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S Kanazawa

Publications and source records attributed to S Kanazawa.

At least 73 records · Page 4Linked to original sources
PubMed1999

Interactions between the class II transactivator and CREB binding protein increase transcription of major histocompatibility complex class II genes.

Class II major histocompatibility (class II) genes are regulated in a B-cell-specific and gamma interferon-inducible fashion. The master switch for the expression of these genes is the class II transactivator (CIITA). In this report, we demonstrate that one of the functions of CIITA is to recruit the CREB binding protein (CBP) to class II promoters. Not only functional but also specific binding interactions between CIITA and CBP were demonstrated. Moreover, a dominant negative form of CBP decreased the activity of class II promoters and levels of class II determinants on the surface of cells. Finally, the inhibition of class II gene expression by the glucocorticoid hormone could be attributed to the squelching of CBP by the glucocorticoid receptor. We conclude that CBP, a histone acetyltransferase, plays an important role in the transcription of class II genes.

Animals↗
PubMed1999

Cepharanthin enhances thermosensitivity without a resultant reduction in the thermotolerance of a murine mammary carcinoma.

Cepharanthin (Ce) is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. The results of our previous in vitro study indicated that Ce reduces thermotolerance by enhancing thermosensitivity. In the present study, we investigated the in vitro and in vivo effects of Ce on thermosensitivity and thermotolerance using a murine mammary carcinoma, MCa, and C3H/HeN mice. Ce enhanced the thermosensitivity of MCa cells for heating at 44 degrees C not only in vitro but also in vivo. The in vivo enhancement ratio +/- SD of Ce at 100 mg/kg for heating at 44 degrees C was 1.3+/-0.3. The fractionated heat treatments at 44 degrees C for 30 and 60 min with an interval time of 0-6 days resulted in the development of remarkable thermotolerance and the expression of heat shock protein 70 in MCa tumors after the first heating. Ce at 100 mg/kg given immediately after the first heating increased the expression of heat shock protein 70 in MCa tumors, and did not reduce the development of thermotolerance. Ce given immediately before the first or second heating also did not inhibit the thermotolerance. The results of this study suggest that Ce enhances the thermosensitivity of MCa tumors as a thermosensitizer, but that this mild thermosensitizing property of Ce might be insufficient to conquer the remarkable thermotolerance in MCa tumors that develops after the first heating.

Alkaloids↗
PubMed1999

Lobar decrease in 99mTc-GSA accumulation in hilar cholangiocarcinoma.

UNLABELLED: Hilar cholangiocarcinoma can obstruct hepatic ducts and involve the portal veins. Both biliary stasis and decrease in portal venous flow are known to reduce 99mTc-diethylenetriamine pentaacetic acid-galactosyl human serum albumin (GSA) accumulation. The specific relationship between these pathological conditions due to hilar cholangiocarcinomas and 99mTc-GSA accumulation has never been clarified. METHODS: Sixteen patients with hilar cholangiocarcinomas who underwent 99mTc-GSA liver scintigraphy were reviewed. The relationship between significant decrease in 99mTc-GSA accumulation and lobar biliary stasis, or decrease in the portal venous flow, was evaluated. Average counts of region of interest placed in both right and left lobes were compared in the same transaxial SPECT section. Count ratios of right and left lobes were calculated. RESULTS: Significant lobar decrease in 99mTc-GSA accumulation was observed in 6 of the 16 patients. Ipsilateral portal venous stenosis or obstruction was seen in all these 6 patients, whereas ipsilateral portal venous stenosis or obstruction was seen in only 1 of the other 10 patients. Symmetric bile duct dilatation was seen in 13 patients, and asymmetric bile duct dilatation was seen in 3. Lobar decrease in 99mTc-GSA accumulation correlated well with decrease in ipsilateral portal venous flow (P < 0.0005). The count ratio was significantly reduced when unilateral portal venous flow decreased (P < 0.05). CONCLUSION: Using 99mTc-GSA liver scintigraphy, we can predict lobar decrease in ipsilateral portal venous flow and monitor hepatic functional lateralities in patients with hilar cholangiocarcinomas.

Aged↗
PubMed1998

Essential role of phosphatidylserine externalization in apoptosing cell phagocytosis by macrophages.

