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Biomedical subjects

Y Morikawa

Publications and source records attributed to Y Morikawa.

At least 181 records · Page 10Linked to original sources
PubMed1992

Seven tumor markers in benign and malignant germ cell tumors of the ovary.

Seven tumor markers were analyzed clinically in 135 patients with germ cell tumors of the ovary who were treated in Tokai Ovarian Tumor Study Group, an association comprising Nagoya University and its affiliated hospitals, between January 1979 and September 1990. Positive rate of AFP was 100% (36/36) in yolk sac tumor, 61.9% (13/21) in immature teratoma, and 11.8% (2/17) in dysgerminoma, but there were no positive cases of mature cystic teratoma with malignant transformation (0/7) and mature cystic teratoma (0/31). Positive rate of CA125 was over 50% in all tumor types except mature cystic teratoma, which showed a positive rate of 23.7%. CA125 was useful for the screening of malignant germ cell tumors. CA19-9 showed a high positive rate in teratomatous tumors, which were immature teratoma, mature cystic teratoma with malignant transformation, and mature cystic teratoma. Dysgerminoma and yolk sac tumor, especially dysgerminoma, had a high positive rate of LDH. TPA and CEA were not considered useful tumor markers for germ cell tumors of the ovary.

Biomarkers, Tumor↗
PubMed1992

Monoclonal antibodies to a CD4 peptide derivative which includes the region corresponding to an immunoglobulin CDR3: evidence of the involvement of pre-CDR3-related region in HIV-1 and host cell interaction.

A CD4 peptide of amino acid residues 68-130 [CD4(68-130)], which had the capacities to inhibit HIV-1 replication and HIV-1-induced syncytium formation, was used as an immunogen for the preparation of mAb. The mAbs prepared were classified into at least five types (I-V) in terms of their recognition sites by ELISA using various kinds of smaller CD4 peptides. Among them, the type I mAb no. 35 recognizing amino acid residues 72-84, which lies just before the region corresponding to an immunoglobulin third complementarity-determining region (CDR3), showed the strongest effects in reducing both HIV-1 infection and HIV-1-induced syncytium formation, although a large amount of no. 35 mAb was necessary to reduce such HIV-1 activities compared with those of anti-Leu-3a and OKT4A mAbs which recognize CD4 epitopes near a portion corresponding to an immunoglobulin CDR2. Western blot analysis showed that the reactivities of CD4 molecule in CD4-positive cells or sCD4 molecule with types I-V mAbs were stronger than that with anti-Leu-3a mAb. Flow cytometry showed that no. 35 mAb was faintly reactive with native CD4 molecule on cell surface at the concn showing the inhibitory effects on HIV-1 infection and syncytium formation. In addition, a smaller peptide CD4(66-92), one of the good epitope peptides for no. 35 mAb, also showed strong inhibitory effect on HIV-1 infection as well as a weaker inhibitory effect on syncytium formation. These results suggest that, in addition to the CD4 CDR2-related region, the pre-CDR3-related region is also involved in the early events of the interactions between the host cell and HIV-1.

Amino Acid Sequence↗
PubMed1992

Human immunodeficiency virus type 1 (HIV-1) superinfection of a cell clone converting it from production of defective to infectious HIV-1 is mediated predominantly by CD4 regions other than the major binding site for HIV-1 glycoproteins.

