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Biomedical subjects

K Shimoda

Publications and source records attributed to K Shimoda.

At least 127 records · Page 7Linked to original sources
PubMed1994

Predominance of myeloid antigens in CD34-positive peripheral blood stem cells over those in bone marrow after administration of granulocyte colony-stimulating factor.

We analyzed the surface phenotype of CD34-positive (CD34+) cells in peripheral blood (PB) during the period of hematopoietic recovery following myelosuppressive chemotherapy. A significantly higher proportion of PB CD34+ cells coexpressed the CD13 and CD33 myeloid antigens (80.8%, 78.1%, respectively) than did BM CD34+ cells (45.8%, 37.8%, respectively) (both p < 0.01). In particular, the CD13 positivity of PB CD34+ cells harvested with granulocyte colony-stimulating factor (G-CSF) was significantly higher than that of those without G-CSF. Most of the PB CD34+ cells possessed the HLA-DR antigen, and less than 10% of the CD34+ cells coexpressed a mature cell antigen, such as CD14, GPA or Plt-1. The administration of G-CSF enhanced the appearance of significantly larger amounts of CD13+ 34+ and CD33+ 34+ cells (both p < 0.01). This G-CSF mobilization also resulted in an increased number of CD13- 34+ and CD33- 34+ cells and all types of colony-forming cells. On the other hand, macrophage colony-stimulating factor administration exerted little influence on the mobilization of PB CD34+ cells. Thus, G-CSF seemed to induce not only an expansion of circulating hematopoietic stem cells but also the myeloid differentiation of stem cells.

Adolescent↗
PubMed1994

The c-kit molecule and the surface immunophenotype of human acute leukemia.

The proto-oncogene c-kit encodes the receptor for a stem cell factor (c-kit molecule). Expression of the c-kit molecule on the gated leukemic blast cells from newly diagnosed patients with leukemia was analysed by flow cytometry using the monoclonal antibody (17F11). Among 35 myeloid leukemia cases examined, significant c-kit-positive blast cells were detected in 24 cases (69%), even though the percentage of positive cells was widely variable. The correlation between the percentage of cells positive for the c-kit molecule and the percentage of cells positive for CD34 was found to be statistically significant (rs = 0.36, p < 0.05). Fifteen cases of myeloid leukemia were positive for lymphoid markers. The mean percentage of the cells expressing c-kit molecule among the lymphoid marker-positive cases was significantly larger than that among the lymphoid marker-negative cases (p < 0.05). All 19 lymphoid leukemia cases were c-kit-negative, including 8 cases which were positive for some myeloid markers. Stem cell factor enhanced the colony growth in five out of six acute myeloblastic leukemia cases expressing the c-kit molecule. On the other hand, SCF did not stimulate colony growth in any of the four cases which were not positive for the c-kit molecule. These findings indicated that the distribution of flow cytometrically detectable c-kit molecules on leukemic cells is related to the morphologic and immunologic classification of these leukemic cells and to the expression of the CD34 cell surface molecule on some myeloid leukemic cells. On such cells, expression of the c-kit molecule may have a functional role and be related to the maturation process.

Adult↗
PubMed1994

[Clinical analysis of patients with chronic hepatitis C who discontinued interferon treatment because of side effects--our experiences and recent reports].

We prospectively studied side effects about 54 patients with chronic hepatitis C treated with 3 to 10 MIU a day of interferon (IFN) alpha, which was administrated for 16 to 24 weeks. Every day, all of them wrote down every symptoms, by themselves, during its treatment. Any symptoms occurred in all patients and each incidence of symptoms such as fever, fatigue, headache, anorexia, arthalgia, myalgia, chill, itching, insomnia, nausea, numbness of hand and foot, irritability, diarrhea, eye ball pain, vomiting, were all higher than those which have been reported by some papers in Japan. So, it was considered that the symptom self-wrighting method by patient was useful to evaluate the entity of side effects. Furthermore, we studied 26 patients, who discontinued IFN treatment because of side effects and analyzed the background factors. Each incidence of symptoms of these patients were not always compatible to those incidences. But by observation of those symptoms, we could know severe side effects earlier.

Adult↗
PubMed1994

[Magnetic resonance imaging (MRI) of bone marrow necrosis].

