Biomedical subjects

S Aizawa

Publications and source records attributed to S Aizawa.

At least 19 recordsLinked to original sources

PubMed2003

Diagnosis and treatment of progressive space-occupying radiation necrosis following stereotactic radiosurgery for brain metastasis: value of proton magnetic resonance spectroscopy.

BACKGROUND: There have been some reports that radiation necrosis can be controlled conservatively. There are rare cases showing progressive space-occupying radiation necrosis (PSORN). It is very difficult to control PSORN by conservative treatment. The purpose of this study was to evaluate the early diagnosis of those cases and the timing of surgery for patients with PSORN. METHOD: We have experienced some cases where quality of life was improved by the removal of PSORN after stereotactic radiosurgery (SRS) for brain metastases. Therefore, we evaluated retrospectively the diagnosis and treatment of six cases of symptomatic PSORN at approximately 6-12 months after SRS for metastatic brain tumours. FINDINGS: In all six cases, on Magnetic Resonance Imaging with Gd contrast material (Gd-MRI), PSORN was revealed as a ring-like enhanced mass with large perifocal oedema coupled with the appearance of neurological deficit. Proton Magnetic Resonance Spectroscopy ((1)H-MRS) enabled us to differentiate PSORN from recurrence of metastases in all six cases. Single Photon Emission Computed Tomography with thallium-201 chloride (201TlCl-SPECT) enabled us to do this in four cases of the six. In four cases of the six, lesionectomy of the ring-like enhanced mass (PSORN) was performed, and in two of these cases the removal was performed within 4 weeks from the time when conservative treatment became ineffective, and the neurological deficit and perifocal oedema was improved as was the quality of life. However, in the other two patients who were left for more than 16 weeks, the deficit was gradually progressive. The two patients who did not receive lesionectomy were treated by conservative means with steroids and/or heparin and warfarin and they had progressive neurological symptoms. INTERPRETATION: Although, the number of patients is small in this study, and more data will be needed, it is recommended that lesionectomy is performed at an early stage, if possible, when conservative management has failed.

Adult↗

PubMed2003

In vivo distribution of receptor for ecotropic murine leukemia virus and binding of envelope protein of Friend Murine leukemia virus.

Ecotropic infection by Murine leukemia virus (MuLV) infection is initiated by the interaction between the receptor-binding domain of the viral surface glycoprotein (SU) and the cell-surface receptor, mCAT-1. To study the in vivo localization of viral binding site in mice, green fluorescence protein (GFP)-tagged Friend SU (F-SU/GFP) was incubated with tissue sections. Lymphohematopoietic organs and a part of the glandular tissues of C3H as well as C57BL/6 mice revealed positive signals for F-SU/GFP binding on the cell surface. In contrast, C4W mice, which is a partial congenic mouse strain carrying the Fv-4 (r) gene on a BALB/c genetic background, exhibited negative signals in most of the organs except for a very weak binding in the pancreas. The expression of mCAT-1 mRNA determined by reverse transcriptase (RT)-polymerase chain reaction (PCR) revealed a similar distribution in C3H, C57BL/6 and C4W mice. Most of the organs including lymphohematopoietic organs and glandular organs revealed significant expression of mRNA for mCAT-1 gene, while the liver, heart and muscle did not. The results from binding assay were consistent with the fact that Friend MuLV-induced pathogenesis was usually associated with lymphohematopoietic systems, although mRNA expression for mCAT-1 was rather ubiquitous. The discrepancy between F-SU/GFP binding and mRNA expression for mCAT-1 in lymphohematopoietic organs of C4W mice would support the receptor interference effect by the Fv-4 (r) gene causing the resistance of C4W mouse to Friend MuLV infection.

Animals↗

PubMed2002

Cytogenetic and cellular events during radiation-induced thymic lymphomagenesis in the p53 heterozygous (+/-) B10 mouse.

