Biomedical subjects

M Yashiro

Publications and source records attributed to M Yashiro.

At least 55 records · Page 3Linked to original sources

PubMed1998

Mesangiolytic glomerulopathy in severe congestive heart failure.

To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.

Adult↗

PubMed1998

Results of the nationwide epidemiologic survey of Kawasaki disease in 1995 and 1996 in Japan.

OBJECTIVE: The objective of the study is to describe recent epidemiologic patterns of Kawasaki disease based on information included in patient records that had been obtained through a nationwide hospital survey in Japan. METHODS: A questionnaire and diagnostic criteria for Kawasaki disease that had been approved by the Kawasaki Disease Research Committee were sent to all pediatric departments of hospitals (2638 hospitals) with a bed capacity of at least 100. The subjects all were new patients who were treated during a 2-year period from 1995 to 1996. RESULTS: A total of 12 531 children contracted the disease during the observation period. The incidence was 102.6 for 1995 and 108.0 for 1996 per 100 000 children younger than age 5 years. The male:female ratio was 1.37. The age distribution pattern showed a peak near 6 months of age. Geographic variations in the incidence suggested the existence of local outbreaks. Cardiac sequelae were seen in 12% of the patients. CONCLUSION: More than 6000 patients suffered from Kawasaki disease each year, and its annual incidence is increasing steadily. The probable existence of local outbreaks is worthy of note. Other epidemiologic patterns were unchanged from previous years.

Age Distribution↗

PubMed1998

TGF-beta1 produced by gastric cancer cells affects mesothelial cell morphology in peritoneal dissemination.

In vitro morphologic change of mesothelial cells was observed following the addition of serum-free conditioned medium (SF-CM) from peritoneal dissemination cell line OCUM-2MD3. The same morphologic change of mesothelial cells was observed following the addition of 10 ng/ml TGF-beta1, but not following the addition of b-FGF, IGF-I, VEGF or PDGF-AA. In the in vivo study, mesothelial cells of mice treated with SF-CM from OCUM-2MD3 and TGF- beta1 were separated from one another, resulting in exposure of the submesothelial connective tissue. The molecular size of the mesothelial morphology changing activity was estimated by running the SF-CM from OCUM-2MD3 through a gel filtration column TSK-gel G2000SW. The mesothelial morphology changing activity was recognized at positions equivalent of Mr 6, 500-30,000. 25 kDa TGF-beta1 was detected in the active fraction from the TSK-gel G2000SW column and the SF-CM of OCUM-2MD3 by Western blotting using a monoclonal antibody against TGF-beta1. These findings suggest that TGF-beta1 produced by gastric cancer cells changes the morphology of mesothelial cells and may thus be closely associated with peritoneal dissemination.

Animals↗

PubMed1998

Tranilast and cisplatin as an experimental combination therapy for scirrhous gastric cancer.

We examined the effect of Tranilast on the reduction of the administered dose of cisplatin using a scirrhous gastric cancer model. Scirrhous gastric cancer cell line, OCUM-2M, and gastric fibroblasts, NF-10, were used. The IC50 values of CDDP to OCUM-2M cells were decreased by Tranilast in vitro. The combination treatment with Tranilast and CDDP decreased the xenografted tumor size. The combination therapy decreased fibrosis and mitosis, and increased apoptosis. These findings suggest that Tranilast increased the CDDP response on scirrhous gastric cancer. The combination treatment with Tranilast and CDDP may be useful as a new therapy for scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗

PubMed1997

Establishment of a cisplatin-resistant gastric carcinoma cell line OCUM-2M/DDP.

