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Biomedical subjects

H Kodama

Publications and source records attributed to H Kodama.

At least 523 records · Page 29Linked to original sources

[Breast cancer-specific immunity evaluated by a new in vitro method--IL-2 enhanced MLTR].

Peripheral blood lymphocytes from 81 patients with breast cancer were stimulated in vitro with solubilized sonicated autologous tumor extract as an antigen source . The significance of tumor-stimulation (mixed lymphocyte tumor reaction; MLTR) was evaluated with or without the addition of interleukin-2 (IL-2,90 U/ml). As a result, MLTR with the addition of IL-2 (IL-2 enhanced MLTR) showed a higher significance even at a stimulation index (S.I.) of 1.5 than MLTR without IL-2. The values of S. I. in IL-2 enhanced MLTR in preoperative cancer patients were the highest in the patients without lymph node metastasis (n0). The patients with advanced lymph node metastasis (n2) showed a lower response preoperatively but their response was similar to that of the n0-patients 1 to 2 was after operation. These difference were not observed in the blastogenic response to IL-2. These results suggest that IL-2 enhanced MLTR is a useful method to assess the tumor-specific immunological status of the cancer patients.

Antigen-Antibody Reactions↗

[Effects of cilastatin sodium, an inhibitor of dehydropeptidase-I, on human urinary peptide excretion. Patients with renal insufficiency].

Effects of imipenem/cilastatin sodium (IPM/CS), a new parenteral carbapenem combination antibiotic, on the excretion of urinary peptides were investigated by amino acid analysis of these peptides from 12 patients with varying degrees of impairment of renal function, after single or multiple doses (9 doses) of 500 mg/500 mg of the combination drug administered by 30-minute drip infusion. In a single dose study, slight increase in glycine (Gly) were observed in patients with mildly impaired renal function (group I). On the other hand, several amino acids including aspartic acid (Asp), glutamic acid (Glu), Gly and alanine (Ala) were increased in patients with moderately (group II) and severely (group III) impaired renal function. Gly showed the greatest increase, 1.029 microM/mg creatinine.2 hours, and the value was 2.4 times as high as the control collected before drug administration. These values were reduced to the control levels within 10-12 hours after the drug administration for amino acids showing small increases and within 12-24 hours after drug administration even for those showing greater increases. In a multiple-dose study employing 3 patients with moderately impaired renal function, Asp and Gly were found to increase after the 1st, 5th and 9th doses. The increased amino acids were reduced to preadministration levels within 10-12 hours or faster, and no tendency for accumulation was observed. From the above results, CS, as a dehydropeptidase-I inhibitor apparently caused increases in some peptides consisting mainly of Asp, Glu, Gly and Ala in patients with impaired renal function. A careful selection of dose levels and frequency of administration will be required in patients with moderately or severely impaired renal function.

Aged↗

Detection of fish antibody against protein antigen of Aeromonas salmonicida by enzyme-linked immunosorbent assay using biotin-avidin system.

Antibody against Aeromonas salmonicida was detected in sera from immunised or experimentally infected rainbow trout by enzyme-linked immunosorbent assay (ELISA) using the biotin-avidin system. The ELISA titre correlated well with the agglutinin titres of the sera, but the ELISA was found to be more sensitive than the agglutination test. When the rainbow trout serum was separated by column chromatography, antibody activity (determined by ELISA and agglutination test) was detected in the IgM fractions. Minimum cross reaction was observed in the ELISA system between antigen prepared from A salmonicida and antibodies against Vibrio species and other species of Aeromonas. The specificity of the ELISA was also confirmed by inhibition test. Immunisation of rainbow trout with a virulent strain of A salmonicida provided good protection, though no correlation was observed between the protection and the ELISA titres of sera.

Aeromonas↗

Regional distribution of gastrin-releasing peptide- and somatostatin-like immunoreactivity in the rabbit hypothalamus.

