Search PubMed⌕ Search

Biomedical subjects

S Hirohata

Publications and source records attributed to S Hirohata.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Hyperosmolality in central nervous system lupus as a possible complication that results in prolonged consciousness disturbance].

We describe a patient with systemic lupus erythematosus (SLE) with lupus psychosis, who showed prolonged consciousness disturbance due to hyperosmolality. A 51-year-old Japanese woman with SLE was admitted to our hospital for the evaluation and treatment of consciousness disturbance on March 5, 1994. She had not been given prednisolone since 1984, and had been depressive since January 1994. She was diagnosed as active SLE with lupus psychosis due to the presence of thrombocytopenia, proteinuria, positive anti-nuclear antibody (x10,240) as well as the elevation of cerebrospinal fluid (CSF) IL-6 level. A treatment with methylprednisolone (mPL) 100 mg/day was started along with 2 courses of steroid pulse therapy (mPL 1 g/day for 3 consecutive days). She recovered partially from the central nervous system manifestations with a decrease in CSF IL-6 level 2 weeks after this treatment. However, her consciousness level was exacerbated again thereafter. Blood examination disclosed the elevation of plasma osmolality (319 mOsm/kg) with poor responses of plasma antidiuretic hormone (4.6 pg/ml). She died from systemic aspergillosis on April 26, 1994. Pathological examination on autopsy showed no abnormality in hypothalamus and pituitary gland. It is suggested that this patient was complicated with lupus psychosis as well as hyporesponsiveness of osmoreceptor. Rheumatologists should be aware of this complication in patients with CNS lupus as a possible cause for intractable CNS manifestations.

Biomarkers↗
PubMed1999

[Central nervous system involvement in rheumatic diseases].

Among various rheumatic diseases, systemic lupus erythematosus and Behcet's disease are frequently complicated with serious neurological involvement, called CNS lupus and neuro-Behcet's syndrome (NB), respectively. CNS lupus includes lupus psychosis, such as organic brain syndrome and non-organic psychosis, as well as non-psychotic CNS lupus, such as epilepsy and focal lesions. Anti-ribosomal P antibody is closely associated with lupus psychosis, whereas anti-phospholipid antibodies appear to be involved in some manifestations of non-psychotic CNS lupus. NB includes acute type and chronic progressive type. Acute NB is characterized by acute meningoencephalitis with focal lesions, which respond to steroid therapy. By contrast, chronic progressive NB is characterized by intractable slowly progressive dementia and/or psychosis with persistent elevation of cerebrospinal fluid IL-6 activity, which is resistant to conventional steroid therapy. However, recent studies suggest the efficacy of low dose methotrexate in chronic progressive NB.

Antibodies, Antiphospholipid↗
PubMed1998

Low-dose weekly methotrexate for progressive neuropsychiatric manifestations in Behcet's disease.

The most serious central nervous system (CNS) manifestation in Behcet's disease is a slowly progressive dementia (progressive NB), which may ultimately lead to the deterioration of the personality of patients. An open trial was designed to investigate the efficacy of low dose weekly methotrexate (MTX) therapy for progressive NB. Six patients with Behcet's disease, whose neuropsychiatric manifestations were judged to be progressive (4 females and 2 males, aged 55.0+/-8.2 years), were given oral MTX (7.5-12.5 mg/week) until the end of the 12-month trial. The clinical responses of the patients to MTX were judged by neuropsychiatric findings, intelligence test, brain MRI scans and cerebrospinal fluid (CSF) IL-6 levels. After the 12-month trial, CSF IL-6 levels were found to be significantly decreased. Accordingly, the neuropsychological manifestations as well as the findings on MRI scans and intelligence quotients were not significantly worsened after the trial. Three patients presented with mild liver dysfunction, which returned to normal by decreasing the dose of MTX. However, 6 months after discontinuation of MTX, all the six patients showed significant exacerbation of the manifestations as evidenced by a decrease in verbal intelligence quotients along with the marked elevation of CSF IL-6. These results suggest that low dose weekly MTX therapy might have a beneficial effect in the treatment of progressive NB, although a trial for a longer period would be necessary.

Aged↗
PubMed1998

Cloning of the human tissue inhibitor of metalloproteinase-4 gene (TIMP4) and localization of the TIMP4 and Timp4 genes to human chromosome 3p25 and mouse chromosome 6, respectively.

