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S Yoshizawa

Publications and source records attributed to S Yoshizawa.

At least 19 recordsLinked to original sources

Prevention of steroid-induced osteonecrosis of femoral head in systemic lupus erythematosus by anti-coagulant.

Although osteonecrosis of femoral head (ONF) is one of the serious complications in systemic lupus erythematosus (SLE) associated with corticosteroid therapy, there has been few trials of prevention of ONF described. We aimed to prevent ONF in steroid-treated SLE patients using anticoagulant, warfarin, conducting a multicenter prospective study. Sixty newly diagnosed SLE patients requiring 40 mg/day or more prednisolone were alternately assigned to either of two groups; a warfarin group and a control one. Warfarin (1 to approximately 5 mg/day) was started together with the beginning of steroid therapy and continued at least for three months. Patients were observed for the development of silent ONF by magnetic resonance imaging (MRI) and symptomatic ONF by plain radiography for over five years. The warfarin group consisted of 31 patients (62 hips) and the control one 29 patients (58 hips). Silent ONF developed in 13 hips (21%) and 19 hips (33%) in the warfarin group and the control group, respectively (P = 0.13). On the other hand, warfarin tended to prevent symptomatic ONF; only three hips of 62 (4.8 %) in the warfarin group and eight hips of 58 (14%) in the control group (P = 0.08) developed silent ONF. It was also found that silent ONF developed, if it did, very early; within three months in 16 of 18 patients (89%). Among risk factors for silent ONF, steroid pulse therapy was most outstanding and it seemed to overcome the effect of warfarin. Taken together, for the time being, anti-coagulant therapy, if not significantly sufficient, may be of use for the prevention of steroid-induced ONF in SLE. We consider that this study added to important evidence for the pathogenesis and prevention of ONF.

Adolescent↗

Very early development of steroid-associated osteonecrosis of femoral head in systemic lupus erythematosus: prospective study by MRI.

The objective of this study was to define prospectively the early development of corticosteroid-induced osteonecrosis of femoral head (ONF) in patients with systemic lupus erythematosus (SLE) and to identify the association of initial steroid treatment with the development of early (silent) ONE Forty-five patients who were newly diagnosed as having SLE and required 40 mg/day or more prednisolone were enrolled. To detect silent ONF, examinations using magnetic resonance imaging (MRI) were done three months after starting steroid therapy, followed by every year's MRI and plain radiography for over five years. Clinical and laboratory data were compared between silent ONF and non-ONF groups. Of 45 patients, 15 (33%) developed silent ONF and five (11%) symptomatic ONE It was of interest that MRI detected silent ONF very early (by three months) in 14 patients (93%). It should be noted that pulse therapy with 1000 mg/day methylprednisolone was found to be done very frequently (13 of 15, 87%) in the silent ONF group compared to non-ONF group (11 of 30, 37%) (P < 0.01) although other clinical features were not significantly different between both groups. High dose corticosteroids caused elevation of serum levels of total cholesterol, albumin, and leukocyte count in most of patients. The degree of elevation of those parameters at one or three months was more prominent in the silent ONF group. In particular, the change ratio of total cholesterol at one month was outstanding in the silent ONF group compared to non-ONF group (0.551 versus 0.374, P < 0.05). In conclusion, pathological ONF develops very early in one-third of SLE patients who received high dose corticosteroids and steroid pulse therapy could be a significant risk factor. An abrupt elevation of serum total cholesterol and/or sensitivity to steroids seem to be associated with the pathogenesis of ONF.

Adolescent↗

Spatiotemporal brain activity in mental rotation.

There are many higher-order cognitive processes whose neural mechanisms are hard to study by using nonhuman primates. The mental rotation task is one of the best studied of these. We investigated the spatiotemporal brain activity underlying mental rotation of different kinds of stimuli by measuring the magnetoencephalogram of subjects performing two kinds of mental rotation tasks. Visual stimuli in one experiment consisted of hand shapes presented at various orientations, and those in the other consisted of a set of alphabetic characters and their mirror images presented at various orientations. All stimuli were presented in the left visual field. Activity associated with visual stimulus processing was estimated in the lateral occipital lobe, basal occipitotemporal area, and inferior temporal gyrus. Activities related to higher visual processing were differed between the two kinds of stimuli we used. For the hand shape experiment, we found right inferior parietal lobule activity at 200-300 ms after the stimulus presentation. For the alphabetic characters, activity was found in the left superior temporal region at about 300 ms. Furthermore, activity related to mental stimulation in the inferior parietal lobule and premotor area were seen in the both experiments. In the experiments with hands, the premotor activity showed left-hemispheric dominance. However, in the experiments with alphabetic characters, the laterality of the premotor activity did not show left-hemispheric dominance. We inferred this difference was influenced by the subjects' familiarity with the mental rotation of visual stimuli.