Regional distribution of gastrin-releasing peptide- (GRP) and somatostatin (SRIF)-like immunoreactivity in the discrete nuclei of the hypothalamus was examined in the rabbit according to Palkovits' microdissection method. GRP-like immunoreactivity (LI) was detected abundantly in the hypothalamus as compared with the cerebral cortex when measured by radioimmunoassay using the antiserum recognizing the C-terminal portion of synthetic porcine GRP. On gel-filtration chromatography of the hypothalamic extracts, two major peaks of GRP-LI were eluted; the peak with larger molecular size corresponded to synthetic porcine GRP1-27 and the smaller size to porcine GRP14-27. A concentration of GRP-LI was highest in the infundibular nuclei (IFN) as well as the ventromedial nuclei (VMN), and next high in the paraventricular nuclei (PVN), suprachiasmatic nuclei (SCN) and periventricular nuclei (PEV). The content of GRP-LI in the median eminence was not so much when compared with them. On the other hand, SRIF was localized in the highest concentration in the ME, followed by the VMN and IFN, as well as the PEV. The findings indicate that porcine GRP-LI exists in the hypothalamus of rabbits with characteristic regional distribution. Concurrent localization of GRP-LI and SRIF in some parts of the hypothalamus may suggest the interaction of both peptides in these areas under various physiological and pathological status.

Animals↗

Renal effects of dichloroacetate in vivo.

We have investigated the effect of dichloroacetate (DCA) on the urinary excretion of lactate and pyruvate in a patient with congenital lactic acidosis and in healthy human controls. DCA administered orally in doses of 50 mg/kg and 30 mg/kg decreased plasma lactate and pyruvate of both the patient and the controls, while the urinary excretion of lactate and pyruvate was increased. However, these urinary increments were too small to contribute to the decrease of plasma lactate and pyruvate.

Acetates↗

MC3T3-G2/PA6 preadipocytes support in vitro proliferation of hemopoietic stem cells through a mechanism different from that of interleukin 3.

Both MC3T3-G2/PA6 preadipocytes and interleukin 3 (IL 3) can support in vitro proliferation of mouse hemopoietic stem cells (CFU-S). We examined whether MC3T3-G2/PA6 cells produce IL 3 and whether a common mechanism might underlie the action of both of these agents. We used cultured mast cells, DA-1 cells, and FDC-P2 cells as the targets of IL 3 and conditioned medium (CM) of WEHI-3 cells as a source of IL 3. MC3T3-G2/PA6 CM did not support the growth of the above cells. IL 3 mRNA was not detected in the preadipocytes. Since CM obtained from the cocultures of bone marrow cells and MC3T3-G2/PA6 cells did not have a significant effect on the growth of the IL 3-dependent cells, none of the bone marrow cells seem to produce IL 3 under the influence of the preadipocytes. When the factor-dependent cells were cocultured with MC3T3-G2/PA6 cells, the former did not survive, whereas mast cells and DA-1 cells intimately associated with the preadipocytes. Even when bone marrow cells, mast cells, and MC3T3-G2/PA6 cells were cocultured, the number of CFU-S increased, but not that of mast cells. These results seem to exclude the possibility of the action of IL 3 in the microenvironment provided by MC3T3-G2/PA6 preadipocytes.

Adipose Tissue↗

Ornithine transcarbamylase deficiency: a case with a truncated enzyme precursor and a case with undetectable mRNA activity.

