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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 253 records · Page 14Linked to original sources
PubMed1996

In vitro differentiation and commitment of CD4+ CD8+ thymocytes to the CD4 lineage, without TCR engagement.

Thymocyte positive selection is based on protection of immature CD4/CD8 double-positive (DP) thymocytes from apoptosis and their differentiation into CD4 or CD8 single-positive (SP) cells. Intracellular signals essential for positive selection appear to be induced through the TCR and some of the accessory molecules including LFA-1, CD4 and CD8 upon interaction with thymic stromal cells. The signals, however, still remain to be identified. Since physiological levels of glucocorticoids potentially induce or enhance thymocyte apoptosis even in vivo, the signals are likely to inhibit the apoptotic effect of glucocorticoids. We have previously shown that proper cross-linking of TCR-CD3 with LFA-1, CD4 or CD8 inhibited glucocorticoid-induced thymocyte apoptosis in vitro, and that a proper combination of the calcium ionophore, ionomycin and the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), mimicked the inhibitory effect. Here we determined whether this combination of ionomycin and PMA induces differentiation of isolated DP thymocytes from normal and TCR transgenic mice. We found that pretreatment of DP thymocytes with ionomycin and PMA followed by 1 day culture of the cells without the reagents resulted in the differentiation of the cells into CD4 SP and CD4+ CD8lo T cells that have mostly committed to the CD4 lineage. The changes in expression of other differentiation markers were also in good accordance with those associated with positive selection, except the final maturation. The results indicate that moderate and transient increases in intracellular Ca2+ level and PKC activity induce differentiation and commitment of DP thymocytes to the CD4 lineage, and suggested that the biochemical pathway leading to positive selection is based on a similar mechanism.

Animals↗
PubMed1996

The 160k alpha 1(IV) chain, a short form of a type IV collagen polypeptide, of bovine lens capsule retains the NC1 domain.

We recently reported that the bovine lens capsule contained a shorter alpha 1(IV) chain (160k) as a major polypeptide in addition to the 180k alpha 1(IV) chain [J. Biochem. (1995) 117, 1298-1304]. Two experiments were performed to examine whether or not the 160k polypeptide retained the carboxyl-terminal NC1 domain. On immunoblotting analysis with a monoclonal antibody (H11) raised against the NC1 domain of the human alpha 1(IV) chain [positions 1643-1650; near the carboxyl-terminal end of the human alpha 1(IV) chain], the 180k and 160k polypeptides showed identical immunoreactivity, suggesting that the two chains had the same human alpha 1(IV) collagen NC1 domain sequence. Another monoclonal antibody (H21) specific for the NC1 domain of human alpha 2(IV) did not react with these polypeptides, but with the bands corresponding to 175k and 155k. The 160k polypeptide was selectively solubilized from bovine lens capsules, leaving the other major polypeptides, 180k and 175k, insoluble. The 160k polypeptide was separated by preparative electrophoresis. Bacterial collagenase digestion of the separated 160k polypeptide produced collagenase-resistant segments of about 29k and 30k in size based on globular standards. These sizes corresponded well with those of the NC1 domains of type IV collagen alpha chains (25-30k). The results indicated that the 160k polypeptide retained the carboxyl-terminal NC1 domain of the alpha 1(IV) chain. In turn, the 20k polypeptide of the amino-terminal region or the 7S domain of 180k alpha 1(IV) would have been excised to yield 160k alpha 1(IV), assuming that the 160k alpha 1(IV) chain is a processed form of the 180k alpha 1(IV) one and not an alternatively spliced chain of the alpha 1(IV) gene.

Amino Acid Sequence↗
PubMed1996

Cloning and characterization of a probenazole-inducible gene for an intracellular pathogenesis-related protein in rice.

Probenazole (3-allyloxy-1,2-benzisothiazole-1,1-dioxide) induces disease resistance in rice against rice blast fungus. To investigate the molecular mechanism of probenazole-induced resistance, we isolated and characterized a cDNA clone of a probenazole-inducible gene in rice, which encoded a protein designated PBZ1. Sequence analysis revealed that significant homology at the amino acid level exists between the predicted PBZ1 protein and intracellular pathogenesis-related (IPR) proteins. Accumulation of PBZ1 mRNA was not induced by wounding, but markedly induced by inoculation with rice blast fungus. In addition, it was induced sooner by inoculation with an incompatible race than that with a compatible race. On the other hand, when the accumulation of the PBZ1 mRNA was examined after treatment with probenazole-related compounds, it was not fully correlated with anti-rice blast activity. However, it was induced after treatment with N-cyano-methyl-2-chloro-isonicotinamide (NCI), which belongs to another group of compounds known to induce disease resistance. Thus, although the accumulation of the PBZ1 mRNA was not fully correlated with anti-rice blast activity, our findings suggest that the PBZ1 gene has an important function during the disease resistance response in rice.

