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T Harada

Publications and source records attributed to T Harada.

At least 361 records · Page 20Linked to original sources
PubMed1997

Synergistic antitumor effects of human interferon-beta and interferon-gamma on human gastric adenocarcinoma cells.

The combined effects of different classes of interferon (IFN) on human gastric adenocarcinoma cell line HPE-GAC-2 (GAC-2) were investigated in vitro. Synergistic effects of IFN-beta and -gamma, causing cell death, were observed in a dose-dependent manner. IFN-gamma modulated the sensitivity of GAC-2 cells to the cytocidal effect of IFN-gamma. The modulatory effect was independent of the cytostatic or cytocidal activity of IFN-beta since brief contact with IFN-beta did not influence the growth kinetics of the cells and was effective in modulate the cellular sensitivity to IFN-gamma. A brief pretreatment of the cells with IFN-alpha or-beta resulted in a variable level of modulation, whereas coculture of the cells with IFN-beta or -alpha and IFN-gamma had a similar cytotoxic effect indicating a different level of activity induced by IFN-alpha and -beta with the common type I receptor. These results suggest that IFN-beta-induced modulation was receptor-mediated. Phase contrast microscopy showed evidence of apoptotic cell death induced by one or more IFN agents. The morphological changes included chromatin condensation and nuclear fragmentation which were apparent at as early as 6 hr of culture with a high concentration of IFN(s). Our results indicate that IFN-beta and IFN-alpha enhance the in vitro apoptotic effects of IFN-gamma against GAC-2 tumor cells.

Adenocarcinoma↗
PubMed1997

[Endothelial cell activation and/or injury in multiple sclerosis: analysis with von Willebrand factor and thrombomodulin].

Breakdown of the blood-brain barrier, which consists of endothelial cells, is implicated essential in the pathogenesis of multiple sclerosis (MS). To examine the endothelial cell damage, we determined the von Willebrand factor and thrombomodulin, markers for endothelial cell activation and/or injury, in the peripheral blood of patients with MS. The subjects were 26 patients with relapsing-remitting MS and 35 control subjects (mean age +/- standard deviation, 44.8 +/- 9.6 years). Patients with systemic vasculitis were excluded. The plasma activity of von Willebrand factor was significantly higher in patients with MS in the active phase (n = 23; 44.6 +/- 9.6 years) than in the age-matched controls. This suggests that von Willebrand factor could be a useful marker for evaluating the breakdown of blood-brain barrier resulting from endothelial damage in MS. In contrast, the serum level of thrombomodulin was not significantly different between patients with active MS and the controls. In MS patients (n = 15; 44.2 +/- 2.2 years), the plasma activity of von Willebrand factor was significantly lowered after immunosuppressive treatment. This suggests that von Willebrand factor could be used as a parameter for assessing the effect of treatment in MS.

Adult↗
PubMed1997

Immunohistochemical, ultrastructural, and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa.

BACKGROUND: Kindler syndrome is a rare, inherited skin disease characterized by acral bullae formation, fusion of fingers and toes, and generalized progressive poikiloderma. The purpose of this study was to clarify the nature of the bullous component of Kindler syndrome and to determine whether this inherited skin disorder represents a variant of dystrophic epidermolysis bullosa or a unique independent clinical entity. OBSERVATIONS: Two unrelated patients with Kindler syndrome were studied. Electron microscopy demonstrated marked duplication of the lamina densa, and clefts were observed in areas where the lamina densa was destroyed or obscured. Hemidesmosomes and anchoring fibrils showed normal features. Indirect immunofluorescence revealed normal linear labeling with antibodies against hemidesmosomal components (alpha 6 and beta 4 integrins, BPAG1, and BPAG2) and against anchoring filament components such as uncein, as detected by the 19-DEJ-1 monoclonal antibody. However, antibodies against the 3 respective laminin 5 chains, type IV collagen, and various type VII collagen epitopes (the aminoterminal NC1 domain, the central triple helical collagenous domain, and the carboxyterminal end of the triple helical collagenous domain) revealed a broad reticular staining pattern. Molecular screening of the type VII collagen gene (COL7A1) in the patients and their parents by heteroduplex analysis failed to detect any band shifts indicative of pathologic mutations. CONCLUSIONS: These results suggest that the bullous component of Kindler syndrome is distinct from dystrophic epidermolysis bullosa caused by mutations in the type VII collagen gene. Additionally, the differential distribution patterns of uncein and laminin 5 in the patients' skin samples support the hypothesis that uncein and laminin 5 are different molecules.

