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Biomedical subjects

Y Hori

Publications and source records attributed to Y Hori.

At least 163 records · Page 9Linked to original sources

Kinetics of immunological parameters in patients with malignant melanoma treated with hyperthermic isolated limb perfusion.

Kinetics of immunological parameters such as natural killer (NK) cell activity and tritium-thymidine uptake rate of T lymphocytes by phytohemagglutinin stimulation were investigated using peripheral leukocyte fractions of melanoma patients treated with hyperthermic isolated limb perfusion (HILP). Also, serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) were quantified during and after HILP. It was found that NK cell activity was augmented during HILP, and T lymphocyte function was stimulated 24 h and 1 week after HILP with statistical significance. NK cell activities in the cells isolated from perfused and non-perfused circulations were equally augmented during HILP in two patients examined. Serum concentrations of sICAM-1 in the patients who received HILP also increased 24 h or even 1 week after HILP. The stimulation of these immune competent cells and upregulation of sICAM-1 by HILP were independent of the stages of melanoma patients at the time of HILP or the doses of agents which were used for the infusion during HILP. The origin of cells which shed sICAM-1 into the serum of the patients who received HILP remains to be further investigated.

Adult↗

Experimental approaches for the treatment of murine B16 melanomas of various sizes. I: Local injection of ethanol with a combination of interleukin-2 or microwaval hyperthermia for B16 melanomas with a size of less than 7 mm in diameter.

The effects of local absolute ethanol injection combined with administration of interleukin-2 (IL-2) or microwaval hyperthermia in murine B16 melanomas with a size of approximately 7 mm in diameter were investigated. The groups of melanoma-burdened mice treated with both local ethanol injection and local or intra-abdominal administration of IL-2 showed clear suppression of any recurrence of melanoma once the melanomas had been destroyed by ethanol injection and a concomitant prolongation of the survival times. Also, local injection of ethanol in combination with local microwaval hyperthermia at 43 degrees C for 15 min twice a week caused complete cures in B16 melanomas with a size of less than 7 mm in diameter. The infiltrations of T lymphocytes and NK cells were augmented in the melanomas treated with ethanol injection and local injection of IL-2. However, the melanomas treated with ethanol injection and intra-abdominal injection of IL-2 hardly showed any infiltration of such immune cells, although the growth of melanomas was effectively suppressed. In the case of treatment with ethanol and hyperthermia, slight infiltration of NK cells was observed in the melanoma nests as well as in the interstitials. Thus, the direct injection of absolute ethanol in combination with IL-2 or microwaval hyperthermia is effective or even curative in the treatment of murine B16 melanomas with a size of less than 7 mm in diameter.

Animals↗

Experimental approaches for the treatment of murine B16 melanomas of various sizes. II: Injection of ethanol with combinations of beta-interferon and microwaval hyperthermia for B16 melanomas with a size of greater than 10 mm in diameter.

Although ethanol injection in combination with microwaval hyperthermia and systemic administration of interleukin-2 was found to be very effective in suppressing the growth of B16 melanoma nodules with a size of less than 7 mm in diameter in our previous experiments, the growth of B16 melanomas with a size of greater than 10 mm in diameter was very difficult to control with any of the therapeutic modalities examined. In subsequent experiments, we investigated whether ethanol injection (150 microliters/injection) in combination with local injection of beta-interferon (2 x 10(4) IU/injection) and local microwaval hyperthermia at 43 degrees C for 15 min was able to suppress the growth of melanoma nodules and to prolong survival times of melanoma-burdened mice. The results were that we successfully suppressed the growth of melanoma nodules of that size for the first time with combinations of the therapeutic modalities described above. Infiltration of immunocompetent cells such as T lymphocytes and NK cells was clearly observed in the melanoma tissues treated with the therapeutic combination. These experimental results should be applied to the treatment of human melanomas in advanced stages which have no indications for surgical operation.

Animals↗

Dyschromatosis.

The dyschromatoses are a group of disorders characterized by the presence of both hyperpigmented and hypopigmented macules, many of which are small in size and irregular in shape. There are two major forms-dyschromatosis symmetrica hereditaria (DSH) and dyschromatosis universalis hereditaria (DUH), both of which are seen most commonly in Japan. DSH was first described by Toyama in 1929 and is characterized by a symmetrical distribution of hyperpigmented and hypopigmented macules on the extremities, especially over the dorsa of the hands and feet. In 1933, Ichikawa and Hiraga were the first to describe DUH as well-demarcated brown macules admixed with various-sized hypopigmented macules in a generalized as opposed to acral distribution. DUH was noted to appear within the first month of life. Some clinicians have suggested that DSH might be a subtype of DUH; however, we have to wait for the cloning of the causal genes of these diseases before coming to any definite conclusions. The differential diagnosis of dyschromatosis includes xeroderma pigmentosum, dyschromic amyloidosis, and exposure to chemicals such as diphenylcyclopropenone and monobenzyl ether of hydroquinone.

