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Biomedical subjects

M Koike

Publications and source records attributed to M Koike.

At least 271 records · Page 15Linked to original sources

[Red cell fragmentation syndrome after bone marrow transplantation presumed to be caused by cyclosporin A].

Red cell fragmentation syndrome (RCFS) appeared in a 19-year-old female with acute lymphocytic leukemia 30 days after receiving allogenic bone marrow transplantation (BMT) with a conditioning regimen of a high-dose of cytosine arabinoside, cyclophosphamide and total body irradiation. Thirty days after BMT, severe anemia, reticulocytosis and red cell fragmentation were recognized. As RCFS due to cyclosporin A was suspected, CsA therapy was immediately stopped and methotrexate was substituted for CsA. After the discontinuation of CsA, rapid resolution of the hemolysis was observed. When we resumed treatment with CsA, similar hemolysis developed and disappeared again after discontinuation of CsA. Though we considered that RCFS occurred due to CsA, the participation of GVHD and cytomegalovirus might be undeniable.

Adult↗

[Effective danazol therapy for a patient with Evans syndrome].

Danazol administered to a 66-year-old man with Evans syndrome, which was refractory to prednisolone therapy and pulse therapy with methylprednisolone. Danazol therapy produced an excellent and sustained improvement, increasing platelet counts and Hb concentrations. Recently, danazol therapy has been reported to be of benefit to severe idiopathic thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). And this case marked a favorable effect also on Evans syndrome, which has both characters as ITP and as AIHA. The aim of this paper is to suggest that the administration of danazol has a positive effect on Evans syndrome and probably on other various thrombocytopenic diseases and syndromes, especially on refractory cases.

Aged↗

[Hypereosinophilic syndrome].

Ten HES cases, which satisfied the Chuside criteria are reviewed. We found several types of HES--mild forms, often accompanied by edema, and more severe forms accompanied by vascular, lung and heart disorders. It is not necessary to treat some milder forms while the more severe forms often respond to large dose of prednisolone. Now that the diseases, which share a common hypereosinophilic factor, have been defined and HES is being seen in variants of various diseases, the concept of HES has reached a turning point. The administration of appropriate treatment to the particular individual case appears to be advisable.

Adult↗

Genetic changes of both p53 alleles associated with the conversion from colorectal adenoma to early carcinoma in familial adenomatous polyposis and non-familial adenomatous polyposis patients.

Mutation and loss of heterozygosity (LOH) in the p53 gene were analyzed in 274 colorectal tumors of 4 histopathological grades. Among 160 tumors from 40 familial adenomatous polyposis patients, none of 58 adenomas with moderate dysplasia had p53 mutations, whereas 8% (3 of 37) of severe adenomas, 15% (6 of 40) of intramucosal carcinomas, and 40% (10 of 25) of invasive carcinomas had p53 mutations. Only 3% (1 of 33) of severe adenomas showed both mutation and LOH, while 25% (6 of 24) of intramucosal carcinomas and 40% (10 of 25) of invasive carcinomas had both mutation and LOH. All intramucosal and invasive carcinomas that had mutations lost the other allele of the p53 gene. In 114 tumors from 86 non-familial adenomatous polyposis patients, similar results were obtained; no adenoma showed both mutation and LOH, but both alterations occurred in intramucosal and invasive carcinoma. As regards specificity in 56 mutations detected in the present study, the frequently affected codons were codons 175, 238, 245, 248, 273, and 282, 4 of these amino acids being arginine, and 72% (39 of 54) of all mutations were GC to AT transition. Although expression into p53 polyadenylated RNA was high in every invasive carcinoma irrespective of the presence of mutation or LOH, there was a correlation between mutation and protein level; immunostaining of p53 protein was negative in almost all adenomas, but it was positive in 86% of invasive carcinomas exhibiting p53 mutation. These data suggest that genetic changes on both alleles of the p53 gene through mutation and LOH, which result in abnormal protein accumulation, are involved in the conversion of adenoma to early carcinoma. Also, carcinoma cells with p53 mutations existing within adenoma tissues are detectable by immunostaining, even in formalin-fixed, paraffin-embedded specimens.

