[Intestinal complications of collagen vascular diseases].
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Collagen Diseases↗
Biomedical subjects
Y Tsukada
Publications and source records attributed to Y Tsukada.
Combined treatment with cyclophosphamide and prednisolone can induce remission of nephrotic syndrome in a patient with renal amyloidosis, associated with rheumatoid arthritis.
A 67-year-old woman, who had been diagnosed with classical rheumatoid arthritis (RA), was admitted to our hospital because of massive proteinuria. Biopsy of the kidney revealed deposition of amyloid fibrils in the subepithelial and subendothelial spaces of the glomerular capillary walls. Though the treatment with prednisolone and dipyridamole against nephrotic syndrome and amyloidosis due to RA was not effective, cyclophosphamide, which was added after tapering of prednisolone, was able to induce remission of nephrotic syndrome after two years. The levels of CRP and serum amyloid A protein (SAA) returned to within the normal limits. As the impairment of renal function is thought to be due to deposition of amyloid supplied from the precursors of amyloid fibrils filtered from the general circulation in RA patients, remission of nephrotic syndrome might result from the suppression of production of SAA or removal of amyloid fibrils. Cyclophosphamide, which has the potential both to suppress disease activity in RA and to produce degradation of amyloid fibrils in glomeruli, may be useful against renal or systemic amyloidosis complicated by RA.
Aged↗
Membranous nephropathy associated with psoriasis vulgaris.
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Autoimmune Diseases↗
Henoch-Schönlein purpura in rheumatoid arthritis.
This is the first report of Henoch-Schönlein purpura associated with permanent joint damage due to rheumatoid arthritis, which was observed in 3 of the 10 adults we treated for Henoch-Schönlein purpura since 1974. Each of 3 women had been admitted with palpable purpura of the lower extremities. The diagnosis was based on various findings including arthralgia, stiffness, and/or swelling of the joints, and on the results of radiographic, immunofluorescence and other studies. Renal biopsy revealed slight mesangial proliferation in 2 of the patients. The nephropathy did not deteriorate following discharge. However, bilateral swelling of the wrists with destructive joint changes was subsequently observed on radiographs in all patients. Since 2 patients showed positivity for human leukocyte antigen DR4, this antigen may have been a genetic factor in the joint disease in these patients.
Adult↗
Bovine serum albumin-doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma.
A bovine serum albumin-conjugated doxorubicin via the glutaraldehyde bridge (BSA-DXR conjugate) showed potent dose-dependent inhibition of cell growth against daunorubicin-resistant AH66 (AH66DR) cells as well as parental AH66 (AH66P) cells in vitro as compared to treatment with DXR or BSA-glutaraldehyde conjugate without DXR (BSA-GA). In the culture of AH66DR with BSA-DXR conjugate, drug accumulation in the AH66DR cells increased as a function of time up to 24 h reaching approximately the same drug level as AH66P cells treated with DXR. The intracellular accumulation of the BSA-DXR conjugate was inhibited by the addition of ammonium chloride, while that of DXR alone was not inhibited. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate or pharmacologically active DXR adduct remained in the cells at a relatively high concentration over a 36-h time period. The life-prolonging effect of the conjugate was assessed using rats inoculated i.p. with AH66P or AH66DR. The rats were treated with the BSA-DXR conjugate, DXR, a mixture of DXR with BSA, or BSA-GA by either the i.p. or i.v. route. Treatment with DXR had no significant surviving effect as compared to that with saline in AH66P-bearing rats. By contrast, BSA-DXR conjugate showed a significant life-prolonging effect as compared with DXR alone in the same degree both in AH66P- and AH66DR-bearing rats. BSA-GA did not show any toxicity in vivo as well as in vitro. These results indicate that the BSA-DXR conjugate allows DXR to escape from the multidrug resistance mechanism.
Animals↗
A synthetic approach to polysialogangliosides containing alpha-sialyl-(2-->8)-sialic acid: total synthesis of ganglioside GD3.
