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Biomedical subjects

E Sato

Publications and source records attributed to E Sato.

At least 271 records · Page 15Linked to original sources

Cytokine expression in the spinal cord lesions in HTLV-I-associated myelopathy.

Immunocytochemical staining of spinal cords from five autopsied patients with HTLV-I-associated myelopathy/tropical spastic paraparesis was performed using a panel of monoclonal or polyclonal antibodies reactive with interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-beta, IFN-gamma and transforming growth factor (TGF)-beta. In the spinal cords of patients with a shorter duration of illness, IL-1 beta, TNF-alpha, and IFN-gamma were expressed on perivascular infiltrating macrophages, astrocytes and microglia in active-chronic inflammatory lesions. In striking contrast, we rarely noted cytokine expression except for IFN-gamma in inactive-chronic lesions of patients with longer durations. In situ expression of these cytokines on microglia and astrocytes, in addition to infiltrating mononuclear cells, suggests that glial cells participate in the inflammatory process, especially in active lesions. In addition, the cytokine expression was gradually downregulated along with duration of illness.

Aged↗

Apoptosis of T lymphocytes in the spinal cord lesions in HTLV-I-associated myelopathy: a possible mechanism to control viral infection in the central nervous system.

Immunocytochemical staining of spinal cords from five autopsied patients with HAM/TSP was performed using the monoclonal antibody TIA-1, a marker of cytotoxic T lymphocytes (CTL). Many TIA-1+, CD8+ cells are distributed in active inflammatory lesions. The number of TIA-1+ cells is related to the amount of HTLV-I proviral DNA in situ. The protein TIA-1 has been associated with the induction of apoptosis in target cells. In active inflammatory lesions, we found cells undergoing apoptosis, most of them identified as helper-inducer CD45RO T lymphocytes, which were consistent with in vivo cellular tropism of HTLV-I in patients with HAM/TSP. These findings suggest that CTL-induced apoptosis of T lymphocytes may be one of the possible mechanisms which eliminate HTLV-I-infected cells from the central nervous system. In addition, many T lymphocytes in the inflammatory lesions expressed bcl-2 oncoprotein, suggesting that infiltrated T lymphocytes may be resistant to apoptosis. Expression of bcl-2 oncoprotein may explain the longstanding inflammatory process in the central nervous system of HAM/TSP.

Antibodies, Monoclonal↗

Enhancement of tumor proliferation by cyclosporine A in early phase of experimental hepatic metastasis.

The effect of cyclosporine A (CsA) on in vivo growth of hepatic metastasis was studied. Murine colon 38 tumor cells (1 x 10(5) were inoculated via the superior mesenteric vein. Mice were grouped depending on CsA dosage and time schedules: Group A: CsA 30 mg/kg body weight on the 7, 8 and 9th post tumor inoculation days by gavage; Group B: CsA 15 mg/kg body weight 30 min before tumor inoculation and 2 times more at 24 h intervals; Group C: CsA 30 mg/kg body weight at the same dose timing as Group B. Measurement of the diameter of the largest tumor serially by weekly laparotomy up to 4 weeks revealed that the tumor growth rates were significantly greater in Groups B and C than those in Group A or the control (without CsA). The mean tumor doubling times in the control, and Groups A, B and C were 2.2 +/- 1.3, 2.0 +/- 0.5, 1.5 +/- 0.4 and 1.3 +/- 0.8 days, respectively. The mean tumor numbers of hepatic metastasis were 13.2 +/- 8.3, 11.3 +/- 7.3, 19.4 +/- 8.7 and 19.6 +/- 6.8, respectively. Values of tumor proliferation index obtained by bromodeoxyuridine immunohistochemistry were 10.0 +/- 6.1%, 14.9 +/- 8.0%, 28.6 +/- 8.2% and 30.1 +/- 12.4%, respectively, with significant differences (Groups B and C vs. A or control, P < 0.05). In vitro MTT assay showed that cell viability rates were greater than 100% in the medium containing CsA concentrations of less than 10(-7) mol/liter. However, a cytostatic effect of CsA was apparent at higher concentrations. In contrast to the previous in vivo finding of a cytostatic effect of CsA on tumor cells, we found a cytoproliferative action when CsA was administered early in the course of metastatic tumor implantation in the liver. The mechanism of cytoproliferative effect of CsA is unknown but may involve multiple factors.

Animals↗

Monoclonal antibody HML-1 reactivity with adult T-cell leukaemia/lymphoma and other lymphomas.

Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1), a causative virus of adult T-cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast-feeding. Using a monoclonal antibody HML-1 which labels human intestinal intra-epithelial T lymphocytes, we have immunohistochemically examined ATLL tissues in order to evaluate the possibility that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Previously this antibody was reported to react with intestinal T-cell malignant lymphomas but not with peripheral tumours, or any B-cell lymphomas. We investigated 181 patients with malignant lymphomas and found that 19 out of 113 ATLLs were positive for HML-1. T-cell malignant lymphomas excluding ATLL also reacted with HML-1 (7/24), but all the B-cell lymphomas 0/33) and non-neoplastic lymph node and skin lesions (0/10) were negative for HML-1. In patients with ATLL and other T-cell malignant lymphomas, the positivity level of HML-1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph nodes (15/100) and skin (8/47). We observed one HML-1 positive ATLL patient with tumour formation in the skin and lymphadenopathy and marked infiltration of the large intestine but minimal involvement of other organs. Although HML-1 was frequently expressed in gastric infiltration of ATLL, the level of positivity was too low in lymph nodes to support the hypothesis that HTLV-1 infected intestinal T cells are the origin of ATLL cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Paraneoplastic vasculitic neuropathy: immunohistochemical studies on a biopsied nerve and post-mortem examination.

We studied a patient with paraneoplastic vasculitic neuropathy (PVN) associated with a carcinoma of the common bile duct. Immunohistochemical analysis of the biopsied sural nerve showed that the cellular infiltrates in the vascular lesions were composed primarily of CD8-positive T lymphocytes and macrophages. Pathogenic significance of the T-cell-mediated immunological reaction was suggested. Post-mortem examination revealed the absence of systemic vasculitis, which may be a characteristic feature of PVN. The patient responded to immunosuppressive treatment. We discuss the efficacy and the risk of immunosuppressive therapy for PVN.

Adenocarcinoma↗

Anatomical distribution of HTLV-I proviral sequence in an autopsy case of HTLV-I associated myelopathy: a polymerase chain reaction study.

HTLV-I associated myelopathy (HAM) is a slowly progressive paraplegia of the lower extremities observed among HTLV-I carriers. An autopsy of a typical HAM case in which perivascular lymphocytic infiltration was not limited to the central nervous system was examined. Spinal dorsal roots, salivary gland, lungs, liver and kidney showed non-specific, but unusual sporadic perivascular lymphocytic infiltration, which resembled the findings in the spinal cord. To investigate the anatomical distribution of HTLV-I provirus, the HTLV-I proviral sequences, tax and pol, were amplified from the formalin-fixed paraffin-embedded tissues of the autopsy case using polymerase chain reaction (PCR). By PCR, strong HTLV-I provirus signals were detected in the spinal cord, peripheral nerve, muscle, lungs and liver. Weak signals were detected in the medulla oblongata, optic nerve and lymph node, while the other organs, including the cerebrum, were negative. The data from this study show the specific distribution of HTLV-I provirus in the distinct organs of a HAM patient.

Aged↗

Inhibitory effect of aspirin on root resorption induced by mechanical injury of the soft periodontal tissues in rats.

The purpose of the present study was to study histologically and histometrically the inhibitory effect of aspirin on root resorption induced by mechanical injury of the periodontal soft tissues in rats. Resorption lacuna in the root surface of the molar in animals given both mechanical injury and aspirin administration contained fewer odontoclasts and was smaller in length and area than that in animals given only mechanical injury. The result of the present investigation indicated that the administration of aspirin might suppress root resorption induced by mechanical injury of the periodontal soft tissues.

Animals↗

Nonadrenergic noncholinergic nerves regulate basal coronary flow via release of capsaicin-sensitive neuropeptides in the rat heart.

Nonadrenergic noncholinergic nerve fibers supposedly modulate basal coronary flow by releasing capsaicin-sensitive neuropeptides, but the physiological effects of this intrinsic action have not been clarified. We investigated the intrinsic function of nonadrenergic noncholinergic innervation in modulating basal coronary flow in rats. We administered capsaicin to 44 rats to deplete neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P and administered inert vehicle to 60 control rats. Four days later, we measured the coronary pressure-flow relation in the basal state and during maximal coronary vasodilation induced by intracoronary adenosine administration using Langendorff's method. Changes in basal coronary flow prompted by intracoronary infusion of CGRP or substance P and their antagonists were measured in 54 and 30 rats, respectively. Capsaicin-treated rats showed a 31.5 +/- 0.9% (mean +/- SEM) reduction (P < .01) of basal coronary flow in the range of perfusion pressures between 60 and 140 mm Hg compared with untreated control rats, but the maximal coronary flow after adenosine was similar between the two groups. Although basal coronary flow was reduced in capsaicin-treated hearts, left ventricular contractile force and myocardial oxygen consumption did not fall significantly. CGRP increased the coronary flow, but substance P did not. CGRP(8-37), a CGRP receptor antagonist, reduced basal coronary flow by 24.5 +/- 2.1% (P < .01), but FK888, a substance P antagonist, had little effect on it. Thus, capsaicin-sensitive neuropeptides in the rat heart modulate basal coronary flow, providing approximately 30% of it.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

A controlled trial of pulse cyclophosphamide versus pulse methylprednisolone in severe lupus nephritis.

