Biomedical subjects
Publications and source records attributed to Y Iwai.
We report a case retroperitoneal mature teratoma showing an abnormally high CA19-9 (carbohydrate antigen 19-9) serum level in a 30-year-old woman. She was hospitalized for an episode of left upper abdominal pain. High CA19-9 tissue level and immunohistochemical findings were found in removed tissue. This case is the third report of a CA19-9-producing teratoma and literature was reviewed and discussed.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor (HGF) that regulates the proliferation and differentiation of cells of the myeloid lineage. It can be produced by a variety of cells. One of the major sources of GM-CSF is activated T cells, which transiently produce this HGF. We used the EL-4 thymoma cell line as a model system to address the molecular basis for GM-CSF regulation in T cells. Both concanavalin A (ConA) and the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) induce GM-CSF expression in EL-4 cells. However, the biological activity of GM-CSF in the supernatants of the TPA-stimulated cells was higher than that of ConA-stimulated cells. To elucidate this difference in biological activity levels, we examined how ConA regulates GM-CSF gene expression in EL-4 cells and compared it to the better-characterized regulation by TPA. Peak mRNA levels of GM-CSF occur 6 h after stimulation with either of these two agents. GM-CSF mRNA levels after ConA treatment are lower and decrease significantly after 10 h compared to TPA treatment, which causes much higher levels that persist for at least 24 h. Neither agent alters GM-CSF gene transcription. Actinomycin D chase experiments show that ConA increases the GM-CSF mRNA half-life from less than 30 to 90 min, whereas TPA prolongs it to greater than 3 h. These results indicate that GM-CSF mRNA induction by ConA (in common with TPA) is regulated predominantly via RNA stabilization and that the difference in prolongation of the mRNA half-life provides the primary explanation for the lower levels of GM-CSF mRNA induced by ConA compared to TPA.
Phorbol esters (TPA) and concanavalin A (ConA) are known to induce granulocyte-macrophage colony-stimulating factor (GM-CSF) production in murine thymoma EL-4 cells by mRNA stabilization. The role of the 3'-untranslated region (3'-UTR) in GM-CSF mRNA stabilization induced by TPA and ConA in EL-4 cells was examined by transfection studies using chloramphenicol acetyltransferase (CAT) constructions. The GM-CSF 3'-UTR contains a 63-nucleotide region at its 3' end with repeating ATTTA motifs which is responsible for mRNA degradation in a variety of cell types (Shaw, G., and Kamen, R. (1986) Cell 46, 659-666). We produced constructs containing most of the GM-CSF 3'-UTR (303 nucleotides, pRSV-CATgm) or the 3'-terminal AT-rich region (116 nucleotides, pRSV-CATau) and measured CAT enzyme activity and CAT mRNA after transient transfection into EL-4 and NIH 3T3 cells. Low levels of CAT activity were seen in both cells with either plasmid compared with levels of CAT activity obtained with pRSV-CAT. TPA treatment caused an approximately 10-fold increase in CAT activity and mRNA in EL-4 cells transfected with pRSV-CATgm. No increases were seen in EL-4 cells transfected with pRSV-CATau or pRSV-CAT. No response to TPA was detected in transfected NIH 3T3 cells, indicating that the response to TPA is relatively cell-specific. There was no increase in CAT activity after ConA treatment in EL-4 or NIH 3T3 cells transfected with any of the constructs suggesting that the GM-CSF 3'-UTR lacks elements that can respond alone to ConA. Nuclear run-on and actinomycin D chase experiments in EL-4 cells showed that TPA induces CAT activity via mRNA stabilization. By linker-substitution mutagenesis we show that TPA inducibility depends on a 60-nucleotide region of the 3'-UTR whose 5' end is located 160 nucleotides upstream of the 5' end of the AU-rich region.
Inhibitory effects of synthetic laminin related peptides on experimental metastasis formation in mice were examined. Of the synthetic peptides, YIGSRG-[amino-poly(ethylene glycol)] hybrid exhibited the most potent inhibitory effect on the metastasis of B16 melanoma BL6.
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An incomplete proviral genome of endogenous mammary tumour virus (MMTV) was found in DNA of several strains of mice. This MMTV-related sequence was assigned to the Y chromosome since it was clearly observed in male mice only. This MMTV provirus contained a sequence related to LTR (long terminal repeat), but not to gag-pol and env genes. NFS, NIH Swiss/S, STS/A, and DD/Tbr mice have this sequence but BALB/cHeA, SHN, SLN, C57BL/6NJcl, C3H/HeNJcl and CBA/JJcl mice are negative. In the strains containing this sequence, a DNA test for the sequence makes it possible to easily distinguish the DNAs of male or female mice.
