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Biomedical subjects

A Nemoto

Publications and source records attributed to A Nemoto.

At least 37 records · Page 2Linked to original sources

Osteopontin involvement in integrin-mediated cell signaling and regulation of expression of alkaline phosphatase during early differentiation of UMR cells.

To clarify the function of osteopontin in osteoblast differentiation, we have examined the signal transduction pathway in an osteoblastic cell line (UMR106-6) bound to osteopontin, fibronectin, vitronectin and collagen type I surfaces. This was done by investigating the production and autophosphorylation of focal adhesion kinase (FAK) and the expression of alkaline phosphatase (ALP) at the transcription level. Results suggest that osteopontin was not only responsible for the autophosphorylation of FAK but regulated the expression of ALP, which was strongly correlated with FAK activity. These results suggest that osteopontin might act as a trigger in the early differentiation of osteoblasts.

Alkaline Phosphatase↗

Ethanolamine modulates the rate of rat hepatocyte proliferation in vitro and in vivo.

A low molecular weight, heat-resistant hepatotrophic factor in an extract from the bovine intestinal mucosa was purified and identified as ethanolamine by structural analyses. The mode of action of ethanolamine in vitro and in vivo coincided with that of the crude extract of the tissue, indicating that ethanolamine is the active component. Ethanolamine synergistically elevated the stimulation of DNA synthesis in hepatocytes in primary culture when added together with a growth factor, such as epidermal growth factor, with the ED50 being 20 microM, although it showed little stimulatory effect by itself. Contrary to these in vitro results, the intraperitoneal administration of ethanolamine hydrochloride (24 mg of ethanolamine per kg of body weight) enhanced hepatocyte proliferation in regenerating rat livers after two-thirds hepatectomy without the administration of any growth factors. In the regenerating liver, hepatocyte proliferation may be initiated by an endogenous growth factor, but the supply of ethanolamine in circulation may not be sufficient for optimal hepatocyte proliferation; thus, the exogenous administration of ethanolamine may further enhance hepatocyte proliferation. Ethanolamine in circulation may be a humoral hepatotrophic factor.

Animals↗

Comparison of various lazaroid compounds for protection against ischemic liver injury.

Lazaroids are a group of 21-aminosteroids that lack steroid action but have a potent cytoprotective effect by inhibiting iron-dependent lipid peroxidation. However, there have been conflicting reports on the effectiveness and potency of the various lazaroid compounds. In this study, we compared the effectiveness of three major lazaroids on warm liver ischemia in dogs using a 2-hr hepatic vascular exclusion model. The agents were given to the animals intravenously for 30 min before ischemia. The animals were divided into 5 groups: Control (n=10), no treatment; Group F (n=6), U-74006F (10 mg/kg); Group G (n=6), U-74389G (10 mg/kg); Group A1 (n=6), U-74500A (10 mg/kg); Group A2 (n=6), U-74500A (5 mg/kg). The effect of treatment was evaluated by two-week animal survival, hepatic tissue blood flow, liver function tests, blood and tissue biochemistry, and histological analyses. Animal survival in all treated groups was significantly improved compared with the control (83-100% versus 30%). Elevation of liver enzymes after reperfusion was markedly attenuated in treated groups, except for an early significant increase in Group G. Postreperfusion hepatic tissue blood flow was much higher in all treated animals (50% of the preischemic level vs. 25% in the control). Lazaroids, particularly U-74500A at 5 mg/kg (Group A2), suppressed adenine nucleotide degradation during ischemia and enhanced the resynthesis of high-energy phosphates after reperfusion. Although structural abnormalities in postreperfusion liver tissues were markedly ameliorated in all treated groups, Group A2 showed significantly less neutrophil infiltration. Liver injury from warm ischemia and reperfusion was attenuated with all lazaroid compounds, of which U-74500A at 5 mg/kg exhibited the most significant protective activity.

Animals↗

Developmental sequence of human fetal body movements in the second half of pregnancy.

