Biomedical subjects
Publications and source records attributed to M Yamamura.
A 65-year-old woman with ocular myasthenia gravis (MG) and thymic tumor underwent expanded thymectomy. Histologically the tumor was thymic cyst and thymolipoma. To our knowledge, there has been no case reported in medical literatures, which is thymic cyst & thymolipoma with ocular MG. This case suggests some effect of steroid therapy.
A 46-year-old woman after renal transplantation 10 years ago underwent CABG using the right internal thoracic artery to LAD, the left internal thoracic artery to Circumflex and the right gastroepiploic artery to RCA, with the diagnosis of unstable angina (triple vessels disease) after failed PTCA. The postoperative course has been uneventful. To our knowledge, this is the first case who underwent GABG after renal transplantation in Japan.
A 45-year-old woman was hospitalized for examination of a cardiac murmur. She had undergone surgery for a membranous ventricular septal defect at the age of 22. Cardiac catheterization showed a membranous ventricular septal aneurysm and a residual shunt. At reoperation, we found the membranous septal aneurysm to be accompanied with a posterior ventricular septal defect. The septal defect was closed with a Dacron patch, and the septal aneurysm was excised, with direct closure. Membranous ventricular septal aneurysm is generally associated with membranous ventricular septal defect. Cases of membranous ventricular septal aneurysm with posterior ventricular septal defect are rare.
Reactional states in leprosy are produced by different immunologic mechanisms and are responsible for a major component of tissue damage of the disease. Reversal reactions exhibit increased CD4 T cell infiltration in lesions and augmented cell-mediated immune reactivity to Ag of Mycobacterium leprae that can rapidly produce nerve damage. Erythema nodosum leprosum (ENL) reactions also have CD4 T cell infiltration but appear to be associated with the formation of immune complexes that are responsible for panniculitis, arthritis, vasculitis, and nerve injury. Because these reactional states may serve as paradigms for other types of human immunologically mediated tissue damage, this study sought to characterize the dynamic changes in cytokines associated with these reactions. Expression of cytokine mRNA in lesions of leprosy reactional states were measured by PCR. In reversal reactions, IL-1 beta, TNF-alpha, IL-2, and IFN-gamma mRNA were prominent and found to increase during the reaction, concomitant with decreases in expression of mRNA for IL-4, IL-5, and IL-10. In ENL, selective increases in the expression of IL-6, IL-8, and IL-10 mRNA was observed, with persistent expression of IL-4 and IL-5 mRNA. Reversal reactions represent naturally occurring delayed-type hypersensitivity reactions that favor macrophage activation and protective immunity, but which can engender concomitant cell injury. In contrast, ENL lesions represent immediate-type hypersensitivity reactions reflecting the selective stimulation of cytokines that attract neutrophils, stimulate antibody production, and down-regulate macrophage activation. The analysis of cytokine dynamics within different inflammatory responses can provide insights into immune mechanisms of tissue damage, and provide a useful framework for developing strategies for therapeutic intervention.
Lipoarabinomannan (LAM), a major cell wall component of Mycobacterium tuberculosis, exhibits a wide spectrum of immunoregulatory effects. To identify cytokines produced by human PBMC in response to LAM, we used PCR amplification to detect cytokine mRNA. LAM-induced transcription of mRNA for cytokines characteristically produced by macrophages, including TNF, granulocyte-macrophage-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, and IL-10. In contrast, LAM did not induce transcription of mRNA for cytokines produced predominantly by lymphocytes, such as lymphotoxin, IFN-gamma, IL-2, IL-3, or IL-4. Measurement of concentrations of TNF, granulocyte-macrophage-CSF, IL-6, IL-10, IFN-gamma, IL-2, and IL-4 in cell culture supernatants indicated that cytokine release correlated with mRNA patterns. Lipomannan (LM) and phosphatidylinositol mannosides (PIM) are simpler versions of LAM. LM lacks arabinan, whereas PIM lacks both arabinan and most mannan residues. LAM, LM, and PIM induced transcription of cytokine mRNA, elicited cytokine production, and suppressed Ag-induced T cell proliferation, indicating that most of the biologic activity of LAM was associated with the phosphatidylinositol end of the molecule. In support of this conclusion, deacylation of LAM abrogated its capacity to induce cytokine production and suppress Ag-induced proliferation. The production of macrophage-derived cytokines induced by LAM may mediate clinical manifestations of tuberculosis such as fever, weight loss, and tissue necrosis, as well as immunoregulatory effects such as inhibition of Ag-induced proliferation and hyperglobulinemia.
