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Biomedical subjects

S Yoshida

Publications and source records attributed to S Yoshida.

At least 685 records · Page 38Linked to original sources
PubMed1998

A novel single basepair insertion in exon 6 of the Bruton's tyrosine kinase (Btk) gene from a Japanese X-linked agammaglobulinemia patient with growth hormone insufficiency.

A novel insertion mutation in exon 6 of the Btk gene was detected in a 17 year-old XLA patient with GH insufficiency. We synthesized cDNA from leukocyte total RNA and amplified every region of the Btk-coding sequence. Sequencing of cDNA fragments revealed a single basepair insertion mutation at codon 157 in exon 6 (CAG-->CAAG) which leads to premature termination at codon 193 in exon 7. To confirm the results, we also performed a PCR-DdeI digestion analysis using leukocyte genomic DNA. The PCR product from the patient's genomic DNA was uncleaved with DdeI, as expected. PCR-DdeI digestion analysis of the family members showed that the mother and elder sister were carriers with the mutation and that the younger sister did not carry the mutation.

Adolescent↗
PubMed1998

Osteochondritis dissecans of the femoral condyle in the growth stage.

The site of lesion, spontaneous healing, onset mechanism, and magnetic resonance imaging findings of 51 knees in 38 patients with osteochondritis dissecans involving the femoral condyle in the growth stage were investigated. tercondylar site, and the remaining 1/4 were in other sites. Compared with those in the other sites, the lesions in a medial intercondylar site had a lower healing rate and required a longer time to heal. T2 weighted images of the lesions showed a progression from low signal areas to the appearance of a high signal line at the fragment to parent to bone interface, to a high signal double line at the interface and parent-bone surface, or to disappearance of the line. Magnetic resonance imaging often revealed discoid menisci or meniscal tears in patients with lesions in the lateral condyle, suggesting that endogenous forces play an important role in the onset of osteochondritis dissecans.

Adolescent↗
PubMed1998

Immunohistochemical study of human advanced glycation end-products (AGE) and growth factors in cardiac tissues of patients on maintenance dialysis and with kidney transplantation.

Cardiovascular disease is one of the most common complications of dialysis and renal transplant patients, and high levels of AGE are present in end-stage renal failure. To address the potential involvement of AGE and growth factors in the pathophysiology of cardiovascular complications, we performed immunostaining using cardiac tissues from autopsy cases of patients on maintenance dialysis (10 cases), long-term surviving renal transplant patients with functioning grafts (8 cases), control subjects with normal renal function (7 cases) and non diabetic subjects with mild renal insufficiency (8 cases). We used two types of AGE-antibodies, 6D12 [monoclonal anti-AGE antibody, recognizing N epsilon-(carboxymethyl) lysine(CML)-modified AGE] (oxidative AGE) and non-CML-PA [polyclonal, not recognizing CML], and antibodies against PDGFs, PDGF receptors and TGF beta. Positive 6D12 staining was observed in the coronary arterial walls and in macrophages. The accumulation of 6D12-reactive AGE in the coronary arterial walls of maintenance dialysis patients was significantly greater than that of control subjects (p < 0.05). Renal transplantation significantly reduced this accumulation (p < 0.05). On the other hand non-CML-PA mainly detected AGE in intracardiac arterioles and neural tissues. There was little difference in the accumulation of non-CML-AGE among the four groups. PDGFs and PDGF receptors were mainly detected in vascular endothelial cells and infiltrating cells of cardiac tissues of renal transplant patients, but not of maintenance dialysis patients. TGF beta was not detected in cardiovascular tissue of transplant patients. Our results indicated that the accumulation of oxidative AGE (CML-AGE) in the cardiac vascular tissue is one of the factors for cardiovascular complications of maintenance dialysis patients, and also that renal transplantation has a reducing effect on CML-AGE accumulation. PDGFs may be involved in the cardiovascular complications after renal transplantation.

Adult↗
PubMed1998

Role of NF-kappaB-mediated interleukin-8 expression in intraocular neovascularization.

