Gel-to-sol transition of 13C-labeled (1-->3)-beta-D-glucan, 13C-SSG, assessed by 13C nuclear magnetic resonance (13C-NMR) spectroscopy.
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Adjuvants, Immunologic↗
Biomedical subjects
Y Adachi
Publications and source records attributed to Y Adachi.
Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome.
Gilbert's and Crigler-Najjar syndromes are characterised by unconjugated hyperbilirubinaemia due to complete and partial absence of bilirubin UDP-glucuronosyltransferase (UGT). Nucleotide sequences of the genes for bilirubin UGT were analysed in six patients with Gilbert's syndrome. All patients had a missense mutation caused by a single nucleotide substitution and the mutations were heterozygous. In addition, relatives of patients with Crigler-Najjar syndrome types I and II, and of those with Gilbert's syndrome were analysed. All ten relatives with mild hyperbilirubinaemia were heterozygotes with respect to each defective allele. These results suggest that Gilbert's syndrome is inherited as a dominant trait.
Adolescent↗
Positive selection of invariant V alpha 14+ T cells by non-major histocompatibility complex-encoded class I-like molecules expressed on bone marrow-derived cells.
V alpha 14+ T cells are a unique subset expressing an invariant T-cell antigen receptor alpha chain encoded by V alpha 14 and J alpha 281 gene fragments with a 1-nt N region. Most invariant V alpha 14+ T cells develop in extrathymic organs, independent of thymus, and expand at a high frequency in various mouse strains regardless of major histocompatibility complex (MHC) haplotype. In this paper, we show that the positive selection of invariant V alpha 14+ T cells requires a beta 2-microglobulin-associated MHC class I-like molecule not linked to the MHC on chromosome 17. This was determined by linkage analysis on DNA from recombinant mice generated by crossing a C57BL/6 mouse with a wild mouse, Mus musculus molossinus, that is negative for invariant V alpha 14 TCR expression. However, the peptide transporter TAP1 is not necessary for positive selection of invariant V alpha 14+ T cells, indicating the direct recognition of the MHC class I-like molecule without peptide by the invariant V alpha 14 TCR. Further, experiments with bone marrow-chimeric mice show that invariant V alpha 14+ T cells in the periphery are selected by bone marrow cells, suggesting a unique lineage of V alpha 14+ T cells differentiated through a selection process distinct from that of conventional alpha beta TCR+ T cells.
Animals↗
Macroscopically node-negative but histologically node-positive gastric carcinoma.
The features of macroscopically node-negative but histologically node-positive (N(-) n(+)) tumours were examined in 521 patients undergoing curative surgery for gastric carcinoma. Of 240 histologically node-positive tumours, 62 (26 per cent) were N(-) n(+). The 10-year survival rate of patients with N(-) n(+) tumour at 66 per cent was worse than that of those with histologically node-negative tumour (91 per cent) (P < 0.01) but better than that of patients with macroscopically and histologically node-positive tumour (40 per cent) (P < 0.01). N(-) n(+) tumour was characterized by size less than 5 cm (47 per cent), invasion not beyond the muscularis propria (53 per cent), lymph node metastasis limited to group 1 nodes (76 per cent), number of positive nodes fewer than seven (90 per cent) and disease of stage II (52 per cent). The survival of patients with N(-) n(+) tumour was determined by the number of positive nodes and stage of disease. N(-) n(+) tumours are associated with a better outcome, owing to less progressive disease, and the number of positive nodes is a prognostic indicator.
Adenocarcinoma↗
Activation of thymic B cells by signals of CD40 molecules plus interleukin-10.