A cis-diamminedichloroplatinum (CDDP)-resistant scirrhous gastric cancer cell line, OCUM-2M/DDP, was established by chronic exposure of cells of the parent scirrhous gastric cancer cell line, OCUM-2M, to CDDP at progressively increasing concentrations. The OCUM-2M/DDP cell line had an 11.3-fold higher level of resistance relative to its parent cell line as determined by a succinate dehydrogenase inhibition test. The biological and biochemical characteristics of the resistant and parent cell line were compared. There were differences in the modal chromosome number and DNA index, suggesting that some alterations of the DNA in the CDDP-resistant cells had occurred. Neither the parent nor resistant cell line expressed mdr-1 mRNA. After exposure to CDDP for 4 h, the intracellular platinum content of OCUM-2M cells was significantly higher than that of OCUM-2M/DDP cells (51.9 +/- 1.8 vs 16.4 plus 1.0 ng/mg protein, mean +/- SD, respectively). The GSH levels in OCUM-2M cells and OCUM-2M/DDP cells were 3.5 +/- 1.0 micrograms/mg protein and 16.8 +/- 1.2 micrograms/mg protein, respectively. These levels were also significantly different. These findings suggest that the possible mechanisms of acquired resistance to CDDP in OCUM-2M/DDP cells may be a decrease in intracellular CDDP accumulation and detoxication by GSH. This OCUM-2M/DDP cell line could be used in further investigations of the mechanism of CDDP resistance in gastric cancer.

Antineoplastic Agents↗

PubMed1997

Transforming growth factor-beta and hepatocyte growth factor produced by gastric fibroblasts stimulate the invasiveness of scirrhous gastric cancer cells.

Scirrhous gastric carcinoma is characterized by cancer cells that infiltrate rapidly in the stroma with extensive growth of fibroblasts. In the present study, we examined the effect of gastric fibroblasts on the invasiveness of a scirrhous gastric cancer cell line, OCUM-2D, using an invasion assay. Gastric fibroblast-derived conditioned medium (CM) significantly stimulated the invasiveness of OCUM-2D cells, as did transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF). The stimulating activity of gastric fibroblast-derived CM was inhibited significantly by anti-TGF-beta neutralizing antibody or anti-HGF neutralizing antibody. TGF-beta and HGF were detected in the gastric fibroblast-derived CM, and TGF-beta receptor and C-met (HGF receptor) were expressed on OCUM-2D cells. Thus, TGF-beta and HGF produced by gastric fibroblasts appear to affect the invasiveness of scirrhous gastric cancer cells. TGF-beta was also detected in the conditioned medium derived from OCUM-2D cells, though HGF was not. TGF-beta appears to affect the invasiveness of OCUM-2D cells in both paracrine and autocrine fashions.

Adenocarcinoma, Scirrhous↗

PubMed1997

Serum C-reactive protein levels in patients with Kawasaki disease: from the results of nation-wide surveys of Kawasaki disease in Japan.

Thirteen nation-wide epidemiological surveys of Kawasaki disease have been carried out successively since 1970 in Japan. In the latest survey, questionnaires on serum C-reactive protein (CRP) levels of the patients were included to clarify whether serum CRP levels could be available for the diagnosis and prediction of prognosis. A questionnaire from and diagnostic guidelines for Kawasaki disease were sent to all paediatric departments of hospitals with 100 or more beds throughout Japan, and information including maximal serum CRP levels was obtained on patients with Kawasaki disease diagnosed during the 2-year period from January 1993 to December 1994. Of the 11458 patients diagnosed during the 2-year period, maximal serum CRP levels were reported in 11040 patients (96.4%). The values of maximal serum CRP were higher in the age groups < 6 months and > 2 years. The mean value and the distribution of serum CRP levels in-suspected cases were lowest among the three diagnostic categories and this difference among diagnostic categories was highly significant in the age groups 6 M-1 Y and 1-2 Y. The proportion of patients with cardiac sequelae increased with serum CRP levels in each age group. The mean value and the distribution of serum CRP levels of the patients with cardiac sequelae was higher than those without it and this difference between cardiac prognoses was outstanding in the age groups 6 M-1 Y and < 6 M. The Receiver/Response Operating Characteristic (ROC) curve for maximal serum CRP levels in Kawasaki disease revealed that accuracy of maximal serum CRP levels for prediction of cardiac sequelae was highest in the age group 6 M-1 Y. A large-scale observation and analysis of serum CRP levels of the patients with Kawasaki disease revealed age-dependent relationships among maximal serum CRP levels, diagnostic categories and prognosis. Serum CRP levels may be helpful for the prediction of prognosis with the consideration of age.

