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Biomedical subjects

S Eto

Publications and source records attributed to S Eto.

At least 91 records · Page 5Linked to original sources
PubMed1995

Biochemical analysis of ferritin subunits in sera from adult Still's disease patients.

To determine the origin of the increased serum ferritin that occurs in adult Still's disease (ASD), we analyzed subunits of the serum ferritin as follows. Gel filtration with Sepharose CL-6B demonstrated that the molecular weight of serum ferritin was about 490 kDa. Western blot analysis revealed only L-subunits (molecular weight 19 kDa) in patients with serum ferritin levels higher than 1,000 ng/ml. Patients with serum ferritin levels higher than 1,000 ng/ml, however, showed G-subunits (molecular weight 23 kDa) in addition to the L-subunits. When concanavalin A (Con-A) Sepharose 4B was used in an absorption test, the percentage absorption was extremely low in the patients with serum ferritin levels higher than 1,000 ng/ml. Isoferritin patterns of the patients determined by chromatofocusing revealed traces of acidic ferritin. The findings suggested that glycosylated ferritin does not account for the major portion of the increased serum ferritin.

Adult↗
PubMed1995

Stimulatory effect of interleukin-1 alpha on proliferation through a Ca2+/calmodulin-dependent pathway of a human thyroid carcinoma cell line, NIM 1.

NIM 1 cells, a human thyroid cell line established from a patient with thyroid papillary adenocarcinoma, produce cytokines such as interleukin-1 alpha (IL-1 alpha) and granulocyte-colony stimulating factor. In the present study, we investigated the signal transduction pathway in the proliferation of NIM 1 cells evoked by IL-1 alpha. Incubation of NIM 1 cells with IL-1 alpha for 48 h increased the incorporation of 3H-thymidine (3H-TdR). The stimulatory effect of IL-1 alpha was evident at 0.01 ng/ml and the maximal effect was seen at 10 ng/ml. IL-1 alpha evoked an influx of 45Ca into NIM 1 cells within 3 min in a concentration-dependent manner (0.01-1 ng/ml). These stimulatory effects of IL-1 alpha on both 3H-TdR incorporation and 45Ca influx were similarly inhibited by nicardipine, an inhibitor of voltage-dependent Ca2+ channels, in a concentration-dependent manner (10-1000 nM). The stimulatory effect of IL-1 alpha on 3H-TdR incorporation was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), an antagonist of calmodulin, but not by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C. While the culture medium initially contained 0.75 mM Ca2+, inhibition of 3H-TdR incorporation by nicardipine and W-7 under these baseline conditions was also recognized. These results suggest that IL-1 alpha stimulates cell proliferation through a Ca2+/calmodulin-dependent pathway in NIM 1 cells.

Biological Transport↗
PubMed1995

Acute rheumatic fever and poststreptococcal acute glomerulonephritis caused by T serotype 12 Streptococcus.

We present a rare case of a 10 year old Japanese boy with acute rheumatic fever accompanied with poststreptococcal acute glomerulonephritis. We isolated group A Streptococcus serotype T 12, a strain that was thought to be nephritogenic but not rheumatogenic, from throat culture. Although rare, physicians should be aware that acute renal disease may accompany rheumatic fever.

Acute Disease↗
PubMed1995

Interleukin-4 inhibits the production of interleukin-1 by adult T-cell leukemia cells.

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) produce high levels of interleukin-1 (IL-1), which is believed to play an important role in neutrophilia, elevation of C-reactive protein, osteolytic bone lesions, hypercalcemia, and fever in ATL. However, relatively little is known regarding the regulatory mechanism of IL-1 production in ATL. Interleukin-4 (IL-4) affects the monocytes- and neoplastic cells-mediated cytokine production. In this study, we investigated the effect of IL-4 on IL-1 alpha and IL-1 beta production by ATL cells in vitro. IL-4 was found to markedly inhibit the release of IL-1 alpha and IL-1 beta into the conditioned medium in a dose-dependent manner. Northern blot analysis of steady-state IL-1 mRNA demonstrated that IL-4 treatment of ATL cells resulted in a reduction of IL-1 mRNA. These results support the notion that ATL cells spontaneously produce IL-1 alpha and IL-1 beta; however, such production can be inhibited by the immunomodulating agent, IL-4. IL-4 may play an important regulatory role in the production of IL-1 in ATL.

Aged↗
PubMed1995

Detection of sarcoma virus family tyrosine kinase activity in coronary arterial tissue.

