PubMed HealthSearch

Biomedical subjects

M Horio

Publications and source records attributed to M Horio.

At least 19 recordsLinked to original sources

Immunohistochemical study of epidermal growth factor and transforming growth factor-beta in the penetrating type of early gastric cancer.

We report that the penetrating type of early gastric cancer (PEN) is a specific type of early gastric cancer and that the poorly differentiated PEN type could be considered an initial lesion of linitis plastica-type cancer. We performed an immunohistochemical study to clarify the role of growth factors (epidermal growth factor [EGF] and transforming growth factor-beta [TGF-beta]) in the PEN type of early gastric cancer. The results indicated that the PEN type of early gastric cancer has a high growth capacity. Moreover, it was suggested that EGF was involved in its specific infiltrative growth and that both EGF and TGF-beta were involved in its specific scirrhous growth. From these findings, it was assumed that the immunohistochemical staining of EGF and TGF-beta in endoscopic biopsy specimens was useful for the diagnosis of the PEN type of gastric cancer and also for the diagnosis of the initial lesion of linitis plastica-type gastric cancer.

Epidermal Growth Factor

Alteration of the c-fms gene in a blood sample from a Thorotrast individual.

We analyzed six different tissue DNA samples from a leukemic individual who received an injection of Thorotrast for alterations in proto-oncogene or tumor-suppressor gene structure. Our examination of the DNA indicated an alteration of the c-fms gene in the blood sample from this individual. This locus showed a deletion in which the 3' end of the deleted region maps between exons 11 and 12. In this particular case, the type of leukemia is unknown but myeloid leukemia is a neoplasm associated with individuals injected with Thorotrast. It is possible that the alteration in the c-fms gene of this individual is a consequence of the radiation exposure. No apparent alterations in the c-mos gene were observed in any of the tissues from the individual. This is in contrast to previous studies that described alterations in methylation patterns associated with the c-mos locus in radium-exposed individuals. A number of the individuals exposed to radium also had alterations of the retinoblastoma gene while no such alterations were observed in any tissue DNA samples from this Thorotrast case. It is possible that our inability to detect alterations of the c-mos and retinoblastoma gene may be attributable to the nature of alpha-emitting radionuclides or their distribution, or to the limited set of tissues available for analysis.

Aged

Marked eosinophilia induced by nafamostat mesilate, an anticoagulant in a hemodialysis patient.

A 61-year-old Japanese female on hemodialysis developed marked eosinophilia induced by nafamostat mesilate as an anticoagulant for hemodialysis. This is the first case of hypereosinophilic syndrome induced by nafamostat mesilate in a hemodialysis patient. The elevated eosinophil counts (51,900/mm3) are the highest for hemodialysis-associated eosinophilia. This eosinophilia was eliminated after cessation of nafamostat mesilate. We confirmed that the cause of this eosinophilia was nafamostat mesilate by using the challenge test.

Anticoagulants

Protein kinase C beta gene expression is associated with susceptibility of human promyelocytic leukemia cells to phorbol ester-induced differentiation.

To study the signal transduction pathway leading to phorbol 12-myristate 13-acetate (PMA)-induced differentiation in human promyelocytic HL-60 leukemia cells, we examined the expression of protein kinase C (PKC) isozyme genes in HL-60 cells that are susceptible or resistant to PMA-induced differentiation. The PKC-alpha, -beta, -gamma, -delta, epsilon, and -zeta transcript levels were assessed by Northern blotting, and the PKC-alpha, -beta, and -gamma protein levels were examined by immunoblotting. The PMA-resistant cell variants HL-525 and HL-534 were found to be deficient in the PKC-beta isozyme RNA and protein as compared with the PMA-susceptible HL-60 and HL-205 cell lines. In addition, a "delta-like" PKC RNA species identified in these cells demonstrated a reduced abundance in the HL-525 and HL-534 cells. Southern blot analysis indicated that the observed reduction in PKC-beta gene expression does not appear to be due to a gross deletion or rearrangement of the gene. The expression of the early response genes junB, c-fos, and c-jun was attenuated in PMA-treated HL-525 and HL-534 cells as compared to the PMA-treated HL-60 and HL-205 cells. These results suggest that the signal transduction pathway that leads to PMA-induced differentiation in the HL-60 cell system requires PKC-beta and/or delta-like PKC for the proper expression of the early response genes, and ultimately the expression of genes that define the mature state.

Cell Differentiation

Agents which reverse multidrug-resistance are inhibitors of [3H]vinblastine transport by isolated vesicles.

