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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 19 recordsLinked to original sources
PubMed1992

Phosphorylation of the Rex protein of human T-cell leukemia virus type I.

Rex protein, the posttranscriptional regulator of human T-cell leukemia virus type I (HTLV-I), is required for the control of viral structural protein expression and virus replication. Rex is a phosphoprotein found predominantly in the cell nucleolus, whose function is thought to be regulated by its nucleolar localization and phosphorylation. Therefore, we investigated the in vivo phosphorylation of Rex protein in more detail. Phosphorylation of Rex occurred in all HTLV-I-infected cell lines examined in vivo, primarily at serine residues and to a very small extent at threonine residues. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) led to significant but transient enhancement of the incorporation of [32P]orthophosphate into Rex protein. N-terminal truncation of Rex protein abolished TPA-dependent phosphorylation. Chymotryptic digestion of phosphorylated Rex yielded two phosphopeptides. In vivo phosphorylation sites were identified as serine residues 70 and 177 and threonine residue 174. Serine 70 was a TPA-dependent phosphorylation site within a regulatory domain. We have already shown that the protein kinase C inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) specifically blocked accumulation of viral unspliced gag-pol mRNA. Therefore, the phosphorylation at serine 70 may be involved in the regulation of Rex function in response to extracellular stimuli.

Amino Acid Sequence↗
PubMed1992

Expression of calpain II gene in human hematopoietic system cells infected with human T-cell leukemia virus type I.

We examined the distribution of calpains I and II in human hematopoietic system cell lines by Western and Northern blot analyses and enzyme activity assay. Expression of calpain I, a low Ca(2+)-requiring cysteine protease, was observed in all human T-cell lines tested. By contrast, expression of calpain II, a high Ca(2+)-requiring form, in human T-cells was closely correlated with human T-cell leukemia virus type I (HTLV-I) infection, which is known to result in the expression of adult T-cell leukemia-associated antigens, interleukin-2 (IL-2) receptor alpha, and Ca(2+)-dependent cell proliferation. Specific expression of calpain II in HTLV-I-infected cells occurred at the mRNA level. Furthermore, expression of calpain II in human natural killer-like cells was augmented by HTLV-I pX gene transfection. In HTLV-I-infected cells, the trans-acting transcriptional activation of the long terminal repeat and control elements for the IL-2 receptor alpha, c-fos, and granulocyte-macrophage colony-stimulating factor genes by the Tax from the pX gene is already known. Our results suggest that the similar trans-activation occurs to the calpain II gene in HTLV-I-infected hematopoietic system cells.

Blotting, Western↗
PubMed1992

Poorly differentiated medullary carcinoma of the stomach.

BACKGROUND: The biologic behavior of poorly differentiated medullary carcinoma of the stomach is unclear. METHODS: A clinicopathologic study on 74 poorly differentiated medullary carcinomas (PMC) and 73 nonmedullary carcinomas (NMC) of the stomach was done. PMC were defined as gastric carcinomas in which more than 50% of the tumor area contained poorly differentiated adenocarcinoma with no fibrous stroma. RESULTS: They were characterized by a location in the upper 33% of the stomach (49%), grossly expansive growth (69%), frequent vascular permeation (57%), and simultaneous liver metastasis (15%). Although the 5-year survival rate was similar for PMC and NMC, death of PMC was related more frequently to liver metastasis (47%) and less frequently to peritoneal dissemination (12%). The outcome of patients with PMC was influenced by frequent vascular permeation, extended lymph node metastasis, and simultaneous liver metastasis. CONCLUSIONS: These results indicate that PMC are characterized by expansive growth of the tumor and simultaneous or recurrent metastasis to the liver. Therefore, the biologic behavior of poorly differentiated medullary carcinoma is similar to that of well-differentiated carcinoma of the stomach.

Carcinoma↗
PubMed1992

Pathology and prognosis of gastric carcinoma. Findings in 10,000 patients who underwent primary gastrectomy.