In many apoptotic cells, phosphatidylserine (PS), that is normally restricted to the inner membrane layer, is externalized and subsequently recognized by phagocytes. However, it has been unclear whether PS externalization is sufficient for phagocytosis induction. In a cultured cell line undergoing Fas-mediated apoptosis, PS externalization preceded other apoptotic events. When transbilayer movement of membrane phospholipids was analyzed, a decrease of the uptake of PS and phosphatidylethanolamine and an increase of phosphatidylcholine incorporation were observed upon apoptosis induction. Apoptotic cultured cells were phagocytosed by macrophages in a manner dependent on externalized PS before plasma membrane permeability increased. Moreover, a N-ethylmaleimide treatment caused PS externalization independent of apoptosis, and such cells underwent PS-mediated phagocytosis. These results suggested that PS is externalized as a result of membrane phospholipid redistribution and externalized PS by itself induces apoptosing cell phagocytosis.

Animals↗
PubMed1998

Significance of parathyroid hormone-related protein as a factor stimulating bone resorption and causing hypercalcemia in myeloma.

Elevated levels of parathyroid hormone-related protein (PTHrP) in hypercalcemic myeloma patients were demonstrated in recent reports, suggesting that PTHrP behaves as a humoral mediator of hypercalcemia in myeloma. Herein we describe a hypercalcemic myeloma patient with a high serum PTHrP level. Moreover, the PTHrP level in the supernatant of bone marrow aspirates was about two-fold of that in serum. Reverve transcriptase-polymerase chain reaction analysis showed PTHrP m-RNA in bone marrow containing myeloma cells. After chemotherapy, the concentrations of calcium and PTHrP decreased and PTHrP mRNA in bone marrow became undetectable. We conclude that PTHrP released by myeloma cells acted as the main bone resorption stimulating factor in this case.

Aged↗
PubMed1998

Mechanism of free radical-induced hemolysis of human erythrocytes. II. Hemolysis by lipid-soluble radical initiator.

Hemolysis of human erythrocytes induced by free radicals initiated from lipid-soluble 2,2'-azobis(2,4-dimethylvaleronitrile) (ADVN) was examined under various conditions. From the ESR spectra of the spin-labeled erythrocytes, it was found that the fluidity of the membrane did not change during the radical-induced hemolysis. The curves of the time courses of the extent of oxidation and the conformational change of band 3 proteins were hyperbolic, though the hemolysis curves were sigmoidal. In spite of the necessity of lipid peroxidation, the peroxidation did not seem to relate directly to the hemolysis. It was observed that the hemolytic holes were formed by a lateral clustering of band 3, an anion exchange protein in erythrocytes. The competitive reaction model between lipid peroxidation and the redistribution of oxidized band 3 proteins, which was previously presented for the hemolysis initiated from water-soluble, 2,2'-azobis(amidinopropane)dihydrochloride (AAPH), could explain well the curves for the hemolysis by ADVN. Further, the rates of lipid peroxidation at various concentrations of ADVN and AAPH were calculated on the basis of the hemolysis curves, and they were compared with the experimental values estimated from the curves for the lipid peroxidation. The curves which showed a dependence of the calculated rate constant on the concentration of radical initiators were similar to those of the experimental values. These results indicate that the competitive reaction model is appropriately represents the hemolysis induced by free radicals which also originated from lipid-soluble initiators.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1998

Novel selective inhibitors for human topoisomerase I, BM2419-1 and -2 derived from saintopin.

Compounds BM2419-1 and -2 were isolated from a culture broth of a fungus Paecilomyces sp. BM2419. It was shown that these novel compounds were artifacts derived from saintopin, a dual inhibitor of topoisomerase I and II by independent processes. In the human topoisomerase I inhibition assay using the recombinant Saccharomyces cerevisiae, BM2419-1 and -2 inhibited selectively the yeast growth dependent on human topoisomerase I induction with IC50 values of 0.3 ng/ml and 6.0 ng/ml, respectively.

Animals↗
PubMed1998

Technetium-99m-DTPA-galactosyl human serum albumin liver scintigraphy evaluation of regional CT/MRI attenuation/signal intensity differences.

