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Biomedical subjects

M Abe

Publications and source records attributed to M Abe.

At least 433 records · Page 24Linked to original sources
PubMed1997

Suppressed bone induction by follistatin in spontaneously hypercholesterolemic rat bone.

Bone inducing activity in demineralized bone matrix (DBM) of young spontaneously hypercholesterolemic (SHC) rats has been shown to be lower than that of aged SHC rats. This study examined the involvement of bone follistatin, an activin-binding protein, in bone induction. Immunoreactive follistatin was higher in DBM from 10-week-old SHC rats (DBM-10wk) than in DBM from 6-month-old SHC rats (DBM-6mo). When DBM without follistatin supplement was implanted, the C-propeptide of type II procollagen and calcium contents on day 12 in implants of DBM-6mo were 68% and 40% higher than those of DBM-10wk, respectively. In contrast, follistatin supplement to DBM decreased C-propeptide of type II procollagen and calcium contents in implants of both DBM-10wk and DBM-6mo, and the levels of these parameters were comparable between DBM-10wk and DBM-6mo, indicating reduced formation of cartilage and bone. These findings suggest that 1) follistatin content in bone matrix decreases with advancing age in SHC rats, and 2) the follistatin interferes with endochondral bone formation. We demonstrate that the lower bone induction of DBM from young SHC rats was partly due to the abundance of follistatin in bone matrix.

Aging↗
PubMed1997

Catabolism of lipoprotein-X induced by infusion of 10% fat emulsion.

The clinical significance of lipoprotein-X (Lp-X) induced by intravenous infusion of 10% fat emulsion was assessed, with special reference to atherogenesis, by in vitro experiment using purified Lp-X from the sera of patients receiving Intralipid 10%. Lp-X appeared after long-term intravenous infusion of 10% fat emulsion in the patients with intestinal fistula due to the anastomotic leakage. To clarify the role of Lp-X in terms of atherogenicity, the cholesterol metabolism of Lp-X in macrophages as scavenger cells and in hepatocytes as parenchymal cells was studied. When [3H]cholesterol-labeled Lp-X or oxidized low-density lipoprotein (o-LDL) was incubated with J-774 macrophages, the incorporation of Lp-X into macrophages was negligible compared with o-LDL. When Lp-X or high-density lipoprotein (HDL) was incubated with J-774 macrophages laden with [3H]cholesterol, the release of cholesterol from macrophages was enhanced by Lp-X as well as HDL. When [3H]cholesterol-labeled Lp-X LDL or HDL was incubated with the human hepatoma cell line of Hep G2 cells, the incorporation of Lp-X into Hep G2 cells was less than that of LDL, but similar to that of HDL. From these findings, it is suggested that the catabolism of Lp-X cholesterol generated with intravenous 10% fat emulsion was mediated by hepatocytes rather than by macrophages, indicating that the hyperlipidemia due to increased Lp-X may not be atherogenic.

Animals↗
PubMed1997

Comparative studies of circulating KL-6, type III procollagen N-terminal peptide and type IV collagen 7S in patients with interstitial pneumonitis and alveolar pneumonia.

KL-6, a MUC1 mucin preferentially expressed in regenerating type 2 pneumocytes, has been reported to be a sensitive serum marker for evaluating the disease activity of interstitial pneumonitis (IP). Type III procollagen N-terminal peptide (PIIIP) and type IV collagen 7S (7S collagen) have also been reported to be useful in the serological evaluation of the activity. Their levels were measured and their serodiagnostic values were compared simultaneously in patients with IP and alveolar pneumonia. The study population was 45 patients with IP and 12 patients with alveolar pneumonia. Serum KL-6 levels were measured by a specific enzyme immunoassay, and both serum PIIIP and 7S collagen concentrations by their correspondent radioimmunoassay kits. There were no significant difference of serum C-reactive protein level, which was evaluated as an indicator of inflammatory process, between IP and alveolar pneumonia patients. In IP, the abnormally elevated rate of KL-6 [80% (36/45)] was significantly higher than those of PIIIP [40% (18/45)] and 7S collagen [40% (18/45)]. In alveolar pneumonia, the rate of KL-6 [0% (0/12)] was significantly lower than those of PIIIP [33% (4/12)] and 7S collagen [25% (3/12)]. There were no significant correlations among serum levels of the markers. These observations indicate that the serodiagnostic value of KL-6 for IP is superior to that of PIIIP and 7S collagen, and that KL-6 has a characteristic to discriminate IP from alveolar pneumonia.

