Age-time patterns for cancer and noncancer excess risks in the atomic bomb survivors.
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Age Distribution↗
Biomedical subjects
Y Shimizu
Publications and source records attributed to Y Shimizu.
Distribution of apoptosis-like cells in sea urchin early embryogenesis.
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Animals↗
Regeneration of the junctional epithelium and connective tissue after transplantation of detergent-processed allo-teeth.
The authors have developed a new artificial dental implant and evaluated it in a dog model in terms of its potential to produce: I) regeneration of junctional epithelium; II) regeneration and attachment of connective tissue. The implants were constructed from allo-teeth. We removed the cell components from the periodontal ligaments of these teeth with a detergent (1% TritonX-100); the remaining acellular periodontal ligament acted as an extracellular matrix upon which regeneration and attachment could proceed. We placed 10 of these implants in the just-extracted sites of three beagle dogs. We observed regeneration of both junctional epithelium and connective tissue at all implant sites after 3 months. The connective tissue was attached in all cases. Use of the acellular periodontal ligament as an extracellular matrix may facilitate regeneration of host periodontal ligament tissue, thus contributing to recovery of host immunological defense and long-term oral function.
Animals↗
[Acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy treated with highly active anti-retroviral therapy].
We reported a patient with acquired immunodeficiency syndrome (AIDS)-associated progressive multifocal leukoencephalopathy (AIDS-PML), whose condition improved after highly active anti-retroviral therapy (HAART). A 70-year-old man was admitted to our hospital because of worsening left hemiplegia and disturbance of consciousness. During the past 30 years, he frequently traveled to the United States and southeast Asia. On neurological examination, he was somnolent and left hemiplegia with severe rigospasticity was present. The deep tendon reflexes showed hyper-reflexes with extensor plantar responses. Laboratory studies showed pancytopenia and positive HIV-1 antibodies. The CD4 cell count was 38/mm3 and his HIV viral RNA load in the blood was 9,500 copies/ml. T2-weighted magnetic resonance imaging (MRI) of the brain revealed asymmetrical high intensity white matter lesions in the right fronto-parietal, and left frontal regions and in the cerebellar hemisphere. The cerebrospinal fluid (CSF) protein elevated to 91 mg/dl with a normal cell count. The diagnosis of PML was confirmed by the detection of JC virus DNA in the CSF using a nested polymerase chain reaction assay. Three weeks after starting HAART with zidovudine, lamivudine, and indinavir, he was able to respond to simple commands. Two months later, the HIV viral RNA load decreased to less than 400 copies/mm3, and no JC virus DNA was detected in the CSF, with an increase of the CD4 cell count to 285/mm3 in the blood. A follow-up MRI of the brain showed a reduction in the cerebellar and cerebral white matter lesions. The recovering immune function by decreasing of the HIV load after HAART might suppress JC virus replication. It was suggested that HAART would become a beneficial treatment for patients with AIDS-PML.
Acquired Immunodeficiency Syndrome↗
Nutritional therapy of chronic hepatitis by whey protein (non-heated).
In an open study the clinical efficacy of milk serum (whey) protein (Immunocal; cysteine content: 7.6-fold higher than that of casein) isolated from fresh milk and purified without heating was evaluated in 25 patients with chronic hepatitis B or C. Immunocal (12 g as protein) food (mousse) was given twice a day, in the morning and evening, for 12 weeks (test period). Casein (12 g as protein) food (mousse) was similarly given for two weeks prior to the start of the supplement with Immunocal food (induction period) and for four weeks after the end of the supplement with Immunocal food (follow-up period). Serum alanine aminotransferase (ALT) activity was reduced, and plasma glutathione (GSH) levels increased in six and five of eight patients with chronic hepatitis B, respectively, 12 weeks after the start of the supplement with Immunocal food. Serum lipid peroxide levels significantly decreased, and interleukin (IL)-2 levels and natural killer (NK) activity significantly increased. However, there were no significant Immunocal-related changes in 17 patients with chronic hepatitis C. These findings suggest that the long-term supplement with Immunocal alone may be effective for improving liver dysfunctions in patients with chronic hepatitis B.
