Biomedical subjects

H Itoh

Publications and source records attributed to H Itoh.

At least 901 records · Page 50Linked to original sources

PubMed1993

Pathological analysis of hypertrophic cardiomyopathy simulating dilated cardiomyopathy.

The pathomorphologic features of hypertrophic cardiomyopathy simulating dilated cardiomyopathy in the late stage (HCM-DCM) were compared with those of ordinary hypertrophic cardiomyopathy (HCM). Seven autopsied hearts with HCM-DCM and 11 with HCM were assessed quantitatively using an image analyzer. Unlike HCM, significant left ventricular enlargement and wall thinning were observed in HCM-DCM, and the percentage areas of massive fibrosis and disarray were significantly greater. In HCM-DCM, the disarray was distributed diffusely, whereas massive fibrosis was distributed more intensively in the ventricular septum and anterior wall than in the lateral and posterior wall. Narrowing of intramyocardial small arteries was observed more frequently in HCM-DCM, especially in the ventricular septum and anterior wall, than in HCM. These results suggest that the enlargement and wall thinning of the left ventricle in HCM-DCM are attributable to non-uniform progression of massive fibrosis, which is closely related to small-arterial lesions.

Adult↗

PubMed1993

Establishment and characterization of a human lung adenocarcinoma cell line (LC-2/ad) producing alpha 1-antitrypsin in vitro.

A new human cell line, LC-2/ad was established from pleural effusion of pulmonary adenocarcinoma of a 51 year old Japanese female. The LC-2/ad cells exhibit an epithelial appearance and a tendency to form small domes as observed with phase-contrast microscopy. The modal chromosome number was 53-56. Plating efficiency and doubling time were 6.8% and 58 h, respectively (32th passage). Immunocytochemically, the cells were strongly positive for CEA and cytokeratins including cytokeratin no. 18 which is present in simple epithelia. Ultrastructurally, the cultured cells were characterized by well-formed junctional complexes and microvilli. Subcutaneous injection of 5 x 10(6) cells into a nude mouse resulted in tumor formation classified histologically as a moderately differentiated adenocarcinoma. This cell line produced at least two functionally active trypsin inhibitors together with several proteinases in vitro. The main inhibitor was purified partially from the serum-free conditioned medium and confirmed immunologically as human alpha 1-antitrypsin (AAT). Immunohistochemically, the xenografted tumor was also positive for AAT. The cell line LC-2/ad is useful for the study of tumor-derived serine proteinase inhibitors, in particular AAT.

Adenocarcinoma↗

PubMed1993

Lupus anticoagulant (LAC) and its relation to pregnancy outcome: a report of five cases.

We examined the relation between the spontaneous remission and prednisolone-induced suppression of lupus anticoagulant (LAC) or anticardiolipin antibody (ACA) and pregnancy outcome in 5 LAC-positive women. Two women showed a spontaneous remission of LAC and ACA during the observation period. One of these 2 women became pregnant and delivered healthy twin infants at 36 weeks of pregnancy without any therapy. The other woman became LAC positive again after 1 year of remission, and experienced 2 more fetal losses. Two of the remaining LAC-positive women received prednisolone and aspirin. Only 1 woman, whose ACA was suppressed by medication, delivered a healthy newborn. The pregnancy of the other woman, whose LAC and ACA remained positive in spite of medication, terminated in an IUFD. These results suggest that the administration of prednisolone and aspirin is the first choice of therapy for LAC-positive women, and that encouraging such women to become pregnant while LAC is negative might be an alternative therapy.

Adult↗

PubMed1993

Malignant lymphoma of Waldeyer's ring. A histological and immunohistochemical study.

The histopathological and immunohistological features of non-Hodgkin's lymphoma limited to the Waldeyer's ring were studied in 22 Japanese patients using a panel of T- and B-cell markers on paraffin-embedded sections. All cases showed a diffuse growth pattern. Twenty cases were B-cell lymphomas and two were T-cell lymphomas. In contrast to the primary malignant lymphomas of the nasal cavity and paranasal sinuses, in which T-cell neoplasms are more frequently seen, the majority of the primary Waldeyer's ring lymphomas were B-cell neoplasms. Sixteen of the 20 cases of B-cell lymphoma were centroblastic lymphomas, and the monomorphic variant comprised the majority of these; the other three B-cell lymphomas were immunocytomas. Two of the T-cell lymphomas showed morphological features of angiocentric lymphomas.

