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Biomedical subjects

H Kodama

Publications and source records attributed to H Kodama.

At least 19 recordsLinked to original sources
PubMed1992

Determination of cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in the urine of a patient with cystathioninuria using column liquid chromatography-mass spectrometry.

A method for the measurement of cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in the urine of a patient with cystathioninuria has been developed, using column liquid chromatography-mass spectrometry. Cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid were determined by scanning the [M + H]+ ions of each compound. The recoveries were 80-92.4% for cystathionine and 80-100% for perhydro-1,4-thiazepine-3,5-dicarboxylic acid after ion-exchange treatment. The results agreed well with those obtained using an amino acid analyser. The concentrations found for cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid were 1.289 +/- 0.099 mg/ml and 0.310 +/- 0.0067 mg/ml, respectively.

Cystathionine↗
PubMed1992

In vitro proliferation of primitive hemopoietic stem cells supported by stromal cells: evidence for the presence of a mechanism(s) other than that involving c-kit receptor and its ligand.

The preadipose cell line, PA6, can support long-term hemopoiesis. Frequency of the hemopoietic stem cells capable of sustaining hemopoiesis in cocultures of bone marrow cells and PA6 cells for 6 wk was 1/5.3 x 10(4) bone marrow cells. In the group of dishes into which bone marrow cells had been inoculated at 2.5 x 10(4) cells/dish, 3 of 19 dishes (16%) contained stem cells capable of reconstituting erythropoiesis of WBB6F1-W/Wv mice, indicating that PA6 cells can support the proliferation of primitive hemopoietic stem cells. When the cocultures were treated with an antagonistic anti-c-kit monoclonal antibody, ACK2, only a small number of day 12 spleen colony-forming units survived; and hemopoiesis was severely reduced. However, when the cocultures were continued with antibody-free medium, hemopoiesis dramatically recovered. To examine the proliferative properties of the ACK2-resistant stem cells, we developed a colony assay system by modifying our coculture system. Sequential observations of the development of individual colonies and their disappearance demonstrated that the stem cells having higher proliferative capacity preferentially survive the ACK2 treatment. Furthermore, cells of subclones of the PA6 clone that were incapable of supporting long-term hemopoiesis expressed mRNA for the c-kit ligand. These results suggest that a mechanism(s) other than that involving c-kit receptor and its ligand plays an important role in the survival and proliferation of primitive hemopoietic stem cells.

Animals↗
PubMed1992

Herbimycin A, an inhibitor of tyrosine kinase, prolongs survival of mice inoculated with myeloid leukemia C1 cells with high expression of v-abl tyrosine kinase.

Herbimycin A, a benzoquinonoid ansamycin antibiotic, reduces intracellular phosphorylation by some tyrosine kinases, including v-abl. The mouse megakaryoblastic cell line C1 expresses v-abl protein at high levels. Herbimycin A at about 20 ng/ml caused 50% inhibition of growth of C1 cells but at 100 ng/ml scarcely affected the growth of another mouse leukemia cell line, M1 cells, or of normal bone marrow cells. Injection of 10(6) C1 cells into nude mice resulted in death of all the mice within 30 days. Administration of herbimycin A significantly enhanced the survival of mice inoculated with C1 cells but scarcely affected the survival of mice inoculated with M1 cells. These results suggest that herbimycin A and/or related compounds may be useful for treatment of some types of leukemia in which tyrosine kinase activity is implicated as a determinant of the oncogenic state.

Animals↗
PubMed1992

Factors influencing the response and survival of patients with liver metastases from breast cancer receiving OK-432-combined adoptive immunotherapy.

