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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 271 records · Page 15Linked to original sources
PubMed1996

[Regulation of thymocyte apoptosis and positive selection].

Developing T cells undergo thymic selection at the CD4+CD8+ stage. Only less than 5% of CD4+CD8+ thymocytes are positively selected to survive and differentiate into mature single positive CD4 or CD8 T cells. Positive selection requires signaling through the T cell receptors (TCR) with assistance of CD4 or CD8 coreceptor and LFA-1, but its molecular mechanism is poorly understood. By using glucocorticoids, anti-apoptotic activity was detected in CD4+CD8+ thymocytes upon proper cross-linking of TCR/CD3 complex with CD4, CD8, or LFA-1, and was mimicked by a combination of a calcium ionophore and a protein kinase C activator. Isolated CD4+CD8+ thymocytes underwent differentiation and commitment to the CD4 T cell lineage by moderate and transient stimulation with this combination of the drugs.

Animals↗
PubMed1996

[Swyer-James syndrome with unilateral pulmonary edema].

A 64-year-old man with ischemic heart disease was admitted to our hospital because of dyspnea. A chest X-ray film showed a butterfly shadow in the right lung. A chest X-ray film obtained before the patient had respiratory symptoms showed hyperlucency of the left lung. CT scans obtained at maximal inspiration and expiration revealed air trapping. Pulmonary arteriography showed that the left pulmonary artery and its branches were very small. Cardiac catheterization showed poor cardiac function. Swyer-James syndrome should be included in the differential diagnosis of patients with unilateral pulmonary edema.

Bronchial Diseases↗
PubMed1996

[Amyloidosis secondary to bronchiectasis].

A 77-year-old woman was hospitalized repeatly due to frequent hemoptysis and production of bloodly sputum for several years. Bronchography in 1989 revealed bronchiectasis. She had complained of abdominal pain and diarrhea since 1991, and her urine was first positive for protein in 1992. She was admitted to our hospital in October 1992 because of edema, anemia, and hypoproteinemia. Despite treatment, renal dysfunction and the gastrointestinal disorder progressed and she died in January 1993. An autopsy revealed diffuse depositions of amyloid in many organs, especially in the kidney and the gastrointestinal tract. This amyloid protein was identified as AA protein, which was suggestive of secondary amyloidosis. Bronchiectasis appears to have been the disease underlying this patient's amyloidosis.

Aged↗
PubMed1996

[Diffuse alveolar septal amyloidosis associated with multiple myeloma (IgA lambda type)].

A 75-year-old man with multiple myeloma presented with fever and respiratory symptoms. A chest roentgenogram showed interstitial shadows and transbronchial lung biopsy revealed diffuse infiltration of amyloid in the alveolar walls. Analysis of bronchoalveolar lavage fluid showed the presence of an IgA-lambda paraprotein, and the IgA/albumin ratio was similar to that in serum. However, plasma cells could not be detected in the cells obtained by lavage. We know of no previous case in Japan in which bronchoalveolar lavage fluid was examined in a case of diffuse alveolar septal amyloidosis.

Aged↗
PubMed1996

Activation of prefrontal and posterior superior temporal areas in visual calculation.

Regional cerebral blood flow was measured with H2(15)O-positron emission tomography during the performance of visually presented calculation tasks to clarify cortical areas involved in arithmetic operations. The findings on a calculation task were compared with those on a covert reading task and with those of a fixation control task. Region of interest-based analysis showed that the left prefrontal area was activated in visual calculation relative to covert reading and the posterior superior temporal gyrus including part of Wernicke's area was activated in calculation relative to fixation control. The role of the prefrontal area in computation (arithmetic operations) and that of the posterior superior temporal gyrus in both comprehension of the stimuli and computation were suggested.

Adolescent↗
PubMed1996

[A case of relapsing Guillain-Barré syndrome following Miller Fisher syndrome].

