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Biomedical subjects

S Aizawa

Publications and source records attributed to S Aizawa.

At least 37 records · Page 2Linked to original sources

Adenosarcoma of the uterine corpus associated with ovarian thecoma.

We describe a case of adenosarcoma of the uterine corpus associated with ovarian thecoma in a 67-year-old woman. The patient underwent surgery under a diagnosis of ovarian carcinoma. The 110 x 70 mm-sized ovarian tumor was diagnosed as thecoma. The polypoid tumor of the uterine corpus which measured 30 x 15 mm was diagnosed as adenosarcoma. Cells of both epithelial and stromal elements of the adenosarcoma expressed estrogen receptors (determined by immunohistochemistry). These findings support the view that estrogen stimulation, including that by a pre-existing ovarian thecoma, may play a role in the development of mesenchymal and mixed epithelial / mesenchymal uterine tumors, including adenosarcoma.

Adenosarcoma↗

Collecting duct carcinoma with long survival treated by partial nephrectomy.

A case is reported of collecting duct carcinoma of the left kidney treated with partial nephrectomy. A 57-year-old woman presented for evaluation of the left renal mass, which was detected by screening ultrasonography. A computed tomography scan and magnetic resonance imaging showed a solid mass at the upper pole of the left kidney. The renal tumor biopsy revealed a low-grade renal cell carcinoma or a tubulopapillary adenoma. Subsequently, left partial nephrectomy was performed. Microscopically, the tumor showed tubulopapillary proliferation with a fibrous capsule. Histochemically, the tumor cells reacted with lectins or antibodies against the collecting duct. Twenty-four months after partial nephrectomy, the patient is alive and has no distant metastatic lesions. We review the literature on collecting duct carcinoma, in addition to the case of partial nephrectomy.

Biopsy↗

The filamentous type III secretion translocon of enteropathogenic Escherichia coli.

Enteropathogenic Escherichia coli (EPEC) uses a type III secretion system (TTSS) to inject effector proteins into the plasma membrane and cytosol of infected cells. To translocate proteins, EPEC, like Salmonella and Shigella, is believed to assemble a macromolecular complex (type III secreton) that spans both bacterial membranes and has a short needle-like projection. However, there is a special interest in studying the EPEC TTSS owing to the fact that one of the secreted proteins, EspA, is assembled into a unique filamentous structure also required for protein translocation. In this report we present electron micrographs of EspA filaments which reveal a regular segmented substructure. Recently we have shown that deletion of the putative structural needle protein, EscF, abolished protein secretion and formation of EspA filaments. Moreover, we demonstrated that EspA can bind directly to EscF, suggesting that EspA filaments are physically linked to the EPEC needle complex. In this paper we provide direct evidence for the association between an EPEC bacterial membrane needle complex and EspA filaments, defining a new class of filamentous TTSS.

Bacterial Proteins↗

Patterns of age-dependent changes in the numbers of lymph follicles and germinal centres in somatic and mesenteric lymph nodes in growing C57Bl/6 mice.

The timing of the first appearance of lymph follicles and germinal centres in various lymph nodes, and the ways in which numbers of these and IgM-synthesising cells increase within the nodes, were investigated in male and female C57Bl/6N mice aged from 4 d to 16 wk. The lymphoid organs examined were the Peyer's patches, spleen, somatic (submandibular, deep cervical, brachial, axillary, inguinal and popliteal) and visceral (mesenteric and lumbar) lymph nodes. Primary follicles appeared in most somatic lymph nodes 6 d after birth. The number of follicles per node then increased rather sharply in larger lymph nodes and slowly in smaller nodes, up to 28 d of age, reaching a level which varied according to the location of the node. Thereafter, the number of follicles in the somatic lymph nodes increased only slightly to moderately, reaching a peak or plateau at 8-12 wk. In the mesenteric (ileocaecal) nodes, primary follicles first appeared at 12 d, then increased linearly during the suckling period and after weaning to reach a plateau at 8 wk of age. Germinal centres appeared in the submandibular and mesenteric nodes at 28 d and their numbers increased consistently in the latter, while remaining low in the former. The impact of possible 'natural' exogenous antigen stimulation of the various lymph nodes was estimated from the presence of IgM-synthesising cells and germinal centres. Differences between the patterns of age-dependent changes in the numbers of lymph follicles observed in the somatic and mesenteric lymph nodes during their ontogeny are discussed in relation to differences in the magnitude of the exogenous antigen stimulatory effect. We also found that the variations in the numbers of lymph follicles produced in somatic lymph nodes at different locations during the first 28 d after birth reflected differences in the dimensions of the body regions drained by a particular somatic lymph node at this stage of development.