Adolescent↗

PubMed1997

Leukocyte counts in patients with Kawasaki disease: from the results of nationwide surveys of Kawasaki disease in Japan.

In the latest survey of Kawasaki disease in Japan, questionnaires on maximal leukocyte counts of the patients were included to clarify whether leukocyte counts could be of value for the diagnosis and prediction of outcome. A questionnaire form and diagnostic guidelines for Kawasaki disease were sent to all pediatric departments of hospitals with > or = 100 beds throughout Japan, and information including maximal leukocyte counts was obtained on patients with Kawasaki disease diagnosed during the 2-y period from January 1993 to December 1994. Of the 11,458 patients diagnosed during the 2-y period, maximal leukocyte counts were reported in 11,062 patients (96.5%). The mean value and the distribution of maximal leukocyte counts were lower in the age group under 1 y. The mean values and the distribution of leukocyte counts were lowest in suspected cases among three diagnostic categories: typical cases of Kawasaki disease, atypical cases, and suspected cases. The mean values of maximal leukocyte counts of the patients with cardiac sequelae were significantly higher than those without cardiac sequelae in each age group. The proportion of patients with cardiac sequelae increased with leukocyte counts in each age group. The Receiver/Response Operating Characteristic (ROC) curve for maximal leukocyte counts in Kawasaki disease revealed that the accuracy of maximal leukocyte counts for prediction of cardiac sequelae was highest in the age group < 6 months, and the most accurate cut-off point was 16 x 10(9)/l. The strongest association between higher leukocyte counts (> or = 16 x 10(9)/l) and cardiac sequelae was observed in the age group < 6 M. A large-scale analysis of leukocyte counts in patients with Kawasaki disease revealed age-dependent relationship between maximal leukocyte counts, diagnostic categories and outcome. Maximal leukocyte counts may be helpful for the prediction of outcome with the consideration of age.

Analysis of Variance↗

PubMed1997

Mechanistic analogy between metal ion-catalyzed self-splicing of protein and RNA.

Recent studies have shown that RNA hydrolysis is remarkably promoted by metal ions and suitably designed metal complexes. We have found that autocleavage of dipeptides X-Ser and a tripeptide Gly-Ser-Ala is catalyzed by Zn(II) at 70 degrees C and pH 7.0. A mechanistic analogy between metal ion-catalyzed hydrolysis of peptides and RNA is suggested.

Cadmium↗

PubMed1997

Non-enzymatic hydrolyses of aryl esters of thymidine 3'-monophosphate as probes for the rate-determining step in DNA hydrolysis.

In order to shed light on the rate-limiting step in DNA hydrolysis, non-enzymatic hydrolyses of aryl esters of thymidine 3'-monophosphate have been kinetically examined. In alkaline solutions, these dinucleotide analogues were hydrolyzed far faster than was thymidylyl(3'-5')thymidine (TpT), indicating that the departure of the leaving group from the phosphorus atom is rate-limiting. The CeIV- and CeIV/PrIII combination-mediated hydrolyses of these analogues were also faster than the corresponding hydrolysis of the dinucleotide.

Cerium↗

PubMed1996

Hepatocyte growth factor (HGF) produced by peritoneal fibroblasts may affect mesothelial cell morphology and promote peritoneal dissemination.

Mesothelial cell monolayers have been reported to prevent infiltration of cancer cells into the peritoneum. We have previously reported that peritoneal fibrosis induced by gastric cancer cells prior to metastatization may provide a congenial environment for peritoneal metastases. In this study, we investigated the effects of peritoneal fibroblasts on peritoneal mesothelial cell morphology. Human gastric cancer (OCUM-2MD3), peritoneal fibroblast (NF-2P) and mesothelial (MS-1) cell lines were established in our laboratory. Histology of the peritoneum was investigated following intraperitoneal inoculation of serum-free conditioned media (SF-CM) from OCUM-2MD3 cells into nude mice. SF-CM from peritoneal fibroblasts was added to monolayer-cultured mesothelial cells, and their morphology was examined by phase-contrast microscopy. This experiment was conducted in the presence and absence of neutralizing antibodies against various factors. Mesothelial cells exposed to fibroblasts proliferation became hemispherical and separated from each other, while unexposed mesothelium remained as a flat monolayer. Cultured-mesothelial cells rounded up or exhibited a fibroblast-like shape following the addition of peritoneal fibroblast SF-CM. Anti-hepatocyte growth factor (HGF) neutralizing antibody partly inhibited this effect. We suggest that soluble factors, such as HGF, produced by peritoneal fibroblasts affect the morphology of mesothelial cells in monolayers so that the resulting environment may become prone to the peritoneal dissemination of cancer cells.

