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Biomedical subjects

K Tashiro

Publications and source records attributed to K Tashiro.

At least 307 records · Page 17Linked to original sources

Structural characterization of porcine enteropeptidase.

Enteropeptidase (EC 3.4.21.9) is a key enzyme in the intestinal digestion cascade responsible for the conversion of trypsinogen to trypsin, which then activates various pancreatic zymogens. In order to structurally characterize the enzyme, we purified the enzyme from porcine duodenal mucosa and showed that it consists of three polypeptide chains, which we named "mini" chain (M chain), light chain (L chain), and heavy chain (H chain) in order of increasing molecular size. Based on their NH2-terminal sequences, a cDNA clone for porcine enteropeptidase was isolated and analyzed. The clone was 3597 base pairs long, which encoded 1034 amino acid residues of a single-chain precursor form of enteropeptidase. The precursor contained an additional NH2-terminal 51-residue sequence including a putative internal signal sequence, followed by the M chain (66 residues), the H chain (682 residues), and the L chain (235 residues) in that order. The H chain had regions partially homologous in sequence with low density lipoprotein receptor and complement components. On the other hand, the L chain was highly homologous with the catalytic domains of trypsin-like serine proteinases. The structural model of the L chain suggests that the sequence, Arg885-Arg-Arg-Lys888, is probably involved in the unique substrate specificity of the enzyme, preferring acidic amino acid residues at the P2-P5 sites.

Amino Acid Sequence↗

Effects of glycyrrhetinic acid on aminonucleoside nephrosis in rats.

The effects of glycyrrhetinic acid (GA), an aglycon of glycyrrhizin extracted from the roots of Glycyrrhizae radix, on puromycin aminonucleoside (PA) nephrosis were studied in rats. Urine protein excretion in female rats (130 g-150 g) receiving PA (50 mg/kg) alone was significantly elevated on the 2nd day after injection of PA and reached a peak on the 14th day. Urinary protein on the 14th day was reduced to 74% in animals treated with GA (20 mg/kg) starting on the 2nd day after injection of PA. The increase in serum cholesterol and the decrease in serum protein were also suppressed by GA. Observation by electron microscopy revealed that the degree of abnormality in glomerular epithelial cells, i.e. loss or fusion of foot processes, was lower in the rats treated with GA after PA injection than in the rat treated with PA alone. Moreover, pretreatment with GA did not suppress urinary protein excretion but when it was given at the same time as PA and after PA a significant decrease in urinary protein excretion was observed.

Animals↗

Endothelial cell heterogeneity in experimentally-induced rabbit atherosclerosis. Demonstration of multinucleated giant endothelial cells by scanning electron microscopy and cell culture.

We investigated the aortic endothelial cells of cholesterol-fed rabbits, using scanning electron microscopy and a cell culture technique. Rabbits were given a 1% cholesterol diet intermittently for up to 40 weeks. In these animals, the area of endothelial cells was increased and the cells showed polymorphism in relation to the progression of atherosclerosis. In animals fed the cholesterol diet for 12, 28 and 40 weeks, the average area of the endothelial cells was 436 +/- 15, 762 +/- 153, and 836 +/- 165 microns2, respectively. In the cholesterol-fed 40-week group, in particular, giant endothelial cells, measuring more than 1200 microns2, accounted for 14% of the population. In animals fed a standard diet there was no significant difference in endothelial cell morphology between control 0-week and control 40-week groups; in both, the luminal surface of the thoracic aorta formed a homogeneous sheet covered by small rhomboidal endothelial cells, the area of most being less than 400 microns2. Primary cultured endothelial cells harvested from those control groups were mononuclear typical small cells with a centrally located nucleus; the proportion of binucleated cells was less than 2% and no multinucleated giant cells with three or more nuclei were detected. Endothelial cells from the cholesterol-fed groups, however, contained larger numbers of binucleated cells, with the number increasing in proportion to the duration of cholesterol feeding. The major distinguishing feature of the endothelial cells in the cholesterol-fed groups was the presence of multinucleated giant cells with three or more nuclei; these accounted for 2.3% and 3.3% of the total cell population in the cholesterol-fed 28- and 40-week groups, respectively. No bromodeoxyuridine uptake was found in the nuclei of the cultured multinucleated giant cells. Heterogeneity of endothelial cells, with the concomitant appearance of multinucleated giant cells, emerges with the progression of diet-induced atherosclerosis. The morphological alterations of endothelial cells observed in the present study intimately reflect changes in their function associated with the progression of atherosclerotic lesions.