Aging↗

Setting characteristics of five autopolymerizing resins measured by an oscillating rheometer.

STATEMENT OF PROBLEM: Ease of handling and the working time of autopolymerizing resins are directly associated with the setting characteristics during polymerization. PURPOSE: This study assessed the setting characteristics of autopolymerizing resins by measuring viscosity changes and tested the hypotheses that: (1) different products have different viscosity increase patterns during polymerization, and (2) the increased rate of viscosity is not proportional to the length of the setting time. MATERIAL AND METHODS: Viscosity change during polymerization was measured in 5 test materials (Unifast II, ADFA, META FAST, Miky, and Trim) with an oscillating rheometer. The working time was defined as the time required for a 5% reduction in the amplitude of the rheometer trace. The setting time was measured as the time required to reach zero amplitude on the rheometer trace. RESULTS: The order of working times from longest to shortest was Trim, Unifast II and META FAST, ADFA, Miky (ANOVA, P<.0001). The order of setting times from longest to shortest was Trim, META FAST, Miky, ADFA, Unifast II. Materials that had rapid setting times did not necessarily have short working times. Unifast II showed well-balanced setting properties that satisfied both longer working time and faster setting time. CONCLUSION: Autopolymerizing resins have setting characteristics specific to the brand. Knowledge of these characteristics is essential for selection of the appropriate resin product depending on the purpose of clinical usage and the individual dentist's technique.

Acrylic Resins↗

Emx2 directs the development of diencephalon in cooperation with Otx2.

The vertebrate brain is among the most complex biological structures of which the organization remains unclear. Increasing numbers of studies have accumulated on the molecular basis of midbrain/hindbrain development, yet relatively little is known about forebrain organization. Nested expression among Otx and Emx genes has implicated their roles in rostral brain regionalization, but single mutant phenotypes of these genes have not provided sufficient information. In order to genetically determine the interaction between Emx and Otx genes in forebrain development, we have examined Emx2(-/-)Otx2(+/-) double mutants and Emx2 knock-in mutants into the Otx2 locus (Otx2(+/Emx2)). Emx2(-/-)Otx2(+/-) double mutants did not develop diencephalic structures such as ventral thalamus, dorsal thalamus/epithalamus and anterior pretectum. The defects were attributed to the loss of the Emx2-positive region at the three- to four-somite stage, when its expression occurs in the laterocaudal forebrain primordia. Ventral structures such as the hypothalamus, mammillary region and tegmentum developed normally. Moreover, dorsally the posterior pretectum and posterior commissure were also present in the double mutants. In contrast, Otx2(+/Emx2) knock-in mutants displayed the majority of these diencephalic structures; however, the posterior pretectum and posterior commissure were specifically absent. Consequently, development of the dorsal and ventral thalamus and anterior pretectum requires cooperation between Emx2 and Otx2, whereas Emx2 expression is incompatible with development of the commissural region of the pretectum.

Animals↗

Kinetic effect of zinc(II) and cadmium(II) ions on configurational inversion of deltaLLL-fac(S)-tris(L-cysteinato-N,S)cobalt(III) complex.

It has been confirmed from circular dichroism (CD) spectral changes of aqueous solutions of deltaLLL-fac(S)-[Co(L-cys-N,S)3]3- that the absolute configurational inversion to the ALLL isomer is remarkably accelerated by zinc(II), while it is retarded by cadmium(II). In the diluted solutions of these metal ions containing excess deltaLLL-fac(S)-[Co(L-cys-N,S)3]3-, the observed inversion rate constant linearly depends on the zinc(II) concentration with an intercept, while it is not affected by the cadmium(II) concentration. The kinetic behavior has been explained by difference between zinc(II)- and cadmium(II)-interactions with lone pairs on sulfur donor atoms of fac(S)-[Co(L-cys-N,S)3]3-. It has also been proposed that concentrations of zinc(II) and cadmium(II) can be simultaneously determined by the kinetic measurements.

Journal Article↗

Subcellular localization of insulin receptor substrate family proteins associated with phosphatidylinositol 3-kinase activity and alterations in lipolysis in primary mouse adipocytes from IRS-1 null mice.