Adolescent↗

PubMed1993

Liquid chromatographic determination of magnolol in urine collected from volunteers after a single dose of saiboku-to, an oriental herbal medicine for bronchial asthma.

Saiboku-To is an anti-asthmatic herbal remedy which consists of ten herbal extracts. To investigate the clinical relationship between the effects and chemical components of Saiboku-To, a simple and sensitive high-performance liquid chromatographic method (HPLC) for determination of magnolol, one of the major urinary products, was developed. Organic solvent extraction of urinary magnolol was conducted by diatomaceous earth column rapid-flow fractionation using ethanol/dichloromethane (8/92, v/v). Recovery rates of magnolol were more than 99% with coefficient of variations less than 6% in the concentration range 9.7-970 ng mL-1. Subsequent HPLC determination of magnolol was achieved using a conventional silica-gel column, a mobile phase mixture of acetic acid/diethyl ether/n-hexane (0.2/17.0/82.8, v/v), and a UV-absorption detector set at 290 nm. Calibration was on the basis of peak height ratio between magnolol and flavone as an internal standard. The method was used to demonstrate excretion profiles of magnolol in healthy and asthmatic subjects following single administration of Saiboku-To.

Adult↗

PubMed1993

Impact of free magnolol excretions in asthmatic patients who responded well to saiboku-to, a Chinese herbal medicine.

Saiboku-To, a mixture of ten different herbal extracts, has been used in Japan and Czechoslovakia for corticosteroid-dependent severe asthma to reduce the maintenance doses of corticosteroid. Magnolol has been considered to be an active component of Saiboku-To as an inhibitor of 11 beta-hydroxysteroid dehydrogenase and T-lymphocyte proliferation resulting in corticosteroid-sparing. To investigate the relationship between magnolol and the clinical effects of Saiboku-To, urinary magnolol excretion was compared in responders and non-responders under long-term Saiboku-To treatment. The clinical outcome of the Saiboku-To treatment was evaluated in nine asthmatic patients at 52 weeks after the onset of the treatment, using individual fluctuation of asthmatic points obtained from the patients' diary cards. Three patients whose clinical conditions were improved by the treatment were termed responders and six others were termed non-responders. The difference in the amounts of the total magnolol excreted were not significant; however, free (or non-conjugated) amounts of magnolol excreted in the responders were 7 times those in the non-responders (P < 0.05). These results suggest that the magnolol might be responsible for the therapeutic effect of Saiboku-To, indicating practical bioavailability in the responders.

Adult↗

PubMed1993

Pulmonary tuberculosis: CT findings--early active disease and sequential change with antituberculous therapy.

To evaluate findings of active pulmonary tuberculosis on computed tomographic (CT) scans and their sequential changes before and after antituberculous chemotherapy, 29 patients with newly diagnosed pulmonary tuberculosis and 12 patients with recent reactivation were studied prospectively. The diagnosis of active pulmonary tuberculosis was based on positive acid-fast bacilli in sputum (n = 29) and changes on serial radiographs obtained during treatment (n = 12). Twenty-six patients were followed up with CT during treatment for 1-20 months. Lungs from the cadavers of nine other patients, who died of pulmonary tuberculosis, were studied to provide a pathologic basis for diagnosis. At examination with CT, centrilobular lesions (nodules or branching linear structures 2-4 mm in diameter) were most commonly seen (n = 39 [95%]); in the 26 patients with follow-up, most of these lesions disappeared within 5 months after the start of treatment. In 11 of 12 patients with recent reactivation, CT clearly differentiated old fibrotic lesions from new active lesions. Lesions in and around the small airways appear to be the most characteristic CT feature of early active tuberculosis and may be a reliable criterion for disease activity.

Adult↗

PubMed1993

Pulmonary sarcoidosis: correlation of CT and histopathologic findings.

