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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 757 records · Page 42Linked to original sources

Expression of MDR1 and glutathione S transferase-pi genes and chemosensitivities in human gastrointestinal cancer.

The relationship was analyzed between drug resistance and MDR1 (with MDR signifying multiple drug resistance) and glutathione S transferase-pi (GST-pi) gene expression in four stomach and four colon cancer cell lines. Northern blot analysis by pmdr1 probe showed that stomach cancer cell lines had no detectable level of MDR1 mRNA expression. By contrast, some levels of MDR1 mRNA expression were found in two colon cancer cell lines, indicating doxorubicin resistance. To examine the MDR1 mRNA in each cell level, in situ hybridization was used. It was found that all colon cell lines and two stomach cell lines had more silver grains per cell than KB cells (a human KB kidney epidermoid carcinoma cell line). However, the number of silver grains in each cell was heterogeneous in the colon and stomach cell lines. Low-level MDR1 mRNA expression could be detected even in cell lines without MDR1 mRNA expression by northern blot hybridization. These results suggest the possibility that all gastrointestinal cell lines can acquire multiple drug resistance. In addition, all examined gastrointestinal cell lines had high GST-pi mRNA expression. This GST-pi gene expression shows cisplatin resistance in the examined cell lines. Heterogeneity of GST-pi mRNA expression also was shown at the cellular level.

Adenocarcinoma↗

Synaptic contacts between CGRP-immunoreactive terminals and enkephalin-immunoreactive neurons in the central amygdaloid nucleus of the rat.

An immunoelectron microscopic method combined with immunofluorescence double staining was carried out to examine the relationship between calcitonin gene-related peptide (CGRP)-like immunoreactive (LI) axon terminals and enkephalin (ENK)-LI neurons in the central amygdaloid nucleus (Ce) of the rat. The latter method showed that many ENK-LI cell bodies are densely surrounded by CGRP-LI axons in the lateral subdivision of the Ce (CeL). After taking fluorescence micrographs, the immunoperoxidase technique was used to examine the CGRP-LI axonal profiles under an electron microscope. CGRP-LI terminals were frequently found to form axo-somatic synaptic contacts with ENK-LI neurons in the CeL.

Amygdala↗

Glass-ceramic implant in acetabular bone defect: an experimental study.

Extensive acetabular defects produced surgically in 25 dogs were repaired using A-W glass-ceramic blocks. No dislocation of the femoral head, and no displacement or breakdown of the blocks was seen 1 year after surgery. All dogs were able to run normally shortly after surgery, except for one that limped for a short time. The failure load between the blocks and the bone had increased markedly 2 months after implantation. The failure load/unit area was 33.2 kgw/cm 2 1 year after implantation. We conclude that glass-ceramic supplementation of the acetabulum is successful experimentally, and that this may be a promising method for repair of large acetabular bone defects.

Acetabulum↗

Multicentre trial of ABO-incompatible kidney transplantation. Japanese Biosynsorb ABO-incompatible kidney transplant study group.

A multicentre study of ABO incompatible kidney transplantation using Biosynsorb was started in Japan in November 1989. A total of 51 cases were registered comprising 23 cases of A incompatibility, 26 cases of B incompatibility and two cases of AB incompatibility. The removal of antibodies (IgG and IgM) was carried out using Biosynsorb in 16 cases, plasmapheresis in four cases and use of both combined in 31 cases. The treatment using Biosynsorb was repeated 3.4 times on average. Serum titres of anti-A (IgG and IgM) antibodies decreased to 4.9 +/- 5.0 and 2.7 +/- 1.7 and for anti-B titres decreased to 2.8 +/- 3.5 and 2.4 +/- 3.2. Rejection was found in 33 cases: hyperacute one, accelerated acute five, and acute 27. In two cases rejection was developed concomitantly with a steep elevation in antibody titres. Three patients died, two with functioning grafts. Eight grafts were lost. Patient and graft survivals at 2 years were 94.1% and 84.3%, respectively. From these results it is concluded that: 1. Biosynsorb and plasmapheresis are effective in removing anti-A and anti-B antibodies; 2. graft and patient survivals are similar to those in ABO compatible cases; 3. anti-A and anti-B titres less than 16 are recommended at the time of transplantation; 4. anti-A and anti-B titres higher than 128 may be considered as a risk factor for rejection in the early stages after transplantation.

ABO Blood-Group System↗

Primary intraosseous meningioma: case report.

A case of 72-year-old Japanese woman with a rare intraosseous meningioma is presented. The tumor was located in the right frontoparietal region, involving the coronal suture. The tumor was excised totally and the pathological diagnosis was meningioma. Similar cases reported in the past literature are reviewed and the possible histogenetic mechanism of the tumor is discussed.

Aged↗

Results of hepatic resection and postoperative arterial chemotherapy for hepatocellular carcinoma.