Adult↗
Underdeveloped uterus and reduced estrogen responsiveness in mice with disruption of the estrogen-responsive finger protein gene, which is a direct target of estrogen receptor alpha.
The biological roles of estrogen-responsive finger protein (efp) in vivo were evaluated in mice carrying a loss-of-function mutation in efp by gene-targeted mutagenesis. Although efp homozygous mice were viable and fertile in both sexes, the uterus that expressed abundant estrogen receptor alpha exhibited significant underdevelopment. When the ovariectomized homozygotes were subjected to 17beta-estradiol treatment, they showed remarkably attenuated responses to estrogen, as exemplified by decreased interstitial water imbibition and retarded endometrial cell increase, at least, attributable to the lower ratio of G1 to S-phase progression in epithelial cells. These results suggest that efp is essential for the normal estrogen-induced cell proliferation and uterine swelling as one of the direct targets of estrogen receptor alpha.
Animals↗
Resistance to pseudorabies virus infection in transgenic mice expressing the chimeric transgene that represses the immediate-early gene transcription.
A chimeric gene encoding a fusion protein consisting of the DNA-binding domain of the immediate-early (IE) protein of pseudorabies virus (PRV) and a tail-truncated VP16 of herpes simplex virus 1, lacking the transcription activation domain, has been shown to repress transcription of the PRV IE gene, resulting in the inhibition of PRV growth in vitro. To assess the antiviral potential of the fusion protein in vivo, transgenic mice containing the chimeric gene under the control of the virus- and interferon-inducible Mx 1 promoter were generated. A transgenic mouse line showed marked resistance to PRV infection when the mice were challenged intranasally with PRV. Inhibition of PRV replication was also observed in monolayers of embryonic cells prepared from the transgenic mice. In the cells infected with PRV, transcription of the PRV IE gene was repressed. The present results indicate that the chimeric gene is able to exert a significant antiviral effect against PRV infection in vivo.
Animals↗
Different frequencies of p53 codon-249 hot-spot mutations in hepatocellular carcinomas in Jiang-su province of China.
Environmental carcinogens often induce specific mutations in the p53 gene, apparent in tumors. The relation between aflatoxin B1 (AFB1 )-related hepatocellular carcinomas (HCCs) and hot spot at codon 249 of the p53 gene has received a great deal of attention, but its significance is still controversial. To clarify this problem, we analyzed the p53-mutational status of HCCs in Jiang-su province in China, where AFB1 contamination of the staple food significantly differs between the northern and southern parts (prominent only in the latter), while other conditions are quite similar. Background liver status and mutations in exons 5 to 8 of p53 in a total of 31 cases were divided approximately equally between the 2 areas. In all, 15 tumors exhibited a total of 17 mutations in the p53 gene; 9 cases from the southern part of the province had the hot-spot mutation at codon 249 (9/16, 56%), but only one case from the northern part (1/15, 8%). These results suggest that AFB1 contamination may correlate with codon-249 mutations in HCC.
Adult↗
Regulation by interleukin-1beta of gene expression of bradykinin B1 receptor in MH-S murine alveolar macrophage cell line.
The effects of recombinant murine interleukin (IL)-1beta on gene expression of murine bradykinin B1 receptor (BDKRB1) in MH-S murine alveolar macrophage cell line were evaluated. BDKRB1 mRNA expression in MH-S cells was increased by IL-1beta (1, 3, and 10 ng/ml) in a time-dependent manner, peaking at 3-4 h by 100-1000 fold. IL-1beta (5 ng/ml, 24h) also induced significant binding to [3H]-des-Arg10-kallidin with a dissociation constant (Kd) of 2.95 nM and a maximal binding density (Bmax) of 670 sites/cell. Des-Arg10-kallidin (10 microM), a BDKRB1 agonist, increased intracellular calcium ion ([Ca2+]i) in IL-1beta (5 ng/ml, 24 h)-exposed cells, an increase not observed in the cells not exposed to IL-1beta. A significant increase of tumor necrosis factor (TNF)-alpha secretion occurred in the IL-1beta (5 ng/ml, 24 h)-exposed cells following addition of des-Arg10-kallidin (the IL-1beta-exposed group: 57. 8 +/- 13.7 vs. the vehicle-exposed group: 16.7 +/- 4.3 pg/ml, p < 0.05 after a 100 nM des-Arg10-kallidin for 8 h), with an optimal effect at 3-100 nM. These data suggest that IL-1beta may up-regulate BDKRB1-mediated functions of alveolar macrophages via an induction of BDKRB1 gene expression.
