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Biomedical subjects

A Sasaki

Publications and source records attributed to A Sasaki.

At least 163 records · Page 9Linked to original sources

Down-regulation of transforming growth factor-beta and interleukin-10 secretion from malignant glioma cells by cytokines and anticancer drugs.

The effect of treatment with interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma), vincristine, and etoposide was evaluated on the secretion of transforming growth factor-beta (TGF-beta) and IL-10 and the expression of major histocompatibility complex (MHC) class I, intercellular adhesion molecule-1 (ICAM-1), and CD80 molecules by malignant glioma cells. Five malignant glioma cell lines were treated with IL-1 beta, IFN-gamma, and/or anticancer agents (vincristine and etoposide). Combined treatment with IL-1 beta and IFN-gamma caused greater inhibition of TGF-beta secretion compared to treatment with IFN-gamma, and almost the same levels of inhibition as treatment with vincristine and etoposide. The greatest inhibition of TGF-beta secretion was achieved by treatment with all agents. Low levels of IL-10 secretion were determined in two out of five malignant glioma cell lines. This IL-10 secretion was inhibited by treatment with IL-1 beta, IFN-gamma, vincristine, and/or etoposide. Treatment with both cytokines and anticancer agents increased the expression of MHC class I and ICAM-1 in all tumor cell lines. The mean increase of expression of MHC class I was 50% and that of ICAM-1 was 12-fold. No tumor cell lines expressed CD80 molecules on the cell surface, and no treatment caused CD80 expression. These results suggest that TGF-beta and IL-10 secretion by malignant glioma cells can be suppressed by treatment with a combination of IL-1 beta, IFN-gamma, vincristine, and etoposide, and the treatment up-regulates MHC class I and ICAM-1 expression on tumor cells. These results have implications for immunotherapy and chemotherapy in patients with malignant tumors.

Antigens, Neoplasm↗

Intrahepatic peripheral cholangiocarcinoma: mode of spread and choice of surgical treatment.

BACKGROUND: Classification of macroscopic appearance and standard operative procedures for intrahepatic cholangiocarcinoma (ICC) are still controversial. METHODS: The mode of spread of 12 resected ICCs was examined by light microscopy, and the appropriate operative procedures for the various tumours were considered. RESULTS: Macroscopically, nine tumours were classified as mass-forming type and three as periductal infiltrating type. All patients were treated by major hepatectomy; resection of the extrahepatic bile duct was included in two cases of the periductal infiltrating type. Microscopically, invasion into the portal vein, intrahepatic metastasis and perineural or lymphatic vessel invasion occurred in none, one and all of three tumours of the periductal infiltrating type and in eight, six and six of nine tumours of the mass-forming type. CONCLUSION: ICC of the periductal infiltrating type has a tendency to spread along Glisson's sheath via lymphatic vessels. By contrast, ICC of the mass-forming type tends to invade the liver via the portal vein system; such tumours begin to invade Glisson's sheath through the lymphatic vessels when the tumour has increased in size. Therefore, major hepatectomy with combined resection of the extrahepatic bile duct should be performed for all ICCs of the periductal infiltrating type and for those of the mass-forming type with invasion of Glisson's sheath.

Adult↗

Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese.

We analyzed the bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT) gene in 42 Japanese newborns with hyperbilirubinemia and determined that 21 infants were heterozygous while 3 was homozygous for Gly71Arg. Allele frequency of Gly71Arg was 0.32 in newborns with hyperbilirubinemia, which was significantly higher than 0.13 in healthy Japanese controls. This mutant allele is also prevalent among Korean and Chinese healthy controls with a frequency of 0.23 in both populations. However, this mutation was not detected in 50 healthy German controls. These data suggest that the high frequency of the Gly71Arg mutation of the B-UGT gene is associated with high incidence of neonatal hyperbilirubinemia in Japanese, Korean and Chinese populations.

Alleles↗

Chronic thyroiditis as a favorable prognostic factor in papillary thyroid carcinoma.

A subgroup of patients with papillary thyroid carcinoma (PTC) also has chronic thyroiditis (CT) as an associated disease of the thyroid. To assess the prognostic value of CT in patients with PTC, we reviewed the histological slides of 2225 patients with PTC who had undergone surgery between 1971 and 1992. Of the 2225 patients, 692 were excluded from the analysis because regional lymph nodes and/or nonneoplastic thyroid tissues were unavailable for histological assessment. The series included 281 patients with CT in nonneoplastic thyroid tissue and 1252 without CT. We performed statistical analyzes by the log-rank test and Cox's proportional-hazard method. Sixty-two (5.0%) of the 1252 patients without CT died of metastatic disease during the follow-up period and the relapse-free 10-year survival rate was 85%. By contrast, only 2 (<1.0%) of the 281 patients with CT died, and their relapse-free 10-year survival rate was 95%. The difference between patients with CT and those without CT in terms of relapse-free and overall survival was statistically significant (p < 0.0001). Risk factors for unfavorable outcome were age 45 years or more, absence of psammoma bodies, and absence of CT (p < 0.0001), followed by vascular invasion (p = 0.0007), male sex (p = 0.0013), and metastasis to regional lymph nodes (p = 0.047). Multivariate analysis indicated that all of these factors with the exception of gender were independent factors in the final model for overall survival. Chronic thyroiditis in the nonneoplastic thyroid of patients with PTC is a powerful prognostic factor for both relapse-free and overall survival.