To improve the outcome of patients who had undergone hepatic resection for hepatocellular carcinoma (HCC), we employed postoperative adjuvant hepatic arterial infusion chemotherapy (AHAI) in 23 patients. Patients showing various risk factors for the recurrence of HCC were given one shot of doxorubicin and mitomycin C suspended in an oily medium (lipiodol) and an infusion of 5-fluorouracil. The 3-year survival value calculated for patients who were treated with AHAI was 75%, which was significantly higher than that found for patients who did not receive AHAI (n = 156; P < 0.05). In addition, among the patients who underwent hepatic lobectomy, the survival of those who received AHAI was also significantly greater than that of those who did not (n = 46; P < 0.01). AHAI did not cause any severe complications. These results indicate that AHAI may be an effective therapy for patients with HCC.

Antineoplastic Agents↗

Proliferating cell nuclear antigen in malignant and pre-malignant lesions of epithelial origin in the oral cavity and the skin: an immunohistochemical study.

Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S phase of the cell cycle and immunohistochemical detection of the protein represents a useful marker for the proliferating fraction of cells in tissue specimens. A series of malignant and pre-malignant lesions of the oral cavity and skin were evaluated by the streptavidin biotin immunoperoxidase method for detection of this protein. Monoclonal anti-PCNA antibody (PC 10) labelled proliferating cells in all cases with varying intensity of nuclear staining. In squamous cell carcinoma (n = 48), PCNA positivity correlated with the differentiation and atypia of the tumour cells; however, in poorly differentiated tumours, the relationship between PCNA expression and proliferation was lost. Basal cell carcinoma showed an increased growth fraction in tiny epithelial nests (mean 43.8, SD 6.0, n = 20) than in neoplastic basal cells (mean 30.1, SD 6.9, n = 8). The growth fractions were significantly higher in the pre-malignant lesions (leukoplakia, mean 22.3, SD 7.7, n = 14; Bowen's disease, mean 45.2, SD 11.7, n = 12; senile keratosis, mean 41.2, SD 7.0, n = 12) than in the normal mucosa (mean 9.8, SD 4.9, n = 10), suggesting that cellular growth fractions correlate with the degree of dysplasia in pre-malignant lesions.

Antibodies, Monoclonal↗

Proliferating cell nuclear antigen in breast lesions: correlation of c-erbB-2 oncoprotein and EGF receptor and its clinicopathological significance in breast cancer.

Monoclonal anti-proliferating cell nuclear antigen (PCNA PC10), which is directed against a 36 kDa auxiliary protein for DNA polymerase delta specific for the S-phase of cell cycle, was used to measure tumour cell proliferation in 4 lactating breasts and 98 benign and malignant breast tumours. The percentage of PCNA-positive cells determined by point counting was significantly lower in the lactating breast [mean 3.6%, standard deviation (SD) 0.67, n = 5] than in fibroadenoma and mastopathy (mean 23.7, SD 5.0, n = 2). Primary breast carcinoma showed a PCNA index ranging from 2% to 36% (mean 12.3, SD 9.3, n = 50), whereas in recurrent carcinoma the index was mean 28.5, SD 4.0. A high index was correlated with c-erbB-2 and epidermal growth factor (EGF) receptor membrane reactivity, worsening histological grade, poor survival and disease-free survival. The expression of c-erbB-2 and EGF receptor was associated with poor survival and disease-free survival in primary breast cancer patients.

Breast Neoplasms↗

C-erbB-2 protein in the sera of breast cancer patients.

The c-erbB-2 protein was measured in sera of patients with breast cancer or benign breast diseases to study the significance of this protein as a tumor marker. The mean value and positive rate for this protein (assuming 20U/ml as the cut-off value) were 11.8 U/ml (0%) in benign breast disease (n = 30), 11.8 U/ml (3.1%) in stage I/II primary breast cancer (n = 64), 38.2 U/ml (29.4%) in stage III/IV primary breast cancer (n = 17), 17.9 U/ml (33.3%) in locally recurrent breast cancer (n = 12), 298.4 U/ml (51.0%) in recurrent breast cancer with distant metastases (n = 51), and 12.9 U/ml (0%) in those with no evidence of recurrence (n = 57). Thus, the serum c-erbB-2 protein level was significantly higher in the distant metastatic group. In patients with distant metastases, there was a close association between expression of c-erbB-2 protein in the primary tumor and the serum c-erbB-2 protein level. On the basis of these results, serum c-erbB-2 protein was thought to be useful as a tumor marker for postoperative monitoring of breast cancer, especially in patients positive for expression of this protein in primary cancer tissue.

Breast Neoplasms↗

Experimental study on the effects of sclerosants for esophageal varices on blood coagulation, fibrinolysis and systemic hemodynamics.

