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Biomedical subjects

M Doi

Publications and source records attributed to M Doi.

At least 73 records · Page 4Linked to original sources

[An autopsied case of progressive spinal muscular atrophy showing tremor and choreiform movement].

A 42-year-old man without family history of neurologic disease developed muscle weakness, and wasting associated with tremor and choreiform movement. He died at age 75 with 33 years of total duration of illness. Autopsy revealed neuronal loss and gliosis in the anterior horns of the spinal cord, hypoglossal nuclei, caudate nuclei, putamen, globus pallidus, and substantia nigra. Bunina bodies or Lewy bodies were not seen. Several similar cases with motor neuron disease, dementia and parkinsonism have been reported in the literature. However, this pattern of chronic spinal neostriato-pallido-nigral degeneration has not been reported.

Aged↗

The Discovery of a High-Redshift Quasar without Emission Lines from Sloan Digital Sky Survey Commissioning Data.

We report observations of a luminous unresolved object at redshift z=4.62, with a featureless optical spectrum redward of the Lyalpha forest region, discovered from Sloan Digital Sky Survey commissioning data. The redshift is determined by the onset of the Lyalpha forest at lambda approximately 6800 Å and a Lyman limit system at lambda=5120 Å. A strong Lyalpha absorption system with weak metal absorption lines at z=4.58 is also identified in the spectrum. The object has a continuum absolute magnitude of -26.6 at 1450 Å in the rest frame (h0=0.5, q0=0.5) and therefore cannot be an ordinary galaxy. It shows no radio emission (the 3 sigma upper limit of its flux at 6 cm is 60 µJy), indicating a radio-to-optical flux ratio at least as small as that of the radio-weakest BL Lacertae objects known. It is also not linearly polarized to a 3 sigma upper limit of 4% in the observed I band. Therefore, it is either the most distant BL Lac object known to date, with very weak radio emission, or a new type of unbeamed quasar, whose broad emission line region is very weak or absent.

Journal Article↗

Microstructure and Viscosity of Aggregating Colloids under Strong Shearing Force.

Disaggregation under strong shearing force is simulated for an aggregating colloid based on a sticky particle model which can describe the disaggregating and aggregating kinetics, the deformation, and the rupture of clusters with a minimum number of parameters. For a 2-dimensional system, the viscosity and coordination number of the model colloid are calculated at each time step, and the changes of microstructure with shear flow are observed directly by displaying the configuration of particles onto a monitor. The viscosity depends on both area fraction and shear rate, but coordination number depends only on shear rate. Furthermore, the viscosity and coordination number at steady state are independent of the initial state of particles, which indicates that the disaggregation and aggregation are mutually reversible. Copyright 1999 Academic Press.

Journal Article↗

Conformational change of ascidiacyclamide caused by asymmetric modification for an isoleucine residue: structural analyses of [Gly], [Leu], and [Phe]ascidiacyclamides by x-ray diffraction and NMR spectroscopy.

Ascidiacyclamide, a cytotoxic cyclic peptide from tunicate, is composed of unusual amino acids and has a repeated sequence, c[-thiazole-D-Val-oxazoline-L-Ile-]2 ([Ile]ASC). The symmetric chemical structure has been assumed to be correlated with the cytotoxicity, and it is reasonable to consider that the disturbance of its structure from the C2 symmetry results in the changes of conformation and activity. In order to quantitatively estimate the molecular conformation-activity relationship, an isoleucine residue was substituted by Gly, Leu, or Phe to disturb the C2 symmetry. The conformations of three derivatives were examined by nmr spectroscopy and the crystal structure of [Leu]ASC was also analyzed by x-ray diffraction method. The 1H-nmr experiments and the constrained molecular dynamics simulations showed the twisted "figure 8" conformers for [Gly] and [Phe]ASCs and the "square" conformer for [Leu]ASC in the DMSO solution. The x-ray crystal analysis of [Leu]ASC also revealed the square form similar to the solution structure. On the other hand, their cytotoxic activities were measured using L1210 leukemia cells and were related with the bulkiness and/or hydrophobicity of the side chain of the substituted amino acid; [Phe] > or = [Ile] > [Leu] >> [Gly]ASCs. As an attempt to consider the correlation between the activity and conformer, the accessible surface area (ASA) was calculated for each derivative to estimate the size or bulkiness of its conformation. Although the ASAs of nmr structures were not directly related to the type of conformer (figure 8 or square form), it was an important probe to consider the cytotoxicity of each derivative.