Amino Acid Sequence↗
PubMed1996

Ultrastructural study of the synapses of central chromatolytic anterior horn cells in motor neuron disease.

This report deals with an ultrastructural investigation of the synapses on the somata of central chromatolytic anterior horn neurons of seven patients with amyotrophic lateral sclerosis (ALS) and four patients with lower motor neuron disease (LMND) who had no upper motor neuron or corticospinal tract involvement. Specimens from 24 age-matched individuals who died of non-neurological diseases served as controls. We examined a total of 171 anterior horn neurons with central chromatolysis (51 from ALS, 42 from LMND and 78 from controls), and 174 normal-appearing anterior horn neurons as controls. The cross-sectional area, the number of synapses, and the length of active zone were significantly reduced in the chromatolytic neurons of both patients and controls as compared with normal-appearing neurons of the controls (p < 0.0001). However, regarding chromatolytic neurons, no significant differences were seen in the number of synapses, length of each individual synapse, and length of its active zone between patients and controls and also in the frequency of presynaptic alterations on the somata. There was no overall difference between ALS and LMND patients in any of these parameters. Our findings suggest that the flow of electrophysiological information from afferent fibers to the somata may be greatly impaired in central chromatolytic neurons of both control individuals and patients with motor neuron disease (MND), and that the observed synaptic alterations may reflect pathological events resulting from anterior horn neuron degeneration. It may represent a compensatory mechanism of the synapses for diminished synaptic function that synapses were relatively well preserved on the somata of central chromatolytic neurons of the MND patients as compared with those of the chromatolytic neurons of the controls despite of markedly reduced cross-sectional area in the former. It also suggests that the pathomechanism involved in central chromatolysis differs between normal individuals and patients with MND.

Aged↗
PubMed1996

Assessment of clinical significance of positive blood cultures of relatively low-virulence isolates.

In Omori Hospital, Toho University School of Medicine, relatively low-virulence blood isolates, including coagulase-negative staphylococci (CNS), enterococci and nonfermentative gram-negative rods other than Pseudomonas aeruginosa comprised c. 60% of total blood isolates. A retrospective study was conducted to assess their clinical significance by reviewing a total of 91 hospital charts. The physicians' assessments of these positive blood cultures as recorded in the charts were classified into four categories--sepsis, possible sepsis, contamination and no comment. The episodes classified as sepsis accounted for 5.0-19.6%. These episodes were also evaluated by a graded clinical significance score based on multiple factors, including number of positive cultures and clinical signs. The scores for the 91 episodes covered a wide range from 1 to 9, indicating that both contaminants and causative organisms may have been involved. The episodes judged as sepsis or possible sepsis tended to have higher scores. The scores for the episodes associated with enterococci were also higher than those involving CNS or non-fermentative gram-negative rods. The scores for episodes associated with intravenous hyperalimentation catheters were higher than those not associated with the catheters.

Bacteremia↗
PubMed1996

Rheological analysis of peripheral blood neutrophils in a patient with cutaneous and arthropathic psoriasis accompanying hypopyon-iridocyclitis.

A 32 year old Japanese male has had several synchronized attacks of psoriatic arthritis and hypopyon-iridocyclitis. During exacerbations, he has a leucocytosis with neutrophilia and elevated C-reactive protein. Assessment for adhesiveness, aggregation and deformation of peripheral neutrophils revealed strikingly high rheological activity whereas during periods of remission the activity was only slightly elevated above normal.

Adult↗
PubMed1996

Modulation of carbachol-induced [Ca2+]i oscillations by Ca2+ influx in single intestinal smooth muscle cells.

