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Biomedical subjects

S Noda

Publications and source records attributed to S Noda.

At least 19 recordsLinked to original sources

The mammalian single-minded (SIM) gene: mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome.

We have recently isolated a human homolog (hSIM) of the Drosophila single-minded (sim) gene from the Down syndrome critical region of chromosome 21 using the exon trapping method. The Drosophila sim gene encodes a transcription factor that regulates the development of the central nervous system midline cell lineage. To elucidate the structure of the mammalian SIM protein, we have isolated cDNA clones from a mouse embryo cDNA library. The cDNA clones encode a polypeptide of 657 amino acids with a bHLH (basic-helix-loop-helix) domain, characteristic of a large family of transcription factors, and a PAS (Per-Arnt-Sim) domain in the amino-terminal half region. Both of these domains have striking sequence homology with human SIM and Drosophila SIM proteins. In contrast, the carboxy-terminal half of the mouse SIM protein consists of a proline-rich region with no sequence homology to the Drosophila SIM protein. A similar proline-rich domain is known for the activator domain of a number of transcription factors. Whole-mount embryo in situ hybridization experiments revealed that the SIM mRNA is expressed prominently in the diencephalon of mouse embryos at 8-9.5 days postcoitum. The structural characteristics of the mouse SIM protein and its expression in the diencephalon during embryogenesis strongly suggest that the newly isolated mammalian SIM homolog may play a critical role in the development of the mammalian central nervous system. We propose that the human SIM gene may be one of the pathogenic genes of Down syndrome.

Animals

Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2.

During T cell development in the thymus, the expression of thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2), a glycosylphosphatidylinositol (GPI)-anchored differentiation antigen, is developmentally regulated. The expression level of TSA-1 is the highest in most immature CD4- CD8- thymocytes, high in CD4+ CD8+ thymocytes, but barely detectable in mature CD4+ CD8- or CD4- CD8- thymocytes and peripheral T cells. We have previously shown that surface TSA-1 expression in peripheral T cells is induced upon activation and that anti-TSA-1 mAb inhibits the T cell receptor (TCR) signaling pathway in activated T cells. In the present study, we have analyzed a role of TSA-1 in thymic selection events, especially in TCR-mediated apoptosis. In in vitro experiments, anti-TSA-1 blocked anti-CD3-induced cell death of T cell hybridomas. When anti-TSA-1 was injected into newborn mice in vivo together with anti-CD3 epsilon or anti-TCR-beta, TCR/CD3-mediated apoptosis of thymocytes was almost completely blocked. The blockade of apoptosis was defined by the inhibition of, first, the decrease in total number of thymocytes; second, the decrease in percentages of CD4+ CD8+ thymocytes; and third, the induction of DNA fragmentation. However, anti-TSA-1 did not block either steroid- or radiation-induced apoptosis, indicating that a signal via TSA-1 does not inhibit a common pathway of thymocyte apoptosis. Since TCR-mediated apoptosis is pivotal in thymic ontogeny, these results suggest that TSA-1/Sca-2 is an important cell surface molecule regulating the fate of a developing T cell.

Animals

Population of hepatic macrophages and response of perfused liver to platelet-activating factor during production of thioacetamide-induced cirrhosis in rats.

The response of hepatic macrophages and the effects of platelet-activating factor (PAF) in perfused liver were studied during production of experimental cirrhosis induced by thioacetamide (TAA) in female Sprague-Dawley rats. Within 4 weeks of TAA administration (300 mg/L drinking water), an increase in hepatic macrophage population and enlargement in cell size preceded the alterations characteristic of cirrhosis. During 12 weeks of TAA administration, the changes in hepatic macrophages were maintained and cirrhosis of the micronodular type developed with a marked increase in hydroxyproline content. Although TAA treatment for 4 weeks had no effect on oxygen consumption or hepatic portal pressure in the perfused liver, the increment in hepatic portal pressure and decrement in oxygen consumption induced by PAF in TAA-treated rats were double those in control rats. The amounts of prostaglandin D2 (PGD2) and thromboxane B2 (TxB2) in perfusate induced by PAF were seven- and fivefold greater, respectively, in TAA-treated rats than in control rats. Zymosan mimicked the effects of PAF. These results are consistent with the hypothesis that hepatic macrophages and PAF play important roles in the development of cirrhosis induced by TAA.