BACKGROUND: Despite recent advances in diagnosis and treatment, gastric carcinoma remains a major cause of death in the world. METHODS: The clinicopathologic profile of 10,000 consecutive patients who underwent primary gastrectomy during 1962-1989 were reviewed and prognostic factors influencing survival in those with gastric carcinoma were analyzed in 7031 patients. RESULTS: Incidence of gastrectomy for carcinoma has increased steadily and the rate of early carcinoma exceeded that of advanced carcinoma in the recent period of 1985-1989. Five-year and 10-year survival rates were 46.1% and 35.2% in 3868 patients with advanced carcinoma, and 88.8% and 77.3% in 3163 patients with early carcinoma, respectively. In patients with advanced carcinoma, significantly poorer survival rates were noticed for patients older than 70 years of age, those who underwent total gastrectomy, tumors involving the entire stomach or greater than 10 cm in diameter, a macroscopic diffusely infiltrative pattern, adenosquamous histologic type, positive surgical resection margins, or lymph node metastasis. None of the above poor prognostic features were identified in patients with early gastric carcinoma group except for those older than 70 years of age. Although lymph node metastases were present in 10% of early gastric carcinomas, this feature did not impart a poor prognosis. Patients with advanced carcinoma grossly resembling an early carcinoma had an intermediate prognosis, suggesting the existence of a developmentally midstage lesion between early and advanced carcinoma. CONCLUSIONS: The study illustrates that the most important role for clinicians treating with gastric carcinoma should be early detection and aggressive surgery for resectable tumors, followed by detailed pathologic examination.

Adenocarcinoma↗
PubMed1992

A clinicopathologic study of mucinous gastric carcinoma.

A clinicopathologic study of 42 mucinous gastric carcinomas (MGC) and 73 nonmucinous gastric carcinomas (NGC) was done. The tumor was defined as MGC when more than one half of tumor area had mucin pools. The 5-year survival rate for curatively treated patients was almost the same in MGC (58%) and NGC (56%), and clinicopathologic features, except for lymphatic permeation, showed no significant difference between MGC and NGC. Findings in MGC patients who died of a recurrence within 3 years included total gastrectomy, upper location, large size, infiltrative growth, extraserosal invasion, positive lymph node metastasis, more advanced stage, and a noncurative operation. There was no significant correlation between the degree of mucin content and other data, including the prognosis. Histologically, MGC were divided into well-differentiated and poorly differentiated types, according to the degree of glandular formation of the tumor cells. In patients with well-differentiated MGC, the age of onset was older, tumor growth was localized, and there were metastases to the liver. In patients with poorly differentiated MGC, the age of onset was younger, tumor growth was infiltrative, and there was peritoneal dissemination. These results show that the biologic behavior of MGC is similar to that of NGC and that the lesion basically is determined by the histologic subtype, not by the mucin content.

Adenocarcinoma↗
PubMed1992

Gastric involvement of oesophageal squamous cell carcinoma.

Among 402 patients with squamous cell carcinoma of the oesophagus, gastric wall involvement was evident in 32 (8.0 per cent). These could be grouped into four types according to the pattern of involvement: group 1 included six patients with gastric involvement via metastases in perigastric lymph nodes; group 2 consisted of 11 patients with gastric intramural metastasis; group 3 contained 12 with direct invasion of the gastric wall by the oesophageal squamous cell carcinoma; and group 4 three patients with intraepithelial spread of oesophageal cancer to the gastric epithelium. Prognosis was poor, all patients dying except for one in each of groups 3 and 4. The mean survival time was 5.6, 8.6, 14.8 and 18.7 months in groups 1, 2, 3 and 4, respectively. Gastric involvement via metastases to lymph nodes and by intramural metastasis therefore indicates an extremely poor prognosis, while the prognosis in groups 3 and 4 was influenced by the depth of invasion and lymph node metastasis of the oesophageal cancer. Histological examination of tissues from group 4 patients demonstrated that malignant squamous cells proliferated and invaded the gastric epithelial layer, that is, there was intraepithelial spread of the oesophageal cancer.