Adult↗
PubMed1997

Intraglomerular C3 synthesis in rats with passive Heymann nephritis.

Passive Heymann nephritis (PHN), a model of human membranous nephropathy, is an immune-complex-mediated glomerulonephritis characterized by the presence of complement-dependent tissue injury. Recent studies have confirmed the synthesis of C3, involved in both the classical and alternative pathways of complement, in injured human and animal renal tissues. However, there is little clear information on the role of local C3 synthesis in the pathogenesis of nephritides such as PHN. In the present study, using nonradioactive in situ hybridization and semiquantitative reverse transcriptase polymerase chain reaction, we examined C3 synthesis in the kidney and its contribution to tissue injury in a rat model of PHN induced by the injection of polyclonal anti-gp330 antibody. C3 mRNA was localized in mesangial cells, glomerular epithelial cells, and cells of Bowman's capsule. During the early stages of PHN, C3 mRNA expression was detected in mesangial cells and glomerular epithelial cells, whereas such expression was limited to mesangial cells during the late stages of the disease. Focal, weak C3 mRNA expression was detected in tubular epithelial cells and occasionally in the interstitium. Semiquantitative polymerase chain reaction demonstrated that the level of C3 mRNA expression correlated with that of proteinuria. Our results suggest that renal cells synthesize C3 mRNA in PHN in a site-specific manner and that locally produced C3 is associated with the development of proteinuria in this model.

Animals↗
PubMed1997

Differential expression of maf-1 and maf-2 genes in the developing rat lens.

PURPOSE: To examine the expression of maf-1 and maf-2 protocogenes in the developing rat lens. METHODS: Maf-1 and maf-2 transcripts were assayed in rat lenses on embryonic days 13 and 16 (E13 and E16) by in situ hybridization using single-stranded RNA probes. Proteins encoded by the maf-2 gene were assayed immunocytochemically in embryonic (E12, 13, 16, 19) and postnatal day 14 and 90 (P14 and P90) lenses. RESULTS: In embryonic lenses, we detected maf-1 messenger RNA (mRNA) in the lens epithelium and maf-2 mRNA diffusely distributed in the lens fiber cells. By immunocytochemistry, Maf-2 was detected on E12 in the nuclei of almost all lens pit cells. On days E13, E16, and E19, however, lens epithelial cells showed no immunoreactivity, but nuclei of fiber cells reacted strongly. On P14, nuclei containing Maf-2 protein were confined to the equator of the lens, but at 3 months of age, no Maf-2 could be detected in the rat lens. Western blotting showed that the anti-Maf-2 antiserum reacted with a single protein, of molecular weight approximately 39 kDa, in rat lens. CONCLUSIONS: Results showed the spatial and temporal regulation of maf gene expression and suggest that these genes participate in transcriptional regulation during the development of the lens in the rat.

Animals↗
PubMed1997

Somatic neurofibromatosis type 2 gene mutations and growth characteristics in vestibular schwannoma.

BACKGROUND: The growth of hereditary and sporadic vestibular schwannomas shows wide variation, but what determines this is poorly understood. HYPOTHESIS: In neurofibromatosis type 2 (NF2), there is some correlation between the nature of the germline NF2 gene mutation and phenotype. Somatic mutations in the NF2 gene occur in sporadic tumors, but their relation to tumor behavior is unknown. METHODS: This study has investigated the molecular pathogenesis of vestibular schwannoma by looking for NF2 gene mutations. The authors have screened 17 exons of the NF2 gene in 91 sporadic vestibular schwannomas, 2 NF2, and 1 vagal schwannoma. These data have been correlated with a clinical growth index and a tumor cell proliferation index, determined using a monoclonal antibody to the proliferating cell nuclear antigen. RESULTS: Of the 94 tumors studied, 40 somatic gene mutations (38%) have been sequenced in 36 tumors. The mutations included 36 protein truncating mutations, 1 in-frame deletion, 2 splice site mutations, and 1 missense mutation. Regression analysis showed no correlation between the nature of the NF2 gene mutation and either the clinical (R2 = 0.006) or the proliferative index (R2 = 4 x 10(-8). CONCLUSION: The results of this study show no association between the nature of the intragenic NF2 gene mutation and tumor behavior. It is likely therefore that NF2 gene inactivation is not the only determinant of tumor behavior in vestibular schwannoma.