The effects of five sclerosants used for treating esophageal varices on blood coagulation and fibrinolysis, systemic hemodynamics, and vascular endothelial cells were studied in mongrel dogs. With each sclerosant, hemolysis and a decrease in the platelet count were observed. Changes in the blood coagulation system occurred immediately after sclerosant administration. Prolongation of the PT and APTT and decreases in fibrinogen and alpha 2-PI were seen in the thrombin (TH), sodium tetradecyl sulfate (STS), and ethanolamine oleate (EO) groups. Polidocanol (PO) and absolute ethanol (ET) had less pronounced effects on these systems. A transient decrease in the cardiac index (CI), pulmonary artery pressure (PAP) and pulmonary artery resistance (PAR) was observed with the administration of the sclerosants, especially in the TH and STS groups. Excessive vascular endothelial damage was observed in the ET group, marked damage was seen in the EO and STS groups and slight damage was recorded in the PO and TH groups.

Animals↗

Microvascular changes of the liver preserved in UW solution. Pathological and immunohistochemical examination.

Rat livers preserved in University of Wisconsin (UW) solution for 24 h were compared with those preserved in Euro-Collins (EC) solution before and after liver transplantation using an immunohistochemical method. Tissue ATP and total tissue adenine nucleotide (TAN) were measured using HPLC. The levels of TAN in the UW group or the EC group were significantly low compared with the control group (no preservation) after 24-h storage. In the EC group, the levels of tissue adenine nucleotides (TAN) decreased 1 h after reperfusion and never reached control levels. In the UW group, the levels of TAN increased a little 1 h after reperfusion and increased more 3 h after reperfusion. After 24-h preservation, the expression of factor VIII-related antigen (FRA) in endothelial cells of central veins was weak in the EC group; in the UW group, FRA was clearly detected in these cells. After reperfusion, although severe endothelial cell damage to the central veins and numerous FRA-positive substances were observed in EC group, endothelial cells of central veins retained their normal structure and FRA-positive substances were rarely noted in the UW group. In both groups, no endothelial changes were detected in portal veins. From these results, it is concluded that UW solution prevents endothelial cell damage and microcirculatory injury in zone III during the preservation period resulting in prevention of initial graft nonfunction. Also, measurement of the TAN level after reperfusion is useful to predict the function of the graft.

Adenine Nucleotides↗

31P nuclear magnetic resonance study of phospholipid metabolites in ischemic liver.

To assess the metabolic alterations induced by normothermic hepatic ischemia, 31P nuclear magnetic resonance analysis was performed on liver samples using perchloric acid extraction. In particular, phosphomonoesters and phosphodiesters, the intermediary metabolites of membrane phospholipid turnover, were characterized precisely and quantitated. Phosphocholine and phosphoethanolamine, the precursors of phospholipid anabolism, did not change, while the phosphodiesters decreased. In contrast, alpha-glycerophosphate, which is both a precursor of phospholipid synthesis and the intermediary product of phospholipid degradation, markedly increased following 30 min of normothermic ischemia. These findings suggest that cellular phospholipids are actively degraded during normothermic hepatic ischemia.

Adenosine Triphosphate↗

Comparisons of several dosages of a GnRH analog with the standard dose of hCG in the treatment of follicular cysts in dairy cows.

Two experiments were carried out to examine therapeutic effect of a gonadotropin-releasing hormone analog, buserelin, on ovarian follicular cysts in dairy cows. Follicular cysts were diagnosed by palpation per rectum as well as by milk progesterone assay. Luteinization of the follicular cysts following treatment was judged by an increase in milk progesterone. In Experiment 1, 35 cows were diagnosed to have follicular cysts on the basis of palpations and low milk progesterone concentrations 1 week before treatment. Another 19 cows which were clinically diagnosed with follicular cysts but showed high milk progesterone levels before treatment were excluded. Sixty-two percent (11/18) of cows with follicular cysts treated with 20 microg of buserelin and 82% (14/17) of cows treated with 10,000 IU of human chorionic gonadotropin (hCG) showed luteinization of follicular cysts within 4 to 5 days after the treatments. The percentage of cows conceiving within 100 days after treatment and the average interval in days between treatment and conception were 44% and 42+/-18 (SD) days for the buserelin-treated cows and 47% and 42+/-18 days for the hCG-treated cows. In Experiment 2, the effects of treatment doses (6, 10, 20 and 30 microg of buserelin and 10,000 IU of hCG) on follicular cysts were compared using 103 cows. An additional 23 cows which were clinically diagnosed as having follicular cysts and which were given treatment showed a high milk progesterone concentration on the day of treatment and were therefore excluded. Fifty to 64% of the cows responded with luteinization of follicular cysts after treatment. There was no significant difference in response among cows given either the different dosages of buserelin or the hCG. However, the percentage of the total number of cows that conceived after a single or a repeated treatment with 6 microg buserelin was lower than that of cows after a single or a repeated treatment with 10 microg buserelin (P<0.05). An increase in the dose of buserelin from 10 to 30 microg did not improve the therapeutic effect of the drug. Thus, it is concluded that a single intramuscular injection of buserelin at a dose of 10 microg or higher is as effective as 10,000 IU hCG, and is, therefore, recommended for the treatment of ovarian follicular cysts in cows.

