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H Hamada

Publications and source records attributed to H Hamada.

At least 433 records · Page 24Linked to original sources

[Significance of twin to twin transfusion syndrome in the prognosis of twin pregnancies and its prenatal diagnosis by ultrasonography].

The reason why TTS worsen the prognosis of twin pregnancies was discussed with reference to case results for perinatal death, and antenatal diagnostic criteria for TTS by ultrasonography was established. Of 12 perinatal deaths in 71 twin pregnancies, eight fetuses were affected with TTS (1 acardia, 4 donors, 3 recipients). Perinatal mortality rate (39.3%), rate of preterm lobar (62.2%), rate of polyhydramnion (50.0%), mean amniotic fluid volume (3.310 ml) and cord cross section area ratio (2.38) in monochorionic discordant twins were higher than in the other three groups (monochorionic concordant twins, dichorionic discordant twins and dichorionic concordant twins). Eight fetuses among 12 monochorionic discordant twins were affected with TTS. All twins which showed a single GS in early pregnancy were monochorionic twins. Therefore TTS was considered to have a poorer prognosis than usually reported for all TTS, and to find monochorionic discordant twins with a high cord cross section area ratio must be the key in the screening of TTS. Antenatal diagnosis of TTS by ultrasonography is summarized as follows: 1) A single GS in early pregnancy. 2) Estimated body weight difference between the twins/estimated body weight of the larger twins greater than or equal to 0.2. 3) Cord cross sectional area ratio greater than or equal to 2.0.

Adult↗

Elimination of drug-resistant myeloma tumor cell lines by monoclonal anti-P-glycoprotein antibody and rabbit complement.

The effectiveness of ex vivo chemotherapy with drugs, such as vincristine, etoposide, and Adriamycin (doxorubicin, Adria Labs, Columbus, OH) for elimination of residual tumor cells from human bone marrow grafts could be undermined by the presence of multidrug-resistant tumor cells in the bone marrow. Therefore, to supplement chemoseparation, we investigated whether MRK-16, a monoclonal antibody (MoAb) to the surface moiety of multidrug resistance-associated P-glycoprotein antigen, can eliminate drug-resistant tumor cells in the presence of rabbit complement (RC). Two doxorubicin (DOX)-resistant human myeloma tumor cell line, 8226/DOX40 (resistant to 4 x 10(-7) mol/L DOX) and 8226/DOX6 (6 x 10(-8) mol/L DOX) with high and low amounts of cell surface P-glycoprotein, respectively, and the drug-sensitive parent cell line 8226/S were used as tumor models in this study. Using the limiting dilution assay, we have shown that three cycles of treatment with 25 micrograms/mL of MRK-16 MoAb and a 1:4 final dilution of RC eliminated 2.90 +/- 0.10 logs of 8226/DOX40 cells and 1.94 +/- 0.18 logs of 8226/DOX6 cells. One and two cycles of treatment were less effective, eliminating 0.47 +/- 0.40 and 1.94 +/- 0.36 logs of 8226/DOX40 and 0.12 +/- 0.20 and 1.63 +/- 0.58 logs of 8226/DOX6 cells, respectively. The 8226/S cell growth was unaffected by one to three cycles of treatment. The cell kill was not impaired when the antibody plus complement treatment was carried out on a mixture of 8226/DOX40 or 8226/DOX6 cells with a ninefold excess of irradiated bone marrow mononuclear cells (MNCs). The three cycles of treatment with antibody plus complement did not adversely affect granulocyte-macrophage colony-forming unit (GM-CFU) survival in hematologically normal marrows (92.5% to 104% survival) or in myeloma patient marrows (85% to 100%). These results show that it is possible to eliminate drug-resistant myeloma tumor cell lines from the admixed human bone marrow by treatment with MRK-16 MoAb plus RC. This method could prove to be effective for elimination of other drug-resistant tumor cell lines including those of leukemia and solid tumors, and will be further useful for supplementing chemopurging, and immunopurging of bone marrow with other antitumor cell antibodies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Increased choline acetyltransferase activity by Chinese herbal medicine Sho-saiko-to-go-keishi-ka-shakuyaku-to in aged rat brain.

