Search PubMed⌕ Search

Biomedical subjects

K Morikawa

Publications and source records attributed to K Morikawa.

At least 235 records · Page 13Linked to original sources
PubMed1990

[Biochemical study on the application of alpha-cyanoacrylate instant adhesives in dentistry].

The author biochemically evaluated the possible application of 4 types of alpha-cyanoacrylate adhesive agents (methyl, ethyl, isopropyl and isobutyl) in dentistry. A semiconductor temperature sensor was used to measure alpha-cyanoacrylate polymerization-temperature maximum heat, and an oscilloscope was employed to measure heat value. Amounts of formaldehyde eluted from the soluble component of alpha-cyanoacrylate was measured colorimetrically. In addition, to evaluate the effects of alpha-cyanoacrylate on pulp tissue, the soluble component of alpha-cyanoacrylate polymer was added to mouse macrophages. Changes in the numbers and morphology of macrophages and their glucose consumption in the supernatant medium were studied and compared with corresponding data obtained when formaldehyde alone was used. (1) During the polymerization of alpha-cyanoacrylate, when a glass fiber disc filter was used, the temperature increased by 19.1 degrees C in 1 microliter with methyl and by 8.6 degrees C with isobutyl. Even with the same alkyl, however, polymerization heat differed depending on the structure and constitution of the adhesive material and varied widely according to experimental conditions. (2) A mean maximum temperature of 1.7 degrees C in the dentin floor during polymerization of 10 microliters of alpha-cyanoacrylate monomer with methyl suggests no thermal injury to the pulp. (3) Formaldehyde was detected in all 4 adhesives when alpha-cyanoacrylate was dropped into distilled water for polymerization. Since, with each alkyl, the amount of eluted formaldehyde reached a maximum after 1 day of immersion, continuous elution of formaldehyde by hydrolysis was negligible. (4) A greater amount of formaldehyde was eluted from the polymer with methyl and ethyl, which have less Cs, than from the polymer with isopropyl and isobutyl, which have more Cs. These findings suggest that alkyl type affects the amount of eluted formaldehyde. (5) The soluble component of the alpha-cyanoacrylate polymer, either methyl or ethyl, had no effect on the number or morphology of mouse macrophages, as compared with corresponding data obtained when sterilized distilled water was used as a control. Isopropyl and isobutyl, however, decreased cell count and inhibited the extension of the sell soma. (6) The effects of isopropyl and isobutyl on the numbers and morphology of macrophages were similar to those of formaldehyde used alone at a concentration of 8 ppm or more. These findings suggest that, under the present experimental conditions, the above-mentioned changes in macrophages are the effects of about 8 ppm of formaldehyde. (7) The rate of glucose consumption by macrophages with methyl or ethyl was as high as that with the control.(ABSTRACT TRUNCATED AT 400 WORDS)

Adhesives↗
PubMed1990

[Antitumor activity of a new platinum complex, (R)-(-)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II), against cisdiamminedichloroplatinum (II)-resistant murine leukemia cell line].

Antitumor activity of a new platinum complex, (R)-(-)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) (DWA 2114 R) against cisdiamminedichloroplatinum (II) (CDDP)-resistant tumor was examined in in vitro and in vivo experiments. CDDP-resistant line was established from L 1210 mouse leukemia cells by continuous exposure to CDDP in dose-escalation manner. Six clones were isolated from parental resistant line and one of these clones, clone f, which was found to be highly resistant (30-40 fold) to CDDP, was used in the following experiments. Clone f showed 4-7 fold cross-resistance to DWA 2114 R and 11-19 fold to cisdiammine-1, 1-cyclobutanedicarboxylatoplatinum (II) (CBDCA) in in vitro growth inhibition assay. DWA 2114 R showed the most effective antitumor activity against mice transplanted with the resistant cells in the increase of life span (ILS%). About 100% of ILS and cured mice were observed in the treatment with DWA 2114 R. On the other hand, CDDP or CBDCA showed a little increase in the survival time (less than 40% of ILS) and all mice died. These results suggest that DWA 2114 R seemed to be more effective against CDDP-resistant tumors clinically than CDDP and CBDCA.