PURPOSE: Computed tomographic (CT) findings of pulmonary sarcoidosis were correlated with histopathologic features determined at open lung biopsy or autopsy. MATERIALS AND METHODS: Eight patients (six men and two women, aged 22-65 years) with pulmonary sarcoidosis diagnosed at histologic examination were studied at CT with a high-spatial-frequency algorithm. RESULTS: The most frequent CT features were irregularly thickened bronchovascular bundles (seven of eight cases [88%]) and small nodules along vessels (four cases [50%]). These features corresponded to granulomas formed in the connective tissue sheath around the pulmonary vessels and airways. This characteristic CT appearance was the result of the bronchovascular distribution of sarcoid granulomas. Granulomas adjacent to the visceral pleura or formed in the pleura in four patients were correlated with pleural or subpleural involvement. Ground-glass attenuation, present in six patients (75%), did not correlate with alveolitis in any patient. CONCLUSION: CT is a valuable technique with which to visualize the characteristic location of sarcoid granulomas in the pulmonary parenchyma.

Adult↗

PubMed1993

Inhibition of myosin light chain phosphatase during Ca(2+)-independent vasocontraction.

Phorbol 12,13-dibutyrate (PDB) induced a sustained contraction of rat thoracic aorta strip in Ca(2+)-free buffer without significant change in intracellular free Ca2+ concentration. NKH477, a water-soluble forskolin derivative, markedly relaxed the PDB-induced contraction. The PDB-induced contraction was associated with the phosphorylation of 20-kDa myosin light chain (MLC). Two-dimensional phosphopeptide mapping of 20-kDa MLC revealed that approximately 90% of the phosphopeptides was derived from an MLC kinase-catalyzed reaction and approximately 10% was due to phosphorylation by protein kinase C. NKH477 inhibited the PDB-induced phosphorylation of 20-kDa MLC. MLC phosphatase activity of intact aorta strips was inhibited by the treatment with PDB, and the inhibition was recovered by the application of NKH477. These results suggest that the regulation of MLC phosphatase in vascular smooth muscle may play important roles in the PDB-induced contraction and the NKH477-induced relaxation in Ca(2+)-free buffer.

Animals↗

PubMed1993

Downregulation of C-receptor by natriuretic peptides via ANP-B receptor in vascular smooth muscle cells.

The natriuretic peptide system comprises at least three ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) and three receptors, the ANP-A receptor, the ANP-B receptor, and the clearance (C) receptor. In the present study, the regulation of natriuretic peptide receptors by their ligands was investigated in cultured rat vascular smooth muscle cells (SMC). The treatment of vascular SMC with ANP, BNP, or CNP decreased the C-receptor density significantly, and the rank order of potency for this downregulation was CNP > ANP > BNP. This rank order was the same as that for guanosine 3',5'-cyclic monophosphate (cGMP) production by ANP, BNP, or CNP in vascular SMC and also the same as that for the ligand selectivity of the ANP-B receptor rather than the C-receptor. The incubation of vascular SMC with 8-bromoguanosine 3',5'-cyclic monophosphate significantly decreased the C-receptor density and its mRNA expression. These results suggest that the down-regulation of the C-receptor by natriuretic peptides is induced not by the binding of natriuretic peptides to the C-receptor but by the activation of the ANP-B receptor-cGMP pathway.

Animals↗

PubMed1993

Brain natriuretic peptide levels in the umbilical venous plasma are elevated in fetal distress.

We measured, by a specific radioimmunoassay, brain-natriuretic-peptide-like immunoreactive (BNP-LI) levels in the umbilical venous and arterial plasma of normal and distressed newborns. The indicated BNP-LI level in umbilical arterial plasma of normal newborns (3.5 +/- 0.9 fmol/ml, mean +/- SEM, n = 10) was significantly higher than that in umbilical venous plasma of the same newborns (2.2 +/- 0.5 fmol/ml). In the distressed newborns at term, the indicated BNP-LI level in umbilical venous plasma was 62.2 +/- 25.7 fmol/ml (n = 4), which was 19-fold higher than that of elective cesarean section cases (3.2 +/- 0.3 fmol/ml, n = 6; p < 0.05). The findings demonstrated that BNP was present in the human fetal circulation and that the plasma BNP level was elevated under fetal distress conditions.