RNA expressions of common integration site (int) genes and several oncogenes were investigated in mammary carcinomas spontaneously developed in different three strains of mice; DD/Tbr, NIH Swiss and BALB/c which harbor DD-MMTV derived from DD/Tbr mouse. Latter two strains of mice were designated NIH/Mtv+ and BALB/Mtv+, respectively. An increased expression of int-1 (wnt-1) and int-2 genes was observed in 56% (9/16) and 50% (8/16) of mammary carcinomas of DD/Tbr mice, respectively. Either int-1 or int-2 RNAs were expressed in 81% (13/16) of the carcinomas of DD/Tbr mice. IN NIH/Mtv+ mice, activation of int-1 and int-2 was observed in 41% (7/17) and 24% (4/17) of mammary carcinomas, respectively. Either int-1 or int-2 RNAs were expressed in 47% (8/17) of the carcinomas examined in this strain. In BALB/Mtv+ mice, on the other hand, either int-1 or int-2 gene were transcribed into RNAs at low frequency (33%: 3/9). These results suggest that the frequency of activation of int genes in mammary carcinomas induced by the same DD-MMTV in three strains of mice is genetically defined characteristics of these strains, and that the involvement of int-1 and int-2 genes in virus-induced mammary carcinogenesis may be influenced by genetic properties of animals. The activation of int-1 and int-2 genes did not clearly correlate with an increase in the expression of oncogenes examined; H-ras, K-ras, N-ras, myc, raf, fgr, fms, erB, mos, and src genes.
Kitasatosporia strains were found to be resistant to an antibiotic, novobiocin. By a new method using novobiocin-containing agar medium, five Kitasatosporia strains, SK-3255, OM-5023, SK-3406, SK-3412 and SK-3421 were efficiently isolated from soils. These five strains were characterized in common by Rectiflexibiles, spores cylindrical with smooth surfaces, and no melanin formation. Two strains, SK-3255 and OM-5023 were taxonomically different from known species of the genus Kitasatosporia, while the two strains, SK-3406 and SK-3412 and the remaining strains SK-3421 were identified with K. phosalacinea and K. papulosa, respectively.
We treated three cases of inflammatory granulomas extending from the sphenoid sinus to the cavernous sinus. Case 1 was that of a 36-year-old male with diplopia and right ptosis. Case 2 was that of a 40-year-old male with frontal headache. Case 3 was that of a 70-year-old female with left impaired vision and frontal headache. In the first case, MRI demonstrated a mass lesion extending from the right half of the sphenoid sinus to the cavernous sinus and retropharyngeal space. In the second case the granuloma extended from the right cavernous sinus to the right retroorbital space. In the last case, MRI demonstrated diffuse Gd-DTPA enhancement of the left cavernous sinus and the left half of the sphenoid sinus. In all cases an operation was performed using the sublabial rhinoseptal approach, and the tumor in the sphenoid sinus was removed. Histological examination revealed an inflammatory granuloma in all 3 cases. In the first case the clinical symptoms improved following administration of glucocorticoids. In the second case the mass in the cavernous sinus decreased in size postoperatively. In the last case, the clinical symptoms gradually improved with administration of antibiotics after surgery. Granuloma of the cavernous sinus is difficult to diagnose, but when a similar pathological lesion coexists in the sphenoid sinus, a definitive diagnosis can be easily made via the sublabial rhinoseptal approach.
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A girl developed acute agranulocytosis (45/mm3), 37 days after the onset of infectious mononucleosis. The bone marrow showed myeloid hyperplasia with maturation arrest and erythroid hypoplasia. A normal amount of colony forming units of granulocytes and macrophages (CFU-GM) colonies with a relative high number of clusters was observed. Neither anti-neutrophil antibodies nor circulating inhibitors of colony growth were found in serum. Granulocyte and macrophage colony stimulating factor (GM-CSF) activity in the patient's serum rose at this time. The agranulocytosis lasted 5 days and her clinical state soon improved. These results suggested that agranulocytosis was presumably not due to serum factors, including auto-antibodies and/or suppressive substances, and that Epstein-Barr virus (EBV) had some direct or indirect effect on the marrow cells of the myeloid series.
