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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 541 records · Page 30Linked to original sources

Requirement of donor-derived stromal cells in the bone marrow for successful allogeneic bone marrow transplantation. Complete prevention of recurrence of autoimmune diseases in MRL/MP-Ipr/Ipr mice by transplantation of bone marrow plus bones (stromal cells) from the same donor.

MRL/MP-Ipr/Ipr (MRL/Ipr) mice possess radioresistant (9.5 Gy) abnormal stem cells and show a recurrence of autoimmune diseases within 5 mo of conventional allogeneic bone marrow transplantation. We recently have found that the MHC preference exists between hemopoietic stem cells and stromal cells; when bones are engrafted, donor-derived stromal cells present in the engrafted bones can migrate into the recipient bone marrows, which are replaced with both donor-derived stromal cells and hematopoietic cells. Based on these findings, we attempted to prevent the recurrence of autoimmune diseases in MRL/Ipr mice by the transplantation of both bone marrow cells and bone (as a source of stromal cells). MRL/Ipr mice were irradiated (8.5 Gy) and then reconstituted with C57BL/6 bone marrow cells plus bone grafts. The mice survived more than 48 wk after this treatment. Immunohistologic studies revealed that the mice were completely free from both lymphadenopathy and autoimmune diseases such as lupus nephritis and rheumatoid arthritis. Sera from these mice showed normal levels of circulating immune complexes and rheumatoid factors. Normal functions of both T cells and B cells were noted. Abnormal T cells such as Thy-1+B220+ cells present in nontreated MRL/Ipr mice could not be seen in the thus-treated mice. In addition, to our surprise, spleen cells from treated mice showed completely normal in vitro primary anti-SRBC responses. These results indicate that stromal cells in allogeneic bone marrow transplantation play a crucial role not only in the prevention of graft failure but also in the successful cooperation among APCs, T cells, and B cells. Although MRL/Ipr mice are radiosensitive and usually die of interstitial pneumonia or fatty liver due to the side effects of radiation, it should be noted that this strategy allows a reduction in the radiation dose (9.5 Gy-->8.5 Gy), and that these mice can survive more than 48 wk without showing any symptoms of autoimmune diseases.

Animals↗

Identification of in vivo phosphorylation sites of SET, a nuclear phosphoprotein encoded by the translocation breakpoint in acute undifferentiated leukemia.

SET, the translocation breakpoint-encoded protein in acute undifferentiated leukemia (AUL), is identified as a 39-kDa phosphoprotein found predominantly in the cell nuclei [1994, J. Biol. Chem. 269, 2258-2262]. SET is fused to a putative oncoprotein, CAN, in AUL and is thought to regulate the transformation potential of SET-CAN by its nuclear localization and phosphorylation. We investigated in detail the in vivo phosphorylation of SET. Phosphorylation of SET occurred in all human cell lines examined in vivo, primarily on serine residues. Endoproteinase Glu-C digestion of phosphorylated SET yielded two phosphopeptides. By radiosequencing, we identified the in vivo phosphorylation sites of SET as Ser9 and Ser24. The surrounding sequences of Ser9 and Ser24 contained an apparent consensus site sequence for protein kinase C.

Acute Disease↗

Preparation and properties of metabolically 3H- or 13C-labeled (1-->3)-beta-D-glucan, SSG, from Sclerotinia sclerotiorum IFO 9395.

Metabolically labeled (1-->3)-beta-D-glucan (SSG) obtained from the culture filtrate of Sclerotinia sclerotiorum IFO 9395, with the radio (3H) or the stable isotope (13C) was prepared. The specific radioactivity of 3H-SSG was increased in accordance with the amount of D-[3H]glucose added, and was 15-20 kBq/mg SSG when 222 kBq/mL of D-[3H]glucose was added. Physicochemical analyses of 3H-SSG suggested a structural similarity between SSG and 3H-SSG. 13C NMR spectra of 13C-labeled SSG (13C-SSG) revealed that a strong signal of the 13C-nucleus was observed at the C-1 or C-2 position when D-[1-13C]glucose or D-[2-13C]glucose was used, respectively, suggesting that most of the glucose residues in SSG were directly taken up from the medium. In addition, part of the 13C-nucleus was incorporated into the SSG molecule at all carbon atoms after metabolic degradation and reconstruction of the glucose molecule. Analyses of the culture filtrate and the mycelium of the fungus suggested that part of the glucose was also metabolized to trehalose and mannitol.