Magnetic resonance (MR) of bone marrow was studied in two cases of acute leukemia which showed bone marrow necrosis. Case 1:A 24-year-old female was admitted because of sternum pain and bleeding tendency. She was diagnosed AML based on the peripheral blood picture. Bone marrow biopsy revealed the presence of bone marrow necrosis. T1 weighted imaging of MR showed low signal intensity in all vertebral marrow. Fatty marrow was demonstrated after achieving complete remission and the MR imaging of bone marrow changed to show high intensity, suggesting fat deposition. Case 2: A 19-year-old female suffered from chest pain and lumbago, and was diagnosed as ALL. DIC and bone marrow necrosis were confirmed during chemotherapy for remission induction. T1 weighted imaging showed the mosaic pattern of low and high signal intensity. She achieved complete remission and bone marrow clot revealed the presence of fatty marrow. Most areas of low signal intensity of T1 weighted imaging changed to those of high signal intensity. These observations suggest that necrotized bone marrow seemed to change to fatty marrow along with achieving remission. MR imaging study of bone marrow is useful for evaluating hematopoiesis in hematologic disorders.

Adult↗
PubMed1994

Depression of cytotoxicity of nonparenchymal cells in the liver after surgery.

BACKGROUND: The nonparenchymal cells (NPCs) of the liver have a strong cytotoxic activity. Our hypothesis is that their activity, which prevents metastases to the liver, may be impaired after operation. METHODS: First, Sprague-Dawley rats underwent either a sham operation consisting of only a laparotomy (group L, n = 10), a laparotomy and resection of a portion of the small intestine (group R, n = 10) or no operation (group C, n = 10). After 2 days liver NPCs were isolated and divided into two fractions, large and small NPCs. The cytotoxicity of the liver NPCs and of the circulating blood mononuclear cells (BMC) was assessed. Second, we measured the growth of tumor metastases 14 days after the inoculation of a cell line (MRMT-1) into the portal vein of rats undergoing similar surgical stress (group Rm, n = 10 and group Lm, n = 10). RESULTS: The natural killer cell activity (anti-YAC-1) of large NPCs was 38% in group R, which was significantly less (p < 0.002) than that in groups L (72%) and C (83%). Small NPCs showed reduced natural killer activity in groups R and L (26% and 35%, respectively) compared with that in group C (70%) (p < 0.02). The natural killer cell activity of BMCs was similar in each group, and the lymphokine-activated killer cell activity (by anti-EL4) did not change in either the NPCs or BMCs. In the second experiment the area of the tumors occupied in the liver in the group Rm rats was significantly greater compared with that in the group Lm rats (p < 0.01). CONCLUSIONS: Surgical stress depressed the cytotoxic activity of liver NPCs and enhanced the growth of metastatic liver tumors. This suggests the possibility that perioperative immunotherapy might be clinically useful in the future to prevent liver metastases after gastrointestinal surgery.

Animals↗
PubMed1994

[Induction of anti-cancer cells and systemic immune response in hepatocellular carcinoma by OK-432].

We examined whether anti-cancer cells are induced in vivo in hepatocellular carcinoma (HCC) by OK-432. Ten patients with HCC were randomly divided into two groups. The group I patient (n = 5) served as the control. In group II (n = 5), OK-432 was preoperatively administered via the hepatic artery. Tumor infiltrating lymphocytes (TILs) were collected from resected tumors. Cytotoxicity of TILs against K562 cells and Raji cells was studied with phenotypic analysis by flow cytometry. Freshly isolated TILs, whether or not treated with OK-432, showed low cytotoxicity. When TILs were co-cultured with recombinant interleukin-2 (rIL-2), the cytotoxicity was significantly activated in the OK-432 treated group, whereas untreated TILs showed no activation. The natural killer (NK) activity and the lymphokine-activated killer (LAK) activity were depressed in group I after hepatic resection, but patients in group II had no depression. Our data indicate that LAK precursor cells are induced in TILs and the prevention of post-operative immune suppression is made possible by OK-432.

Carcinoma, Hepatocellular↗
PubMed1994

Myasthenia gravis after allogeneic bone marrow transplantation.