To clarify the roles of insulin receptor substrate (IRS) family proteins in phosphatidylinositol (PI) 3-kinase activation and insulin actions in adipocytes, we investigated the intracellular localization of IRS family proteins and PI 3-kinase activation in response to insulin by fractionation of mouse adipocytes from wild-type and IRS-1 null mice. In adipocytes from wild-type mice, tyrosine-phosphorylated IRS-1 and IRS-2, which were found to associate with PI 3-kinase in response to insulin, were detected in the plasma membrane (PM) and low-density microsome (LDM) fractions. By contrast, tyrosine-phosphorylated IRS-3 (pp60), which was found to associate with PI 3-kinase, was predominantly localized in the PM fraction. In adipocytes from IRS-1-null mice, insulin-stimulated PI 3-kinase activity in anti-phosphotyrosine (alphaPY) immunoprecipitates in the LDM fraction was almost exclusively mediated via IRS-2 and was reduced to 25%; however, insulin-stimulated PI 3-kinase activity in the PM fraction was primarily mediated via IRS-3 and was reduced to 60%. To determine the potential functional impact of the distinct subcellular localization of IRSs and associating PI 3-kinase activity on adipocyte-specific metabolic actions, we examined lipolysis in IRS-1 null mice. The level of isoproterenol-induced lipolysis was increased 5.1-fold in adipocytes from IRS-1 null mice as compared with wild-type mice. Moreover, hormone-sensitive lipase (HSL) protein was increased 4.3-fold in adipocytes from IRS-1-null mice compared with wild-type mice, and HSL mRNA expression was also increased. The antilipolytic effect of insulin in IRS-1 null adipocytes, however, was comparable to that in wild-type mice. Thus, discordance between these two insulin actions as well as the transcriptional and translational effect (HSL mRNA and protein regulation) and the PM effect (antilipolysis) of insulin may be explained by distinct roles of both PI 3-kinase activity associated with IRS-1/IRS-2 and PI 3-kinase activity associated with IRS-3 in insulin actions related to their subcellular localization.

Adipocytes↗

Characterization of immortalized human chondrocytes originated from osteoarthritis cartilage.

Immortalized cloned human chondrocytes isolated from a normal (Ch-4, 8, N) and an osteoarthritis patient (Ch-8-OA) were established by introduction of recombinant SV40-adenovirus vector containing SV40 early gene. These cells exhibited continuous proliferative capacity in monolayer culture and showed chondrocytic characteristics in that they were positive for alkaline phosphatase and collagen type II. When cells were treated with IL-1alpha, the growth was inhibited. IL-1alpha induced the production of IL-6, GM-CSF and TNFalpha from immortalized chondrocytes. Significantly high amounts of cytokines including IL-6, GM-CSF and TNFalpha were produced from Ch-8-OA cells, even in the absence of IL-1alpha stimulation. Interestingly, TNFalpha, exogenously added into the culture, inhibited the growth of Ch-8-OA cells. Further studies are required to clarify the different mechanisms on chondrocytes originating from osteoarthritis cartilage underlying the biological reaction to various cytokines and the production of these cytokines as compared with chondrocytes from normal cartilages. However, the novel chondrocyte cell lines established in the present study may provide researchers with a useful model for studying the pathogenesis of osteoarthritis.

Alkaline Phosphatase↗

Noninvasive, microinvasive, and invasive mucinous carcinomas of the ovary: a clinicopathologic analysis of 40 cases.

BACKGROUND: Whether ovarian mucinous tumors with epithelial stratification of more than three cell layers in the absence of stromal invasion (i.e., carcinomas diagnosed according to the Hart and Norris criteria) should be placed in the same category as mucinous tumors with stromal invasion (i.e., unquestionable carcinomas) remains controversial. Because individual mucinous tumors frequently contain benign, borderline, and malignant components, the adequacy of sampling has been emphasized. METHODS: We examined 21 mucinous carcinomas with no destructive stromal invasion (MCNI), 4 mucinous carcinomas with microinvasion (MCMI) of < 2 mm, and 15 mucinous carcinomas with invasion (MCI) of > or = 2 mm. Tumors were diagnosed as MCNI according to Hart and Norris criteria (12 tumors) or when severe nuclear atypia was present (9 tumors). Cases of MCNI were selected for review if a section had been taken for each 2 cm or less of the tumor's greatest diameter. The International Federation of Gynecology and Obstetrics stage and follow-up data of each case were examined, and differences among MCNI, MCMI, and MCI were analyzed. RESULTS: All 21 patients with MCNI and all 4 patients with MCMI had Stage I disease; there was no recurrence or death in these cases. In contrast, 7 of 15 patients with MCI had Stage II or III disease, and 8 patients died. CONCLUSION: MCNI clearly should be distinguished from MCI and be classified as noninvasive carcinomas after the absence of destructive stromal invasion has been confirmed by examining a sufficient number of sections.