Animals↗

Increased pulsatile movement of the hindbrain in syringomyelia associated with the Chiari malformation: cine-MRI with presaturation bolus tracking.

Cine-MRI with presaturation bolus tracking was used in patients with syringomyelia associated with a Chiari malformation to study pulsatile movement of the hindbrain, cervical spinal cord, cerebrospinal fluid and the fluid within the syrinx. Nine patients had 13 examinations, 6 preoperative, 3 after syringosubarachnoid shunting and 4 after posterior fossa decompression. Five controls were also examined. Dynamic display of the acquired images demonstrated downward displacement of the presaturation bolus on the cerebellar tonsils and medulla oblongata (or upper cervical cord) at the C1 level in all preoperative examinations and in two patients after syringosubarachnoid shunting but with residual foramen magnum obstruction. Downward displacement of the bolus on the cervical spinal cord was also demonstrated in 7 examinations, but not observed in the controls. Thus, the hind-brain-spinal cord axis showed larger pulsatile movements in patients with foramen magnum obstruction. Based on these observations and a review of the literature, a new theory on the mode of extension of syringomyelia, emphasising the role of increased pulsatile movement of the hind-brain-spinal cord axis is proposed: that the pulsatile movements, together with a one-way valve mechanism in the syrinx cavity act as a "vacuum-pump" to enlarge the syrinx.

Adolescent↗

Genetic heterogeneity of dominantly inherited olivopontocerebellar atrophy (OPCA) in the Japanese: linkage study of two pedigrees and evidence for the disease locus on chromosome 12q (SCA2).

We did a linkage study of 2 multigenerational pedigrees with dominant olivopontocerebellar atrophy (OPCA) other than SCA1, with chromosome 12q microsatellites. Multipoint linkage analysis led to the conclusion that the disease locus locates within the 6.2 cM interval between IGF1 and D12S84/D12S105. This result coincides with that of Cuban ataxia pedigrees designated as SCA2. Our study provides genetic evidence that dominant OPCA in the Japanese consists of at least two genetically different disorders; SCA1 and SCA2.

Adolescent↗

Sixty new STSs (sequence-tagged sites) of human chromosome 21.

From human chromosome 21-specific libraries, 22 SfiI linking clones and 38 P1 clones were isolated and regionally mapped on the chromosome. The terminal sequences of these clones were determined and pairs of PCR primers were generated which could specifically amplify the sequenced regions. These sequence-tagged sites (STSs) should be useful for constructing a high resolution map of human chromosome 21.

Base Sequence↗

Changes in ornithine metabolic enzymes induced by dietary protein in small intestine and liver: intestine-liver relationship in ornithine supply to liver.

Compared with the activity obtained with a high-protein diet in rats, a low-protein diet doubled the activity of ornithine aminotransferase [EC 2.6.1.13] (OAT), a key enzyme for citrulline synthesis, in the small intestine. The induction of ornithine aminotransferase in the small intestine by the low-protein diet and its suppression by the high-protein diet, and the converse in the liver, were immunohistochemically verified with anti-OAT antiserum. The immunohistochemical studies revealed that ornithine aminotransferase molecules localized in the villous surface epithelia, but not in the cryptic epithelia, were most responsive to the changes in dietary conditions, these results indicating that intestinal ornithine aminotransferase may be involved in the ornithine supply to the liver, with the reversal of the enzyme reaction occurring with a low-protein diet. Reconstituted model experiments on citrulline synthesis revealed that the addition of ornithine carbamoyl-transferase and carbamoyl phosphate was essential to overcome the unfavorable equilibrium of the reverse reaction, and the further addition of glutamate dehydrogenase and ammonia resulted in a stimulating effect.