1. Oscillations of cytosolic Ca2+ concentration ([Ca2+]i) evoked by carbachol (CCh; 2 microM), a muscarinic agonist, were detected as oscillatory changes of muscarinic receptor-coupled cationic current (Icat) in guinea-pig ileal smooth muscle cells by the whole cell patch-clamp technique. 2. Reduction of extracellular Ca2+ from 2 mM to 0.2 or 0.05 mM, during CCh-induced Icat oscillations, caused them to disappear or to decrease markedly in frequency. A return to 2 mM Ca2+ concentration restored the initial Icat oscillations. 3. Application of nifedipine (1-3 microM) or D600 (2-5 microM) to block the voltage-gated Ca2+ channel (VGCC) decreased the frequency of the ongoing Icat oscillations in the cells held at -20 mV, but it was without effect in cells held at -60 mV. 4. Displacement of the holding potential of -20 mV to -60 mV to deactivate VGCC produced a decrease, an increase or no noticeable change in the frequency of the Icat oscillations in different cells. Displacement to 20 mV to inactivate VGCC invariably produced a decrease in the frequency. In nifedipine-treated cells, the Icat oscillations varied in frequency voltage-dependently in a reverse and linear way within the range -80 to 40 mV. 5. Application of thapsigargin (1 or 2 microM), an inhibitor of Ca(2+)-ATPase in the membrane of internal Ca2+ stores, caused CCh-induced Icat oscillations to disappear with a progressing phase during which their amplitude, but not frequency, declined. 6. The results suggest that membrane Ca2+ entry has a crucial role to play in regulation of the frequency of CCh-induced [Ca2+]i oscillations in addition to persistence of their generation, and that the effect is brought about by a potential mechanism independent of Ca2+ store replenishment. They also provide evidence that two types of Ca2+ permeant channels, VGCC and an as yet unidentified channel, are involved in the Ca2+ entry responsible for modulation of [Ca2+]i oscillations.

Animals↗
PubMed1996

A clinical profile of corticobasal degeneration presenting as primary progressive aphasia.

We report a patient with primary progressive aphasia who first presented with amnesic aphasia that developed over the course of 3 years into nonfluent aphasia with buccofacial apraxia, followed in the next year by cognitive impairment and parkinsonism. Pathological findings were typical for corticobasal degeneration except for the distribution of cortical atrophy. This case suggests that corticobasal degeneration should be included in the differential diagnosis of primary progressive aphasia, especially in association with parkinsonism.

Aphasia, Primary Progressive↗
PubMed1996

Psoriatic arthritis and hypopyon-iridocyclitis. Possible mechanism of the association of psoriasis and anterior uveitis.

BACKGROUND: We present a 32-year-old Japanese man with psoriatic arthritis who developed recurrent episodes of hypopyon-iridocyclitis associated with exacerbations of the arthropathy. OBJECTIVE: To evaluate the mechanism of the association between psoriasis and uveitis, we analyzed the rheological characteristics of the patient's peripheral blood neutrophils during attacks and during remissions. METHODS: The rheological activity of neutrophils was determined by the micropore filtration method. It was expressed as micropore filtration time when a neutrophil-erythrocyte suspension passes through a micropore filter (pore size 5 microns). RESULTS: The micropore filtration time in this patient was longer than that of healthy control subjects (p < 0.01) and of psoriatic patients without uveitis (p < 0.05); it was also longer during the appearance of the eye disorder with the exacerbation of psoriatic arthritis than during remissions. CONCLUSIONS: Activated neutrophils in the peripheral blood of our patient were probably responsible for the attacks of hypopyon-iridocyclitis as well as the exacerbation of psoriatic skin lesions and/or arthritis.

Adult↗
PubMed1996

Bronchiolar disease in rheumatoid arthritis.

The pulmonary manifestations of rheumatoid arthritis (RA) include bronchiolar diseases such as follicular bronchiolitis (FB) and bronchiolitis obliterans (BO). In this study, we investigated the clinical and pathologic features of FB and BO, as well as the effect of erythromycin (EM) on these diseases. The subjects included 15 RA patients with biopsy-proven bronchiolar disease (eight with FB, seven with BO). None of the patients had Sjögren's syndrome. Eleven patients (73%) had chronic sinusitis, and 14 (93%) had a chronic cough with sputum. Bacterial culture of sputum was positive in 50% and 71% of the FB and BO patients, respectively. High-resolution computed tomography (HRCT) revealed small nodular shadows in the centrilobular regions (FB and BO), patchy areas of low attenuation (BO), and peribronchial thickening (FB and BO). Eleven patients who received EM therapy showed a significant improvement of symptoms. In addition, none of the 15 patients died of the bronchiolar disease during follow-up. In conclusion, RA patients with FB or BO basically have a chronic clinical course with main complaint of productive cough, and EM may be useful for the management of these diseases.

Anti-Bacterial Agents↗
PubMed1996

Impairment of fast axonal transport in the proximal axons of anterior horn neurons in amyotrophic lateral sclerosis.

