[An automatic recording system for visual acuity].
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Biomedical subjects
Publications and source records attributed to H Tsuchiya.
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In patients with atherosclerosis, fibrosclerotic focuses are induced by multiplication of vascular smooth muscle cells (VSMC), and they are regulated by cytokines and regulators. There have been few reports about the atheroprotective effect of estriol (E(3)). Estrone sulfate (E(1)-S) is the predominant estrogen of conjugated equiline estrogens, which is commonly used in hormone replacement therapy, but it should be hydrolyzed by steroid sulfatase (STS) to enter the cells of target tissues. The purpose of this study was to detect STS in VSMC and to investigate whether E(3) and E(1)-S have atheroprotective effects like E(2). First, we detected the presence of STS mRNA in VSMC by in situ hybridization. We then examined the changes in the expression of mRNAs of cytokines, namely, PDGF-A chain, IL-1, IL-6 and TGF-beta, in VSMC, in the presence and absence of E(3) and estrogens. As a result, the expression of PDGF-A chain, IL-1 and IL-6 mRNAs was suppressed by E(3) (P<0.05 vs control) significantly like E(1)-S and E(2), but that of TGF-beta mRNA was not significantly affected by any estrogen. These results indicate that E(1)-S can be hydrolyzed by STS in VSMC, and that E(3) may regulate the cytokines by suppressing the production of mRNAs. It is suggested that there is a possibility of E(1)-S and E(3) having a direct effect on vessels in atherogenesis.
To investigate the interrelation of heavy metals and the influence on next generation, total mercury and methylmercury, lead, cadmium, manganese, copper, zinc, and iron were determined in the maternal blood, placenta, umbilical cord, and umbilical cord blood. Samples were collected at delivery from 231 pregnant women who were living in the city of Nagoya, located in the central district of Japan, during 1974 and 1978. Total mercury and methylmercury, cadmium, and iron were higher in cord blood than in maternal blood, whereas copper and zinc were lower. Significant positive correlations were observed between maternal and cord blood with regard to total mercury and methylmercury, lead, cadmium, and manganese contents. Significant correlations were also observed between many pairs of metals, particularly in umbilical cord and its blood.
PURPOSE: At least one type of Rathke cleft cyst has unique MR findings, specifically, high intensity on T1-weighted images and iso- to low intensity on T2-weighted images relative to white matter. To clarify the influence of cyst content on MR images, we analyzed the cyst content by biomedical methods after surgical removal. METHOD: We studied five patients diagnosed with Rathke cleft cyst, whose MR images showed high intensity on T1-weighted images and iso- to low intensity on T2-weighted images. After surgery, total protein and cholesterol levels were quantified, and correlations of protein and cholesterol content with T1 and T2 signal intensities were performed in vitro. RESULTS: All five cysts had very high concentrations of protein (11,700-26,600 mg/dl, mean 17,940 mg/dl) with nearly no cholesterol (at most 2.0 mg/dl). Along with increases in protein concentration in vitro, the signal intensity of T1-weighted images increased, while that of T2-weighted images decreased. In contrast, the cholesterol concentration sequence influenced the signal intensity of neither T1- nor T2-weighted images. CONCLUSION: The unique MR finding of Rathke cleft cysts--high signal intensity on T1-weighted images and low signal intensity on T2-weighted images--might depend mainly on protein concentration, not on cholesterol.
In this study, an experiment was performed to investigate the optimal concentration of branched chain amino acid (BCAA) in hyperalimentation to be administered when protein catabolism is accelerated by sepsis or bodily injury. Amino acid solutions containing BCAA 25%, 30%, 40%, 45% and 50% were prepared and were administered iv for three days with other essential amino acid-containing nitrogen in the same volume into rats with peritonitis which had been developed by ligature and puncture at the cecum, and the results were compared. After observing for three days, the influence over nitrogen balance, improvement of 3-methyl-histidine/creatinine in urine, weight loss in muscles, and aminogram in serum and muscles indicated that the hyperalimentation under stress is utilized most effectively when amino acid contains 45% of branched-chain amino acid.
Electromagnetic field (EMF) radiation has been found to induce arteriolar dilatation, but the mechanism of action remains largely unknown. This study investigated the effect of EMF radiation on the production of endothelin-1 (ET-1), a potent vasoconstrictor, by cultured endothelial cells. EMF radiation reduced ET-1 basal levels in human umbilical vein and microvascular endothelial cells, but failed to reduce ET-1 basal levels in bovine and human aortic endothelial cells. EMF radiation significantly inhibited thrombin-stimulated ET-1 production in all four endothelial cell types in a dose-dependent manner. EMF radiation significantly inhibited thrombin-induced endothelin-1 mRNA expression in all four cell types. The inhibitory effect of EMF radiation on ET-1 production was abolished by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (10(-3) mol/1). These results demonstrate that EMF radiation modulates ET-1 production in cultured vascular endothelial cells and the inhibitory effect of EMF radiation is, at least partly, mediated through a nitric oxide-related pathway.