Animals↗

MR appearance of subacute combined degeneration of the spinal cord.

Subacute combined degeneration (SCD) of the spinal cord is well known to produce degenerative lesions in the spinal cord histopathologically, but a few reports on the neuroradiological findings have so far been reported. We presented the MRI findings of the spinal cord in a case of SCD. The localization of the radiologically proven lesions was similar to that of the previous pathological reports.

Aged↗

Residual neurobehavioural effects associated with chronic exposure to mercury vapour.

To find the residual effects of long term exposure to mercury vapour, neurobehavioural tests were given to ex-mercury miners about 18 years after the end of mercury exposure. Seventy six male ex-mercury miners who had been exposed to high concentrations of mercury vapour (over 1.0 mg/m3) and with a history of mercury intoxication were compared with controls matched for age (within 3 years), sex, and education. Although the extent of the workers' symptoms caused by mercury poisoning, termed erethismus merculialis, decreased considerably after the end of exposure, matched paired comparison showed that performances of motor coordination, simple reaction time, and short term memory had deteriorated significantly in the exposed group. Multiple linear regression analysis of exposure variables with neurological examination measures showed positive correlations between poorer neurological performance and variables related to mercury exposure. Thus the duration of exposure correlated with poorer performance of hand-eye coordination, tapping, and a colour card reading test. Job categories classified by exposure to mercury also had a significant negative correlation with these performances. The period of years after the end of exposure had a significant correlation with better performance of reaction time and digit span. On the other hand, the history of intoxication itself had no significant correlation with any of the current neurobehavioural performances. These results suggest that there are slight but persistent effects on neurobehavioural function, especially on motor coordination, among mercury miners even more than 10 years after the end of exposure.

Aged↗

Seven-year follow-up study of bromocriptine therapy for Parkinson's disease.

A 7-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Of 22 patients who had been on bromocriptine monotherapy for 7 years (group B), 16 remained improved or remained in the same stages of Hoehn and Yahr, and no wearing-off phenomenon or dyskinesia was observed. In another 56 patients who were started on bromocriptine alone, but in whom combination therapy with levodopa was instituted at some time in the 7 years (group BL), disease progressed faster than in group B. A wearing-off phenomenon and dyskinesia occurred in 34% and 5.4% of the patients, respectively. These manifestations appeared only after initiation of levodopa. The favorable course of group B suggests possible neuroprotective effects of bromocriptine or may be due to the inevitable selection of patients who had a favorable course originally.

Adult↗

Relationship between antisaccades and the clinical symptoms in Parkinson's disease.

We studied voluntary control of saccadic eye movement in 32 parkinsonian patients using the antisaccade task (the subjects were instructed not to look at the target but to look in the opposite direction). Mean latencies and error rates in the antisaccade task were significantly increased in advanced parkinsonian patients. The latencies of the antisaccades correlated with the severity of bradykinesia as well as the results of the Wisconsin Card Sorting Test. Patients taking anticholinergics showed significantly higher error rates. These results suggest that disturbance in the initiation of voluntary saccades in advanced patients may be associated with frontal lobe dysfunction, while anticholinergics may affect the inhibitory control of reflexive saccades.

Analysis of Variance↗

[Possible roles of airway epithelial cells in the control of airway smooth muscle tone].

While the airway epithelium provides a diffusion barrier to the access of inhaled stimulants, it has recently been considered to have a more active physiological and pharmacological role in the regulation of the airway smooth muscle tone. The initial evidence for this comes from the fact that mechanical removal of the airway epithelium increases the in vitro responsiveness of airway smooth muscle to various spasmogens 3-5 times, although the nature of these regulatory mechanisms on the smooth muscle by the epithelium remains largely unresolved. One of the possible explanations is that the epithelium a generates factor(s) that inhibits the responsiveness of the underlying smooth muscle cells (epithelium-derived inhibitory or relaxing factor EpDIF/EpDRF). Furthermore, recent investigations revealed that airway epithelial cells also release a factor(s) that modulates the vascular smooth muscle tone, excitatory-neuroeffector transmission and resting membrane potential of the airway smooth muscle cells (epithelium-derived hyperpolarizing factor: EpDHF). This review will present and discuss the evidence indicating that the epithelium generates and releases a factor(s) that modulates smooth muscle tone, resting membrane potential of airway smooth muscle cells (EpDHF) and excitatory neuro-effector transmission in the airway.