We carried out a prospective randomized trial comparing pulse cyclophosphamide and pulse methylprednisolone in 29 patients with severe lupus nephritis in activity. Patients were assigned to one of two regimens: monthly pulse cyclophosphamide (0.5-1.0 g/m2 body surface area) for 4 months, followed by bimonthly doses for 4 months and quarterly doses for 6 months (14 patients) or pulse methylprednisolone (10-20 mg/kg weight) initially for 3 consecutive days and thereafter in the same intervals as the alternative regimen (15 patients). The mean follow-up was 15 months. Two patients in the cyclophosphamide group and three in the methylprednisolone group died. Renal failure (doubling of serum creatinine) developed in four patients in the cyclophosphamide group compared with five patients in the methylprednisolone group. Cumulative probability of not doubling serum creatinine was similar for cyclophosphamide and methylprednisolone groups (0.66 vs 0.69, respectively, P > 0.20, after 18 months). Cumulative probability of survival without renal failure was also not significantly different (0.61 and 0.63, respectively, P > 0.20, after 18 months). These results suggest that pulse cyclophosphamide is as effective as pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis.

Adult↗

Glycosaminoglycans prevent induction of fragmentation of porcine oocytes stimulated by dibutyryl cyclic adenosine 3',5'-monophosphate in culture.

The in vitro effects of derivatives of cyclic adenosine 3',5'-monophosphate (cAMP) and glycosaminoglycans (GAGs) on the spontaneous induction of fragmentation of cultured porcine oocytes were examined. Oocytes cultured for 72 h or longer undergo spontaneous fragmentation, and the percent of fragmented oocytes increased thereafter. The fragmented oocytes consisted of several "blastomeres" showing uneven distribution of DNA among the "blastomeres". Cytoplasmic bodies were also identified on the surface of fragmented oocytes and in the space among fragmented "blastomeres". Dibutyryl cyclic adenosine 3',5'-monophosphate (dbcAMP) at concentrations exceeding 50 microM markedly increased the induction of fragmentation. 8-bromoadenosine 3',5'-cyclic monophosphate, butyrate, cAMP and GAGs isolated from porcine follicular fluid (pFF) did not stimulate the induction of fragmentation. pFF-GAGs added to the suspending medium at concentrations of 10 micrograms/ml or greater prevented the occurrence of dbcAMP-stimulated fragmentation of isolated porcine oocytes in a dose-dependent manner. Preparations of hyaluronic acid and chondroitin sulfate from a commercial source prevented the occurrence of fragmentation stimulated by dbcAMP. The present findings suggest that cAMP may involve the induction of fragmentation of porcine oocytes and GAGs prevent the activation of cAMP-dependent fragmentation.

Animals↗

The effect of pig follicular fluid fractions on cumulus expansion and male pronucleus formation in porcine oocytes matured and fertilized in vitro.

The aim of this study was to analyse the substance(s) present in porcine follicular fluid that promotes cumulus expansion and male pronucleus formation in pig oocytes matured and fertilized in vitro. The follicular fluid was separated into four fractions by ultracentrifugation at 220,000 g at 10 degrees C for 48 h. Oocyte-cumulus-cell complexes obtained from prepubertal gilts were cultured in vitro for 48 h in each of the fractions after reconstitution with a modified Krebs-Ringer bicarbonate solution. Each fraction containing oocyte-cumulus complexes was then fertilized in vitro with frozen-thawed and preincubated epididymal boar spermatozoa. After 24 h of culture, oocytes that matured in fraction 1 showed a marked expansion of the surrounding cumulus, as did those matured in pig follicular fluid. However, complexes cultured in the remaining fractions exhibited very little or no expansion. No difference was observed in the degree of expansion caused by follicular fluid collected from small, medium or large follicles. Further analysis of fraction 1 by HPLC gave several subfractions, one of which (22) induced a significantly greater expansion of the cumulus than did others (P < 0.01). Fraction 1 also induced higher rates of male pronuclei formation (62%) than did fractions 2, 3 and 4 (22%, 35% and 30%, respectively). The rate of male pronuclei formation in pig follicular fluid from large follicles was significantly lower (33%) than in fluid from small or medium follicles (89% and 78%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes of plasma lipid and lipoproteins by rehabilitation therapy for stroke.

Changes of the plasma levels of lipid by rehabilitation therapy for approximately 10 weeks were studied in 14 cases of stroke. Hypercholesterolemia or hypertriglyceridemia was present in a half cases of stroke, and HDL cholesterol was lower than the normal level in most cases before starting rehabilitation therapy. After rehabilitation therapy, hypertriglyceridemia was normalized in most cases. On the other hand, the plasma levels of cholesterol and LDL cholesterol were decreased slightly. HDL cholesterol was increased and atherogenic index was improved by rehabilitation therapy.

Cerebrovascular Disorders↗

Novel antibiotics SF2738A, B and C, and their analogs produced by Streptomyces sp.

Three new antibiotics SF2738A, B and C, and their analogs were isolated from the culture broth of Streptomyces sp. The antibiotics are active against Gram-positive bacteria, Gram-negative bacteria and fungi, and exhibited cytotoxic activity against P388 murine leukemia cells with IC50 values of 0.08, 0.25 and 7.5 micrograms/ml, respectively. Their structures were determined by spectral analyses and chemical conversion. Especially, the structure of SF2738A was confirmed to be (E)-((4-methoxy-5-methylthio-2-(2-pyridyl)pyridin-6-yl)methylene)azan ol by X-ray crystallographic analysis.

Animals↗