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Biomedical subjects

H Itoh

Publications and source records attributed to H Itoh.

At least 973 records · Page 54Linked to original sources

Cyclosporin reduces proteinuria in rats with aminonucleoside nephrosis.

The effect of cyclosporin (CS) was assessed in Sprague-Dawley rats with puromycin aminonucleoside (PA) nephrosis induced by a single intraperitoneal injection of PA. Three groups of rats were injected intraperitoneally with CS (10 mg/kg body weight) daily, beginning 1 day before PA administration, or 5 or 10 days after PA administration, for 10 days. CS significantly reduced proteinuria in rats with PA nephrosis in comparison with untreated nephrotic controls. After discontinuation of the CS treatment, proteinuria gradually increased, reaching values similar to those in control nephrotic rats. CS pretreatment did not prevent the induction of PA-induced nephrotic syndrome. Light microscopy and assessment of anionic sites in the glomerular basement membrane revealed no differences between normal rats, nephrotic controls, and CS-treated rats. These results show that CS can reduce proteinuria in PA nephrosis, but cannot ameliorate the glomerular changes.

Animals↗

Chum salmon (Oncorhynchus keta) stanniocalcin inhibits in vitro intestinal calcium uptake in Atlantic cod (Gadus morhua).

Chum salmon (oncorhynchus keta) stanniocalcin was purified, partially identified and tested for bioactivity in an assay on the intestinal calcium uptake in a marine teleost (Gadus morhua). Basic ethanol extraction, ion exchange chromatography, gel filtration and reverse-phase high-performance liquid chromatography resulted in the isolation of a homogeneous glycoprotein that appears as a 46-kDa product under nonreducing conditions and as a 23-kDa product under reducing conditions after sodium dodecylsulphate-polyacrylamide gel electrophoresis. The glycoprotein is likely to be a homodimer composed of two subunits of 23 kDa each. Further characterization indicates homology to Australian eel, sockeye salmon, coho salmon and rainbow trout stanniocalcin, and the glycoprotein is thus concluded to be stanniocalcin. Stanniocalcin-like immunoreactivity was demonstrated in the corpuscles of Stannius of the Atlantic cod, with a specific antiserum raised against purified chum salmon stanniocalcin. The physiological importance and the biological activity of chum salmon stanniocalcin was tested by evaluating its effect on intestinal calcium uptake by the Atlantic cod in vitro. The intestine was perfused, both vascularly and through the intestinal lumen, and the calcium mucosa-to-serosa flux was measured using 45Ca2+ as a tracer. Stanniocalcin decreased the intestinal calcium uptake in a dose-related manner by 13.5% and 22.4% at doses of 2.2 and 10.9 nM stanniocalcin, respectively. The results establish the intestine as a target organ for stanniocalcin in marine teleosts.

Amino Acid Sequence↗

Damage of cultured chondrocytes by hydrogen peroxide derived from polymorphonuclear leukocytes: a possible mechanism of cartilage degradation.

To study the mechanisms of chondrocyte damage, chondrocyte cytotoxicity as shown by chromium-51 release induced by polymorphonuclear leukocytes (PMNLs) was examined. PMNLs significantly enhanced chondrocyte cytotoxicity in the presence of phorbol dibutyrate. This chondrocyte damage was abolished by the addition of catalase, whereas superoxide dismutase and scavengers of hydroxyl radicals and protease inhibitors failed to reverse it. When cartilage matrix components such as hyaluronic acid and various proteoglycans were added to the PMNL-chondrocyte cultures, these components failed to affect the chromium-51 release. These results suggest that the increase in chondrocyte cytotoxicity is due to hydrogen peroxide generated by the PMNLs, and that cartilage matrix components do not prevent it. Hydrogen peroxide from PMNLs may therefore play an important role in cartilage degradation through direct damage of chondrocytes during inflammatory process.

Animals↗

Properties of common carp gonadotropin I and gonadotropin II.