The response and survival of 26 patients with liver metastases from breast cancer, who received OK-432-combined adoptive immunotherapy from 1984 to 1990, were evaluated. OK-432-combined adoptive immunotherapy was comprised sequential treatment via the hepatic artery with a streptococcal preparation, OK-432 (1-5 KE), and adoptive transfer of lymphocytes expanded in T-cell growth factor and sonicated tumor extract antigen. Seventeen (65%) patients responded to the therapy. The median survival time of all patients after treatment was 13 months (range, 2-63 months). Of the 20 prognostic factors analyzed, performance status (PS) alone was related to response (P less than 0.01). The response rate of the patients with a PS of 0-2 was 83% but only 25% in those with a PS of 3 or 4. In univariate analysis, 11 factors significantly influenced the survival: tumor response; size of primary tumor; menopausal status; PS; serum bilirubin, albumin, lactate dehydrogenase and glutamate-oxalate transaminase (aspartate aminotransferase); the extent of liver involvement; and the number and the proliferation rate of transferred lymphocytes. The MST was 22.8 months for the responders versus 2.8 months for the nonresponders (P less than 0.01). In multivariate analysis, the most important factor associated with survival was the tumor response, as well as PS, liver involvement, lactate dehydrogenase and albumin. These results suggest that OK-432-combined adoptive immunotherapy can be considered a candidate for a randomised control study and these factors should be used for stratification.

Breast Neoplasms↗
PubMed1992

Therapeutic and life-prolonging effect of intrapleural injection with a streptococcal preparation, OK-432, and IL2-cultured effusion lymphocytes to breast cancer patients with malignant pleural effusion.

We developed a local AIT using PEL cultured with TCGF combined with preadministration of OK-432. Twenty-six patients of breast cancer with pleural effusion have been treated with this therapy since 1983. PEL expanded and tumor cells collapsed by day 9 in culture with TCGF. Cultured PEL possessed significantly higher cytotoxic activity against autologous tumor cells than PBL cultured in the same condition (p less than 0.05), but there was no difference between their cytotoxic activities against K562. The proliferation rate of PEL obtained after intrapleural administration of OK-432 was higher than that obtained before OK-432 (p less than 0.01). Moreover, the cytotoxic activities against both autologous tumor and K562 of cultured PEL obtained after OK-432 administration was significantly (p less than 0.05) higher than those cultured PEL obtained before. Cultured PEL (1 x 10(8)-6 x 10(9)) were transferred into the pleural cavity after the intrapleural administration of OK-432 (1-5 KE). The volume of pleural effusion increased temporarily after the administration of OK-432 but significantly (p less than 0.01) decreased after AIT. Tumor cells disappeared cytologically in 22 patients at the last puncture of pleural effusion. Pleural effusion disappeared completely in 19 of 26 patients and decreased by more than 50% in volume in 6 patients. Performance status improved in 22 patients. The response rate for OK-432-combined AIT in the present study was 96%. The survival period of the patients treated by OK-432-combined AIT in this trial was significantly (p less than 0.002) prolonged compared to that of the patients receiving chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of danazol at the immunologic level in patients with adenomyosis, with special reference to autoantibodies: a multi-center cooperative study.

OBJECTIVE: We attempted to evaluate the effects of danazol on autoantibodies, in particular, to phospholipids, and on the immune system in patients with adenomyosis. STUDY DESIGN: Forty-two patients with adenomyosis who had high titers of autoantibodies were randomly chosen, and they received 400 mg/day of danazol for 4 months (n = 22) or underwent hysterectomy (n = 20). RESULTS: Among the six autoantibodies we investigated, the incidence of antiphosphatidylinositol immunoglobulin G was the highest (42.9%), followed by antiphosphatidylglycerol immunoglobulin G (38.1%). The autoantibody titers decreased with time and were comparable to the control values 16 weeks after treatment in both groups. Total serum levels of immunoglobulin G and M were high before treatment, but immunoglobulin M levels decreased significantly in week 8 during treatment with danazol, whereas C4 levels increased and C3 levels decreased with danazol. CONCLUSION: Danazol has an inhibitory effect on the autoimmunologic response associated with adenomyosis.

Autoantibodies↗
PubMed1992

[Enteropathogenicity and enteropathogenic toxin production of Vibrio mimicus].