We have isolated genomic DNA containing the human tissue inhibitor of metalloproteinases-4 gene (TIMP4) and determined the structure of the exons comprising the gene. Like other members of the TIMP family, the TIMP-4 protein is encoded by five exons. These span 6 kb of genomic DNA, so that TIMP4 is similar in size to Timp1 but considerably smaller than TIMP2 and TIMP3. The exon-intron boundaries of TIMP4 are at locations very similar to those of the other TIMP genes, demonstrating the high degree of conservation of gene structure in this family. The human and mouse TIMP-4 genes map to comparable locations in the respective genomes, localizing to human chromosome 3p25 and mouse chromosome 6.

Animals↗
PubMed1998

Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus.

OBJECTIVE: To compare the role of antibodies against the ribosomal P protein (anti-P) with that of antibodies against neuronal cells (anti-N) in the pathogenesis of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS: Sera from 87 SLE patients (27 with non-CNS SLE, 34 with lupus psychosis, and 26 with nonpsychotic CNS lupus) and from 20 control patients with neurologic manifestations without SLE and cerebrospinal fluid (CSF) from 41 patients with CNS lupus and from the 20 control patients were assayed for IgG anti-P and anti-N by an enzyme-linked immunosorbent assay (ELISA) using ribosomal P synthetic peptides and by a cell ELISA using paraformaldehyde-fixed SK-N-MC neuroblastoma cell lines, respectively. RESULTS: Serum anti-P levels were significantly elevated in patients with lupus psychosis compared with those with non-CNS SLE or those with nonpsychotic CNS lupus, whereas there were no significant differences in serum anti-N levels among these 3 groups. In contrast, CSF anti-N levels were significantly elevated in patients with lupus psychosis compared with those with nonpsychotic CNS lupus and compared with non-SLE controls, whereas CSF anti-P were not detected in most of the patients. CONCLUSION: The results indicate that anti-P in the systemic circulation and anti-N in the CSF are involved in the development of lupus psychosis.

Antibody Specificity↗
PubMed1998

Abnormal T cell responses to bacterial superantigens in Behçet's disease (BD).

This study examines the nature of T cell hypersensitivity in BD. Highly purified T cells from 32 BD patients, from 29 rheumatoid arthritis (RA) patients and from 14 healthy individuals were cultured with various concentrations of Staphylococcal enterotoxins (SE) B and C1 in the presence of monocytes for 5 days, after which the production of interferon-gamma (IFN-gamma) was assessed. High concentrations of SE (1 ng/ml) stimulated BD T cells as well as control T cells to produce comparably high amounts of IFN-gamma, whereas low concentrations of SE (1 pg/ml) stimulated BD T cells much more effectively than normal or RA T cells. The hypersensitivity of BD T cells to low concentrations of SEC1 was restored with RA monocytes instead of BD monocytes, whereas BD monocytes could not elicit the SEC1-induced IFN-gamma production of RA T cells. Moreover, there were no significant differences between BD T cells and RA T cells in monocyte-independent IFN-gamma production stimulated with low or high concentrations of immobilized anti-CD3, or in the monocyte-mediated enhancement of IFN-gamma production stimulated with a low concentration of immobilized anti-CD3. These results confirm that T cell hypersensitivity is not confined to certain specific antigens in BD. More importantly, the data strongly suggest that abnormalities in signal transduction triggered by perturbation of T cell receptors, but not in that induced by cross-linking of CD3 molecules nor in that delivered through costimulation molecules, play an important role in the pathogenesis of BD.

Adult↗
PubMed1998

[A case of severe neuropsychiatric lupus erythematosus treated by plasmapheresis: diagnostic values of serum antiribosomal P protein antibodies and interleukin-6 in cerebrospinal fluid].

We report here a case of neuropsychiatric lupus erythematosus with organic brain syndrome and transverse myelitis which was successfully managed by plasmapheresis. A 27-year-old female with facial rash, arthralgia and fever was diagnosed as having SLE and treated with oral prednisolone (PSL) in June 1996. After 6 weeks she demonstrated muscle pain and a spiking temperature. The dose of PSL was increased but clinical symptoms did not improve. In August, pulse methyl-PSL was performed and she subsequently-developed delirium, impairment of orientation, memory and perception, which were followed by paraplegia of the lower extremities and loss of sphincter control. Intravenous bolus cyclophosphamide was not effective, but liver dysfunction, bone marrow suppression and respiratory failure due to an infection of pneumocystis carinii were observed. We then performed plasmapheresis or immunoabsorption several times. After this treatment steady improvement was observed. High values of antiribosomal P protein antibodies in the serum and interleukin-6 in the cerebrospinal fluid decreased. Small foci of increased signal intensity detected on cranial magnetic resonance imaging and hypoperfused areas on single-photon emission CT diminished. The patient was maintained on low-dose PSL and no recurrence has been observed 15 months from the onset.