A cell clone, L-2, which produces non-infectious doughnut-shaped human immunodeficiency virus type 1 (HIV-1) particles, was permissive for HIV-1 superinfection, which resulted in the production of infectious particles. The superinfection showed slow kinetics compared with primary HIV-1 infection of M10 cells, the parent of the L-2 cell clone. Inhibition studies on the superinfection of L-2 cells using several CD4-related reagents showed that the CD4 molecule was an essential component of the receptor for superinfection. Strong inhibitory effects were obtained using CD4 peptides such as CD4(68-130), which includes a portion homologous to the immunoglobulin third complementarity-determining region (CDR3), as well as recombinant soluble CD4. In contrast, a CD4(45-60) peptide, which includes most of the CDR2-related region, was not effective, although the Leu-3a monoclonal antibody (MAb), which recognizes a site near the CDR2-related region, did slightly, but significantly, delay the superinfection kinetics. Comparative flow cytometry of L-2 and M10 cells revealed that the cell surface of L-2 cells despite expressing HIV-1 env protein, reacted slightly with OKT4 or anti-CD4(68-130) MAb, but not with Leu-3a or OKT4A MAb. In contrast, no reaction was detected with any of these anti-CD4 MAbs on the surface of another HIV-1 superinfection-resistant cell clone, MOLT-#8IIIB-14, which expresses HIV-1 env proteins but does not produce infectious HIV-1 particles. These results strongly suggest that expression of the CD4 major receptor site for primary HIV-1 infection is preferentially decreased on the surface of L-2 cells, but that the OKT4 epitope and the nearby region corresponding to immunoglobulin CDR3 remain exposed on the cell surface. Consequently, the CD4 CDR3-related region could play a major role as the receptor for the superinfection reported here.

Binding Sites↗
PubMed1992

Complementation of human immunodeficiency virus glycoprotein mutations in trans.

The external glycoproteins of human immunodeficiency virus type 1 (HIV-1) (gp120) and HIV-2 (gp105) are responsible for binding the cellular receptor CD4. The proteins are functionally identical although their affinity for CD4 varies, with gp120 binding 10- to 20-fold more efficiently than gp105. To investigate the structural requirements for CD4 binding in each molecule we have constructed a number of hybrid glycoproteins in which sequences are exchanged between the two molecules via conserved residues and subsequently tested for their ability to bind to CD4. We found that two constructs in which the V1/V2 or V3 loops of gp105 are exchanged for those of gp120 continue to bind to CD4. Surprisingly, however, all other domain exchange mutants failed to bind to CD4 suggesting that long-range interactions within the molecule are sequence-specific. Mixing mutant molecules in vitro did not rescue CD4 binding. However, co-expression of a number of mutant glycoprotein pairs within the same cell produced complementation of CD4 binding ability; complementing molecules were shown to be heteromeric in structure. Alignment of the molecules within each complementation group allowed the interactive sequences necessary for receptor binding to be determined. These sequences constitute a novel target for the disruption of gp120 function.

Animals↗
PubMed1992

Accumulation of cis-diamminedichloroplatinum (II) and its analogues in sensitive and resistant human ovarian carcinoma cells.

Human ovarian carcinoma cell line (NOS2), established from a patient with serous cystadenocarcinoma of the ovary, has been exposed to a stepwise increase in cis-diamminedichloroplatinum (II) (CDDP) concentration to produce a CDDP-resistant cell line NOS2CR) as an experimental model for resistance to CDDP. NOS2CR cells showed a 7-fold resistance to CDDP and a lesser degree of cross-resistance to diammine (1,1-cyclobutanedicarboxylato)-platinum (II) (CBDCA) and (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato) platinum (II) (DWA2114R). In the absence of CDDP, cross-resistance to DWA2114R was reduced to the original level by 2 months, although 83% resistance to CDDP remained up to 6 months. To investigate CDDP-resistant mechanisms, alterations in the intracellular accumulation of CDDP and analogues were assayed by atomic absorption. In both NOS2 and NOS2CR cells, accumulation of CDDP increased linearly with time and was concentration-dependent. NOS2CR cells demonstrated 71, 52 and 12% reduction in accumulation of CDDP, CBDCA, and DWA2114R, respectively. These reductions did not seem to be due to P-glycoprotein, because expression of multidrug-resistant 1 gene was not detected in either NOS2 or NOS2CR cells. These studies indicate that the mechanisms of resistance to CDDP and analogues in NOS2CR cells are related in the main to reduced intracellular accumulation of drugs. DWA2114R might be helpful to treat CDDP-resistant and recurrent tumors which were treated by CDDP.