A tumor with the light microscopic and immunohistologic characteristics of chordoma in the sacrococcygeal region in a 48-year-old man was examined by electron microscopy and immunohistochemistry for tubulin. A large population of cells exhibited prominent parallel arrays of long, straight microtubules in the rough endoplasmic reticulum in addition to the well-described ultrastructural features of chordoma. Immunoreaction to tubulin recognized in the juxtanuclear regions of the large number of tumor cells was in accordance with the ultrastructural localization of the microtubular aggregates. This seems to be the first report of microtubular aggregations in rough endoplasmic reticulum in classic chordoma. Furthermore, the present electron microscopic and immunohistochemical findings suggest that tubulin is a constituent of the unusual structures.
During the response of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methylation occurred at the Hpa II site of c-myc exon I, which is located downstream of the P1 initiation site, as evidenced by the assays of Hpa II-PCR. The Hpa II spite of the 5' flanking region did not undergo methylation. UV-irradiation also led to methylation in exon I. The extent of methylation increased depending on the dose of MNNG and UV. The results suggested that methylation takes place in transcriptionally active c-myc responsible for carcinogens and is caused by mechanisms different from that of alkylation in a specific CpG site. Possible contribution of methylation to less repair found in c-myc is discussed.
BACKGROUND: Initial p53 status is a useful determinant of chemoresistance or chemosensitivity of primary tumors, however, it remains unclear whether p53 status is a critical chemoresistant marker in tumors that acquire drug-resistance after the initiation of chemotherapy. We investigated the relationship between p53 status and the development of resistance to cisplatin in osteosarcoma cell lines. MATERIALS AND METHODS: Cisplatin-sensitive human osteosarcoma OST cells and acquired cisplatin-resistant OST/R cells derived from OST cells were used. Single-strand conformation polymorphism (SSCP) analysis of exons 5 to 8, and immunohistochemistry using anti-p53 antibodies were analyzed to detect mutations of p53. Fluorescence in situ hybridization (FISH) and enzyme immunoassay (EIA) were performed to detect deletions of p53. RESULTS: SSCP and immunohistochemistry revealed that both cell lines had wild-type p53 gene and protein. However, in OST/R cells, genomic instability of chromosome 17 and de novo deletion of the p53 gene located in chromosome 17p were detected by FISH. The constitutive levels of wild-type p53 protein measured by EIA were significantly lower in OST/R cells than in OST cells. Furthermore, p53 induction was lost in OST/R cells after cisplatin exposure. CONCLUSIONS: De novo deletions of the p53 gene and wild-type p53 were associated with the acquisition of cisplatin-resistance in osteosarcoma.
The present study was performed to investigate whether the introduction of a wild-type p53 gene into human osteosarcoma cells could alter the growth rate and enhance the cytocidal effect of cisplatin (CDDP) and the synergistic antitumor effect of caffeine. The lipofection method was used to transfect a wild-type p53 expression plasmid into the human osteosarcoma cell line, Saos2, which has both p53 alleles deleted. The transfected cells, Saos2/p53, had a reduced growth rate compared with the parental cell line. The colorimetric WST-1 assay demonstrated that Saos2/p53 cells were twice as sensitive to CDDP alone at a 50% inhibition concentration than the parental Saos2 cells. Caffeine significantly potentiated the cytocidal effect of CDDP in the Saos2/p53 cells. Furthermore, the TUNEL assay revealed that following treatment both with CDDP alone and with CDDP combined with caffeine, a higher percentage of the Saos2/p53 cells underwent apoptosis than did the parental Saos2 cells. Therefore the cytocidal effect of CDDP and the synergistic antitumor effect of caffeine are enhanced by the introduction of a wild-type p53 gene into a human osteosarcoma cell line null for p53. This raises the possibility that gene therapy using the p53 gene may prove efficatious for human osteosarcomas lacking p53 and which are resistant to standard chemotherapy.
Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer drugs and radiation. We present a preliminary report on the results of a new treatment, "radiochemotherapy combined with caffeine" (K3 protocol), for high-grade soft tissue sarcomas. Seventeen patients with various high-grade soft tissue sarcomas were included in this study. Preoperatively, three to five courses of intra-arterial chemotherapy using cisplatin, caffeine and doxorubicin after radiation therapy were administered. Following the preoperative therapy, function-saving surgery was performed for all cases. Complete response was observed in six patients, partial response in six and no change in five. The effectiveness rate of caffeine-potentiated radiochemotherapy was therefore 71%. The histological response for radiochemotherapy was better than that for chemotherapy alone, that is, total tumor necrosis was identified in six patients and over 90% necrosis in another six. Complications resulting from the preoperative radiation comprised of serious inflammation in three patients and skin necrosis in another three. Twelve patients have remained free of disease, two patients are alive with disease and three have died of metastatic disease with a mean follow-up period of 36 months. There was no local tumor recurrence. These preliminary findings suggest that caffeine-potentiated radiochemotherapy contributed to a satisfactory local response and the success of function-saving surgery for high-grade soft tissue sarcomas.