Enteropathogenicity and enteroreactive-toxins were examined in 66 strains of Vibrio mimicus and the following results were obtained. Frequencies of enteropathogenic strains judged by the result of suckling mouse tests were 11/13 (85%) for clinical isolates and 37/53 (70%) for fish or environmental isolates. Frequencies of preservation of cholera toxin gene and NAG-ST gene were 2 and 15%, respectively, for 48 enteropathogenic strains, and 0 and 6%, respectively, for 18 non-enteropathogenic strains. Frequencies of production of NAG-rTDH, FAF and hemolysin were 4, 63 and 100%, respectively, for 48 enteropathogenic strains, and 6, 50, and 100%, respectively, for 18 non-enteropathogenic strains. No correlation between serovar and enteropathogenicity was observed in the suckling mouse test. Six out of 12 enteropathogenic strains produced hemolysin in ligated rabbit ileal loop, while 1 out of 12 non-enteropathogenic strains did so under the same condition. A significant inhibition of fluid accumulation in the ligated rabbit ileal loop test with viable cells was noted in rabbits immunized with hemolysin of non-O1 V. cholerae. These results suggest that approximately two-thirds of environmental isolates are enteropathogenic and that hemolysin is the most important toxin in the enteropathogenic mechanism of V. mimicus strains.

Animals↗
PubMed1992

Immunologic characteristics of cytokines in otitis media with effusion.

Levels of cytokines, interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in samples of the middle ear effusions (MEEs) from 144 ears with otitis media with effusion (OME) by enzyme-linked immunosorbent assay, followed by cytologic analysis. Middle ear effusions of the acute purulent type contained a significantly higher concentration of cytokines compared with normal control sera (p < .001). Cytokines were observed at lower levels in MEE in adults than in children. Tests of children at the chronic stage of MEE showed higher levels of TNF than IL-1 and GM-CSF. Meanwhile, IL-1 beta showed significantly higher concentrations in acute purulent types than in serous and mucoid types (p < .01). In cytologic analysis, the mean level of IL-1 beta was significantly higher in the neutrophil-rich group than in other groups (p < .05). Cytokines possess several biologic properties, some of which are associated not only with acute otitis media but also with chronic otitis media. This study showed that cytokines, especially IL-1 beta, contribute to infiltration into the middle ear by inflammatory cells. This implies that the persistent presence of cytokines in MEE could be a factor in prolonged OME.

Acute Disease↗
PubMed1992

Insulin dependent diabetes mellitus accompanied by nephrocalcinosis and renal failure.

Renal failure was found in a five-year-old patient who had been treated with insulin since he was diagnosed as having insulin dependent diabetes mellitus (IDDM) at 3 years of age. Laboratory data showed that his renal failure was caused by a renal tubular dysfunction. The autopsy findings of his pancreas were compatible with those of IDDM. The kidneys were atrophied with an innumerable number of crystals in the proximal tubuli. Staining by Kossa indicated that the crystals contained calcium salt. The calcium content of his kidneys was significantly higher than that of control. The nephrocalcinosis seems to be caused by hypercalciuria associated with IDDM.

Child, Preschool↗
PubMed1992

Sulfur amino acid levels and related enzyme activities in various brain regions (and other tissues) in normal mice and rolling mice Nagoya.

The contents of the sulfur amino acids, and the activities of cystathionine beta-synthase and cystathionine gamma-lyase were measured in various regions of the brain and several other tissues in both normal mice and rolling mice Nagoya. The cystathionine content and cystathionine beta-synthase activity were found to be unevenly distributed in various regions of the brain in both normal mice and rolling mice Nagoya, being highest in the cerebellum. Except for the mesencephalon and thalamus plus hypothalamus, the cystathionine content and cystathionine beta-synthase activity in the brain regions of rolling mice Nagoya were much higher than those of the normal mice. The cystathionine content after D,L-propargylglycine treatment was also found to be unevenly distributed in various brain regions in both normal mice and rolling mice Nagoya. The concentrations of cystine and methionine were also higher in all regions of the brain of rolling mice Nagoya than those of normal mice, while the concentration of taurine in the various regions of the brain was almost the same in normal mice and rolling mice Nagoya. Cystathionine beta-synthase and cystathionine gamma-lyase activities in the liver, kidney, and pancreas were almost the same in both the normal mice and rolling mice Nagoya.