We studied the possible impairment of fast axonal transport in patients with amyotrophic lateral sclerosis (ALS) to gain some insight into the pathogenesis of the disease. We carried out an ultrastructural investigation of the proximal axons (axon hillock and initial segment) of the anterior horn neurons on samples from 11 ALS patients; specimens from 12 age-matched individuals who died of nonneurological diseases served as controls. Eighty-seven proximal axons that emanated directly from normal-appearing neurons were examined in each group of subjects. Increased smooth endoplasmic reticulum (SER) and the formation of bundles of fibrillary SER with a single unit membrane were not uncommonly observed in the initial segment of the patients with ALS. In some instances, there was loss of the parallel SER arrangement along the longitudinal axis. When viewed in transverse sections, the bundles had a tubular appearance. These morphologic changes of SER were exclusively demonstrated in patients with ALS. A marked increase or accumulation of mitochondria and lysosomes was more common in the proximal axons, particularly in the axon hillock, of ALS patients than of control subjects. The accumulation of these membrane-bounded cytoplasmic organelles suggests that fast axonal transport is impaired in the proximal axons of individuals with ALS. In addition, there were Lewy body-like hyaline inclusions, lipofuscin granules, and multiple membranous structures in the proximal axons. The presence of these unusual structures may also be a reflection of axonal transport dysfunction. By contrast, in the central chromatolytic neurons, there was not only a decrease in the number of neurofilaments in the axon hillock and initial segment, but also of mitochondria, lysosomes, and SER. In some instances, none of these cytoplasmic organelles was seen. These findings support the notion that the outflow of cytoplasmic constituents from the anterior horn cell body into the proximal axon may be impaired in central chromatolytic neurons.

Aged↗
PubMed1996

Phospholipase A2-induced cytoprotection of proximal tubules: potential determinants and specificity for ATP depletion-mediated injury.

Addition of phospholipase A2 (PLA2) to isolated proximal tubular segments (PTS) has previously been shown to decrease hypoxic cell death without altering ATP concentrations. The study presented here was undertaken to identify determinant(s) of this protection, and to define the spectrum of injuries against which it can operate. PTS were extracted from mouse kidneys and subjected to diverse forms of injury (hypoxia/reoxygenation, antimycin A, Ca2+ ionophore, amphotericin B, FeSO4, and myohemoglobin). In subtoxic doses, addition of PLA2 significantly reduced hypoxic- and antimycin A-induced injury (percentage of lactate dehydrogenase release); however, a dose-dependent exacerbation of all other forms of injury resulted. The ability of PLA2 to mitigate hypoxic injury remained intact despite the inhibition of Na,K-ATPase (ouabain) or the inducement of cytoskeletal disruption (cytochalasin D). However, it was negated by minimally toxic amphotericin B or Ca2+ ionophore doses, indicating its dependence on preserved ionic gradients. Nevertheless, neither lowering/removing buffer Ca2+ or NaCl concentrations, nor hypertonic mannitol addition reproduced the cytoprotective effect of PLA2. PLA2 induced synergistic deacylation in hypoxic tubules, suggesting that unsaturated fatty-acid accumulation might mediate its cytoprotective effect. The fact that the addition of exogenous arachidonate, but not palmitate, to tubules protected against hypoxia, but worsened nonhypoxic forms of injury, supported this hypothesis. Since arachidonate might induce "feedback" inhibition of intracellular PLA2, the ability of an intracellular phospholipase inhibitor (ONO-RS-082; Biomol, Plymouth, PA) to blunt hypoxic damage was tested. This agent fully reproduced the cytoprotective effect of PLA2. It was concluded that: (1) PLA2-induced cytoprotection is relatively specific for ATP depletion injury; (2) it is dependent on, but not explained by, maintenance of NaCl and Ca2+ gradients; (3) it does not require Na,K-ATPase activity or cytoskeletal integrity for its expression; and (4) extracellular PLA2, via arachidonate release, may cause feedback inhibition of intracellular PLA2, thereby protecting critical intracellular targets from attack.

Adenosine Triphosphate↗
PubMed1996

[Increased CA19-9 level in serum and bronchoalveolar lavage fluid from a patient with pulmonary tuberculosis].

A 66-year-old woman was admitted to the hospital because of general malaise and loss of appetite. Laboratory examination revealed an abnormally high level of CA19-9 in serum and a chest roentgenogram revealed soft reticular shadows in the right mid-lung field. An extensive examination revealed no malignant disease. Bronchoalveolar lavage fluid obtained from the right B5 contained an abnormally high level of CA19-9. Immunochemical staining for CA19-9 was positive in the epithelial cells of respiratory bronchioles. The level of CA19-9 decreased during anti-tuberculosis therapy. This case suggests that the CA19-9 level can reflect the activity of pulmonary tuberculosis.

