Trisomy 2 found in proliferative myositis cultured cell.
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Cells, Cultured↗
Biomedical subjects
T Isayama
Publications and source records attributed to T Isayama.
Preproenkephalin mRNA expression in the developing and adult rat brain.
[Met5]-Enkephalin is derived from the protein precursor, proenkephalin A, which in turn is encoded by the preproenkephalin (PPE) gene. [Met5]-Enkephalin is not only a putative neuromodulatory substance, but also serves as a growth factor (= opioid growth factor, OGF). OGF exerts an inhibitory influence on the developing nervous system and is especially targeted to cell proliferative and differentiative events. This study examined the relationship of PPE mRNA expression to late prenatal and postnatal rat brain development. Northern blot analysis of the whole brain and cerebellum showed that message is present in the fetal nervous system on prenatal day 15 (the earliest timepoint examined), is expressed at relatively similar levels within each tissue during the first 2 postnatal weeks, and reaches adult levels by the beginning of the 3rd postnatal week. In situ hybridization methodology revealed that PPE mRNA was prominent in areas associated with cell generation. Message was found in sites of primary (i.e., ventricular region) and secondary (e.g., external germinal layer of the cerebellum) cellular replication, as well as in discrete foci of cell proliferation (e.g., medullary layer of the cerebellum). PPE mRNA was also present for varying periods of time in postmitotic cells. During development, a number of patterns (decrease, increase, and no perceptible change) of PPE mRNA could be detected in relationship to the fetal/neonatal period. Given the strong evidence (e.g., regulation of cell proliferation and differentiation, temporal and spatial patterns of peptide and zeta opioid receptor) that enkephalin immunoreactivity is associated with proliferating and differentiating neurons and glia, these results suggest that the source of [Met5]-enkephalin is both autocrine and paracrine in nature.
Aging↗
Analysis of the genes encoding the variable regions of human IgG rheumatoid factor.
OBJECTIVE: To better understand the immunoglobulin variable (V) region repertoire of rheumatoid factors (RF). METHODS: We characterized the heavy (H) and light (L) chain gene segments utilized in a monospecific IgG RF secreting hybridoma (AEE111F) which were derived from a patient with rheumatoid arthritis (RA). The hybridoma was established by fusion of a mouse myeloma cell line with bone marrow derived mononuclear cells from a patient with RA. First strand complementary DNA (cDNA) was generated and used for a polymerase chain reaction amplification of the H and L chain V domains. The amplified V domains were sequenced and compared with an extensive database of germline and cDNA V gene segments. RESULTS: The VH sequence was found to be 96% homologous to a previously described fetal VH3 cDNA (60P2). The VL sequence was also highly homologous to the previously described V lambda II gene (96%) derived from a patient with systemic lupus erythematosus which correlated with an 8.12 idiotype (Id), and to an antibacterial antibody against the Haemophilus influenzae type b capsular polysaccharide (94.7%). CONCLUSION: The overlap among this RF VL gene and the 2 reported V lambda sequences of antibodies that expressed anti-DNA related Id and an environmental pathogen specificity suggests that a part of the IgG RF isolated from patients with RA may thus be derived from the physiological natural antibody repertoire during an abnormal immune response and then develop high affinity, monospecific RF by the selection of an antigen driven mechanism.
Amino Acid Sequence↗
[Intra-arterial combination chemotherapy using both regimen selected by chemosensitivity test and caffeine to increase effect for osteosarcoma in extremity].
We treated three patients with osteosarcoma in extremity with intra-arterial combination chemotherapy using a regimen selected by succinate dehydrogenase inhibition chemosensitivity test, and used caffeine to enhance its effect. In two patients with osteosarcoma in distal diametaphysis of the radius and extraskeletal osteosarcoma in sole of the foot, the effect of intra-arterial combination chemotherapy was increased and followed by the functional limb salvage procedure. But in one patient with osteosarcoma in the proximal tibia, the effect of pre-operative intra-arterial combination chemotherapy could not be increased, so amputation was required. He was changed to a post-operative intra-venous combination chemotherapy regimen selected by chemosensitivity test of the surgical material. All patients have been continuously disease-free at five to twelve months after surgery.