Ascomycota↗

Identification and characterization of SET, a nuclear phosphoprotein encoded by the translocation break point in acute undifferentiated leukemia.

The translocation (6;9) in acute nonlymphocytic leukemia results in the formation of a dek-can fusion gene. In a case of acute undifferentiated leukemia, the oncogene can is fused to a different gene, named set, instead of dek and is assumed to be activated. Transcripts of set encode a putative SET protein with a predicted molecular mass of 32 kDa. We identified SET as a 39-kDa protein by immunoprecipitation with rabbit antiserum against each of three synthetic peptides predicted from the open reading frame of the set gene. We confirmed this identification of SET by protein sequencing. We also observed that SET is expressed ubiquitously in various human cell lines. SET is phosphorylated on serine residue(s) in cultured cells and is localized predominantly in nuclei. Although the function(s) of SET and SET-CAN is not known, we propose that SET plays a key role in the mechanism of leukemogenesis in acute undifferentiated leukemia, perhaps by activating CAN in nuclei and stimulating the transformation potential of SET-CAN. This proposed role would therefore be similar to the roles observed for BCR and DEK of the chimeric oncoproteins BCR-ABL and DEK-CAN in acute myeloid leukemia and acute nonlymphocytic leukemia, respectively.

Acute Disease↗

Prognostic significance of the number of positive lymph nodes in gastric carcinoma.

A total of 195 patients with node-positive gastric carcinoma who were treated by curative gastrectomy and lymphadenectomy were studied to evaluate the prognostic significance of the number of metastatic lymph nodes. Univariate analysis showed that the number and level of positive nodes, tumour size and depth of invasion, and type of gastrectomy were significantly related to patient survival. Multivariate analysis indicated that the number of positive nodes (up to six versus seven or more; relative risk 2.91), depth of invasion (three levels; relative risk 1.83) and histological type (well versus poorly differentiated; relative risk 0.63) were independently correlated with survival. The results indicate that the total number of positive nodes is the most significant prognostic factor in patients with node-positive gastric carcinoma.

Adenocarcinoma↗

Induction of bcl-2 gene expression by intercellular information from hemopoietic supportive stromal cells to DA-1 cells.

When interleukin-3 (IL-3) dependent DA-1 cells were cultured on hemopoietic supportive stromal cells (MS-5), DA-1 cells survived and proliferated in the absence of detectable IL-3. Although IL-3 was not produced by the MS-5 cells, their production of granulocyte-macrophage colony-stimulating factor (GM-CSF) was increased when they were co-cultured with DA-1 cells. This suggests that DA-1 cells transmit signals to stromal cells that enhance growth factor(s) production. Expression of bcl-2 by DA-1 cells was induced when they were co-cultured with MS-5 cells, suggesting that DA-1 cells express bcl-2 strongly in response to a signal produced by MS-5 cells. These data indicate the existence of a two-way interaction between DA-1 cells and hemopoietic supportive stromal cells.

Animals↗

S100 protein positive human breast carcinomas: an immunohistochemical study.

An immunohistochemical study for S100 protein was performed on 95 human breast carcinomas. S100 protein positive carcinoma cells were recognized in 54 cases (57%). The S100 protein positive and negative carcinomas were then compared in terms of stage, histologic type, nuclear grade, appearance of minute calcification, immunoreactivity for estrogen receptor (ER), tumor recurrent pattern, and prognosis. The S100 protein positive cases had a tendency to show a low nuclear grade (P < 0.01). They were also more often seen in the ER positive group. For further analysis of the nature of S100 protein positive carcinoma cells, immunoreactivity for neuron-specific enolase (NSE) and actin was investigated. The positive staining for NSE and actin was seen in 46 cases (48%) and 3 cases (3%), respectively. There was, however, no specific correlation among the S100 protein. NSE, or actin staining. The nature of S100 protein positive carcinoma cells still remains unclear. The S100 protein positive carcinomas, however, exhibit relatively better characteristics.

Actins↗

Growth pattern and prognosis of gastric cancer invading the subserosa.