Adult↗

An evaluation of the biomechanical response of the tooth and periodontium to orthodontic forces in adolescent and adult subjects.

This study was designed to quantify the magnitude of tooth mobility in adolescents and adults, and to investigate the differences in the biomechanical response of tooth and periodontium to orthodontic forces. The initial displacement of the maxillary central incisor was measured in 50 adolescent and fifty adult patients and the biomechanical properties of the periodontium were examined using the finite element method (FEM) and supporting experimental data. The magnitude of tooth mobility was significantly greater in the adolescent group than in the adult group. By integrating the differences in tooth mobility in both subject groups with analytical tooth displacements, the Young's modulus of the periodontal ligament (PDL) was demonstrated to be greater in the adults than in the adolescent subjects. The differing biomechanical properties of the PDL in adults were demonstrated to result in almost equivalent or somewhat increased stress levels in the PDL in adult subjects. It is suggested that this might produce a reduction in the biological response of the PDL and thus lead to a delay in tooth movement in adults.

Adolescent↗

Expression of interleukin-1beta mRNA and protein in human gliomas assessed by RT-PCR and immunohistochemistry.

To characterize the expression and localization of interleukin (IL)-1beta in human gliomas, both reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used on surgically excised human gliomas, human malignant glioma xenografts, and human glioblastoma cell lines. The RT-PCR products for IL-1beta mRNA were quantified by computerized image analysis. IL-1beta mRNA was detectable in 30 out of 35 (86%) surgically resected gliomas. An abundant expression of IL-1beta mRNA was often found in the glioblastomas, anaplastic astrocytomas, and pilocytic astrocytomas, but not in other types of gliomas. Quantitatively, in both the grade 2 astrocytomas and the oligodendrogliomas, the IL-1beta mRNA levels were significantly (p < 0.05) lower than those of the grade 3/4 astrocytomas. Immunohistochemically, IL-1beta was localized in the pleomorphic tumor cells of the astrocytic tumors and in macrophages. In contrast to the astrocytic tumors, low and high grade oligodendrogliomas showed no or little expression of IL-1beta antigen. IL-1beta was present less frequently than IL-1alpha and IL-1 receptor type 1 in 4 malignant gliomas transplanted into nude mice by RT-PCR. All 2 cell lines showed IL-1beta expression at both the mRNA and protein levels. It is concluded that in human gliomas, both high-grade astrocytomas and pilocytic astrocytomas often express high IL-1beta production, and that IL-1beta is mainly localized in astrocytic tumor cells and macrophages.

Adolescent↗

Immunohistochemical characterization of two novel monoclonal antibodies that recognize human perivascular cells of the central nervous system and macrophage subsets.

Two monoclonal antibodies to cells of monocyte/macrophage lineage were established using a human glial cell-rich fraction as the immunogen. The antibodies, named GP-1 and GP-2, were originally found to react with perivascular cells of the central nervous system. They are immunohistochemically applicable on routinely formalin-fixed, paraffin-embedded tissue sections. GP-1 binds to a lysosomal protein, and GP-2 to a carbohydrate epitope of the cell membrane and lysosomes. Among the visceral organs, GP-1 labeled blood monocytes, almost all kinds of tissue and infiltrating macrophages in both normal and diseased states, and renal tubules. GP-1 staining of tissue macrophages tends to be intensified under inflammatory conditions. GP-1 staining also suggested that perivascular cells and macrophages had different ontogeny. GP-2 immunostained monocytes, Kupffer's cells, red pulp macrophages, infiltrating macrophages and reactive microglia, but not alveolar or tingible body macrophages. Besides those macrophages, GP-2 stained mantle zone lymphocytes, some hematopoietic cells, pneumocytes and renal collecting ducts. The staining pattern of ligands on THP-1 and HL-60 neoplastic human macrophage cell lines was dissimilar to that of other macrophage markers, suggesting that they recognize unknown macrophage-related antigens.

Adult↗

Solitary true cyst of the pancreas in two adults: analysis of cyst fluid and review of the literature.