Age Factors↗

Inhibition of experimental metastasis and cell adhesion of murine melanoma cells by chondroitin sulfate-derivatized lipid, a neoproteoglycan with anti-cell adhesion activity.

Chondroitin sulfate dipalmitoylphosphatidylethanolamine (CS-PE), when immobilized onto substratum, inhibited the adhesion of B16F10 mouse melanoma cells to fibronectin-coated dishes (anti-adhesion activity). CS-PE showed the most potent anti-adhesion activity for the melanoma cells among various GAG-PEs. CS-PE also inhibited the adhesion of B16F10 cells to Matrigel and the invasion of the cells into Matrigel. In the in vivo system of experimental metastasis, administration of B16F10 cells with CS-PE into C57BL/6 mice significantly inhibited lung metastasis. The inhibition degree of CS or hyaluronic acid-PE was lower than CS-PE. CS-PE administered intravenously into mice before the injection of B16F10 cells also inhibited metastasis. Pretreatment of B16F10 cells with CS-PE caused some but a lower degree of inhibition. When CS-PE was injected intravenously into mice, more binding in the lung was found than when CS was injected. CS-PE but not CS inhibited the retention in the lung of fluorochrome-labeled B16F10 cells when injected intravenously into mice. Since there was no significant effect of CS-PE on the viability and growth of B16F10 cells, the results suggest that CS-PE immobilized onto the subendothelial matrix may prevent melanoma cells from adhering to the subendothelial substrata of lung capillaries and inhibit subsequent invasion processes of metastasis.

Animals↗

Tyrosine kinase dependent expression of TGF-beta induced by stretch in mesangial cells.

Increased glomerular hydraulic pressure has been suggested as a major causative factor in the development of glomerular sclerosis. The elevation of glomerular pressure increases the magnitude of stretch to mesangial cells. The study was, therefore, designed to investigate the effect of mechanical stretch on expression of TGF-beta and extracellular matrix components in cultured rat mesangial cells. The results showed that mechanical stretch stimulated mRNA expression for TGF-beta1 and TGF-beta3 in a time dependent manner, and that mesangial cells secreted substantial amounts of TGF-beta proteins in response to stretch. Stretch was also shown to stimulate mRNA expression for collagen types I and IV, and fibronectin, major components of mesangial extracellular matrix. The stretch-induced mRNA expression for extracellular matrix components was inhibited by neutralizing antibody to TGF-beta. Moreover, stretch-induced mRNA expression of TGF-beta was inhibited by tyrosine kinase inhibitors, genistein or herbimycin A, whereas Ca channel blockers nitrendipine or Gd3+, and inhibitors for protein kinase A or C had no effect. These findings indicate that stretch induced TGF-beta mRNA primarily through tyrosine kinase-dependent mechanisms in cultured rat mesangial cells, and the secreted TGF-beta may play a significant role for the stretch-induced expression of extracellular matrix proteins. Our results suggest that stretch-induced TGF-beta of mesangial cells might be a mediator in the progression of glomerular sclerosis as an autocrine/paracrine factor.

Angiotensin II↗

The efficiency and timing of initiation of replication of multiple replicons of Saccharomyces cerevisiae chromosome VI.

BACKGROUND: A complete set of nine ARSs was identified (the tenth ARS in this paper), mapped on chromosome VI of Saccharomyces cerevisiae, and characterized for functional elements. RESULTS: The level of activity of all ARSs as chromosomal replication origins was determined by neutral/neutral 2D gel-electrophoresis. These origins were classified into three groups: (i) three high frequency origins used once nearly every cell cycle, (ii) four intermediate frequency origins used once in two to three cycles and (iii) two low frequency origins used in fewer than 5% of cell cycles. These variations in initiation frequency among origins of chromosome VI are present in three common laboratory wild-type strains. Each origin is initiated at a fixed time and passively replicated by incoming replication forks at a fixed time during a synchronous S phase. Replication of each arm of the chromosome starts from one major origin located one-fifth (left arm) and one-third (right arm) of the distance from the centromere, and expands sequentially in both directions. Two telomere vicinity origins are replicated last. Time of initiation and replication of the last replicating origin, Ori609, was remarkably variable from cell to cell. CONCLUSIONS: Chromosome VI of S. cerevisiae contains nine replication origins that comprise five active replicons under normal cell growth conditions. A clear correlation was found between the efficiency of initiation and the order of replication. The timing of initiation of most origins, except for the first and last, is coincident with the time of passive replication by incoming forks from neighbouring origins.