Adult↗
PubMed1997

The role of CD40-CD40 ligand interactions in suppression of human B cell responsiveness by CD4+ T cells.

Although human T cells have been shown to regulate humoral immune responses by directly inhibiting B cells, the precise sequelae for the mechanism of suppression have not yet been delineated. The present study was therefore examined to explore the nature of T cell-B cell collaboration to suppress B cell responses. Special attention was directed to the roles of Fas (CD95)-Fas ligand (FasL) interactions and CD40-CD40 ligand (CD40L) interactions. The suppressive activity was assessed by the effects of mitomycin C untreated CD4+ T cells (control CD4+ T cells) activated by immobilized anti-CD3 for 72 h on the production of IgM and IgG of B cells stimulated for 72 h with immobilized anti-CD3-activated mitomycin C treated CD4+ T cells. In this model system, B cells stimulated with anti-CD3-activated CD4+ T cells have been shown to express functional Fas receptor. Thus, anti-Fas mAb CH11 inhibited the production of IgM and IgG induced by anti-CD3-activated mitomycin C treated CD4+ T cells in a manner that was completely reversed by a neutralizing anti-Fas mAb ZB4. However, neither ZB4 nor anti-FasL mAb reversed the suppression of B cell responses by anti-CD3-activated control CD4+ T cells. Anti-CD40L mAb inhibited the production of IgM and IgG stimulated with anti-CD3-activated mitomycin C treated CD4+ T cells when it was added at the initiation of cultures. By contrast, anti-CD40L mAb markedly reversed the suppression of B cell production of IgM and IgG by anti-CD3-activated control CD4+ T cells when it was added after 72 h from the initiation of cultures. Consistently, the extent and intensity of CD40L on anti-CD3-stimulated CD4+ T cells declined upon treatment with mitomycin C in parallel with the loss of suppressive activities on B cell responses. These results indicate that signals achieved by direct interactions through CD40-CD40L exert bidirectional effects on the outcome of humoral immune responses depending on the state of activation of B cells and on the extent of CD40 ligation. Moreover, the data suggest that CD40-CD40L interactions rather than Fas-FasL interactions may play more critical roles in direct cellular collaboration between B cells and anti-CD3 stimulated CD4+ T cells to prevent the extension of responses of inappropriately activated B cells.

Adult↗
PubMed1997

Suppression of human B cell responsiveness by CD4+ T cells does not involve CD95-CD95 ligand interactions.

Although human CD4+ T cells have been shown to regulate humoral immune responses by directly inhibiting B cells, the precise sequelae for the mechanism of suppression have not yet been delineated. The present study was therefore designed to explore the nature of T cell-B cell collaboration to suppress B cell responses. Special attention was directed to the roles of Fas (CD95)-Fas ligand (FasL) interactions. The suppressive activity was assessed by the effects of mitomycin C-untreated CD4+ T cells activated by immobilized anti-CD3 for 72 h (CD4+ suppressors) on the production of IgM and IgG of B cells stimulated for 72 h with immobilized anti-CD3-activated mitomycin C-treated CD4+ T cells. In this model system, B cells stimulated with anti-CD3-activated mitomycin C-treated CD4+ T cells expressed functional Fas receptors. Accordingly, addition of anti-Fas mAb CH-11 inhibited the cluster formation and differentiation of activated B cells as a result of apoptotic cell death in a manner that was completely reversed by a neutralizing anti-Fas mAb ZB4. However, neither ZB4 nor anti-FasL mAb reversed the suppression of B cell responses by anti-CD3-induced CD4+ suppressors. Of interest, ZB4 significantly enhanced the production of IgM and IgG induced by anti-CD3-activated mitomycin C-treated CD4+ T cells in the absence of CD4+ suppressors. Consistently, mitomycin C-treated CD4+ T cells as well as mitomycin C-untreated CD4+ T cells expressed comparable levels of FasL upon activation with immobilized anti-CD3, although their intensities were very modest. These results indicate that B cells activated with anti-CD3-stimulated CD4+ T cells express functional Fas receptors and are sensitive to Fas-mediated apoptosis. However, the data also suggest that interactions other than Fas-FasL may play a critical role in direct cellular collaboration between activated B cells and anti-CD3-induced CD4+ suppressors to inhibit B cell responses.