Atrial Natriuretic Factor↗

PubMed1993

Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II.

Angiotensin (Ang) II stimulates hypertrophic growth of vascular smooth muscle cells (VSMC). Accompanying this growth is the induction of the expression of growth-related protooncogenes (c-fos, c-jun, and c-myc), as well as the synthesis of the autocrine growth factors, such as PDGF-A and TGF-beta 1. In this study, we demonstrate further that Ang II also induces the synthesis of basic fibroblast growth factor (bFGF), a potent mitogen for VSMC. To examine how these factors interact to modulate the growth response of VSMC to Ang II, we used antisense oligomers to determine the relative contribution of these three factors. Treatment of confluent, quiescent smooth muscle cells with specific antisense oligomers complementary to bFGF, PDGF-A, and TGF-beta 1 efficiently inhibited the syntheses of these factors. Our results demonstrate that in these VSMC, TGF-beta 1 affects a key antiproliferative action, modulating the mitogenic properties of bFGF. Autocrine PDGF exerts only a minimal effect on DNA synthesis. An imbalance in these signals activated by Ang II may result in abnormal VSMC growth leading to the development of vascular disease.

3T3 Cells↗

PubMed1993

Cytokine-induced C-type natriuretic peptide (CNP) secretion from vascular endothelial cells--evidence for CNP as a novel autocrine/paracrine regulator from endothelial cells.

We previously demonstrated that C-type natriuretic peptide (CNP), originally isolated from the porcine brain, is produced by endothelial cells and proposed that CNP can exert local control over vascular tone and growth as a local regulator from endothelial cells. Since cytokines play pivotal roles in the control of vascular tone and structure, we have examined effects of various cytokines on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP. While interleukin (IL)-2 had no significant effect on CNP secretion, IL-1 alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha stimulated CNP secretion in a time- and dose-dependent manner. Among them, TNF-alpha, one of the key mediators for inflammation and vascular remodeling, induced more than two orders of magnitude increase in CNP secretion. In addition, lipopolysaccharide (LPS) potently stimulated CNP secretion. These results indicate that IL-1, TNF-alpha and LPS, the endotoxin itself, can regulate local vascular tone and growth through the activation of CNP secretion from endothelial cells. Therefore, CNP could be of clinical relevance as an autocrine/paracrine regulator from endothelial cells for systemic and local cytokine-associated disorders, such as endotoxin shock and atherosclerosis.

Animals↗

PubMed1993

Brain natriuretic peptide is present in the human amniotic fluid and is secreted from amnion cells.

The presence and biochemical characteristics of human brain natriuretic peptide (hBNP) in the amniotic fluid at various gestational ages were investigated. The hBNP-like immunoreactivity (hBNP-LI) levels in amniotic fluid, determined by RIA, were 118.7 +/- 57.6 pmol/L (mean +/- SEM; n = 5) and 107.7 +/- 8.7 pmol/L (n = 9) in the first and second trimesters of pregnancy, respectively; it was significantly decreased to 28.4 +/- 5.1 pmol/L (n = 9) in the third trimester. However, human atrial natriuretic peptide-like immunoreactivity (hANP-LI) was not detected (< 0.3 pmol/L) in any of these samples. Northern blot analysis demonstrated hBNP mRNA in human amnion tissue. Moreover, cultured amnion cells secreted a significant amount of hBNP-LI (100-200 fmol/10(6) cells/day), but not hANP-LI, into the culture medium. The synthesis of hBNP in cultured amnion cells was further confirmed using the polymerase chain reaction. High performance gel permeation chromatography of hBNP-LI extracted from human amniotic fluid and the culture medium of amnion cells revealed that the predominant molecular form of hBNP-LI in both samples was the hBNP precursor, with an approximate mol wt of 12 kilodaltons. These findings indicate that hBNP is present in the human amniotic fluid, and that amnion cells synthesize hBNP and secrete it into the amniotic cavity.

Amniotic Fluid↗

PubMed1993

Antitumor activity of a novel nucleotide derivative, 5'-(1,2-dipalmitoyl-sn-glycero-3-phospho)-5-fluorouridine (TJ14026) on murine tumors.