Cell Cycle↗

Further analysis of Del (D-elute) using polymerase chain reaction (PCR) with RHD gene-specific primers.

Del (D-elute) in the Rh blood group system is a variant with very weak D antigen and no agglutination is found by the indirect antiglobulin test. This variant is characterized by the presence of anti-D eluate obtained after an adsorption-elution test using anti-D antibodies. We studied here the molecular genetic status of Del by using polymerase chain reaction with sequence-specific primers (PCR-SSP). We screened 306 serologically apparent D-negative Japanese donors comprising 102 Del types for exons 7, 4 and 10 of the RHD gene. No PCR product was found in all 204 non-Del samples from the D-seronegative donors. However, PCR products were found in all 102 Del samples and all 70 D-seropositive samples tested by the three PCR methods for exons 7, 4 and 10 analysis. Del was found with CCee, CcEe and Ccee, but not with CCEe, CcEE, ccEE, ccEe or ccee phenotype. The incidences of Del in the samples with the serological phenotypes CCee, CcEe and Ccee were 80.0% (4/5), 68.2% (45/66) and 61.6% (53/86), respectively. The results provide evidence that Del samples have exons 4, 7 and 10 of an RHD gene present in some form. This is consistent with the evidence that D antigen is present on the cells although only detected by antibody adsorption and elution. The PCR-SSP method in the present study is useful to confirm Del among serologically apparent D-negative samples.

Asian People↗

Proliferative fasciitis. Report of a case with histopathologic and immunohistochemical studies.

We present a case of proliferative fasciitis arising adjacent to an operative scar of the right lower leg of a patient with chronic lymphatic leukemia, diabetes mellitus, and multiple subcutaneous angiolipomas. A 61-year old man had a hard mass in his right lower leg that had rapidly increased in size in the past 10 days. The mass was microscopically composed of a dense proliferation of spindle cells forming interlacing fascicles admixed with an inflammatory infiltrate of lymphocytes and eosionphils, focal hemorrhage, and myxomatous change as typically seen in nodular fasciitis as well as many characteristic ganglion cell-like giant cells. Immunohistochemically, most of the spindle-shaped cells were positive for vimentin and alpha-actin, whereas the ganglion cell-like giant cells were positive for vimentin and negative for alpha-actin and lysozyme. We suggest that the main component cells of proliferative fasciitis are fibroblastic in nature, many of which are myofibroblasts in large part, whereas the ganglion cell-like giant cells are related more closely to fibroblasts rather than histiocytes or pericytes. Additionally, proliferating cell nuclear antigen (PCNA) stain revealed that many of the fibroblastic cells showed high proliferative activity, especially in the hypercellular areas, although there was no significant difference in PCNA staining between the focus traumatized by the needle biopsy and the nontraumatized areas.

Actins↗

In vitro comparison between mouse B16 and human melanoma cell lines of the expression of ICAM-1 induced by cytokines and/or hyperthermia.

The expression of intercellular adhesion molecule-1 (ICAM-1) in mouse B16 and human melanoma cell lines was investigated by indirect immunofluorescence using a FACScan analyzer. Mouse B16 melanoma cell lines (B16-F1 and F10) did not express ICAM-1 under ordinary culture conditions. Neither in vitro hyperthermia at 41 degrees C for 3 or 6 hr nor cytokines such as gamma interferon (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha) induced ICAM-1 expression in B16 melanoma cell lines. A combination of IFN-gamma with TNF-alpha caused slight induction of ICAM-1 expression in the B16-F10 melanoma cell line. Hyperthermia at 41 degrees C for 3 hr in combination with the cytokines induced a slight expression of ICAM-1 in the B16-F1 melanoma cell line. Hyperthermia at 41 degrees C for 3 hr or 6 hr did not induce de novo ICAM-1 expression but hyperthermia at 43 degrees C for 6 hr caused rather suppression of the expression of ICAM-1 in the three human melanoma cell lines tested. In contrast, they showed a clear increase in the expression of ICAM-1 after treatment with either with IFN-gamma or TNF-alpha, and the expression was further augmented by a combination of the two cytokines. Treatment with cytokines in combination with hyperthermia at 41 degrees C or 43 degrees C for 3 hr did not augment the expression of ICAM-1 over that in cytokine-treated human melanoma cell lines, at normal temperatures. Thus, it is concluded that mouse B16-F1 and F10 melanoma cell lines are different from human melanoma cell lines in terms of induction of ICAM-1 expression by cytokines and/or hyperthermia.