Adenoma↗

Transport and metabolism of cyclosporine in isolated rat hepatocytes. The effects of lipids.

The effects of lipids on the uptake and metabolism of cyclosporine (CyA) were investigated in isolated rat hepatocytes. In the absence of lipids, CyA was rapidly taken up (reaching apparent steady state within 5 min) and highly associated with the cells (more than 80%). The CyA uptake was concentration independent over the concentration range studied (0.6 to 11.2 micrograms/mL). Metabolism, however, was relatively slow and saturable. Except for cholesterol (at concentrations up to 15.5 mM), all lipids tested [oleic acid; low density lipoproteins (LDL); and high density lipoproteins (HDL)] reduced CyA cell uptake as well as its metabolism in a concentration-dependent manner. The effects of LDL were much more pronounced when compared to those of HDL and oleic acid. At an LDL concentration of 1 microM, drug uptake, indicated by the cell-associated concentration at steady state, was about 49% of the control value, while CyA metabolism was inhibited completely. Drug uptake of about 82 and 91% and CyA disappearance of 75 and 68% of the relevant control values were observed with HDL and oleic acid at concentrations of 10 microM and 0.7 mM, respectively. Apparently, lipids decreased CyA metabolism by reducing the concentration of CyA available for transport into the cells. These findings further support the suggestion of an important role for plasma lipids in the disposition of CyA.

Animals↗

Gluconeogenesis stimulated by extracellular ATP is triggered by the initial increase in the intracellular Ca2+ concentration of the periphery of hepatocytes.

Extracellular ATP, ADP and GTP increased the intracellular free Ca2+ concentration ([Ca2+]i) in a suspension of isolated rat hepatocytes. The [Ca2+]i was determined by measuring fura-2 fluorescence, and its increase was biphasic. The initial transient rise was followed by a longer-lasting plateau. The peak of the early component preceded the plateau level of the second component. A time course of change in [Ca2+]i in single cells at 100 microM-ATP was very similar to that observed in the suspension system. Preincubation of hepatocytes with 40 mM-caffeine, 2 mM-oxalate or 60 microM-dantrolene sodium inhibited the P2 purinergic response. The plateau phase was not observed when measured in the presence of extracellular 100 microM-LaCl3 or in the absence of extracellular Ca2+. The distribution of [Ca2+]i in single hepatocytes was also determined by fluorescence image analysis. In the initial phase, the increase in [Ca2+]i is greater in the peripheral region than the central region of the cell. Degradation of extracellular ATP by ecto-ATPase in the hepatocyte suspension was measured; the amount of ATP degradation was less than 10-15% of the initial amount (100 microM) during the measurement of the intracellular [Ca2+]i in the cell suspension. Extracellular ATP stimulated glucose synthesis. The rate of glucose production also showed two components, the initial fast component within 1 min and the subsequent slower component. The rate of the initial fast component did not depend on the presence or absence of extracellular Ca2+, whereas the rate of the subsequent component depended on it. The present study shows that the initial transient rise in [Ca2+]i plays an important role in triggering the gluconeogenesis.

Adenosine Diphosphate↗

Histopathologic characteristics of early stage esophageal carcinoma. A comparative study with gastric carcinoma.