Antigens↗
PubMed1997

Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts.

Signaling pathways mediated by tyrosine phosphorylation and dephosphorylation have been reported to be involved in the regulation of cytoskeletal organization in osteoclasts, the principal cells responsible for bone resorption. We examined the effects of tiludronate [(4-chlorophenyl)thiomethylene bisphosphonate] on the cytoskeleton and the balance of phosphotyrosine levels in osteoclast-like multinucleated cells (OCLs) formed in cocultures of mouse osteoblastic cells and bone marrow cells. When OCLs were placed on plastic dishes in the presence of 10% fetal bovine serum, they formed a ringed structure of F-actin dots (actin ring) within 2 h. Tiludronate did not inhibit the process of actin ring formation, but it disrupted preformed actin rings in a time- and a dose-dependent manner. Western blot analysis using an antiphosphotyrosine antibody revealed that tyrosine phosphorylation of certain proteins in OCLs was stimulated by tiludronate added to the purified OCLs. Tyrosine kinase activity of the p60c-src immunoprecipitated from cell lysates of the purified OCLs was not affected by tiludronate directly added to the kinase assay. OCL lysates stimulated dephosphorylation of tyrosine-phosphorylated substrates such as phosphoneuroprotein 14 and epidermal growth factor receptors. Like sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, tiludronate dose-dependently inhibited tyrosine dephosphorylation of those substrates induced by OCL lysates. These findings suggest that tiludronate disrupts the preformed actin rings and suppresses bone-resorbing activity by inhibiting protein tyrosine phosphatases in osteoclasts.

Actins↗
PubMed1997

Bisphosphonate tiludronate increases bone strength by improving mass and structure in established osteopenia after ovariectomy in rats.

We examined the mechanical properties of bone in ovariectomized rats treated with tiludronate. 186 Sprague-Dawley (SD) rats, 6 months of age, were assigned to 13 groups and were maintained for 3-9 months after surgery. Ovariectomy (ovx) groups were given tiludronate orally at the respective doses of 0 (vehicle), 12.5 (low), 25 (medium), and 50 (high) mg/kg body weight daily for 3 months beginning 3 months after surgery. Rats were killed at 0 (start), 3, 6, and 9 months. Whereas bone mineral density (BMD) values of the midfemur did not increase after ovx, the values in the sham-operated groups increased age-dependently. Bending moment to failure of the femur in the sham group was larger than that of the ovx control group at 9 months. In the ovx control groups, the ultimate compressive load values of the third lumbar body were reduced compared with those in the sham groups at 3 months and thereafter. Although serum osteocalcin levels were decreased in the medium- and high-dose tiludronate groups, both serum PTH and 1,25(OH)2D levels were increased only in the high-dose group. Femoral BMD, mechanical properties, and the cortical bone area were increased by the high dose at 9 months. Lumbar ultimate compressive load and the circumscribing cortical shell area in the high-dose group were increased at 6 months and thereafter. The trabecular number values were maintained at 6 and 9 months by the high dose. These data demonstrate that tiludronate administration increased the mechanical properties of bone by preserving the age-dependent increases in the cortical bone mass and three-dimensional structure of trabecular bone. These effects seemed to be due to reduced bone turnover by the agent.

Animals↗
PubMed1997

Reduction of hypoxic cells in solid tumours induced by mild hyperthermia: special reference to differences in changes in the hypoxic fraction between total and quiescent cell populations.

