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Biomedical subjects

H Mano

Publications and source records attributed to H Mano.

143 records · Page 8Linked to original sources

[Multidisciplinary treatment of choriocarcinoma].

The remarkable improvement has been recently made in the treatment of choriocarcinoma, about 80% of survival rate has been achieved. This improvement was acquired according to appearance and betterment on administration method of MTX and ACTG, surgical treatment for pulmonary and cerebral metastases and irradiation for cerebral metastases. Recent died cases were analysed and divided into two groups; one group consisted of recurrent cases and the other consisted of those who, at first showed good response to therapy resulted in drop of hCG value and reduction of tumor, however, then showed gradual reincrease of hCG and expired at latt. Therefore for achieving the 0% of mortality rate, it is a important subject to exterminate the death from recurrence and clarify more aggressive treatment method at the time when reduction of the tumor is obtained.

Antineoplastic Combined Chemotherapy Protocols↗

[Specific in vitro effects of methotrexate entrapped into liposomes bearing antibody fragments against human chorionic gonadotropin on cell growth of cultured human choriocarcinoma cells].

Methotrexate (MTX) was entrapped into liposomes, to which rabbit antibody fragments (Fab') against human chorionic gonadotropin (hCG) had been coupled covalently, using N-[4-(p-maleimidophenyl) butyryl] phosphatidyl ethanolamine. By this system, The resulting molar ratio in the prepared liposomes was 15 MTX per Fab', and the activities of both MTX and the antibody were well preserved. The inhibitory effects of MTX entrapped in liposomes bearing anti-hCG Fab' (Lip[MTX, anti-hCG]) on the growth of choriocarcinoma cells (BeWo) in vitro were examined. The 50% inhibitory concentration of Lip[MTX, anti-hCG] was found to be 1 X 10(-3) micrograms MTX/ml, which was significantly lower than the concentrations of control groups, free MTX (2.5 X 10(-3) micrograms/ml) or MTX entrapped in liposomes bearing no antibody (Lip [MTX], 1.3 X 10(-2) micrograms/ml). The effect of the coupling of the specific antibody was more clearly demonstrated by a short-time incubation (60 min) experiment. Lip [MTX, anti-hCG] exhibited marked inhibition on cell growth, compared to MTX entrapped in liposomes bearing non-immunized Fab' (Lip[MTX, non-immunized Fab']). On the other hand, free MTX showed no effect in this experiment. We may conclude that Lip [MTX, anti-hCG] has a specific inhibitory effect on the growth of choriocarcinoma cells in vitro, which suggests the possibility of a specific immunochemotherapy for this disease, using the specific antibody to this tumor coupled to liposomes.

Antibodies↗

Monoclonal antibodies to human chorionic gonadotropin and its beta-subunit.

Using the technique of somatic cell fusion, monoclonal antibodies to human chorionic gonadotropin (hCG) and its beta-subunit were produced. Spleen cells from immunized mice were fused with the myeloma line NS-1 using 50% polyethylene glycol and cultured in a selection medium. A sensitive enzyme immunoassay was performed for antibody screening using immobilized solid-phase antigen and anti-mouse IgG Fab' (rabbit)-beta-D-galactosidase complex. Three double-cloned hybridomas (named 4H10, 4G2 and 1D12) were obtained. Anti-hCG 4H10 antibody reacted with hCG, the alpha-subunit of hCG (alpha-hCG) and human luteinizing hormone (hLH); and anti-hCG 4G2 antibody reacted with hCG and the beta-subunit of hCG (beta-hCG). It was interesting that anti-beta-hCG 1D12 antibody had the capacity to bind with free beta-hCG but not with intact hCG, which suggests that the 1D12 antibody can recognize a determinant site that is unique to beta-hCG. This unique epitope in beta-hCG might be expressed in or near a part which is hidden in the intact hCG molecule which is composed of alpha- and beta-subunits.

Animals↗

Huge lipomatous pseudohypertrophy of the pancreas.

A rare case of lipomatous pseudohypertrophy of the pancreas associated with multiple cysts in an adult is presented. Endoscopic retrograde pancreatography showed a long, willow-like main pancreatic duct. Resected body and tail of the pancreas weighed 1,200 gm.

Adult↗

Replication of human immunodeficiency virus type 1 in primary cultured placental cells.