PURPOSE: Cellular and cytogenetic events in radiation-induced thymic lymphomagenesis were investigated in the p53 heterozygous (+/-) mouse following a single dose of whole-body irradiation. MATERIALS AND METHODS: The loss of the wild-type p53 allele and microsatellite markers of chromosome 11 in thymic lymphomas that developed in the p53 heterozygous (+/-) mouse after irradiation, and the stage at which prelymphoma cells appeared were analysed. RESULTS: The p53 heterozygous mouse developed thymic lymphomas in a dose-dependent manner. The loss of the wild-type p53 allele (loss of heterozygosity; LOH) occurred in almost all thymic lymphomas induced in the irradiated p53 heterozygous mouse. Cytogenetic analysis for the mechanism of LOH strongly suggested that the loss of the wild-type p53 gene in the lymphomas was caused by duplication of the disrupted allele through either homologous recombination or non-disjunctional chromosome duplication. The assay for prelymphoma cells suggested that a critical event in the development of prelymphoma cells occurred at least 3 weeks after irradiation. CONCLUSIONS: The loss of the wild-type p53 gene in thymocytes of the p53 heterozygous mouse may precede the development of prelymphoma cells after irradiation and be a valuable marker of radiation-induced leukemogenesis.

Animals↗

PubMed2001

Lipid peroxidation end products-responded induction of a preneoplastic marker enzyme glutathione S-transferase P-form (GST-P) in rat liver on admistration via the portal vein.

The in vivo induction mechanism of a preneoplastic marker enzyme, glutathione S-transferase P-form (GST-P), by a number of carcinogens and some noncarcinogens such as anti-oxidants [Proc. Natl. Acad. Sci. U.S.A. 85 (1984) 3964] has remained to be solved. Among the various administration routes tested, GST-P became immunohistochemically demonstrable in the liver centrilobular zone 3 after 24-48h on administration of prostaglandin J2's, 15-deoxy-Delta(12,14)-PGJ2, PGJ2 and Delta(12)-PGJ2 to male rats via the portal vein, whereby the animals had been pretreated with Soya oil intraperitoneally to exhaust fatty acid binding proteins. Unsaturated aldehydes, 4-hydroxynonenal, crotonaldehyde and acrolein, given by the same route induced putatively preneoplastic single cells positive for GST-P. As these lipid peroxidation end products are the substrates as well as inducers of the enzyme, its physiological function could be their detoxication. These results indicate that GST-P expression can be mediated through lipid peroxidation possibly accounting for induction observed with a wide variety of carcinogens. In addition, present method may also be of use as a direct, simple, rapid, and sensitive in vivo test in examination of other biological responses.

Animals↗

PubMed2001

Impairment in the expression and activity of Fyn during differentiation of naive CD4+ T cells into the Th2 subset.

We previously showed that the amounts of Fyn protein in Th2 clones were approximately one-third to one-fifth of those in Th1 clones. In this study we examined the role of Fyn in the polarization of naive CD4+ T cells toward the Th2 subset using fyn(-/-) mice. The fyn(-/-) naive CD4+ T cells efficiently produced Th2 cytokines and polarized toward the Th2 subset even in the absence of IL-4 and IL-13. The expression of Fyn in wild-type CD4+ T cells decreased at a transcription level concomitant with polarization toward the Th2 subset. These results suggest that Fyn plays a role in the down-regulation of the differentiation of naive CD4+ T cells into the Th2 subset.

Animals↗

PubMed2001

Establishment of left-right asymmetric innervation in the lancelet oral region.