A 37-year-old Japanese man with chronic myeloid leukemia (CML) developed myasthenia gravis 29 months after bone marrow transplantation (BMT) from an HLA one locus-mismatched brother. Proximal muscle weakness and bilateral ptosis occurred along with the exacerbation of chronic GVHD shortly after sudden cessation of cyclosporine (CYA) and prednisolone. The diagnosis of myasthenia gravis was made based on clinical symptoms and elevation of an anti-acetylcholine receptor antibody titer and all symptoms related to myasthenia gravis promptly diminished with the start of treatment for chronic GVHD. In most previously reported cases, the underlying disease was aplastic anemia (6 of 7 cases) and donors were of the opposite sex (6 of 7 cases). The haplotypes HLA B7 (3 of 5 cases), B35 (3 of 5 cases), and DR2 (3 of 3 cases) were common. All cases suffered from chronic GVHD. The present case had only chronic GVHD and HLA B7 as a background for myasthenia gravis after BMT. The abrupt cessation of immunosuppressive therapy may also be related to the development of myasthenia gravis after BMT.

Adult↗
PubMed1994

Induction by OK-432 of lymphokine activated killer precursor cells in hepatocellular carcinoma.

We investigated the question whether lymphokine-activated killer precursor (pre-LAK) cells are induced by OK-432 in vivo, in hepatocellular carcinoma (HCC). Ten patients with HCC were randomly divided into two groups. In group A (n = 5), OK-432 was pre-operatively administered via the hepatic artery. The group B patients (n = 5) served as controls. Tumor-infiltrating lymphocytes (TILs) were collected from the resected tumors. The cytotoxicity of TILs against natural killer (NK)-sensitive K562 cells and NK-insensitive Raji cells was examined by phenotypic analysis with flow cytometry. Freshly isolated TILs, whether treated with OK-432 or not, showed low cytotoxicity against both tumor cells. However, OK-432 pretreatment increased the T-lymphocyte population of TILs, particularly with interleukin-2 (IL-2) receptor positive cells. When TILs were co-cultured with recombinant interleukin-2 (rIL-2), the cytotoxicity was significantly activated in the OK-432 treated group, while untreated TILs showed no activation (P < 0.05). We postulate that pre-LAK cells are induced by OK-432 in TILs, mainly from the T-lymphocyte population. The possibility that LAK cells can be endogenously induced in HCC if OK-432 and rIL-2 are concomitantly administered needs to be considered for immunotherapy to HCC.

Adult↗
PubMed1994

[DNA stemline heterogeneity as preoperative prognostic factor in esophageal cancer].

Flow cytometric nuclear DNA analysis was performed on 36 preoperative endoscopic biopsy specimens and 89 surgically resected specimens of esophageal carcinomas without preoperative radiotherapy. Carcinomas with aneuploid or DNA stem-line heterogeneity had a higher frequency of lymph node metastasis (p < 0.01). The correspondence rate of nuclear DNA ploidy patterns was 97% between biopsy and resected specimens, and that of heterogeneity was 72%. Though only six cases showed heterogeneity in biopsy specimens out of 12 cases which showed heterogeneity in resected specimens, preoperative detection of heterogeneity was supposed to be more accurate by an increase of biopsy specimens. DNA analysis of biopsy specimens may be a possible indicator of the malignant potential of esophageal carcinoma.

Biopsy↗
PubMed1993

DNA stem line heterogeneity in esophageal cancer accurately identified by flow cytometric analysis.

BACKGROUND: This study was designed to evaluate the importance of DNA stem line heterogeneity in determining the malignant potential of esophageal cancer. METHODS: Flow cytometric analysis of intratumor heterogeneity of DNA contents was performed on step-sectioned slices of 57 resected esophageal carcinomas. RESULTS: DNA stem line heterogeneity, as assessed by DNA content measurements, was present in 25 (44%) tumors; 6 (11%) were a combination of diploid and aneuploid DNA pattern, and 19 (33%) had two or more aneuploid peaks with different DNA contents (multiploid). Of the remaining 32 homogeneous tumors, 4 showed only a diploid DNA pattern in all samples examined, whereas 28 tumors had only the aneuploid pattern. Tumors with the heterogeneous DNA pattern had a significantly higher frequency of lymph node metastasis than did those with the homogeneous DNA pattern (P < 0.05). CONCLUSIONS: For evaluation of the highly malignant potential of esophageal carcinoma by nuclear DNA contents, it is important to identify accurately intratumoral heterogeneity. Because different DNA stem lines were evident in different areas of the lesion, evaluation of multiple specimens from a wide area of each lesion is needed to determine with accuracy the degree of intratumor DNA stem line heterogeneity.