Adenocarcinoma, Mucinous↗

Visceral endoderm mediates forebrain development by suppressing posteriorizing signals.

The anterior visceral endoderm (AVE) has attracted recent attention as a critical player in mouse forebrain development and has been proposed to act as "head organizer" in mammals. However, the precise role of the AVE in induction and patterning of the anterior neuroectoderm is not yet known. Here we identified a 5'-flanking region of the mouse Otx2 gene (VEcis) that governs the transgene expression in the visceral endoderm. In transgenic embryos, VEcis-active cells were found in the distal visceral endoderm at 5.5 days postcoitus (dpc), had begun to move anteriorly at 5.75 dpc, and then became restricted to the AVE prior to gastrulation. The VEcis-active visceral endoderm cells exhibited ectodermal morphology distinct from that of the other endoderm cells and consisted of two cell layers at 5.75 dpc. In the Otx2(-/-) background, the VEcis-active endoderm cells remained distal even at 6.5 dpc when a primitive streak was formed; anterior definitive endoderm was not formed nor were any markers of anterior neuroectoderm ever induced. The Otx2 cDNA transgene under the control of the VEcis restored these Otx2(-/-) defects, demonstrating that Otx2 is essential to the anterior movement of distal visceral endoderm cells. In germ-layer explant assays between ectoderm and visceral endoderm, the AVE did not induce anterior neuroectoderm markers, but instead suppressed posterior markers in the ectoderm; Otx2(-/-) visceral endoderm lacked this activity. Thus Otx2 is also essential for the AVE to repress the posterior character. These results suggest that distal visceral endoderm cells move to the future anterior side to generate a prospective forebrain territory indirectly, by preventing posteriorizing signals.

Animals↗

Temperature gradient across the skin's layers has no influence on local skin vasomotor responses.

The normal negative temperature gradient within the skin of the cheek was reversed by simultaneously heating the skin externally with an infrared lamp and cooling it internally, inside the mouth, with ice. Cutaneous blood flow was measured locally under four different conditions: negative and positive gradient of local skin temperature in hypothermia and hyperthermia. There were no significant differences between negative and positive skin temperature gradients. Cutaneous blood flow depended on the core body temperature. These results show that the local skin temperature gradient can not induce vasomotor responses.

Journal Article↗

Supramolecular structure of the Shigella type III secretion machinery: the needle part is changeable in length and essential for delivery of effectors.

We investigated the supramolecular structure of the SHIGELLA: type III secretion machinery including its major components. Our results indicated that the machinery was composed of needle and basal parts with respective lengths of 45.4 +/- 3.3 and 31.6 +/- 0.3 nm, and contained MxiD, MxiG, MxiJ and MxiH. spa47, encoding a putative F(1)-type ATPase, was required for the secretion of effector proteins via the type III system and was involved in the formation of the needle. The spa47 mutant produced a defective, needle-less type III structure, which contained MxiD, MxiG and MxiJ but not MxiH. The mxiH mutant produced a defective type III structure lacking the needle and failed to secrete effector proteins. Upon overexpression of MxiH in the mxiH mutant, the bacteria produced type III structures with protruding dramatically long needles, and showed a remarkable increase in invasiveness. Our results suggest that MxiH is the major needle component of the type III machinery and is essential for delivery of the effector proteins, and that the level of MxiH affects the length of the needle.

Adhesins, Bacterial↗

Role of p53 in DNA strand break-induced apoptosis in organotypic slice culture from the mouse cerebellum.

Apoptosis occurs not only in mitotic cells but also in postmitotic neuronal cells. We previously suggested that the tumor suppressor gene p53 is required for DNA strand break-induced apoptosis in dissociated culture of cerebellar granule neurons. In this study, we examined the role of p53 in apoptosis using organotypic slice culture of cerebellum from p53 null and wild-type mice. Exposure to bleomycin significantly increased the numbers of TUNEL-, p53-, and c-Jun-positive neurons in the wild-type mouse cerebellar internal granular layer (IGL) and Purkinje cell layer (PL). However, in p53-deficient mice, these responses were not observed. These results are consistent with our previous observations in dissociated neuronal culture showing that the amount of c-Jun protein increases significantly after addition of bleomycin in p53 wild-type cerebellar granule cells. The results presented here also indicate that p53 is involved in DNA strand break-induced apoptosis of fully postmitotic central nervous system neurons and suggest that c-Jun expression occurs downstream of p53 expression.

