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Biomedical subjects

F Hino

Publications and source records attributed to F Hino.

At least 19 recordsLinked to original sources

Cardiogenic shock following recombinant alpha-2b interferon therapy for chronic hepatitis C. A case report.

A 57-year-old woman with chronic hepatitis C was treated with alpha-2b interferon (IFN). Forty-five days after the initiation of IFN therapy, she developed cardiogenic shock. Acute perimyocarditis as a cause of cardiogenic shock was clinically suspected by the findings of complete atrioventricular block, regional wall motion abnormality and pericardial effusion. Since IFN therapy may induce cardiogenic shock in some patients, it is important to carefully monitor patients under treatment with IFN for abnormal cardiac signs.

Acute Disease

Adverse effects of interferon on the cardiovascular system in patients with chronic hepatitis C.

The therapeutic effects of interferon in chronic hepatitis C and many of its adverse effects have been well documented. However, there are only a few reports regarding its adverse effects on the cardiovascular system. The aim of this study was to clarify the clinical features of the adverse effects of interferon on the cardiovascular system in patients with chronic hepatitis C. We monitored 295 patients with chronic active hepatitis C during 312 courses of interferon therapy and for 1 year after the end of treatment for the presence of cardiovascular adverse effects. We found 6 patients with cardiovascular adverse effects during interferon therapy and 4 more patients within 1 year after the end of therapy (10/312, 3.2%). The adverse effects of interferon on the cardiovascular system included arrhythmia (n = 4), ischemic heart disease (n = 4) and myocardial disease (n = 2). None of the clinical factors, including history of cardiovascular disease, were related to these cardiovascular adverse effects. In all instances the patient's condition improved after discontinuation of interferon and adequate therapy. The cardiovascular adverse effects of interferon occurred frequently in patients with chronic hepatitis C, even after the end of therapy and they were unpredictable. Thus, all patients undergoing interferon therapy should be monitored not only during but also after the end of treatment.

Arrhythmias, Cardiac

Sarcoidosis after interferon therapy for chronic active hepatitis C.

Sarcoidosis is characterized by multisystemic granulomatous lesions of unknown etiology. A 62-year-old woman developed sarcoidosis after treatment with alpha-2a interferon (IFN) for 24 weeks (total dose: 522 million units) for chronic hepatitis C. She developed complete atrioventricular block and multiple noncaseating granulomatous lesions in the lung. IFN therapy, which may disturb cellular immune activation in some patients, may have contributed to the onset and progression of sarcoidosis.

Antiviral Agents

Effects of fluvastatin on human biliary lipids.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have rapidly become widespread in the treatment of hypercholesterolemia and are known to be variable in efficacy. To investigate the effect on biliary lipids, a 3-month study using fluvastatin was devised. A total of 19 patients were enrolled in this study: all had hypercholesterolemia (7 men, 12 women; 13 with type IIa, 6 with type IIb). After an observation period of 4-6 weeks with placebo, fluvastatin at a daily dose of 30 mg was administered for 3 months. Fasting blood samples were taken early in the morning, before, and once a month during 3 months of fluvastatin treatment, for measurement of serum lipids. Cerulein-stimulated bile in the gallbladder was sampled using a duodenal tube, and the changes in biliary lipids were assessed. There was a marked decrease in serum total cholesterol after 12 weeks of treatment (21%; p < 0.001). However, there was no significant difference in the bile cholesterol saturation index (CSI): values before and after 3 months of drug administration were 0.93 and 0.99, respectively (Admirand-Small method). There were no significant changes in either the fatty acid composition of biliary lecithin or in the bile acid composition of bile. In conclusion, on the basis of these results, short-term (3 months) administration of fluvastatin does not appear to affect CSI.

Adult

[Osteocalcin].

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Aged

Increased fragmentation of urinary fibronectin in cancer patients detected by immunoenzymometric assay using domain-specific monoclonal antibodies.

Monoclonal antibodies (MoAbs) recognizing the distinct domains of human fibronectin had previously been established and they were used to construct several sandwich immunoenzymometric assays (IEMAs) for the structural analysis of fibronectin found in the urine of cancer patients. Urinary fibronectin (UFN) was immunodetectable only with FN12-8 and FN30-8 MoAbs against cell-binding domains and was less reactive with other IEMAs using MoAbs directed to terminal domains, indicating that UFN was almost completely fragmented and consisted mainly of cell-binding regions. The IEMA using MoAbs against cell-binding domains had sufficient immunoreactivities with the antigen fragmented by artificial proteolysis, but these fragments could hardly be detected by other IEMAs. UFN levels were significantly elevated in various cancer patients and extremely elevated in some patients with distant metastasis. It is presumed that UFN fragments which increase in cancer patients are generated by extracellular matrix destruction. Thus UFN levels and the ratio of the fragmented UFN level to the non-fragmented UFN level appear to be informative clinical indicators of tumor malignancy or metastatic ability in cancer patients.