Miller Fisher syndrome (FS) is thought to be a variant of Gullain-Barré syndrome (GBS), both of which rarely relapse. We report a rare case of GBS that followed FS. A 38-year-old woman had ophthalmoplegia, ataxia and areflexia following an upper respiratory tract infection with a diagnosis of FS. Serum anti-GQ1b IgG antibody was found to be increased, but decreased through immunoadsorption as the neurological symptoms of the patient improved. She became completely asymptomatic three months after the onset of FS. Following a common cold two months later, however, she developed weakness of all four limbs and dysesthesia of hands and feet with albuminocytologic dissociation of cerebrospinal fluid, which was consistent with the diagnosis of GBS. Moreover, serum anti-GQ1b IgG antibody had increased again. Anti-GQ1b IgG antibody frequently becomes positive not only in FS but also GBS with ophthalmoplegia. However, the antibody was positive in this particular patient with GBS, even in the absence of ophthalmoplegia. This case suggests that anti-GQ1b IgG antibody might be a common pathogenesis of both FS and GBS.

Adult↗
PubMed1996

[Peripheral nerve myelin antigen-specific T cells in human].

In recent years, anti-myelin glycolipid antibodies have been reported to be specific for acute inflammatory demyelinating polyneuritis (AIDP) so the involvement of autoimmune mechanism by such autoantibodies was strongly suggested as a cause of AIDP. However, the cellular immunity of AIDP has been seldom reported yet. To examine the T cell response to peripheral nerve antigens in human, we tried to establish T cell lines reactive to peripheral myelin antigens. P0 56-71, P0 180-199 and P2 59-78 peptides from human peripheral blood of controls and patients with inflammatory demyelinating polyneuritis. Frequencies of T cells reactive with P0 56-71, P0 180-199 and P2 59-78 peptides in five controls were (0.59 +/- 0.81) x 10(-7), (1.53 +/- 0.53) x 10(-7) and (0.11 +/- 0.24) x 10(-7), respectively. Frequency of P0 180-199-reactive T cells in one AIDP patient of acute stage was 3.5 x 10(-7) and approximately 2 times high value of controls. There is no significant association between their frequency and specific MHC class II genotypes in subjects until now. Thus, peripheral myelin antigen-specific T cell lines in particular recognizing P0 180-199 were established from the majority of controls and polyneuritis patients. These results suggest that the residues of P0 180-199 might be one of T cell epitopes also in human subjects.

Autoantigens↗
PubMed1996

[Follicular bronchiolitis associated with rheumatoid arthritis].

A 52-year-old man with an 8-year history of rheumatoid arthritis was admitted to the hospital because of coughing and purulent sputum. A chest X-ray film obtained on admission showed small nodular shadows without overinflation in both lower lung fields, and a high-resolution CT scan showed many micronodular shadows in the centrilobular regions. Follicular bronchiolitis was diagnosed from the results of an open-lung biopsy, and prednisolone therapy was started at a dosage of 40 mg/day. Sinusitis developed 4 years later. Five years after the start of steroid therapy, dilation of bronchi and thickening of bronchial walls appeared on a CT scan, which also showed areas of low attenuation that were presumed to be bronchiolitis obliterans. These findings suggest that the pattern of airway disease can vary during the course of rheumatoid arthritis.

Anti-Inflammatory Agents↗
PubMed1996

[Bronchiolitis obliterans preceding rheumatoid arthritis: effect of clarithromycin].

A 62-year-old man was referred to our department because of exertional dyspnea and a 6-year history of coughing and sputum production. He had never smoked, and had had an operation for chronic paranasal sinusitis. Coarse crackles and rhonchi were audible over both lower lung fields. The cold hemagglutinin titers were high. pulmonary function tests showed airflow obstruction, and a sputum culture revealed Hemophilus influenzae A chest X-ray film and a CT scan showed diffuse micronodular shadows in the centrilobular regions, mild ectasis of bronchioles mainly in the lower lung fields, and mild hyperinflation. A specimen of lung tissue was obtained by thoracoscopic biopsy, and histologic examination showed bronchiolitis obliterans, with bronchiolar narrowing or obliteration due to submucosal fibrosis and inflammation. Rheumatoid arthritis was diagnosed 14 months after the operation. The patient was treated with clarithromycin for 3 years. Respiratory symptoms were relieved and pulmonary function gradually improved.

Anti-Bacterial Agents↗
PubMed1996

[Fulminant interstitial pneumonia associated with polyarteritis nodosa].