Adult↗
PubMed1993

Prediction of operative mortality based on impairment of host defense systems in patients with esophageal cancer.

To determine whether operative risk based on impaired defense systems can be predicted, we examined 21 markers in 32 patients with esophageal cancer seen between 1983 and 1985 and related them to postoperative deaths. A discriminant analysis proved useful in determining whether the patient would be at risk of operative mortality, based on impaired defense systems. This model, the host defense index (HDI), was then used clinically to evaluate findings in 64 patients seen between 1986 and 1991. During this period, a change in policy for performing transthoracic esophagectomy on and perioperative care for patients with impaired defense systems was associated with a decrease in operative mortality. Thus, the HDI is beneficial to predict the risk of operative mortality based on impaired defense systems in patients with esophageal cancer.

Aged↗
PubMed1993

Methicillin-resistant Staphylococcus aureus infections following esophageal surgery in patients with impaired defense mechanisms.

This study was conducted to determine whether or not compromised host defense mechanisms prior to surgery are related to postoperative infections with methicillin-resistant Staphylococcus aureus (MRSA). Neutrophil cytocidal activities, serum complement and immunoglobulin levels, the in vivo antibody-producing capacity against pneumococcal polysaccharide (PPS), and cell-mediated immunity (CMI) were evaluated in 22 patients who underwent esophagectomy for esophageal cancer between 1989 and 1990. Postoperatively, nine patients developed MRSA infections. Anti-PPS IgG was found to be significantly lower in patients with MRSA infections than in those without (P < 0.01). All the patients with MRSA infections showed a titer < 600 EU, while all but one of the non-infected patients showed a titer > 600 EU. Impairment in other components of the defense mechanisms, apart from a partial deficiency of CMI, did not differ between the groups. Thus, a preoperative evaluation of the antibody-producing capacity may serve to predict the development of MRSA-related infections following major surgery such as esophagectomy.

Aged↗
PubMed1993

The characterization of peritoneal and pleural exudate cells from malignant effusions.

The immune function of peripheral blood cells and cells from the pleural and abdominal effusions of patients with advanced cancer was compared to that of peripheral blood cells from controls. The parameters examined included lymphocyte subsets, natural killer (NK) cell activity, and anti-Daudi and lymphokine-activated killer (LAK) cell activity. The percentage of CD4+ pleural and peritoneal exudate cells (PEC) was significantly higher than the percentage of peripheral blood mononuclear cells (PBMC) in the patients. The percentage of CD8+CD11+ PEC and PBMC, being the suppressor T-cells, of the patients was increased compared with controls, while the percentage of CD8+CD11- PEC, being the cytotoxic T-cells, was identical to the PBMC of both patients and controls. The NK activity of PEC was significantly lower than that of PBMC in both patients and controls, and there was no correlation between the NK activity of PBMC and PEC. Although the anti-Daudi activity of PEC was markedly low, LAK cells with high activity could be induced by culture with interleukin-2 for 4 days. These results suggest that the immune function of cells in malignant effusions may be depressed due to a low population of cytotoxic T cells, low NK activity and increased suppressor T cells, while the local administration of interleukin-2 may induce LAK cells. Therefore, effective local immunotherapy for malignant effusions should not only augment effector cells, but also inhibit suppressor cells.

Adult↗
PubMed1993

Levels of serum granulocyte colony-stimulating factor in patients with cerebrovascular diseases.