Two gonadotropins, GtH I and GtH II, were extracted with 35% ethanol-10% ammonium acetate, pH 6.1, from female common carp pituitary glands and purified by ion-exchange chromatography on a DE-52 column followed by gel filtration on a Sephadex G-75 column. Molecular weights of GtH I and GtH II as determined by SDS-PAGE were 45,000 and 35,000, respectively. Both GtHs dissociate into two subunits following reduction with beta-mercaptoethanol. These subunits contain different N-terminal amino acids (Tyr and Gly for GtH I; Tyr and Ser for GtH II). GtH I was acid stable and did not dissociate into subunits following treatment with 0.1% trifluoroacetic acid; GtH II readily dissociated into subunits by this treatment. GtH I and GtH II have distinct elution profiles on reverse-phase HPLC. The N-terminal amino acid sequence of the beta-subunit of GtH II was identical to that of common carp maturational GtH described by other workers suggesting that GtH I is a newly identified molecule. This was supported by radioimmunoassay analysis. GtH II and a common carp maturational GtH preparation (F11 cGtH; Peter et al., 1982, J. Interdiscipl. Cycle Res. 13, 229-239) had similar immunological activity in tests with antisera to the beta-subunit of maturational GtH whereas GtH I had low (less than 6%) cross-reactivity. GtH I, GtH II, and F11 cGtH were equipotent in tests with antisera to the alpha-subunit of maturational GtH suggesting these molecules contain a similar alpha-subunit. In vitro bioassays using goldfish revealed that GtH I and GtH II share the same spectrum of biological activities causing stimulation of ovarian and testicular steroidogenesis and induction of oocyte final maturation. The demonstration of two chemically distinct GtHs in common carp is similar to what has been described for chum and coho salmon.

Amino Acid Sequence↗

Purification of a mature form of 60 kDa heat-shock protein (chaperonin homolog) from porcine kidney and its partial amino acid sequence.

1. We have purified a 58 kDa collagen-binding protein from a 4 M guanidine hydrochloride extract of porcine kidney. 2. This protein was identified as a mature form of 60 kDa heat-shock protein (HSP60, chaperonin homolog) based on its partial amino acid sequence. 3. Among 98 determined sequences of the porcine protein, 97 residues were identical with those deduced from nucleotide sequence of the cDNA encoding human HSP60.

Amino Acid Sequence↗

Regression of coronary atherosclerosis by combined LDL-apheresis and lipid-lowering drug therapy in patients with familial hypercholesterolemia: a multicenter study. The LARS Investigators.

The purpose of the LDL-Apheresis Regression Study (LARS) group, which included 13 institutions in Japan, was to investigate the effects on coronary atherosclerosis of LDL-apheresis combined with cholesterol-lowering drugs. Changes in coronary artery stenosis were assessed angiographically in 37 patients with familial hypercholesterolemia (7 homozygotes and 25 heterozygotes) and hypercholesterolemia which had not been defined as familial hypercholesterolemia (5 patients) by visual judgement and computer analysis. Definite regression was observed in 14 cases, including 4 homozygotes and 10 heterozygotes and others. Regression occurred as often in patients with severe coronary artery disease (2 or more vessel disease) as in those having less severe disease. Our results encourage initiation of aggressive cholesterol-lowering therapy to produce regression of coronary atherosclerosis in FH patients at high risk for cardiovascular events.

Adult↗

Catecholaminergic nucleus tractus solitarius lesions in anesthetized rats alter baroreflexes differently with age.

To explore whether catecholaminergic lesions produced chemically in the nucleus tractus solitarius (NTS) would alter the baroreflex impairment that normally occurs with age, we compared baroreflex responses in 3- and 14-month-old rats given bilateral microinjections of 6-hydroxydopamine (6-OHDA) or its vehicle into the NTS. After 2 weeks, basal pressures were unaffected but heart rates were lower in 14- than in 3-month-old rats. Sympathetic nerve inhibition elicited reflexly during intravenous infusions of sodium nitroprusside was reduced in 3-month-old rats, but increased in 14-month-old rats. Depressor, bradycardiac, and sympatho-inhibitory responses to afferent aortic nerve stimulation were likewise reduced in 3-month-old rats and oppositely enhanced in 14-month-old rats. Enhanced bradycardia probably does not depend on increased parasympathetic sensitivity because responses to vagal stimulation did not differ between age groups. Although underlying mechanisms remain uncertain, by showing that baroreflex responses become altered differently in 3- and 14-month-old rats by 6-OHDA these results suggest that the baroreflex changes normally occurring with age may be due, at least in part, to modified catecholaminergic mechanisms in the NTS.