A 54-year-old man was referred to our hospital because of fever, abdominal pain, hematemesis, and dyspnea on exertion. Laboratory examination on admission revealed elevations of WBC count and CRP. a low serum complement level, hypoxemia, and microhematuria. A chest X-ray film and a CT scan showed bilateral interstitial pneumonia and cardiomegaly. Angiography showed microaneurysms in peripheral branches of the superior mesenteric artery, the hepatic artery, and the right renal artery. Examination of a specimen of the right quadriceps muscle revealed arteritis with fibrinoid necrosis in a small artery, which was consistent with polyarteritis nodosa (PN). A specimen obtained by transbronchial lung biopsy before treatment showed interstitial mononuclear cell infiltration and edema. PN with interstitial pneumonia was diagnosed and the patient was treated with 1 g of methylprednisolone for 3 days, followed by 60 mg of prednisolone and 100 mg of cyclophosphamide daily. The interstitial pneumonia progressed. Despite a second trial of steroid pulse therapy in addition to mechanical ventilation and various kinds of antibiotics, the patient died of respiratory failure on the 35th hospital day. A specimen obtained by transbronchial lung biopsy 3 days before death revealed proliferation of fibroblasts, mononuclear cell infiltration in the interstitium, and hyaline membrane formation in air spaces. No evidence of infection was found. Interstitial pneumonia associated with PN had been considered to be quite rare, but recently some cases resembling the present case have been reported. We believe that interstitial pneumonia associated with PN might not be rare, and the present case shows that it can be fulminant.

Humans↗
PubMed1996

[A case of neuroborreliosis with unilateral radiculoneuropathy and elevated serum antibodies for Borrelia garinii and Borrelia afzelii].

A 24-year-old male patient was admitted to our hospital because of dysesthesia and weakness of the right leg. Six weeks before admission he traveled to southern China. A week later he noticed multiple papules with itching on his right leg that were suspected to be insect bites. Four days later numbness of the right leg developed. Then he began to limp because of the leg weakness. Two weeks before admission severe pain in the right leg developed. On admission neurological examination revealed hypesthesia, muscle weakness and atrophy, areflexia, radicular pain and Lasègue sign of the right leg, and patchy hypesthesia of the left leg. The cranial nerves were intact, and meningeal signs were negative. Complete blood counts and serum biochemistry were unremarkable except for eosinophilia and mild elevation of IgE. A test for antinuclear antibody was positive. Cerebrospinal fluid was normal. Nerve conduction study and sural nerve biopsy showed multifocal severe axonopathy. Although antibody for Borrelia burgdorferi sensu stricto was negative, antibodies for B. garinii and for B. afzelii were positive in serum immunoblotting. Neurological symptoms improved after administration of intravenous ceftriaxon following oral doxycycline. In Japan, this is the second case of neuroborreliosis not due to B. burgdorferi sensu stricto. To test antibodies for B.garinii and for B. afzelii is recommended in patients with suspected neuroborreliosis.

Adult↗
PubMed1995

Embryonic development of gonadotropin-releasing hormone neurons in the sockeye salmon.

Immunocytochemistry and in situ hybridization were used to test the hypothesis that gonadotropin-releasing hormone (GnRH) neurons are formed in the olfactory placode during embryonic development in a salmonid, Oncorhynchus nerka. The development of GnRH neurons and the pituitary cell types was examined from 19 through 910 days after fertilization. Immunoreactive GnRH was first detected at 19 days in the cells of the olfactory placode. GnRH immunoreactivity was not detected in any other structure of the central nervous system at this age. By day 24, GnRH-immunoreactive neurons were seen in the apical, intermediate, and basal layers of the olfactory placode. From days 30 through 51, GnRH neurons were seen emerging from the epithelium, along the olfactory nerve, and at the rostral olfactory bulb. By day 41, GnRH immunoreactivity was lost in the nasal epithelium. In the 72-day-old fish, most of the GnRH neuronal population was found in ganglia of the nervus terminalis, at the cribriform bone (gCB), and at the rostral olfactory bulb (gROB). On day 293, a decrease in GnRH-immunoreactive neurons in the gCB and gROB was concomitant with an initial appearance of GnRH-immunoreactive neurons and fibers along the caudoventral olfactory bulb. By day 462, the distribution of GnRH neurons and fibers was almost similar to adults. In maturing adults (910 days), GnRH-immunoreactive neurons were rarely seen in the nasal regions, but were primarily found in the basal forebrain. GnRH fibers were widespread in the brain, proximal para distalis, and in the pars intermedia of the pituitary. Our study supports the notion that neurons expressing salmon-GnRH mRNA and peptide originate in the medial olfactory placode and migrate into the basal forebrain during development. The midbrain neurons did not express salmon-GnRH mRNA or peptide in the larval and juvenile fish.