Amino Acid Substitution↗

Increased levels of nitrite/nitrate in the cerebrospinal fluid of patients with subarachnoid hemorrhage.

The role of nitric oxide (NO) in the mechanism of delayed cerebral vasospasm (VS) after subarachnoid hemorrhage (SAH) was investigated by analyzing the stable metabolites of NO, nitrite and nitrate, by the Griess method in the cerebrospinal fluid (CSF) and venous blood of 29 patients with SAH, the CSF of 22 control patients, and venous blood from eight normal subjects. VS was defined as diffuse and severe angiographical vasospasm detected by angiography performed around days 7-9 after the onset. Six of the 29 patients had VS. The nitrite/nitrate levels in the blood of patients with SAH were almost within the range of those in normal subjects, but the levels in the CSF of patients with SAH were significantly higher than those of the control group. Patients with VS after SAH had significantly lower levels in the CSF than patients without VS on days 7-9, when VS is most likely to occur. These observations suggest that NO production in the CSF environment occurs following SAH, but possibly may not provoke VS.

Humans↗

Chronic progressive hematomyelia: case reports and review of the literature.

BACKGROUND: Hematomyelia usually has an acute onset and rapid progression, which results in a poor prognosis. However, there have been a few cases in which the clinical symptoms have progressed chronically, with a good prognosis. These two different clinical courses should be analyzed separately. The differential diagnosis of spinal tumor and other chronic progressive diseases due to the similarity of the clinical courses is also important. CASE DESCRIPTION: Two cases of hematomyelia with slowly progressive symptoms are reported. Unlike the acute onset and rapid progression or recurrent episodic deterioration usually seen in hematomyelia, the symptoms of chronic hematomyelia progressed over months and resulted in a better clinical prognosis than the acute course. The cases of "chronic progressive hematomyelia" from the literature are briefly summarized. CONCLUSIONS: Chronic progressive hematomyelia should be considered as a different clinical entity from the acute version because of its slowly progressive clinical course and good outcome. Magnetic resonance imaging is the procedure of choice to exclude spinal tumors or other slowly progressive intraspinal diseases.

Chronic Disease↗

Case report. Kerion Celsi effectively treated with terbinafine. Characteristics of kerion Celsi in the elderly in Japan.

A 75-year-old non-working male living in Sagamihara, Kanagawa Prefecture, had erythematous plaques with scales associated with follicular pustules in the head area extending from the occipital to right temporal regions about 1 month prior to his initial visit, when hair loss increased. The diagnosis was kerion Celsi. Trichophyton rubrum was isolated from scales and tissues taken from lesions in the head. Histopathological examinations showed irregular epidermal thickening with dense cell infiltration from the dermis to subcutaneous adipose tissues. Granulomatous reactions involving neutrophils, histiocytes and giant cells were seen mainly in the hair follicles. Periodic acid-Schiff (PAS) and Grocott-positive microbial elements were detected in the horny layer, and inside and outside the hair follicles. Pustules disappeared 1 week after starting the oral treatment with terbinafine (125 mg day-1). A cure was achieved 2 weeks after starting the treatment, with only slight scales remaining. No recurrence has been observed to date. Terbinafine was thought to be very effective and safe for kerion Celsi. We reviewed 27 cases of kerion Celsi reported in patients, aged at least 70 years, in Japan and found that the major characteristics of this disease in Japan include the following: (1) female cases outnumber male cases; (2) the causative organism was T. rubrum in 14 of 27 patients (51.9%); and (3) topical application of steroids often induces this disease in patients with superficial tinea capitis.

Administration, Oral↗

Effects of pranlukast hydrate on serum eosinophil cationic protein levels in patients with adult bronchial asthma.

Pranlukast hydrate (CAS 103177-37-3, ONO-1078) was administered to 20 patients with bronchial asthma, and examined the effects of this agent on serum eosinophil cationic protein (ECP) levels and peripheral blood eosinophil counts. The mean serum ECP level in the group comprised of patients with bronchial asthma was significantly higher than that in the control group comprised of healthy adults. In responders in whom improvement in asthmatic symptoms was observed, serum ECP levels were significantly decreased compared to the pretreatment values 4 weeks after commencement of pranlukast hydrate administration. However, there were no changes in non-responders. There was no correlation between serum ECP level and peripheral blood eosinophil count before administration of pranlukast hydrate. However, there was a correlation 4 weeks after administration was started. It is suggested that pranlukast hydrate inhibits eosinophilic activity in patients with bronchial asthma.