Animals↗

Molecular genetic analysis of HLA class II alleles in Japanese patients with melanoma.

Distribution of HLA-DQA, -DQB and -DPB alleles in ninety-six Japanese patients with melanoma was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and the association between clinical parameters and the presence of certain HLA class II alleles investigated. The frequency of HLA-DQB1*0302 was increased, while those of DQA1*0101(04), -DQA1*0401 and DRB1*0802 were decreased in melanoma patients compared with controls. Moreover, the frequency of HLA-DQA1*0103 in patients with acral lentiginous melanoma was increased compared with controls. However, none of these HLA class II alleles showed significant positive or negative associations after correction of the P value. In addition, there was no correlation between these antigens and clinical parameters. These results indicate that HLA class II alleles may not contribute to a strong susceptibility to melanoma in the Japanese.

Adult↗

Increased activity of group II phospholipase A2 in plasma in rat sodium deoxycholate induced acute pancreatitis.

BACKGROUND: Two different types of secretory phospholipase A2 (PLA2), pancreatic group I (PLA2-I) and non-pancreatic group II (PLA2-II), have been identified and postulated to be associated with the pathogenesis of various diseases, such as acute pancreatitis, septic shock, and multiple organ failure. AIMS: To investigate the type of secretory PLA2 responsible for its catalytic activity found in plasma and ascites of experimental acute pancreatitis. METHODS: Acute pancreatitis of differing severity was induced by the injection of different concentrations (1% or 10%) of sodium deoxycholate (DCA) into the common biliopancreatic duct in rats, and catalytic PLA2 activity in plasma and ascites were differentiated by anti-PLA2-I antibody and specific inhibitor of PLA2-II. Survival rate and plasma amylase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were also measured. RESULTS: In 1% and 10% DCA induced acute pancreatitis, plasma amylase values as well as PLA2 activity in ascites were greatly increased. PLA2 activity in plasma was also notably increased in 10% DCA induced acute pancreatitis, but not in 1% DCA induced acute pancreatitis. PLA2-I specific polyclonal antibody significantly inhibited PLA2 activity in ascites but not that in plasma. In contrast, plasma PLA2 activity was completely suppressed by PLA2-II specific inhibitor. In addition, a high mortality (93% at five hours) and a significant increase in plasma AST and ALT were noted in 10% DCA induced pancreatitis. CONCLUSION: Ascites PLA2 activity is mainly derived from PLA2-I, whereas plasma PLA2 activity is mostly derived from PLA2-II in severe acute pancreatitis, suggesting that increased plasma PLA2-II activity might be implicated in hepatic failure arising after severe acute pancreatitis.

Acute Disease↗

Effect of lecithinized-superoxide dismutase on the rat colitis model induced by dextran sulfate sodium.

Lecithinized-superoxide dismutase (PC-SOD), which is synthesized with a lecithin derivative bound covalently to recombinant human Cu,Zn-SOD, has a longer half-life in blood and higher cell affinity than unmodified SOD. The effects of PC-SOD were evaluated using the rat ulcerative colitis model induced by 3% dextran sulfate sodium. Intravenous injection of rats with 0.5 or 1 mg/kg of PC-SOD suppressed the progression of bloody stools, the formation of erosion, and the infiltration of the colon with inflammatory cells. Furthermore, it also reduced the increase of leukocytes in blood. Thus, PC-SOD may have therapeutic potential in the treatment of ulcerative colitis.

Animals↗

Effect of lecithinized-superoxide dismutase on the interstitial pneumonia model induced by bleomycin in mice.

Superoxide anion (O2-) acts as an exacerbation factor in interstitial pneumonia. Lecithinized-superoxide dismutase (PC-SOD), which is synthesized with a lecithin derivative bound covalently to recombinant human Cu,Zn-SOD, has a longer half-life in plasma and higher affinity to cell membranes than unmodified SOD. The effect of PC-SOD was evaluated using the bleomycin-induced interstitial pneumonia mouse model. Treatment with PC-SOD at 10 mg/kg significantly reduced the hydroxyproline content and fibrosis score. Namely, PC-SOD suppressed the progression of pulmonary fibrosis on the bleomycin-induced interstitial pneumonia mouse model. PC-SOD may be a potential drug for interstitial pneumonia therapy.