Animals↗
PubMed1995

Sphingosine: a mediator of acute renal tubular injury and subsequent cytoresistance.

The goal of this study was to determine whether sphingosine and ceramide, second messengers derived from sphingolipid breakdown, alter kidney proximal tubular cell viability and their adaptive responses to further damage. Adult human kidney proximal tubular (HK-2) cells were cultured for 0-20 hr in the presence or absence of sphingosine, sphingosine metabolites (sphingosine 1-phosphate, dimethylsphingosine), or C2, C8, or C16 ceramide. Acute cell injury was assessed by vital dye exclusion and tetrazolium dye transport. Their subsequent impact on superimposed ATP depletion/Ca2+ ionophore-induced damage was also assessed. Sphingosine (> or = 10 microM), sphingosine 1-phosphate, dimethylsphingosine, and selected ceramides (C2 and C8, but not C16) each induced rapid, dose-dependent cytotoxicity. This occurred in the absence of DNA laddering or morphologic changes of apoptosis, suggesting a necrotic form of cell death. Prolonged exposure (20 hr) to subtoxic sphingosine doses (< or = 7.5 microM) induced substantial cytoresistance to superimposed ATP depletion/Ca2+ ionophore-mediated damage. Conversely, neither short-term sphingosine treatment (< or = 8.5 hr) nor 20-hr exposures to any of the above sphingosine/ceramide derivatives/metabolites or various free fatty acids reproduced this effect. Sphingosine-induced cytoresistance was dissociated from the extent of cytosolic Ca2+ loading (indo-1 fluorescence), indicating a direct increase in cell resistance to attack. We conclude that sphingosine can exert dual effects on proximal renal tubular viability: in high concentrations it induces cell necrosis, whereas in low doses it initiates a cytoresistant state. These results could be reproduced in human foreskin fibroblasts, suggesting broad-based relevance to the area of acute cell injury and repair.

Acute Kidney Injury↗
PubMed1995

AG dinucleotide insertion in a patient with chronic granulomatous disease lacking cytosolic 67-kD protein.

The 67-kD cytosolic protein (p67-phox) is an essential component of the superoxide-generating system in phagocytes, and its defect is known to cause chronic granulomatous disease (CGD). We sequenced p67-phox cDNA from one of seven patients found in Japan and his parents. In the patient's cDNA, homozygous AG dinucleotide insertion at position 399 (or 401) was found together with three other homozygous substitutions in a coding region (A-542 to G, T-895 to C and A-983 to G) compared with the sequence reported for HL-60 cells. In cDNA from his parents, the AG insertion was found to be heterozygous. In contrast, the other three substitutions were found homozygously in his father's specimen and the latter two in his mother's specimen. The substitution of A-542 to G was heterozygous in his mother's cDNA. The AG insertion would induce a frame shift and bring about a stop codon at the position of 433. However, the other three differences would give insignificant changes for the protein function, if any, because the substitutions of A-542 to G and A-983 to G result in the conservative amino acid transitions, ie, Lys-180 to Arg and Lys-327 to Arg, and that of T-895 to C no amino acid change. Neutrophils from the patients completely lacked superoxide generating activity whereas those from his parents generated substantial amounts of superoxide anion upon stimulation. Thus, it is concluded that the AG dinucleotide insertion is responsible for the disease in this patient.

Adult↗
PubMed1995

Calcineurin activation protects T cells from glucocorticoid-induced apoptosis.

In T cell hybridomas, TCR/CD3 complex-mediated stimulation induces apoptosis but inhibits that induced by glucocorticoids. A combination of ionomycin (IM), a calcium ionophore, and PMA, a protein kinase C activator, mimics the effects of the TCR/CD3-mediated stimulation. Glucocorticoid-induced apoptosis is, however, markedly inhibited by IM alone, and less markedly by PMA alone. The immunosuppressant FK506 canceled the inhibition by IM but not that by PMA. As calcineurin (CN) is one of the target molecules of FK506, we examined whether CN activation might have an anti-apoptotic effect. BOG8, a T cell hybridoma, was stably transfected with a mutant CN catalytic subunit with Ca2+/calmodulin-independent, constitutive but FK506-sensitive phosphatase activity. The transfectant clones were fairly resistant to glucocorticoid-induced death. Their resistance, however, was hardly affected by FK506 when added simultaneously with glucocorticoid, but was lost after a prolonged preincubation with FK506. In the parent BOG8 cells, FK506 failed to cancel the inhibitory effect of IM on glucocorticoid-induced death when the addition of FK506 was delayed for 1 h or more. These results suggest that CN activation is required for the resistance only as an early event. The transfectant clones produced IL-2 but failed to undergo apoptosis upon stimulation with PMA alone, whereas apoptosis was induced by a combination of IM and PMA. These results suggest that activation-induced cell death may require a higher level of CN activity than IL-2 production or may require another Ca(2+)-dependent pathway.