BACKGROUND: Immmunosuppression and infectious disease in cancer patients receiving chemotherapy is a serious problem. Immunopotentiating drugs may show a therapeutic efficacy. MATERIALS AND METHODS: The protective effect of Hochu-ekki-to (TJ-41), a Japanese traditional herbal medicine, on mitomycin C (MMC)-induced immunosuppression has been investigated. Spleen weight, the number of forming colonies of granulocytes and macrophages (CFU-GM) in the bone-marrow cells, natural killer (NK) activity in splenocytes and susceptibility to lethal herpes simplex virus type-1 (HSV-1) infection were evaluated. RESULTS: Oral administration of TJ-41 (2000 mg/kg/day) restored MMC-induced decline of spleen weight. CFU-GM and NK activity (20.6% to 68.4%, 48.8% to 77.7%, 21.1% to 95.1%, respectively). Moreover, MMC treatment resulted in a lethal HSV-1 infection and TJ-41 showed a preventive effect. CONCLUSION: TJ-41 may be beneficial for the treatment of infectious diseases in immunocompromised patients receiving chemotherapeutic drugs.
Hemodynamic and hormonal responses to bolus intravenous injections of synthetic porcine endothelin (pET) were examined in anesthetized dogs. There were no significant changes in mean blood pressure (MBP), right atrial pressure (RAP), or plasma atrial natriuretic factor (ANF) concentration in response to 40 pmol/kg of the peptide. However, responses to 400 pmol/kg of the peptide were significant: MBP rose from 114 +/- 6 mmHg (mean +/- SE) to 139 +/- 7 mmHg (p less than 0.01), RAP rose from 5.4 +/- 0.9 mmHg to 7.8 +/- 1.1 mmHg (p less than 0.01), and ANF increased from 45 +/- 10 pg/ml to 277 +/- 33 pg/ml (p less than 0.01). Peak value of RAP was observed 2.6 +/- 0.4 min, while peak of ANF was 11.4 +/- 0.9 min after peptide injection. There was a strongly positive correlation (r = 0.93, p less than 0.01) between the increase in RAP and the increase in ANF in dogs given 400 pmol/kg of pET. These results indicate that exogenously administered pET to anesthetized dogs alters hemodynamics and induces ANP release, and are compatible with a postulate that the ANF release is caused by elevated RAP.
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Human osteosarcoma cells, that were cultured to confluence and maintained under low nutrient conditions, showed potentially lethal damage repair after cisplatin treatment. This repair was inhibited by a non-toxic dose of caffeine. Flow cytometric analysis indicated that cisplatin-treated cells accumulated in the S phase by 24 hr, followed by accumulation in the G2/M phase. Caffeine inhibited the initial accumulation in the S phase and the release of cells from the G2/M block. DNA synthesis was also inhibited by the cisplatin treatment. The addition of caffeine significantly reversed this inhibition. The content of DNA-bound platinum decreased over time after cisplatin treatment. Caffeine did not influence platinum content, nor did it directly affect the DNA excision repair. Cisplatin inhibits DNA synthesis in the S phase, but caffeine reduces this inhibition. Caffeine-treated cells that pass through S phase are incapable of recovery.
OBJECTIVE: The relationships between age and diastolic left ventricular function, and age and mitral valve motion were studied. DESIGN: The maximum velocity of circumferential fibre lengthening (negative peak Vcf) of left ventricular function and mitral valve motions, such as mitral valve E and A wave amplitude, D-E and E-F slopes, and their relationships were assessed. SUBJECTS: Twenty young, healthy persons (10 males and 10 females) from 20 to 47 years old (mean 34.5), and 26 older healthy subjects (five males and 21 females) from 62 to 94 years old (mean 80.0) were studied. INTERVENTION: M-mode echocardiography of left ventricular function and mitral valve motion were recorded and digitized for the assessment. MAIN RESULTS: Age showed a significant (P = 0.0001) correlation with negative peak Vcf (r = -0.62), with E wave amplitude (r = -0.83), with D-E slope (r = -0.71) and with E-F slope (r = -0.83). Negative peak Vcf was correlated with E wave amplitude (r = 0.51, P = 0.0007), with D-E slope (r = 0.31, P = 0.058), with E-F slope (r = 0.53, P = 0.0005). Its relations with mitral valve A wave amplitude was r = -0.30, P = 0.17 in the elderly group and r = 0.003, P = 0.99 in the younger group. A significant (P < 0.001) positive, linear correlation was observed between age and mitral A/E ratio (r = 0.82). CONCLUSIONS: The easily measurable mitral valve E-F slope and E wave amplitude can be used to assess early diastolic left ventricular function in ageing. Left atrial contraction appears to play a more important role in the elderly, compensating for the decline in early diastolic left ventricular function.