The effect of a Chinese herbal medicine Sho-saiko-to-go-keishi-ka-shakuyaku-to (TJ-960) on the brain choline acetyltransferase (CAT) activity was studied in adult (3.5 months of age) and aged (24 months of age) rats. After oral administration of 5% TJ-960 solution for 3 months, CAT activity in the hippocampus, pons-medulla oblongata and striatum of aged rats was significantly lower than that of adult rats. CAT activity in the cerebellum, however, was significantly higher in the aged rats, as compared to the adult rats. TJ-960 significantly increased CAT activity in the hippocampus and striatum of aged rats, but did not affect the activity of the enzyme in the adult rat brain.

Aging↗

High-level expression of MRK 16 and MRK 20 murine monoclonal antibody-define proteins (170,000-180,000 P-glycoprotein and 85,000 protein) in leukaemias and malignant lymphomas.

Using flow cytometry and immunocytochemistry, we investigated the reactivities of two different murine monoclonal antibodies (MAbs), MRK 16 and MRK 20, specific to adriamycin-resistant K562 cells (K562/ADM) with peripheral human mononuclear cells (MNC) (mainly blastic cells and lymphocytes) from 31 patients with leukaemia or malignant lymphoma. Reactivity with MRK 16 MAb was observed in five cases and reactivity with MRK 20 MAb in 18 cases. The cases were divided into three groups according to their reactivity patterns: group I, only the proportion of MRK 16-positive cells was increased; group II, only the proportion of MRK 20-positive cells was increased; group III, both MRK 16-and MRK 20-positive cells were increased. Some cases reflected the prior administration of adriamycin, vincristine, vinblastine and VP-16, which are known to induce P-glycoprotein expression. Expression of Mr 85,000 protein was observed more frequently than that of P-glycoprotein in leukaemia and malignant lymphoma, and this was not associated with either the total dose or period of administration of anticancer drugs. The expression of Mr 85,000 protein recognised by MRK 20 was further confirmed by Western blot analysis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16.

Forty cultured human leukemia and lymphoma cell lines never exposed to anticancer agents in culture, apart from doxorubicin (ADM)-resistant K562/ADM, were examined for reactivity with a monoclonal antibody, MRK16 in F(ab')2 form [MRK16-F(ab')2], which recognizes P-glycoprotein (P-gp). The relative resistance index to various drugs was calculated by dividing the 50% growth inhibitory concentration (IC50) of the test cell line by IC50 of K562, which was the negative control in the antibody experiment. MRK16-F(ab')2 reacted with four cell lines, K562/ADM, KYO-1, HEL and CMK, which had relative resistance index values of 2 or more to vincristine (VCR), vindesine, vinblastine, ADM, daunorubicin, mitoxantrone (MIT), etoposide (VP-16) and actinomycin-D (ACT-D). The level of resistance to VCR and ADM in these cell lines decreased significantly in the presence of 10 microM verapamil in vitro. Significant expression of mRNA of P-gp gene was also detected in K562/ADM, KYO-1 and HEL. MRK16-F(ab')2 did not react with 36 other cell lines. Among them, three cell lines, PL-21, P31/FUJ and KOPM-28, had relative resistance index values of 2 or more to anthracyclines, MIT and VP-16, but not to vinca alkaloids or ACT-D. The level of ADM-resistance in these cell lines did not decrease significantly in the presence of 10 microM verapamil. Five cell lines, ATL-1K, HL-60, KMOE-2, ML-1 and U266, had relative resistance index values of 2 or more to some of the drugs, but not to the others, and 19 other cell lines did not. These results indicate that the reactivity of MRK16-F(ab')2 correlates with a relative resistance index of 2 or more to all these drugs in cultured human leukemia and lymphoma cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Further characterization of the human adrenal-derived P-glycoprotein recognized by monoclonal antibody MRK 16 reacting with only human P-glycoprotein.

This paper describes further characterization of the 170-180-kDa glycoprotein (P-glycoprotein) recognized by the monoclonal antibody MRK 16 in the human adrenal. By electron microscopy, P-glycoprotein was observed in the adrenal cell membranes. However, MRK 16-defined P-glycoprotein was not found in cow, pig, horse, monkey or rabbit adrenal, indicating that MRK 16 recognizes the non-homologous part of P-glycoprotein of various species. Eleven out of 16 adrenal tumors including 4 cases of primary aldosteronism and 7 cases of Cushing syndrome were intensely stained with MRK 16, whereas pheochromocytoma, non-functioning adrenocortical adenoma with no associated increase of serum adrenal-derived hormones and myolipoma of the adrenal were not. Finally, P-glycoprotein-MRK 16-protein A-Sepharose complex derived from human adrenal possessed marked ATPase activity. Taken together, these data suggest that P-glycoprotein may play a physiological role in the human adrenal.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Inhibition of multidrug-resistant human tumor growth in athymic mice by anti-P-glycoprotein monoclonal antibodies.