UNLABELLED: Regional attenuation/signal intensity differences seen on CT/magnetic resonance imaging can be a clue in detecting regional hepatic blood flow abnormality. Sometimes, however, they can be misinterpreted as a hepatic neoplasm or, in the case of a true neoplasm, they can lead to an overestimation of its size because these regions often have similar attenuation or signal intensity to hepatic neoplasms. We evaluated 99mTc-diethylenetriaminepentaacetic acid-galactosyl human serum albumin (99mTc-DTPA-GSA) liver scintigrams in patients manifesting regional attenuation/signal intensity differences to further analyze the findings. METHODS: Technetium-99m-DTPA-GSA scintigrams of 23 patients with regional attenuation/signal intensity differences in the liver at dynamic contrast-enhanced CT/magnetic resonance imaging were evaluated. The causes of the differences were arterioportal (AP) shunts in seven patients, decreases in the portal venous flow in seven patients, occlusion of right hepatic vein in one patient, confluent hepatic fibrosis in one patient and unknown in seven patients. The accumulation of 99mTc-DTPA-GSA was compared with each known cause of attenuation/signal intensity difference. Count ratios of the regions to normal hepatic parenchyma also were calculated in all cases. RESULTS: In AP shunts, none of seven patients showed any decreased accumulation in the region. Accumulation of 99mTc-DTPA-GSA decreased in six of seven patients who had decreases in portal venous flow; this incidence was significantly higher than that in patients who had AP shunts (p < 0.005). In cases of unknown cause, two of seven patients showed a decrease in accumulation, but the other five showed no such decrease. The one patient with occlusion of the right hepatic vein showed no decrease, but the confluent hepatic fibrosis showed a significant decrease. The count ratio in AP shunts was significantly larger than that of the decrease in the portal venous flow (p < 0.005). CONCLUSION: Technetium-99m-DTPA-GSA accumulation in AP shunts has a different pattern from that found in patients with a decrease in portal venous flow. Therefore, differentiation between AP shunts, which showed no decrease in 99mTc-DTPA-GSA accumulation, and hepatic neoplasms can be made more easily.

Carcinoma, Hepatocellular↗
PubMed1998

Flare response seen in therapy for osteomalacia.

We report an interesting case of osteomalacia in which flare response was seen during therapy. The first 99mTc-methylene diphosphonate bone scan showed increased bilateral and symmetric uptake in the ribs, clavicles and iliac bones. Thoracic CT showed symmetric radiolucent seams (Looser's zones) in both ribs, which were pathognomonic of osteomalacia. After initiation of therapy with vitamin D, the patient's subjective symptoms gradually were relieved. On a second bone scan 4 mo. after initiation of therapy, the hot spots in the ribs remained unchanged. Uptake in the bilateral clavicles had become more intense, and new hot spots were recognized in the right lower ribs and left tibia. A third bone scan after 10 mo. demonstrated an obvious decrease in the number and intensity of the hot spots. Increased uptakes in the second scan were thought to be a flare response caused by therapy.

Aged↗
PubMed1997

Universal skew of T cell receptor (TCR) V beta usage for Crohn's disease (CrD).

It would be of clear interest and importance to identify T cell populations which correlate with the initiation of some T cell-mediated diseases; however, it is difficult to observe the initial response of T cells in these diseases because of modification due to immunosuppressive treatment. We investigated T cell receptor (TCR) V beta usage in both affected and unaffected mucosa from 16 patients with active Crohn's disease (CrD), undergoing nutritional therapy without any immunomodulatory medications. Semiquantitative reverse transcriptase-polymerase chain reaction showed increased expression of V beta 12 and 13 in the entire mucosa of CrD but not in the controls. This was confirmed by introducing a random cloning method. Such skewing was observed primarily in CD4+ lamina propria lymphocytes. DNA sequence analysis demonstrated a striking clonal expansion of V beta 12 T cells, but the dominant clones were not identical in the patients. These findings suggest the importance of superantigen as well as specific T cell response in the pathogenesis of CrD.

Adult↗
PubMed1997

Skin abnormality in aged fyn-/- fak+/- mice.

Focal adhesion kinase (FAK) is a novel non-receptor protein tyrosine kinase implicated in transducing signals from cell surface receptors. Its association with Fyn, a member of the Src family of tyrosine kinases, has been observed in cell lines. To examine in vivo the interaction between these two proteins, Fyn-deficient mice were bred with fak heterozygous mutants (Fak deficiency is embryonic lethal). A majority of animals with the double mutation (fyn-/- fak+/-) displayed a transient impairment in thymocyte development at four weeks of age. However, all of them developed skin abnormalities at the age of 8-12 months. The most prominent among abnormalities was a greatly increased number and size of sebaceous glands. Also, the epidermis was thickened and hyperkeratotic. These observations would suggest involvement of Fyn and FAK in keratinocyte differentiation.

Age Factors↗
PubMed1997

Reduced radioactivity in the periphery of the liver in a patient with idiopathic portal hypertension.

