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Biomedical subjects

T Igawa

Publications and source records attributed to T Igawa.

At least 19 recordsLinked to original sources

Absence of association between the MCP-1 gene polymorphism and histological phenotype of lupus nephritis.

Lupus nephritis presents two polar histological patterns, diffuse proliferative glomerulonephritis (DPGN) and membranous glomerulonephritis (MGN). In the kidney tissue of DPGN, numerous mononuclear cells were seen in the interstitium and glomeruli; on the other hand in MGN, infiltrating cells were less frequent. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for monocytes, T-cells, and natural killer cells. In this study we assessed the significance of the MCP-1 gene in determination of the histological phenotype in lupus nephritis. There was no association between the risk of DPGN and the MCP-1 gene genotype.

Adolescent↗

[Evaluation of bone metastases from renal cell carcinoma].

Forty-two cases of bone metastasis from renal cell carcinoma were examined. Thirty of the cases had bone metastases at the time of renal cell carcinoma. Bone metastasis appeared after treatment of the primary site in 12 cases. Fifteen cases had only bone metastasis and another 27 had metastasis in multiple organs. The total cause-specific survival curve of these patients was 10% at 5 years. All patients with bone metastases died of cancer within 5 years after the bone metastases had developed. There was no significant difference in the survival rate between patients with bone metastases and patients with lung metastases. We investigated the prognostic value of laboratory studies in bone metastases of renal cell carcinoma. However, no significant markers were detected for bone metastases. The 6 patients were treated with decompressed laminectomy (2), wide resection (3) and excision of the metastatic lesions (3). The quality of life was improved in all the patients although they died of cancer.

Adult↗

Hydrolysis of DNA by Ce(IV)/EDTA complexes--the mechanism of DNA cleavage and design of artificial restriction enzymes.

Homogeneous Ce(IV) complex of EDTA promptly hydrolyzes oligonucleotides under physiological conditions. Moreover, the activity of Ce(IV)/EDTA for DNA hydrolysis is promoted by the addition of amines. When [Ce(IV)/EDTA] = 5 mumol dm3 and [ethylenediamine] = 100 mmol dm3, the catalytic activity is about 50 times as large as that of Ce(IV)/EDTA. The combination of Ce(IV)/EDTA and amines is eminent tools for the future molecular biology and biotechnology.

Catalysis↗

Increased platelet sensitivity to collagen in individuals resistant to low-dose aspirin.

BACKGROUND AND PURPOSE: The purpose of this study was to assess individual differences in the pharmacological effects of acetylsalicylic acid (ASA) on bleeding time as measured by in vitro platelet aggregation and to examine the consistency of responses over time. METHODS: We measured template IIR bleeding time and platelet aggregation in 8 healthy male volunteers before and 2 hours after ingestion of 324 mg of ASA. An individual was considered a nonresponder if his post-ASA bleeding time was not 2 SDs above his baseline bleeding time, where SD was estimated from the baseline bleeding times of the 8 volunteers. The same experiment was done after a 30-month interval. RESULTS: Five volunteers were identified as ASA responders, and 3 were identified as nonresponders. Bleeding time before and after ingestion of ASA was 408+/-121 seconds (mean+/-SD) and 720+/-225 seconds, respectively, in ASA responders and 330+/-30 seconds and 330+/-52 seconds, respectively, in ASA nonresponders. The mean ED(50) for collagen-induced platelet aggregation, that is, the mean concentration of collagen that caused a response at 50% of maximum, was 0.91 microg/mL (95% CI, 0.73 to 1. 14) in ASA responders and 0.48 microg/mL (95% CI, 0.38 to 0.60) in nonresponders. When optimum concentrations of collagen, ie, concentrations that yielded 90% maximum aggregation, were used as stimuli, the mean IC(50) for ASA, that is, the mean concentration that yielded 50% inhibition, was 322.5 micromol/L (95% CI, 264.8 to 392.6) in ASA responders and 336.1 micromol/L (95% CI, 261.0 to 432. 8) in nonresponders. The variability in individual responsiveness in the second experiment remained consistent with that in the first experiment. CONCLUSIONS: ASA resistance may be caused by an increased sensitivity of platelets to collagen. A platelet aggregation study specific for collagen dose response may be useful for strict selection of ASA responders for low-dose ASA therapy and for identifying ASA nonresponders for high-dose ASA therapy.

Adult↗

An anti-platelet agent, OPC-29030, inhibits translocation of 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid production in human platelets.