In an effort to devise an effective treatment for human drug-resistant cancers, we have developed monoclonal antibodies, MRK16 and 17, reactive to the multidrug transporter protein, P-glycoprotein. The monoclonal antibodies given intravenously effectively prevented tumor development in athymic mice inoculated subcutaneously with drug-resistant human ovarian cancer cells 2780AD. Treatment with MRK16 induced rapid regression of established subcutaneous tumors and apparent cures of some animals. Complement-dependent cytotoxicity (MRK16) and antibody-dependent cell-mediated cytolysis (MRK16 and 17) were observed with these antibodies. These monoclonal antibodies may have potential as treatment tools against multidrug resistant human tumors possessing the P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A novel multidrug resistance in cultured leukemia and lymphoma cells detected by a monoclonal antibody to 85-kDa protein, MRK20.

A monoclonal antibody, MRK20, in F(ab')2 form [MRK20-F(ab')2], which reacts with 85-kDa membrane protein in a doxorubicin (ADM)-resistant subline (K562/ADM) of human myelogenous leukemia cell line, K562, was examined for reactivity with 41 cultured human leukemia and lymphoma cell lines. None of these cell lines had ever been exposed to any anticancer agent in vitro except K562/ADM. The relative resistance index to various drugs was calculated by dividing the 50% growth-inhibitory concentration (IC50) of the test cell line by IC50 of K562 (the negative control in the antibody experiment). MRK20-F(ab')2 reacted with seven cell lines, KYO-1 derived from chronic myelogenous leukemia in blastic crisis (CMLbc), CMK from acute megakaryoblastic leukemia, HEL from erythroleukemia, P31/FUJ from acute monocytic leukemia, KOPM-28 from CMLbc, PL-21 from acute promyelocytic leukemia and K562/ADM. MRK20-F(ab')2 did not react with 34 other cell lines. All seven MRK20-F(ab')2-positive cell lines had relative resistance index values of 2 or more to anthracyclines (ADM, pyrarubicin, daunorubicin), mitoxantrone, etoposide, bleomycin, and pepleomycin. There was no distinct correlation between the reactivity to MRK20-F(ab')2 and a higher relative resistance index than 2 to vinca alkaloids, actinomycin-D, cisplatin, 4-hydroperoxycyclophosphamide, nimustine hydrochloride, methotrexate or cytarabine. These results indicate that MRK20-F(ab')2 detects a novel multidrug resistance to anthracyclines, mitoxantrone, etoposide, bleomycin and pepleomycin in cultured human leukemia and lymphoma cells.

Antibiotics, Antineoplastic↗

Immunocytochemical identification and localization of the Mr 22,000 calcium-binding protein (sorcin) in an adriamycin-resistant myelogenous leukemia cell line.

Monoclonal antibody against the Mr 22,000 calcium-binding protein (sorcin) from an adriamycin-resistant myelogenous leukemia cell line K562 (K562/ADM) was prepared and used as a probe to study the localization of sorcin in K562/ADM cells and the parental cell line, K562. Analysis of extracts from K562/ADM cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorescence image analysis showed that K562/ADM cells possessed abundant sorcin in the cytoplasm which was almost entirely absent from the drug-sensitive parental cell line, K562. Furthermore, immuno-electron microscopic studies revealed that sorcin was closely associated with free ribosomes, rough endoplasmic reticulum, mitochondria, microfilament bundles and perinuclear membranes. These observations provide the first clue that the Ca-binding protein, sorcin, may play an important role in the development of the multidrug resistance phenomenon, although the relationship between sorcin and P-glycoprotein is still unknown.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein.