Adult↗
PubMed1997

[A case of systemic lupus erythematosus associated with minimal change nephrotic syndrome].

A case of systemic lupus erythematosus (SLE) associated with minimal change nephrotic syndrome (MCNS) in a 25-year-old female is described. The patient suddenly manifested butterfly rash and proteinuria was first pointed out on March, 1994. On admission, her skin biopsy indicated SLE. Subsequently, she developed nephrotic syndrome. Urinalysis showed heavy proteinuria (4.1 g/day), with no other abnormalities in the urinary sediment. Immunological examination revealed positive antinuclear antibody at a titer of 1:80 with a speckled pattern. Anti-ssDNA and anti-SS-A antibodies were positive, but other antibodies were negative. Serum complement (CH50) was within the normal range (30.5 U/ml). The renal biopsy showed no apparent cellular proliferation or increase of extracellular matrices in glomeruli by light microscopy. Slight deposition of IgG, IgM, C3 and C1q was focally seen in the mesangium and capillary wall by immunofluorescence. Electron microscopic examination revealed small and scattered dense deposits in the mesangium, subepithelium and subendothelium, associated with diffuse fusion of the foot processes of epithelial cells along the glomerular basement membrane. According to the WHO classification, the histological features were compatible with those of lupus nephritis (LN), class Ib. The patient was treated with PREDNISOLONE, Mizorbine and Dilazep, resulting in the disappearance of proteinuria and a normal serum level of total protein. The association of LN and MCNS is very rare. We also investigated the relationship between the intensity of proteinuria and histological types of 53 cases with LN examined in our laboratory. The cases with heavy proteinuria were mostly classified as WHO-Class IV and Class V. We report here a case of LN associated with MCNS and also review the literatures.

Adult↗
PubMed1997

A novel variant of acquired epidermolysis bullosa with autoantibodies against the central triple-helical domain of type VII collagen.

Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus are autoimmune bullous disorders, with tissue-bound and circulating autoantibodies reactive with the noncollagenous NC1 domain of type VII collagen (C-VII). Here, we describe a novel acquired bullous dermatosis with autoantibodies against the triple-helical domain of C-VII. Three patients, all Japanese children, presented with widespread inflammatory tense blisters. Histologically, subepidermal tissue separation was noted with inflammatory infiltrate in the superficial dermis. Direct immunofluorescence staining revealed linear IgG/C3 deposits along the dermal-epidermal junction. Circulating IgG anti-basement membrane zone autoantibodies stained the dermal side of normal skin separated with 1 M NaCl. Direct and indirect immunoelectron microscopy using colloidal gold labeling showed that patient sera reacted with anchoring fibrils. The gold particles were localized both near the lamina densa and on the central banded portion of the fibrils. The sera reacted with C-VII in immunoblots. Epitope analyses with natural and recombinant fragments of C-VII disclosed that the sera did not recognize the NC1 domain of C-VII, but the central triple-helical domain of this anchoring fibril protein. Thus, the present probands show a hitherto unrecognized variant of epidermolysis bullosa acquisita, with autoantibodies against epitopes in the collagenous domain of C-VII.

Autoantibodies↗
PubMed1997

A case of bilateral optic neuropathy and recurrent transverse myelopathy associated with perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA).

A case involving a 52-year-old man having bilateral optic neuropathy and recurrent transverse myelopathy is reported. His clinical features resembled multiple sclerosis, but neuroimaging failed to show evidence of demyelination or inflammation in the brain or the optic nerves. The patient experienced sudden visual loss despite massive steroid therapy. Positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) is suggestive that optic neuropathy and recurrent transverse myelopathy may have been caused by some common inflammatory processes associated with p-ANCA, however, having a different etiology from multiple sclerosis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

[Successful operation on giant solitary fibrous tumor of the pleura].

A 68-year-old man began complaining of dizziness and dyspnea on exertion 2 months ago. Chest X-ray and CT scan taken on admission revealed a giant tumor occupying almost all of the right thoracic cavity. The mediastinum, especially RA and IVC, was markedly oppressed and shifted by the tumor. MRI showed no invasive lesions of the tumor into adjacent organs. An operation was performed under the tentative diagnosis of solitary fibrous tumor (SFT) of the pleura by transcutaneous needle biopsy. The tumor was encapsulated and resected from the lower lobe of the right lung using a surgical stapler. Then the tumor was carefully dissected from the chest wall, pericardium and diaphragma, and removed completely. It weighed 3920 g and measured 22 x 20 x 20 cm. Various immunohistochemical properties of the specimen were morphologically compatible with SFT. The postoperative course was uneventful and the patient is now free of complaints. Because malignant cases of SFT have been reported a careful follow-up will be performed.