Aging↗

Electron beam intraoperative radiation therapy (EBIORT) for localized pancreatic carcinoma.

Treatment results for 37 patients with localized pancreatic carcinoma treated using electron beam intraoperative radiation therapy (EBIORT) with curative intent from 1978 to 1990 in National Shikoku Cancer Center Hospital and the related hospitals were presented in comparison with those of a control group comprising 40 patients treated with no use of EBIORT. With additional treatment of EBIORT, 37 patients survived longer than the control 40 patients (p less than 0.05 during the 19th and 31st month). In the macroscopically total or partial resection, patients treated with EBIORT survived slightly longer than the controls. In the unresectable lesions, patients treated with EBIORT survived longer than the control patients (p less than 0.05 during the 7th month). In this group, there was one 5-year survivor who received EBIORT plus postoperative external radiation therapy (ERT) to the unresectable pancreatic head lesion but died 5 years later of massive bleeding from the duodenal ulcerations. Patients with unresectable carcinoma treated by EBIORT plus ERT survived longer than patients treated with EBIORT alone (p = 0.065). Pain relief was obtained in 95.0% of the unresectable patients with pain. Major adverse effects caused by irradiation were gastrointestinal troubles in five patients (leakage of choledochojejunostomy, gastric ulcerations, duodenal stenosis, gastric ulcerations and duodenal stenosis, duodenal perforation and ulcerations). EBIORT proved to be effective in the relief of serious pain and in the improvement of the survival of patients with localized pancreatic carcinoma.

Adult↗

Aging reduces cardiovascular and sympathetic responses to NTS injections of serotonin in rats.

Serotonergic mechanisms for baroreflex modulation could become altered with age. This possibility was explored by comparing cardiovascular and sympathetic effects elicited in 2-month- and 24-month-old rats by injecting serotonin (5-HT) directly into the nucleus tractus solitarius (NTS) which is the primary baroreflex relay station in the medulla. Ensuing decreases in mean pressure, heart rate, and renal nerve firing were significantly smaller in 24-month-old than in 2-month-old rats. By contrast, similar injections into the NTS of the vehicle alone were ineffective in both age groups. Postmortem examination of brain sections showed that NTS injection sites were equally distributed in both age groups, thereby indicating that the brain areas affected by 5-HT were identical regardless of age. Reduced sensitivity of peripheral myocardial beta-adrenergic and vascular alpha-adrenergic receptors was considered partly responsible because 5-HT injected into the NTS lowers blood pressure by decreasing sympathetic vasomotor tone and slows the heart by increasing vagal tone with reciprocal sympatho-inhibition. But since reduced adrenergic sensitivity would not account for the concurrent decrease in renal nerve firing, a more logical explanation is that the sensitivity of serotonergic mechanisms in the NTS for inhibiting blood pressure, heart rate, and renal nerve activity decreases with age.

Aging↗

Simultaneous resection of abdominal aortic aneurysms and early gastric cancer by retroperitoneal and transperitoneal approach.

The surgical approach to patients with abdominal aortic aneurysm and gastrointestinal malignancy remains controversial. We experienced two cases with abdominal aortic aneurysm and gastric cancer, which were treated by a one-stage operation using a different approach. At first, the operation for the aneurysm was done through a retroperitoneal approach and then, a partial gastrectomy for gastric cancer was done through a transperitoneal approach. The postoperative course of both cases was uneventful. The patients were discharge on the 19th and 21st postoperative days, respectively. This one-stage operation using different isolated approaches, such as the retroperitoneal approach for abdominal aortic aneurysm and transperitoneal approach for gastric cancer, was useful for the patients with abdominal aortic aneurysm and particularly early gastric cancer in terms of preventing an infection of the prosthetic graft.

Adenocarcinoma↗

Renal localization of the constitutive 73-kDa heat-shock protein in normal and PAN rats.