Aged↗
PubMed1992

Origin of thymic and peritoneal Ly-1 B cells.

Murine Ly-1 B cells were first found in the peritoneal cavity (Per C). It has been thought that Ly-1 B cells are responsible for the development of autoimmune diseases, since they spontaneously produce autoantibodies. However, we have found that such Ly-1 B cells are present in the thymus of normal mice, and that they play a crucial role in negative selection in the Mls system. In addition, thymic Ly-1 B cells and Per C Ly-1 B cells have been found to differ in function, ontogeny and location. In this communication, we report on the different origins of these cells. C57BL/6 mice are lethally irradiated and reconstituted with fetal (day 14) liver cells or bone marrow cells from 4-, 6- or 12-week-old mice. Fetal liver cells are shown to have the capacity to reconstitute both thymic and Per CLy-1 B cells, whereas bone marrow cells from 6- or 12-week-old mice have the capacity to reconstitute thymic Ly-1 B cells, but not Per C Ly-1 B cells, indicating that fetal hemopoietic stem cells (HSC) differ from HSC in the bone marrow of adult mice, and that thymic and Per C Ly-1B cells have different origins.

Age Factors↗
PubMed1992

Preoperative hyperthermia combined with chemotherapy and radiotherapy for patients with rectal carcinoma may prevent early local pelvic recurrence.

We examined retrospectively the results of hyperthermia combined with irradiation and chemotherapy (HCR) prescribed preoperatively for patients with adenocarcinoma of the rectum. We compared two groups of patients: Group A: 23 were treated surgically between 1986-1988 and received HCR therapy; group B (controls) 48 were treated with surgery alone or surgery plus chemotherapy from 1980-1985. The recurrence rate within 2 years was compared. Although there was a difference in follow-up time, the two groups were comparable with regard to various prognostic factors. The incidences of local recurrence and of lung metastasis were nil in those given the HCR therapy. In group B, however, the incidences were 15% and 10%, respectively. These differences were statistically significant (P < 0.05). The incidence of liver metastasis was much the same between the two groups. All patients tolerated the HCR therapy well except for one with myelosuppression and who refused local hyperthermia because of mild anal pain. There were no other side effects requiring cessation of this treatment. These findings suggest that preoperative HCR therapy for patients with rectal carcinoma decreases the frequency of local recurrence and the likelihood of tumour cell spread during surgical procedures.

Adenocarcinoma↗
PubMed1992

Enhancement of rat hepatic macrophages by treatment with interleukin-2 and streptococcal preparation OK432, with reference to antitumor activity, soluble factor production and Ia expression.

The effect of biological response modifiers, such as interleukin-2 (IL-2) and streptococcal preparation OK432, on the functions of hepatic macrophages was investigated. The macrophages, even with no exogenous stimulation, produced superoxide anion (O2-) and tumor necrosis factor (TNF), displayed cytotoxicity against K562 cells and cytostasis against P815 cells and expressed immune-region-associated antigen (Ia). IL-2 administered in vitro or in vivo enhanced O2- production by hepatic macrophages and the intravenous injection of OK432 also enhanced O2 production. Furthermore, IL-2 added to the culture medium of hepatic macrophages isolated from OK432-injected rats augmented O2- production even more. The TNF production and Ia expression of the macrophages were also increased by the intravenous injection of OK432. As with O2- production, the cytotoxicity of the cells was enhanced by OK432 injection or by IL-2 added to the culture medium and the combination of OK432 and IL-2 augmented their cytotoxicity even more. Thus, the present study suggested that IL-2 and OK432 induce the augmentation of the antitumor activity of hepatic macrophages, partly as a result of the increase in production of O2- and TNF and Ia expression.

Animals↗
PubMed1992

Tumoricidal activity of Kupffer cells augmented by anticancer drugs.