We have previously found that thymic B cells, particularly thymic CD5+ B cells, show low responsiveness to the usual B cell stimulants such as lipopolysaccharide or anti-IgM plus interleukin (IL)-4, although they proliferate and produce antibodies after direct interaction with major histocompatibility complex class II-restricted T blasts. These findings raise the possibility that a CD40-CD40 ligand (L) interaction is involved in the activation of thymic B cells. In the present study, we therefore examine this possibility using CD40L-transfected Chinese hamster ovary (CHO) cells or anti-CD40 monoclonal antibody (mAb). When B cells in the spleen and peritoneal cavity were stimulated, they proliferated and produced immunoglobulin (Ig) in the presence of CD40L-CHO cells or anti-CD40 mAb alone. However, another signal delivered by IL-10 in addition to CD40L-CHO cells or anti-CD40 mAb was found to be necessary for thymic B cells to proliferate and secrete Ig. Other interleukins acting on B cells, such as IL-4, IL-5, and IL-6, had no effect on the activation of thymic B cells, which thus have unique characteristics not found in peripheral B cells. This report discusses the physiological significance of IL-10- and CD40-driven signals in the activation of thymic B cells.
Animals↗
Expression of matrix metalloproteinase matrilysin (MMP-7) was induced by activated Ki-ras via AP-1 activation in SW1417 colon cancer cells.
The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metalloproteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.
Choline O-Acetyltransferase↗
Nuclear DNA content and nucleolar organizer regions in colorectal cancer.
The prognostic value of nuclear DNA content and argyrophilic nucleolar organizer regions (AgNOR) is still controversial in colorectal cancer. Sixty patients with colorectal cancer were studied by flow cytometric DNA analysis and AgNOR measurement, and their prognostic significance was tested. DNA index was closely linked to depth of invasion and lymph node metastasis, while AgNOR count did not correlate with such parameters. The survival curve was strongly influenced by depth of invasion, lymph node metastasis, and Dukes' stage but was not affected by DNA ploidy and AgNOR count. These results indicate that neither DNA ploidy nor AgNOR count correlates with survival of patients, although DNA ploidy is linked to progression of colorectal cancer.
Aged↗
Participation of hepatic macrophages and plasma factors in endotoxin-induced liver injury.
The present study was designed to investigate the mechanism responsible for endotoxin-induced liver injury, based on the working hypothesis that hepatic macrophages activated by endotoxin play a key role in the development of this injury. At both the protein and the transcription levels, the intravenous administration of endotoxin was shown to have increased the capacity of hepatic macrophages to produce chemical mediators. To inhibit the function of hepatic macrophages, gadolinium chloride (GdCl3), a specific inhibitor of resident hepatic macrophages, was preadministered to rats before endotoxin injection. GdCl3 reduced the elevated glutamic oxaloacetic transamiase and lactate dehydrogenase serum levels produced by endotoxin treatment, suppressed the increased mRNA expression of tumor necrosis factor (TNF-alpha) produced in liver nonparenchymal cells by endotoxin, and then improved the survival rate of lipopolysaccharide-injected rats. These results indicated that hepatic macrophages played a crucial role in liver injury and that TNF-alpha was the most likely factor implicated in the development of endotoxin-induced liver injury. Furthermore, we found that liver injury did not progress during perfusion of endotoxin-pretreated extirpated liver with lactate Ringer's solution, whereas liver perfused with plasma developed remarkable hepatic impairment, which was inhibited almost completely by GdCl3-pretreatment; moreover, addition of heparin to the perfusate also prevented this deterioration. Thus, the present study showed that the activation of hepatic macrophages and factors in the plasma were two essential elements in the occurrence and development of endotoxin-induced liver injury.
Animals↗
Long-term effects of intrasplenically transplanted adult hepatocytes and fetal liver in hyperbilirubinemic Gunn rats.