Lancelets (amphioxus) exhibit a remarkable asymmetric development in the anterior body region, which is reflected in the peripheral nervous system even at adulthood. Not all of the anterior nerves are involved, but the left third to fifth nerves are clearly asymmetric. To trace the developmental process responsible for asymmetric innervation, the peripheral nerves in the anterior region were studied in pre- and mid-metamorphic larvae, 1-cm-long juveniles, and in adults by using whole-mount immunostaining. The mouth changes in size and location during larval life before moving ventrally and, in conjunction with this change, nerves in the oral region are also modified. The left second nerve initially innervates the oral region, but this connection is secondarily lost. As the mouth expands and shifts posteriorly, the left fifth to ninth nerves join the left third and fourth in the innervation of the oral region. The left third to sixth nerves anastomose with the oral nerve ring, which encircles the mouth on the left side. In the juveniles and adults, there are two nerve plexuses that run parallel to the margin of the oral hood. The innermost of these, the "inner oral-hood nerve plexus", is asymmetrically connected with the left third to fifth nerves on both sides. The other, the "outer oral-hood nerve plexus", is ipsilaterally connected with the third to seventh nerves on both sides. The velar nerve ring is also innervated asymmetrically by the left fourth and fifth nerves. From these observations, we suggest that the oral nerve ring is the precursor of both the inner oral-hood nerve plexus and the velar nerve ring, and that the asymmetric innervation retained in adult lancelets is related to the early anastomosis of the left nerves with the oral nerve ring. We also show that, contrary to the persistent asymmetric innervation, the axonal patterns of the anterior peripheral nervous system in developing lancelets can change.

Animals↗

PubMed2001

Complementary functions of Otx2 and Cripto in initial patterning of mouse epiblast.

The development of the mammalian antero-posterior (A-P) axis is proposed to be established by distinct anterior and posterior signaling centers, anterior visceral endoderm and primitive streak, respectively. Knock-out studies in mice have shown that Otx2 and Cripto have crucial roles in the generation and/or functions of these anterior and posterior centers, respectively. In both Otx2 and Cripto single mutants, the initial formation of the A-P axis takes place in a proximal-distal (P-D) orientation, but subsequent axis rotation fails to occur. To examine the developmental consequences of the lack of these two genes, we have analyzed the Otx2(-/-);Cripto(-/-) double homozygous mutant phenotype. In the double mutants, the expression of the A-P axis markers Cer-l, Lim1, and Wnt3 was not induced, while expression of Fgf8 and T was expanded throughout the epiblast, indicating that the double mutants could not form the A-P axis even in its initial P-D orientation. In addition, the double mutants displayed defects in differentiation of the visceral endoderm overlying the epiblast, as well as in the extraembryonic ectoderm. Furthermore, differentiation of neuroectoderm was accelerated as judged by the reduction of Oct4 expression and emergence of Sox1 and Gbx2 expression in the double mutant epiblast. The resulting ectoderm only displayed characteristics of anterior hindbrain, implicating it as a ground state in the mammalian body plan. Our results indicate that complementary functions of Otx2 and Cripto are essential for initial patterning of the A-P axis in the mouse embryo.

Animals↗

PubMed2001

Isolation of Dlx and Emx gene cognates in an agnathan species, Lampetra japonica, and their expression patterns during embryonic and larval development: conserved and diversified regulatory patterns of homeobox genes in vertebrate head evolution.

Agnathan cognates of vertebrate homeobox genes, Emx and Dlx, were isolated from embryonic cDNA of a Japanese marine lamprey, Lampetra japonica. Analyses of amino acid sequences indicated that the Dlx cognate was closely related to the common ancestor of gnathostome Dlx1 and Dlx6 groups and termed LjDlx1/6. Southern blot analyses could not rule out the possibility that L. japonica possesses more than one paralog for both LjDlx1/6 and LjEmx, the lamprey cognate of Emx. Expression of LjDlx1/6 was regulated spatially as well as developmentally, and its transcripts were mainly found in the craniofacial and pharyngeal mesenchyme and in the forebrain. The expression pattern of LjEmx changed dramatically during embryogenesis; expression was seen initially in the entire neural tube and mesoderm, which were secondarily downregulated, and secondarily in cranial nerve ganglia and in the craniofacial mesenchyme. No specific expression of LjEmx was seen in the telencephalon. Comparisons of Dlx and Otx gene expression patterns suggested a shared neuromeric pattern of the vertebrate brain. Absence of Emx expression implied that the patterning of the lamprey telencephalon is not based on the tripartite plan that has been presumed in gnathostomes. Expression domains of LjDlx1/6 in the upper lip and of LjEmx in the craniofacial mesenchyme were peculiar features that have not been known in gnathostomes. Such differences in expression pattern may underlie distinct morphogenetic pathway of the mandibular arch between the agnathans and gnathostomes.