To describe fetal body movements precisely and to clarify their developmental sequence in the second half of pregnancy, fetal body movements were observed in 31 normal fetuses between 20 and 41 weeks of pregnancy by using multiple ultrasonic machines. All movements of the whole trunk were able to be classified into six fundamental movements: flexion, stretch, rolling, startle, stepping, and writhing. Startle was always observed as a single movement, but others were more frequently observed as a part of combination rather than as a single movements. The incidence of flexion and stretch peaked at 28-31 weeks, whereas the incidence of startle and stepping lowered at the period. The incidence of rolling and upper half trunk movements increased at 40-41 weeks. Limb movements were frequent and did not exhibit characteristic change in the incidence. In conclusion, we classified fetal body movements into several fundamental movements instead of using the expression of "general movements" by focusing principally on movements of the trunk. In particular, some of the fundamental movements seem to appear in characteristic ways as related to gestational age. In view of that fetal behaviors are closely related to the neural activity, the present findings may contribute to an understanding of the developmental process of the central nervous system.

Abdomen↗

The binding ability to matrix proteins and the inhibitory effects on cell adhesion of synthetic peptides derived from a conserved sequence of integrins.

The beta peptide (113-125), derived from a conserved sequence of the beta subunit of integrins, was synthesized to investigate its adhesive properties to matrix proteins and the effects on cell adhesion to immobilized fibronectin. In this study, we observed that the biotinylated beta peptide was able to bind efficiently to immobilized fibronectin, fibrinogen, collagen Type I and vitronectin with different degrees of affinity. It was also demonstrated that biotinylated fibronectin or fibrinogen could bind to the coated beta peptide. This kind of binding, which might be non-covalent linkage, was partially blocked by coincubation with the peptide GRGDS or EDTA, but not by SDGRG. Cell adhesion experiments were performed to study the effect of the beta peptide. The data showed that the beta peptide partially inhibited both fibroblast L929 and MC3T3-E1 osteoblastic cells from adhering to immobilized fibronectin in a dosage-dependent manner. In the presence of 100 microM concentration of the beta peptide, the inhibition rate of cell adhesion was 34% for fibroblast L929 cells and 54.1% for MC 3T3-E1 osteoblastic cells. This research suggests that the beta peptide might act independently as an adhesive region of the beta subunit of integrins and may occupy the cell-binding site within fibronectin.

Amino Acid Sequence↗

Interferon-alpha therapy for individuals with normal serum alanine aminotransferase levels before treatment.

While interferon (IFN) therapy is approved for patients with chronic hepatitis C infection, the effectiveness of IFN therapy for anti-hepatitis C virus (HCV)-positive individuals with normal ALT levels remains poorly understood. Twenty-five individuals (M:F = 9:16; age = 51.8 +/- 15.1 years) who showed a normal alanine aminotransferase (ALT) level (< 30 IU/L) at least 6 months before treatment and were positive for both anti-HCV and serum HCV-RNA by reverse transcription polymerase chain reaction (RT-PCR) were studied. Of these, 16 received IFN therapy for 24 weeks (780 million units total IFN-alpha 2b) and nine were followed for 12 months as controls. The serum HCV-RNA level was determined by bDNA assay and HCV genotype was detected by enzyme immunoassay. All were shown to have chronic hepatitis by liver biopsy. Six (37.5%) of 16 individuals lost serum HCV-RNA by RT-PCR 6 months after cessation of therapy (complete response; CR), while the remaining individuals were defined as non-responders (NR). Of the six individuals in the CR group, five had HCV type 2 infection, compared with none of 10 individuals in the NR group (P < 0.01). There was a trend towards a lower pretreatment viraemia level in the CR group than in the NR group. These data suggest that IFN therapy for individuals with HCV type 2 infection and normal ALT levels was effective.

Alanine Transaminase↗

Recognition of osteopontin by rat bone marrow derived osteoblastic primary cells.

To study the role of osteopontin, we did cell adhesion and ALP assays of rat bone marrow osteoblastic cells (RBMO) on collagen Type I and osteopontin surfaces. The RBMO proved to adhere much more strongly to the osteopontin and to have higher ALP activity on the osteopontin, which suggests that pre-osteoblasts differentiate into osteoblasts that form bone by recognizing osteopontins.

Alkaline Phosphatase↗

Brasilinolide A, a new macrolide antibiotic produced by Nocardia brasiliensis: producing strain, isolation and biological activity.

A new 32-membered macrolide antibiotic, brasilinolide A was isolated from the fermentation broth of Nocardia sp. IFM 0406. The producer was identified as Nocardia brasiliensis. The antibiotic was only active against Aspergillus niger, but not active against other fungi including yeasts as well as other filamentous like fungi and bacteria. Brasilinolide A exerted an immunosuppressive activity in the assay system of a mixed lymphocyte reaction (MLR).