Animals

[A case of giant hepatocellular carcinoma effectively treated by UFT].

An 84-year-old woman who suffered from heart failure was admitted to our hospital in July 1991. We found a hepatocellular carcinoma, of about 9 cm in diameter in her right liver lobe. The patient could not be operated on, TAE and PEIT, so she has been administered UFT (300 mg/day) orally every day. After seven months, observing the patient by means of computerized tomography, we noticed that the tumor had decreased in size until only a small cyst was left. PIVKA-II reached the normal range (under 0.063 AU/ml) from its previous level (42.940 AU/ml). She has maintained a good state of health for about two years now. This is considered a very rare case in which chemotherapy proved to be completely effective, and the patient has survived for a long time afterwards.

Aged

Urinary laminin fragments as a tumour marker potentially reflecting basement membrane destruction.

The presence of soluble laminin fragments in urine of healthy subjects, patients with diabetes, and patients with tumours was studied using sandwich immunoenzymometric assay technique. The form of urinary laminin (ULN) fragments was dramatically different from that of intact laminin, so ULN could be detected only by using monoclonal antibodies. Mean levels of ULN in lung tumour were significantly higher (171 micrograms gram-1 creatinine) than those in healthy subjects, patients, with diabetes, patients with stomach tumour, and patients with colon tumour (respectively 91, 92, 77 and 53 micrograms gram-1 creatinine). Immunopurified ULN fragments showed an apparent molecular mass of 42 KD on electrophoresis. This fragment was recognised as being derived from the N-terminal region of laminin B2 chain, because the N-terminal residues of ULN were found to be completely homologous to B2 chain. These data suggested that ULN was almost all fragmented, consisted mainly of N-terminal domain of the B2 chain, and was suspected of a tumour-associated protein fragments probably derived from basement membrane degraded proteolytically by tumour cells. ULN, increased in tumour patients, could be a potential clinical marker for monitoring the turnover of basement membrane in tumours.

Amino Acid Sequence

Sandwich enzyme immunoassay for serum integrins using monoclonal antibodies.

We produced monoclonal antibodies (mABs) against human integrins. Competitive enzyme-linked immunosorbent assay (ELISA) revealed that each mAB bound to different antigenic determinants. We then developed sandwich-type enzyme immunoassays (EIAs) to measure the concentration of fibronectin receptor (FNR) and vitronectin receptor (VNR). Serum immunoreactive integrin levels were measured using these EIAs in various liver and malignant diseases. In almost all cases of liver cirrhosis (LC) and hepatocellular carcinoma (HCC), serum integrin levels were significantly elevated, but were in the normal range in gastric, colon, lung cancer, and acute hepatitis (AH). The correlation between serum FNR and VNR levels was statistically significant in all cases of liver disease, and no correlation was observed between these integrin levels and conventional biochemical markers such as AST, ALT, and GGT. The serum integrin levels were demonstrated to be a potential diagnostic marker for hepatic fibrogenesis and carcinogenesis, and these sandwich EIAs could be useful for determination of these integrins in clinical laboratory tests.

Animals

A one step sandwich enzyme immunoassay for gamma-carboxylated osteocalcin using monoclonal antibodies.

A highly sensitive, simple and reliable one-step sandwich enzyme immunoassay (EIA) for the gamma-carboxylated form of osteocalcin (Gla-OC) has been developed using a monoclonal antibody. The minimum amount of Gla-OC detected by this EIA was approximately 0.2 ng/ml when a 10 microliter aliquot of the sample was used. The serum Gla-OC level in 30 healthy subjects was 3.6 +/- 2.19 ng/ml (mean +/- SD). A significant increase was seen in patients with chronic renal failure (20.3 +/- 4.60 ng/ml), atherosclerosis (8.3 +/- 4.94 ng/ml) and osteoporosis (10.1 +/- 4.60 ng/ml). The correlation between the values obtained by the sandwich EIA and competitive RIA methods was given by the linear regression equation, y = 2.896 + 0.759 chi, for which the correlation coefficient (r) was 0.815 (n = 58). This newly developed Gla-OC specific EIA may be useful for the diagnosis of metabolic bone disease and ectopic calcification.

Animals

Direct measurement of calpastatin subtypes by sandwich enzyme immunoassay using monoclonal antibodies.