Adult↗

Aberrant HS1 molecule in a patient with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of autoreactive B lymphocytes, which are supposed to carry aberrant signal transduction after the stimulation of B-cell receptor (BCR). To investigate abnormalities in BCR-mediated signaling pathway in lupus B lymphocytes, we analyzed HS1, a molecule downstream of BCR, in 80 Japanese SLE patients. We identified 37 amino acid deletion of HS1 in a 25-year-old female patient, and the aberrant HS1 lacked a part of a functional motif. Analysis of genomic DNA revealed that the aberrant HS1 was caused by exon skipping. Family study showed that the patient as well as her father and sister are heterozygous for the abnormality. WEHI-231 cell, a mouse B cell line, transfected with the aberrant HS1 displayed a significantly increased cell death upon cross-linking of BCR. Additionally, peripheral B lymphocytes from the patient exerted increased apoptosis after BCR stimulation compared to those from control SLE patients. These data suggest that the aberrant HS1 molecule may transmit an accelerated signal after BCR stimulation and may play a role in the activation of autoreactive B lymphocytes.

Adaptor Proteins, Signal Transducing↗

Solution structure of conserved AGNN tetraloops: insights into Rnt1p RNA processing.

Rnt1p, the yeast orthologue of RNase III, cleaves rRNAs, snRNAs and snoRNAs at a stem capped with conserved AGNN tetraloop. Here we show that 9 bp long stems ending with AGAA or AGUC tetraloops bind to Rnt1p and direct specific but sequence-independent RNA cleavage when provided with stems longer than 13 bp. The solution structures of these two tetraloops reveal a common fold for the terminal loop stabilized by non-canonical A-A or A-C pairs and extensive base stacking. The conserved nucleotides are stacked at the 5' side of the loop, exposing their Watson-Crick and Hoogsteen faces for recognition by Rnt1p. These results indicate that yeast RNase III recognizes the fold of a conserved single-stranded tetraloop to direct specific dsRNA cleavage.

Base Sequence↗

Detection of pinpoint tenderness on the appendix under ultrasonography is useful to confirm acute appendicitis.

HYPOTHESIS: Ultrasonography can be efficiently performed using new criteria for the diagnosis of acute appendicitis. DESIGN: Prospective trial. PATIENTS: Eighty-nine patients admitted to the hospital with suspected appendicitis between March 1998 and November 2000. INTERVENTION: At hospital admission, a staff surgeon evaluated each patient and determined whether the patient had appendicitis requiring immediate surgery or another disease. Patients then underwent ultrasonography. A sonographic transducer was placed on the area of maximal tenderness. When the pathological manifestation was depicted, the examiner slipped a fingertip between the transducer and the patient's skin and then pressed the area of depicted pathological manifestation to find pinpoint tenderness. When maximal pinpoint tenderness was noted on the appendix or on pathological manifestations contiguous to the appendix, we diagnosed the condition as appendicitis. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and overall accuracy. RESULTS: The diagnosis of appendicitis by this criteria had a sensitivity of 86.7%, a specificity of 89.7%, a positive predictive value of 94.5%, a negative predictive value of 76.5%, and overall accuracy of 87.6%. All 50 patients with pinpoint tenderness noted on the appendix had appendicitis. The surgeon's initial clinical impression had a sensitivity of 83.3%, a specificity of 44.8%, a positive predictive value of 75.8%, a negative predictive value of 56.5%, and overall accuracy of 70.8%. CONCLUSIONS: The efficacy of ultrasonography using the simple criteria was superior to that of the surgeon's initial clinical impression (P<.001). Our ultrasonographic criteria for the diagnosis of appendicitis are simple to use and efficient.

Acute Disease↗

Factors associated with anxiety, depression and suicide ideation in female outpatients with SLE in Japan.