1. In human platelets, arachidonic acid is mainly metabolized by the two enzyme systems; cyclo-oxygenase and 12-lipoxygenase. Cyclo-oxygenase produces prostaglandin H(2) which is further converted to thromboxane B(2). 12-Lipoxygenase synthesizes 12(S)-hydroperoxyeicosatetraenoic acid which is reduced to 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). 2. An anti-platelet compound, OPC-29030, dose-dependently inhibited 12(S)-HETE production with an IC(50) of 0.06+/-0.01 microM, but not synthesis of thromboxane B(2) in human platelets. Although the compound suppressed 12(S)-HETE production in human platelets, cytosolic 12-lipoxygenase activity was not inhibited up to 10 microM. Essentially identical data were obtained with a 12-lipoxygenase of human erythroleukaemia cells which had megakaryocyte/platelet-like properties. 3. OPC-29030 also suppressed production of 5(S)-HETE, a 5-lipoxygenase product, in rat basophilic leukaemia cells without inhibiting enzyme activity. It has been shown that 5-lipoxygenase binds to membrane 5-lipoxygenase-activating protein (FLAP) to produce 5(S)-HETE, and thus FLAP inhibitor suppresses cellular 5(S)-HETE production. 4. A FLAP inhibitor, L-655,238, suppressed platelet 12(S)-HETE production, but had no effect on the 12-lipoxygenase activity. 5. Western blot analysis showed that platelet 12-lipoxygenase translocated from cytosol to membranes upon thrombin stimulation, and OPC-29030 suppressed this process in a dose-dependent manner. 6. These results suggest that the 12-lipoxygenase of human platelets binds to FLAP or a similar protein, and OPC-29030 suppresses 12(S)-HETE production by inhibiting a certain step of the 12-lipoxygenase translocation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Clinical experiences of microsurgical side-to-end epididymovasostomy for epididymal obstruction.

BACKGROUND: Some surgical treatments are performed for obstructive azoospermia in urology and good results have been reported. Of 61 azoospermic patients who visited our department of urology, nine were diagnosed as having epididymal obstruction of unknown etiology. METHODS: We describe nine consecutive side-to-end epididymovasostomy procedures performed on these patients. These procedures are microsurgical two-layer anastomosis. RESULTS: Of the nine men, five (55.6%) had sperm in the ejaculate postoperatively and, up until publication, the pregnancy rate was 33.3% (three of nine). CONCLUSIONS: These results suggest that reconstruction of the seminal tract should be considered first for obstructive azoospermia.

Constriction, Pathologic↗

Improvement of efficiency of the Ce(IV)-induced DNA scission--relationship between the kinetic parameters (k(cat) and Km) and the DNA structure.

The Michaelis constant (Km) for double-stranded DNA, single-stranded DNA, and dinucleotide hydrolysis by Ce(IV) ion are 4.4, 15, and more than 40 mM, respectively. The order of the k(cat), however, is dinucleotide >> oligonucleotides. Not only the improvement of k(cat) but also that of Km is important for the design of an efficient artificial nuclease.

Base Sequence↗

Evaluation of the Clot Signature Analyzer as a hemostasis test in healthy volunteers exposed to low doses of aspirin.

Several variables affect bleeding time that make it difficult to obtain consistent measurements. The Clot Signature Analyzer (CSA) has been developed to assess in vitro hemostasis using well-controlled flow chambers. In this study, the equivalencies in the CSA parameters with the conventional bleeding time or platelet aggregation methods were evaluated in subjects exposed to aspirin. The CSA parameters, platelet hemostasis time (PHT) and collagen-induced thrombus formation (CITF), were compared to bleeding time (Surgicutt2) and collagen-induced platelet aggregation, respectively. Fifty-three healthy volunteers were given two doses of aspirin (81 and 243 mg) in one day. Following the baseline period, the volunteers took 81 mg of aspirin and then took 243 mg 2 hours later. The changes in each value from the baseline to that at either aspirin dose (2 hours after dosing) were evaluated. Platelet hemostasis time and CITF correlated well with bleeding time and aggregation, respectively, but PHT was not significantly increased after 81 mg of aspirin, whereas bleeding time was significantly increased. The variation in PHT was slightly higher than that of bleeding time. At 81 mg, CITF was significantly increased but aggregation was not, even though the variation was comparable. This suggests that PHT and CITF can simulate the changes in bleeding time and aggregation, respectively, but the sensitivity of PHT for detecting the changes in bleeding time was no better than the conventional method. Also, CITF was more sensitive than aggregation in detecting platelet response to collagen. In conclusion, the proposed CSA is not always suitable for detecting hemostatic abnormalities.

Adolescent↗

[Measurements and clinical usefulness of carboxyterminal propeptide of type I collagen and cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer].