Adult↗

Prediction of movement at laryngeal mask airway insertion: comparison of auditory evoked potential index, bispectral index, spectral edge frequency and median frequency.

We have studied 46 patients to compare the efficacy of the auditory evoked potential (AEP) index, bispectral index (BIS), 95% spectral edge frequency (SEF) and median frequency (MF) in predicting movement in response to insertion of the laryngeal mask airway (LMA). Anaesthesia was induced with target-controlled infusions of propofol and alfentanil. After loss of eyelash reflex and adequate jaw relaxation, the LMA was inserted without the assistance of a laryngoscope or neuromuscular blocker. Patients who showed any visible spontaneous muscle movement within 1 min of LMA insertion were defined as movers. Values in movers and non-movers at 30 s before LMA insertion were analysed. Only AEP index discriminated between movers and non-movers with a prediction probability of 0.872. BIS, SEF and MF could not predict movement at LMA insertion. AEP index was the most reliable predictor of movement in response to LMA insertion.

Adolescent↗

Comparison of bispectral EEG analysis and auditory evoked potentials for monitoring depth of anaesthesia during propofol anaesthesia.

We have compared the auditory evoked potential index (AEPIndex) and bispectral index (BIS) for monitoring depth of anaesthesia in spontaneously breathing surgical patients. Twenty patients (aged 17-49 yr) undergoing day surgery were anaesthetized with computer-controlled infusions of propofol. The mean (SD and range) of each measurement was determined during consciousness and unconsciousness and at specific times during the perioperative period. Mean values for AEPIndex during consciousness and unconsciousness were 74.5 (SD 14.7) 36.7 (7.1), respectively. BIS had mean values of 89.5 (SD 4.6) during consciousness and 48.8 (16.4) during unconsciousness. AEPIndex and BIS were greater during consciousness compared with during unconsciousness. The average awake values of AEPIndex were significantly higher than all average values during unconsciousness but this was not the case for BIS. BIS increased gradually during emergence from anaesthesia and may therefore be able to predict recovery of consciousness at the end of anaesthesia. AEPIndex was more able to detect the transition from unconsciousness to consciousness.

Adolescent↗

Comparison of the effect-site k(eO)s of propofol for blood pressure and EEG bispectral index in elderly and younger patients.

BACKGROUND: Drug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients. METHODS: A target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 microg/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (k(eO)) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile. RESULTS: The half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P < 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P < 0.05) in the elderly than in the younger patients. CONCLUSIONS: The effect of propofol on BIS occurs more rapidly than its effect on SBP. Age has no effect on the rate of BIS reduction with increasing propofol concentration, whereas with increasing age, SBP decreases to a greater degree but more slowly.

Adult↗

Clinical, neuropathological, and molecular study in two families with spinocerebellar ataxia type 6 (SCA6).

To clarify the clinical, neuropathological, and molecular characteristics of spinocerebellar ataxia type 6 (SCA6), two unrelated Japanese families with SCA6 were studied. A clinical feature of the two families was late onset "pure" cerebellar ataxia. Pathologically, three SCA6 brains consistently showed Purkinje cell dominant cortical cerebellar degeneration. Morphometric analysis showed that loss of the cerebellar granule cells and inferior olivary neurons were very mild compared with the severity of Purkinje cell loss. There was no obvious ubiquitin immunoreactive nuclear inclusions. All affected patients had identical expanded alleles, and the expansion was also homogeneously distributed throughout the brain without mosaicism. The present study showed that SCA6 is characterised by Purkinje cell dominant cortical cerebellar degeneration, highly stable transmission of the CAG repeat expansion, and lack of ubiquitin immunoreactive nuclear inclusions.

Adult↗

Suppression of airway inflammation by theophylline in adult bronchial asthma.