C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps in order to label all proliferating (P) cells. The tumours were then heated at 40 degrees C for 60 min. At various time points after heating, tumour-bearing mice were irradiated while alive or after being killed. Immediately after irradiation, the tumours were excised, minced and trypsinized. The tumour cell suspensions obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labelling, which could be regarded as quiescent (Q) cells, was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P+Q) tumour cell population was determined from the irradiated tumours that were not pretreated with BrdU. The MN frequency of BrdU unlabelled cells was then used to calculate the surviving fraction of the unlabelled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total (P+Q) tumour cells. In general, Q cells contained a greater hypoxic fraction (HF) than the total tumour cell population. Mild heating decreased the HF of Q cells more markedly than in the total cell population, and the minimum values of HFs of both total and Q cell populations were obtained 6 h after heating. Two days after heating, the HF of total tumour cells returned to almost that of unheated tumours. In contrast, the HF of Q cells did not return to the HF level of unheated tumours until 1 week after heating. It was thought that irradiation within 12 h after mild heating might be a potentially promising therapeutic modality for controlling radioresistant Q tumour cells.

Animals↗
PubMed1997

A phase I/II study of a hypoxic cell radiosensitizer KU-2285 in combination with intraoperative radiotherapy.

A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given before intraoperative radiotherapy (IORT) to 30 patients with unresectable, unresected or macroscopic residual tumours. Twenty-three patients had pancreatic cancer and five had osteosarcoma. The IORT dose was 30 Gy for unresectable pancreatic cancer and 60 Gy for osteosarcoma. The dose of KU-2285 administered ranged from 1 to 9 g m-2. Four patients received a dose of 9 g m-2, and ten received 6.8-7 g m-2. All patients tolerated KU-2285 well, and no drug-related toxicity was observed. The average tumour concentration of KU-2285 immediately after IORT was 166 microg g-1 at dose of 6.8-7 g m-2 and 333 microg g-1 at 9 g m-2. The average tumour-plasma ratio was > or = 0.82. Eleven patients with unresectable but localized pancreatic cancer treated with KU-2285 plus IORT and external beam radiotherapy had a median survival time of 11 months and 1-year local control rate of 50%, which compares favourably with those of 8 months (P = 0.26) and 28% (P = 0.10) for 22 matched historical control patients. The five patients with osteosarcoma attained local control. The results of this first study on KU-2285 and IORT appear encouraging, and further studies of this compound seem to be warranted.

Adolescent↗
PubMed1997

Absence of prostaglandin E2-induced hyperalgesia in NMDA receptor epsilon subunit knockout mice.

1. We have previously found that intrathecal administration of prostaglandins E2 (PGE2) and D2 (PGD2) into conscious mice induced hyperalgesia by the hot plate test. The present study investigated the involvement of N-methyl-D-aspartate (NMDA) receptor in the prostaglandin-induced hyperalgesia by use of mice tacking NMDA receptor epsilon 1, epsilon 4, or epsilon 1/epsilon 4 subunits. 2. PGE2 induced hyperalgesia over a wide range of doses from 50 pg to 500 ng kg-1 in wild-type mice. But PGE2 could not induce hyperalgesia in epsilon 1, epsilon 4, or epsilon 1/epsilon 4 subunit knockout mice. 3. The NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (D-AP5), the non-NMDA receptor antagonist 7-D-glutamylaminomethyl sulphonic acid (GAMS), and the nitric oxide synthase inhibitor N epsilon-nitro-L-arginine methyl ester (L-NAME) inhibited the PGE2-induced hyperalgesia in wild-type mice. 4. PGD2 induced hyperalgesia at doses of 25 ng to 250 ng kg-1 in both wild-type and epsilon 1/epsilon 4 subunit knockout mice. The substance P receptor antagonist OP 96.345 blocked the PGD2-induced hyperalgesia in wild-type and epsilon 1/epsilon 4 subunit knockout mice. 5. These results demonstrate that the pathways leading to hyperalgesia are different between PGD2 and PGE2, and that both epsilon 1 and epsilon 4 subunits of the NMDA receptor are involved in the PGE2-induced hyperalgesia.

Animals↗
PubMed1997

Immunolocalization of type I or type II activin receptors in the rat brain.