Journal Article↗

Delayed appearance of G-protein coupled signal transduction system in developing cerebellar Purkinje cell dendrites.

To investigate the relation between the function of Ca(2+)-activated K+ channels and phosphoinositide turnover, we have examined the physiological and pharmacological characteristics of ionotropic and metabotropic quisqualate (QA) receptors in rat cerebellar Purkinje cells during development using the slice-patch method combined with Ca2+ imaging. The typical response to QA obtained from a rat on postnatal day (PND) 21 consisted of three components: (1) a fast inactivating inward current, (2) a slow inward current, and (3) a slow outward current. The slow inward current was abolished in Ca(2+)-free medium, while the fast inactivating inward current and the slow outward current remained unaffected. The slow outward current which appeared to be activated via a metabotropic receptor was not observed in the Purkinje cell of PND 7 rat, in which dendrites were poorly developed but its amplitude increased linearly with PND. QA caused significant increases in [Ca2+]i in the fully developed dendritic region of the Purkinje cells even in Ca(2+)-free medium, suggesting a dendritic localization of the metabotropic receptors.

Animals↗

Morphological features of cat thalamo-parietal projection fibers investigated by PHA-L immunohistochemistry and electron microscopy.

Thalamo-parietal fibers originating from the ventroanterior-ventrolateral (VA-VL) complex in the cat were labeled with Phaseolus vulgaris leucoagglutinin (PHA-L) and examined by light and electron microscopy. PHA-L (2.5% aqueous solution) was injected iontophoretically through micropipets with anodal current pulses into the VA-VL complex. PHA-L-labeled terminals were distributed in the lateral and the suprasylvian gyri in the superficial and deep cortical layers. In layer I, horizontal varicose fibers and terminals were conspicuous in the upper one-third and were widely distributed. In the deeper cortical layers (layers III-V), varicose fibers and terminals were detected in moderate numbers. Electron microscopic examination revealed that the labeled terminals formed asymmetrical synapses on the dendritic spines of spiny neurons. These morphological findings appeared to be consistent with our previous intracellular recordings in this cortex.

Animals↗

Co-expression of glycine receptor beta subunit and GABAA receptor gamma subunit mRNA in the rat dorsal root ganglion cells.

We examined the expression of the beta subunit mRNA of the glycine receptor and the gamma subunit mRNA of the GABAA receptor in the rat dorsal root ganglion (DRG) using in situ hybridization histochemistry with oligonucleotide probes. About 44% and 37% of the all DRG neurons were labeled by the probes for glycine receptor beta subunit and GABAA receptor gamma subunit mRNAs. Labeled neurons were mostly large cells that simultaneously expressed both glycine receptor beta subunit and GABAA receptor gamma subunit mRNA as demonstrated using consecutive sections. Thus, we suggest the possibility that both GABA and glycine presynaptically regulate the activity of neurons involved in low-threshold mechanoreception at axo-axonic synapses in the spinal cord.

Animals↗

Hepatic accumulation and hepatotoxicity of luteoskyrin in mice.

HPLC analysis revealed that luteoskyrin administered orally to male mice accumulated selectively in the liver, with minor distribution to the serum and kidneys. Elevation of serum GOT and GPT values was maximal 3 days after administration. In mice administered this mycotoxin intravenously, selective accumulation was also observed in the liver, and the half-life of hepatic luteoskyrin in males was significantly longer than that in females. Increment of serum transaminases was also marked in males with maximum accumulation at 24 h after administration. Histopathologically, cellular membrane damage was an early effect of luteoskyrin on cell necrosis, and these morphological changes were also marked in males. Luteoskyrin also elevated hepatic lipid peroxides, the maximum elevation being 8 h after injection; this increase was suppressed by alpha-tocopherol and Bi(NO3)3. HPLC-ECD analysis indicated that the level of 8-hydroxy-deoxyguanosine, one of the markers of hydroxy-radical-mediated modification of DNA guanine residues, was increased in hepatic DNA. These findings indicate that luteoskyrin has a high affinity for the liver, resulting in induction of lipid peroxidation, hepatocellular membrane damage, and elevation of serum transaminase activities. It is suggested that the hydroxy radicals derived from this anthraquinone contribute to these toxicological changes.

8-Hydroxy-2'-Deoxyguanosine↗