Using peroxidase immunohistochemistry, we examined the distribution of P170, a multidrug transport protein, in normal tissues by use of two different monoclonal antibodies (MAb). MAb MRK16 is a MAb that has been shown to react with an epitope in P170 located on the external face of the plasma membrane of multidrug-resistant human cells. MAb C219 has been shown to react with P170 in many mammalian species, and detects an epitope located on the cytoplasmic face of the plasma membrane. Using MRK16, we have previously described the localization of P170 on the bile canalicular face of hepatocytes, the apical surface of proximal tubular cells in kidney, and the surface epithelium in the lower GI tract in normal human tissues. In this work, we report that MRK16 also detects P170 in the capillaries of some human brain samples. A similar pattern was found using MAb C219 in rat tissues. in addition, MAb C219 showed intense localization in selected skeletal muscle fibers and all cardiac muscle fibers in rat and human tissues. ATPase cytochemistry showed that these reactive skeletal muscle fibers were of the type I (slow-twitch) class. Other additional sites of C219 reactivity in rat tissues were found in pancreatic acini, seminal vesicle, and testis. Electrophoretic gel immunoblotting showed two protein bands reactive with MAb C219. In liver, MAb C219 reacted with a approximately 170 KD band. In skeletal and cardiac muscle, MAb C219 reacted with a approximately 200 KD band which migrated in the same position as myosin. This band also reacted with an antibody to skeletal muscle myosin. This result suggests that C219 may crossreact with the heavy chain of muscle myosin in cardiac and skeletal muscle. Because MAb C219 reacts with proteins other than P170, it should be used with caution in studies of multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A successful delivery of an extremely immature infant in Rh incompatibility after plasma exchange.

When Rh incompatible pregnancies occur, intrauterine fetal transfusion (IUT) and plasma exchange (PE) have made it possible to prolong the prenatal duration and to dramatically decrease the neonatal mortality. We administered a total of 10 PEs (from 20 weeks to 27 weeks of gestation) and one IUT (at 27 weeks and 1 day) for an Rh-isoimmunized gravida who already had a high maternal serum Rh antibody titer at the 14th gestational week, and delivered by Caesarian section (CS) an extremely immature infant of only 873 grams at 27 weeks and 4 days of gestation. The infant was hydropic with hyperbilirubinemia, therefore exchange transfusions were administered immediately after birth. The infant's weight reached the lowest point of 669 grams on the 13th day after birth, but began to increase thereafter. The baby weighted 3,052 grams on the 144th day and left the hospital without any complications.

Blood Transfusion, Intrauterine↗

[Clinical study of intrahepatic arterial infusion of unresectable hepatoblastoma and hepatocarcinoma in children].

Six cases of unresectable hepatic cancer in infant were treated with intra-arterial infusion therapy. The histological types were hepatoblastoma and hepatocellular carcinoma, 3 cases respectively. The clinical stages were 1 recurrent case in I, 1 in IIIA, 2 in IIIB and 2 in IV. Seldinger method and cannulation at laparotomy were employed in 4 cases and 2 cases, respectively. In the eldest case, a catheter with dual lumen reservoir developed in our department was inserted, making it possible to infuse drugs into hepatic artery and cutting off hepatic arterial blood flow temporarily. The anticancer drug used was ADM, CDDP, 5-FU, THP-ADM, and MMC; antiAFP-anticancer drug conjugate missile therapy was employed in 4 cases. According to image diagnosis, reduction or necrosis of tumor was observed in 5 cases. In all cases, AFP scores decreased. In 5 dead cases, 4 cases died of tumor enlargement (average survival time 16.3 months); 1 case died of DIC during chemotherapy. The other case could eventually undergo complete resection and is now alive. Intra-arterial infusion therapy seemed to be useful for patients of infant unresectable hepatic cancer.

Adolescent↗

[Three cases of effective hepatic arterial infusion with OK-432, mitomycin C and 5-fluorouracil in liver metastasis from gastric cancer].

A combined therapy with OK-432. mitomycin C (MMC) and 5-fluorouracil (5-FU) by administration through hepatic arterial infusion was performed in three patients with liver metastasis from gastric cancers. A catheter was introduced into hepatic artery by laparotomy. The dosage was 250 mg/day for 5-FU continuously, 10 mg/week for MMC and 5 KE/week for OK-432, respectively. Two cases with advanced gastric cancer and synchronous hepatic metastasis were treated by hepatic arterial infusion after surgical removal of primary lesion. Metastatic lesion in liver was completely eliminated. Another case with metastatic liver tumor from gastric cancer was also treated by the same protocol. The reduction rate of this case was 70% by CT scan. These results suggested that combined therapy with OK-432, MMC and 5-FU by hepatic arterial infusion is a good modality for liver metastases from gastric cancers.