A stereocontrolled, facile total synthesis of ganglioside GD3 is described as an example of a proposed systematic approach to the preparation of gangliosides containing an alpha-sialyl-(2-->8)-sialic acid unit alpha-glycosidically linked to O-3 of a D-galactose residue in their oligosaccharide chains. Glycosylation of 2-(trimethylsilyl)ethyl 6-O-benzoyl-, 3-O-benzoyl-, or 3-O-benzyl-beta-D-galactopyrano-sides, or 2-(trimethylsilyl)ethyl 2,3,6,2',6'-penta-O-benzyl-beta-lactoside (7), with methyl [phenyl 5- acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D- glycero-alpha-D-galacto-2-nonulopyranosylono-1',9 lactone)- 4,7-di-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyrano sid] onate (3), using N-iodosuccinimide-trifluoromethanesulfonic acid as a promoter, gave the corresponding alpha glycosides 8 (32%), 13 (33%), 14 (48%), and 17 (31%), respectively. The glycosyl donor 3 was prepared from O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosy lonic acid)-(2-->8)-5-acetamido-3,5- dideoxy-D-glycero-D-galacto-2-nonulopyranosonic acid by treatment with Amberlite IR-120 (H+) in methanol, O-acetylation, and subsequent replacement of the anomeric acetoxy group with phenylthio. Compound 8 was converted into the methyl beta-thioglycoside via O-benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group by reaction with methylthiotrimethylsilane. Compound 17 was converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the alpha-trichloroacetimidate, which was coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol to give the beta-glycoside. This glycoside was easily transformed, via selective reduction of the azido group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester and lactone functions, into ganglioside GD3.
Carbohydrate Sequence↗
Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. A report of the Gilda Radner Familial Ovarian Cancer Registry.
BACKGROUND: According to previous reports, primary peritoneal carcinoma indistinguishable from primary ovarian adenocarcinoma had developed in five women with a history of familial ovarian cancer who had undergone prophylactic oophorectomy. METHODS: The records from the Gilda Radner Familial Ovarian Cancer Registry were reviewed for instances of prophylactic oophorectomy and cases of primary peritoneal carcinoma occurring after prophylactic oophorectomy. RESULTS: From 1981 through July 1992, the Gilda Radner Familial Ovarian Cancer Registry accessioned 931 families (a total of 2221 cases of familial ovarian cancer). Currently, 324 women in these families have undergone prophylactic oophorectomy as a preventive measure against the subsequent development of ovarian cancer. Primary peritoneal carcinoma indistinguishable histologically from primary ovarian adenocarcinoma has developed in six of these women 1-27 years after prophylactic oophorectomy. CONCLUSIONS: Based on this finding and other reports of such primary peritoneal carcinoma, a prospective international study is planned. This study will compare the incidence of peritoneal carcinoma in first- or second-degree relatives who underwent prophylactic oophorectomy because of a family history of ovarian cancer with that of those who did not undergo prophylactic oophorectomy.
Adenocarcinoma↗
Familial ovarian cancer. A report of 658 families from the Gilda Radner Familial Ovarian Cancer Registry 1981-1991.
BACKGROUND: Because of the small number of cases (five) reported between 1929 and 1969 and a significant increase reported in the decade of the 1970s, the Familial Ovarian Cancer Registry was established in 1981 to study the occurrence of familial ovarian cancer in the United States. METHODS: Any woman (with or without ovarian cancer herself) who contacted the Registry and demonstrated a familial history of ovarian cancer was added to the Registry as an index case. RESULTS: From 1981 through May 31, 1991, 658 families for a total of 1568 cases of familial ovarian cancer were accessioned into the Registry. Of the 219 mothers and 251 daughters with familial ovarian cancer, the mean (58.5 years) and median (57.0 years) age at diagnosis of the mothers was significantly older than the mean (49.8 years) and median (49.0 years) ages of their daughters with ovarian cancer. Significantly more index cases without ovarian cancer had used oral contraceptives as compared to index cases with ovarian cancer (P < 0.001). Significantly more index cases with ovarian cancer used other estrogens as compared to index cases without ovarian cancer (P < 0.001). The Registry cases exhibited a higher proportion of serous adenocarcinoma, poorly differentiated adenocarcinoma, borderline carcinoma, and gonadoblastoma as compared to the 1978 SEER data. Mother and a minimum of one daughter was the most common relationship and was represented in 49.5% of the families with familial ovarian cancer. Sister-sister relationships were the second most frequent and accounted for 38.5% of the 658 families. CONCLUSIONS: Familial ovarian cancer occurs most frequently in mother-daughter relationships followed by sister-sister and appears to be an autosomal dominant inheritance with variable penetrance.
Adult↗
Molecular cloning of the kainate-binding protein and calmodulin genes which are induced by an imprinting stimulus in ducklings.
For the formation of imprinting in birds, protein synthesis is known to be essential in the medial hyperstriatum ventrale (MHV) of the forebrain after presentation of an imprinting stimulus. We have searched for the genes whose expressions are increased in duckling's MHV during formation of imprinting, and identified kainate-binding protein and calmodulin genes. This may reflect the formation of glutamatergic pathways in MHV.
Amino Acid Sequence↗
Chemotherapeutic efficacy of the protein-doxorubicin conjugates on multidrug resistant rat hepatoma cell line in vitro.