The subjects consisted of 84 female SLE outpatients who were all over 20 years of age. These patients were able to maintain relatively stable physical conditions and lead normal daily lives, and they were regularly treated at the outpatient clinic. All subjects were Japanese. Psychological features (trait anxiety, state anxiety, depression and suicide ideation) were evaluated using psychological tests, and the relationships between the respective psychological features and background factors were statistically evaluated using stepwise multiple logistic regression analyses. In this study, we found that 'the self-evaluation of not having understood SLE at the time of starting SLE treatment' was the background factor significantly affecting depression or trait anxiety. 'No spouse' had a statistically significant effect on depression, and 'self-awareness as problems of side-effects due to steroids' had a statistically significant effect on state anxiety. We also found 'human relations among family members' and 'high daily steroid dosage' to be significantly correlated with suicide ideation. However, there were no correlations between the psychological features and 'disease activity at the time of investigation' or 'history of neuropsychiatric diseases'. In female SLE outpatients, performing psychological approaches focusing on 'understanding SLE at the beginning of treatment', 'the human relationships among family members', or 'issues related to steroid therapy' may be useful for the early treatment or prevention of various major mental problems.

Adult↗

Simultaneous double or triple coil technique for closure of moderate sized (> or = 3.0 mm) patent ductus arteriosus.

One important complication of coil occlusion of patent ductus arteriosus using the conventional Gianturco coil is migration of coils into peripheral vessels. Especially in patients having relatively larger size ductus, the risk for such complication could be increased. In this regard, a detachable coil may have some technical benefits in performing coil occlusion and reducing the incidence of complications such as migration of coil. Based on our clinical experiences, we describe the clinical efficacy of a simultaneous double or triple coil occlusion technique using the Cook detachable coil system to close the ductus arteriosus, especially in patients whose ductus diameter more than 3.0 mm.

Adolescent↗

Analysis of fas ligand gene mutation in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the possible association of a Fas ligand (FasL) gene mutation(s) or polymorphism(s) with systemic lupus erythematosus (SLE). METHODS: For amplification of the introns of the FasL gene, long polymerase chain reaction (PCR) using exon-based primers was utilized, followed by partial sequencing to construct exon-specific oligonucleotide primers for the analyses of FasL genomic DNA in SLE patients. Structural defects were studied by use of a composite analysis of reverse transcriptase-PCR/single-strand conformational polymorphism (SSCP) analysis of messenger RNA (mRNA) transcripts of the FasL gene in 35 SLE patients and PCR/SSCP analysis of FasL genomic DNA in 143 SLE patients. RESULTS: The sizes of the introns were approximately 0.6 kb for intron 1, 4.3 kb for intron 2, and 1.3 kb for intron 3. By SSCP analysis, we did not identify any mutations or polymorphisms in the FasL mRNA transcripts or in any of the 4 exons or areas of the introns adjacent to the exons. CONCLUSION: Using the same methods used in the present studies (PCR/SSCP), one group of investigators identified a structural defect of the FasL molecule in 1 of 75 SLE patients evaluated. Among the 143 SLE patients in the present study, however, we did not identify any mutations or polymorphisms of the FasL gene. Our results suggest that a FasL defect is not the major contributing factor in the pathogenesis of SLE.

DNA Mutational Analysis↗

Anticentromere antibody as a risk factor for cancer in patients with systemic sclerosis.

This study has estimated the cancer risk among patients with systemic sclerosis (SSc) using a population-based analysis. Using the inpatient and outpatient registries for patients at Kyushu University Hospital between 1982 and 1996, standardised incidence rates (SIRs) (ratio of observed-to-expected cancers) were calculated in 43 patients with SSc, 24 patients with polymyositis (PM) and 17 patients with dermatomyositis (DM). Risk factors predisposing to cancers were also investigated in the SSc patients. Compared with the Japanese general population, the SIR for developing cancer in SSc patients was 5.1 (95% confidence interval (CI), 1.7-10.8), while the SIRs for cancer in the PM and DM groups were 4.7 (95% CI, 1.5-10.3) and 61.2 (95% CI, 46.8-77.6), respectively. A statistically significant risk factor for cancers in the SSc patients was positivity for anticentromere antibody (ACA) (p<0.05), while the erythrocyte sedimentation rate, serum lactate dehydrogenase concentration, serum gamma-globulin concentration, titre of antinuclear antibody and positivity for antitopoisomerase I antibody were not associated with cancer in SSc. Our population-based study confirms the increased risk of cancer among patients with SSc in Japan and provides new evidence that positivity for ACA should be considered as a risk factor for cancer in future monitoring of patients.