Animals↗

OTX2 directly interacts with LIM1 and HNF-3beta.

Otx2 is a paired-class homeobox gene, and its functions in anterior visceral endoderm and/or anterior mesendoderm have been suggested to be vital for head development in mammals. Several transcription factors are expressed in these tissues, and mutant mice analyses have suggested the interactions of the Otx2 gene cascade with the Lim1 or HNF-3beta cascade. Here we show that OTX2 directly associates with LIM1 and HNF-3beta; OTX2 binds to the LIM1 homeodomain (HD) with its C-terminal region, whereas both HD and C-terminal regions of OTX2 bind to the HNF-3beta fork head domain or OTX2 HD. The luciferase assay with the P3C sequence, a specific DNA binding sequence for paired-class homeobox genes, has demonstrated that LIM1 enhances, but HNF-3beta represses, OTX2-directed gene expression. Direct interactions of OTX2 with LIM1 or HNF-3beta may play important roles in anterior visceral endoderm and/or anterior mesendoderm to constitute transcriptional regulatory networks for head development.

Animals↗

Substance P-induced cadherin expression and its signal transduction in a cloned human corneal epithelial cell line.

Although the absence of Substance P (SP), a neurotransmitter in the trigeminal nerve, has been speculated as a cause for developing neurotrophic keratitis, its exact pathogenesis is still not clarified. In a previous report, we showed with electron microscopic examination that epithelial cell attachment was weakened in denervated corneas. In this study, SV40-transformed human corneal epithelial cells (HCE-Ts) were used to explore the molecular mechanisms responsible for mediating regulation of E-cadherin expression in response to Substance P receptor stimulation. Expression of the mRNAs for specific SP receptors, neurokinin (NK)-1R, NK-2R, and NK-3R, was demonstrated with RT-PCR. The cells were treated with various concentrations of SP in vitro, and the expression of an adhesion molecule E-cadherin was analyzed by immunofluorescence, immunoblotting, and enzyme-linked immunosorbent assay (ELISA) using an anti-E-cadherin antibody. E-cadherin expression was increased by SP in a dose-dependent manner both in the cytosolic fraction and in the cell membrane fraction. This increase in E-cadherin expression was completely inhibited by Calphostin C (PKC inhibitor) and KN-62 (CaMK inhibitor), but not by H-89 (PKA inhibitor), indicating that SP-induced E-cadherin expression involves the activation of protein kinase C (PKC) and calmodulin kinase (CaMK). SP did not affect cell proliferation at all. All these findings indicate that SP induced E-cadherin expression through PKC and CaMK activation and suggest that a lack of SP may account in part for the pathogenesis of neurotrophic keratitis.

Cadherins↗

Effects of cyclic polylactate (CPL) on the growth of cloned leukemic cells in vitro.

A novel supramolecular oligomer, cyclic polylactate (CPL), was first discovered in the culture medium of HeLa-S tumour cells, and was reported to inhibit the growth of FM3A ascites tumour cells by inhibiting the activities of pyruvate kinase (PK) and lactic dehydrogenase (LDH). We have now synthesized CPL-containing oligomers with polymerization numbers ranging from 9 to 19, by prolonged heating and rapid mixing of a carbohydrate compound of the L-lactic acid monomer (C(3)H(6)O(3)) under decreased pressure and have studied its effects on the growth of leukemic cells. Treatment with 0.02 mg/ml CPL inhibited the growth of HL60 and TF-1 cells, while the growth of K562 cells was inhibited by 0.2 mg/ml CPL. A concentration of 2 mg/ml CPL was required to inhibit granulocyte-macrophage progenitor cell (CFU-GM) and burst-forming unit erythroid (BFU-E) precursor colony formation among normal bone marrow cells. Furthermore, 7A6 antigen expression and DNA ladder formation were observed in leukemic cells cultured with CPL, indicating that CPL induces apoptotic changes in these cells. These findings suggest that CPL might be a useful chemotherapeutic agent for leukemia.

Antineoplastic Agents↗