[Present status and clinical therapy of pancreatic diseases].
Explore the source record for details and available documents.
Acute Disease↗
Biomedical subjects
M Ogawa
Publications and source records attributed to M Ogawa.
Magnocellular neurosecretory neurons with ferritin-like immunoreactivity in the hypothalamic supraoptic and paraventricular nuclei of the rat.
Immunohistochemistry for rat liver ferritin (FRT) revealed an intensive labeling in some structures of the rat brain. In the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei, almost all neurosecretory neurons with vasopressin (AVP)-like immunoreactivity were immunostained with FRT. After water deprivation, a marked enlargement of cell body and an immunoreactivity to transferrin receptors were found in AVP-, FRT- and double (AVP+FRT)-labeled neurons in the SON and PVN.
Animals↗
Abundant expression of immunoreactive endothelin 1 in mammary phyllodes tumor: possible paracrine role of endothelin 1 in the growth of stromal cells in phyllodes tumor.
Immunoreactive endothelin 1 (irET-1) concentrations were measured in extracts prepared from 4 phyllodes tumors and 14 fibroadenomas. irET-1 was detectable in all tissue extracts by specific radioimmunoassay, and the mean concentration of irET-1 was 18-fold and 27-fold higher in tissue extracts from phyllodes tumors than in those from intracanalicular fibroadenomas and pericanalicular fibroadenomas, respectively. Reverse-phase high-performance liquid chromatography coupled with radioimmunoassay in the extracts from phyllodes tumors revealed one major irET-1 component corresponding to human standard ET-1. Furthermore, immunocytochemical staining for ET-1 revealed that numerous ET-1-immunoreactive cells were seen in the epithelial cells but not in the stromal cells, suggesting that ET-1 is synthesized by the epithelial component of phyllodes tumors. A possible paracrine role of ET-1 in the growth of this rare tumor which is characterized by its prominent stromal cellularity is discussed.
Adenofibroma↗
Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients.
Recently we have isolated the adenomatous polyposis coli (APC) gene which causes familial adenomatous polyposis (FAP), and its germ-line mutations in a substantial number of FAP patients have been identified. On the basis of this information, we compared the location of germ-line mutations in the APC gene in 22 unrelated patients (12 of whom have been reported previously) with the number of colorectal polyps developed in FAP patients; 17 were sparse types and five were profuse types. All but one of the mutations were considered to cause truncation of the gene product by frame-shift due to deletion (14 cases) or nonsense mutation (seven cases). The location of the germ-line mutations seems to correlate with the two clinical types; germ-line mutations in five FAP patients with profuse polyps were observed between codon 1250 and codon 1464, whereas mutations in 17 FAP patients with fewer polyps were observed in the other regions of the APC gene. The result suggests that the number of colorectal polyps in FAP patients may be associated with a difference in the stability or biological function of the truncated APC protein.
Adenomatous Polyposis Coli↗
Clonal proliferation of murine lymphohemopoietic progenitors in culture.
We have used a two-step clonal culture system to unequivocally demonstrate that individual primitive lymphohemopoietic progenitor cells have the capacity for differentiation along either the myeloid or the B-lymphoid lineage. Highly enriched murine marrow cells were plated individually in culture by micromanipulation in the presence of pokeweed mitogen-stimulated spleen cell conditioned medium, erythropoietin, steel factor (SF), and interleukin (IL) 7. Forty-five percent of the single cells formed primary colonies expressing multiple hemopoietic lineages. When aliquots from individual colonies were replated in secondary methyl cellulose culture containing SF and IL-7, 41% of the primary colonies gave rise to lymphocyte colonies. Cells of the lymphocyte colonies were blast-like and B220+, sIg-, Mac-1-, Gr-1-, Ly-1-, L3T4-, Ly-2-, and CD3-. Thirty to 70% of the cells were Thy-1+. mu-chain mRNA was detected in most of the cells by in situ hybridization with an antisense RNA probe. When lymphocyte colonies derived from a single cell were pooled and individually injected into scid mice, donor-type IgM was measurable in the serum of mice and spleens contained donor-type B cells. We then carried out initial screening of growth factors to identify growth factors that might replace pokeweed mitogen-stimulated spleen cell conditioned medium in the primary culture. Combinations of two factors that included SF plus IL-6, IL-11, or granulocyte colony-stimulating factor were all effective in the primary culture in the maintenance of the B-lymphoid potential. Interestingly, IL-3 could neither replace nor act synergistically with SF to support the lymphoid potential of the primary cultures. Our observations demonstrate that many primitive progenitors previously believed to be myeloid-committed also possess B-lymphoid potential. This culture system should prove valuable for elucidation of the mechanisms regulating early stages of lymphohemopoiesis.