Resistance of human cancer cells to multiple cytotoxic hydrophobic agents (multidrug resistance) is due to overexpression of the MDR1 gene whose product is the ATP-dependent multidrug transporter, P-glycoprotein. We have previously reported that plasma membrane vesicles partially purified from multidrug-resistant human KB carcinoma cells, but not from drug-sensitive cells, accumulated [3H]vinblastine in an ATP-dependent manner (Horio, M., Gottesman, M.M. and Pastan, I. (1988) Proc. Natl. Acad. Sci. USA 85, 3580-3584). Certain calcium-channel blockers, quinidine, and phenothiazines are able to overcome multidrug resistance in cultured cells. In this work, the effect of these reversing agents on ATP-dependent vinblastine (VBL) transport by vesicles from drug-resistant KB cells has been characterized. Azidopine was the most potent inhibitor of ATP-dependent VBL uptake tested (ID50: concentration of inhibitor such that the transport of vinblastine is inhibited by 50%, less than 1 microM). Verapamil, quinidine, and the tiapamil analogue RO-11-2933 were potent but less effective inhibitors (ID50 less than 5 microM). Diltiazem, nifedipine and trifluoperazine were even less effective. These agents had no effect on Na(+)-dependent and Na(+)-independent L-leucine uptake by the vesicles, indicating that the inhibition of ATP dependent VBL transport by these agents is not a non-specific effect, as might result from leaks in the vesicle membrane. Verapamil, quinidine, azidopine and trifluoperazine increased the apparent Km value of vinblastine transport, suggesting that these agents may be competitive inhibitors of vinblastine transport.

ATP Binding Cassette Transporter, Subfamily B, Mem

[De-endothelialization and re-endothelialization in autogenous vein grafts--fundamental and clinical study].

Preparation for preserving endothelial cells (ECs) of autogenous vein grafts (AVGs) and the process of de-endothelialization (de-E) and re-endothelialization (re-E) were studied. Jugular veins (n = 31) from mongrel dogs were immersed in saline solution (SS), heparinized blood (HB), and other three kinds of solution. Then jugular veins (n = 26) immersed in SS for 3 hours, were used for AVGs to the abdominal aorta. Intimal changes were observed by scanning electron microscopy. ECs showed irreversible changes about 60 minutes after immersion in SS and about 150 minutes in HB. Eleven (92%) of 12 graft specimens within 1 day after implantation showed wide areas of de-E, while ECs on the venous valve were satisfactorily preserved in 6 (55%) of 11 valves. Re-E was observed predominantly around the valve from 3 days after implantation, and completed within 3 weeks. Clinically, specimens in 35 AVGs were collected before anastomosis. Severe EC damage was observed in 23 (66%) of them. Long-term observation revealed graft stenosis in 2 due to intimal hyperplasia (IH) in grafts with severely damaged EC. These results suggest that venous valves are an important source of re-E, and that the preservation of ECs in graft preparation is an important factor to prevent IH.

Animals

[A case of increased 123I-IMP uptake in adenocarcinoma of the lung].

It has been reported that delayed 123I-IMP lung scintigraphy shows a defect corresponding to the tumor with increased accumulation around the tumor, and that an increased accumulation is associated with atelectasis and inflammation. We presented a case of increased uptake of 123I-IMP in lung cancer. None of the other reported case of increased uptake in lung cancer, to our knowledge, occurred. A 55-year-old man had a 6 cm mass in the lower lobe of the right lung. Cytologic examination with a small curette diagnosed the case as an adenocarcinoma. The 123I-IMP scintigraphy was performed 24 hours after intravenous injection of 111 MBq of 123I-IMP. The 123I-IMP SPECT lung images showed an area of increased 123I-IMP concentration corresponding to the tumor mass. The patient's subsequent course was characterized by massive pleural effusion caused by extensive invasion to the pleura despite chemotherapy. He died about 2 months after the 123I-IMP scintigraphy. The right lung removed at necropsy confirmed that the area of high 123I-IMP concentration corresponded to the mass, which proved a poorly differentiated adenocarcinoma. One should note that there is an unusual case with high 123I-IMP uptake in lung cancer.

Adenocarcinoma

Transepithelial transport of vinblastine by kidney-derived cell lines. Application of a new kinetic model to estimate in situ Km of the pump.