Adolescent↗
Localization of spectrin isoforms in the adult mouse heart.
The distribution of two isoforms of spectrin in the adult mouse heart was investigated by Western blotting and immunocytochemistry by use of monospecific antibodies to erythrocyte spectrin and nonerythroid brain spectrin (240/235). Western blotting revealed proteins analogous to both isoforms of alpha-spectrin in adult heart. Light-microscopic immunocytochemistry indicated that erythroid spectrin was distributed throughout the myocardium, with immunofluorescence localized to plasma membranes, Z-lines, and intercalated discs. Antibodies to brain spectrin (240/235) exhibited staining throughout the heart, with a generally diffuse distribution except for the prominent immunoreactivity associated with the intercalated discs. Nonerythroid spectrin immunofluorescence was detected in the endothelial cells of the endocardium and the mesothelial cell lining of the epicardium. Erythrocyte spectrin was not detected in the endocardium or the epicardium. The identification and localization of spectrin isoforms in the mammalian heart suggest the importance of spectrin proteins in the structural integrity and proper function of cardiac cells and tissues. This is the first demonstration of two different alpha-spectrin subunits in the mammalian heart.
Animals↗
The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells.
It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase, and that such degradation is regulated by metalloproteinase inhibitors (TIMP). Therefore, the balance between collagenase and TIMP is an important factor for tissue destruction in inflammatory joints. In the present study the effects of cytokines on collagenase and TIMP production in chondrocytes as well as the effects of cytokines on TIMP production in connective tissue cells were studied. IL-1 beta inhibited TIMP production in endothelial cells while enhancing TIMP production in synovial cells and chondrocytes. In addition, tumour necrosis factor-alpha (TNF-alpha) significantly inhibited and IL-6 significantly enhanced TIMP production in endothelial cells, synovial cells and chondrocytes. In the chondrocyte supernatant, collagenase activity/TIMP ratio was significantly elevated by the addition of either IL-1 beta or TNF-alpha to the cells, whereas the ratio was significantly decreased by IL-6. These results suggest that the cytokine effects on TIMP production are different among the different cell types, and that either IL-1 beta or TNF-alpha induce cartilage matrix degradation by disrupting the collagenase/TIMP balance, while, on the other hand, IL-6 protects the tissue through an opposite effect.
Cartilage↗
[Post-operative intra-arterial chemotherapy for high grade malignant musculoskeletal sarcoma].
Twenty-nine patients with high grade malignant musculoskeletal sarcoma were treated with chemotherapy. Intra-arterial chemotherapy was performed post-operatively for patients with local recurrence, patients with poor response to pre-operative chemotherapy or patients with intra-lesional or marginal surgical margin. The local recurrence rate in patients with intra-arterial chemotherapy (8.8%) was lower than in those with intravenous chemotherapy (37.5%). Patients with post-operative intra-arterial chemotherapy showed no local recurrence. Of the 29 patients except stage 3 with intra-arterial chemotherapy, the metastatic rate in patients with intra-arterial chemotherapy (41.4%) was lower than in chemotherapy patients with intravenous chemotherapy (83.3%). The rate in the post-operative group (28.6%) was lower than in the pre-operative group (42.9%) or pre- and post-operative group (50.0%). The ten-year survival curve of patients given intra-arterial chemotherapy (51.0%) was higher than in patients on intravenous chemotherapy (17.9%). Among the 34 patients who underwent intra-arterial chemotherapy, the survival rate in the other pre- and post-operative groups and the post-operative group (55.6%) was higher than in the pre-operative group and pre- and post-operative group (49.8%).
Antineoplastic Combined Chemotherapy Protocols↗
Malignant fibrous histiocytoma. A tumor of facultative histiocytes showing mesenchymal differentiation in cultured cell lines.