Aged↗

[Clinical evaluation of limb-salvage procedures in malignant bone tumors--a study of 54 cases].

Recent advances in therapy such as local and systemic chemotherapy, wide resection, and aggressive thoracotomy improved the survival of the patients with malignant bone tumors. Since 1981, we have performed limb-salvage operations for 54 cases of malignant bone tumors of the extremities. In this study, we report the rate of local recurrence and the prognosis of the patients. We treated 37 osteosarcomas, 8 malignant fibrous histiocytomas of bone, 3 Ewing's sarcomas, 3 parosteal osteosarcomas, 2 chondrosarcomas, and one fibrosarcoma. The age of the patients ranged from 11 to 65 years (mean, 18.5). The male/female ratio was 2:1. The surgical stage was 47 at II B and 7 at III. The follow-up period was 14 to 84 months (mean 36). They received preoperative chemotherapy including intraarterial infusion of Adriamycin, and postoperative chemotherapy for ten months. Local recurrence was detected in 2/54 (3.7%). Lung metastases (Stage II B) developed in 9/47 (19.1%). Five of them (10.7%) died of metastasis, one is alive with metastases, and 41 cases are now disease-free. Six of seven cases (Stage III) died of metastasis, despite aggressive chemotherapy and thoracotomies.

Adolescent↗

[Expression and function of proteins associated with multidrug resistance].

We have identified the proteins specifically expressed in multidrug-resistant tumor cells and studied the functions of these proteins. The 170-to 180-kDa membrane glycoprotein (P-glycoprotein) is an ATPase which works as a pump molecule transporting chemotherapeutic drugs outside the resistant cells. The 22-kDa soluble protein (sorcin) is a calcium binding protein of unknown function. The 85-kDa membrane protein is specifically expressed in adriamycin-resistant cells and induced by treatment with adriamycin, suggesting a mechanism unique for adriamycin resistance. Our monoclonal antibodies to these proteins may well become useful tools for the diagnosis of clinical drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Anesthetic management in surgery of thoracic aortic aneurysms--a report of eleven cases].

Anesthetic management of patients with thoracic aneurysm is discussed. During a period of two years, 11 cases were observed; 7 cases of dissecting aneurysm and 4 cases of true aneurysm. Dissecting aneurysms were of DeBakey's type 1 in 5 cases and of DeBakey's type 2 in 2 cases. Four cases had hypertension. As many of these patients often have hypertension, it is important not to change the circulatory dynamics during induction of anesthesia. We employed high dose fentanyl in 9 cases and used nitroglycerin or nitroprusside to control systolic blood pressure at about 100-120 mmHg. Massive bleeding can occur during intraoperative period and it is important to secure a sufficient number of intravenous routes to protect the central nervous system during cardio-pulmonary bypass.

Aged↗

[Fetal therapy in utero by blockage of the umbilical blood flow of acardiac monster in twin pregnancy].

We studied a life-saving method for the unaffected twin in two recent patients who had acardiac monster in twin pregnancy. We succeeded in blocking the umbilical blood flow of the acardiac monster in utero as radical treatment for this abnormality in one of the patients. In case 1, tocolysis and amniocentesis with puncture to the cyst of the acardiac monster were performed to prevent premature labor. However, the patient underwent premature labor at 27 weeks of gestation, and the newborn died. In case 2, fetal treatment was given: A steel coil was placed in the umbilical cord close to the abdominal wall of the acardiac monster under ultrasonographic guidance at 23 weeks of gestation to block blood flow. As a result, no enlargement of the acardiac monster was observed, and the cardiac function of the unaffected fetus improved. At 38 weeks of gestation, the patient delivered a normal baby weighing 2,237g and an acardiac monster weighing 110g. There were no complications in either the mother or newborn. There has been no report describing blockage of the umbilical blood flow of an acardiac monster in utero. Our method is considered efficient and less risky to the mother and the unaffected twin.

Abnormalities, Severe Teratoid↗