The cell-free translation of ornithine transcarbamylase (OTC) mRNA from the livers of two heterozygous patients (from different families) with OTC deficiency was performed. The enzyme activities and the immunoreactive proteins in both patients were about 5% of those in controls. Immunoblotting assay of liver extracts from both patients showed decreased amounts of the OTC protein. The mRNA from the liver of patient 1 directed the synthesis of a very small amount of OTC precursor of normal subunit size (40,000 Da), whereas that from patient 2 directed the synthesis of small amounts of two distinct in vitro products; one was 40,000 Da and the other was about 30,000 Da. The in vitro product of normal precursor synthesized with mRNA from patient 2 was converted to mature-sized OTC by isolated rat liver mitochondria, whereas the smaller product was degraded during the incubation with the mitochondria. These results indicate that in both patients the translatable level of mRNA for active OTC from liver cells was much lower than that in the controls. The results also suggest that in patient 2, the smaller product presumably derived from an abnormal gene could not be transferred to the mitochondria.

Child↗

Activation of cytomegalovirus infection in immunosuppressed cynomolgus monkeys inoculated with varicella-zoster virus.

A systemic activated cytomegalovirus (CMV) infection was fortuitously detected in almost all monkeys which had been immunosuppressed with antithymocyte globulin (ATG), cyclophosphamide (CY), and cortisone acetate (CS) before and after experimental inoculation with varicella-zoster virus (VZV). They developed exudative pneumonia, and the lesions in visceral organs and tissues contained cytomegalic cells with intranuclear inclusion bodies, in which viral antigens, specific for CMV, but not inoculated VZV, were detected by immunofluorescence. Serological study of paired sera from these monkeys ascertained preexisting CMV infection. Under the present experimental conditions, this infection was highly reproducible and always occurred within three, but not two, weeks of immunosuppression in monkeys inoculated with VZV. We therefore examined the host factors involved in activation of latent CMV. The immunocompetence of the host was destroyed almost completely with treatment of ATG, CY, and CS, but not with combinations of two of these agents, revealing the systemic depletion of lymphoid cells in tissues including the thymus medulla. Although the role of VZV in the induction of CMV remains uncertain, the heterologous VZV inoculum may have produced some effects equivalent to the allogeneic reaction to release latent CMV. These monkeys may represent an animal model of "opportunistic" CMV infection in immunocompromised and/or allografted humans.

Age Factors↗

Plasma disappearance half-time and metabolic clearance rate of exogenous human growth hormone-releasing hormone-(1-44)-NH2 in normal subjects.

By means of human growth hormone-releasing hormone (hGHRH)-RIA using an antiserum directed toward the C-terminal region of hGHRH-(1-44)-NH2, the plasma disappearance half-time and metabolic clearance rate (MCR) of immuoreactive hGHRH (IR-hGHRH) were examined in normal subjects after an iv bolus injection of synthetic hGHRH-(1-44)-NH2 (1 microgram/kg BW). The disappearance of IR-hGHRH from plasma was characterized by a biexponential decay curve, with initial distribution and subsequent metabolic t1/2 value of 5.0 +/- 1.0 and 29.6 +/- 5.4 min (mean +/- SE), respectively. The MCR of IR-hGHRH was 6.1 +/- 1.2 ml/min X kg. The volume of distribution of IR-hGHRH was 3.3 +/- 0.4 liters. The molecular size of the plasma IR-hGHRH was not different from that of hGHRH-(1-44)-NH2 for at least 90 min after the injection of hGHRH-(1-44)-NH2 when examined by gel-filtration chromatography. This prolonged clearance of hGHRH from human plasma relative to that of other hypothalamic hormones may in part explain the sustained plasma GH rises after hGHRH injection in man.

Adult↗

Monoclonal antibody to chicken fetal antigen on Marek's disease lymphoblastoid cell line MDCC-MSB1.