PURPOSE: To investigate the role of interleukin (IL)-8 in intraocular neovascularization and the mechanism of its production. METHODS: Interleukin-8 was measured with enzyme-linked immunosorbent assays in vitreous and aqueous fluid obtained from patients with neovascular diseases. Localization of IL-8 was examined by immunohistochemistry. An in vitro angiogenesis assay was performed on collagen gels, by using bovine aortic endothelial cells to determine the effect of the vitreous fluid. In bovine retinal glial cells under hypoxia, NF-kappaB activation was evaluated by immunoblot analysis and by electrophoretic mobility shift assay, and IL-8 and vascular endothelial growth factor (VEGF) mRNA expression was determined by semiquantitative reverse transcription-polymerase chain reaction. RESULTS: The concentration of IL-8 in vitreous fluid of patients with retinal neovascularization was significantly higher than that of patients without neovascular disease. Interleukin-8 immunostaining was detected in vascular endothelial cells and glial cells in the retinas with neovascularization. Vitreous fluid with high concentrations of IL-8 induced tubular morphogenesis in endothelial cells, and this effect was inhibited to a similar extent by neutralizing antibodies to IL-8 or to VEGF. In glial cells, in vitro, hypoxia induced NF-kappaB activation and increased IL-8 and VEGF mRNA. Furthermore, pyrrolidine dithiocarbamate, a specific inhibitor of NF-kappaB activation, prevented the induction of the IL-8 gene, but not that of the VEGF gene. CONCLUSIONS: These results suggest that IL-8 induced by hypoxia and mediated by NF-kappaB may contribute to the pathogenesis of intraocular neovascularization.

Animals↗
PubMed1998

Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum. The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S-transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the formalin-fixed biopsy samples of primary tumors before chemotherapy was examined immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate than did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53 negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on survival than performance status (0 versus 1 or 2), age (> 60 years versus < or = 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic). Immunohistochemical examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

Adult↗
PubMed1998

Improved myocardial fatty acid metabolism after coronary angioplasty in chronic coronary artery disease.

UNLABELLED: This study assessed the utility of myocardial fatty acid imaging using 123I-labeled 15-(beta-methyl-p-iodophenyl-pentadecanic acid (BMIPP) to evaluate improvement after percutaneous transluminal coronary angioplasty in patients with chronic coronary artery disease. METHODS: Thirty-eight patients (18 old myocardial infarction and 20 angina pectoris patients) with chronic coronary artery stenosis and 8 control subjects were enrolled in this study. All patients underwent successful angioplasty, and BMIPP SPECT was performed before and after angioplasty. SPECT images were divided into 13 segments and scored visually from 0 (normal uptake) to 4 (defect). The defect score was calculated as the summation of the total scores in each patient. The regional washout rate was calculated in both the reperfused areas and normal uptake areas using a bull's-eye map. RESULTS: In nonrestenosis patients, BMIPP defect scores before and after angioplasty did not change on the initial image (9.6 +/- 9.3 compared to 9.0 +/- 9.2, nonsignificant p value), whereas they improved significantly on the delayed image (9.9 +/- 8.8 compared to 8.2 +/- 8.7, p < 0.05). In nonrestenosis patients, BMIPP washout rate in reperfused areas after angioplasty was significantly lower than that before angioplasty and the washout rate in control subjects (22.9% +/- 8.4% compared to 31.5% +/- 10.6% and 29.5% +/- 8.0%, p < 0.01 and p < 0.05, respectively). In restenosis patients, BMIPP washout rate in both reperfused areas and normal uptake areas did not change after angioplasty. CONCLUSION: These data suggest that decreased BMIPP washout rate after angioplasty indicates improved fatty acid utilization in patients with chronic coronary artery disease.

Adult↗
PubMed1998

Development of perioral muscle activity during suckling in infants: a cross-sectional and follow-up study.

The activity of the perioral muscles during breastfeeding in infants was investigated using EMGs. Fifty-six infants aged from 1 to 5 months were classified into five groups according to month of age in the cross-sectional study. Follow-up was carried out on 18 infants whose mean age was 2.5 months at the initial examination, and 4.8 months at the second. During suckling, EMGs were recorded unilaterally from the temporalis (TM), the masseter (MM), the orbicularis oris (OM), and the suprahyoid (SM) muscle groups. The activity of the SM increased significantly with age, while there was no appreciable increase in the activity of the TM, MM, and OM in either the cross-sectional study or the follow-up. However, total muscle activity was shown to increase significantly in both parts of the study. These findings suggest that the active tongue- and jaw-lowering movement may play a primary role in increasing sucking strength during the suckle-feeding period in infants.

Cross-Sectional Studies↗
PubMed1998

[Complete disappearance of metastatic pulmonary tumors in a case of hepatocellular carcinoma treated with UFT].