Aged↗
PubMed1997

Pace-mapping conduction delay at reentry circuit sites of ventricular tachycardia after myocardial infarction.

This study was carried out to determine the relationship of conduction delay during pace-mapping, as indicated by the stimulus to QRS interval to different reentry circuit sites and bystanders, as identified by entrainment criteria, in patients with ventricular tachycardia late after myocardial infarction. Catheter mapping and ablation were performed in 40 patients with ventricular tachycardia after myocardial infarction. Data were retrospectively analyzed from 122 endocardial sites which met the following the criteria: a 12-lead electrocardiogram was recorded during pace-mapping, ventricular tachycardia was then induced and entrained by pacing to classify the type of the site relative to the reentry circuit exit. By entrainment criteria 77 sites were in the reentry circuit (28 exit sites, 49 other circuit sites) and 45 sites were bystanders not in the reentry circuit. The average stimulus conduction delay at central/proximal sites was 103 +/- 43 ms, which was significantly longer than at exit (57 +/- 31 ms), outer loop sites (57 +/- 32 ms), and bystander sites (57 +/- 37 ms); P < 0.05. Pace-mapping revealed evidence of greater conduction delay at sites proximal to the reentry circuit exit, consistent with slow conduction between these regions and the border of the infarct. Exit sites and outer loop sites were more likely to be located along the border of the infarct, with less conduction delay evident during pace-mapping.

Cardiac Pacing, Artificial↗
PubMed1996

Molecular cloning and expression of a novel peptide (LN1) gene: reduced expression in the renal cortex of lupus nephritis in MRL/lpr mouse.

A gene has been identified by mRNA differential display whose expression is reduced in the renal cortex of MRL/lpr mouse. The nucleotide sequence of the cDNA contains an open reading frame that encodes a protein of 338 amino acids (termed LN1). In situ hybridization showed that LN1 mRNA is present in glomeruli, and a 39 kDa protein was detected in the kidney by immunoblot. A human LN1 cDNA was also isolated, the deduced amino acid sequence of which is 78% identical to that of mouse LN1. Although the function of LN1 remains to be elucidated, its reduced expression may contribute to the pathogenesis of lupus nephritis.

Amino Acid Sequence↗
PubMed1996

Characterization of a germline Vk gene encoding cationic anti-DNA antibody and role of receptor editing for development of the autoantibody in patients with systemic lupus erythematosus.

We found previously that cationic anti-DNA autoantibodies (autoAbs) have nephritogenic potential and usage of a specific germline Vk gene, A30, has major influences on cationic charge of the autoAb in human lupus nephritis. In the present study, we have characterized A30 germline Vk gene using cosmid cloning technique in patients with SLE. A30 gene locus locates in less than 250 kb from the Ck region, and the cationic anti-DNA mRNA used the upstream Jk2 gene, indicating that cationic anti-DNA mRNA is a product of primary gene rearrangement. By using PCR technique, we found that A30 gene locus in the genome was defective in eight out of nine SLE patients without nephritis. In contrast, all nine patients with lupus nephritis had intact A30 gene. The presence and absence of A30 gene was associated with the development of lupus nephritis or not (P < 0.01, by Fisher's exact test, two-sided). It was thus suggested that absence of functional A30 gene may rescue from developing lupus nephritis in the patients. A30 is reported to be a potentially functional but rarely expressed Vk gene in humans. It is possible that normal B cells edit primarily rearranged A30 gene with autoreactive potentials by receptor editing mechanism for changing the affinity of the B cell Ag receptor to avoid self-reactivity, whereas SLE B cells may have a defect in this mechanism. Indeed, we found that normal B cells edit A30-Jk2 gene in their genome possibly by inversion mechanism, whereas SLE B cells contain rearranged A30-Jk2-Ck gene in the genome and express A30-associated mRNA, suggesting that receptor editing mechanism is also defective in patients with SLE. Our study suggests that polymorphism of Ig Vk locus, and failure of receptor editing may contribute to the development of pathogenic anti-DNA responses in humans.

Adolescent↗