Animals↗
PubMed1989

Metastatic potential of human colorectal carcinomas implanted into nude mice: prediction of clinical outcome in patients operated upon for cure.

To determine whether the production of experimental hepatic metastases in athymic nude mice by human colorectal carcinomas (HCC) correlated with the clinical outcome in patients, we harvested colorectal carcinomas from 82 patients, dissociated the tumors with collagenase and DNase, and injected them into groups of nude mice, either in the flank to assess experimental tumorigenicity or into the spleen to produce experimental metastasis in the liver. Growth in mice was then associated with clinicopathological factors and clinical outcome. Growth of HCC in either the flanks or the livers of nude mice was associated with the time to recurrence in a Wilcoxon analysis. Analysis of the outcome data in a Cox proportional hazards model suggested that there was an interaction between tumorigenicity and metastatic potential of HCC in nude mice and serum CEA concentration in the patient and stage of disease. A univariate analysis indicated that both tumorigenicity and metastatic potential of HCC in nude mice were significantly associated with the serum CEA concentration of the patient but not with the other variables of stage of disease, mucin production, local tissue invasion, state of differentiation, or sex. A subset of 57 patients was operated upon for cure and followed prospectively for up to 61 months. Tumorigenicity and, to a lesser extent, experimental metastatic potential were associated with disease recurrence in 23 of these patients. Seventy-eight % of the subset of patients who were operated upon for cure developed liver metastasis as one site of their progressive disease. Thus, the ability of HCC cells isolated from surgical specimens to grow in athymic nude mice correlates with the development of advanced disease in patients.

Adult↗
PubMed1989

Overproduction and preliminary crystallographic study of ribonuclease H from Escherichia coli.

To facilitate the preparation of ribonuclease H from Escherichia coli in an amount sufficient for crystallographic studies, we have constructed an overproduction system for the enzyme. The structural gene for the enzyme was subcloned from pSK750 (Kanaya, S., and Crouch, R. J. (1983) J. Biol. Chem. 258, 1276-1281) to make a plasmid vector pPL801, in which the gene was under the control of bacteriophage lambda PL promoter. Thermal induction of the gene accumulated the enzyme in E. coli N4830-1 to approximately 8% of the total cytosolic protein. The level of production of the enzyme in N4830-1 harboring pPL801 was 14 mg/liter culture, which was 3000 times as high as that in the host cell. The enzyme was purified with a yield of more than 80% and crystallized by utilizing the property that the solubility of the enzyme decreased at pH values close to its isoelectric point (pI = 9). Crystals were grown by successive seeding (hanging drop method) for x-ray crystallographic analysis. The crystals belong to space group P212121 with unit cell dimensions of alpha = 44.1 A, b = 87.0 A, c = 35.5 A and contain one molecule in an asymmetric unit. They diffracted x-rays beyond 2.5 A resolution.

Bacteriophage lambda↗
PubMed1989

Mechanisms of combined effects of gamma-interferon and 5-fluorouracil on human colon cancers implanted into nude mice.

The purpose of these studies was to determine the possible mechanisms responsible for the therapeutic effects of systemic administration of 5-fluorouracil (FUra) and gamma-interferon on disseminated human colon cancer. We used several human carcinoma cell lines that were established from different surgical specimens. Some lines were selected in nude mice for increased metastatic potential, and one line was selected in vitro for resistance to human recombinant gamma-interferon (r-IFN-gamma). In initial in vitro studies, FUra was cytostatic against all the human cell lines but did not produce cytolysis in any of the lines tested. The two r-IFN-gamma were species specific for both antitumor and immunomodulatory effects. Human r-IFN-gamma produced cytostatic and cytolytic effects against sensitive human colon carcinoma cells but did not activate tumoricidal properties in mouse macrophages. In contrast, mouse r-IFN-gamma had no direct cytotoxic effects against any of the human colon carcinoma lines but did activate tumoricidal properties in mouse macrophages. Human colon carcinoma cells (sensitive or resistant to human r-IFN-gamma) were implanted into the spleens of nude mice. Three days later, we began treatments with FUra and human or mouse r-IFN-gamma. In all experiments, the combination of FUra with mouse r-IFN-gamma produced the best therapeutic effects against growth of the cells in the spleen and in the liver. Because the mouse r-IFN-gamma is devoid of direct antitumor effects (against human tumor cells) but is a potent macrophage activator, these results suggest that the antitumor effects were due to direct antitumor effects of FUra and to activation of host defense mechanisms by the r-IFN-gamma.