Unlike the stomach, the esophageal mucosal layer has abundant vessels. To study the histopathologic character of cancer of the esophagus in comparison with that of stomach, the histologic findings (such as vascular or lymphatic permeation and lymph nodal involvement of cancer) were surveyed in 52 lesions of superficial esophageal carcinoma in which carcinoma invasion was limited to the submucosal layer, 448 cases of so-called early gastric carcinoma in which the carcinoma invasion was limited to the submucosal layer, and 109 cases of gastric carcinoma invading the proper muscle layer (PM-carcinoma). With respect to lymph node metastasis and lymphatic and vascular permeation, there was a particularly high incidence of carcinoma extending to the submucosal layer (SM-carcinoma) of the esophagus and a similar high incidence of PM-carcinoma of the stomach. Carcinoma limited to the mucosal epithelium and mucosal layer of the esophagus (MM-carcinoma) has an incidence similar to carcinoma in the mucous membrane and SM-carcinoma of the stomach, respectively. Thus, the cases in which carcinoma invasion was limited to the muscle layer of the mucosa of the esophagus were shown to have a prognosis similar to that of so-called early carcinoma of the stomach.

Carcinoma↗

Differences in the mode of the extension of gastric cancer classified by histological type: new histological classification of gastric carcinoma.

By combining two of the morphological characteristics of gastric cancer, the degree of differentiation of the glandular tubules and the amount of mucus in the cytoplasm, the histological type of the gastric carcinoma was categorised into four groups. Group I: tubular differentiation--well; mucus in cytoplasm--poor; group II: tubular differentiation--well; mucus in cytoplasm--rich; group III: tubular differentiation--poor; mucus in cytoplasm--poor; group IV: tubular differentiation--poor; mucus in cytoplasm--rich. A study of the relation between the types of primary lesion and the mode of extension and recurrence of gastric carcinoma in 200 autopsy cases was then undertaken. In group I, the frequency and extent of haematogenous metastasis such as in the liver was high, while in group IV, that of lymph node metastasis, direct invasion into surrounding organ, and peritoneal dissemination were higher. In group III, which showed the intermediate mode of extension in nature to those of group I and IV, although the frequency and severity of the bone marrow metastasis was the highest. There were significant differences in the modes of development and the extent of infiltration in all groups.

Bone Marrow↗

[Cytomegaloviral interstitial pneumonia after autologous bone marrow transplantation in a case of acute lymphoblastic leukemia. Bone Marrow Transplantation Team].

A 22-year-old man with T cell type acute lymphoblastic leukemia in first remission underwent autologous bone marrow transplantation (BMT). The preparative regimen included cytosine arabinoside, cyclophosphamide and fractionated total body irradiation. His harvested bone marrow cells were purged with 4-hydroperoxycyclophosphamide. His serological test was positive for cytomegalovirus (CMV) before the BMT. On day 53 after the BMT, he developed dry cough and his chest X-ray film showed bilateral basilar infiltration. Bronchoalveolar lavage was performed and cytology of the specimen revealed typical cytomegaloviral inclusion bodies. DNA analysis and viral culture of the specimen were also positive for CMV. The patient was started on ganciclovir and immunoglobulin with high dose methylprednisolone. His respiratory status deteriorated, however, and the patient expired because of respiratory failure. Autopsy revealed severe interstitial pneumonitis with suppression of CMV replication from the treatment. Interstitial pneumonitis due to CMV should be considered as a significant complication of autologous BMT.

Adult↗

[Salvage therapy for recurrent or refractory non-Hodgkin's lymphoma with etoposide, methotrexate, vindesine and prednisolone (EMVP)].

Seventeen patients with recurrent or refractory non-Hodgkin's lymphoma were treated with EMVP (Etoposide 75 mg/m2 i.v. d 1-5, Methotrexate 100mg/m2 i.v. d 1, Vindesine 3 mg/body i.v. d 1, Prednisolone 60 mg/m2 p.o. d 1-5), repeating every 3 weeks. Six complete responses (35%) and five partial responses (30%) were obtained with an overall response rate of 65%. The median duration of response was 26 months (range 8-49+months) for complete response (CR) and 4 months (range 2-6 months) for partial response (PR). The median duration of survival was 31 months for CR, 11 months for PR and 10 months for all patients, respectively. The major toxic effect was myelosuppression. Leukopenia less than 1,000/mm3 and thrombocytopenia less than 25,000/mm3 occurred in 5 and 3 patients, respectively. The other toxicities were alopecia, nausea and mucositis. However, these toxicities were well tolerated and clinically manageable. These results suggested that EMVP therapy was an effective regimen for patients with recurrent or refractory lymphoma.