The histogenesis of malignant fibrous histiocytoma (MFH) is controversial. To elucidate the cellular origin and characteristics of this neoplasm, the authors analyzed cell lines grown from 17 patients (15 soft tissue MFH and 2 bone MFH) by using light and electron microscopy, immunocytochemistry, enzyme cytochemistry, and functional tests for receptors for the Fc portion of immunoglobulin (Fc receptors) and immunophagocytosis. Each culture exhibited a storiform/pleomorphic pattern with mixed cellular populations consisting of spindle cells, polygonal cells, and bizarre giant cells; these morphologic features corresponded to the histologic characteristics of the primary tumors. The cells in each MFH line displayed histiocytic functional markers such as lysosomal enzymes, Fc receptors and immunophagocytosis. However, these cells differed from monocyte-derived macrophages (histiocytes) in immunoreactivity; the MFH cells expressed a mesenchymal antigen (FU3) distributed among perivascular cells and fibroblasts but demonstrated no positive reactions with Leu-M1 (CD15) and Leu-M3 (CD14), which recognize the cells of the monocyte-macrophage lineage. In conclusion, these findings suggest that MFH is not a tumor of true histiocytes but of facultative histiocytes showing mesenchymal differentiation in vitro. Chromosomal analysis performed in one MFH line demonstrated abnormal karyotypes; the modal chromosome number was 58, with 5 marker chromosomes.
Adult↗
Malignant fibrous histiocytoma. Proliferative compartment and heterogeneity of "histiocytic" cells.
To elucidate the precise origin and characteristics of the proliferating cells in malignant fibrous histiocytoma (MFH), the authors analyzed 33 MFH tumors, using immunohistochemical techniques with a panel of 12 antibodies. All three types of MFH cells (spindle cells, polygonal cells, and bizarre giant cells) stained positively for mesenchymal antigens (FU3 and vimentin) but did not stain for macrophage/histiocyte markers (HAM 56 and CD68). Therefore, the MFH cells may not represent true histiocytes, although they may be mesenchymal-derived cells behaving as "facultative histiocytes" with superficial resemblance to actual histiocytes. Normal histiocytes in the stroma tested positive for macrophage/histiocyte antigens; the most common cells were HAM 56-positive cells constituting 30-80% of nonneoplastic stromal cells, followed by those positive for CD68 (10-50%), Mac 387 (less than 2%), and S-100 protein (less than 1%). Our results indicate the presence of heterogeneity of "histiocytic" cells in MFH. Proliferating-cell nuclear antigen (PCNA) was expressed not only in the spindle and polygonal MFH cells but also in the bizarre giant cells. These findings suggest that all three types of MFH cells participate in the proliferative compartment of MFH. Uneven PCNA staining of the irregular nuclear segments of the bizarre giant cells may result in abnormal DNA synthesis, possibly contributing to the marked diversity of nuclear morphology in MFH. Touton-type and osteoclast-like giant cells did not stain for PCNA but stained positively for histiocytic markers. Therefore, these giant cells may lack proliferative activity and probably result from normal histiocytes fusing together.
Adult↗
Endogenous opioids regulate cell proliferation in the retina of developing rat.
The role of endogenous opioids and opioid receptors (endogenous opioid systems) in modulating cell proliferation in the developing mammalian retina was examined in 1-day-old rats. In contrast to a labeling index (LI) of 35.8% in control animals, administration of the opioid peptide [Met5]-enkephalin (100 micrograms/kg) significantly reduced (10.6%) the proportion of cells incorporating [3H]thymidine; concomitant injection of 1 mg/kg naloxone blocked the inhibitory effects of [Met5]-enkephalin on cell division. Naloxone (1 mg/kg) alone did not alter the LI. The interruption of endogenous opioid-opioid receptor interaction by naltrexone (50 mg/kg), a potent opioid antagonist, was accompanied by a significant increase (6.4%) in the LI relative to control levels. Immunocytochemical experiments revealed the presence of enkephalin-like immunoreactivity, with staining of the cortical cytoplasm of proliferating and differentiating retinal cells recorded; no immunoreactivity was noted in the adult retina. In vitro autoradiography using 125I-[Met5]-enkephalin indicated that [Met5]-enkephalin binding sites were localized to the developing retina; no binding of the radiolabeled ligand was recorded in the adult retina. These results demonstrate the presence of growth-related endogenous opioids and opioid receptors in the developing mammalian retina, but not in adult retina, and suggest that endogenous opioids serve as natural inhibitory trophic factors that tonically regulate cell proliferation.