The disappearance of multiple pulmonary metastatic lesions in hepatocellular carcinoma patient following the oral administration of UFT is reported. Pulmonary and pelvic metastases were detected in a 71-year-old female hepatocellular carcinoma patient treated by TAE (Trans-Arterial Embolization with epirubicin, mitomycin C, lipiodol and Gelform) three times in one year. Four months after beginning oral administration of UFT-E granule 1.5 g/day (tegafur 300 mg/day, uracil 672 mg/day), three pulmonary metastatic lesions markedly reduced in size, and disappeared completely 6 months after beginning UFT. A pelvic metastatic tumor markedly reduced in size by the combined effect of radiation, TAE (epirubicin, mitomycin C, lipiodol, Gelform) and oral UFT. We consider UFT was effective in the disappearance of multiple pulmonary metastatic lesions, because three TAE administrations of epirubicin and mitomycin C could not prevent systemic spreading of hepatocellular carcinoma.

Administration, Oral↗
PubMed1998

Regional cerebral blood flow evaluated by 99mTc-HMPAO-SPECT in patients with axillo-axillary bypass for subclavian steal syndrome.

BACKGROUND: Clear evidence of cerebral blood circulation has not been shown after axillo-axillary bypass surgery in patients with subclavian steal syndrome. METHODS: We investigated the cerebral circulation and blood flow in 3 patients receiving axillo-axillary bypass by RI angiography using 99mTc-dl hexamethyl propylene amine oxime (99mTc-HMPAO). Two patients had vertebral basilar cerebral symptoms which were related to decreased cerebral blood flow evidenced by 99mTc-HMPAO. RESULTS: After the correction, cerebral symptoms disappeared and improved cerebral blood circulation detected by 99mTc-HMPAO-SPECT. CONCLUSIONS: We concluded that axillo-axillary bypass was a fairly effective procedure to improve cerebral blood circulation evidenced by 99mTc-HMPAO-SPECT.

Axillary Artery↗
PubMed1998

[Cone beam CT utilizing a rotational digital radiographic system: early clinical experience on pulmonary and skeletal lesions].

Utilizing a rotational digital radiographic system (SF-VA 100, Hitachi) 289 digital images were obtained during a 360-degree rotation in 4.8 seconds. The images were transferred to a high-speed workstation and post-processed to create volume data in 9 minutes. The multi-planar reconstruction method reconstructed high-quality tomographic images with equal resolution in any direction. We applied this system as a cone beam CT in order to demonstrate pulmonary and spinal lesions. Early clinical experience suggested the usefulness of the method in the evaluation of diseases in organs with high radiographic contrast.

Arteriovenous Fistula↗
PubMed1998

Analysis of bax protein in sphingosine-induced apoptosis in the human leukemic cell line TF1 and its bcl-2 transfectants.

Sphingosine, a sphingolipid breakdown product, has been proposed as an apoptosis-inducing agent. In this study, we examined the effect of sphingosine in bcl-2-overexpressing cells compared with cells that do not express the bcl-2 gene. The human erythroleukemic cell line TF1, which lacks bcl-2 expression, was easily induced to undergo apoptotic cell death by a variety of stimuli, including depletion of granulocyte-macrophage colony-stimulating factor (GM-CSF) or exposure to methylmethane sulfonate (MMS) (100 microg/mL), ultraviolet light (15 J/m2), X-ray irradiation (20 Gy), or sphingosine, a sphingolipid breakdown product (5 microM). In contrast, bcl-2 transfectants of TF1 (TF1-bcl2), which we established, were resistant to most of these treatments but remained sensitive to sphingosine. Neither C2- nor C6-ceramide (short-chain ceramide) induced apoptosis in TF1-mock and TF1-bcl2 cells. Sphingosine-induced apoptosis could not be inhibited by fumonisin B1, which can prevent conversion of sphingosine to ceramide, suggesting that sphingosine itself, not ceramide, possesses apoptosis-inducing capability. Western blotting, which revealed a 21-kDa bax protein in untreated cells, revealed the presence of an additional 18-kDa protein in GM-CSF-depleted and MMS- or sphingosine-treated TF1-mock cells. In TF1-bcl2 cells, this protein was not detected after GM-CSF depletion or MMS treatment, but was observed after sphingosine treatment. Immunoprecipitation with anti-bcl2 antibody, followed by immunoblotting with anti-bax antibody, showed that both the 21-kDa bax protein and the 18-kDa protein heterodimerized with bcl-2 protein. These results suggest that sphingosine is a unique reagent for apoptosis and that it can overcome bcl-2 gene expression. Furthermore, induction of 18-kDa bax-related protein may play an important role in apoptosis. Sphingosine, but not ceramide, may prove applicable as a reagent for future cytotoxic drugs used to treat intractable tumors overexpressing bcl-2.