Gastric cancer invading the subserosa with infiltrative growth was classified as part of the serosal invasion group and named prognostic serosal invasion positive [ps(+)] histologically. We analyzed clinicopathological features and prognosis of 166 Japanese patients with gastric cancer invading the subserosa, according to the growth pattern. All patients were treated in the Department of Surgery II, Kyushu University. Patients with infiltrative growth (ss gamma) were younger and their tumors were frequently undifferentiated compared to findings in those with noninfiltrative growth: expansive (ss alpha) and intermediate growth (ss beta). There was no difference in any other clinicopathological characteristic between those with infiltrative and noninfiltrative growth tumors. The 10-year survival rate was 66.7% for the infiltrative type and 54.2% for the noninfiltrative type, with no statistically significant difference. Lymph node metastasis, curative resection, and extended lymph node dissection, but not growth pattern, proved to be independent prognostic factors, as determined by multivariate analysis. Our findings suggest that it is not the growth pattern which affects the prognosis of ss cancers. Extensive lymph node dissection should be done when lymph node metastasis is present.

Adult↗

Immunohistochemical detection of CEA, CA19-9, and DF3 in esophageal carcinoma limited to the submucosal layer.

The immunohistochemical expression of CEA, CA19-9, and DF3 was studied in 20 normal epithelia, 11 cases of dysplasia, 32 squamous cell carcinomas restricted within the submucosal layer (SM carcinoma), and 42 advanced squamous cell carcinomas of the esophagus. The modes of expression were grouped into three patterns, i.e., negative, focal, and diffuse patterns. No diffuse expression of CEA, CA19-9, or DF3 was found in the normal squamous epithelium and dysplasia. In the carcinomas (32 SM carcinomas and 42 advanced carcinomas) the diffuse expression of CEA and CA19-9 was found in four lesions, and only one of the four lesions was an SM carcinoma, while the diffuse expression of DF3 was found in 16 of the 32 SM carcinomas and 25 of the 42 advanced carcinomas. These results indicated that the diffuse expression of these tumor-associated antigens were characteristic of tumor tissue in the esophagus, and particularly DF3 was diffusely expressed earlier than CEA or CA19-9. The expression of DF3 in the esophagus may, therefore, be a marker of the early stage of tumor growth.

Antigens, Neoplasm↗

Prognostic value of the histochemical expression of helix pomatia agglutinin in advanced colorectal cancer. A univariate and multivariate analysis.

PURPOSE: The expression of helix pomatia agglutinin in advanced colorectal cancer was evaluated in order to determine whether helix pomatia agglutinin could serve as an effective prognostic indicator. METHODS: Using the histochemical procedure, the expression of helix pomatia agglutinin was studied in 117 patients with primary colorectal cancer. Sixty of 117 patients who died of either recurrence or metastasis within two years (Group 1) after resection were compared with the other 57 patients who survived for five years or longer (Group 2). RESULTS: The helix pomatia agglutinin-positive expression was seen in 34 cases of Group 1 and in only 15 cases of Group 2 (P < 0.01). Lymph node metastasis, lymphatic invasion, venous invasion, mucin production, and helix pomatia agglutinin expression all had a significant correlation with the prognosis in the univariate analysis; however, only lymph node metastasis, venous invasion, and helix pomatia agglutinin expression were prognostic factors with a significant difference in the multivariate analysis. CONCLUSIONS: Histochemical expression of helix pomatia agglutinin will indeed aid in accurately predicting the prognosis of patients with advanced colorectal cancer.

Aged↗

A clinical analysis of multiple organ failure following elective surgery.

A retrospective analysis was made of 58 patients who unexpectedly developed multiple organ failure (MOF) following elective surgery, and the results were compared with those of 168 control patients who did not develop MOF. In 33 patients with liver cirrhosis, MOF was related to poor liver function, a low albumin level, excessive blood loss, many transfusions, and a high incidence of hypotension. MOF, rather than liver failure alone, was featured by postoperative bleeding and infection. In 15 patients with esophageal carcinoma, MOF was correlated with many transfusions, anastomotic leakage, and postoperative infection. In 10 patients who underwent surgery for an aortic aneurysm, poor renal function and extended anesthesia time were associated with MOF. These results indicate that to prevent MOF following elective surgery, it is important to: (1) Select patients for liver surgery according to their liver function, and minimize the risk of bleeding and infection, (2) avoid too many blood transfusions, and minimize the risk of leakage and infection in esophageal surgery, and (3) select patients for aortic surgery based on renal function and reduce the anesthesia time as much as possible.

Aortic Aneurysm↗

Type II crigler-Najjar syndrome with intrahepatic cholestasis.