We performed adult hepatocyte transplantation (HCTx) and fetal liver transplantation (FLTx) into the spleens of hyperbilirubinemic Gunn rats in congenic combination and we compared the long-term effects of these procedures for as long as 12 months. Proliferative activity of intrasplenic hepatocytes was evaluated using antiproliferating cell nuclear antigen (PCNA) immunohistochemical staining. The serum total bilirubin levels (T. Bil) significantly decreased from 7.16 +/- 0.25 mg/dl to 4.38 +/- 0.60 mg/dl 2 months after HCTx and gradually decreased thereafter until 12 months after transplantation (3.23 +/- 0.37 mg/dl, P < 0.05 vs preoperative value). The T. Bil change after FLTx was similar to that of HCTx: 7.22 +/- 0.24 mg/dl before FLTx, and 4.92 +/- 0.24 and 3.06 +/- 0.47 mg/dl, 2 and 12 months after FLTx (P < 0.05), respectively. Bilirubin glucuronides, which were not detectable in the bile from untreated Gunn rats, appeared in considerable amounts 4 months after HCTx and FLTx (27.5% and 36.0% of total bile, respectively). PCNA labeling indices of intrasplenic hepatocytes (4.9% +/- 0.9% and 3.7% +/- 0.7%, 6 months after HCTx and FLTx, respectively) were slightly higher than those of normal hepatocytes (1.0% +/- 0.1%) in the host liver. In conclusion, both adult and fetal rat hepatocytes transplanted into the spleen in congenic combination functioned for at least a year in terms of bilirubin glucuronidation. The spleen is considered to be one of the optimal grafting sites for hepatocytes, with nearly lifelong significant function and proliferative activity.
Animals↗
Antibiotics prevent liver injury in rats following long-term exposure to ethanol.
BACKGROUND/AIMS: Kupffer's cells participate in alcohol-induced liver injury, and endotoxemia is observed in human alcoholics and in a rat model. This study evaluated the effect of reducing bacterial endotoxin production by intestinal sterilization on alcohol-induced liver injury. METHODS: Male Wistar rats were exposed to ethanol continuously for up to 3 weeks via intragastric feeding. The gut was sterilized with polymyxin B and neomycin. RESULTS: Fecal culture of stool samples from ethanol-fed rats treated with antibiotics showed virtually no growth of gram-negative bacteria. Endotoxin levels of 80-90 pg/mL in plasma of ethanol-fed rats were reduced to < 25 pg/mL by antibiotics. Antibiotic treatment also completely prevented elevated aspartate aminotransferase levels and significantly reduced the average hepatic pathological score in rats exposed to ethanol. Oxygen tension on the surface of the liver measured in vivo was decreased significantly from control values of 48 +/- 1 to 39 +/- 1 mumol/L in ethanol-treated rats. This hypoxia was prevented by treatment with antibiotics. Moreover, the increase in rates of ethanol elimination due to long-term ethanol treatment was prevented by antibiotic treatment. CONCLUSIONS: Intestinal sterilization prevented alcohol-induced liver injury in the rat, supporting the idea that hypermetabolism and consequent hypoxia caused by activation of Kupffer's cells by endotoxin is involved in the mechanism.
Animals↗
Myasthenia gravis, acute transverse myelitis, and HTLV-I.
We present the unusual case of a 49-year-old female carrier of HTLV-I with myasthenia gravis who presented with acute transverse myelitis. Laboratory data suggested a recent infection with varicella zoster virus and demyelination by an autoimmune process in the central nervous system. Adult T-cell leukemia-like cells were observed in the cerebrospinal fluid. T-cell-mediated immune responses modulated by HTLV-I infection may be involved in the pathogenesis of myasthenia gravis and acute transverse myelitis in this case.
Acute Disease↗
Effectiveness of extended lymphadenectomy in noncurative gastrectomy.
PURPOSE: We examined the efficacy of extended lymph node dissection for prolonging survival in macroscopically or histologically proven incurable gastric cancer. PATIENTS AND METHODS: We analyzed clinico-pathologic data on 119 patients with serosally invasive gastric cancer who underwent noncurative gastrectomy, with respect to the relation between the extent of lymphadenectomy and survival benefit. RESULTS: The 5-year survival rate was significantly higher among patients treated with extensive lymphadenectomy (R2/3) compared to simple gastrectomy (R1). Extensive lymphadenectomy significantly prolonged survival time even after noncurative gastrectomy in cases where there was no evidence of hepatic metastasis, peritoneal seeding, or extensive nodal metastasis beyond the tertiary lymph node, and regardless of the extent of direct invasion to adjacent organs. CONCLUSIONS: Gastrectomy combined with extended lymphadenectomy and/or resection of adjacent organs is recommended for gastric cancer patients without distant metastasis, even when the operation is histologically noncurative. Gastrectomy and perioperative intensive chemotherapy are called for when patients have distant metastasis.