Apoptosis↗
PubMed1998

[Clinical results of three types of intraocular lenses for small incision surgery].

We implanted three types of intraocular lens (IOL) in 30 eyes each by small-incision surgery. They were: foldable acryl IOL, foldable silicone IOL and polymethylmethacrylate (PMMA) IOL. We evaluated the following items during three years after surgery: visual acuity, astigmatism, glare disability, contrast sensitivity, tilt and decentering of IOL, corneal endothelial population, aqueous flare and aftercataract. Eyes foldable IOLs were more excellent than PMMA IOLs regarding visual acuity, astigmatism and aqueous flare which are indices for the early postoperative period. PMMA and acryl IOLs were more excellent than silicone IOLs regarding decentration of IOL and aftercataract which are indices for the late postoperative period.

Acrylates↗
PubMed1998

[Phase I study of raltitrexed (ZD-1694)].

A multicenter cooperative phase I study of ZD-1694 (raltitrexed), a novel, folate-based thymidylate synthase (TS) inhibitor, was conducted with single and repeated doses in 30 patients with various malignant tumors. ZD-1694 was intravenously infused over 15 minutes. In the single-dose study, the initial dose was fixed at 1.0 mg/m2 (1n), and the dose was escalated stepwise up to 3.5 mg/m2 (3.5 n). Based on the results of the single-dose study, in the repeated-dose study, doses of 2.5 n and 3 n were infused every three weeks (3 weeks/one course). In principle, patients received 2 courses or more. Of the 29 eligible patients, 16 were in the single-dose study and 13 in the repeated-dose study. Adverse reactions were evaluated in all eligible patients. In the single-dose study, neutropenia, nausea/vomiting, diarrhea, and transaminase (GOT, GPT) increases, of grade 3 or higher, occurred at high doses of 3 n and 3.5 n. These were regarded as dose-limiting toxicities (DLT). DLT of grade 3 or higher were observed in 1 of 4 patients given 3 n and 2 of 4 patients given 3.5 n. These results suggested that the maximum tolerated dose (MTD) of ZD-1694 was 3.5 n (3.5 mg/m2). In the repeated-dose study, DLT of grade 3 or higher was observed in no more than one third of each dose group, 2 of the 6 patients given 2.5 n and 2 of the 7 patients given 3 n. These results suggested that 3 n (3.0 mg/m2), a dose nearer to MTD, was the recommended dose for the phase II study. Although transaminase increases were observed in all patients, in 12 of them the increase was grade 2 or lower and reversible. A pharmacokinetic investigation showed the mean elimination half life of ZD-1694 plasma concentration was 91.5 hours in the single-dose group and 119.1 hours in the repeated dose group. It was suggested that ZD-1694 is metabolized to polyglutamates after uptake and retained in the cells for a long duration. However, no accumulation was seen in plasma concentration of ZD-1694 following repeated doses at 3-weekly intervals. One PR was observed in a patient with colorectal cancer receiving 2.5 n in the repeated-dose study. Based on these results, the recommended dosage and administration for the phase II study of ZD-1694 was 3 n (3.0 mg/m2) intravenously infused over 15 minutes every 3 weeks.

Adult↗
PubMed1998

[Clinicopathological study of cases with Mycobacterium szulgai infection].

Pulmonary mycobacteriosis is usually caused by Mycobacterium tuberculosis, Mycobacterium avium complex, or Mycobacterium kansasii. There are, however, other slow-growing mycobacteria which can cause pulmonary infection. Mycobacterium szulgai, first reported in 1972, is a scotochromogenic species which can affect human lungs, although human-to-human spread of infection is thought to be unlikely. We have recently treated three cases of middle-aged to elderly persons (45-87 year-old), two of them had underlying diseases (one with intrapulmonary and the other with extrapulmonary). All patients had constitutional symptoms (cough, sputum, dyspnea), and chest roentgenograms demonstrated either cavitation with scattered nodules or peripheral infiltrates predominantly in upper lobes, resembling pulmonary tuberculosis. In two cases, M. szulgai was identified by using DNA-DNA hybridization method. The in vitro susceptibility of M. szulgai to antimycobacterial drugs was better than that of M. avium complex, and it was resistant only to paraaminosalicylate, cycloserine, and partially to isoniazid. Pulmonary disease of three patients were successfully treated with a combination of multiple antimycobacterial agents including rifampin, ethambutol, isoniazid, or streptomycin.

Aged↗
PubMed1998

Diastolic dysfunction coincides with early mild transplant rejection: in situ measurements in a heterotopic rat heart transplant model.