Autoantibodies↗

A 5-day course of oral desensitization to trimethoprim/sulfamethoxazole (T/S) in patients with human immunodeficiency virus type-1 infection who were previously intolerant to T/S.

BACKGROUND: Trimethoprim/sulfamethoxazole (T/S) is an essential drug in patients with human immunodeficiency virus type-1 (HIV-1) infection to prevent opportunistic infections. About 40% to 60% of them develop skin rash which leads to discontinue the medication. A precise mechanism of the reaction is not known. OBJECTIVE: To make the patients more tolerable to the medication and to make clear whether or not the reaction is caused by serum sulfamethoxazole-specific IgE. METHODS: We established a 5-day protocol, in which T/S was administered orally as a granular form in increasing doses beginning with 0.005 g (it contains trimethoprim 0.4 mg and sulfamethoxazole 2 mg) and doubled every 12 hours until the therapeutic dose was achieved. We tried to desensitize T/S in 17 patients with HIV-1 infection who were previously intolerant to T/S and measured the specific IgE in sera. RESULTS: Desensitization was successfully completed in 15 (88.2%) of the patients. In two patients who failed the desensitization, one was due to fever and the other was gastric irritation. During followup in a mean period of 16.6 months (range, 8 to 23 months) as of May, 1999, none has had Pneumocystis carinii pneumonia (PCP) while receiving T/S after desensitization. Sulfamethoxazole-specific IgE did not increase, indicating that it was not the major cause of skin rash due to T/S in our cases. CONCLUSION: These preliminary results show that most patients who were thought to be intolerant to T/S and had no sulfamethoxazole-specific IgE can be safely desensitized and received the drug subsequently as an effective prophylaxis for PCP.

Administration, Oral↗

Anti-HIV effect of saquinavir combined with ritonavir is limited by previous long-term therapy with protease inhibitors.

Combination therapy of saquinavir (SQV) and ritonavir (RTV) seems to have a strong antiretroviral effect pharmacokinetically. The purpose of this study was to examine the effectiveness of combined therapy using SQV and RTV in patients previously treated with protease inhibitors (PIs) and to identify the factors compromising the response to such combination therapy. Nineteen HIV-infected Japanese patients participated in this trial between June 1997 and July 1998, and were monitored until November 1998. Patients were treated with SQV (400 mg twice daily) and RTV (300 or 400 mg twice daily). Among the 17 patients who continued such therapy for longer than 3 months, 6 were responders. Among nonresponders, the duration of PI therapy was longer and a higher frequency of preexisting PI resistance viral mutations was detected than in responders. No significant differences were found in previous use of reverse transcriptase inhibitor therapy, CD4+ and CD8+ T cell counts, viral load at baseline, and plasma concentrations of SQV and RTV between responders and nonresponders. Our results suggest that the response to SQV combined with RTV therapy is complicated by previous long-term treatment with PIs, probably owing to multiple PI resistance mutations. Even in patients with a PI-sensitive HIV genotype, however, resistance mutations can develop during therapy and abrogate the effect of high plasma SQV concentrations.

Adolescent↗

Recognition of the codon-anticodon helix by ribosomal RNA.

Translational fidelity is established by ribosomal recognition of the codon-anticodon interaction within the aminoacyl-transfer RNA (tRNA) site (A site) of the ribosome. Experiments are presented that reveal possible contacts between 16S ribosomal RNA and the codon-anticodon complex. N1 methylation of adenine at position 1492 (A1492) and A1493 interfered with A-site tRNA binding. Mutation of A1492 and A1493 to guanine or cytosine also impaired A-site tRNA binding. The deleterious effects of A1492G or A1493G (or both) mutations were compensated by 2'fluorine substitutions in the mRNA codon. The results suggest that the ribosome recognizes the codon-anticodon complex by adenine contacts to the messenger RNA backbone and provide a mechanism for molecular discrimination of correct versus incorrect codon-anticodon pairs.

Adenine↗

A new method for magnetoencephalography: a three-dimensional magnetometer-spatial filter system.