Animals↗
PubMed1989

Bestatin, an inhibitor of aminopeptidase B, suppresses the proliferation and differentiation of human B-cells in vitro.

Bestatin, an inhibitor of aminopeptidase B, was examined for its effect on B-cell activation. Small, dense B-cells from human tonsil samples were isolated by Percoll density gradients from non-rosetted (E-) cells and were used as target cells. Although bestatin was not cytotoxic towards B-cells, it inhibited the proliferative response of B-cells induced by SAC- or PMA-stimulation. The inhibition of cell proliferation by bestatin was manifested as cell arrest caused by the selective block of G1b to S phase transition. This inhibitory effect was prevented by the addition of B-cell growth factor (BCGF) or interleukin-2 (IL-2). The presence of BCGF or IL-2 at the initiation of the culture prevented the bestatin-mediated suppressive effect on B-cell proliferation. Bestatin also has a direct inhibitory effect on the differentiation of B-cells independent of its suppressive effect on B-cell proliferation, which was not relieved by T-cell help. Conversely, bestatin suppressed neither proliferation nor Ig secretion of human B lymphoblastoid cell lines, although aminopeptidase activities on the membrane of these cell lines were strongly inhibited by bestatin. These results indicated that bestatin selectively suppressed normal B-cell proliferation and differentiation. Although several studies have demonstrated that bestatin has immunopotentiating effects in tumor-bearing subjects, the above results indicated that the mechanism of immunopotentiation by bestatin is not a direct stimulatory effect on B-cells.

Adjuvants, Immunologic↗
PubMed1989

Mean cellular volume of urinary red blood cells in investigation of hematuria.

The mean cellular volume (MCV) of urinary red blood cells (RBCs) of pediatric patients with glomerular (group I; n = 52) and nonglomerular (group II; n = 21) hematuria was determined using an automated blood-cell analyzer. Group I patients had a significantly lower MCV than group II (61 +/- 8 vs. 88 +/- 15 microns 3, mean +/- SD; p less than 0.001). With a MCV of 75 microns 3 taken as the dividing line between glomerular and nonglomerular hematuria, correct assessment of the site of bleeding was made in 67 of the 73 (92%) patients studied. Determination of the MCV of urinary RBCs is a simple noninvasive test for localizing the site of hematuria in pediatric patients.

Adolescent↗
PubMed1989

Effects of various drugs on bladder function in conscious rats.

In the present study, we attempted to evaluate the effects of various intravenous administered drugs, which had been shown to influence bladder function in anesthetized animals, on the cystometrogram in conscious rats placed in a restraining cage. Thiopental, diazepam, baclofen, clonidine and flavoxate, considered to act on the micturition center in the brain stem, hardly increased bladder capacity (time to micturition in cystometrogram) in conscious rats, but morphine, indomethacin and lidocaine, considered to act on the micturition center in the sacral cord or bladder mechanoreceptors, increased it. In a chronic conscious rat, histopathological findings show that the bladder tissue at 2 days after implantation of the catheter to the bladder showed experimental cystitis characterized by severe edema in the submucosa and an increase in prostaglandin E2 content, which is thought to stimulate directly and/or indirectly the capsaicin-sensitive sensory fiber in the afferent branch of the micturition reflex, and there was hyperreflexia characterized by decreases in both bladder capacity and urine volume. In conclusion, cystometrography in conscious rats placed in a restraining cage is thought to be a useful model for evaluating the true effect of a newly developed agent on bladder function.