We have studied immunolocalization of activin receptors in the central nervous system using polyclonal antibodies (IgG) to type I (50-55 kDa, ActRI), type II (70-75 kDa, ActRII) or a subtype of type II known as type IIB (ActRIIB) receptors of activin. A total of 7 antisera to rat activin receptors was generated, i.e. 3 kinds of antisera to the extracellular domain (ActRI(81-89), ActRII(91-100), or ActRIIB(90-99)) and 4 antisera to the kinase domain (ActRI(323-333), ActRII(307-319), ActRII(407-420) or ActRIIB(306-319)). The region of aa 407-420 of ActRII is identical with that of ActRIIB. At first, we characterized these antibodies by Western blot analysis using ovarian proteins fractionated by preparative SDS-PAGE. All antibodies to ActRII and ActRIIB specifically reacted with 75 kDa-proteins which could also bind to activin-A. Anti-ActRII(91-100) antibody also reacted with 62 kDa-proteins which were capable of binding with activin-A. Although no positive reactions to anti-ActRI(81-89) antibody were seen in ovarian proteins, a positive reaction was detected at 52 kDa only when the proteins were deglycosylated. By use of these antibodies, immunolocalization of activin receptors was examined in the rat brain. The patterns of expression of activin type I and type II receptors were different. Positive reactions to anti-ActRII(91-100) antibody were detected in neurons of the cerebral cortex, hippocampus, medial amygdala and thalamus. In the hypothalamus, some neurons of the supraoptic nucleus were weakly stained, and widely scattered neurons of the lateral hypothalamic area were moderately stained. On the contrary, the most intense reactions to anti-ActRI(81-89) antibody were detected in neurons of the lateral hypothalamic area. In addition, many neurons of the cerebral cortex were also stained, but neurons of the hippocampus and the amygdala were not stained. These results suggest that activin may have physiological roles not only for hypothalamic neuroendocrinological and feeding-related systems as suggested previously but may also have functions in cortical and limbic pathways as a neuromodulator or for maintenance of neurons.

Activin Receptors↗
PubMed1997

Clinical study of 16 fully grown cerebral aneurysms.

The mechanismus of recurrence and enlargement of 16 cerebral aneurysms have been analyzed: 2 dissecting aneurysms, 6 fully grown aneurysms after neck clipping, 1 case after treatment with dome clip, 3 ruptured aneurysms that developed at the same sites and 4 cases that developed at other sites. From our investigation we concluded it was fundamentally important that the factor of the elastic lamina interna must attach in whole around the neck with precise neck clipping or adequate tight embolization involving positioning of the remaining elastica lamina interna in coil embolization.

Aortic Dissection↗
PubMed1997

Comparison of accelerated hyperfractionated radiotherapy and conventional radiotherapy for supratentorial malignant glioma.

Between 1988 and 1993, 71 patients with glioblastoma or anaplastic astrocytoma were treated either with accelerated hyperfractionation radiotherapy (1.5 Gy twice daily to a total dose of 69 Gy, n = 35) or with conventional fractionation radiotherapy (1.8 Gy daily to 64.8 Gy, n = 36). Two patients in each group did not complete radiotherapy, leaving 67 evaluable. All patients received the chemotherapeutic regime ACNU intraarterially (50 mg/m2) or intravenously (100 mg/m2) prior to and after radiotherapy. Between 1990 and 1992, 19 patients also received intravenous interferon-beta (3 x 10(6) U, three times weekly) during radiotherapy. The median survival time was 14.5 months for the accelerated hyperfractionation group and 14 months for the conventional fractionation group. The median time to progression was 12 months for the accelerated hyperfractionation group and 9.5 months for the conventional fractionation group. There was no significant difference in either survival (P = 0.89) or progression-free survival (P = 0.25) between the accelerated hyperfractionation and conventional fractionation groups. Interferon therapy was associated with poorer survival. Brain necrosis developed in four out of 10 patients receiving accelerated hyperfractionation radiotherapy plus interferon-beta, but in none of nine patients receiving conventional fractionation radiotherapy plus interferon (P = 0.033). In conclusion, our study failed to demonstrate any possible benefit of accelerated hyperfractionation radiotherapy for malignant glioma. The incidence of brain necrosis may be increased by combining accelerated hyperfractionation radiotherapy and interferon-beta.

Adult↗
PubMed1997

Appropriate osteotomy site and number in limb lengthening.