Animals↗

Effects of anodal polarization on protein kinase Cγ (PKCγ) in the rat brain.

An anodal direct current of 0.3 microA or 30.0 microA was unilaterally applied for 30 min or 3 hr to the surface of the sensorimotor cortex of rats, and the effects of anodal polarization on protein kinase C (PKCgamma) activity were examined. The brains were processed by means of immunocytochemistry using the monoclonal antibody 36G9 raised against purified PKCgamma. In sham-operated animals, PKCgamma-like-immunoreactivity (PKCgamma LI) was noted in neuronal cytoplasm, as well as in processes in the cerebral cortex and in the hippocampus. Anodal polarization with 3.0 miroA for 30 min resulted in a pronounced increase in the number of PKCgamma-like-positive neurons in accordance with the intensity of immunostaining in the cerebral cortex, and an increase in the polarized hemispheres was highlighted by repeated applications of the currents. Polarization with 0.3 microA for 3 hr also increased the PKCgamma LI, but 0.3 microA for 30 min or 30.0 microA for any duration had no effects. The effect of polarization on PKCgamma activity, as evaluated by the intensity of immunostaining and the number of neurons, began to increase 1 h after polarization, peaked at 3 hr and thereafter decreased to the control levels by 72 hr. These results indicated the involvement of the gamma-isoform of PKC in the neurochemical mechanism of long-standing central and behavioral changes induced by anodal polarization.

Animals↗

[Dermatological findings in the annual examination of the patients with Yusho in 1995-1996].

We reported the grades of severity of skin symptoms and the blood PCB patterns and concentrations in Yusho patients who had the annual examinations in 1995 and 1996. The skin severity grades and the skin severity scores showed the same tendency as recorded in the last 10 years. Yusho patients who were scored as more than 6.7 were around 8% of the total patients both in 1995 and 1996. The correlation between the blood PCB patterns and the severity grades of skin symptoms was clear. Thus, the mean skin severity scores in patients showing A pattern were higher than those in patients showing either B or C pattern. The same results were obtained when the correlation between the blood PCB patterns and the skin severity grades was analyzed. Patients whose ages were 50-70 years old were found to show the highest blood PCB concentrations and the skin severity scores.

Adult↗

Immunohistochemical localization of latent transforming growth factor-beta binding protein in IgA nephropathy.

It has been demonstrated that cultured mesangial cells (MC) express latent transforming growth factor (TGF)-beta binding protein (LTBP) mRNA, and that LTBP might be essential for the extracellular matrix (ECM) accumulation stimulated by TGF-beta in cultured MC. We performed a study to test the pathophysiological role of LTBP in mesangial ECM accumulation in human glomerulonephropathies. The expression of LTBP in 64 renal biopsies of patients with renal diseases was examined by immunohistochemical staining with the specific antibody raised against human LTBP. The biopsy specimens were divided into three groups: Group 1, IgA nephropathy; Group 2, IgA negative mesangial proliferative glomerulonephritis, which mainly consisted of diabetic nephropathy and lupus nephritis; and Group 3, non-proliferative nephropathy, which consisted of minimal change and membranous nephropathy. Immunohistochemical staining of LTBP was significantly detected in mesangial/paramesangial area of glomerulus in Group 1, but not observed in Group 2 or Group 3. The intensity of staining was well related to the grade of mesangial ECM accumulation in Group 1. These findings suggest that the LTBP-TGF-beta complex may play a pivotal role in ECM accumulation in IgA nephropathy, and that modification of LTBP-ECM interaction might provide a new therapeutic strategy against the progression of glomerulosclerosis.

Carrier Proteins↗

A case of esophagectomy for corrosive esophageal stricture caused by swallowing strong alkali. A case report.

We report herein the case of a 22-year old woman who underwent esophagectomy for corrosive esophageal stricture. This patient with mental disturbance swallowed a strong alkali in a suicide attempt and suffered from esophageal stenosis instead of steroid therapy. Because the stiffness and stricture of the esophagus proved to be refractory, transhiatal esophagectomy by blunt finger with gastroesophagostomy was performed four months after injury. Operative findings revealed severe stiffness and inflammation of the esophagus which had spread to the adjacent organs, especially the carina. As for pathological findings, most of the esophageal mucosa showed defects resulting from infiltration of inflammatory cells and capillary vascularization from the lamina propria to the extra-esophageal wall. The postoperative course was uneventful and perioperative psychological state had been stable leading to a decrease in tranquilizer dosage. This experience indicates that esophagectomy is the treatment of choice for such mental disturbed patients with severe stenosis.

Adult↗