We present a new transport model that may be useful for many kinds of transepithelial transport experiments. The model permits estimation of a pump Km and pump activity solely on the basis of transepithelial tracer fluxes. We apply the model to studies of a multidrug efflux pump, P-glycoprotein, which is normally located in the apical plasma membrane of certain transporting epithelia such as kidney proximal tubule cells. To determine the functional properties of this multidrug transporter in an epithelium, we studied the transepithelial transport of the chemotherapeutic drug, vinblastine, in epithelia formed by the kidney cell lines MDCK, LLC-PK1, and OK. We have previously shown that basal to apical flux of 100 nM vinblastine was about five times higher than apical to basal flux in MDCK epithelia, indicating that there is a net transepithelial transport of vinblastine across MDCK epithelia. Addition of unlabeled vinblastine reduced basal to apical flux of tracer and increased apical to basal flux of tracer in a concentration-dependent manner, a pattern expected if there is a saturable pump that extrudes vinblastine at the apical plasma membrane. The model permits estimation of a pump Km and pump activity solely on the basis of transepithelial tracer fluxes. According to the transport model the apical membrane pump has Michaelis-Menten kinetics with an apparent Km = 1.1 microM. Net basal to apical transport of vinblastine was also observed in LLC-PK1 cells and OK cells which are other kidney-derived cell lines. The order of potency of the transport is LLC-PK1 greater than MDCK greater than OK cells. The organic cation transporter is not involved in this vinblastine transport because vinblastine transport in MDCK cells was not affected by 3 mM tetramethyl- or tetraethylammonium. Inhibitors of vinblastine transport in MDCK cells was not affected by potency, were verapamil greater than vincristine greater than actinomycin D greater than daunomycin. The transport pattern we observed is that predicted to result from the function of the multidrug transporter in the apical plasma membrane.

Animals

[Distribution pattern of Dirofilaria immitis microfilariae in peripheral blood of a dog and their intake by mosquitoes].

Experiments were made in which Aedes aegypti mosquitoes fed on a dog infected with Dirofilaria immitis, in order to determine the distribution pattern of microfilariae (Mf) in the dog's periphery blood and the number of Mf taken by the mosquitoes. Mosquitoes fed on an anesthetized dog at some 50 shaved skin spots and they were weighed immediately before and after feeding. This enabled us to examine not only the Mf number taken by each mosquito but also the Mf intake density in terms of Mf number per mg of blood. The Mf intake density showed a wide variation at the different parts of the dog's body, and the frequencies of Mf showed uneven distributions which were fitted best by the negative binomial. Significant differences were detected in the Mf intake density at different parts of the skin, but these differences were concluded as a non-consistent result because a similar result was not reproduced in the next experiment. It was presumed that not only the Mf number per mosquito but also the Mf intake density increased as the blood intake by the mosquitoes increased. This increase of both the Mf number per mosquito and the Mf intake density was also supported by another experiment in which mosquitoes were fed at the same skin spots consecutively one after another.

Aedes

[A study on cisplatin adsorbed to activated carbon particles as a new drug delivery system and its anti-cancer effect against human bladder cancer cell lines].

Activated carbon characteristically shows an extremely high transmigration to the lymph node, as well as a sustained release of the adsorbed drugs. Therefore, several attempts to use activated carbon as a carrier in cancer chemotherapy have been done. In the present study, we first introduced a new drug-dosage form of cisplatin (CDDP) adsorbed to activated carbon particles (CDDP-CH), and examined its characteristics and anti-cancer effect against human bladder cancer cell lines. CDDP solution of varied concentrations (Randa) was mixed with activated carbon particles (Norit A) and examined for adsorption and discharge by atomic absorption spectrophotometry and high performance liquid chromatography. Total CDDP adsorption increased in proportion to the amount of activated carbon. CDDP-CH was successfully prepared at an efficient concentration for cancer chemotherapy and CDDP-CH slowly discharged CDDP, indicating it as a useful means for the anti-cancer drug. Using cultured human bladder cancer cell lines (KU-1, HTB9), the anti-cancer effect was compared between CDDP and CDDP-CH by MTT-assay and double layer soft agar colony assay. CDDP-CH revealed an inhibitory effect against human bladder cancer cell lines. In view of the fact that activated carbon readily migrates to the lymph node, clinical application of this drug dosage form may be useful in cases of malignant tumor metastasis to the lymph node.

Cell Line

A new mutant, White larva, of the mosquito Toxorhynchites splendens: genetics and cannibalism.

A strain of a new body-color mutant, white larva (wl), was established from a field-collected wild-type strain of Toxorhynchites splendens. The mutant can be distinguished from the wild type in both the larval and pupal stages, but not in the adult. Crossing experiments confirmed its mode of inheritance to be a single recessive system. This is the first visible mutant found in Tx. splendens. Larvae of the wl phenotype seem to be recognized as prey by other individuals in mass larvae rearing.

Animals

[An autopsy case of extramural malignant leiomyoblastoma of the stomach with ovarian cancer: an immunohistochemical study].