Adult↗

[Pulmonary lesions of acquired immunodeficiency syndrome--analysis of 24 Japanese autopsy cases with AIDS].

The pulmonary lesions were studied in 24 autopsy cases of Japanese patients with AIDS. The major pathological findings were opportunistic infections, which were the major clinical symptoms in some patients. The pathogens identified were as follows; Pneumocystis carinii (PC) in 10, cytomegalovirus (CMV) in 14, atypical mycobacterium in 5, cryptococcus in 2, candida in 2, and nocardia in 1. PC pneumonia was prominent in 8 cases and was the cause of death. In such patients, the lung were heavy and appeared parenchymatous. Histological examination revealed numerous protozoa in the foamy material in the alveolar spaces, associated with swelling of the alveolar lining cells and edematous thickening of the alveolar septa. In some cases, only hyaline membrane formation was prominent without foamy material in the alveolar spaces. Immunostaining with anti-PC monoclonal antibody or in-situ hybridization with oligopeptide demonstrated pathogens in the hyaline membranes. Many cases with PC pneumonia had concomitant opportunistic infections such as CMV, Herpes simplex virus, and atypical mycobacterium. Extrapulmonary infection of PC was seen in only one case. CMV infection was found in 14 cases; 7 had innumerable inclusion bodies, and in some cases the lesions were most prominent around the bronchioles. Of the 5 cases of atypical mycobacterial infection, 2 were caused by M. kansaii (MK) and 3 by M. avium intracellulare (MAI). Both lesions of MK infection showed necrosis and cavitation. One of three cases of MAI infection showed cavitation. Around the cavitary lesions, numerous cytomegalic inclusion bodies were identified in the mesenchymal cells, which may have been the cause of necrosis and cavitation of the lesions. MAI infection was systemic and pronounced in the lymph nodes, spleen, and intestinal mucosa. Neoplastic lesions comprised 2 cases of Kaposi's sarcoma and 4 of extranodal non-Hodgkin lymphoma in other organs. Lung involvement was seen in only one case of Kaposi's sarcoma although very small in size. The lesion was situated along the pulmonary vein and appeared hemorrhagic macroscopically. Pulmonary lesions in AIDS are complicated, and many of opportunistic pathogens were identified in single patients.

Acquired Immunodeficiency Syndrome↗

Correlation between bromodeoxyuridine-labeling indices and patient prognosis in cerebral astrocytic tumors of adults.

Bromodeoxyuridine (BUdR), a nonradioactive thymidine analogue, is taken up by cells in S-phase, and the ratio of BUdR-positive nuclei to the total number of cells counted is defined as the labeling index (LI). In this study, BUdR LI and the clinical course of 50 cerebral astrocytic tumors in adults were analyzed. The obtained LI distributed continuously in a broad range from 0% to 19%. The mean LI of 28 glioblastomas, 12 anaplastic astrocytomas, and ten astrocytomas were 8.5%, 4.2%, and 1.2%, respectively, and these differences were statistically significant (P = 0.05). In the analysis of LI and the recurrence-free period (RFP), regardless of the histologic findings, 23 patients with LI more than 5% had a median RFP of 9.0 months; the median RFP of nine patients with LI of 3% to 5% was 14.7 months. Nine of 13 patients with LI less than 3% have not yet recurred after a median follow-up of 36 months. These differences were also statistically significant by the generalized Wilcoxon test (P = 0.05). The proliferative potential reflected by the BUdR LI is a good clinical indicator for predicting the rate of tumor growth in cerebral astrocytic tumors. In combination with histologic diagnosis, BUdR LI could help in determining a patient's prognosis more precisely.