A monoclonal antibody (2H3) to chicken fetal antigen (CFA) expressed on the cell surface of the Marek's disease lymphoblastoid cell line MDCC-MSB1 was generated. 2H3 reacted specifically with various cells from chicken embryos, especially with fetal red blood cells, fetal bursa-derived lymphocytes, fetal liver cells, and embryo fibroblasts but not with fetal peripheral blood lymphocytes. 2H3 reacted also with all lymphoblastoid cell line cells tested: Marek's disease, avian leukosis, and reticuloendotheliosis line cells. On the basis of 2H3 specificity, CFA detected by 2H3 seemed to be similar to chicken fetal red blood cell antigen previously reported, but not to chicken alpha-fetoprotein. A transient increase of reactivities with 2H3 was observed in lymphocytes prepared from thymus, spleen, and bursa of chickens inoculated with Marek's disease virus or herpesvirus of turkeys from 7 to 21 days postinoculation. The average percentage of CFA-positive cells in lymphoid cells from Marek's disease virus-infected chickens at the peaks was higher than that of the cells in Marek's disease tumor cells from 146- and 156-day-old chickens in the field. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting analysis revealed that the monoclonal 2H3 is recognized a Mr 50,000 oncodevelopmental cell surface antigen present on MDCC-MSB1 cells. The possible differences between CFA detected by 2H3 and chicken fetal red blood cell antigen expressed on normal chicken fetal erythrocytes are discussed.

Animals↗

Cystamine-enkephalin dimer. Syntheses and biological activities of enkephalin analogs containing cystamine and cysteamine.

A cystamine-enkephalin dimer, containing two molecules of [D-Ala2, Leu5] enkephalin cross-linked at the COOH-terminal leucine residue with cystamine, (NH2-CH2-CH2-S-)2, has been synthesized in order to examine directly the dimerization effect of an enkephalin molecule on the opiate receptor interactions. In a comparison of potencies against [3H]-[D-Ala2,D-Leu5] enkephalin (3H-DADLE) and [3H]-[D-Ala2,MePhe4,Gly-ol5] enkephalin (3H-DAGO) as delta and mu tracers, respectively, enkephalin dimer showed a very high affinity, especially for the delta opiate receptors. Dimer was almost threefold more potent than DADLE, which is one of the most utilized delta ligand to date. When the binding affinity of cystamine-dimer was compared with that of its reduced thiol-monomer, namely [D-Ala2,Leu5,cysteamine6] enkephalin, the increment in affinity was four to fivefold for both delta and mu receptors. The results strongly indicate that the dimeric enkephalin is more potent presumably due to the simultaneous interaction with the two binding sites of the opiate receptors.

Animals↗

[An in vitro sensitivity assay for anti-cancer agents by measuring the inhibition rate of DNA synthesis (3H-thymidine uptake of cancer cells). II. Clinical study of 110 cases of breast cancer].

The sensitivity of cancer cells to anti-cancer agents (ACA) was assessed in 110 cases of breast cancer (87 primary cases and 23 recurrent cases). The cancer cells were cultured with ACAs: Mitomycin C (MMC), Adriamycin (ADR), 5-Fluorouracil (5-FU), Cytosine Arabinoside (Ara-C), Carboquone (CQ), Nimustine Hydrochloride (ACNU), Cis-platinum Diammine Dichloride (CPDD) or Vincristine (VCR) for 3 days and their sensitivity was estimated by the inhibition rate (I.R.) of DNA synthesis (3H-thymidine uptake) of cancer cells. The DNA synthesis was higher in recurrent cases than in primary cases. The primary cases showed high sensitivity to ADR or CQ, and the recurrent cases showed high sensitivity to ADR. Histologically, papillotubular or medullary tubular carcinoma showed high sensitivity to CQ, and scirrhous carcinoma showed high sensitivity to ADR, CQ or 5-FU. The sensitivities of medullary tubular or scirrhous carcinoma to ADR, 5-FU and CQ in patients with stage III and IV were lower than those in patients with stages I and II. No difference of ACA sensitivity was observed between estrogen receptor (+) and (-) cases. All recurrent cases were treated with 5-FU or its derivatives. The 50% survival period in the 5-FU high sensitivity (I.R. greater than 80%) group was 7.0 months and that of the low sensitivity (I.R. less than 80%) group 3.0 months, respectively.

Adenocarcinoma↗