The antitumor activity of a nucleotide derivative, 5'-(1,2-dipalmitoyl-sn-glycero-3-phospho)-5-fluorouridine (TJ14026), was confirmed following both intraperitoneal and oral administration against a number of murine experimental tumor systems in vivo, which included Meth A fibrosarcoma, B16 melanoma, 5-fluorouracil (5-FU) resistant P388 leukemia, P815 mastocytoma and L5178Y-ML lymphoma. Successive i.p. injections of a small dose (10 mg/kg/d x 10) or intermittent i.p. injections of a larger dose (50 mg/kg/d x 3) were equally effective against the solid form of Meth A fibrosarcoma. Intraperitoneal injection of TJ14026 prolonged the life of mice with 5-FU resistant P388 leukemia. Oral administration of TJ14026 was also effective against P815 mastocytoma and L-5178Y-ML lymphoma in the liver, an P388 leukemia metastasized to the lymph nodes. Glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels were elevated in the serum of un-treated mice bearing P815 mastocytoma but not in mice treated with TJ14026.

Administration, Oral↗

PubMed1993

Mitogenic activity and lethal toxicity of lipid A analogs, glucosamine-phosphate carrying aromatic alkyl groups, in mice.

The mitogenicity and lethal toxicity of four synthetic lipid A analogs, glucosamine-4-phosphate with a 7-hydroxy-heptanoyl group (A-166), with a 7-phenyl-heptanoyl group (A-167), or with a 8-(1-phenyl-hexanoyl)-nonanoyl group (A-168), at the C-2 and C-3 positions, and glucosamine-6-phosphate with the same substituents as A-168 at C-2 and C-3 (A-169), were compared. The compound A-166 exhibited no mitogenic activity at various concentrations ranging from 3.13 to 50 micrograms/ml in the splenocytes of BALB/c mice, but A-167 exhibited weak mitogenic activity at concentrations of 12.5 and 25 micrograms/ml. A-168 and A-169, as well as A-103, glucosamine-4-phosphate carrying (R)-3-tetradecanoyl-oxytetradecanoyl groups, have remarkable mitogenic activity at concentrations ranging from 12.5 to 100 micrograms/ml; the activity of A-169 (6-phosphate) was stronger than that of A-168 (4-phosphate). Compound A-167 failed to cause death at doses of 25 and 50 micrograms/mouse in galactosamine-loaded C57BL/6 mice while A-166 and A-169 were toxic to 2 out of 6 mice at 50 micrograms/mouse; no deaths were observed at 25 micrograms/mouse. A-168 showed the highest toxicity of any of the compounds tested at 25 and 50 micrograms/mouse. The lethal effect of A-103 appeared to be somewhere between that of A-168 and A-169. These findings indicate that lipid A analogs, carrying an aromatic alkyl group as well as a hydroxyacyl group, are mitogenic and lethal when given to mice.

Animals↗

PubMed1993

Syntheses and biological activities of selenium analogs of alpha-rat atrial natriuretic peptide.

alpha-Rat atrial natriuretic peptide (7--28) (rANP (7--28)) and a series of its analogs in which half cystine residue(s) were substituted with half selenocystine residue(s) were synthesized by using the Fmoc-based solid-phase method followed by cyclization by means of dimethylsulfoxide (DMSO)-trifluoroacetic acid (TFA) oxidation. These analogs possess comparable activities in both receptor binding and cGMP accumulation in rat vascular smooth muscle cells to those of rAMP (7--28).

Amino Acid Sequence↗

PubMed1993

Synthetic study on selenocystine-containing peptides.

N-9-Fluorenylmethoxycarbonyl-Se-4-methoxybenzylselenocysteine++ + [Fmoc-Sec(MBzl)-OH] was synthesized from selenocystine and successfully applied to Fmoc-based solid-phase peptide synthesis. The stability and the deprotection conditions of the Se-MBzl group were examined. The diselenide bond of a peptide was directly and effectively established between Sec(MBzl) residues by treatment with iodine or the dimethyl sulfoxide-trifluoroacetic acid system. Reduction kinetics of diselenide and disulfide in model peptides by reduced glutathione were also studied comparatively.

Amino Acid Sequence↗