The role of placental cells in transplacental transmission of human immunodeficiency virus type 1 (HIV 1) was investigated. Placental macrophages and trophoblasts, which together represent the main cell components of the placenta, were cultivated separately and then compared to foetal monocyte-derived macrophages for susceptibility to HIV 1 infection. Placental macrophages treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) were less easily infected with HIV 1 than were GM-CSF-treated foetal monocyte-derived macrophages. HIV 1 replication in cocultures consisting of infected placental macrophages together with a highly HIV 1-permissive cell line (CEM) was detected persistently for at least 6 weeks by reverse transcriptase assay, even though placental macrophages expressed no detectable CD4 receptor, as indicated by indirect immunofluorescence. HIV 1-specific DNA sequences were also detected in infected placental macrophages. Trophoblasts exhibited no detectable CD4 expression and did not support the replication of HIV 1, although low levels of HIV 1-specific DNA sequences could be detected in infected trophoblasts. Placental macrophages or trophoblasts (or both) may thus play an important role in transplacental HIV 1 transmission.

Base Sequence↗

Expression of human placenta alkaline phosphatase in placenta during pregnancy.

To clarify the expression of PLAP during the course of pregnancy, the amount of PLAP mRNA and its activity in normal placental villi were measured. Both PLAP and its mRNA were found in placentae of as early as 7 weeks of gestation, and they continued to increase throughout pregnancy. But they showed different patterns of increase. The amount of PLAP mRNA began to increase dramatically around 13th week and probably continued to increase gradually until term. PLAP activity per gram of villi showed a gradual increase from around 13th week and a marked increase was observed after about 20th week. PLAP levels in sera from pregnant women were also measured, and they showed a pattern of increase imilar to that of PLAP activity per gram of villi. The continuous increase in the expression of PLAP throughout pregnancy suggests that PLAP may play a role in feto-maternal metabolism and placental differentiation.

Alkaline Phosphatase↗

Tec family of protein-tyrosine kinases: an overview of their structure and function.

The Tec family is a recently emerging subfamily of non-receptor protein-tyrosine kinases (PTKs) represented by its first member, Tec. This family is composed of five members, namely Tec, Btk. Itk/Emt/Tsk, Bmx and Txk/Rlk. The most characteristic feature of this family is the presence of a pleckstrin homology (PH) domain in their protein structure. The PH domain is known to bind phosphoinositides; on this basis, Tec family PTKs may act as merge points of phosphotyrosine-mediated and phospholipid-mediated signaling systems. Many Tec family proteins are abundantly expressed in hematopoietic tissues, and are presumed to play important roles in the growth and differentiation processes of blood cells. Supporting this, mutations in the Btk gene cause X chromosome-linked agammaglobulinemia (XLA) in humans and X chromosome-linked immunodeficiency (Xid) in mice, indicating that Btk activity is indispensable for B-cell ontogeny. In addition, Tec family kinases have been shown to be involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, heterotrimeric G-protein-coupled receptors and integrin molecules. Efforts are being made to identify molecules which interact with Tec kinases to transfer Tec-mediated signals in vivo. Candidates for such second messengers include PLC-gamma2, guanine nucleotide exchange factors for RhoA and TFII-I/BAP-135. This review summarizes current knowledge concerning the input and output factors affecting the Tec kinases.

Amino Acid Motifs↗

A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome.

Patients with a myelodysplastic syndrome (MDS) which has a risk of leukaemic change exhibit a variable clinical course. It has been suggested that the development of leukaemia in patients with MDS may be related to chromosomal abnormalities or genetic alterations: somatic mutation of the N-ras gene is now considered to be a critical step in the genetic basis of human leukaemogenesis. Here we report that DNAs of bone-marrow cells from three out of eight patients with MDS contained an activated N-ras oncogene, as detected by an in vivo selection assay in nude mice with transfected NIH 3T3 cells. Molecular analysis revealed the same single nucleotide substitution at codon 13 in all three transforming N-ras genes. Each of the three patients showed a progression of the disease and a resulting leukaemic change within the following year. Our observation of the mutation at codon 13 in leukaemic cell DNAs from all three cases suggests that activation of the N-ras gene is important in the development of leukaemia in some MDS cases.

Amino Acid Sequence↗

ECG-gated NMR-CT for cardiovascular disease.

We have developed an ECG-gated NMR-CT, and used it with 16 patients. The saturation recovery images are not able to separate heart muscle from the blood pool, but in inversion recovery images, heart muscle can be differentiated from the ventricles. The region of myocardial infarction is revealed as wall thinning and/or wall motion abnormality. From the two-gated inversion recovery images (the end-diastole and end-systole images) we obtained, we evaluated a wall motion abnormality in the left ventricle, and calculated the ejection fraction of the left ventricle. This information was then compared with the findings of a nuclear medicine study carried out one week interval and which included 10 of the 16 patients tested with the ECG-gated NMR-CT. The wall motions in both methods are well correlated, with the exception of the inferior wall. The values of the ejection fraction in the NMR image were moderately low, but two modalities showed a satisfactory correlation (r = 0.85).

Adult↗