Animals↗

Clinico-radiological findings of neuro-Behçet's syndrome.

We examined 21 cases of Neuro-Behçet's syndrome in detail, and present here their clinicoradiological characteristics. Clinically, signs of pyramidal tract and meningeal irritation were frequently observed. In contrast to previous reports, our study demonstrated a near equal frequency in the occurrence of focal cerebral lesions and that of focal brain stem lesions. Notably, our results showed that the atrophy of both the cerebrum and the brain stem was often observed, indicating the presence of continuous disease activity in the central nervous system (CNS). In accordance with the high frequency of meningeal irritation signs, all of our cases exhibited pleocytosis in the cerebrospinal fluid (CSF). These results indicated the possibility that chemical mediators secreted from infiltrating cells in the CSF may somehow inflict damage to the CNS in Neuro-Behçet's syndrome.

Adult↗

Sequential magnetic resonance features of encephalopathy induced by systemic mastocytosis.

A 37-year-old man developed encephalopathy with prominent eosinophilia. Magnetic resonance imaging (MRI) revealed multiple T2-weighted high signal intensity lesions with dimeglumine gadopentetate (Gd-DTPA) enhancement on T1-weighted images, which were distributed in the cerebral cortex, thalamus, deep white matter and cerebellum. He was diagnosed as having systemic mastocytosis on the basis of proliferating mast cells in the bone marrow and peripheral eosinophilia. Following steroid administration, there was a rapid improvement of his symptoms and laboratory data. To our knowledge, this was the first reported case of systemic mastocytosis provoking encephalopathy with serial MRI findings.

Adult↗

Temporal alterations of immunohistochemical findings in polymyositis.

To investigate the pathological mechanisms of polymyositis, we performed immunohistochemical analyses with biopsied muscles. Comparative studies using specimens obtained from the same patient enabled us to analyze the pathological alterations at different sequential clinical phases without taking into account each immunogenetic difference. Expression of MHC (major histocompatibility complex) antigens, especially ectopic MHC-class-II antigens, in muscle fibers and infiltrating T-cells were shown to increase concomitantly with the clinically observed exacerbation. Moreover, other observations seem to support the possibilities that 1) administration of steroids lowers the number of invading CD8-positive cells, 2) induction of MHC-class-I antigens in muscle fibers precedes the inflammatory cell infiltration and that 3) remaining MHC-class-I antigens in muscle fibers may explain the recurrence of myositis often observed in the follow up period.

Adrenal Cortex Hormones↗

[A case of multiple sclerosis associated with granulomatous panuveitis].

A case of multiple sclerosis (MS) associated with granulomatous panuveitis was reported. A 45-year-old woman developed diplopia in 1972, at age 24, optic neuritis in 1974 and acute transverse myelopathy in 1981. Subsequently, while being under our care with the clinical diagnosis of MS, right abducens palsy in 1989, deterioration of paraparesis with remission in 1991, and weakness of left arm in 1992 occurred. CSF study revealed high IgG index and brain MRI showed multiple abnormal intensity areas in the deep white matter and periventricular areas bilaterally. On the beginning in March, 1993, she noticed left hazy vision and the ophthalmological examinations revealed marked mutton-fat like keratic precipitates, posterior synechiae, cells and flare in anterior chamber, retinal phlebitis and snow ball vitreous opacity. Granulomatous panuveitis was diagnosed and treated by topical steroid with improvement within two months. During this episode, no neurological deterioration was seen. Granulomatous uveitis in MS was rarely documented in the literatures, but this seems to be more common in women, mildly symptomatic or asymptomatic and responds well to topical steroid treatment.

Female↗