We purified the constitutive 73-kDa heat-shock protein (HSP73) from the bovine brain, and produced a specific antibody against the protein in a rabbit. On immunoblotting, the antibody cross reacted only with a protein band with a molecular mass of 73 kDa in a crude extract from normal rat kidneys, which was regarded as rat renal HSP73. The intrarenal immunohistochemical distribution of HSP73 was examined by using this antibody, on both normal rat kidneys and kidneys with puromycin aminonucleoside nephrosis. HSP73 was predominantly present in epithelial cells of the glomeruli and the tubules. In normal kidneys, HSP73 was generally localized in both the cytoplasm and the nucleus of these epithelial cells, except for proximal tubular epithelial cells. On the other hand, in kidneys with puromycin aminonucleoside nephrosis, HSP73 accumulated in the cytoplasm at a level higher than in the nucleus in association with the severity of renal dysfunction and proteinuria. These findings indicate that HSP73 is mainly expressed in glomerular and tubular epithelial cells in the kidney under a physiological condition, and that its expression changes from the nucleus to the cytoplasm under pathological conditions such as a protein overload to these epithelial cells.

Animals↗

Interaction of rat lecithin-cholesterol acyltransferase with rat apolipoprotein A-I and with lecithin-cholesterol vesicles.

The interaction of rat plasma lecithin-cholesterol acyltransferase with lecithin-cholesterol vesicles and with rat apo-A-I was studied in comparison with that of human plasma lecithin-cholesterol acyltransferase to clarify the reaction mechanism of rat plasma lecithin-cholesterol acyltransferase. The interaction of both human and rat lecithin-cholesterol acyltransferase with lecithin-cholesterol vesicles was investigated by gel permeation chromatography on Superose 12. Both enzymes had almost the same affinity to the vesicles. The affinity of rat enzyme to rat apo-A-I was stronger than that of human enzyme to human apo-A-I when estimated on the apo-A-I-Sepharose 4B column. When human apo-A-I was added to the human enzyme/vesicle mixture which contained the enzyme-vesicle complex, the enzyme was effectively dissociated from the complex. But when rat apo-A-I was added to the rat enzyme/vesicle mixture, apo-A-I-enzyme-vesicle complex was still recognized by its elution pattern on gel permeation chromatography. This suggests that the mixture of rat enzyme, rat apo-A-I, and vesicles, which are the major components in the rat lecithin-cholesterol acyltransferase reaction, forms a stronger complex than do the components of the human reaction.

Animals↗

Ga-67 citrate scintigraphy for the early detection of radiation pneumonitis.

To evaluate the usefulness of Ga-67 citrate scintigraphy in the early detection of radiation pneumonitis, scintigrams from 103 patients who were treated with radiation therapy for lung cancer were retrospectively analyzed with regard to abnormal Ga-67 uptake after radiation therapy in sites other than the original or recurrent tumors. Sixteen (20%) of the 80 asymptomatic cases showed positive Ga-67 scintigrams. All of the other 23 symptomatic cases showed positive Ga-67 scintigrams. Thirteen (57%) of these 23 cases had negative chest radiographs although their Ga-67 scintigrams were positive. Detection of radiation pneumonitis by Ga-67 scintigraphy was significantly earlier than that possible by chest radiography (P less than 0.01). These data suggest that Ga-67 scintigraphy is more useful and sensitive than chest radiography for the early detection of radiation pneumonitis.

Aged↗

Pulmonary large cell carcinoma expressing neuroendocrine markers: the morphological, biological, and neuroendocrine features of their cell lines and surgical cases.

A cell line expressing neuroendocrine (NE) markers, designated as KTS9, was established from a human large cell carcinoma of the lung using serum-free medium, ACL-3. KTS9 cells showed morphological characteristics of large cell undifferentiated carcinoma (LCUC) and expressed some general NE markers including neuron-specific enolase (NSE), protein gene product (PGP) 9.5, neural cell adhesion molecule (N-CAM), synaptophysin and neurofilaments (NF) of 200 kd. Some cells of this cell line were positive to chromogranin-A (CG-A), but did not express Leu7 or aromatic L-amino acid decarboxylase (AADC). Such a cell line derived from LCUC with NE properties has not previously been reported. The biological and NE properties of the KTS9 cell line were compared with those of 2 surgical cases of LCUC with NE markers and of the KTA7 cell line previously reported to derive from large cell carcinoma and to possess NE markers such as alpha-hCG, PGP9.5 N-CAM and AADC. Tumor cells of 2 large cell carcinomas expressed NSE, PGP9.5, N-CAM and NF. The KTS9 and KTA7 cell lines and 2 large cell carcinomas were thus considered to be LCUCs with NE differentiation. Both lines had the morphological characteristics of LCUC, relatively short doubling time and discordant expression of NE markers, indicating them to be closely related to the variant type of small cell carcinoma cell lines and thus possibly to represent high-grade malignancy. They may be useful for examining the biological behavior and NE features of large cell-type NE tumors of the lung.