Carboxyterminal propeptide of type I collagen (P1CP) and cross-linked carboxyterminal telopeptide of type I collagen (1CTP) are known as parameters of bone metastasis in patients with prostate cancer (PCa). We measured the serum P1CP and 1CTP levels in 52 PCa patients and evaluated the clinical usefulness of these serum markers. Both serum levels of P1CP and 1CTP were significantly higher in patients with extent of disease (EOD) grade 2 or 3 bone metastases than in patients without bone metastasis. Thus, P1CP and 1CTP are not as useful at first detection of bone metastases as bone scintigram. On the other hand, in the patients who indicated high serum levels of P1CP or 1CTP before initial treatment, the changes in the concentrations of these markers may be helpful in evaluating the response to treatment or the progression of disease. Our results suggest that P1CP and 1CTP are useful markers for monitoring the metastatic burden in the bone of PCa patients, but the efficacy is limited in high EOD grade cases.

Aged↗

12(S)-HETE plays a role as a mediator of expression of platelet CD62 (P-selectin).

The role of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE), an abundant lipoxygenase product from arachidonic acid in platelets, remains unknown. We investigated and characterized the role of 12(S)-HETE in platelet activation. 12(S)-HETE production and CD62 expression were increased by stimulation with thrombin at 0.03 U/ml or higher, while TXB2 synthesis was increased by thrombin at 0.1 U/ml or higher. The platelet 12(S)-HETE production was increased 10 s after stimulation and this was earlier than CD62 expression. The expression of CD62 was inhibited by the lipoxygenase (LOX) inhibitors quercetin and nordihydroguaiaretic acid but was not affected by the cyclooxygenase (COX) inhibitors aspirin and indomethacin. Exogenously added 12(S)-HPETE and 12(S)-HETE enhanced CD62 expression, but other HETEs did not. Consequently, 12-LOX products play a role in the expression of CD62 and could be a second messenger for platelet activation.

Journal Article↗

[Primary adrenal schwannoma].

We report a rare case of retroperitoneal schwannoma arising from left adrenal gland. A 45-year-old man with upper abdominal discomfort was found to have a tumor in the left adrenal gland by abdominal ultrasonographic scan. The laboratory findings were all normal but angiogram indicated slightly hypervascular adrenal tumor. Eventually, he was underwent left adrenalectomy. The removed mass was measured 6.5 x 5.7 x 5.0 cm and weighed 75.5 g. Pathological study revealed benign schwannoma arising from the adrenal gland, consisting mainly of the Antoni A type. A review of the literature on adrenal schwannoma is included.

Adrenal Gland Neoplasms↗

[Usefulness of initial chemoendocrine therapy for advanced prostate cancer].

The 5 year cancer specific survival rate of advanced prostate cancer, especially in metastatic cancer is less than 40%. Recently, maximum androgen blockade showed some beneficial effects in cases of minor disease but no additional usefulness in major cases. The treatment modality referred to as initial chemoendocrine, used to treat prostate cancer, seems to be a reasonable method because prostate cancer cells contain heterogeneity. This procedure means that the endocrine treatment is best suited to treat hormone sensitive cells, whereas chemotherapy is more appropriately used as a firstline therapy for hormone insensitive cells. We reported that the initial chemoendocrine method showed superiority in the 5 year cancer specific survival category than in the endocrine therapy analyzing non-randomized trials. From that stage on we reviewed the beneficial point of the treatment, and are now trying randomized control studies.

Antineoplastic Agents↗

Cytoplasmic delivery of calcein mediated by liposomes modified with a pH-sensitive poly(ethylene glycol) derivative.

Previously, as a new type of pH-sensitive liposome, we prepared egg yolk phosphatidylcholine (EYPC) liposomes bearing succinylated poly(glycidol), that is a poly(ethylene glycol) derivative having carboxyl groups, and showed that fusion ability of the liposomes increases under weakly acidic and acidic conditions (Kono, K., Zenitani, K. and Takagishi, T. (1994) Biochim. Biophys. Acta 1193, 1-9). In this study, we examined intracellular delivery of a water-soluble molecule, calcein, mediated by the succinylated poly(glycidol)-modified liposomes. When CV-1 cells, an established line of African green monkey kidney cells, were incubated with bare EYPC liposomes containing calcein at 37 degrees C, only weak and vesicular fluorescence of calcein was observed by using a fluorescence microscope. In contrast, the cells treated with the polymer-modified liposomes containing calcein displayed more intensive and diffuse fluorescence, indicating that calcein was transferred into the cytoplasm. Uptake of the polymer-modified liposomes by the cells was shown to decrease slightly as amount of the polymer fixed on the liposome increases. However, the fluorescence of calcein observed in the liposome-treated cell was, on the contrary, enhanced as amount of the polymer fixed on the liposome increases, indicating that the liposome modified with a higher amount of the polymer transfers its content into cytoplasm more efficiently after internalization into the cell. Fusion assay by resonance energy transfer using N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine and lissamine rhodamine B-sulfonylphosphatidylethanolamine suggested occurrence of fusion between the polymer-modified liposomes and endosomal and/or lysosomal membranes. Moreover, the liposome with a higher polymer content revealed higher percent fusion after internalization into the cell. These results imply that the polymer-modified liposomes transfer the content into the cytoplasm by fusing with the endosomal membrane after internalization into the cells through an endocytic pathway.