The effect of Mitomycin-C (MMC) and Adriamycin (ADM) on the antitumor-associated function of Kupffer cells was examined. MMC and ADM enhanced the production of superoxide by Kupffer cells in cultures at low concentrations likely to occur in clinical use. The expression of interleukin-2 receptor, Ia antigen and asialoGM1 antigen, measured by flowcytometry, was increased by contact with MMC. Growth inhibition of AH130, rat ascites hepatoma, and P815, murine mastocytoma, by Kupffer cells treated with anticancer drugs was greater than that by Kupffer cells alone or anticancer agent alone. These results show that MMC and ADM activate Kupffer cells, leading to synergistic antitumor activity. The results suggest that some anticancer agents act through immunological mechanisms as well as through direct antineoplastic activity.

Animals↗
PubMed1992

Effect of PGE2 on interleukin-1 and superoxide release from primary-cultured human hepatic macrophages.

In order to learn more about how human hepatic macrophages function, we analyzed the effect of exogenous PGE2 on the amounts of interleukin-1 (IL-1) and superoxide (O2-) released from primary-cultured human hepatic macrophages (HHM phi). When endogenous PGE2 production was blocked by indomethacin, exogenous PGE2 reduced IL-1 release from HHM phi in a dose-dependent manner, whereas it tended to increase O2- release from HHM phi. These results may suggest the probable contribution of PGE2 in regulating HHM phi mediator release in vivo.

Cells, Cultured↗
PubMed1992

Hepatic macrophage malfunction in rats with obstructive jaundice and its biological significance.

The present study was designed to investigate the pathophysiology of obstructive jaundice by analyzing the function of hepatic macrophages and their role in immune responses and homeostasis in rats. The phagocytic index, determined by the rate of disappearance of 51Cr-endotoxin from the peripheral blood after intravenous injection, was increased in obstructive jaundice 2 weeks after bile duct ligation. The superoxide production of isolated hepatic macrophages and peripheral blood monocytes, measured by the superoxide dismutase inhibitable ferricytochrome c reduction method, was increased. Prostaglandin E2 release, measured by RIA, was markedly increased in rats with obstructive jaundice, but there was no significant difference in interleukin-1 release between jaundiced and control rats. The flow-cytometric analysis of surface molecules of hepatic macrophages showed decreased expression of interleukin-2 receptor in rats with obstructive jaundice. Thus, the functions of hepatic macrophages in rats with obstructive jaundice were impaired. This malfunction may disturb the immunoregulatory network and metabolism, although the exact implications of the altered function of hepatic macrophages have not yet been clarified.

Animals↗
PubMed1992

Identification of nuclear pre-replication centers poised for DNA synthesis in Xenopus egg extracts: immunolocalization study of replication protein A.

We demonstrate by immunofluorescence that a 70-kD protein (P70) purified from Xenopus egg extracts is associated with subnuclear foci (about 200) which we propose to be an assembly of DNA pre-replication centers (preRCs). A cDNA encoding this protein reveals that P70 is the Xenopus homologue of replication protein A (RPA also called RF-A). RPA is know to be a cellular, three-subunit single-stranded DNA binding protein, which assists T-antigen in the assembly of the pre-priming complex in the SV40 replication system. The punctated preRCs exist transiently; they form post-mitotically during the period of nuclear membrane breakdown and disappear during ongoing DNA replication. P70 is homogeneously associated with chromatin at the later stages of the S-phase and is displaced from chromatin post replication, so that P70 cannot be detected on mitotic chromosomes. Double-immunofluorescence studies using biotin-dUTP demonstrate that initiation of DNA synthesis is confined to preRCs, resulting in the punctated replication pattern observed previously by others. PreRCs form efficiently on decondensed chromatin in membrane-free egg extracts if ATP and divalent cations are present. Our results suggest that preRCs are composed of an assembly of a large number of pre-initiation replication complexes poised for initiation at discreet subnuclear regions prior to nuclear reconstruction and initiation of DNA synthesis.