SHN and SLN mice originating from the same Swiss albino stock are genetically very close to each other. The incidence and latent period of mammary tumor development in SHN mice were higher and shorter than those in SLN. To elucidate these differences in the behavior of mammary tumorigenesis, the frequency of insertion of mammary tumor viral genes within the int-1 and int-2 regions in spontaneous mammary tumors from their two substrains, SHN/S and SLN/S, were compared. The frequency of provirus integration into either int-1 or int-2 in DNAs from mammary tumors was 52% (11/21) in SHN/S and 45% (5/11) in SLN/S. The frequency of insertion within int-1 or int-2 could not account for the different susceptibilities of SHN/S and SLN/S.
Fourteen specimens of normal, benign, or malignant tumor cells from the head and neck region were subjected for culture using 0.2% of irradiated collagen gel embedding technique. Re-differentiation of glands within the gel in serum-free medium was observed. There were marked differences in the growth patterns within the gel between normal or benign and malignant cells. Four normal glands and 5 out of 6 benign tumors showed branch-like growth patterns. On the other hand, malignant tumors showed no branch-like pattern, or could not grow at all. The results showed that the collagen gel technique could be useful for the differential diagnosis of malignancy in head and neck tumors.
Muramyl dipeptide (MDP) is the minimal adjuvant-active structure of mycobacterial cell walls and is known to activate monocytes/macrophages, but mechanisms involved with uptake and activation of these cells have not been completely defined. Earlier studies addressing uptake of MDP and the question of receptors have utilized radioligands and murine peritoneal macrophages. We used fluorescent congeners of MDP and flow cytometry to explore kinetics and specificity of uptake by bronchoalveolar cells of normal rabbits. Both washed cells and cell suspensions from which the fluorescent congeners were not washed were used, and incubation was carried out primarily at 4 degrees C. Fluorescence microscopy consistently revealed intracellular but no visible membrane fluorescence of alveolar macrophages. Uptake was dose dependent but was not saturable up to concentration limits of fluoresceinated muramyl tripeptide (MTP-FITC) imposed by the system, and was partially inhibited by excess unlabeled MDP, consistent with specific inhibition. Alveolar macrophages, but not lymphocytes, demonstrated specific uptake at 4 degrees C, with rapid on- and off-times. Uptake was enhanced 7-fold at 37 degrees C. Uptake was greater by larger, more granular macrophages than by smaller, less granular macrophages, but no difference in uptake was found when cells of similar size but different densities were compared. The exact mechanism of the rapid uptake at 4 degrees C is uncertain but appears to be competed for by unlabeled MDP.
Embedding culture was performed on normal salivary gland cells from five subjects using 0.2% irradiated collagen gel. Collagen was collected from rat tail tendon and gelatinized at the final concentration of 0.2%. D-MEM added BSA (5mg/ml), insulin (10 micrograms/ml) and EGF (5 micrograms/ml) was used as a serum-free medium. Within the collagen gel, the cells were found to grow in a branch-like pattern, and then to form a lot of radial duct-like structures containing alcian blue positive secretions. Immunohistochemical observation of myoepithelial cells with monoclonal antibody from human mammalian cancer suggested that these cells play an important role in the process of glandular ducts formation. Salivary gland cells being able to grow in collagen gel in a very similar fashion to in-vivo condition, the present collagen gel embedding culture is useful for morphological or functional studies on salivary gland cells.
Southern blot analysis revealed no difference between the DNA from radiation-induced thymic lymphomas and DNA from normal NFS mice. The probes used in the Southern blot analyses used a murine leukemia virus (MuLV) env DNA probe (pXenv), which specifically hybridizes with xenotropic and recombinant viral env genes, and mouse mammary tumor virus (MMTV) DNA probes (MMTV gag-pol, MMTV env, and MMTV LTR). This suggests that radiation leukemogenesis was not associated with gross alteration of the organization of these retroviral genomes. In DNA from radiation-induced thymic lymphoma, there was no indication of gross rearrangement in the common integration site of MuLV, pim-1, or in the common integration sites of MMTV, int-1 and int-2. Dot blot analysis of RNA from radiation-induced thymic lymphomas and normal thymuses demonstrated that there was no substantial difference between them in the expression of retroviral sequences, pim-1, pvt-1, int-1, or int-2, although transcripts that could be hybridized to the retroviral sequences were slightly elevated in some radiation-induced thymic lymphomas. These results show that radiation leukemogenesis does not appear to involve the activation of endogenous type-C and type-B retroviruses.
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