Animals↗
PubMed1995

Cell-mediated catabolism of aggrecan. Evidence that cleavage at the "aggrecanase" site (Glu373-Ala374) is a primary event in proteolysis of the interglobular domain.

A rat chondrosarcoma cell line and primary bovine chondrocytes have been used to study cell-mediated aggrecan catabolism. Addition of 1 microM retinoic acid to chondrosarcoma cultures resulted in aggrecan proteolysis with the release of greater than 90% of the cell layer aggrecan into the medium within 4 days. NH2-terminal sequencing of chondroitin sulfate-substituted catabolic products gave a single major NH2-terminal sequence of ARGNVILTXK, initiating at Ala374. This showed that the proteinase, commonly referred to as "aggrecanase," which cleaves the Glu373-Ala374 bond of the interglobular domain of aggrecan (Sandy, J. D., Neame, P. J., Boynton, R. E., and Flannery, C. R. (1990) J. Biol. Chem. 266, 8683-8685), is active in this cell system. Aggrecan G1 domain, generated by cleavage of the interglobular domain, was also liberated during catabolism and this was characterized with three antipeptide antisera. Anti-CDAGWL was used as a general probe for G1 domain. Anti-FVDIPEN was used to specifically detect G1 domain with COOH terminus of Asn341, the form which is readily generated by cleavage of aggrecan by a wide range of matrix metalloproteinases. Anti-NITEGE antiserum was used to specifically detect G1 domain with COOH terminus of Gln373, the form which is the expected product of "aggrecanase"-mediated cleavage of aggrecan. Western blot analysis indicated that a single form of G1 domain of about 60 kDa was formed. G1 domain of this size reacted with both anti-CDAGWL and anti-NITEGE but not with anti-FVDIPEN. Similar experiments with primary bovine chondrocyte cultures, treated with either retinoic acid or interleukin 1, showed that two forms of catabolic G1 domain, of about 62 and 66 kDa, were formed. Both of these forms reacted on Western blots with anti-CDAGWL and also with anti-NITEGE. It is suggested that cell-mediated catabolism of the aggrecan interglobular domain in these culture systems, whether promoted by retinoic acid or interleukin 1, primarily involves cleavage of the Glu373-Ala374 bond by aggrecanase. The accumulation of G1 domain with a COOH-terminal of Glu373 shows that such aggrecanase-mediated cleavage can occur independent of the cleavage of the Asn341-Phe342 bond by matrix metalloproteinases.

Aggrecans↗
PubMed1995

Structural organization of the gene for CD40 ligand: molecular analysis for diagnosis of X-linked hyper-IgM syndrome.

CD40 ligand (CD40L) on activated T cells plays a crucial role for Ig heavy-chain class switching and the mutation of the gene for this ligand in the X-chromosome causes immunodeficiency with hyper-IgM (X-HIM). We isolated and characterized the human genomic clone for CD40 L to obtain information about the transcriptional regulatory regions of the gene and to develop a molecular diagnostic method for X-HIM patients. The genomic DNA isolated was over 12 kb long containing 5 exons that cover full sequence of mRNA for the ligand. DNA motif analysis based on transcription factor database revealed the presence of a GATA 1 box at around -265 bp. The typical TATA box, CAT site or GC rich region was not found in the 5' flanking region. However, two possible TATA like sequences were found at around -27 and -136 bp. Using the oligonucleotide primers corresponding to the introns, we performed a PCR-SSCP analysis of each exon from a patient with X-HIM syndrome and detected abnormality in exon 5. When sequenced, dinucleotide deletion in this exon was found in the patient and in one X allele of his mother as the only different sequence from that of the control gene. This procedure is simple and could be used for diagnosis of the X-HIM syndrome.

Adolescent↗