Animals↗
Influence of antigenic forms and adjuvants on the IgG subclass antibody response to Aujeszky's disease virus in mice.
The influence of antigenic forms of Aujeszky's disease virus (ADV) and adjuvant types on the production of IgG subclass antibodies in mice was investigated. Particulate antigen, inactivated ADV, alone induced IgG1 and lower IgG2a antibody production, while the antigen adsorbed onto aluminum phosphate gel (alum) enhanced IgG1 antibody production but suppressed IgG2a antibody production as well as solubilized ADV antigen adsorbed onto alum. QS21 saponin purified from Quillaja saponaria promoted the production of IgG1 and IgG2a antibodies in a large extent against the both particulate and soluble antigens, while this saponin has strong hemolytic activity. Lablaboside F saponin isolated from Dolichos lablab without hemolytic activity, also induced the production of large IgG1 and little IgG2a antibody against both antigens. Oil-based adjuvant, ISA70 of water-in-oil type and ISA25 of oil-in-water type, increased IgG1 and IgG2a antibodies against the both soluble and particulate antigens, whereas a combination of ISA25 and soluble antigen reduced IgG2a antibody response. These results indicate that IgG1 antibody production was not suppressed by a combination of antigenic form and adjuvant type, however, IgG2a antibody production was influenced.
Adjuvants, Immunologic↗
Cloning of a novel gene specifically expressed in clonal mouse chondroprogenitor-like EC cells, ATDC5.
We cloned a full-length cDNA encoding a novel mouse protein, A-C2, by differential display method using mouse embryonic fibroblast C3H10T1/2 cells and mouse chondroprogenitor-like EC cells, ATDC5. The deduced amino acid sequence of A-C2 consisted of 106 amino acids with no significant homology to the sequences previously reported. Northern blot analysis showed two major bands of 2.1 and 1.8 kb sizes. Expression of A-C2 mRNA was exclusive to ATDC5 cells at their undifferentiated stage. None of ATDC5 cells at their differentiated stage and adult mice tissues examined expressed A-C2 gene.
Amino Acid Sequence↗
High affinity very late antigen-4 subsets expressed on T cells are mandatory for spontaneous adhesion strengthening but not for rolling on VCAM-1 in shear flow.
The very late Ag-4 (VLA-4) integrin supports both rolling and firm adhesion of leukocytes on VCAM-1 under shear flow. The molecular basis for the unique ability of a single adhesion molecule to mediate these versatile adhesive processes was investigated. VLA-4 occurs in multiple activation states, with different affinities to ligand. In this study we tested how these states regulate VLA-4 adhesiveness under shear flow in Jurkat T cells and PBL. VLA-4 on nonstimulated Jurkat cells supported rolling and spontaneous arrest on VCAM-1, whereas a Jurkat activation mutant with reduced VLA-4 affinity failed to spontaneously arrest after tethering to or during rolling on VCAM-1. The contribution of VLA-4 affinity for ligand to rolling and spontaneous arrests on immobilized VCAM-1 was dissected using soluble VLA-4 ligands, which selectively block high affinity states. VLA-4 saturation with ligand completely blocked spontaneous adhesion strengthening post-tethering to VCAM-1, but did not impair rolling on the endothelial ligand. High affinity VLA-4 was found to comprise a small subset of VLA-4 on resting Jurkat cells and PBL. This subset is essential for firm adhesion but not for tethering or rolling adhesions on VCAM-1. Interestingly, low and high affinity VLA-4 states were found to mediate similar initial tethering to ligand. High affinity VLA-4, constitutively expressed on circulating T cells, may control their early adhesion strengthening on VCAM-1-expressing endothelium before exposure to vascular chemokines and activation of additional integrins.