The role of leukocytes in the pathogenesis of cerebrovascular disease, in particular, cerebral ischemic disease has recently become a focus of research. Several studies have reported that a positive correlation between increased functional activities of neutrophils and the risk of cerebral ischemic disease. Granulocyte colony-stimulating factor (G-CSF) is known to be not only a granulocyte proliferating factor but also a potent activator of mature neutrophils. In this study, we measured the serum G-CSF levels in 143 patients with cerebrovascular diseases and in 100 patients with other diseases, using our established enzyme-linked immunosorbent assay (ELISA) for G-CSF The minimal detection level was 20 pg/ml G-CSF. In patients with cerebral infarction, G-CSF could be detected in 18.3% and in patients with cerebral hemorrhage, it could be detected in 9.8% of analyzed samples. On the other hand, 6% of the patients with other diseases had measurable levels of G-CSF. The differences among these three groups were statistically significant according to the chi 2 test (p < 0.01). Our findings that there was a significantly high frequency of elevated levels of G-CSF among patients with cerebrovascular diseases, may indicate that the action of G-CSF as a potent activator of neutrophils plays some role in the occurrence of cerebrovascular disease, in particular, cerebral infarction.

Adult↗
PubMed1993

Clinical significance of plasma levels of clomipramine, its hydroxylated and desmethylated metabolites: prediction of clinical outcome in mood disorders using discriminant analysis of therapeutic drug monitoring data.

We measured the plasma concentrations of clomipramine and its metabolites, N-desmethylclompiramine, 8-hydroxy-N-desmethylclomipramine, 8-hydroxyclomipramine in 65 depressed patients with subtypes of DSM-III-R mood disorders receiving clomipramine hydrochloride. There were large interindividual variations in the concentrations of the parent and each of the metabolic compounds, though the overall correlations between drug concentrations and daily doses of clomipramine were highly significant. Metabolic ratios for both desmethylation and hydroxylation varied by 15-35-fold interindividually. Discriminant analysis of the data from drug concentrations and scores of Global Assessment of Functioning revealed that it is useful to monitor the concentrations of both desmethylated and hydroxylated metabolites in order to predict the clinical effects of clomipramine.

Adolescent↗
PubMed1993

Expression of the rat calmodulin gene II in the central nervous system: a 294-base promoter and 68-base leader segment mediates neuron-specific gene expression in transgenic mice.

Deletion analysis of the rat CaMII promoter demonstrated that the segment from -294 to +68 bases of CaMII was efficient as a promoter in NIH3T3 by transient assay. We developed transgenic mice carrying a fusion gene of this promoter segment and a beta-galactosidase reporter gene. This short CaMII promoter mediated the transgene expression in pyramidal cells of the cerebral neocortex, the pyriformcortex and the hippocampal regions CA1 to CA3, in granule cells of the dentate gyrus, in Purkinje cells of the cerebellum, and in neurons of the lateral vestibular nucleus of pons and the spinal cord of adult transgenic mice. The expression of endogenous CaMII was precisely analyzed by in situ hybridization in the nervous tissues. The localization of transgene expression was consistent with those of the endogenous CaMII in the adult transgenic mice. In the embryos at 13.5-15.5 days of gestation, the transgene was expressed in various neurons similarly to the endogenous CaMII but certain subtle differences were observed in the localization of expression. This short promoter of rat CaMII carried two sequence stretches highly conserved in the mouse, dog, chicken and Xenopus CaMII promoters. These conserved stretches may be involved in the observed neuron-specific expression of rat CaMII gene.

Animals↗
PubMed1993

Antiserum against neuropeptide Y enhances the nicotine-mediated release of catecholamines from cultured rat adrenal chromaffin cells.

A primary culture of chromaffin cells was prepared from adult rats and the stability of cell contents, NPY and catecholamines (CAs), during the culture was studied. The responsiveness of cultured chromaffin cells to NGF or secretagogues and the possible role of NPY on the CA secretion from cultured chromaffin cells were investigated. After plating of isolated cells, there was marked decrease in the cell content of CAs but a significant increase in the cell content of NPY. Though both NPY and CAs in the cultured cells were positively regulated by NGF, the results of this study seemed to suggest a differential regulation for NPY and CAs in the chromaffin cell. The cultured chromaffin cells secreted NPY and CAs in response to stimulation by nicotine. The nicotine stimulated secretion of CA was enhanced by the presence of IgG fraction, prepared from NPY antiserum, in the secretion medium. The results suggested that NPY was co-released with CAs from chromaffin cells and then acted as a modulator on CA secretion.

Adrenal Glands↗