The effects of the placement of osteotomy site on osteogenesis during monofocal and bifocal lengthening were investigated in 47 immature rabbits allocated to 4 groups according to osteotomy site: (1) monofocal in the proximal diaphysis; (2) monofocal in the distal diaphysis; (3) bifocal in the proximal and distal diaphysis; and (4) bifocal in the proximal diaphysis. The right tibia was distracted at an overall rate of 1.0 mm per day for 15 days. These groups were compared by assessment of soft radiograph findings and torsional strength 2 and 6 weeks after the end of distraction. Microangiography was done in 5 rabbits in the bifocal proximal and distal group. The proximal distracted site showed favorable bone regeneration compared with the distal site, and torsional strength was significantly greater in the proximal than in the distal osteotomy group. Less bone formation and lower torsional strength were observed in the bifocal proximal diaphysis group, with short intermediate segment, than that in the other bifocal group, with long intermediate segment. The nutrient artery in the latter group was preserved in the intermediate segment and reanastomosed to the metaphyseal arteries. These results suggest that the proximal diaphysis is more suitable for the osteotomy site than is the distal diaphysis. In a 2-level osteotomy, the inflow site of the nutrient artery should be included within the intermediate segment.

Animals↗
PubMed1997

Morphological study of bovine pregnant corpus luteum cells.

The bovine pregnant corpus luteum was examined morphologically, to clarify the appearance and properties of the intramitochondrial bodies (IMB) in mitochondria of the large luteum cell (LLC). The incidence and diameter of the IMB (200-900 nm) showed a tendency to increase with the advance of pregnancy. Histochemically, the IMB reacted positively with protein, and immunohistochemically, they reacted IMB with 11 alpha-hydroxyprogesterone-1-11 succinyl-bovine serum albumin (P-BSA). The IMB seemed to combine with protein, and these granules did not undergo exocytosis. The cytoplasm of LLC contained another type of small electron-dense granules that were 150-200 nm in diameter, had an orifice for secretion, and reacted with relaxin. Small luteum cells (SLC) revealed crystalline-like inclusions. It is suggested that these inclusion cells participate in the synthesis of steroids.

Animals↗
PubMed1997

Clinical and histological features of cytomegalovirus hepatitis in previously healthy adults.

It is well known that cytomegalovirus infection is often accompanied by hepatitis, but there have been few comparative studies with respect to clinical features of cytomegalovirus-associated hepatitis and other acute viral hepatitides. In the present study, clinical and pathological features of 11 acute sporadic cytomegalovirus hepatitis infections in previously healthy adults were compared with those of 45 acute sporadic viral hepatitis, including type A, type B and type C. As a result, the characteristics of cytomegalovirus hepatitis were a long-lasting fever, splenomegaly, atypical lymphocytosis, a mild transaminasemia, a low ratio of alanine aminotransferase level to lactate dehydrogenase level, and mild hepatic histopathological changes.

Acute Disease↗
PubMed1997

Cross sectional echocardiographic demonstration of the mechanisms of abnormal interventricular septal motion in congenital total absence of the left pericardium.

OBJECTIVE: To investigate the influence of the absence of the pericardium on the left ventricular wall, particularly on interventricular septal motion, using M mode and cross sectional short axis echocardiography in patients with congenital total absence of the left pericardium. METHODS: 21 patients with, congenital total absence of the left pericardium were divided into three groups according to the interventricular septal motion; systolic type (n = 6) with paradoxical motion during systole, diastolic type (n = 11) with abnormal posterior motion during mid to late diastole, and mixed type (n = 4) with paradoxical motion during systole and abnormal posterior motion during diastole. RESULTS: On cross sectional short axis echocardiograms of the left ventricle, in the diastolic type the degree of angular displacement of the papillary muscles during end diastole to end systole showed excessive anticlockwise rotation about the long axis of the left ventricle without marked anteroposterior displacement. In the systolic type, there was shift of the left ventricle towards the anteromedial portion in systole and towards the posterolateral portion in diastole without significant rotation. There was a significantly positive correlation between the degree of angular displacement and the amplitude of diastolic interventricular septal motion during mid to late diastole in all patients. CONCLUSIONS: There was abnormal interventricular septal motion during systole and diastole in patients with total absence of the left pericardium. Abnormal systolic motion was induced by anteroposterior displacement of the left ventricle, and abnormal diastolic motion by left ventricular rotation about the long axis of the heart during the cardiac cycle. Analysis using cross sectional echocardiography was useful for elucidating the mechanisms of abnormal interventricular septal motion.

Adult↗