Animals↗

PubMed1996

Fibrosis in the peritoneum induced by scirrhous gastric cancer cells may act as "soil" for peritoneal dissemination.

BACKGROUND: Peritoneal metastases are one reason for the poor prognosis of scirrhous gastric cancer. However, the mechanism of peritoneal metastasis remains unclear. We therefore investigated the interaction between gastric cancer cells and peritoneal fibroblasts, in vivo and in vitro. METHODS: A human scirrhous gastric cancer cell line, OCUM-2MD3, and a human peritoneal fibroblast cell line, NF-2P, were established in our laboratory. We then investigated the effect of OCUM-2MD3 cells on the peritoneum of nude mice and on the proliferation of NF-2P cells, the effect of NF-2P cells on the migratory capability of OCUM-2MD3 cells, and the peritoneal fibrosis on the development of peritoneal metastasis. RESULTS: The proliferation of peritoneal fibroblasts was recognized in areas with and without cancer cell infiltration. Serum-free conditioned medium from the OCUM-2MD3 cells had induced peritoneal fibrosis in vivo and significantly stimulated the proliferation of NF-2P cells in vitro. The molecular weight (molecular weight ratio 25,000-43,000) of the growth factors produced by the OCUM-2MD3 cells was estimated by gel filtration high performance liquid chromatography. The migratory capability of the OCUM-2MD3 cells was significantly increased by the presence of NF-2P cells. Tumorigenicity in mice with peritoneal fibrosis was greater than in mice with normal peritoneum. CONCLUSIONS: Peritoneal fibrosis, formed by a factor secreted by scirrhous gastric cancer cells, may be congenial environment ("soil") for peritoneal metastases of scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗

PubMed1996

Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice.

We established a peritoneal-metastatic model for scirrhous gastric carcinoma. Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM-2MD3 cells in nude mice. This cell line was derived from a peritoneal-metastatic nodule at the mesenterium after orthotopic implantation of OCUM-2M cells which developed no peritoneal metastasis after intraperitoneal inoculation. The histologic findings of orthotopic-implanted tumor in the stomach show scirrhous type while those of subcutaneous-implanted tumor show medullary type. There might be factors, in OCUM-2MD3 cells, which are responsible for peritoneal metastasis. We next investigated the differences in the biological behavior of the original OCUM-2M and the derived variant OCUM-2MD3. Morphology and growth activity of the two cell lines were similar to each other. The specific chromosomes, add(6)(q13), del(7)(q21.2) and inv(11)(p13q21), were found in OCUM-2MD3 cells but not in OCUM-2M cells. While the oncogenes amplification by OCUM-2M cells was found in K-sam and c-myc, that by OCUM-2MD3 cells was found only in c-myc. The expression of E-cadherin by OCUM-2MD3 cells was decreased compared with that of OCUM-2M cells. Expression level of beta 1-integrin of OCUM-2MD3 cells were higher than that of OCUM-2M cells. The binding and invasion activity of OCUM-2MD3 cells were higher than those of OCUM-2M cells, and were decreased by anti-beta 1-integrin antibody. The invasion activity of OCUM-2MD3 cells was increased in the presence of peritoneal fibroblast. In this study, it was suggested that orthotopic implantation of cancer cells might have an effect on the acquisition of metastatic ability. beta 1-integrin and peritoneal fibroblasts might be correlated with peritoneal metastasis. This peritoneal-metastatic model should be useful for analysing the mechanism of peritoneal metastasis of human scirrhous gastric cancer.