Antineoplastic Agents↗
PubMed1992

[Study of an outbreak of itai-itai disease].

We studied an outbreak of itai-itai disease in the Jinzu River basin, in Toyama, Japan. One hundred and fifty females recognized as itai-itai disease patients till by 1990 were studied for the ages and years of onset and residence in the cadmium-polluted area. 1. Cases were recognized from as early as 1929, increased gradually to the peak of 1955-1959 and rapidly decreased up to the 1970s. 2. It was found that the later the patients was born, the younger the age of onset, though there was no difference of ages of onset between the cases born in the 1910s and the cases born from 1920. 3. The onset of itai-itai disease was most frequently seen at 50-59 years of residence in the cadmium-polluted area. It was found that the later a person started to inhabit the cadmium-polluted area, the shorter the period of residence in the cadmium-polluted area up to onset of itai-itai disease. 4. Comparing the patients who inhabited the cadmium-polluted area from birth and those who had moved there from non-polluted areas, the age of onset was higher in the latter, but there were no significant differences in the period of residence up to onset. From these findings, it appeared that itai-itai disease was not caused by aging, but by cadmium exposure starting from the 1910s.

Cadmium Poisoning↗
PubMed1992

In vitro monitoring activation by the ligands and specific DNA-binding of the glucocorticoid receptors.

The glucocorticoid receptor is a member of the steroid and thyroid hormone receptor superfamily and acts as a ligand-activated transcription factor. To reconstitute the molecular mechanisms underlying the cellular response to soluble receptor ligands, we have exploited a cell-free system that exhibits glucocorticoid-induced activation of the latent cytosolic glucocorticoid receptor to an active DNA-binding species. We demonstrate here that cytosol from a rat hepatoma cell, M1.19, contains glucocorticoid receptor-specific immunoreactivities and target DNA-binding activities. Moreover, specific DNA-binding activities of M1.19 cytosol were dose-dependently induced by dexamethasone treatment, and linearly correlated with the hormonal induction of chloramphenicol acetyltransferase activity at the corresponding concentrations. These results indicate that the cytosolic glucocorticoid receptor could be converted in a DNA-binding form under cell-free conditions and the ligand appears to play a crucial role in the direct control of the level of functional activity of a given ligand-receptor complex.

Animals↗
PubMed1992

[[Comparison of mortality rates of elderly people in China and Japan]].

"The mortality rates and causes of death among elderly people aged sixty five and over were compared between China and Japan. The data used for comparison was China's 1990 and Japan's 1990 vital statistics. It appears that the mortality rate in China was higher than Japan. Comparing the causes of death, it was found that the death rates involving cerebrovascular diseases, malignant neoplasms and heart diseases in urban districts of China [were] higher than those in Japan. Also the death rate of people with bronchitis in rural districts was significantly higher in China.... The differences in the medical systems and life styles in China and Japan were suspected as the reasons for the differences of death rates and causes of death...." (SUMMARY IN ENG)

Adult↗
PubMed1992

Small cell carcinoma of the stomach: an immunohistochemical and electron microscopic study.

A 4 x 6 cm ulcerative mass in the antrum was found to consist of papillary adenocarcinoma in the surrounding wall and the small round cell neoplasm at its base. Immunohistochemical staining revealed that elements of the papillary adenocarcinoma were positive for carcinoembryonic antigen, epithelial membrane antigen, keratin, endocrine granule constituent, and CA19-9, while components of the small cell carcinoma were weakly positive only for neuron-specific enolase. In one portion of the small cell carcinoma, particularly large cells with pleomorphic nuclei which were intensely positive for desmin were detected. Electron microscopic examination revealed dense-cored granules and intercellular junctions in the small neoplastic cells and bundles of intermediate filaments in the desmin-positive large cells. These findings suggest that ultrastructural examination is vital in diagnosis of small cell carcinoma and they reveal the capability of this carcinoma toward multidirectional differentiation.