In vitro studies were initiated to study the antitumour effect of protein-doxorubicin (DXR) conjugate on the growth of the multidrug resistant rat ascites hepatoma cell line, AH66DR. The 50% inhibitory concentration (IC50) for DXR in AH66DR cell line was 16 mumol l-1 (AH66 parental cell line, AH66P, IC50 was 0.08 mumol l-1). Treatment of AH66P and AH66DR cells with various concentrations of DXR or conjugates at equivalent concentrations of DXR was performed. The two types of conjugates used were bovine serum albumin (BSA)-DXR conjugate and immunoglobulin G (IgG)-DXR conjugate. Both of these conjugates showed potent dose-dependent inhibition of cell growth against AH66DR cells as compared with the cells treated with DXR or other controls. The IC50 for BSA-DXR and IgG-DXR conjugates in AH66DR cell line was 0.05 (equivalent DXR) mumol l-1 and 0.07 (equivalent DXR) mumol l-1, respectively. These values were similar to that of the AH66P treated with DXR. Cellular uptake and accumulation of DXR or BSA-DXR conjugate was also quantitated in both cell lines. The cellular concentration of DXR in AH66DR cells was 2-fold lower than that of AH66P cells throughout the experiment. In contrast, by the treatment of AH66DR cells with BSA-DXR conjugate, the intracellular drug concentration increased as a function of time up to 24 h (639.1 +/- 41.8, equivalent DXR, ng 10(-5) cells) and reached the same drug level as AH66P cells treated with DXR (617.9 +/- 17.3 ng-5 cells). Ammonium chloride treatment inhibited the effects of the conjugates but did not inhibit the free drugs. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate remained in the cells at relatively high concentration for a long time. These results indicate that by chemically modifying DXR, such as by conjugation of the drug with proteins, it may be possible to overcome multidrug resistance.
Animals↗
[ADH 2, 3 and ALDH 2 gene frequency in Japanese alcoholics].
To elucidate genetic susceptibility to alcoholic liver injury (ALD), polymerase chain reaction (PCR) method assay was developed to detect point mutations in each gene and gene frequency in various liver diseases was studied. It was shown previously that ALDH2(1) gene was more frequently found in patients with ALD (confirmed in this study), probably because they are able to consume too much alcohol (non-flushing type). This study revealed that, in addition to this ALDH heterogeneity, ADH heterogeneity may correlate with the severity of alcoholic liver injury, especially in those was low ADH activity and tend to have severe damage.
Alcohol Dehydrogenase↗
Urine glycosaminoglycans and heparan sulfate excretions in adult patients with glomerular diseases.
We measured the concentrations of urine glycosaminoglycans (GAG) by the modified dimethylmethylene blue method and the concentration of urine heparan sulfate (HS) by enzyme-linked immunosorbent assay (ELISA) in patients with various glomerular diseases. The GAG/creatinine(Crea) ratios in patients with IgA nephropathy (mean +/- SD, 0.31 +/- 0.056) and membranous nephropathy (0.41 +/- 0.115) were significantly greater than in healthy controls (0.18 +/- 0.045). Urine GAG/Crea ratios in minimal change nephrotic patients increased during remission (0.38 +/- 0.102) and decreased to normal values during the nephrotic stage (0.25 +/- 0.088). In contrast, urine HS/Crea ratios in patients with minimal change nephrotic syndrome decreased during remission (0.0069 +/- 0.0029) and increased markedly during the nephrotic period (0.047 +/- 0.0007 versus controls 0.0158 +/- 0.0046). Serial measurement in three minimal change nephrotic patients showed the similar change for the HS/Crea ratio and urine albumin excretion in the course of steroid therapy. The loss of HS from the glomerular basement membrane (GBM) may therefore be related to the pathogenesis of increased albumin excretion and measurement of urine HS excretion may be helpful for studying metabolism in renal disease, especially in patients with minimal change lesions.
Adult↗
PAF acetylhydrolase activities in human systemic lupus erythematosus and lupus-prone mice.
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1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Determination of nucleotide sequence of active site for catalytic properties of ADH3 genes.
Alcohol dehydrogenase genes show polymorphism. gamma subunits, which are encoded by ADH3 genes, have two subtypes according to the single base substitution of codon 271 and 349. This mutation of codon 271 directly determines subtypes with different catalytic properties. However, there has been no simple technique to detect nucleotide changes at codon 271. Specific amplification of nucleotides around codon 271 was difficult because of homologous nucleotide sequences around the region among 3 ADH genes (ADH1, 2 and 3). We have developed a method to amplify the ADH3 gene alone with a modification on 3'-end of primer by polymerase chain reaction. Approximately 200 nucleotides including codon 271 of ADH3 gene were sequenced, and genotypes of ADH3 gene were determined in 30 Japanese individuals. This method may facilitate the studies on racial differences of genotypes and involvement of ADH genes in patients with alcoholic liver disease.