Amino Acid Sequence↗

PubMed2001

Functional disorders of the sympathetic nervous system in mice lacking the alpha 1B subunit (Cav 2.2) of N-type calcium channels.

N-type voltage-dependent Ca(2+) channels (VDCCs), predominantly localized in the nervous system, have been considered to play an essential role in a variety of neuronal functions, including neurotransmitter release at sympathetic nerve terminals. As a direct approach to elucidating the physiological significance of N-type VDCCs, we have generated mice genetically deficient in the alpha(1B) subunit (Ca(v) 2.2). The alpha(1B)-deficient null mice, surprisingly, have a normal life span and are free from apparent behavioral defects. A complete and selective elimination of N-type currents, sensitive to omega-conotoxin GVIA, was observed without significant changes in the activity of other VDCC types in neuronal preparations of mutant mice. The baroreflex response, mediated by the sympathetic nervous system, was markedly reduced after bilateral carotid occlusion. In isolated left atria prepared from N-type-deficient mice, the positive inotropic responses to electrical sympathetic neuronal stimulation were dramatically decreased compared with those of normal mice. In contrast, parasympathetic nervous activity in the mutant mice was nearly identical to that of wild-type mice. Interestingly, the mutant mice showed sustained elevation of heart rate and blood pressure. These results provide direct evidence that N-type VDCCs are indispensable for the function of the sympathetic nervous system in circulatory regulation and indicate that N-type VDCC-deficient mice will be a useful model for studying disorders attributable to sympathetic nerve dysfunction.

Animals↗

PubMed2001

Establishment of an androgen-responsive prostatic cell line "PEA5" from a p53-deficient mouse.

BACKGROUND: We demonstrated that p53-deficiency is sufficient for the establishment of clonal cell lines from the uterus and prostate. In the present study, we improved cloning methods to establish androgen-responsive cell lines. METHODS: In our previous study, a prostatic cell line was established from the ventral prostate of a p53-deficient mouse and was maintained in a medium containing heat-inactivated fetal calf serum at 10% supplemented with insulin (10 microg/ml), transferrin (10 microg/ml), cholera toxin (10 ng/ml) and selenium (10(-8) M). In the present study, 5alpha-dihydrotestosterone (10(-8) M) was added to the medium from the beginning of cloning procedures. RESULTS: We succeeded in the establishment of an androgen receptor positive prostatic cell line, designated PEA5. PEA5 cells exhibited a typical epithelial morphology in culture and growth was stimulated by androgens in a dose-dependent manner. In addition, they grew and formed three-dimensional structures in collagen gel, in which growth was also stimulated by androgen. CONCLUSIONS: Although PEA5 lacks p53 gene, it still retains androgen sensitivity. In collagen gel culture, PEA5 cells can grow and form three-dimensional structures similar to those of the primary cultures reported previously. Furthermore, prostates of p53-deficient mice are shown to be useful sources for obtaining androgen-responsive cells lines.

Animals↗

PubMed2001

Expression of receptor for ecotropic murine leukemia virus on hematopoietic cells.