Adenocarcinoma, Papillary↗
PubMed1992

The role of antigen-presenting cells in the regulation of delayed-type hypersensitivity. I. Spleen dendritic cells.

A previously unreported mechanism for the induction of delayed-type hypersensitivity (DTH) was studied in detail. The subcutaneous injection (without adjuvant) of spleen dendritic cells (DC) pulsed with keyhole limpet haemocyanin (KLH) into syngeneic BALB/c mice caused DTH when the ear was later injected with the same antigen. When KLH-pulsed DC were transferred intravenously, DTH was not induced, although the titre of anti-KLH antibodies rose after such transfer. The intravenous transfer of KLH-pulsed DC into mice immunized subcutaneously with KLH in complete Freund's adjuvant (CFA) at the same time (in the sensitization phase), but not when the ear was challenged with KLH (in the effector phase), had a suppressive effect on DTH, in an H-2-restricted way. When radiolabelled DC were transferred intravenously, they migrated into the spleen, but when transferred by subcutaneous injection, they stayed in the skin or migrated into the lymph nodes. In splenectomized mice immunized with KLH, the intravenous transfer of KLH-pulsed DC did not cause production of anti-KLH antibodies and did not suppress DTH. These findings suggest that the anatomical sites in which antigens are presented (i.e. the spleen or lymph nodes) rather than the type of cell that first presents antigens to the immune system governs whether DTH or antibody production is induced. Antibody production was induced when antigens were presented in the spleen.

Animals↗
PubMed1992

[Clinical study of prophylactic therapy of interferon on postoperative renal cell carcinoma].

A clinical trial using interferon alpha 2b (IFN alpha-2b) for prophylactic therapy was done on 44 patients who had received nephrectomy for renal cell carcinoma. Principally, the daily intramuscular injection of 3 of 6 million units of IFN alpha-2b was done for 4 consecutive weeks after 2 weeks postoperatively and thereafter followed by injection once every 2 weeks. The clinical evaluation was done for the recurrence rate, the survival rate, the IFN alpha and IFN gamma producing ability, the activity of 2',5' oligoadenylate synthetase (2-5AS) and the side effect. Out of 44 cases entered, 42 were completely evaluable and recurrence was observed in 5 (11.9%) of the 42 cases. The recurrence rate was 5.5% and 16.4%, at the first and second year, respectively. Three (7.1%) of the 42 patients died. The survival rate was 97.6% at the first year, 89.7% at the second year for the followup study. The IFN alpha producing capacity was low in all of the 4 evaluable cases. The IFN gamma producing capacity was high in 3 cases and normal in 1 case. 2-5AS, the enzyme produced by IFN, was activated by IFN alpha-2b administration in all of the 4 evaluable cases. Side effects were observed in 24 (54.5%) of the 44 cases. The main side effect was fever. Leucopenia, general fatigue, appetite loss, temporary elevation of liver transaminase were also observed. However, there were only 5 cases (11.4%) in which administration of IFN alpha-2b had to be discontinued.

Adult↗
PubMed1992

[Study of preventive effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU) or combination of HCFU and 2.5-di-O-acetyl-D-glucaro (1-4) (6-3) dilactone (SLA) after preservative operation against bladder cancer].

To treat superficial bladder cancer or invasive bladder cancer presenting as a solitary tumor, conservative therapy such as transurethral resection of bladder tumor or partial cystectomy has long been carried out. We studied the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU), and the effects of the combination of HCFU and 2.5-di-O-acetyl-D-glucaro-(1-4)(6-3) dilactone (SLA) which is an anti-beta-glucuronidase agent, for preventive therapy. In the patients treated with HCFU, the recurrence rate was 3.6% and 26.6% one year and two years, respectively, after conservative operation. In the patients treated with both SLA and HCFU, the recurrence rate was lower than in those treated with HCFU one year or more after conservative operation, and a long-term preventive effect was expected for nondrinkers.