Animals↗
Enhancement of murine hematopoiesis by synergistic interactions between steel factor (ligand for c-kit), interleukin-11, and other early acting factors in culture.
Entry into the cell cycle of dormant hematopoietic progenitors appears to be regulated by multiple synergistic factors, including interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), IL-11, and the ligand for c-kit, which is also known as steel factor (SF). We have tested the effects of these and other hematopoietic factors on the proliferation of partially enriched dormant murine progenitors in the presence and absence of serum. In serum-containing cultures, SF and IL-11 interacted to support the formation of multilineage colonies; the level of colony formation was comparable with the colony formation supported by other effective two-factor combinations. In serum-free cultures, colony formation supported by two factors was significantly less than that in serum-containing culture and the most effective two-factor combination in serum-free culture was SF plus IL-3. In serum-free cultures, three-factor combinations consisting of SF, IL-3, and one of IL-6, G-CSF, or IL-11 yielded colony formation that was comparable with that seen in serum-containing cultures. These studies indicate that IL-11 belongs to a group of early-acting hematopoietic synergistic factors that now includes IL-6, G-CSF, and IL-11. In contrast, SF is unique among the synergistic factors in that it interacts either with growth factors such as IL-3 or GM-CSF or with synergistic factors such as IL-6, IL-11, or G-CSF.
Animals↗
Vasoactive intestinal polypeptide presynaptically enhances the synaptic transmission in cultured sympathetic neurons.
We studied the effects of vasoactive intestinal polypeptide (VIP) on the cholinergic synaptic transmission that was developed between rat sympathetic neurons in culture. Electrophysiological examinations revealed that the amplitude of fast excitatory postsynaptic potential (fast EPSP) was increased by VIP (0.2-0.8 microM) reversibly and dose-dependently, whereas transient nicotinic depolarization evoked by pressure application of acetylcholine (ACh) was not affected by VIP. In most of the cells examined, VIP depolarized membrane potential by a few millivolts with concomitant increases in membrane conductance. Furthermore, the VIP-induced depolarization was suppressed by Co2+ but not by hexamethonium or atropine. Hence it is highly likely that the peptide augmented the amplitude of fast EPSPs by increasing ACh release from the presynaptic cell. These results demonstrate that VIP influences the presynaptic phase of cholinergic synaptic transmission between sympathetic neurons.
Acetylcholine↗
Growth factor requirements for survival in G0 and entry into the cell cycle of primitive human hemopoietic progenitors.
In this study we have isolated populations of dormant human hemopoietic progenitors by two different approaches. First CD34+ cells isolated by panning were further separated on the basis of absence of HLA-DR expression by using fluorescence-activated cell sorting. Second, CD34+ HLA-DR- cells were isolated by nonadherence to soybean agglutinin, negative immunomagnetic bead selection with lineage-specific antibodies, and two-color cell sorting. Progenitors in either cell population were unable to form colonies in the presence of interleukin (IL)-3 alone but yielded a substantial number of colonies, including multilineage colonies, in the presence of combinations of IL-3 and IL-6. Similarly, IL-3 plus any one of the other synergistic factors, including granulocyte colony-stimulating factor, IL-11, leukemia inhibitory factor, and steel factor, effectively supported colony formation from CD34+ HLA-DR- progenitors. Sequential observation of colony formation from single CD34+ HLA-DR- cells provided definitive evidence that the synergistic factors trigger cell divisions of dormant cells. Studies with delayed addition of factors to the cultures provided evidence that this population of cells also requires IL-3 or granulocyte/macrophage colony-stimulating factor (GM-CSF) to survive even while dormant. In contrast, none of the synergistic factors were able to replace IL-3 or GM-CSF in this function. These findings confirm and extend the model that multiple factors with overlapping functions operate both independently and in combination to regulate early stages of hemopoiesis.
Antigens, CD↗
Mixed type cryoglobulinemia found by an abnormal RBC cytogram in an automated cell counter.
Explore the source record for details and available documents.
Adult↗
Screening for germ-line mutations in familial adenomatous polyposis patients: 61 new patients and a summary of 150 unrelated patients.