We have observed that the tyrosine kinase inhibitors genistein and tyrphostin can selectively block angiotensin II mediated and vasopressin-mediated contractions in porcine coronary arterial strips, without affecting the action of acetylcholine. Therefore, we assessed the presence of tyrosine kinase activity in the porcine coronary artery tissue, using an assay specific for sarcoma virus (src) related tyrosine kinases. In both membrane and cytosolic fractions of porcine coronary artery, we detected src-related tyrosine kinase activity that could be inhibited by both genistein and tyrphostin. The tyrosine kinase activity in membrane extracts was separated into two peaks by sequential chromatography on hydroxylapatite and Mono-Q columns. Protein in both peaks exhibited Western blot cross-reactivity with anti-src antibodies and contained tyrosine kinase activity that was inhibited by genistein and tyrphostin. We conclude that porcine coronary artery tissue contains src-related tyrosine kinase activity. However, because of the comparatively low sensitivity of the isolated src kinase activity towards genistein and tyrphostin, compared with the much higher sensitivity of the contractile response to these inhibitors, a direct role for c-rsc in the regulation of contractions elicited by agonists such as angiotensin II and arginine vasopressin cannot yet be assigned.

Amino Acid Sequence↗
PubMed1995

Determination and properties of acetyl conjugate of N-desisopropylpropranolol, AcNDP.

1-Acetamino-3-(1-naphthyloxy)-2-propanol (AcNDP) detected in human urine was formed as a metabolite of propranolol (PL) via 1-amino-3-(L-naphthyloxy)-2-propanol (N-desisopropylpropranolol, NDP). The excreted amount of AcNDP was determined by GC-MS using an isotope dilution method. More than 40% of total AcNDP in 24 h urine was detected 10 h after the oral administration of PL to two volunteers, and the total amounts during 24 h urine were at least 1.9-3.9% of the PL dose. As AcNDP is an intermediate metabolite of PL, its urinary amount cannot be determined exactly. Incidentally, AcNDP was chemically stable and was not formed from NDP when acetyl CoA was added to the inactivated hepatocyte system. Thus, the acetylation of NDP, an aliphatic primary amine, was confirmed to be catalyzed by N-acetyltransferase, and interestingly, the acetyl conjugation was inhibited not by sulfamethazine but by p-amino benzoic acid.

Acetamides↗
PubMed1995

9-Hydroxymethyl-10-carbamoylacridan in human serum is one of the major metabolites of carbamazepine.

In sera of 29 patients under the chronic administration of carbamazepine (CBZ, dose: 10.9 +/- 4.3 mg/kg/day), a ring-contracted metabolite of CBZ was detected at a relatively higher concentration of 0.57 +/- 0.30 mu g/ml (mean +/- S.D.) by high-performance liquid chromatogaphic assay. The structure of the metabolite was identified as 9-hydroxymethyl-10-carbamoylacridan (HMCA) by the liquid chromatography-mass spectral examination, and also by comparison with the authentic sample. Although HMCA was already reported in a few papers as a minor metabolite of CBZ in human urine, any reliable report for the determination of HMCA in human blood has never been published. Our results show that HMCA is one of the major metabolites of CBZ.

Acridines↗
PubMed1995

Autopsy findings of Addison's disease caused by systemic cytomegalovirus infection in a patient with acquired immunodeficiency syndrome.

We previously reported a case of Addison's disease associated with acquired immunodeficiency syndrome (AIDS) (Endocr J, 41:13, 1994). A 46-year-old man with hemophilia B and AIDS was diagnosed as Addison's disease. The positive cytomegalovirus (CMV) antigen in urine suggested that CMV adrenalitis may have caused the adrenal insufficiency. Despite treatment with ganciclovir, the patient died one year later. Autopsy findings revealed that the typical inclusions of CMV were seen in the lung, adrenal glands (both cortex and medulla) and small intestine. Here, we describe the subsequent clinical course and postmortem findings of this case.

AIDS-Related Opportunistic Infections↗
PubMed1995

Sjögren's syndrome terminating with multiple myeloma.

We describe a patient (49 years old, female) with a more than 7-year history of both Sjögren's syndrome (SjS) and benign monoclonal gammopathy (BMG) of IgG lambda who later developed multiple myeloma (MM). SjS is frequently complicated with malignant lymphoproliferative disorders, especially malignant lymphoma or Waldenström's macroglobulinemia. Association of SjS with MM seems to be extremely rare, although BMG has been observed frequently in SjS, and there are many reports concerning the association between rheumatoid arthritis and MM.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Germ line mutation in the RET proto-oncogene associated with familial multiple endocrine neoplasia type 2B: a case report.

Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome. MEN 2B is characterized by the combined occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuroma and Marfanoid habitus. Recently, a missense mutation in codon 918 of the proto-RET has been reported in the germ line of apparently distinct families with MEN 2B. In the present paper we first show a familial case of MEN 2B in Japan also to be associated with a germ line mutation in codon 918 of the proto-RET. The mutation was the substitution of a threonine for a methionine in the tyrosine kinase domain of the protein. The germ-like mutations of the proto-RET in MEN 2A and MEN 2B are the first examples of a dominantly acting oncogenic point mutation initiating human hereditary neoplasia.

Adrenal Gland Neoplasms↗
PubMed1995

Human T-cell leukemia virus type I tax transactivates the interleukin-6 gene in human rheumatoid synovial cells.