Amino Acids, Sulfur↗
PubMed1992

Properties of hammerhead-type RNA enzyme derivatives which contain a G-to-I replacement in the loop region.

Three hammerhead-type ribozyme derivatives containing a G-to-I replacement in the loop regions were chemically synthesized and their properties were examined. All three complexes showed a markedly reduced RNA-cleaving activity. NMR studies suggested that the complex with mutation at the third guanosine of the longer internal loop region has the greatest influence on the conformation of the loop regions.

Base Sequence↗
PubMed1992

Survey of conformational role of ester bonds in a cyclic depsipeptide. Study on cyclo(-L-Ala-L-Hmb-)2 by energy calculation and NMR spectroscopy.

The effect of ester bond on the conformation of peptide molecule was studied by designing and synthesizing a model tetradepsipeptide cyclo(-L-Ala-L-Hmb-)2 and by analyzing the conformation both theoretically and experimentally. Theoretical analysis showed that both ester and peptide bonds in the calculated low-energy conformations within 3 kcal/mol of the global minimum take a trans but distorted configuration. The distortion is larger in ester bonds than in peptide bonds. Further, the four carbonyls project from one side of the plane of the cyclic backbone, whereas the side chains project from the other side. These results are consistent with the experimental results obtained by NMR measurement; first, the coupling constant deduced from 1H-NMR species in DMSO-d6 is consistent with the dihedral angles of the calculated low-energy conformations; second, results of NOE measurement can reproduce the calculated configuration of the carbonyls and side chains. From the consistency between theoretical and experimental results, it is concluded that this model tetradepsipeptide takes an all-trans backbone conformation in solution and this backbone conformation is stabilized by large distortion in the ester bond, which compensates the strain resulted from the 12-membered cyclic backbone structure consisting only of L-residues.

Amino Acid Sequence↗
PubMed1992

[A role of interpectoral (Rotter's) lymph node dissection in modified radical mastectomy for breast cancer].

To study the influence of interpectoral lymph node (IPN) dissection on the prognosis of patients who underwent modified radical mastectomy, IPN was carefully dissected and studied pathologically on 168 cases of our breast cancer patients operated with modified radical mastectomy. There were 1.2 lymph nodes on an average in the interpectoral region, and they were almost 1-2mm in diameter. IPN metastases were found in 10 cases. (Tis: 0%, Stage I: 4.9%, Stage II: 5.7%, Stage III: 13%). Tumors located in outer quadrant in almost all these cases. Positive IPN were found in 6 (16%) of n1 alpha group, 1 (10%) of n1 beta group, and in 3 (50%) of n2 group. All these 3 cases of n2 died of distant metastasis and local recurrence. Two (1.7%) of axillary node (1a, 1b) negative patients had microinvolvement of cancer only in IPN, and are currently disease-free. These data suggest that IPN metastasis may occur even in the early breast cancer patients, and that may be controllable by lymph node excision. Therefore, routine and careful dissection of IPN through wide opening of sulcus interpectoralis is necessary for modified radical mastectomy and even for breast preserving operation.

Adult↗
PubMed1992

[Augmentation of therapeutic effect of adoptive immunotherapy through a synergy between transferred killer cells and host's fresh lymphocytes].

Among several approaches to augment the therapeutic effect of adoptive immunotherapy, we focused the antitumor synergy between transferred killer cells and host's fresh lymphocytes. Immunotherapy models using murine tumors or clinical experiments revealed that preadministration of immunostimulator such as OK-432, followed by chemotherapeutic agents such as cyclophosphamide, can induce host's non-cytotoxic fresh lymphocytes that act synergistically with cultured killer cells against autologous tumor cells. Immuno-chemo-lymphocytotherapy (a sequential treatment with OK-432, chemotherapy and adoptive immunotherapy) is useful to treat the patients with advanced cancer even if the number of transferred lymphocytes is limited.

Animals↗