Adult↗
PubMed1991

Effects of maternal bilateral ureteral ligation on the differentiation of glomerular anionic sites in fetal rat kidney.

Effects of maternal bilateral ureteral ligation on the differentiation of glomerular anionic sites in fetal kidney were studied with the colloidal iron method. The ligation was performed on days 17, 19, and 21 of pregnancy, and the animal were euthanized 1 day after each ligation. On fetal day 20, in the fetuses from ligated mothers, colloidal iron was concentrated in laminae rarae interna and externa of the glomerular basement membrane. In the fetuses from sham-ligated mothers, however, a different pattern of iron distribution was noted. In most areas of the glomerular basement membrane, colloidal iron was randomly distributed as in both fetuses of fetal day 18. In the remaining areas, the same pattern of colloidal iron distribution as was noted in the fetuses from ligated mothers of fetal day 20 was observed. On fetal day 22, colloidal iron was densely accumulated in laminae rarae interna and externa of the glomerular basement membrane in both groups. However, the iron-free zone was slightly thicker in the fetuses from the ligated mothers. These findings suggest that maternal bilateral ureteral ligation accelerates the differentiation of glomerular anionic sites in the kidney of fetal rats.

Animals↗
PubMed1991

The morphology of the developing canine conducting system: bundle branch and Purkinje cell architecture from birth to week 12 of life.

This is a qualitative and quantitative study of dog bundle branch and Purkinje cell development from day 0 to week 12 of life; we correlate the morphologic data with changes observed in the functional properties of developing dog Purkinje tissue. The bundle branch itself has a roughly cylindrical shape and is surrounded by a collagen sheath covered with endocardium. Within the bundle, Purkinje cells are packed closely together in fascicles distributed evenly around a central artery. Cross-sectional area doubles in the right bundle and increases 5-fold in the left bundle system between day 0 and week 12 of life. About one third of the bundle by volume is Purkinje tissue; the rest is extracellular space containing an increasing amount of collagen as the animal ages. Purkinje cell cross-sectional area is constant during the first week of life, but its length doubles and the cell changes from a relatively round to a more cylindrical shape. Between day 7 and week 12, cell diameter doubles; Purkinje cell surface area increases 5-fold and its volume almost 10-fold. As a consequence, the surface to volume ratio halves and approaches the value reported for adult dogs by week 12 of life. The percent of the intercalated disc occupied by nexal junctions virtually doubles by week 12, the same period over which Purkinje fiber conduction velocity increases. The disc itself becomes less dominant as the cell enlarges; the total percent of sarcolemma involved in its formation decreases by a fourth and has achieved the adult value by week 12 of life. As this happens, the percent of cell membrane facing on clefts increases almost 6-fold, so that the total percent of sarcolemma facing on small spaces (approximately 340A wide) is constant over the age period studied. The paucity of clefts in newborn tissue compared with the value reported for the adult dog may help explain the relative lack of responsiveness to extracellular potassium concentration of the resting membrane potential described for fetal Purkinje tissue. Within the Purkinje cell itself, the percent by volume occupied by mitochondria remains relatively constant over the age span studied, while sarcomeric mass increases 3-fold over the same period of time; these data are consonant with the relative resistance of this tissue to hypoxia.

Animals↗
PubMed1991

Reduction in CD4 binding affinity associated with removal of a single glycosylation site in the external glycoprotein of HIV-2.

The role of selected glycosylation sites in the ability of the envelope glycoprotein of HIV-2 (gp 105) to bind to CD4 has been investigated. Loss of glycosylation sites at amino acids 410 and 447 did not affect the CD4 binding ability of gp 105 even when removed in pair combination. Loss of a single glycosylation site at amino acid 400, however, was sufficient to cause a reduction of at least 50-fold in the efficiency of receptor binding. These data support the hypothesis that some of the carbohydrate side chains on gp 105 have a profound effect on biological activity.

Base Sequence↗