BACKGROUND: Chronic continuous airway inflammation caused by eosinophils has been noted to play critical roles in the pathophysiology of bronchial asthma, in addition to reversible obstruction and hypersensitivity of the respiratory tract. Therefore, suppression of chronic airway inflammation has become more important in asthma treatment. Although theophylline has been a conventionally used bronchodilator, it has been recently reported to have concurrent anti-inflammatory effects. OBJECTIVE: Accordingly, we studied the effects of a slow-release theophylline preparation, Theolong, on airway inflammation. METHODS: Administration of Theolong 400 mg/day to 24 patients with mild or moderate asthma and measuring eosinophil cationic protein (ECP), a marker of airway inflammation, and eosinophils in sputum and peripheral blood at 4 and 8 weeks. RESULTS: As a result, sputum ECP, serum ECP and sputum eosinophil count (%) were significantly lowered after 4 and 8 weeks. CONCLUSION: Thus, in the theophylline-administered group, slow-release theophylline, Theolong, was effective in treating asthma, with anti-inflammatory effects on inflammatory cells besides its bronchodilator action.

Administration, Oral↗

Induction of max by adrenomedullin and calcitonin gene-related peptide antagonizes endothelial apoptosis.

Adrenomedullin is a novel vasodilatory peptide originally isolated from pheochromocytoma. Recently, we found that adrenomedullin acts as an autocrine/paracrine apoptosis survival factor for rat endothelial cells. In the present study, we show that adrenomedullin induces the expression of Max, a heterodimeric partner of c-Myc, which may contribute to its ability to rescue endothelial cells from apoptosis. Max is a basic-helix-loop-helix-leucine zipper protein that forms heterodimers with its alternative partners, Mad and Mxi-1, to behave as an antagonist for Myc-Max heterodimer through competition for common DNA targets. The expression of Max is reported to be constitutive and more stable than c-Myc, and serum induces immediate c-Myc stimulation followed by modest Max up-regulation. In quiescent rat endothelial cells, adrenomedullin stimulated the expression of Max without affecting c-Myc. Quantitation with real-time quantitative PCR detected on the ABI Prism 7700 Sequence Detection System revealed that adrenomedullin and calcitonin gene-related peptide (CGRP), as well as serum, up-regulated Max mRNA levels and that down-regulation of Max mRNA after serum deprivation was prevented by adrenomedullin. Neither adrenomedullin nor CGRP affected c-Myc expression. Transfection of a Max-expressing plasmid into endothelial cells rescued the apoptosis induced by serum deprivation. Neutralization with anti-adrenomedullin antiserum or blockade with a CGRP receptor antagonist, CGRP(8-37), reduced Max mRNA levels in growing endothelial cells and enhanced apoptosis after serum starvation. Introduction of an antisense oligodeoxynucleotide against Max mRNA using transferrin receptor-operated transfer led to inhibition of both adrenomedullin-induced up-regulation of Max transcripts and its cell survival effect, whereas random, sense, or missense oligonucleotides were without effect. The negative regulation of E-box-driven transcription by adrenomedullin was demonstrated by using preproendothelin-1 promoter containing c-Myc-Max binding consensus sequence; the promoter activity of preproendothelin-1 was reduced by cotransfecting Max- and Mad-expressing plasmids as well as addition of adrenomedullin and CGRP. The present results demonstrate that adrenomedullin antagonizes serum deprivation-induced endothelial apoptosis by up-regulation of the max gene in an autocrine/ paracrine manner.

Adrenomedullin↗

Electrophysiological studies on the mechanism for enhanced intestinal transport of water-soluble compounds by antibiotic peptide bacitracin.

Bacitracin is an antibacterial cyclic dodecapeptide produced by Bacillus licheniformin. Besides antibacterial activity, it is reported to have a protease inhibitory activity and an absorption enhancing action. Here we determined the effects of bacitracin on transport of water-soluble dye fluoresceinisothiocyanate (FITC)-dextran across the rat intestinal mucosal membrane using an electrophysiological technique. Bacitracin enhanced the intestinal mucosal-to-serosal transport of FITC-dextran in concentration-dependent and pH-dependent manners. In particular, the addition of bacitracin to the mucosal side led to a remarkable enhancement of FITC-dextran transport across the colonic membrane. Furthermore, its exhibition of transport enhancement required the existence of metal divalent cations, Ca2+ and Mg2+, in the mucosal compartment. Electrophysiological study using voltage-clamp technique revealed that a relatively lower concentration of bacitracin (5 mM) enhanced the transport of 6-carboxyfluorescein via a paracellular pathway in the colonic membrane and higher concentration of bacitracin (20 mM) affects both transcellular and paracellular routes, resulting in significant enhancement of 6-carboxyfluorescein across the colonic membrane. These findings might provide the useful information for enhancing the intestinal transport of poorly absorbable drugs by bacitracin which has multiple functions.

Animals↗