The authors report a case of idiopathic portal hypertension in which radioaccumulation in the peripheral region of the liver decreased markedly. On dynamic CT, peripheral regional enhancement of the liver was seen in the arterial phase. The region was hypointense on T1-weighted MR images and hyperintense on T2-weighted images. On portograms via the superior mesenteric artery, markedly decreased portal venous perfusion was seen in the peripheral region of the liver. Tc-99m galactosyl human serum albumin (GSA) liver scintigrams showed decreased accumulation in the peripheral region and unchanged accumulation in the central region of the liver. Tc-99m GSA liver scintigraphy clearly showed localized liver dysfunction in the peripheral region.

Female↗
PubMed1997

[Plateau iris configuration as a risk factor for malignant glaucoma].

To provide evidence for diagnosing malignant glaucoma, as well as to elucidate the pathogenetic mechanism of the disease, ultrasound biomicroscopy (UBM) is a useful tool. We examined the anterior segments of three patients with post-operative malignant glaucoma with UBM regarding the state before operation, the state of the opposite eye, and the state after the release of the cilio-lenticular block. Case 1 was a 76-year-old female who was diagnosed as having chronic angle-closure glaucoma (CACG) and was treated by trabeculectomy, phacoemulsification, aspiration (PEA), and simultaneous intraocular lens (IOL) implantation. Case 2 was a 22-year-old male diagnosed as having CACG secondary to plateau iris syndrome and was treated by trabeculectomy. Case 3 was a 73-year-old female diagnosed as having normal-tension glaucoma with narrow angle and was treated by PEA and IOL implantation. Slit-like anterior chamber angle and anteriorly positioned ciliary body were observed in all 3 cases, which were identical to those Pavlin reported in 8 cases with plateau iris syndrome. UBM seems to be an important pre-operative examination to evaluate the risk of malignant glaucoma and to consider which surgical procedure and post-operative management is proper. The pre-operative configuration of the ciliary body may be associated with the onset of malignant glaucoma in some patients with CACG or narrow angle.

Adult↗
PubMed1997

The diagnosis and management of splanchnic artery aneurysms. Report of 8 cases.

The purpose of this report is to describe the clinical characteristics and surgical technique for splanchnic artery aneurysms. Over the past 10 years we have surgically resected 8 cases of splanchnic artery aneurysms including 2 cases involving the superior mesenteric artery, 3 involving the renal artery, 1 involving the hepatic artery and 2 involving the splenic artery. Diagnosis was established preoperatively in all patients by splanchnic angiography. Surgical treatment for splanchnic artery aneurysms is indicated in any symptomatic patient, in all symptomatic patients with suspected renal aneurysmal expansion and in patients who have renal aneurysms occurring with functionally important renal stenosis, usually associated with hypertension, in all patients with surgical accessible hepatic artery aneurysms, in all patients who have superior mesenteric artery aneurysms having a high tendency to rupture, and in all patients with an asymptomatic splenic artery aneurysms 1.5 cm or larger in diameter. Although splanchnic artery aneurysms are uncommon and asymptomatic, we recommend that splanchnic arteries should be treated surgically because of their tendency to rupture or organ failure.

Adult↗
PubMed1996

Impaired development of CD4+ CD8+ thymoyctes by csk-'knock-in' into fyn locus.

p59fyn is one of the Src-family kinases thought to play an important role in signaling through T cell receptor. However, Fyn deficiency has caused no overt defects in vivo on T cell development, nor has it caused any changes in the phosphorylation status of molecules such as ZAP-70 which have been proposed as p59fyn substrates. This could be explained as being due to compensation of Fyn deficiency by other Src-family kinases. Here, we have 'knocked-in' the csk gene, a negative regulator of Src-family kinases, into fyn locus to challenge the problem of redundant functions among Src-family kinases. The csk-'knock-in' mice displayed atrophy of the thymic cortex and impaired development of CD4+ CD8+ thymocytes. This was concomitant with decrease in tyrosine phosphorylation of ZAP-70 and p120cbl.

Animals↗
PubMed1996

Impairment of mobility in endodermal cells by FAK deficiency.

Focal adhesion kinase (FAK) is a novel nonreceptor protein tyrosine kinase that localizes in focal adhesions. It is expressed in a variety of cell types, and we reported earlier that is deficiency causes a decrease of mobility in mesodermal cells with enhanced formation of focal adhesions. With embryoid bodies generated from embryonic stem cells, we also observed a decrease of mobility in FAK-deficient endodermal cells with enhanced focal adhesion formation.

Animals↗