Amino Acid Sequence↗
PubMed1992

Modification of immunopharmacological activities of synthetic monosaccharide lipid A analogue, GLA60, by lysozyme.

Recent studies by our group suggested that lysozyme has a high affinity for bacterial lipopolysaccharide (LPS) of both the smooth and rough forms, and inhibits various immunomodulatory activities of LPS. GLA60 is a synthetic monosaccharide analogue of bacterial lipid A well known as having most of the activities of lipid A with very low toxicity. In this study, we characterized the interaction of lysozyme with GLA60 in comparison to that with Escherichia coli 0111 LPS (smooth form) by means of an immunopharmacological approach. Using dansylated lysozyme (DNS-LZM) as a probe, LZM was found to bind to GLA60. The mitogenic and polyclonal B-cell activating activities were significantly reduced by complex formation. However, there was no inhibitory effect on GLA60 induced production of IL-1 and TNF of macrophages. Interestingly, the activities of macrophages induced by the complex were found to be significantly higher than those induced by GLA60 itself. In contrast, the activities of 0111 LPS were significantly inhibited by LZM. Since the GLA60-LZM complex produced a turbid suspension but the 0111 LPS-LZM complex remained soluble, we consider that the activities of GLA60 alone were mediated by the common functional LPS receptor for dispersed form in both macrophages and B-lymphocytes, but activation of macrophages by the complex was mediated either by another LPS receptor not present in B-lymphocytes or through the phagocytic function of macrophages.

Adjuvants, Immunologic↗
PubMed1992

Inflammatory fibroid polyp of the stomach. Report of three unusual cases.

Three patients with inflammatory fibroid polyp (IFP) of the stomach underwent operation with a diagnosis of submucosal tumor, polyp, and intramural tumor of the stomach, respectively. Resected specimens grossly showed a deep ulcer accompanied by surrounding upheaval, a sausagelike polyp 6.5 cm long, and a pedunculated tumor with a short pedicle, respectively. Histologic examination showed that each lesion was typical of IFP of the stomach, with a mixture of fibroblasts and thin-walled blood vessels, and further by an intense infiltrate of eosinophils. These cases indicate that IFP of the stomach can vary in gross appearance. Practitioners and pathologists must remember that not only a polypoid lesion, but also a pedunculated or even ulcerated lesion, in the gastric antrum may be IFP.

Adult↗
PubMed1992

Fission yeast pap1-dependent transcription is negatively regulated by an essential nuclear protein, crm1.

The fission yeast pap1+ gene encodes an AP-1-like transcription factor that contains a leucine zipper motif. We identified a target gene of pap1, the p25 gene. The 5' upstream region of the p25 gene contains an AP-1 site, and by DNase I footprint analysis, we showed that the pap1 protein binds to the AP-1 site as well as to a 14-bp palindrome sequence. p25 is overproduced when the pap1+ gene is overexpressed, whereas p25 is not produced at all in the pap1 deletion mutant. p25 was previously found to be overproduced in strains carrying cold-sensitive crm1 mutations whose gene product is essential for viability and is thought to play an important role in maintenance of a proper chromosomal architecture. Deletion and site-directed mutagenesis of sequences upstream of the p25 gene demonstrated that the AP-1 site as well as the palindrome sequence are crucial for transcriptional activation either by pap1 overproduction or by the cold-sensitive crm1 mutation; pap1+ is apparently negatively regulated by crm1+. Moreover, we found that cold-sensitive crm1 mutations are suppressed by the deletion of pap1+, further indicating a close relationship between crm1+ and pap1+. The crm1 protein is highly conserved; the budding yeast homolog, CRM1, which complements the fission yeast cold-sensitive crm1 mutation, was isolated and found to also be essential for viability. These results suggest the functional importance of chromosome structure on the regulation of gene expression through the pap1 transcription factor.

Amino Acid Sequence↗