Animals↗
Localization of preproenkephalin A mRNA in the neonatal rat retina.
An opioid growth factor, [Met5]-enkephalin, is known to regulate developmental events in the neonatal rat retina. This growth factor interacts with the zeta (zeta) opioid receptor to modulate retinal ontogeny. Both peptide and receptor are present in developing retina, but not in adult retina. We have used in situ hybridization histochemistry to identify and localize preproenkephalin A mRNA in the neonatal rat retina. Preproenkephalin mRNA was localized to the ganglion cell layer, with some radiolabeling found in the neuroblast layer. This result indicates that 1) the mRNA to preproenkephalin A is present during the critical stage of development in the neonatal retina that coincides with the presence of the growth-regulating peptide, [Met5]-enkephalin, and 2) that the source of the opioid growth factor controlling the production of retinal cells appears to be autocrine (i.e., retinal neuroblasts) and paracrine (i.e., ganglion cells) in nature.
Animals↗
[Two different types of monoclonal antibodies against gallbladder carcinoma cell line].
Monoclonal antibody FU-W-H6 whose immunoglobulin subclass was IgG2a kappa was produced against gallbladder carcinoma cell line FU-GBC-2. In normal tissue, this antibody has a strong reactivity specific to the mucosa of the gallbladder (14/15, 94%), bile duct (5/5, 100%), and pancreatic duct (4/5, 80%) in comparison with the lack of the gastric mucosa, and colorectal mucosa with statistically significant differences (p less than 0.01). In cancerous tissue, gallbladder cancer (11/12, 92%), bile duct cancer (5/5, 100%), and pancreatic cancer (2/2, 100%) reacted gastric cancer (4/12, 33%), and colorectal cancer (1/16, 6%) with statistically significant differences (p less than 0.05). On the other hand, another monoclonal antibody FU-W-E2 whose immunoglobulin was IgM has specificity to the gastrointestinal or gallbladder cancers. Eleven of 13 (85%) gastric cancers, 12 of 16 (75%) colorectal cancers, and 9 of 12 (75%) gallbladder cancers reacted positively with statistically significant differences with each normal epithelia (p less than 0.05). Immunoelectron microscopical study revealed that the antigen recognized by FU-W-H6 was localized by FU-W-H6 or E2 antigens were suggested to be a carbohydrates on the glycoprotein, and were thought to have relation to sialic acid by treatment of acid Sciff and enzymes. Western blot analysis demonstrated that their molecular weights were about 87000, and 92000.
Adenocarcinoma↗
Spectrin isoforms in the mammalian retina.
Spectrin is a major component of the mammalian neuronal cytoskeleton. In the CNS, three isoforms of brain spectrin are known to exist: a cellular and dendritic isoform, (240/235E), related to neurons and glia; a cellular and axonal isoform, (240/235), related to neurons; and an isoform specific for astrocytes, (240/235A). In the present study, brain spectrins (240/235E) and (240/235) were localized within the mouse retina and optic nerve. Immunoblot analyses of proteins isolated from mouse retinas utilizing polyclonal antibodies to either brain spectrin (240/235) or brain spectrin (240/235E) revealed that these spectrins are present in the retina and that the two isoforms are the same molecular weights as those found in the brain. Immunocytochemical studies revealed that spectrin (240/235E) was localized in cell bodies of the inner nuclear, outer nuclear, and ganglion cell layers, and processes arborizing within the inner and outer plexiform layers. Spectrin (240/235) was distributed diffusely within the retina, lightly staining neurons in both the inner nuclear and outer nuclear layers, and the ganglion cell layer. In contrast to the situation found in the brain, spectrin (240/235) was but one of the axonal forms in the retina. We found that spectrin (240/235E) was also present in the axon-rich fiber layer and in the optic nerve and was often associated with fibrous elements. Spectrin (240/235) was also detected in the nerve fiber layer and optic nerve, but this isoform was not localized to fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Chondroblastomalike extraskeletal chondroma.