We report here the result of a screening for germ-line mutations in the adenomatous polyposis coli (APC) gene in 61 new familial adenomatous polyposis (FAP) patients as well as a summary of the results of 150 patients. Examination of the entire coding region of the APC gene, based on a ribonuclease protection assay coupled with the polymerase chain reaction (PCR), disclosed mutations that were considered to cause significant defects in the APC product in 97 of 150 unrelated FAP patients. Our findings revealed the following characteristics of the germ-line mutations of APC: 1) the great majority of the mutations were found to truncate the APC product; 2) almost all of the mutations were located within the first half of the coding region; 3) no correlation was observed between the locations of germ-line mutations and extracolonic manifestations in FAP patients; 4) more than 80% of base substitutions in the APC gene were from cytosine to other nucleotides, nearly one-third of which occurred at the GpG site. Our results provide information helpful to an understanding of the APC gene and will also contribute to presymptomatic diagnosis of members in FAP families.
Adenomatous Polyposis Coli↗
Control of intramarrow B-cell genesis by stromal cell-derived molecules.
Explore the source record for details and available documents.
Animals↗
Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison of lipiodol-transcatheter arterial embolization with and without adriamycin (first cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.
A randomized, controlled clinical trial comparing the use of lipiodol-transcatheter arterial embolization (L-TAE) in the presence versus the absence of Adriamycin (ADR) for the treatment of hepatocellular carcinoma was conducted from August 1988 through September 1989. In all, 125 Japanese hospitals participated in this study and 289 patients were entered in the trial. The patients were randomly allocated into group A (L-TAE) or group B (L-TAE + ADR) by telephone registration. There was no significant difference in background factors between group A and group B. Additional treatment, including repeated TAE or hepatic resection, was given to 189 patients. Among the four endpoints analyzed, the rate of tumor reduction and lipiodol accumulation in the tumor did not significantly differ between the two groups. The 3-year survival values for groups A and B were 33.6% and 34.9%, respectively; the difference was not significant. The serum alpha-fetoprotein level, however, decreased to a significantly greater extent in the group that received ADR than in the group that did not (P < 0.05). This result suggests that ADR has some favorable additional effect in L-TAE for the treatment of hepatocellular carcinoma.
Adult↗
Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison of L-TAE with Farmorubicin and L-TAE with adriamycin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.
A randomized clinical trial comparing L-TAE with Farmorubicin (FARM) and L-TAE with Adriamycin (ADR) in the treatment of hepatocellular carcinoma was conducted from October 1989 through December 1990. In all, 192 hospitals participated in this study and 117 patients were entered. The patients were randomly allocated to group A (L-TAE+FARM) or group B (L-TAE+ADR). There was no significant intergroup difference in background factors. Additional treatment consisting of repeated TAE or surgery was given to 66 patients. Four factors were analyzed in this study: the percentage of reduction in tumor size, the change in the AFP level, lipiodol accumulation, and survival. None of these factors differed significantly between the two groups. The final evaluation of this study will be based on differences in survival after a long-term follow-up. Toxic effects manifested less frequently in group A than in group B, and the decrease in the platelet count in the peripheral blood was significantly lower in group A than in group B. These results suggest that FARM exerts a more favorable effect than does ADR in the treatment of hepatocellular carcinoma.
Adult↗
Demonstration of a possible link between high grade malignancy in dimethylbenz[a]anthracene-induced rat mammary carcinoma and increased urokinase plasminogen activator content.
Recent reports have suggested that tissue-type plasminogen activator activity is regulated by estrogen in 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma type I cells but is not necessarily regulated by estrogen in type II mammary carcinoma cells. We have compared the biological features of these two types of mammary carcinoma cells and have found that, although there is no difference in estrogen receptor content between these two cell types, the plasminogen activator activity markedly differs. Tissue-type plasminogen activator activity is significantly higher in type I carcinoma than in type II carcinoma, urokinase-type activity is significantly higher in type II carcinoma than in type I carcinoma. When these two types were compared in terms of rate of tumor growth, type II carcinomas clearly showed more rapid growth than type I carcinomas. Survival studies showed significantly shorter survival of type II tumor-bearing rats compared with type I tumor-bearing rats. Furthermore, type II carcinomas contained a greater proportion of aneuploid cells than type I carcinomas. These results suggest that type II carcinoma cells, in which estrogen is unable to regulate tissue-type plasminogen activator activity, are considered to be of a higher grade of malignancy than type I carcinoma cells.
9,10-Dimethyl-1,2-benzanthracene↗
Interleukin-8 is constitutively and commonly produced by various human carcinoma cell lines.