A fusion protein (F-SU/GFP) which is comprised of the surface (SU) subunit of the Friend MuLV envelope glycoprotein and the green fluorescence protein (GFP) was generated by a baculovirus expression system. The F-SU/GFP specifically bound to mammalian tissue cultured cells expressing the mCAT-1, the receptor for ecotropic murine leukemia virus (ECO-MuLV). The expression level of mCAT-1 on hematopoietic cells was measured based on the capacity of cells to absorb the F-SU/GFP. In BALB/c mice susceptible to Eco-MuLV infection, all hematopoietic cell subpopulations absorbed the F-SU/GFP with the most prominent absorption observed in the TER119+ erythroblasts. Hematopoietic cells from C4W and AKR mice did not absorb the F-SU/GFP as readily as the BALB/c cells, probably due to expression of the envelope glycoproteins of endogenous Eco-MuLVs in these mice. Although AKR mice are susceptible to Eco-MuLV infection while C4W mice are resistant, these mice showed no apparent difference in the F-SU/GFP-absorbing capacity.

Amino Acid Transport Systems, Basic↗

PubMed2001

Role of lymphoid cells in age-related change of susceptibility to Friend leukemia virus-induced leukemia.

Susceptibility for Friend leukemia virus (FLV)-induced leukemogenesis was examined in the C3H/He (C3H)-->C57BL/6 (B6) radiation bone marrow chimeras of various age groups, and the effect of aging of host mice on the susceptibility was determined. The bone marrow chimera system provided the various age of FLV-resistant host mice (B6) possessing the same age of FLV-susceptible target cells from C3H mice. Using this system, we could determine the aging effect on the host resistancy against FLV without an influence of the aging effect on target cells. First, the young C3H-->young B6 chimeras and young C3H-->old B6 chimeras were compared. The young-->old chimeras were more susceptible to FLV-induced acute disease than the young-->young chimeras. The spleen CD4+ as well as CD8+ T cells were reduced in young-->old chimeras compared with young-->young chimeras. Similarly, the old C3H-->old B6 chimeras were more susceptible than old-->young chimeras and revealed the lower CD4+ T cell ratio in the spleen. Discussion was made on the possible implication of these findings on the role of T cells in age-related change of resistance to FLV-induced leukemogenesis.

Aging↗

PubMed2001

A gene therapy model for retrovirus-induced disease with a viral env gene: expression-dependent resistance in immunosuppressed hosts.

At the initial stage of retroviral infection, virion envelope glycoprotein (env product) binds to cell surface receptors. Cells infected with retrovirus or into which the env gene was introduced, become resistant to superinfection by other retroviruses with the same receptor specificity, a phenomenon known as receptor interference. We have demonstrated previously that the introduction of an env gene from a truncated endogenous ecotropic murine leukemia virus (MuLV), the Fv-4 resistance (Fv-4r) gene, into the bone marrow hematopoietic cells of Fv-4 sensitive (Fv-4s) mice protected mice from ecotropic retrovirus-induced disease. Using the gene transfer system under the control of the retroviral vector and bone marrow transplantation (BMT), here we could show that the expression of an introduced Fv-4r gene in hematopoietic cells continued for more than 1 year after BMT. To determine the inhibitory mechanism of Fv-4r env gene expression against FLV-infection in this model system, peripheral blood mononuclear cells (PBMCs), or spleen cells from chimeras with various degrees of env-expression, were mixed with green fluorescence protein (GFP)-conjugated Friend MuLV envglycoprotein (GFP-Fr-ENV). The amount of GFP-Fr-ENV bound to these cells inversely correlated with the expression intensity of the transduced env gene indicating the receptor interference effect. Next, to see whether transduction of the Fv-4r gene would protect an immunosuppressed host from FLV-induced leukemogenesis, we generated immunocompromised chimeras by transplanting env-transduced bone marrow cells into a thymectomized host. These chimeras also resisted FLV-induced leukemogenesis, indicating that receptor interference-based gene therapy could become a therapeutic basis for immunodeficiency virus-induced diseases in vivo.

AIDS-Related Opportunistic Infections↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