Animals↗

Brasiliquinones A, B and C, new benz[alpha]anthraquinone antibiotics from Nocardia brasiliensis. I. Producing strain, isolation and biological activities of the antibiotics.

New benz[alpha]anthraquinone antibiotics (brasiliquinones A, B and C) with an ethyl group at C-3 were isolated. The producer was identified as Nocardia brasiliensis. The antibiotics were active against Gram-positive bacteria including Mycobacterium sp., but not active against Gram-negative bacteria or fungi. They were also active against multiple drug-resistant P388/ADR tumor cells.

Animals↗

Zinostatin stimalamer-transcatheter arterial embolization for hepatocellular carcinoma: a comparison with lipiodol-transcatheter arterial embolization.

Twenty patients with unresectable hepatocellular carcinoma were treated by zinostatin stimalamer-transcatheter arterial embolization (SMANCS-TAE). After administration of SMANCS, a superselective catheterization technique was used to inject gelatin sponge particles into the artery or artery branch supplying the cancer-bearing segment. We compared the results of SMANCS-TAE with Lipiodol (Yamanouchi, Tokyo, Japan)-TAE performed during the same period. In 18 of 20 patients (90%), a tumor necrosis rate of 100% (grade 4) was obtained after one or two courses of SMANCS-TAE. The SMANCS group was superior to the Lipiodol-TAE group in terms of the tumor reduction rate, alpha-fetoprotein reduction rate, and cumulative 1.5-year survival rate, but not significantly. No severe side effects were noted after SMANCS-TAE. SMANCS-TAE appears to have potential as a new treatment for hepatocellularcarcinoma, and patients treated with this technique will be monitored to elucidate the long-term effects.

Aged↗

[Changes in metabolism and peritumoral circulation after radiosurgery of metastatic brain tumors: evaluation by three dimensional dual isotope SPECT].

Concurrent use of two different isotopes, 201T1C1 and 123I-IMP, in SPECT is useful in separative evaluation of tumor metabolism and peritumoral circulation. Three dimensional SPECT employed in our study has an obvious advantage over two dimensional SPECT for its accurate imaging of tumors and peritumoural areas. Changes of tumor metabolism and regional circulation in peritumoral edematous tissues were investigated by fused 3-D SPECT images using 201T1C1 and 123I-IMP. In this study, the volume of isotope accumulative and isotope defective regions were measured. Fusion of SPECT images was performed by the use of panning visualization software; Application Visualization System Medical View (K.G.T.). The threshold of 3-D rendering was determined by conforming the volume of the hemisphere and of the tumor estimated on CT to the volume of 123I-IMP and 201T1C1 accumulating area respectively. Accumulative volume of 201T1C1 in the tumor decreased remarkably at 7 days after radiosurgery (p < 0.01). Defective volume of peritumoral hypoperfusion was measured on 3-D SPECT. The average volume was 80.5 + 32.5cm3 before radiosurgery. It decreased by approximately 60% at 7 days after radiosurgery (p < 0.05). Analysis of 3-D SPECT images using two different isotope tracers is reliable and useful to evaluate early the changes of metabolism and peritumoral circulation in or around intracerebral tumors.

Aged↗

Lazaroid U-74389G for 48-hour canine liver preservation.

Lazaroids have been reported to attenuate preservation and reperfusion injury. In this study, we examined whether lazaroids can improve the outcome after 48-hr canine liver preservation and transplantation. Adult female beagle dogs were randomized into 4 dosage groups (5 animals each). Lazaroid U-74389G was intravenously administered at a dose of 0 mg/kg, 6 mg/kg, 10 mg/kg, or 15 mg/kg to donors 30 min before harvesting and also to recipients 30 min before revascularization. Control animals (0 mg/kg) were given the lazaroid vehicle. The liver grafts were orthotopically transplanted after 48 hr of hypothermic preservation in UW solution. Lazaroid treatment significantly improved outcome after transplantation. Five-day animal survival increased from 0% in the control to 60% in the 6 mg/kg group, 100% in the 10 mg/kg group, and 80% in the 15 mg/kg group. Lazaroid protected the hepatocytes from damage during preservation, and enhanced energy charge and hepatic blood flow after reperfusion. Histological alterations were significantly less severe in the lazaroid-treated groups. The area of necrotic hepatocytes decreased from 43.7 +/- 17.7 in the control to 13.5 +/- 3.0 in the lazaroid 10 mg/kg group. These results indicate that lazaroid U-74389G has potential for improvement of clinical liver preservation.