Adenocarcinoma↗
A simple classification of lymph node level in gastric carcinoma.
BACKGROUND: Because insufficient lymph node examination can cause erroneous listing of earlier-nodal-stage gastric carcinoma (stage migration phenomenon), surgical results must be evaluated based on a highly accurate examination of the dissected lymph nodes. To establish a simple and useful classification of lymph node level, we analyzed the frequency and distribution of lymph node metastasis by using curatively treated node-positive gastric carcinoma. PATIENTS AND METHODS: Various clinicopathologic data were analyzed with reference to the degree of lymph node metastasis by using 240 patients with curatively resected node-positive gastric carcinoma. The cases were divided into the following three groups: 142 with positive level I (perigastric) nodes, 71 with positive level II (intermediate) nodes, and 27 with positive level III (distant) nodes, irrespective of the location of tumors. RESULTS: The level of lymph node metastasis clearly correlated with the survival of patients, with the 5-year survival rates for level I, II, and III cases being 67%, 35%, and 26%, respectively (P < 0.01). The degree of lymph node metastasis was determined by the number of positive nodes (P < 0.01), the depth of invasion (P < 0.01), the size of tumors (P < 0.01), and the location of tumors (P < 0.05). CONCLUSION: This simple classification of lymph node level (level I, II, and III) is useful for the evaluation and prediction of surgical results in gastric carcinoma.
Arteries↗
Effect of lymph node dissection on the prognosis in patients with node-negative early gastric cancer.
BACKGROUND: Our objective was to evaluate the long-term benefit of R2/3 lymph node dissection compared with that of R1, even in node-negative cases. METHODS: We analyzed clinicopathologic data on 373 surgically treated patients with early gastric cancer and without microscopic nodal involvement. RESULTS: Five- and 10-year survival rates for patients treated with R2/3 gastrectomy were 97.3% and 95.4%, respectively. These values were significantly higher than the 90.1% and 81.1% noted for R1 gastrectomy (p < 0.01). Although no difference was found in morbidity and mortality, the incidence of death from a recurrence of the gastric cancer was significantly higher in patients treated with R1 gastrectomy than those with R2/3. Multivariate analysis with the Cox's proportional hazard model revealed patients' age and R2/3 gastrectomy to be independent prognostic factors in patients with node-negative early gastric cancer. CONCLUSIONS: These data show that prophylactic lymph node dissection can potentially prolong the survival time of patients with node-negative early gastric cancer by preventing a recurrence of the gastric cancer.
Age Factors↗
Effect of bone marrow transplantation on antiphospholipid antibody syndrome in murine lupus mice.
The (NZW x BXSB)F1 (W/BF1) mouse is known to be an animal model of systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP). These mice produce not only anti-DNA antibodies but also anti-platelet antibodies, resulting in decreased platelet counts. They show a high level of proteinuria, increased white blood cell (WBC) counts, hypertension, and myocardial infarction due to the high levels of anti-cardiolipin antibodies. When W/BF1 mice (4-5 months) were lethally irradiated and then reconstituted with T cell-depleted bone marrow cells of normal BALB/c mice (8 weeks), 60% of the mice survived more than one year. The WBC and platelet counts in the mice were normalized, and the levels of anti-DNA and anti-platelet antibodies decreased. The renal dysfunction was also ameliorated as indicated by a lower level of proteinuria, lower levels of serum creatinine (S-CRTN) and blood urea nitrogen (BUN), and by improved histology. The blood pressure (BP) of the treated W/BF1 mice decreased due to the improved renal functions. In contrast to the non-treated W/BF1 mice which died of myocardial infarction or renal failure by the age of 7 months, the treated W/BF1 mice showed no evidence of myocardial infarction even one year after BMT. This was due to the lower cardiolipin levels.