Alcohol Dehydrogenase↗
Plasma platelet-derived growth factor levels in coronary circulation in unstable angina pectoris.
To examine whether plasma platelet-derived growth factor (PDGF) levels are elevated in the coronary circulation of patients with unstable angina, the plasma PDGF levels in the coronary sinus and aortic root were simultaneously examined in 14 patients with unstable angina, 15 with stable exertional angina, and 15 control subjects. The mean plasma PDGF level (pg/ml) in the coronary sinus was significantly higher (p less than 0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (502.1 +/- 98.7 vs 301.3 +/- 62.5, and 312.7 +/- 62.6). However, there were no significant differences in mean plasma PDGF levels in the aortic root among the 3 groups. It is concluded that PDGF release is increased in the coronary circulation in patients with unstable angina.
Aged↗
Elevation of platelet-associated IgG in aplastic anemia.
We determined platelet-associated IgG (PAIgG) levels in patients with aplastic anemia, idiopathic thrombocytopenic purpura (ITP), iron deficiency anemia, and systemic lupus erythematosus (SLE), as well as in normal healthy adults as a control group. To determine PAIgG levels, we used a competitive micro enzyme-linked immunosorbent assay, which had excellent reproducibility, recovery, and dilution. We confirmed its reliability by comparing it to the immunoradiometric assay. Both the aplastic anemia group (n = 27, mean +/- SD = 218.6 +/- 244.6 ng/10(7) platelets) and the ITP group (n = 82, mean +/- SD = 212.5 +/- 327.8 ng/10(7) platelets) had higher PAIgG levels than the SLE group (n = 4, mean +/- SD = 38.4 +/- 22.4 ng/10(7) platelets), iron deficiency anemia group (n = 10, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets), and normal control group (n = 69, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets. The higher platelet-associated IgG levels in aplastic anemia suggest that autoimmune mechanisms are involved.
Adolescent↗
Growth of a human yolk sac tumor cell line with yolk sac-derived functions in selenium-supplemented chemically defined synthetic medium.
A human yolk sac tumor cell line, TG1, which was established from a testicular yolk sac tumor, was found to replicate continuously in a chemically defined medium supplemented with Na2SeO3 (ISRPMI). TG1 produced several plasma proteins and growth factors: albumin, alpha-fetoprotein (AFP), ferritin, carcinoembryonic antigen, beta-2-microglobulin, polyamine, neuron specific enolase, tissue polypeptide antigen, transferrin (Tf), epidermal growth factor, and platelet derived growth factor. By analysis of lentil lectin (LcHA)-affinity electrophoresis, to examine the microheterogeneity of carbohydrate chains of synthetic glycoproteins, TG1 cells cultured with ISRPMI produced only LcHA reactive Tf and AFP based on core fucose attached to asparagine-linked N-acetylglucosamine residues instead of LcHA-nonreactive Tf and AFP produced by TG1 cells cultured with fetal bovine serum (FBS)-containing medium. alpha 1-6 Fucosyltransferase activity was significantly greater in the TG1 cells cultured with ISRPMI (39.9 +/- 1.5 pmol.h-1.mg-1 protein) than cultured with FBS-containing media (18.2 +/- 1.2 pmol.h-1.mg-1 protein). These results have indicated that the selective increase of alpha 1-6 fucosyltransferase occurred when the cells were cultured with the FBS-free synthetic media.
Carcinoembryonic Antigen↗
Production of chromogranin A and B derived peptides in human small cell lung carcinoma cell lines.
Production of chromogranin (Cg)A and B derived peptides [pancreastatin (PST), GAWK, CCB] was studied using human lung carcinoma derived cell lines. PST-like immunoreactivity (LI) was detected in the culture medium in 3 of 6 small cell lung carcinoma (SCLC) cell lines, while GAWK- and CCB-LIs were detected in 5 of 6 and all the 6 SCLC cell lines, respectively. CCB-LI was produced in large amounts in SCLC cell lines as compared to PST- and GAWK-LIs. In non-SCLC cell lines, on the other hand, PST- and GAWK-LIs were not detected. CCB-LI was detected in 1 of 7 non-SCLC cell lines, but not detected in the remainder. PST, GAWK and CCB-LIs, secreted by these cell lines, consisted of several peaks, and these peaks were different among cell lines. This suggests that processing of CgA and B is different in the cell lines. Production of CgA and B derived peptides seems to be a characteristic feature of SCLC, and among them, CCB LI may be a useful marker for SCLC.
Carcinoma, Small Cell↗