Animals↗

An automated and portable low-flow pulsatile perfusion system for organ preservation.

While machine preservation reduces the incidence of delayed graft function in renal transplant recipients, it is only used in 10% of kidney transplantations. The performance of our portable, low-flow-pulsatile organ perfusion system was examined in a canine kidney autotransplantation model. Grafts were stored for 72 h by simple cold preservation in University of Wisconsin (UW) solution, or by high or low-flow machine preservation After preservation, the grafts were autotransplanted and the animals were followed for 15 days. Graft function was better in machine-preserved kidneys. Tissue biochemistry indicated that machine preservation resulted in higher levels of adenine nucleotides and better histological integrity than the cold storage. While histology and biochemistry of machine-preserved groups were similar, electromicroscopy of high-flow grafts showed mild accumulation of intravenous debris and endothelial swelling. This study shows that a simplified machine perfusion technique is effective for organ preservation.

Animals↗

[Changes of regional perfusion in metastatic brain tumor and peritumoral area after radiosurgery: a study by 123I-IMP dynamic SPECT].

Changes of regional perfusion in the tumor, peritumoral edematous area and juxtatumor brain after radiosurgical treatment for metastatic brain tumor were investigated by dynamic SPECT using 123I-IMP. The SPECT was performed in 12 patients before and 1, 7 and 30 days after stereotactic irradiation. A region of interest (ROI) was selected each in the tumor, peritumoral edematous area, juxtatumor brain and ipsilateral cerebellum. Radioactivity in each ROIs was counted on early SPECT based on dynamic SPECT from 0 to 5 minutes. Mean count/pixel in each ROIs was divited by mean count/pixel in the ROI of the ipsilateral cerebellum and its value was designated as a count ratio (CR). Assuming the pre-treatment CRs are 1.0, relative changes of post-treatment CRs investigated. rCR in the tumor did not show any significant change after radiosurgical treatment. rCR in the edematous area and the juxtatumor brain increased at 7 days after irradiation [Mean +/- SD 1.43 +/- 0.409 (p < 0.05), 1.248 +/- 0.228 (p < 0.05) by Mann-Whitney test] and at 30 days [1.359 +/- 0.245 (p < 0.01), 1.301 +/- 0.287 (p < 0.01)] respectively. Computed tomography revealed no change in the maximum diameter of the tumor at 1 month after irradiation but a significant reduction in the diameter [0.744 +/- 0.227 (p < 0.02)] at 2 months. Early improvement of regional cerebral blood flow in the juxtatumor areas after radiosurgery suggested that radiosurgery could be effective treatment for metastatic brain tumor.

Adenocarcinoma↗

[High uptake of N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) demonstrated by dynamic SPECT in some cases of glioma].

Selective high uptake of N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) in the brain tumors is not common, the mechanism of uptake in the brain tumor is not yet clearly understood. Among 26 cases of gliomas investigated by dynamic SPECT, 4 cases including 2 cases of anaplastic astrocytoma and 2 cases of oligodendroglioma, showed high uptake of 123I-IMP. New three detector type camera which enables us to investigate rapid successive scanning, was used in our study. In dynamic SPECT, 15 successive scans of 2 minutes interval were made for 30 minutes after administration of 123I-IMP. In addition, quick dynamic SPECT was tried in 2 cases, in which 10 quick successive scans of 24 seconds interval were investigated for initial 4 minutes immediately after administration of 123I-IMP. Radioactivity in the region of interest inside the tumor (T) and radioactivity of the corresponding site in the contralateral hemisphere (C) was measured respectively, and T/C ratio was calculated. Time course change of radioactivity (time activity curve: TAC) was analyzed in all cases. Radioactivity was always higher in the tumor and the average T/C ratio was 1.40. TAC showed rapid increase of 123I-IMP in the tumor during initial 2 minutes after administration and keeping its high plateau level for 30 minutes. Angiography in these cases revealed a remarkable tumor stain. On the other hand, these gliomas showed no or slight enhancement effect in CT or MRI. These findings are interpretable as that early high uptake of 123I-IMP in some gliomas is attributable to an increased vascular bed and blood flow with no or minimal derangement of blood brain barrier in these tumors.

Adult↗