A new mutant alpha-1-antichymotrypsin (variant ACT) was found by direct sequencing and PCR-single strand conformation polymorphism (PCR-SSCP). This variant ACT was a point mutation of exon V of ACT, with the substitution of Met by Val. Four out of six individuals with this variant ACT had occlusive-cerebrovascular disease, leading to one hypothesis that there might be an association between this mutation and occlusive-cerebrovascular disease.
Using chromogranin (CG) immunohistochemical staining, the prognostic significance of endocrine differentiation was investigated in 212 patients with primary colorectal adenocarcinoma (including 6 patients with mucosal carcinoma). CG-immunoreactive cells were found to be an integral component of the tumor in 67 of 206 patients (32.5%, excluding mucosal carcinoma). The intracellular localization of CG in the CG-immunoreactive cells in cancer tissue was completely different from that in the normal endocrine cells of the large bowel. In addition, morphologic changes such as nuclear hyperchromasia and pleomorphism also indicated that the CG-immunoreactive cells in the cancer tissue were malignant. The tumors were divided into three groups based on the frequency of CG-immunoreactive cells: Group I (n = 139), negative; Group II (n = 38), less than 1 positive cell/mm2; and Group III (n = 29), more than 1 positive cell/mm2. No correlation was observed between CG-immunoreactivity (CG-IR) and tumor location, grade, depth of invasion, or stage, regardless of lymph node involvement. However, patients with numerous endocrine tumor cells (Group III) had a significantly worse prognosis compared with patients without endocrine cells (Group I) (multivariate Cox's model, P less than 0.01). Similar findings were observed in patients with node-negative tumor (multivariate Cox's model, P less than 0.05). These results indicated that the neuroendocrine differentiation is an independent prognostic factor and that CG-immunohistochemistry is useful for detecting a subgroup with a worse prognosis among patients with colorectal cancer.
The cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in combination with hydroxyurea (HU) or 2'-deoxyguanosine (GdR) on human gastric carcinoma MK-1 cells and colon carcinoma HT-15 cells was studied. Synergistic interaction between ara-C and HU on MK-1 cells and HT-15 cells, or ara-C and GdR on MK-1 cells was shown using the combination index method. HU increased the accumulation of ara-C triphosphate (ara-CTP) in the acid-soluble pool and diminished the cellular deoxyCTP (dCTP) pool. HU had no effect on the incorporation of ara-C into DNA and RNA. These results indicate that HU-induced elevation in ara-CTP and decrease in dCTP are the basis for synergy among ara-C and HU in MK-1 cells. GdR diminished cellular dCTP slightly, but it decreased the accumulation of ara-CTP in the acid-soluble pool and did not increase the incorporation of ara-C into DNA. On the other hand, ara-C increased cellular deoxyGTP (dGTP) level in the presence of GdR. These results indicate that synergy between ara-C and GdR is mediated through increased cellular dGTP which might inhibit DNA synthesis directly.
Explore the source record for details and available documents.
A new mutant alpha-1-antichymotrypsin (variant ACT) was found by polymerase chain reaction single strand conformation polymorphism and direct sequencing. In this variant ACT, two bases (AA) were deleted from codon 391. This resulted in a different amino acid sequence downstream of the deletion point, elongating the peptide chain by 10 amino acids.
Kallikrein activity in human stomach tissue was measured and found to be about threefold higher in cancer tissue than in normal tissue. To clarify the physiological role of this tissue kallikrein, we investigated its effects on the spontaneous metastasis and tumor growth of Lewis tumors (3LL). Antiprotease, aprotinin, and gabexate mesilate (FOY) inhibited spontaneous metastasis but did not inhibit tumor growth, while tissue kallikrein and plasmin enhanced the spontaneous metastasis of 3LL. The results suggest that the inhibitory effects of aprotinin and FOY on metastasis are not only due to an inhibition of tumor cells released by tissue kallikrein, but that tissue kallikrein, a protease, also participates in metastasis. We thus conclude that aprotinin or FOY should be administered either before or immediately after operation to inhibit spontaneous metastasis.