Animals↗
PubMed1989

Clonal stimulation or inhibition of human colon carcinomas and human renal carcinomas mediated by transforming growth factor-beta 1.

We examined various human carcinomas and cells populating a single human neoplasm to determine whether they exhibit a heterogeneous response to the effects of transforming growth factor-beta 1 (TGF-beta). Using recently established human colon carcinoma and renal cell carcinoma under defined in vitro conditions, we observed intertumoral and intratumoral heterogeneity and polarity of responses to TGF-beta (growth inhibition or stimulation) that did not correlate with the metastatic phenotype of the cancer cells as assessed in athymic nude mice. TGF-beta mediated both cytostatic and cytolytic effects against sensitive tumor cells, and these responses were not related to the effects of TGF-beta on the cell-cycle traverse. The human colon carcinoma and renal cell carcinoma, however, exhibited differences in the expression of TGF-beta receptors.

Animals↗
PubMed1989

[The size of the mastoid pneumatization and otitis media with effusion in children].

It is generally believed that a cause and effect relationship exists between chronic middle ear inflammatory conditions and suppressed growth of the pneumatized cellulae. We already demonstrated the normal process of pneumatization and the suppressive process of pneumatization in experimental studies using pigs. In that study, the process of suppression of the pneumatization was caused by the continuous inflammatory changes of the epithelium of the middle ear cavity, and the degree of the suppression of the pneumatization was caused by the degree and duration of the air cavity's inflammatory condition at the growing stage of the mastoid process. We also carried out the histological study of the normal process of pneumatization using 100 sides of human fetuses between 16th and 36th week of pregnancy. In these studies the bone metabolisms which were found in the normal processes of pneumatization in pigs and human fetuses were same, and the normal pneumatization occurred at the growing stage of the mastoid process. This growing period of the mastoid is from 0 to 6 months after birth in pigs, and 0 to 15 years in humans. So in humans, we can infer that the suppression of the growth of the cellulae is closely related to a persistent state of otitic inflammation like an otitis media with effusion in the early stages of growth. From these studies, in children who have otitis media with effusion, it will be possible to realize the previous middle ear pathology by the degree of the suppression of pneumatization on x-ray film.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Heterogeneous response of human colon cancer cells to the cytostatic and cytotoxic effects of recombinant human cytokines: interferon-alpha, interferon-gamma, tumor necrosis factor, and interleukin-1.

We examined whether different human colorectal carcinomas (HCC) and cells populating a single neoplasm exhibit a heterogeneous response to the cytostatic and cytolytic effects of recombinant human cytokines used clinically for cancer therapy. The effects of interferon-alpha (IFN-alpha) hybrid BBDD, interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin-1 (IL-1), and the chemotherapeutic drug 5-fluorouracil (used as a positive control for cytostasis) were examined in six recently established HCC cell lines. One cell line was sensitive to the cytostatic and cytotoxic effects of IFN-alpha BBDD, whereas five cell lines were sensitive to IFN-gamma. Tumor cell sensitivity to IFN-alpha BBDD was independent of sensitivity to IFN-gamma. Only one cell line was somewhat sensitive to the cytostatic and cytotoxic effect of TNF, and none was sensitive to IL-1. The heterogeneous response to cytokines by a single neoplasm was demonstrated by analysis of multiple clones. Clonal populations exhibited different levels of susceptibility to cytostatic effects mediated by cytokines. The combination of IFN-gamma with IFN-alpha BBDD or with TNF produced additive or even synergistic cytostasis in HCC lines sensitive to the cytokines but not in cell lines that were resistant to either one or both agents. Collectively, these studies demonstrate intra- and intertumoral heterogeneity in sensitivity to recombinant cytokines, a finding that should receive consideration for clinical application.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Evaluation of leukocyte oxidative metabolism using whole blood samples by chemiluminescence and flow cytometric assays].