An unusual extraskeletal tumor occurring in the right thumb of a 44-year-old man exhibited histologically a chondroblastomalike appearance. The tumor was characterized by dense proliferation of chondroblastic cells admixed with a few multinucleated giant cells of osteoclast type. The patient had no evidence of local recurrence or metastasis three-and-a-half years after a simple excision.
Adult↗
Neuroectodermal tumor of bone. Evidence for neural differentiation in a cultured cell line.
A new cell line was established from a "neuroectodermal tumor of bone" affecting the right scapula of an 18-year-old man. The original neoplasm had dense proliferation of small round cells with abundant glycogen content and numerous Homer-Wright rosettes. The culture showed proliferation of small spindle cells with uniform oval nuclei and slender cytoplasmic processes. When the culture reached maximum density, rosette-like structures similar to those in the original tumor were formed. Under the influence of N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphoric acid (dibutyryl cAMP), the cultured cells expressed these rosette-like structures even in the lower cell concentration. Electron microscopy revealed that the cultured cells treated with dibutyryl cAMP contained high-density granules, well-developed microtubules, and abundant 10-nm filaments. By immunocytochemistry, neuron-specific enolase (NSE), and N-myc oncogene product were detected in the cultured cells as well as the original tumor. These results indicated the neuroectodermal origin of some of the small round cell tumors of bone.
Adolescent↗
[Mass screening for diabetes among the workers].
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Blood Glucose↗
A human gallbladder adenocarcinoma cell line.
A cell strain (FU-GBC-1) was established from cancerous ascites of a 68-year-old male patient with well-differentiated adenocarcinoma of the gallbladder. By light and electron microscopy, the cultured cells showed the morphologic features of adenocarcinoma characterized by gland-like structures, intracellular microcystic spaces, and mucous production. Immunoperoxidase stains showed that FU-GBC-1 cells expressed several epithelial tumor antigens including CA 19-9, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA). The cell strain has been in continuous culture up to passage 44 for 1 1/2 years, with the population doubling time of 120 hours. The cytogenetic analysis by a G-band technique showed a constant loss of chromosome Y in FU-GBC-1 cells. The modal chromosome number at passage 12 was 82 with a range of 77 to 85. Flow cytometry with an ethidium bromide technique additionally confirmed aneuploid DNA content (4C) in the cultured cells at passage 12 and 35. Inoculation of FU-GBC-1 cells into the dermis of BALB/c nude mice produced transplantable adenocarcinoma identical to the original tumor. Because no continuous cell lines of the well-differentiated type of gallbladder adenocarcinoma have been reported in the literature currently, the newly established cell strain we report may yield a useful system for studying the morphologic and biologic characteristics of gallbladder adenocarcinoma.
Adenocarcinoma↗
[Post-operative intra-arterial chemotherapy in patients with malignant bone and soft tissue tumors].
Fourteen patients with bone and soft tissue sarcoma were treated with post-operative intra-arterial chemotherapy. Three drugs (Adriamycin, vincristine, carboquone or THP-adriamycin, cisplatin, vindesine) or two drugs (cisplatin, vindesine) were used post-operatively for patients with local recurrence, patients with poor response of pre-operative intra-arterial chemotherapy or patients with intra-lesional or marginal surgical margin. Of the 14 patients treated with post-operative intra-arterial chemotherapy, 8 (57.1%) were continuously disease-free (7.1%) were disease-free after treatment of lung metastasis, 2 (14.3%) had a local recurrence and/or multiple distant metastasis, and 3 (21.4%) died with multiple distant metastases. The rate of local recurrence was 14.3%. The Kaplar-Meier disease free survival curves showed 59.6%). Evaluation of limb function were excellent or good in 9 (69.2%) of 13 patients treated with limb-saving procedures.
Adolescent↗