Cell Adhesion↗
Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection.
BACKGROUND AND OBJECTIVES: Free cancer cells in the abdominal cavity exfoliated from a tumor are considered to be responsible for peritoneal dissemination, the most frequent pattern of failure in gastric carcinoma patients treated with curative surgery. METHODS: A prospective survival analysis was performed with 91 gastric carcinoma patients treated by potentially curative resection. Cytology was performed for all the patients. The method of Kaplan and Meier was used to construct curves with diagnosis of peritoneal dissemination and cancer death as the end points. Multivariate analysis by Cox's proportional hazards model was performed to identify independent prognostic factors of significance. RESULTS: Patients with a positive cytology result were confirmed to have a greater risk for recurrence in the pattern of peritoneal carcinomatosis and hence a significantly inferior prognosis. Positive cytology was the only significant independent prognostic factor among the curatively resected patients with advanced gastric carcinoma. CONCLUSIONS: Peritoneal lavage cytology should be employed for all advanced cancer undergoing potentially curative resection for added accuracy in the stage classification. The results should also reflect the eligibility of the patients for future clinical trials involving perioperative intraperitoneal chemotherapy.
Ascitic Fluid↗
In vivo evaluation of a novel alginate dressing.
Alginate dressings are currently used in the management of epidermal and dermal wounds, and provide a moist environment that leads to rapid granulation and reepithelialization. However, a cytotoxic effect on proliferation of fibroblasts and residual material with inflammation in healing wounds have been reported recently. We have developed a new alginate dressing (AGA-100), which does not have an inhibitory effect on proliferation of fibroblasts. The purpose of this study was to evaluate the new alginate dressing with respect to wound healing in full- and partial-thickness pig wounds and with respect to biodegradation following implantation into rabbit muscle. Kaltostat and Sorbsan, both well-established commercial dressings, were used as control. The closure rate of full-thickness wounds treated with AGA-100 was significantly higher on day 15 compared with that with Kaltostat and Sorbsan. Reepithelialization rate of partial-thickness wounds treated with Sorbsan was statistically significantly lower on day 3 than those with the other two dressings. As to dressing debris remained in the healing wound, a large amount of foreign debris was noted in all the full-thickness wounds treated with Kaltostat or Sorbsan, while only about one-third of wounds treated with AGA-100 showed a little dressing debris. AGA-100 implanted into the muscle of rabbits was bioresorbed completely within 3 months. Therefore, dressing residue in AGA-100-treated full-thickness wounds might be fully absorbed in a few months. In conclusion, it is shown that our newly developed AGA-100 possesses superior properties compared with typical alginate dressings.
Alginates↗
Functional B-cell response in intrahepatic lymphoid follicles in chronic hepatitis C.
Intrahepatic lymphoid follicle (ILF) formation is one of the most characteristic and commonly observed histological features in patients with chronic hepatitis C. However, little is known regarding whether follicles in the liver belong to functional lymphoid tissues, where B cells are activated, differentiated, and proliferated, or if the lymphocytes are merely infiltrated after recruitment from the secondary lymphoid organs. To ascertain this possibility, we examined the expression of markers for B-cell activation, differentiation, and proliferation in ILFs in patients with chronic hepatitis C using surgically resected specimens, and compared them with specimens of perihepatic lymph nodes by an immunohistochemical technique. Germinal center (GC) formation in the ILFs was frequently found in HCV-positive cases. The distribution of immunoglobulin M (IgM)-, IgD-, and IgG-positive cells and the expression patterns of Ki-67, CD23, or bcl-2 and bcl-6 gene products in the follicles with GC formation in the liver of patients with chronic hepatitis C were similar to those of lymph nodes, indicating that B cells are activated, proliferated, and differentiated in the ILFs with GC formation in patients with chronic hepatitis C. Oligoclonal expansion of B cells in the livers with ILFs was confirmed by an analysis of immunoglobulin heavy chain (IgH) gene rearrangement determined by polymerase chain reaction (PCR). These data strongly suggest that ILFs with GC formation, which are frequently found in patients with chronic hepatitis C, may functionally be the same as those found in lymph nodes with respect to B-cell expansion and maturation.