Hepatic metastasis of colorectal cancer was found in 40 (16%) of 250 patients with colorectal cancer treated in our department during the past 5 years. Liver cirrhosis was not found among the 40 patients with metastases (16%) but was present in 46 (21.9%) of the 210 nonmetastatic patients, with a significant difference between the two groups (p less than 0.001). The rate of patients who were positive for hepatitis B surface antibody was 10% in the metastatic group and 34.3% in the nonmetastatic group, with a significant difference (p less than 0.01). These findings suggest that colorectal cancer does not metastasize to the injured liver, especially the cirrhotic liver.
Explore the source record for details and available documents.
Several N-substituted C-normorphinans (VIII and IX) were synthesized and tested for their analgetic and narcotic antagonist activities and physical dependence capacity. Treatment of N-formyl- octahydro-2-pyrindine (IIIc) with polyphosphoric acid readily gave N-formyl-C-normorphinan (IV). The N-nor bases (V and VII) obtained from IV were converted to VIII and IX. The N-methyl derivative (I), which was previously reported to be inactive by Haffner's method, exhibited potent analgetic activity by the hot plate method and the AcOH-induced writhing test. Compounds VIII and IX showed pharmacological properties similar to those of N-substituted morphinans and exhibited agonist (analgetic) and/or narcotic antagonist activities. The C-nor analogue (IXa) of cyclorphan (IIc) exhibited potent analgetic and antagonist activities with no physical dependence capacity in the single-dose suppression tests both in rats and monkeys.
Novel cyclic sulfoxides, such as 2-octyl, 2-dodecyl and 2-hexadecyltetrahydrothiophene-1-oxide were prepared by the alkylation of tetrahydrothiophene-1-oxide. Additionally, 2-methyl, 2-ethyl and 2-propyl-5-dodecyltetrahydro-thiophene-1-oxide were conducted by further alkylation. Their enhancing activity on the penetration of indomethacin through rabbit skin was evaluated in in vitro experiments, and the effect of the alkyl length on the enhancing activity was discussed. Among the 2-alkyl-tetrahydrothiophene-1-oxides, the compounds containing dodecyl and hexadecyl groups promoted a much greater penetration of the drug through the skin than the compound containing an octyl group. A stronger effect was observed in the experiment using 2-dodecyl-5-alkyltetrahydrothiophene-1-oxide, as compared with the that of 2-dodecyl-tetrahydrothiophene-1-oxide. The substitution of the alkyl groups to the next position of the sulfoxide group seemed to make the enhancing activities large.
Explore the source record for details and available documents.
The liver and spleen volume ratio (S/L ratio) was estimated with X-ray computed tomography. Clinical usefulness of S/L ratio was evaluated by comparison with other liver functions (retention rate of ICG, total bilirubin, serum albumin and cholinesterase activity) in 42 hepatocellular carcinoma patients with liver cirrhosis. The correlation between S/L ratio and retention rate of ICG, total bilirubin, serum albumin or cholinesterase activity was good (r = 0.870, r = 0.719, r = -0.691, or r = -0.606, respectively p less than 0.001). Positive correlation was observed between S/L ratio and retention rate of ICG or total bilirubin. Negative correlation was observed between S/L ratio and serum albumin or cholinesterase activity. In conclusion, the measurement of S/L ratio on computed tomography was considered to be useful as an evaluation for the degree of severity in liver cirrhosis by considering both effective hepatic blood flow and portal hypertension.
A 58-year-old man was admitted to our department because he had been diagnosed as hepatocellular carcinoma, which was located at S6 segment, and posterior segmentectomy was performed. After 6 months, right lung metastases of HCC were found and right bronchial arterial infusion of CDDP and MMC was performed twice. Dramatic effects were obtained such as disappearance of lung metastases. We emphasize the useful effect of CDDP and MMC for metastases of HCC.