Animals↗

Activity of keratinocyte growth factor-like substance extracted from rabbit liver on renal tubular cell growth during compensatory renal hyperplasia.

BACKGROUND: In response to unilateral nephrectomy, the rabbit liver transiently produces 2 growth regulators for cultured renal cortical tubular cells: a tubular cell growth factor and a growth inhibitor. We report on the effects of the tubular cell growth factor on a variety of cell lines. METHODS: The tubular cell growth factor activity was partially purified from the rabbit liver by using gel filtration and ion-exchange chromatography. The activity was monitored by the incorporation of iododeoxyuridine into DNA of cultured cells. Expression of the fibroblast growth factor receptor-2 in the rabbit kidney was determined by the immunoblot analysis. RESULTS: This growth factor stimulated the DNA synthesis in LLC-PK1 cells, LLC-RK1 cells, and human keratinocytes. It did not affect the growth of BS-C-1 cells, MDCK cells, BALB/c 3T3 fibroblasts, or rat parenchymal hepatocytes. The additive effect of this factor on the DNA synthesis of cultured tubular cells maximally was stimulated by insulin-like growth factor-I, basic fibroblast growth factor, and epidermal growth factor, but was not stimulated by keratinocyte growth factor. The amount of this activity also increased in the liver after sham operation. In the days after surgery, expression of fibroblast growth factor receptor-2, which includes the keratinocyte growth factor receptor, was down-regulated in the kidneys of both uninephrectomized and sham-operated rabbits. CONCLUSION: These findings indicate that tubular cell growth factor in the liver seems to be a keratinocyte growth factor, and acts in an endocrine manner in renal tubular hyperplasia.

3T3 Cells↗

Human simple renal cyst fluid contains a cyst formation-promoting activity for Madin-Darby canine kidney cells cultured in collagen gel.

Simple renal cysts are commonly observed in the elderly, but few examinations have been performed to study the mechanism of this disease. We have previously shown that simple renal cyst fluid contains some growth factors, including epidermal growth factor (EGF; less than 54 pg mL-1) and insulin-like growth factor I (IGF-I; 30-2070 pg mL-1) (M. Taide et al. Clin Chim Acta, 1993; 217:199-203). In this report, the biological significance of growth factors or of human simple renal cyst fluid on the formation of renal epithelial cyst was determined using Madin-Darby canine kidney (MDCK) cells cultured in collagen gel. Both EGF (200 pg mL-1 or more) and IGF-I (100 pg mL-1 or more) were found to stimulate cyst formation in MDCK cells. Additionally, 12/21 human simple renal cyst fluid samples were found to be capable of stimulating cyst formation in MDCK cells. This activity was due to a heat- and acid-labile protein and not inhibited by the anti-IGF-I neutralizing antibody. These results indicate that in some instances simple renal cyst fluid would thus appear to contain specific activity for cyst formation, which may affect cyst formation in vivo.

Animals↗

A possible common cell surface autoantigen in islet beta-cells and thyroid follicular cells in patients with non-insulin dependent diabetes mellitus and chronic thyroiditis.

By an indirect immunofluorescence method with In-111 cells (hamster insulinoma cell line), circulating islet cell surface antibodies (ICSA) were detected in 7 (20%) out of 36 patients with non-insulin dependent diabetes mellitus (NIDDM), 9% of 68 chronic thyroiditis (CT) patients, or 16% of 19 NIDDM patients associated with CT, but not in 18 normal subjects. Sera from five out of nine ICSA-positive patients examined further also showed cell-surface immunofluorescence on TPC-1 cells (human thyroid papillary adenocarcinoma cell line), and prior absorption of the sera with In-111 cells abolished the immunofluorescence. The 64 kDa protein from In-111 cells or human thyroid follicular cells was immunoprecipitated with ICSA-positive sera. In one case of NIDDM associated with CT, 64 kDa protein was detected in both cells. The results indicate that some ICSA in NIDDM patients recognize the same or a very closely-related autoantigen(s) in both islet beta-cells and thyroid follicular cells, suggesting an explanation, at least in part, for the autoimmune mechanism(s) in clinical association of NIDDM and CT.

Adenocarcinoma, Papillary↗