Solitary true cyst of the pancreas in adults is extremely rare. We report two adult cases of solitary true cyst of the pancreas. In a 53-yr-old woman there was discovered, incidentally, a unilocular cyst of 7.0 x 6.5 cm in size in the tail of the pancreas that was noted on abdominal US and CT scan. A 16-yr-old boy presented with abdominal pain, and an abdominal US and CT scan revealed a 6.5 cm cystic mass located in the tail of the pancreas. Both patients underwent distal pancreatectomy. Histologically, the cyst was lined with flattened cuboidal and squamous epithelium without morphological alterations. Analysis of the cyst fluid revealed high CA 19-9 (>100,000 U/L) and Span-1 levels (>60,000 U/L) in both cases. Immunohistochemically, the lining epithelial cells of true cyst were positive for CA 19-9 staining. The clinicopathological features of solitary true cyst of the pancreas in adults are briefly reviewed.

Adolescent↗

Chemotactic adaptation is altered by changes in the carboxy-terminal sequence conserved among the major methyl-accepting chemoreceptors.

In Escherichia coli and Salmonella typhimurium, methylation and demethylation of receptors are responsible for chemotactic adaptation and are catalyzed by the methyltransferase CheR and the methylesterase CheB, respectively. Among the chemoreceptors of these species, Tsr, Tar, and Tcp have a well-conserved carboxy-terminal motif (NWET/SF) that is absent in Trg and Tap. When they are expressed as sole chemoreceptors, Tsr, Tar, and Tcp support good adaptation, but Trg and Tap are poorly methylated and supported only weak adaptation. It was recently discovered that CheR binds to the NWETF sequence of Tsr in vitro. To examine the physiological significance of this binding, we characterized mutant receptors in which this pentapeptide sequence was altered. C-terminally-mutated Tar and Tcp expressed in a receptorless E. coli strain mediated responses to aspartate and citrate, respectively, but their adaptation abilities were severely impaired. Their expression levels and attractant-sensing abilities were similar to those of the wild-type receptors, but the methylation levels of the mutant receptors increased only slightly upon addition of attractants. When CheR was overproduced, both the adaptation and methylation profiles of the mutant Tar receptor became comparable to those of wild-type Tar. Furthermore, overproduction of CheR also enhanced adaptive methylation of wild-type Trg, which lacks the NWETF sequence, in the absence of any other chemoreceptor. These results suggest that the pentapeptide sequence facilitates effective adaptation and methylation by recruiting CheR.

Adaptation, Physiological↗

An autopsy case of systemic hemangiomatosis with honeycomb-like liver and focal splenic sarcomatoid changes.

An unusual autopsy case of systemic hemangiomatosis associated with honeycomb-like liver and splenic sarcomatoid changes is presented. The patient suffered from high-output ventricular heart failure secondary to hepatic arteriovenous shunting with hepatic failure, ending fatally due to disseminated intravascular coagulation and pulmonary bleeding. Postmortem examination revealed the characteristic distribution of vasoformative tumors presenting in the hematopoietic system including the liver, bone marrow, and spleen, with the liver appearing characteristically honeycomb-like. While these vasoformative tumors were mostly benign-appearing, partial shifts toward sarcomatoid change were observed in the splenic lesions.

Angiomatosis↗

A prospective cohort study on National Health Insurance beneficiaries in Ohsaki, Miyagi Prefecture, Japan: study design, profiles of the subjects and medical cost during the first year.

To examine the impact of health-related lifestyle upon medical care utilization and its costs, we conducted a cohort study among all National Health Insurance beneficiaries aged from 40 to 79 years living in the catchment area of Ohsaki Public Health Center, Miyagi, Japan. The baseline survey, using self-completed questionnaire regarding health-related lifestyle, was conducted between October and December 1994. Out of 54,996 eligible subjects, 52,029 (94.6%) responded and formed the cohort under study. Medical care utilization (number of outpatient visits and days of inpatient care) and the costs for each subject have been obtained from National Health Insurance Claim History files since January 1995. The baseline characteristics of health-related lifestyle and medical history at the study subjects were consistent with those at our another cohort subjects (so-called Miyagi cohort study; N = 47,605), which included all the residents aged from 40 to 64 years at 14 municipalities in Miyagi Prefecture, Japan conducted in 1990. The medical costs per capita in this cohort was quite compatible with the national average. This prospective cohort study would quantitatively demonstrate the economic impact of health-related lifestyle, thus would lead us to better provision of cost-effective preventive health services.

Adult↗

L-selectin expression in CD34 positive cells in chronic myeloid leukemia.