The subject was an 85-year-old woman, who had been diagnosed as having an ovarian cancer and carcinomatous peritonitis and had been treated conservatively. She subsequently died from respiratory and renal insufficiency, and the autopsy that followed revealed that her pelvic cavity had been filled by a tumorous mass that size of a child's head. Histologically, the tumor was a serous cystadenocarcinoma of the ovary. Moreover another tumor, also the approximate size of a child's head, was found sited extramurally, beneath the posterior wall mucosa of the stomach body. Histological inspection of this tumor revealed a proliferation of round oval, and spindle-shaped tumor cells. A vacuolation of the cytoplasms and karyomitosis to the extent of 10/50 HPF also were observed. Based on the findings of being positive for Vimentin and a negative EMA, this tumor was diagnosed as being a malignant leiomyoblastoma of the stomach smooth muscle. The leioblastoma is a relatively uncommon neoplasm, and recent advances in immunohistochemical staining have indicated that some of these tumors are not only of smooth muscle derivation but also of nerve origin. Therefore, this tumor, given its morphological characteristics, had been generalized in this case as a gastric stromal tumor, and with negative findings for Desmin and S-100 protein, as well as positive for Vimentin.

Aged

[Chromosome aberrations and genes in human and experimental leukemias].

Although determination of chromosomal abnormalities may be of limited usefulness for the diagnosis of leukemia, the recent advances in the molecular mechanism associated with chromosome aberration has been rapid. Chromosome translocation in Burkitt lymphoma and chronic myeloid leukemia was the most striking evidence for the oncogene activation. Other specific chromosome abnormalities for FAB-classified leukemias are also known. Translocated type of chromosome abnormalities between immunoglobulin or T-cell receptor genes and oncogenes may also affect the T and B-cell leukemogenesis. However, the role of trisomies found in human and experimental leukemias and the gene dosages had been thought to be most important until 1982, has not been unclear. Many types of phenotypically heterogeneous leukemias have been reported. t(4 ; 11) acute leukemia is one such leukemia which shows early B-cell and myelomonocytic nature. Heterogeneous leukemias have been called biphenotypic, hybrid and acute mixed leukemias. The terminology must be used the unified. Recent trials to use paraffin-fixed tissues and bone marrow smear for molecular analysis has been successfully reported. Basic analysis on the DNA degradation mechanism revealed the enzymatic activity might play an important role before the complete fixation.

Animals

[A case of perianeurysmal fibrosis treated by the thrombo-exclusion technique].

A very rare case of perianeurysmal fibrosis was presented. A 65-year old man was admitted with the complaint of abdominal pulsatile mass and intermittent claudication of right lower limb. Aortography revealed fusiform, calcified aneurysm of the infrarenal abdominal aorta and severe stenosis of right common iliac artery. CT scan demonstrated a soft tissue density structure around the aortic aneurysm which was enhanced after contrast medium injection. At surgery, the aneurysm had a thick, firm, smooth wall which was shiny white in appearance and adherent perianeurysmal fibrosis was marked. In order to avoid injury to surrounding tissue such as the duodenum or vena cava, thrombo-exclusion method was chosen. Histological examination of the aneurysmal wall showed fibrous tissue infiltrated with mononuclear cells such as lymphocytes and plasma cells. The postcontrast enhancement of aortic wall and perianeurysmal sheet disappeared on CT on the post-operative 57th day and no recurrence has been observed.

Aged

Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epithelia.

We studied transepithelial transport of 3H-labeled hydrophobic cationic drugs in epithelia formed by wild-type and by drug-resistant Madin-Darby canine kidney (MDCk) cells that had been infected with a retrovirus carrying the multidrug-resistance (MDR1) cDNA which encodes the P-glycoprotein. P-glycoprotein is an ATP consuming plasma membrane multidrug transporter responsible for the efflux of cytotoxic chemotherapeutic drugs from resistant cancer cells. Wild-type MDCK cells have small amounts of P-glycoprotein detected by immunoprecipitation. Net transepithelial transport across wild-type MDCK epithelia was demonstrated. Basal to apical flux of 100 nM vinblastine was about six times higher than apical to basal flux. Addition of unlabeled vinblastine reduced basal to apical flux of tracer and increased apical to basal flux of tracer, a pattern expected if there is a saturable pump that extrudes vinblastine at the apical plasma membrane. Daunomycin, vincristine, and actinomycin D were also actively transported and at 20 microM these agents inhibited transport of vinblastine, suggesting that wild-type MDCK cells have a common transporter for all these drugs. Vinblastine transport was also inhibited by 20 microM verapamil, which inhibits the multidrug transporter and reverses multidrug-resistance in non-polarized cells. Net transepithelial transport of all these cytotoxic drugs and of verapamil was much higher in epithelia formed by MDCK cells infected with a human MDR1 virus (MDR-MDCK) which is expressed on the apical surface of MDR-MDCK monolayers. Because the transport of these cytotoxic drugs and verapamil is increased in MDR-MDCK epithelia compared to wild-type MDCK epithelia, transport in both these cell populations can be attributed to P-glycoprotein. These results are consistent with a role for P-glycoprotein in multidrug secretory transport across the epithelium of the proximal tubule since P-glycoprotein is normally expressed on the apical membrane of proximal tubule cells.

ATP Binding Cassette Transporter, Subfamily B, Mem