Adenocarcinoma, Scirrhous↗

PubMed1996

[Evaluation of a nationwide surveillance system for Kawasaki disease over an eleven-year period from 1984].

OBJECTIVE: The Japan Kawasaki Disease Research Committee has conducted a surveillance of Kawasaki disease in order to monitor changes in incidence continually, and to provide timely incidence data to the hospitals and related organizations. This study aims at clarifying the 11-year time trend between 1984 and 1995 of the incidence of Kawasaki disease in Japan and evaluating the validity of the surveillance system. METHODS: Incidence data were obtained from 143 monitor hospitals throughout Japan with a postcard notification form, which included the number of patients with Kawasaki disease by sex for each of three 10-day periods every month. RESULTS: 1. The total number of patients thus reported in the 11-year period by the 143 facilities was 21,406. 2. After experiencing the two major outbreaks observed in 1984 and 1985, no abnormal increase has been seen for a least 8 1/2 years. 3. The changes in the time trend of the incidence from the surveillance data was almost identical to those of the nationwide surveys, indicating the high validity of the surveillance system for timely estimation of an abnormal increase in incidence. 4. Because about one-third of the total number of the patients reported by the nationwide surveys come from only about 9% of the total number of hospitals included in the nationwide survey, efficiency in data collection without serious distortion was confirmed for the surveillance system. 5. The estimated number of patients in 1993 and 1994 calculated from the ratio of the numbers of patients between the surveillance and nationwide surveys was 5700 in 1993 and 6000 in 1994. The average yearly incidence rates per 100,000 children aged 0-4 years was 90. CONCLUSION: From the above results it is recommended that the surveillance system be continued in order to provide timely data on changes in the incidence of Kawasaki disease in Japan. It appears that the methods of data collection adopted in this system is applicable to the surveillance of other diseases.

Female↗

PubMed1996

Differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts.

Scirrhous gastric cancer cells proliferate rapidly with fibrosis, when the cancer cells invade into the submucosa of the stomach. To investigate the mechanisms responsible for the rapid proliferation, the growth interaction between gastric cancer cells and fibroblasts was examined. Human gastric cancer cell lines established from scirrhous carcinoma or well-differentiated adenocarcinoma were used. Human fibroblast cell lines were obtained from various organs. The growth interaction between gastric cancer cells and fibroblasts was examined by calculating the number of cancer cells or by measuring [3H]thymidine incorporation of cancer cells. Gastric fibroblasts specifically stimulated the growth of scirrhous gastric cancer cells, but not that of well-differentiated adenocarcinoma cells. The growth factor(s) produced from gastric fibroblasts were then partially purified and characterised. The growth-promoting factor(s) had apparent molecular weights of 10000 dalton and was sensitive both to heat and proteinase treatment. No inhibition for the factor(s) was achieved with defined anti-growth factor antibodies. In this study, differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts were shown. Rapid proliferation of scirrhous gastric carcinoma should be partly controlled by orthotopic fibroblasts. The growth factor(s) from gastric fibroblasts, which was distinct from various defined growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (b-FGF), transforming growth factor-alpha (TGF-alpha), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-I), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and transforming growth factor beta 1 (TGF-beta 1) may play an important role in the progression of scirrhous gastric cancer cells.

Adenocarcinoma, Scirrhous↗

PubMed1996

Role of alpha 2 beta 1- and alpha 3 beta 1-integrin in the peritoneal implantation of scirrhous gastric carcinoma.