We examined the production of interleukin-8 and interleukin-6 by 30 human carcinoma cell lines. Serum levels of interleukin-8 were measured in 14 patients with hepatocellular carcinoma by enzyme-linked immunosorbent assay and Northern blotting. Furthermore, serum interleukin-8 was also investigated in a nude mouse bearing a tumor of the HuH7 hepatoma cell line producing interleukin-8. Of the 30 cell lines, 29 (96.7%) constitutively produced interleukin-8, and 19 of the 29 (65.5%) were high producers (> 1 ng/ml culture supernatant). Among the high producers, 4 cell lines released both interleukin-8 and interleukin-6. Interleukin-6 was constitutively produced by 17 of the 30 (56.7%) cell lines, 4 of which (23.5%) were high producers (> 1 ng/ml). By Northern blot analysis, mRNAs of interleukin-8 and interleukin-6 were detected in producing cell lines. Of 14 patients with hepatocellular carcinoma 4 (28.5%) showed increased levels of serum interleukin-8. Furthermore, inoculation of the HuH7 hepatoma cell line which produced the highest amount of interleukin-8 into a nude mouse resulted in tumor production accompanied by an elevated level of human interleukin-8 (646 pg/ml) in the peripheral blood. Thus, interleukin-8 is constitutively and commonly produced by various carcinoma cell lines. The production of interleukin-8 by carcinoma cells may be related to the elevation of serum interleukin-8 in patients with hepatocellular carcinoma. Finally, these cell lines may be valuable for studying the relationship between interleukin-8 and cancer.
Animals↗
Tissue-type plasminogen activator is involved in skeletal metastasis from human breast cancer.
This study was undertaken to determine if primary breast tumor plasminogen activator expression correlates with skeletal metastasis in breast cancer. Total plasminogen activator activity was significantly lower in tumors of patients with recurrence than in recurrence-free patients. Similarly, the primary tumors of patients with skeletal metastasis contained considerably less enzyme activity compared with those of patients surviving without skeletal metastasis. When patients with skeletal metastasis were categorized in terms of their recurrence pattern, those who had skeletal metastasis without other organ metastasis had significantly less tissue-type plasminogen activator antigen in their primary breast tumors than did those who had metastasis to other organs. Furthermore, a significantly lower level of tissue-type plasminogen activator antigen was found in primary tumors associated with axial bone metastasis than in those associated with appendicular bone metastasis. These results suggest that tissue-type plasminogen activator is involved in skeletal metastasis formation by its effects through the vertebral venous plexus.
Bone Neoplasms↗
In vivo-in vitro replicative DNA synthesis (RDS) test using perfused rat livers as an early prediction assay for nongenotoxic hepatocarcinogens: I. Establishment of a standard protocol.
To establish a standard protocol for an in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test using male F344 rats for screening nongenotoxic (the Ames-negative) hepatocarcinogens, experimental conditions were examined. After treatment with three model hepatocarcinogens, isolated hepatocytes showed highest RDS incidences when plated at a density of 5 x 10(4) cells/ml. Spontaneous RDS incidences in hepatocytes from rats aged 9 weeks or older showed a constant value. The use of hepatocytes from 9-week-old rats at the 5 x 10(4) cells/ml plating density was therefore determined as the standard. Based on the distribution of mean spontaneous RDS incidences over 105 additional experiments (0.4 +/- 0.18%, with SEM), an RDS incidence of over 1% was adopted as the criterion for a positive response in our rat liver RDS test.
Age Factors↗
In vivo-in vitro replicative DNA synthesis (RDS) test using perfused rat livers as an early prediction assay for nongenotoxic hepatocarcinogens: II. Assessment of judgement criteria.
To better establish in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test using male F344 rats as a screening assay for nongenotoxic (the Ames-negative) hepatocarcinogens, judgement criteria were assessed after single-gavage treatment with seven model compounds. The profiles of RDS induction by the compounds were analysed in terms of both time-course and dose-dependence. Our data reveal that a value of 2% or more for RDS incidence should be judged as positive and that of less than 1% RDS incidence as negative using maximum tolerance dose (MTD) concentrations in time-course experiments at 15, 24, 39, 48 and 63 h. In the case of an incidence value between 1 and 2%, the finding of a clear dose-dependence was considered to justify the conclusion of a positive effect for 1/4 MTD, 1/2 MTD, MTD and 2 x MTD at a fixed time. The established judgement criteria are planned for introduction in detection of nongenotoxic hepatocarcinogens (the Ames-negative carcinogens) using the RDS test.
Animals↗