A novel three-dimensional magnetometer-spatial filter system was developed to study human brain activity with high spatiotemporal resolution. The system combines the high temporal resolution of magnetoencephalography with the high spatial resolution achieved by using three-dimensional magnetometers and spatial filters to measure the direction and intensity of magnetic fields generated during brain activity. Simulation and phantom studies indicate that the system is capable of mapping current sources of magnetic fields with a spatial resolution comparable to that of any other brain functional imaging technique while maintaining millisecond temporal resolution. Application of this system to the human brain resolved magnetoencephalographic responses evoked by motion stimuli on a millisecond scale into responses occurring in visual cortical areas V1, V2/3 and V5. It also revealed signals related to contextual modulation in V1 and V2/3. This system provides a new way of studying the dynamics of human brain function.

Brain↗

Establishment and characterization of a Fas-resistant T cell line.

Fas is a cell surface receptor that controls a signal transduction pathway leading to apoptosis. We established an antihuman Fas monoclonal antibody (mAb)-resistant variant, kit-225-FR, from the human T cell line, kit-225. Flow cytometric analysis revealed that the expression of Fas molecules on kit-225-FR was preserved. The defect in Fas molecule was not detected either by reverse transcription polymerase chain reaction (PCR) analysis of the Fas transcript or by PCR-single strand conformation polymorphism analysis of the Fas gene in kit-225-FR. Although kit-225-FR was resistant to a high concentration of anti-Fas mAb, apoptosis could be induced, as with the wild type, by exogenous C2-ceramide exposure. MORT1/FADD was expressed at wild-type level in kit-225-FR, as determined by Western blot analysis. It therefore appears that the apoptotic signal transduction in kit-225-FR is defective between FADD and the sphingomyelin-ceramide pathway. By comparing the differences from the wild-type kit-225, kit-225-FR would serve as a useful cell line for analyzing Fas-specific signal transduction pathways in detail.

Apoptosis↗

[A case of systemic sclerosis with crescentic glomerulonephritis associated with perinuclear-antineutrophil cytoplasmic antibody (p-ANCA)].

A 50-year-old female with systemic sclerosis (SSc) developed rapidly progressive renal insufficiency. Laboratory findings showed rapid elevation of serum creatinine level (3.8 mg/dl) and a high titer of perinuclear-antineutrophil cytoplasmic antibody (p-ANCA) (504 EU/ml). Renal pathology revealed crescentic glomerulonephritis (CrGN) without mucoid intimal proliferation of the interlobal arteries and fibrinoid necrosis of the afferent arterioles, Immunofluorescent micrography showed focal segmental granular deposition of IgG and C 3 in the mesangium and along the capillary loop and was in agreement with pauci-immune type. Recently, a subtype of renal involvement in SSc that is associated exclusively with normotensive renal failure and recognizable by p-ANCA is suggested. On the other hand, SSc with p-ANCA-positive glomerulonephritis as this case can be considered to be overlap syndrome of SSc and microscopic polyangitis nodosa (microscopic PN) because in microscopic PN, p-ANCA is detected at the range of 50% to 80% and renal pathology reveals necrotizing glomerulonephritis. In this point, we may describe this case as a suggestive one about p-ANCA-positive glomerulonephritis.

Antibodies, Antineutrophil Cytoplasmic↗

[The blood sugar levels after hypothermic cardiopulmonary bypass in diabetic patients: their relation to preoperative values of hemoglobin-A1c and medication].

We studied the blood sugar levels after hypothermic cardiopulmonary bypass (CPB) in diabetics and non-diabetics. Twenty eight patients were divided to the following four groups by the preoperative value of hemoglobin-A1c (HbA1c) and medication; (1) HbA1c < 6.0 and given oral anti-diabetic medication, (2) HbA1c > 6.0 and given oral anti-diabetic medication, (3) HbA1c > 6.0 and given insulin injection, and (4) non-diabetics. Both in diabetics and non-diabetics, the blood sugar levels were higher than 300 mg.dl-1 during cardiopulmonary bypass. In group (1) and (4), the blood sugar levels went down lower than 250 mg.dl-1 at 60 minutes after CPB, without any treatment. In group (2) and (3), the blood sugar levels after 60 minutes of CPB were higher than 250 mg.dl-1, and insulin 8 units were given. After 30 minutes of insulin injection, the blood sugar levels of group (2) were lower than 250 mg.dl-1, but those in group (3), the blood sugar levels were still higher than 250 mg.dl-1, and another 8 units of insulin were given. The diabetic patients whose HbA1c levels were higher than 6.0 and given anti-diabetic medication before operation, need insulin after CPB.

Adult↗