BACKGROUND: Diastolic dysfunction seen in early clinical transplant rejection has been difficult to demonstrate in experimental rodent models because of the inability to make sensitive in situ measurements of systolic and diastolic functions. We have developed a heterotopic heart transplant model with Fisher 344 and ACI rats (without immunosuppression), where in situ measurements of diastolic and systolic functions were made sequentially (daily) by use of an implanted left ventricular balloon. METHODS: Syngeneic and allogeneic heterotopic heart transplants were performed. In situ function was determined by varying balloon volume to measure the developed pressure, the rates of pressure rise (+dp/dt) and pressure fall (-dp/dt), diastolic pressure-volume relationship, and the time constant of diastolic relaxation (tau). These results were compared with function measurements in transplanted hearts that were excised and perfused in a Langendorff mode (ex vivo) during the same posttransplantation period. RESULTS: Histologic examination revealed that at day 3 after transplantation, allografts showed mild lymphocytic infiltration indicative of mild or early rejection, and by day 5, there was severe rejection with myocyte necrosis. By day 3, the slope of the diastolic pressure-volume relationship (ie, left ventricular stiffness) was significantly higher in allografts as compared with isografts (436 +/- 96 vs 177 +/- 26 mm Hg/mL, p < .05). Similarly, tau was significantly longer in allografts by day 3 after transplantation. Developed pressure and +dp/dt became significantly lower in allografts beginning on day 6. Function measurements made in the isolated perfused ex vivo hearts yielded the same results at day 3 after transplantation as the in situ group of hearts. CONCLUSION: Using a chronically implanted left ventricular balloon, we have developed a heterotopic heart transplant model where sensitive measurements of systolic and diastolic functions can be made. With this preparation, the early changes in the diastolic dysfunction seen clinically can be reproducibly detected. Thus this model may be useful to study mechanisms and interventions during early transplant rejection.

Animals↗
PubMed1998

[A phase II study with high-dose cytarabine (NS-075) in adult patients with relapsed and refractory acute leukemia].

A multi-center phase II clinical study with high dose cytarabine (NS-075) was conducted in adult patients with relapsed and/or refractory acute leukemia. 2 g/m2 cytarabine was given 12 times by 3-hour intravenous infusion every 12 hrs. 46 patients were registered, and 44 were evaluable: 35 with acute myeloid leukemia (AML) and 9 with acute lymphoblastic leukemia (ALL). There were 28 males and 16 females, with a median age of 37.5 years (range 15-68), including 6 of more than 60 years. Among 35 patients with AML, there were 16 (45.7%) complete and 2 (5.7%) partial remissions. Among 9 patients with ALL, there were 2 (22.2%) complete and 1 (11.1%) partial remissions. The major non-hematologic toxicities were gastrointestinal symptoms such as nausea/vomiting, anorexia and diarrhea, as well as fever, infection, conjunctivitis, alopecia, hepatic and renal dysfunctions. Central nervous system (CNS) toxicity was mild and reversible. Therapy-related death occurred in 5 patients resulting from prolonged pancytopenia, which suggests the necessity of strict countermeasures for infections as well as good patient care. These results indicate that high-dose cytarabine is a promising therapy for treatment of relapsed and/or refractory acute leukemia.

Adolescent↗
PubMed1997

Stimulation of cell-surface urokinase-type plasminogen activator activity and cell migration in vascular endothelial cells by a novel hexapeptide analogue of neurotensin.

To investigate if neurotensin (NT) could induce activation of urokinase-type plasminogen activator (uPA) in vascular endothelial cells, we utilized the acetyl-NT (8-13) analogue, TJN-950, in which the C-terminal leucine is reduced to leucinol. TJN-950 inhibited the binding of 125I-NT to membranes of newborn rat brains and of COS-7 cells transfected with rat NT receptor cDNA, but at 10(4) higher doses than NT (8-13). However, TJN-950 was as effective as NT in inducing the fibrinolytic activity in bovine vascular aortic and human umbilical vein endothelial cells, and enhanced the migration of vascular endothelial cells. Moreover, administration of TJN-950 induced neovascularization in the rat cornea in vivo. TJN-950 had no effect on expression of uPA, plasminogen activator inhibitor-1 or uPA receptor mRNA. The binding of 125I-TJN-950 to cell membranes was blocked by unlabeled uPA and TJN-950, but not the amino-terminal or 12-32 fragment of uPA. TJN-950 may enhance uPA activity in vascular endothelial cells by interacting with the uPA receptor, resulting in induction of angiogenesis.

Animals↗