We established a highly peritoneal-seeding cell line, OCUM-2MD3, from a poorly peritoneal-seeding cell line, OCUM-2M, of human scirrhous gastric carcinoma. The intraperitoneal inoculation of OCUM-2MD3 cells produced peritoneal dissemination in nude mice, whereas that of OCUM-2M cells did not. We then investigated the correlation between seeding potential and adhesion molecule beta 1-integrins or alpha 6 beta 4-integrin. alpha 2 beta 1- and alpha 3 beta 1-integrin expression on OCUM-2MD3 cells (91.6% and 93.6%) was increased compared with that of OCUM-2M cells (47.8% and 34.3%) by flow cytometric analysis, and the expression level of the other integrins was not different between the two cell lines. The binding ability of OCUM-2MD3 cells to matrigel, fibronectin, laminin and type I collagen was significantly increased, approximately seven times, three times, eight times, and three times greater than that of OCUM-2M cells respectively. The invasiveness of OCUM-2MD3 cells was also significantly increased 8-fold over OCUM-2M cells. The binding and invasive ability of OCUM-2MD3 cells was significantly decreased following the addition of anti-alpha 2 beta 1- and alpha 3 beta 1-integrin antibody, but not by anti-alpha 6 beta 1- and alpha 6 beta 4-integrin antibody. These results suggest that adhesiveness and invasiveness in peritoneal implantation of scirrhous gastric carcinoma might be closely associated with alpha 2 beta 1- and alpha 3 beta 1-integrin.

Adenocarcinoma, Scirrhous↗

PubMed1996

Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice.

To investigate the relationship between high serum levels of IgA and glomerular lesions, selective mating was performed in high serum IgA ddY mice, a murine model of spontaneously developing mesangioproliferative glomerulonephritis mimicking human IgA nephropathy. The selection and mating of high IgA ddY mice were accomplished when the mice were three to four months old. In the 12th generation of high IgA ddY (HIGA) mice, significantly higher levels of serum IgA from 10 age weeks to 60 weeks (P < 0.0002 to 0.0001) were observed in comparison with BALB/c mice. Relatively high proteinuria was observed at 40 weeks of age, although hematuria was consistently negative. Microscopic observations of renal tissue disclosed a marked glomerular mesangial matrix increase and a reduction of cell proliferation with age by both semiquantitative and morphometric analyses with moderate tubulointerstitial damage. These mesangial matrices were stained markedly by antisera for collagen type IV and by fibronectin, but not by collagen type I. Localization of TGF-beta protein was also detected in the mesangium of the HIGA mice. The positive mesangial IgA deposition was maintained consistently by this mating procedure and became more marked with age. Size analysis of IgA from ten pooled HIGA mice aged 50 to 60 weeks revealed dominant polymeric IgA in sera and dimeric IgA in glomerular eluates. Clonal analysis of serum IgA disclosed heterogeneous spectrotypes in a wide pH range (4.5 to 6.5), in contrast to very limited spectrotypes in the acidic pH range (4.5 to 5.2) of IgA in the glomerular eluates from these mice. The analyses of retroviral gp70 antigen involvement in the HIGA mice disclosed a significant increase of serum levels of gp70 anti-gp70 immune complexes with age, with no relationship to the severity of glomerular gp70 deposition. Northern blot analysis of renal tissue revealed markedly high mRNA expression of collagen type I, IV, fibronectin and TGF-beta even in 10-week-old HIGA mice in comparison with BALB/c mice. The expression became more significant in 60-week-old animals. The genetic background required to induce the expansion of IgA-producing B-cell clones is suggested to be closely related to the increased gene expression of TGF-beta, which induces enhanced glomerular extracellular matrix (especially fibronectin) accumulation in HIGA mice, being possibly mediated by the mesangial deposition of dimeric and highly acidic IgA. This newly established strain may provide a model for investigating the relationship between progressive glomerular sclerotic lesions and the induction of pathogenic IgA in human IgA nephropathy.

Aging↗

PubMed1996

Dinuclear lanthanum(III) complex for efficient hydrolysis of RNA.

A dinuclear La3+ complex hydrolyzes the phosphodiester bond in diribonucleotides efficiently under mild conditions. The rate of hydrolysis is remarkably accelerated on the complex formation between La3+ and TPHP (TPHP = N,N,N',N'-tetrakis [(2-pyridyl)methyl]-2-hydroxy-1,3-diaminopropane), and the highest activity is attained when the dinuclear structure is formed. The half-life of ApA hydrolysis by the dinuclear La3+ complex (1 mM) is 350 s, whereas that by the free La3+ ion (1 mM) is 23,000 s at pH 7.2 and 50 degrees C. The dinuclear La3+ complex is promising as a catalytic center of artificial nucleases.

Binding Sites↗