Adult↗
PubMed1997

Relation of iodine-123 metaiodobenzylguanidine myocardial scintigraphy to endomyocardial biopsy findings in patients with dilated cardiomyopathy.

BACKGROUND: Iodine-123 metaiodobenzylguanidine (123I-MIBG) concentrates in adrenergic neurons and has been developed for evaluation of the sympathetic nervous system. Recent studies have demonstrated that the normal heart is clearly visualized by 123I-MIBG cardiac scintigraphy, whereas abnormal 123I-MIBG myocardial uptake and washout have been demonstrated in patients after myocardial infarction and in patients with congestive cardiomyopathy, long QT syndrome, and ventricular tachycardia. HYPOTHESIS: Based on evidence from recent studies, it can be hypothesized that 123I-MIBG uptake is related to histopathologic changes in the myocardium. METHODS: The relation of 123I-MIBG uptake to the histologic findings for the heart was studied in 24 patients with dilated cardiomyopathy (DCM). The study group did not include patients with complicating disorders that primarily affect the adrenergic nervous system. The 123I-MIBG uptake was visually assigned one of four grades using the two criteria of the mean score for six regional uptake grades (mean score) and the global score obtained by visual evaluation of the entire image (global score). The 123I-MIBG uptake score was also determined for the region at which the biopsy specimen was obtained (biopsy region score). The histologic findings were evaluated by assigning one of four grades for each of the following five factors: myocyte hypertrophy, myocardial fibrotic change, myocyte degeneration and necrosis, mononuclear cell infiltration, and myocyte disarray. The sum for all grades was defined as the total score, and the global score was also assigned to the overall histologic findings. RESULTS: All of the global, mean, and biopsy region scores for 123I-MIBG uptake correlated significantly with the global and total scores for the histologic findings. Among the histologic factors, myocyte degeneration showed score correlated with all global, mean, and biopsy region scores for the uptake. Myocyte hypertrophy was associated weakly with the 123I-MIBG uptake scores. CONCLUSION: These results indicate that 123I-MIBG uptake imaging is associated with histopathologic abnormalities in patients with DCM.

3-Iodobenzylguanidine↗
PubMed1997

Cerebrospinal fluid interleukin-6 in progressive Neuro-Behçet's syndrome.

Central nervous system (CNS) involvement in Behçet's disease, usually called neuro-Behçet's syndrome (NB), is one of the most serious complications of the disease. The present study examined cerebrospinal fluid (CSF) interleukin-6 (IL-6) activity in patients with NB to explore its relevance to the progressive CNS disease. Paired CSF and serum specimens were obtained from 11 patients who were diagnosed as having progressive NB based on careful clinical observation and from 11 patients with active Behçet's disease but lacking progressive CNS disease. IL-6 levels in the CSF and sera were determined using IL-6-dependent murine hybridoma MH60.BSF2 cells. All 11 patients with progressive NB showed marked elevation of CSF IL-6 activity [0.18-3.90 U/ml, 1.19 +/- 1.18 (mean +/- SD), normal range, <0.010 U/ml]. In contrast, only 5 of the 11 control patients showed very modest CSF IL-6 activity below 0.10 U/ml, and CSF IL-6 was not detected in the other 6 patients. There was no difference in the serum IL-6 activities of patients with progressive NB and control patients. There was no significant correlation of CSF IL-6 activity with serum IL-6 activity, CSF cell counts, CSF total protein levels, or the CSF/serum albumin quotient. These results indicate that persistent chronic CNS inflammation, as evidenced by the enhanced production of IL-6 within the CNS, plays an important role in the pathogenesis of progressive neuropsychiatric manifestations in Behcet's disease.

Adult↗
PubMed1997

Differential influences of gold sodium thiomalate and bucillamine on the generation of CD14+ monocyte-lineage cells from bone marrow of rheumatoid arthritis patients.