A 58-year-old Japanese man was admitted to our hospital with appendicitis and marked unconjugated hyperbilirubinemia (11.6 mg/dl). The jaundice worsened following appendectomy, and the direct-reacting bilirubin increased, probably due to the ceftizoxime administered postoperatively. Bilirubin diglucuronide was the main component of the serum direct-reacting bilirubin (51%) in serum measured by liquid chromatography. Because the discontinuation of ceftizoxime did not markedly improve the jaundice, epomediol, 200 mg tid, was administered orally. There was a marked decrease of serum bilirubin with an increase in the delta bilirubin/(conjugated bilirubin + delta bilirubin) ratio. After improvement of jaundice to below the pre-surgical level (4.4 mg/dl), we analyzed the duodenal bile for bilirubin fractions; those showed a marked reduction in bilirubin diglucuronide and a marked increase in bilirubin monoglucuronide, which was consistent with type II Crigler-Najjar syndrome. A marked increase of bilirubin diglucuronide in serum of this patient during cholestasis suggests that bilirubin conjugation proceeds in this syndrome when excretion of conjugated bilirubin decreases.

Ceftizoxime↗

Chemical mediator release and surface marker expression of hepatic macrophages in rats with CCl4-induced liver cirrhosis.

The present study was performed to analyze possible functional alterations of hepatic macrophages (HM phi) in rats with carbon tetrachloride (CCl4)-induced liver cirrhosis. HM phi from rats injected with CCl4 for 13 weeks and cultured for 24 hours released less than normal amounts of prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) and very large amounts of interleukin-1 (IL-1). In rats injected with CCl4 for 9 weeks, only PGE2 production was reduced. Interleukin-2 receptor (IL-2R), Ia antigen and asialo GM1 antigen expressions on HM phi from both the 9- and 13-week groups were significantly decreased. IL-2R and Ia antigen expressions showed larger decreases in the 13-week group. Thus, it is concluded that HM phi derived from CCl4-induced cirrhotic livers show a functional alteration in the release of cytokines (except for IL-1) and a decrease in surface marker expression, as cirrhosis advances. These results should provide a basis for further investigation into the host-compromised status in the presence of liver cirrhosis.

Animals↗

Synthesis of recombinant baculoviruses expressing the outer capsid protein VP2 of five BTV serotypes and the induction of neutralizing antibodies to homologous and heterologous BTV serotypes.

DNA representing RNA segment L2 of 5 different bluetongue virus (BTV) serotypes (BTV-1, -2, -11, -13 and -17) corresponding to the gene that codes for the BTV neutralization antigen VP2, have been inserted individually into baculovirus transfer vectors in lieu of the 5' coding region of the polyhedrin gene of Autographa california nuclear polyhedrosis virus (AcNPV). After co-transfection of Spodoptera frugiperda cells with wild-type AcNPV DNA in the presence of the derived transfer vector DNAs, polyhedrin-negative recombinant baculoviruses were recovered. When S. frugiperda cells were infected with each of these viruses, protein was made similar in size and antigenic properties to the authentic BTV VP2 protein. To evaluate the biological activities of these proteins, antibodies were raised to them in guinea pigs. The neutralization capabilities of these antisera were tested against homologous and, for two of the higher titered sera, heterologous BTV serotypes. Each antiserum neutralized the infectivity of the homologous virus serotype. In heterologous virus challenges, the serum raised to the VP2 protein of BTV-13 also neutralized the infectivity of BTV-1, and to lesser extents BTV-3, -16, -8 and -9 (BTV-2, -10, -11, -15 were not tested). The serum raised to the VP2 of BTV-17 neutralized BTV-20 and -21, and to lesser extents BTV-4 and -8 (again, BTV-2, -10, -11, -15 were not tested).

Animals↗

High level of noncollagenous protein of spermatic vein in patients with varicocele.

Spermatic vein specimens were removed from 46 patients with varicocele who underwent high ligation of the left spermatic vein and 11 men with renal cancer who underwent radical nephrectomy. Semen analysis was performed preoperatively and after 3 months, and the contents of noncollagenous protein, collagen and elastin in the spermatic vein were determined. The noncollagenous protein contents in the spermatic vein were greater in patients with grades 2 and 3 varicocele than in those with renal cancer (p < 0.001) and grade 1 varicocele (p < 0.01), respectively. Similar results, to a lesser extent, were also obtained for the contents of collagen. The content of elastin in each group was identical. Noncollagenous protein content correlated inversely with sperm count and sperm motility in all varicocele groups, as did collagen content in patients with grades 2 and 3 varicocele. These results indicate that there is an association between a large amount of noncollagenous protein and collagen in the spermatic vein and deterioration of the spermiogram in patients with grades 2 and 3 varicocele.