Adult↗
Comparison of pathogenic factors expressed by group A Streptococci isolated from patients with streptococcal toxic shock syndrome and scarlet fever.
Streptococcal toxic shock syndrome (STSS) is an illness with high mortality. To obtain clues to understanding the pathogenesis of STSS, we investigated the expression of several pathogenic factors in ten group A streptococcus (GAS) isolates from ten patients with STSS in Japan, in comparison with ten GAS isolates from children with scarlet fever. The ten scarlet fever-derived GAS isolates were equally low in lethality and anti-phagocytic activity in mice and in the production of streptolysin O (SLO), and equally high in production of superantigenic exotoxins (SAGTs) and cysteine proteinase. By comparison, the ten STSS-derived GAS isolates were heterogeneous in the expression of the above pathogenic factors, which ranged from low to high values. Most of the ten STSS-derived isolates were higher in lethality and anti-phagocytic activity and production of SLO, and lower in the production of SAGTs and cysteine proteinase than the ten scarlet fever-derived isolates. The results suggest that the lethality and anti-phagocytic activity examined in mice and SLO may be involved mainly in the development of most of the ten STSS cases.
Animals↗
The effect of vaginal delivery on the pelvic floor.
This study was undertaken to determine the effects of vaginal deliveries on anorectal function, and to analyze the possible clinical, physiological, and radiological risk factors predisposing to damage of the pelvic floor musculature. We studied 25 consecutive women with a mean age of 32 years old, 3 months after vaginal delivery, 17 of whom were primiparae and 8, multiparae. The symptoms of anal incontinence were assessed, and anorectal manometry, rectal sensation, and radiological measurements of the anorectal angle and pelvic floor position at rest, on squeezing, and on straining were performed. As a control, six nulliparous women underwent the same examinations. Pelvic floor descent in both the primiparae and multiparae was significantly greater at rest and on squeezing than that in the nulliparous women. Furthermore, pelvic floor descent on straining was greater in the multiparae than in the nulliparous women (P = 0.028). An analysis of the 17 primiparae showed that prolonged duration of the second stage of labor and third-degree perineal tears were important factors predisposing to pelvic floor descent. In fact, 3 of the 17 primiparae (17%) had anal incontinence. These findings indicate that vaginal delivery may cause pelvic floor descent, an obtuse anorectal angle, and bowel symptoms.
Adult↗
Case of intraductal papillary mucinous tumor (noninvasive adenocarcinoma) of the pancreas resected 27 years after onset.
A case of intraductal papillary mucinous tumor (IPMT) of the pancreas resected 27 yr after onset is presented. In March of 1997, a 71-yr-old man was admitted to our hospital with a complaint of severe epigastric pain. He had initially undergone endoscopic retrograde pancreatography (ERP) in April 1971 in our hospital and the patient had been followed up for pancreatografic changes for 26 yr. Dilatation of the main pancreatic duct gradually progressed during follow-up, and the filling defect owing to the tumor became demonstrable. On admission, ERP revealed diffuse dilatation of the main pancreatic duct, which was 20 mm in diameter, and the filling defect of 35 mm in diameter. We diagnosed this patient as having an IPMT of the pancreas. Considering his general condition, pancreatic segmentectomy was carried out, and the postoperative course was favorable. Histological findings were compatible with those of noninvasive papillary adenocarcinoma. This is a precious case for studying the natural history of intraductal papillary tumor of the pancreas and to evaluate the application of surgery, because the biologic behavior of this tumor is much less aggressive than that of pancreatic ductal cell carcinoma.
Adenocarcinoma↗