An adequate supply of peripheral blood monocytes, granulocytes, and platelets is necessary for an optimal inflammatory process. We have previously demonstrated that the generation of CD14(+) monocyte-lineage cells from the bone marrow is accelerated in patients with rheumatoid arthritis (RA). The current studies examined the influences of gold sodium thiomalate (GST) and bucillamine (BUC), two potent disease-modifying antirheumatic drugs (DMARDs), on the capacity of bone marrow progenitor cells to generate CD14(+) cells in patients with RA, in order to delineate their mechanisms of action. CD14(-) cells purified from bone marrow specimens of 13 patients with active RA who were not taking DMARDs were cultured in the presence or absence of pharmacologically attainable concentrations of GST (25 microM) or intramolecular disulfide form of bucillamine (BUC-ID, 3 microM), a major metabolite of BUC. After incubation for 14 days, the cells were analyzed by flow cytometry for expression of CD14, HLA-DR, and CD54. The generation of CD14(+) cells from RA bone marrow CD14(-) progenitor cells was significantly suppressed by GST, but not by BUC-ID. The expression of HLA-DR on the bone marrow-derived CD14(+) cells was also significantly inhibited by GST, but not by BUC-ID. Of note, neither GST nor BUC-ID influenced the expression of CD54 on the bone marrow-derived CD14(+) cells, indicating that the expression of HLA-DR and CD54 on the bone marrow-derived CD14(+) cells is regulated by different mechanisms. The results are consistent with the hypothesis that one of the effects of DMARDs may involve the interference with monocyte differentiation in the bone marrow. Moreover, the data emphasize that in contrast with BUC, GST is a potent inhibitor of monopoiesis in RA patients.

Adult↗
PubMed1997

Time dependent alterations of serum matrix metalloproteinase-1 and metalloproteinase-1 tissue inhibitor after successful reperfusion of acute myocardial infarction.

OBJECTIVE: To test the hypothesis that changes in serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase-1 (TIMP-1) after acute myocardial infarction reflect extracellular matrix remodelling and the infarct healing process. PATIENTS: 13 consecutive patients with their first acute myocardial infarction who underwent successful reperfusion. METHODS: Blood was sampled on the day of admission, and on days 2, 3, 4, 5, 7, 14, and 28. Serum MMP-1 and TIMP-1 were measured by one step sandwich enzyme immunoassay. Left ventricular volume indices were determined by left ventriculography performed four weeks after the infarct. RESULTS: Serum concentrations of both MMP-1 and TIMP-1 changed over time. The average serum MMP-1 was more than 1 SD below the mean control values during the initial four days, increased thereafter, reaching a peak concentration around day 14, and then returned to the middle control range. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum MMP-1 on day 5, when it began to rise, and for the magnitude of rise in MMP-1 on day 5 compared to admission. Serum TIMP-1 at admission was more than 1 SD below the mean control value, and increased gradually thereafter, reaching a peak on around day 14. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum TIMP-1 on days 5 and 7, and for the magnitude of rise in TIMP-1 on days 5 and 7 compared to admission. CONCLUSIONS: Both MMP-1 and TIMP-1 showed significant time dependent alteration after acute myocardial infarction. Thus MMP-1 and TIMP-1 may provide useful information in evaluating the healing process as it affects left ventricular remodelling after acute myocardial infarction.

Adult↗
PubMed1997

Laminin alpha 1, alpha 2, alpha 4 and beta 1 chain mRNA expression in mouse embryonic, neonatal, and adult hearts.

We examined the relative expression of laminin alpha 1, alpha 2, alpha 4 and beta 1 chain genes in the heart of embryonic, neonatal and adult BALb/c mice. The reverse transcriptase-polymerase chain reaction was employed to determine the mRNA expression of these chains because of the relatively small amount of RNA extracted from rat embryonic hearts. Glyceraldehyde 3-phosphate dehydrogenase and beta-actin were used as internal controls. Among the hearts examined, a relatively high expression of laminin alpha 1 chain was observed in the embryonic hearts, while its expression was very weak in the neonatal and negligible in the adult hearts. Conversely, expression of laminin alpha 2 chain was virtually not observed in the embryonic hearts, but this chain was expressed weakly in the neonatal and substantially in the adult hearts. Similar to laminin alpha 1, laminin alpha 4 was expressed in the embryonic hearts, while its expression was relatively weak in the neonatal and adult hearts. Laminin beta 1 was expressed in the hearts of mice at all stages examined. These results demonstrate that the laminin chain gene expression changes in the different developmental stages of the hearts of BALb/c mice.

Animals↗