Adult↗

Chemotactic peptide from ropalidian wasp as well as the authentic chemotactic tripeptide stimulates two distinct pathways in neutrophils, but the [LYS7] analog does only one of them.

In our previous study on chemotactic peptide isolated from Ropalidian wasp, it was found to induce not only chemotaxis but also other cellular responses, such as superoxide generation and lysosomal enzyme release, but [Lys7] analog was found to induce only chemotaxis but not others. Here, studies on intracellular Ca2+ changes and receptor-binding revealed that the wasp chemotactic peptide and the authentic tripeptide stimulated two distinct receptors, but that the [Lys7] peptide could have access to only one of them.

Animals↗

Left-hand preference in frightened mother monkeys in taking up their babies.

The hand preference of mother monkeys taking up their babies in an emergency situation was investigated. When a relaxed mother monkey was frightened, the hand used to take up a baby and flee was monitored with eight pairs of Old World Monkeys of three different species. Each mother-child pair was given 17-32 trials, all mothers showed a left-hand preference in this behavior.

Animals↗

Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas.

Pancreatic involvement in primary sclerosing cholangitis (PSC) is an extremely rare condition, and its pathologic features are poorly documented. We report two cases of an unusual lymphoplasmacytic sclerosing inflammatory disease involving the total pancreas, common bile duct, gallbladder, and, in one patient, the lip. Two elderly men presented with waxing and waning obstructive jaundice, and exhibited radiologic and ultrasonographic findings highly suggestive of pancreatic carcinoma. Gross appearance of the pancreas showed firm and mass-like enlargement with regional lymph node swelling. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis and acinar atrophy, obliterated phlebitis of the pancreatic veins, and involvement of the portal vein. Similar inflammatory processes involved the bile duct and the gallbladder. Lymphoplasmacytic sclerosing pancreatitis with cholangitis is thought to be a more appropriate term for this condition, of which a similar lesion has been previously noted in a single case of "PSC involving pancreas". Differences in age, radiologic appearance, and the negative history of ulcerative colitis exist, but the two cases in this study could be considered as a variant of PSC extensively involving pancreas, which can readily be mistaken for pancreatic carcinoma.

Aged↗

Effects of bestatin (Ubenimex) on human T-cell colony formation.

The antitumor action of bestatin is considered to be an indirect action mediated by T-cells. Therefore, we investigated the effects of bestatin on the differentiation and proliferation of human precursor T-cells using a colony formation technique. Bestatin did not increase the overall number of T-cell colonies, but it significantly increased in CD4+ cell and significantly decreased in CD8+ cell subpopulations. It also induced CD4+.8+ cells. These findings indicated that bestatin acts on precursor T-cells to induce the differentiation of these cells into CD4+ cells.

Adult↗

Neuropathology of the central nervous system in acquired immune deficiency syndrome (AIDS) in Japan. With special reference to human immunodeficiency virus-induced encephalomyelopathies.

The neuropathological features of the central nervous system in 15 autopsy cases of Japanese male with AIDS were reported. Nine patients had various histological changes including a variety of opportunistic infections in six patients (40%), primary malignant lymphoma of the brain in two (13%), AIDS encephalopathy in four (27%) and vacuolar myelopathy in one (7%). Usually, these pathological changes were present concomitantly. AIDS encephalopathy was characterized by infiltration of mono- and multinucleated cells and myelin pallor with astrogliosis located predominantly in the cerebral white matter and subcortical gray matter. Furthermore, unevenly distributed neuronal loss of the cerebral cortex was apparent in one case. Diffuse astrocytosis of the gray matter out of proportion to neuronal loss was also an outstanding finding in another case. The present study suggested that not only the white matter changes but also gray matter alterations might be the morphological substrates of AIDS encephalopathy.

AIDS Dementia Complex↗