Adult↗

Malignant lymphomas of the nasal cavity and paranasal sinuses. A clinicopathologic and immunohistochemical study.

The clinicopathologic and immunohistological features of 20 Japanese patients with non-Hodgkin's lymphomas (NHLs) limited to the sinonasal area were studied using a broad panel of T- and B-cell markers on paraffin-embedded and fresh frozen tissue. All cases showed a diffuse growth pattern. Nine cases were B-cell lymphomas (immunoblastic n = 4, centroblastic n = 3, immunocytoma n = 1, centrocytic n = 1), and nine were T-cell lymphomas (pleomorphic medium and large cell n = 8, angioimmunoblastic n = 1). In two cases, the cell lineage could not be determined. No morphologic features of angiocentric/angiodestructive lymphoproliferative lesions or lymphoepithelial lesions in ductal or glandular epithelium were seen in our series. Eight (89%) of the nine T-cell tumors and four (44%) of the nine B-cell neoplasms involved both the nasal cavity and paranasal sinuses. Six of the nine T-cell neoplasms showed a clinical presentation of rhinitis, whereas all of the B-cell neoplasms showed tumor masses in the nasal cavity and/or paranasal sinuses. The two-year survival rate for T-cell lymphomas was poorer than that for B-cell lymphomas. The five-year survival of patients with NHLs involving both the nasal cavity and paranasal sinuses was also poorer than that of patients in whom NHLs were limited to the nasal cavity.

Adult↗

Immunohistochemical study of transforming growth factor beta, fibronectin, and fibronectin receptor in invasive mammary carcinomas.

Thirty-one cases of mammary carcinoma were examined immunohistochemically for the expression of transforming growth factor (TGF) beta, fibronectin (FN) and fibronectin receptor (FNR) in order to clarify the reason for the reported relationship between TGF beta expression and a high incidence of lymph node metastasis. It was revealed that TGF beta expression is closely related to the expression of FN, an intercellular matrix protein, and its cellular receptor FNR, one of the integrins. The interaction between FN and FNR in a tumor is considered to form the basis of the invasive nature of carcinoma cells. Thus, it is suggested that TGF beta expression in carcinoma cells induces the interaction between FN and FNR, which may lead to carcinomatous invasion resulting in lymph nodal metastasis.

Adult↗

Preliminary results of concurrent cisplatin and radiation therapy in locally advanced bladder cancer.

Between March 1981 and March 1990, 15 patients with locally advanced transitional cell carcinoma of the bladder were treated concurrently with cisplatin and radiotherapy. Treatment comprised a radiation dose of 40-50 Gy in 20-25 fractions over 4-5 weeks and intravenous infusion of cisplatin with hydration during days 1-5 and 22-26. The total scheduled dose of cisplatin was 200 mg. A complete response (CR) was seen in 3 patients (2 T2 tumours and 1 T3) and the other 12 were regarded as partial responders. Two of the 12 partial responders (1 T2 tumour and 1 T4) underwent cystectomy after treatment, but 9 patients (2 T2, 6 T3 and 1 T4) underwent only transurethral resection. The remaining patient (with a T4 tumour) died from systemic disease, further treatment not being possible because of unrelated heart failure. In 3 CR patients and 9 with a partial response (PR), bladder function was preserved and they have survived for a mean of 18.3 months (range 5-47) after therapy. Although 4 patients in this group had recurrent bladder tumours and 1 died from cancer in another part of the body, 7 have survived with normal bladder function and no recurrence. It is concluded that concurrent cisplatin and radiation therapy is a safe and viable regimen and may be considered as a means of preserving the bladder in patients with locally advanced transitional cell carcinoma.

Aged↗