To examine granulocyte oxidative metabolism (GOM) quantitatively, we evaluated two methods, one for assaying luminol-dependent chemiluminescence (CL) and the other for changes in fluorescence by dichlorofluorescin (DCF). The CL assay was carried out using a lumiphotometer (TD-4000, Laboscience) after stimulating granulocytes in whole blood by n-formyl-methonyl-leucyl-phenylalanine (FMLP, 100 nmol/l) or by opsonized zymosan (OZ, 2 mg/ml). To reduce hemoglobin (Hb) interference, each sample was diluted with autologous plasma to a Hb concentration of 3 g/dl. The DCF assay was performed on whole blood samples (100 microliters) labeled with DCF (5 mumol/l) following stimulation by phorbol myristate acetate (PMA, 100 ng/ml). Changes in fluorescence were determined using a flow cytometer that gave the delta mean channel fluorescence intensity (DMCF) as an indicator of GOM. The coefficients of variance (CV) in within-run assays for the CL and the DCF were 10% and 5%, respectively. These CV-values were almost the same even when separated granulocytes as a test sample were used instead of whole blood. CL determined by FMLP stimulation in 27 renal failure patients on hemodialysis (HD), was significantly lower than that in 10 normal controls, but no difference was found in that determined by OZ stimulation. In HD patients, the DMCF values tended to increase in those at 15 min and the end of HD sessions compared to the value prior to HD. This suggested that the HD membrane and/or extracorporeal circulation stimulates GOM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Antitumor activity of a new platinum complex (R)-(-)-2-aminomethylpyrrolidine (1,1-cyclobutane dicarboxylato) platinum (II) (DWA2114R) by its serial administration].

Antitumor activity of a newly synthesized platinum complex, DWA2114R, by the serial administration was examined and compared with that of cis-diammine-1,1-cyclobutane dicarboxylato platinum (II) (CBDCA). In mice transplanted s.c. with tumor, the serial i.p. administration resulted in the increases of both maximal tolerated dose (MTD) and growth inhibitory ratio (GIR) of DWA2114R than single administration. Such increases in MTD and GIR were also shown by CBDCA, but the degree of these increases, such as the ratio of MTD or GIR by the serial administration compared to that at the single administration, was higher in DWA2114R than CBDCA. GIR of DWA2114R by the serial administration was higher than that of CBDCA at the doses to induce the same toxicity which was estimated by body weight loss. In addition, in the experiment using ascites tumor-bearing mice, better antitumor activity of DWA2114R was shown by the elongation of survival time. These results indicate that the cumulative toxicity of DWA2114R is lower than that of CBDCA, which causes the therapeutic advantages of DWA2114R in the serial administration.

Animals↗
PubMed1988

Overcoming suppression of antitumor immune reactivity in tumor-bearing rats by treatment with bleomycin.

We investigated the immunological role of bleomycin (BLM) in the treatment of KMT-17 fibrosarcoma-bearing rats. We were able to detect antitumor immune reactivity by using a mixed-lymphocyte tumor culture in spleen cells shortly after the transplantation of a KMT-17 fibrosarcoma in syngeneic Wistar King Aptekman/HMK rats. The reactivity declined following the progression of the tumor and was completely inhibited 11 days after the tumor transplantation. After the 11th day, however, spleen cells from BLM-treated KMT-17-bearing rats demonstrated higher antitumor immune reactivity. This result corresponds to those we obtained from an in vivo tumor-neutralizing assay (Winn assay). Macrophages from untreated tumor bearers were unable to inhibit the immune reactivity against KMT-17 cells in the mixed-lymphocyte tumor culture. Neither the tumor-bearing state nor the BLM treatment seemed to have any significant influence on another macrophage function, the antigen-presenting cell activity. However, a T-enriched fraction from untreated KMT-17 bearers showed a definite suppression activity on the generation of cytotoxic T-lymphocyte activity against KMT-17 tumor in the mixed-lymphocyte tumor culture; in contrast, no T-suppressor activity could be detected in the same fraction taken from BLM-treated tumor bearers. Our investigation suggests that BLM eliminates the tumor-specific T-suppressor activity without having any influence on responder T-lymphocytes in the cell-mediated antitumor immune reactivity.

Animals↗