Animals↗
Cytotoxic effects of irradiation and deoxyguanosine on fetal thymus.
Effects of irradiation and deoxyguanosine on the fetal thymus were examined both in vitro and in vivo. Fetal thymi (gestation day 15) of C57BL/6 mice that had been irradiated (0-25 Gy) or treated with various doses of deoxyguanosine (dGuo) were engrafted under the renal capsules of BALB/c nu/nu mice, and the differentiation of T cells was investigated in the engrafted thymi or spleens of these mice. After in vitro treatment of fetal thymi with 1.35 mM dGuo (which was previously reported to be an optimal dose), T cell precursors still remained in some cultures, whereas 1.80 mM dGuo was highly cytotoxic not only to T cell precursors but also to thymic epithelial cells. In contrast, 25 Gy irradiation totally eliminated the T cell precursors from the fetal thymi, though the capacity of epithelial cells to induce T cell differentiation was retained. Although irradiated thymi had the capacity to induce T cell differentiation when assayed in an in vitro organ culture system, long-term observation of thymi engrafted into BALB/c nu/nu mice revealed that, if they had been irradiated (9.5 Gy or 25 Gy), the thymi became scarred by 12 wks after their transplantation. Furthermore, the expression of cell interaction molecules such as ICAM-1 and MHC class II on the thymus stromal cells decreased after irradiation. The interaction molecules decreased 3 wks after 25 Gy irradiation and 7 wks after 9.5 Gy irradiation. The alteration in T cell subsets in the thymus (decreases in both double- and single- positive cells and an increase in double-negative cells) correlated with the decreases in the interaction molecules. This indicates that irradiation (even 9.5 Gy) impairs the T cell-induction capacity of the thymus stromal cells, resulting in an alteration of the T cell subsets followed by a change in the T cell counts in the thymus. Therefore, the long-term effects of irradiation of the thymus should be considered in cases of fetal thymus grafts or total body irradiation before bone marrow transplantation, particularly in the newborn.
Animals↗
Malignant lymphoma of the rectum treated preoperatively with hyperthermia and radiation.
A 58-year-old Japanese woman with primary malignant lymphoma of the rectum was treated preoperatively with radiation and intraluminal hyperthermia, after which abdominoperineal rectal amputation (Miles' operation) was done. The rectal tumor disappeared and there were no lymphoma cells in the resected specimens. The postoperative course was smooth and she is being followed in the outpatient department. At this writing, five years after the surgery, she remains well.
Combined Modality Therapy↗
Cytophotometric study of nuclear DNA content in scirrhous gastric carcinoma.
We made a cytophotometric DNA analysis using 21 scirrhous gastric carcinomas (SGC), and compared the results with those of 12 undifferentiated type early gastric carcinomas (EGC) located in the gastric body. Nuclear DNA content of tumor cells was measured in the mucosa of SGC (SGCm), serosa of SGC (SGCs) and mucosa of EGC (EGCm). DNA distribution pattern was high ploid in 18 SGCm (86%), 16 SGCs (71%) and 4 EGCm (33%). Mean DNA content was 4.02c in SGCm, 3.91c in SGCs and 3.26c in EGCm. Percentage of tumor cells with a DNA content over 3c was 77.4% in SGCm, 69.1% in SGCs and 49.5% in EGCm. Statistically significant differences in these 3 factors were present between SGCm and EGCm, but absent between SGCm and SGCs. Furthermore, DNA distribution pattern was not different between the mucosa and serosa in 19 SGC (90%). The results suggest that most scirrhous gastric carcinomas are high ploid in origin and do not change their biologic behaviour throughout the tumor progression.
Adenocarcinoma, Scirrhous↗