well-differentiated adenocarcinomas were observed in the prepyloric antrum of 6/18 (33%) animals with duodeno-glandular-forestomach reflux. These findings indicate that chronic reflux of duodenal contents may cause oesophageal carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1994

Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene.

Hereditary progressive dystonia with marked diurnal fluctuation (HPD) (also known as dopa responsive dystonia) is a dystonia with onset in childhood that shows a marked response without any side effects to levodopa. Recently the gene for dopa responsive dystonia (DRD) was mapped to chromosome 14q. Here we report that GTP cyclohydrolase I is mapped to 14q22.1-q22.2. The identification of four independent mutations of the gene for GTP cyclohydrolase I in patients with HPD, as well as a marked decrease in the enzyme's activity in mononuclear blood cells, confirms that the GTP cyclohydrolase I gene is a causative gene for HPD/DRD. This is the first report of a causative gene for the inherited dystonias.

Age of Onset↗
PubMed1994

Comparative conformational analyses of mu-selective dermorphin and delta-selective deltorphin-II in aqueous solution by 1H-NMR spectroscopy.

Two-dimensional 1H-NMR methods have been used to obtain complete proton resonance assignments and possible solution conformations of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) and deltorphin-II (H-Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2), naturally occurring mu- and delta-selective opioids, respectively, in order to examine the conformational characteristics that are closely related to the selectivities towards mu/delta-opioid receptors. With the use of the proton-proton distances derived from ROESY measurements in aqueous solution, 50 possible 3D structures are generated by means of distance geometry calculations. The conformers which satisfy the distance constraints and the torsion angles estimated from JNHC alpha H vicinal coupling constants within the allowable range are then subjected to molecular dynamics simulations for 10 ps after equilibration. Although dermorphin and deltorphin-II are both in equilibrium among many flexible conformers, some conformational differences are observed between these peptides: many conformers of dermorphin show a structure rounded at the N-terminal Tyr-D-Ala-Phe-Gly-Tyr and C-terminal Gly-Tyr-Pro-Ser-NH2 moieties, which are almost at right angles to each other, while those of deltorphin-II are characterized by a 'hook'-shaped backbone structure in which the nearly extended conformation of the Val-Val-Gly-NH2 sequence is located under the folded conformation of the N-terminal Tyr-D-Ala-Phe-Glu sequence. The possible relationship between these conformational characteristics and the mu/delta-opioid receptor selectivities is discussed.

Amino Acid Sequence↗
PubMed1993

Conformation of deltorphin-II in membrane environment studied by two-dimensional NMR spectroscopy and molecular dynamics calculations.

Two-dimensional homonuclear Hartmann-Hahn spectroscopy and NOESY (nuclear Overhauser effect and exchange spectroscopy) 1H-NMR techniques have been used to obtain complete proton resonance assignments and to perform a conformational investigation of deltorphin-II (Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2), a naturally occurring delta-selective opioid peptide, in the membrane-mimetic micelles of perdeuterated dodecylphosphocholine. This was done in order to examine conformational characteristics that would be closely related to the selectivity towards the delta-opioid receptor. With the use of the proton-proton distances derived from NOESY measurements, 50 possible three-dimensional structures were generated by means of distance-geometry calculations, and 25 of them were subjected to the molecular-dynamics simulations of 10 ps, which were energetically constrained for the NOE interproton distances. Most of the possible conformers simulated showed a common feature such that the conformation of deltorphin-II is characterized by the S-shaped back-bone structure in which the turn conformation of the Val-Val-Gly-NH2 sequence is located under the helically folded conformation of the N-terminal Tyr-D-Ala-Phe-Glu sequence. The possible relationship between this conformational characteristic and the delta-opioid-receptor selectivity has been discussed.

Amino Acid Sequence↗
PubMed1993

Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31-33.

Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. Twenty-one FCMD families, 13 of them with consanguineous marriages, were analysed by genetic linkage analyses with polymorphic microsatellite markers to map the FCMD gene. Significant lod scores were obtained with the markers D9S58 (Zmax = 5.81 at theta = 0.06), D9S59 (Zmax = 4.33 at theta = 0.02), and HXB (Zmax = 3.28 at theta = 0.09) on chromosome 9q31-33. Multipoint analysis placed FCMD between D9S58 and D9S59, with a maximum lod score of 16.93. These markers will be useful for presymptomatic, prenatal and carrier diagnosis of family members carrying FCMD, and they represent important resources for the identification of a gene responsible for FCMD.

Chromosome Mapping↗
PubMed1993

Development of the sleep and wakefulness rhythm in preterm infants discharged from a neonatal care unit.

The purpose of this study was to investigate the effect of constant light in a neonatal care unit on the development of the sleep-and-wakefulness rhythm in preterm infants. Two groups of infants (57 preterm infants without other complications and 58 healthy term infants) were prospectively studied over infancy by a day-by-day plot method, by which sleep-and-wakefulness states were recorded at home for more than 14 d to compare developmental courses of the sleep-and-wakefulness rhythm between the two groups at corrected and postnatal ages. In the two groups, there were no significant differences in distribution of emergence of periodicity of sleep states and wakeful states, total sleep time, nocturnal sleep time, diurnal sleep time, longest sustained sleep period, and longest sustained wakeful period at the same corrected ages. Moreover, the SD of the time of onset of the longest sustained sleep period of each subject diminished with increase in postconceptional weeks. The results suggest that the development of the sleep-and-wakefulness rhythm in preterm infants is not necessarily retarded if they are discharged from the neonatal care unit under constant light before an infant's innate biologic clock is mature enough to respond to an environmental cycle; rather it depends on their corrected ages.

Circadian Rhythm↗
PubMed1993

The development of sleep-wakefulness rhythm in normal infants and young children.

The development of circadian sleep-wakefulness rhythm was investigated by a longitudinal study of two normal newborns for two and a half years and by a transversal study of 182 normal infants and young children living in three different areas of Japan. The circadian rhythm became established before 4 months of age, and daytime sleep became concentrated within two time periods from 7 months of age, and then within a single peak from 14 months of age. The time period 00:00-04:00 developed into the "absolute sleep period" from 3 months of age, and the "absolute wakefulness period" appeared first in the time period 08:00-11:00 from 14 months of age, and then in the time period 16:00-21:00 from one and a half years of age. Establishment of circadian rhythm as indicated by the numbers of sleep epochs in daytime and in nighttime, and the longest continuous sleep or wakefulness periods reflect the development of the nervous system and were influenced by the change of light-dark in the environment. These parameters showed critical ages, but not sexual or regional differences. However, regional differences were found in the times of waking up in morning and falling asleep at night. This indicated the phase of the circadian rhythm was also influenced by natural and social environmental factors.

Aging↗
PubMed1993

[Evaluation regarding effect and quality of life after distal pancreatectomy combining total gastrectomy].

Distal pancreatectomy combined with total gastrectomy for gastric carcinoma was evaluated in regard to the availability and quality of life for patients. We performed a question-naire survey of their daily life, especially regarding postpancreatectomy diabetes, for 67 patients passed 5 years after total gastrectomy inclusive of five cases without pancreatectomy as control. Eleven cases developed diabetes mellitus which needed insulin injection after distal pancreatectomy excluding three patients with glucose intolerance before operation. These were 19% of cases performed pancreatectomy, while there was no diabetes in cases without pancreatectomy. The incidence of postpancreatectomy diabetes was 60 per cent of the cases which underwent Appleby operation (65% pancreas resection), while it was 50 percent of the cases which underwent total gastrectomy combined with distal pancreatectomy (50% resection). There is significant difference at < 0.05 level. The incidence of postpancreatectomy diabetes was increased as passing of years after operation. These results suggest that distal pancreatectomy combining total gastrectomy improves the prognosis of patients with nodal metastasis. But considering the occurrence of postpancreatectomy diabetes, it should be emphasized the adequate indication is needed for the operation, and close and long-term follow up is essential for keeping QOL.

Diabetes Mellitus↗