OBJECTIVE: To determine the effect of the human T cell leukemia virus type I (HTLV-I) tax gene on interleukin-6 (IL-6) production and gene transcription in synovial cells, we established the synovial cell line, E-11, from a patient with rheumatoid arthritis. METHODS: E-11 cells were transfected with tax expression vector using the calcium phosphate coprecipitation method. IL-6 production and gene expression were investigated by ELISA and Northern blot analysis, respectively. To clarify how tax induces IL-6 gene expression, we used deletion analysis and chloramphenicol acetyltransferase (CAT) assay, and electrophoretic mobility shift assay (EMSA). RESULTS: Transfection of the tax gene induced markedly high levels of IL-6 mRNA. Furthermore, the tax gene strongly transactivated IL-6 gene promoter activity assayed by CAT assay. By using deletion and site specific mutations, we have identified a nuclear factor (NF)-kappa B sequence (positions -73 to -63) which is essential for tax transaction. EMSA demonstrated the induction of specific binding of nuclear extracts to the NF-kappa B sequence by HTLV-I tax. CONCLUSION: The HTLV-1 tax gene may transactivate IL-6 gene in the synovial cells through NF-kappa B and may contribute in the pathophysiology of HTLV-I associated arthritis.

Arthritis, Rheumatoid↗
PubMed1994

Transcriptional regulation of the human interleukin-6 gene promoter in human T-cell leukemia virus type I-infected T-cell lines: evidence for the involvement of NF-kappa B.

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of interleukin-6 (IL-6) protein and mRNA. To clarify the mechanisms that lead to the activation of IL-6 gene in HTLV-I-infected cells, we first studied the regulatory regions in the IL-6 gene transcription by transfection of chloramphenicol acetyltransferase (CAT) reporter plasmids containing the IL-6 promoter. When transfected into HTLV-I-infected T-cell lines MT-2 and HUT-102, IL-6 promoter/CAT plasmids were strongly activated without any stimulation. By deletion analysis of 5' upstream region of IL-6 promoter, the DNA region between -73 and -59 bp from the transcription start site of IL-6 gene was important in the expression of IL-6/CAT activities in HTLV-I-infected cells. This region contains nuclear factor (NF)-kappa B binding site. The site-directed mutation of the kappa B motif in IL-6/CAT plasmid resulted in the complete abrogation of IL-6 promoter activity in these cells. Furthermore, when IL-6 promoter/CAT plasmid was introduced into an HTLV-I-uninfected T-cell line, Jurkat, IL-6 promoter activity was silent in the basal level, but strongly increased by the cotransfection with an HTLV-I tax expression plasmid. However, tax expression plasmid showed no transactivation activity, when kappa B site was mutated in IL-6 promoter/CAT plasmid. We found that the IL-6 kappa B site specifically formed a complex with NF-kappa B-containing nuclear extracts from MT-2 and HUT-102 cells. Finally, transfection of HTLV-I tax into Jurkat cells resulted in induction of specific binding of nuclear extracts to the NF-kappa B sequence. These results strongly suggest that HTLV-I tax gene may transactivate IL-6 gene through kappa B site in HTLV-I-positive T-cell lines and activation of NF-kappa B may be crucial in HTLV-I-induced IL-6 gene activation in ATL.

Base Sequence↗
PubMed1994

Simultaneous determination of antiepileptic drugs and their metabolites, including chiral compounds, via beta-cyclodextrin inclusion complexes by a column-switching chromatographic technique.

Using beta-cyclodextrin as a mobile-phase additive, a column-switching chromatographic system equipped with two 25-mm short ODS cartridge columns and two UV detectors was successfully employed for the simultaneous determination of some antiepileptic drugs and their metabolites, including chiral compounds, in human serum. The compounds examined were phenobarbital, zonisamide, phenytoin and its metabolites, S- and R-5-(p-hydroxyphenyl)-5-phenylhydantoin, R- and S-mephobarbital, carbamazepine and its main metabolites, 10,11-dihydro-10-11-epoxycarbamazepine and trans-10,11-dihydroxy-10,11-dihydrocarbamazepine (as a racemate), and allobarbital (as an internal standard).

Anticonvulsants↗
PubMed1994

Stimulatory effect of IL-1 beta on catecholamine secretion from cultured bovine adrenal medullary cells.

We investigated the effect of recombinant human interleukin-1 beta (IL-1 beta) on catecholamine secretion from cultured bovine adrenal medullary cells. Treatment of cultured cells with IL-1 beta (10 ng/ml) for 24 hr caused an increase in accumulation of catecholamines in the cultured medium. The accumulation of catecholamines stimulated by IL-1 beta was observed in time (4-48 hr)- and concentration (3-30 ng/ml)-dependent manners. The stimulatory effect of IL-1 beta (10 ng/ml) was completely inhibited by recombinant human IL-1 receptor antagonist (1 microgram/ml). IL-1 beta had little effect on [3H]norepinephrine uptake to cultured cells. These results suggest that IL-1 beta stimulates catecholamine secretion through activation of IL-1 receptors in adrenal medullary cells.

Adrenal Medulla↗