L-selectin is a cell adhesion molecule, expressed on leukocytes and involved in the regulation of leukocyte traffic. This adhesion receptor is implicated in hematopoiesis by the interaction of hematopoietic stem cells and progenitors to stroma in the bone marrow microenvironment. We found that L-selectin expression on CD34++ cells from patients with chronic myelogenous leukemia (CML) is decreased or deficient, reflecting one of the features of malignant CML progenitors. In this review, we briefly describe the structure and function of L-selectin, and its role in hematopoiesis and its expression in leukemia and lymphoma. Finally, we discuss the abnormal adhesiveness of CML progenitor cells, and the role of L-selectin in this defect.

Animals↗

Resistance to growth inhibition by transforming growth factor-beta in malignant glioma cells with functional receptors.

OBJECT: The aim of this study was to investigate the mechanism by which malignant glioma cells escape from growth inhibition mediated by transforming growth factor-beta (TGF-beta), a ubiquitous cytokine that inhibits cell proliferation by causing growth arrest in the G1 phase of the cell cycle. METHODS: The authors measured the response of eight malignant glioma cell lines to the growth-inhibiting activity of TGF-beta in vitro and the expression of TGF-beta Types I and II receptors in malignant glioma cells. The effect of TGF-beta on the expression of a p27Kip1 cyclin-dependent kinase inhibitor was also investigated to assess the downstream signal transmission from TGF-beta receptors. All malignant glioma cell lines were insensitive to growth inhibition by TGF-beta1 and TGF-beta2. Analyses of TGF-beta receptors by means of affinity labeling in which 125I-TGF-beta1 was used showed that six glioma lines had both TGF-beta Types I and II receptors on their cell surfaces, whereas two lines had very small amounts of TGF-beta Type I and/or Type II receptors. Northern blot analysis showed that all tumor lines expressed variable levels of messenger RNAs for both TGF-beta Types I and II receptors. Flow cytometric analyses revealed that treatment of malignant glioma cells with TGF-beta1 significantly downregulated the expression of p27Kip1 protein in all malignant glioma cell lines except one. CONCLUSIONS: The authors suggest that most malignant glioma cells express TGF-beta Types I and II receptors, which can transmit some signals downstream and that the loss of response to TGF-beta growth inhibition may not be caused by an abnormality of the TGF-beta receptors.

Adenocarcinoma↗

[An autopsy case of P-ANCA-positive microscopic polyangiitis with multiple cerebral hemorrhagic infarction].

A 78-year-old man who had presented with a left hemiparesis was hospitalized and diagnosed as having cerebral infarction. He developed a rapidly progressive glomerulonephritis and a massive hemorrhage of the alimentary tract, and was serologically positive for perinuclear pattern antineutrophil cytoplasmic autoantibody (p-ANCA). He passed away 19 days after the onset of the illness. The autopsy diagnosis was microscopic polyangiitis based on the histological findings of necrotizing angiitis of the small vessels, necrotizing and crescentic glomerulonephrits and alveolar hemorrhage of the lung. Neuropathological examination revealed multiple hemorrhagic infarction of the cerebral cortex caused by necrotizing angiitis. In the literature, central neurological disorders are rare in p-ANCA related vasculitis. In the case of p-ANCA related vasculitis, however, there is the possibility of cerebral infarction seen as in this case.

Aged↗

Induction of temporary otitis media in specific-pathogen-free pigs by intratympanic inoculation of Mycoplasma hyorhinis.

OBJECTIVE: To examine whether Mycoplasma hyorhinis inoculated into the tympanic cavity can cause otitis media in pigs. ANIMALS: 17- or 22-day-old specific-pathogen-free pigs. PROCEDURE: Histologic and bacteriologic examinations were performed on specimens from the tympanic cavity and auditory tube at 0, 7, 14, and 25 days after intratympanic inoculation of M hyorhinis (auditory tube cloning strain 14). RESULTS: In M hyorhinis-inoculated pigs, mild to moderate inflammation of the auditory tube and tympanic cavity first appeared at postinoculation day (PID) 7. In pigs euthanatized at PID 14, the degree of inflammation was aggravated. Immunohistochemical analysis revealed M hyorhinis antigens on the luminal surface of the auditory tube and tympanic cavity. By PID 25, lesions had lessened. By use of transmission and scanning electron microscopic examinations, mycoplasmal organisms were identified among the cilia in the auditory tubes at PID 14 but not at PID 25. Results of bacteriologic examination indicated that 10(4) to 10(6) color-changing units of M hyorhinis were isolated from the tympanic cavity at PID 0. Variable numbers of M hyorhinis were isolated at PID 7 and 14, and numbers were decreased at PID 25. CONCLUSIONS: M hyorhinis inoculated into the tympanic cavity can cause a self-limiting otitis media in SPF pigs.

Animals↗