Aged↗
PubMed1996

[Middle lobe syndrome--incidence and relationship to atypical mycobacterial pulmonary disease].

We evaluated the incidence of middle lobe syndrome in the Haibara area, and its relationship to atypical mycobacterial infection. Of the 30,588 persons who underwent annual mini-chest roentgenography in 1992 or 1993 or both, 51 (0.17%) had middle lobe syndrome, diagnosed from posteroanterior and lateral chest X-ray films. The incidence was significantly higher in persons over 50 years old than in persons under 50 years old (0.26% vs 0.02%: p < 0.001), and was higher in femals than in males (0.20% vs 0.11%: p = 0.527). Of 16 patients examined by bronchoscopy and computed tomography, 7 showed evidence of cylindrical bronchiectasis, and four had mycobacterium avium complex pulmonary disease presenting as middle lobe syndrome. All four were women who were 51 years of age or older and none had predisposing pulmonary disorders. Computed tomography showed multiple nodular shadows with or without bronchiectasis located in the middle lobe or the lingula. Cavitary lesions were not seen. These results indicate that middle lobe syndrome is not rare, and that infection with mycobacterium avium complex should be considered when multiple nodular shadows are seen in the middle lobe or the lingula.

Adult↗
PubMed1996

[Diagnosis of intracardiac thrombi by various imaging techniques and activation of platelets and coagulation-fibrinolysis in patients with cardioembolic stroke].

Recent epidemiological studies have suggested that 15 to 30% of all ischemic stroke is comprised of cardioembolic stroke. The presence of intracardiac thrombi might prove to be the most reliable tool when making a diagnosis of cardioembolic stroke, although not always easy to determine even with recent advanced technique. In this study, sensitivities to detect intracardiac thrombi of transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), cardiac-enhanced CT (CCT) and scintigraphy with indium-111-tropolone-labelled platelets (PSG) were compared, in order to provide a relevant guideline for the diagnosis of intracardiac thrombi in 83 patients suspected of cardioembolic stroke. Also studied was the correlation of intracardiac thrombi with activation of platelets and coagulation-fibrinolysis through performing various hemostatic tests in order to investigate their utility for the evaluation of in situ thrombosis or prothrombotic state in the heart chamber. Detection rates of intracardiac thrombi were 35% in TEE, 26% in CCT, 19% in PSG, and 11% in TTE. There was a significant difference in the sensitivity between TEE and TTE (p < 0.05). Left atrial thrombi were frequently detected in TEE (4 out of 5 patients) and CCT (7 out of 10), while they were found less in PSG (2 out of 4) an TTE (4 out of 10). Thrombi in the left appendage were visualized in 3 out of 3 by TEE, while only in 1 out of 3 by PSG, 1 out of 4 by TTE and 1 out of 4 by CCT. Left ventricular thrombi; CCT (3 out of 3), TTE (2 out of 3), PSG (1 out of 1); TEE was not performed since this technique could not be expected to provide high-quality images of left ventricular thrombi. Thus, left atrial thrombi were considered to be more sensitively detected by TEE and CCT, left appendage thrombi by TEE, and left ventricular thrombi by TTE and CCT. There was no patient in whom an intracardiac thrombus was visualized by PSG alone. On the basis of the results above, we propose the following guideline for the detection of intracardiac thrombi in patients presented with cardioembolic stroke. First, TTE and CCT appear to be relevant for screening tests because of simple and non-invasive techniques. These two tools might be sensitive enough to find left ventricular thrombi. Second, TEE should be recommended when a thrombus is suspected in the left atrium or appendage. Finally, PSG may be used to determine the activity of the thrombus, according to its necessity. Among the patients having intracardiac thrombi, frequently observed was the increase of beta-thromboglobulin, platelet factor 4, platelet lysis, thrombin-antithrombin III complex, D-dimer in 67%, 75%, 71%, 80% and 80%, respectively, as well as the shortening of platelet survival in 100%, while anrithrombin III was reduced in only 38%. In addition, when hemostatic abnormalities were compared between positive and negative groups of intracardiac thrombi, the shortening of platelet survival (p < 0.0001), the increase of platelet lysis, and the increase of D-dimer (p < 0.04) were more frequent in the positive group than in the negative group. These results indicate that the findings of activation of platelets and coagulation-fibrinolysis, except for the reduction of antithrombin III, especially the findings of platelet consumption and lysis as well as fibrinolysis activation are useful as sensitive parameters of in situ thrombosis or prothrombotic state, which may lead to the formation of intracardiac thrombi.

Adolescent↗