Adolescent↗

Functional analysis of thymic B cells.

The expression of low- and high-affinity interleukin-5 receptors (IL-5Rs) on thymic B cells and reactivity of thymic B cells to IL-5 was investigated. Thymic B cells consist of two populations (CD5+ and CD5- B cells), as previously described. Three-color FACS analyses using anti-CD5, anti-IgK, and anti-IL-5R mAbs reveal that approximately 60% of both populations (CD5+ and CD5-) in the thymus possess IL-5R, detected by mAb H-7. In Scatchard plot analyses, IL-5Rs on thymic B cells are observed as low affinity receptors; the high-affinity IL-5R, which is known to be expressed on some IL-5-activated splenic B blasts or some IL-5-dependent cell line cells, is not clearly detected on thymic B cells. The reactivity of thymic B cells to IL-5 is found to be significantly lower than that of splenic B cells both in proliferative responses and LPS-induced IgM and IgA antibody responses. These findings are compatible with the expression of the low-affinity IL-5R on thymic B cells. The responsiveness of thymic B cells to either IL-6 or the combination of IL-4, IL-5 and IL-6 is also lower than that of splenic B cells. Furthermore, the thymic B cells are found to induce neonatal tolerance. Therefore, thymic B cells act as antigen-presenting cells in the negative selection of thymocytes, rather than as antibody-producing cells under the influence of foreign antigens and/or regulatory cytokines.

Animals↗

Proliferative activity as a prognostic factor in Borrmann type 4 gastric carcinoma.

Proliferative activities in 181 primary Borrmann type 4 gastric carcinomas were investigated using percentage labelling of proliferating cell nuclear antigen (PCNA) and an argyrophilic nucleolar organiser region (AgNOR) count. Tumours with a high proliferative activity often metastasised to lymph nodes (P < 0.01), and these patients had a lower survival rate (P < 0.05). A significant correlation was recognised between the PCNA labelling percentage and AgNOR count (r = 0.452, P < 0.001). Cox's regression analysis showed that PCNA labelling percentage is an independent prognostic factor. These results indicate that estimating proliferative activity may be useful in predicting lymph node metastasis and patients' prognosis in cases of Borrmann type 4 gastric carcinoma.

Adenocarcinoma↗

Different susceptibility to phospholipase A2 treatment of the fluorescence intensity changes in the vicinity of Cys-964 and Lys-501 in the alpha-chain of probe-labeled Na+,K(+)-ATPase.

Phospholipase A2 [EC 3.1.1.4] treatment of pig kidney Na+,K(+)-ATPase [EC 3.6.1.3] labeled with fluorescence probes at the alpha-chain reduced the extent of the fluorescence intensity change of an N-[p-(2-benzimidazolyl)phenyl]maleimide (BIPM) probe at Cys-964 to below one-third of the control level accompanying the accumulation of phosphoenzymes. However, it only induced a slight decrease in that of a fluorescence isothiocyanate (FITC) probe at Lys-501 with a large decrease in the rate of change. The addition of phosphatidylserine (PS) or phosphatidylinositol (PI) to the phospholipase-treated BIPM-FITC-labeled enzyme increased the rate of the FITC fluorescence change. Phospholipase treatment of the BIPM-enzyme greatly reduced the Na+,K(+)-ATPase activity. The addition of PS or PI to the treated enzyme induced reactivation. These data and others suggest that Cys-964 and Glu-953 (Rb+ protectable dicyclohexyl carbodiimide binding site) are located in the vicinity of the surface area of the enzyme where hydrocarbon chains of phospholipids are present, and conserved H-bonding amino acids, Thr-955 and Ser-962, are located rather near the center of a domain forming a cation binding route or cage with other hydrophobic transmembrane segments. These data may indicate that the interaction between the BIPM probe and the hydrocarbon chains of phospholipids changes in such a way as to sense the change in the binding state of various ligands accompanying the sequential appearance of reaction intermediates of the enzyme.

Acrylamides↗