Six stable hybridoma cell lines secreting monoclonal antibodies to human calpastatin were established. All monoclonal antibodies belong to the IgG1 subclass and recognized different epitopes on calpastatin. At least two groups were distinguished; the first group was specific for muscle-type (M-) calpastatin and the second group recognized not only M-calpastatin but also erythrocyte-type (E-) calpastatin. The inhibitory effect of all monoclonal antibodies on calpastatin activity was relatively low even at high concentrations of antibodies. Enzyme immunoassay systems were developed for direct determination of calpastatin subtypes in human cells requiring no other sample treatment than the disruption of the cells. The assay methods were, in principle, based on the sandwich enzyme immunoassay using epitope-specific monoclonal antibodies. The enzyme immunoassay system for M-calpastatin was specific for M-calpastatin and could not detect E-calpastatin. The enzyme immunoassay system for total calpastatin detected not only M-calpastatin but also E-calpastatin. The sensitivity of these assay systems was 10 pmol l-1 of calpastatins. Antigenicity of calpastatins was found to be unchanged in the presence of EDTA and haemoglobin. Good reproducibilities of within-and between-assay series and excellent recovery of exogenous calpastatins from cell lysates were observed. From these results, it seems that our newly developed subtype-specific enzyme immunoassay systems for calpastatins are useful in biochemical studies and clinical testing for determination of calpastatin subtypes.

Antibodies, Monoclonal

Urinary fibronectin fragments (a potential tumor marker) measured by immunoenzymometric assay with domain-specific monoclonal antibodies.

We found that urinary fibronectin (UFN) in cancer patients was almost all fragmented and consisted mainly of the cell-binding domain. We developed a two-site immunoenzymometric assay for UFN, using two monoclonal antibodies that both recognize this domain of fibronectin. The amount of UFN was expressed as arbitrary units per milligram of creatinine. Some 2% of the 623 healthy subjects had UFN above the clinical cutoff point (200 arb. units/mg creatinine), as did 14% of the 271 patients with nonmalignant diseases. In contrast, concentrations of UFN exceeded the cutoff point in 59% of the 589 patients with cancer. In 37 patients with gastrointestinal cancer tested for UFN and for one or more of three established serum tumor markers, UFN was found in 25, significantly more often than the other markers. These results indicated that UFN is a marker that may be helpful in evaluating many kinds of cancer.

Adult

Rapid, simple enzymatic assay of free L-fucose in serum and urine, and its use as a marker for cancer, cirrhosis, and gastric ulcers.

We devised a kit for use with automated analyzers, for assay of urinary free L-fucose by means of a newly isolated L-fucose dehydrogenase (EC 1.1.1.122), and we measured L-fucose in healthy subjects, cancer patients, and patients with other diseases. It takes 10 min to complete one assay. Absorbance and L-fucose concentration were linearly related up to at least 3.0 mmol/L, analytical recovery was 90-104%, and intra- and interassay coefficients of variation were less than 4.2% and 7.8%, respectively. The concentrations of L-fucose, corrected for creatinine, were significantly higher than those in healthy subjects in nine of 18 patients with gastric ulcers, 19 of 21 patients with cirrhosis of the liver, and 206 of 366 patients with some type of cancer, reflecting a changed L-fucose metabolism. Because urine specimens are analyzed and the test is rapid and inexpensive, this method may be suitable for mass screening for some kinds of cancer, cirrhosis, and gastric ulcers.

Adult

Isolation and characterization of two monoclonal antibodies that recognize remote epitopes on the cell-binding domain of human fibronectin.

Two monoclonal anti-fibronectin antibodies that inhibit fibronectin-mediated cell adhesion have been established and characterized. One antibody, FN12-8, inhibited attachment of rat kidney fibroblasts on the fibronectin-coated substrate in a concentration-dependent manner, attaining a maximal inhibition of greater than 85% at 850 micrograms/ml. Another antibody, FN30-8, caused about 70% inhibition at a concentration as low as 0.85 microgram/ml, although further increase of the antibody concentration did not significantly augment the inhibitory effect. Immunoblot analysis with defined proteolytic fragments revealed that both antibodies are directed to the cell-binding domain of fibronectin. The epitopes for these antibodies were further narrowed down using recombinant cell-binding fragments expressed in Escherichia coli. FN12-8 recognized the 11.5-kDa cell-binding fragment previously characterized by Pierschbacher et al. (1981, Cell 26, 259-267), suggesting that FN12-8 blocks the Arg-Gly-Asp (RGD) cell adhesion signal. FN30-8 could not bind this fragment but did recognize a longer cell-binding fragment containing additional greater than 111 amino acid residues upstream of the 11.5-kDa fragment. Since the RGD-dependent cell adhesion seems to require another signal located at a region 50-160 residues upstream of the 11.5-kDa fragment for full activity, FN30-8 may exert its inhibitory effect by blocking the latter signal.

Amino Acids