Animals

Cumulative renal damage in dogs by repeated treatment with extracorporeal shock waves.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) has become a routine method for the treatment of renal and ureteral calculi. Occasionally, multisequential ESWL treatments and high energy shock waves are required to treat large calculi. The purpose of the study was to compare renal histopathologic damage caused by varying the application of shock waves. METHODS: Six groups of dogs were defined by the frequency of shocks, application time and numbers of sessions. Bilateral nephrectomies were performed immediately, 3, 7 and 60 days after the application of shock waves. Histopathologic features of the kidneys were assessed by both light and electron microscopy. RESULTS: Irreversible damage was observed in all exposed kidneys. After a single session of low application frequency, damage by shock waves occurred with progressive deterioration of the nephron. At any frequency rate, the damage was caused by tissue hypoxia due to rupturing of the interstitial capillaries. As the application frequency increased, capillary rupture became more severe, and consequently, morphological damage tended to be more intense. Repeated sessions at any application frequency made the damage more intense, suggesting that an accumulation of damage had occurred. CONCLUSIONS: Minimal doses of shock waves cause renal damage and repeated ESWL sessions may result in an accumulation of damage. Considering that the damage is dose-dependent, divided ESWL treatments at a low frequency rate are advisable in a clinical setting.

Animals

Unilateral acute posterior multifocal placoid pigment epitheliopathy.

A 24-year-old woman complained of paracentral scotomas in her left eye. Her visual acuity was good bilaterally. Multifocal, creamy, yellow-white lesions were seen at the level of the pigment epithelium and choroid in the left fundus. Fluorescein angiography showed blockage at the early phase and hyperfluorescence at the late phase in the left eye. The right fundus remained normal during the follow-up period of 1 year. We believe that unilateral acute posterior multifocal placoid pigment epitheliopathy, as found in our patient, may be uncommon.

Acute Disease

Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2).

Thymic shared antigen-1 (TSA-1) is a glycosyl-phosphatidylinositol (GPI)-anchored differentiation Ag expressed on murine lymphocytes, and is identical to stem cell Ag-2 (Sca-2). Using newly established mAb against TSA-1/Sca-2, we have previously shown that surface TSA-1 expression is induced upon activation in T cells, and that anti-TSA-1 inhibits IL-2 production induced by anti-CD3 stimulation in T cell hybridomas. In the present study, we have analyzed the functional role of TSA-1 during T cell activation using normal T cells, T cell hybridomas, and transfected Jurkat cell lines that expressed either GPI-anchored or transmembrane form of TSA-1. Anti-TSA-1 inhibited IL-2 production from normal T cells stimulated with soluble anti-CD3 plus accessory cells. Anti-TSA-1 exhibited the inhibitory effect on T cells, but not on accessory cells, because anti-TSA-1 inhibited IL-2 production in Jurkat cells transfected with TSA-1 cDNA, but not in control transfectant. A transmembrane form of TSA-1 was expressed in Jurkat cells by fusing the extracellular portion of TSA-1 to the transmembrane and cytoplasmic regions of the class 1 Db. The analysis using this transfectant revealed that anti-TSA-1-mediated inhibition of IL-2 production did not require the GPI anchor of TSA-1. Finally, in addition to the inhibition of IL-2 production, tyrosine phosphorylation of CD3 zeta-chains observed following TCR stimulation, one of the important early activation events, was markedly reduced by anti-TSA-1. These results imply that TSA-1/Sca-2 plays an important regulatory role in the TCR signaling pathway of activated T cells in addition to its role in T cell differentiation.

Animals

Phylogeny of symbiotic methanogens in the gut of the termite Reticulitermes speratus.

The phylogeny of a symbiotic methanogen inhabiting the gut of a lower termite. Reticulitermes speratus, was analysed without cultivation. The small subunit ribosomal RNA gene (ssrDNA) and a 640-bp portion of the gene encoding subunit A of methyl coenzyme M reductase (mcrA) were amplified from a mixed-population DNA of the termite gut by polymerase chain reaction and cloned. The nucleotide sequence of the ssrDNA and the predicted amino acid sequence of the mcrA product were compared with those of the known methanogens. Both comparisons indicated that the termite symbiotic methanogen belonged to the order Methanobacteriales but was distinct from the known members of this order.

Animals

Regulatory mechanisms for production of IFN-gamma and TNF by antitumor T cells or macrophages in the tumor-bearing state.

Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1 M) 2 to 3 wk after inoculation with CSA1 M cells produced IL-2, IFN-gamma, and TNF upon in vitro cultures. This was previously demonstrated to be a result of collaboration between tumor-primed CD4+ T cells and APCs binding CSA1 M tumor Ags in vivo. The IL-2- and IFN-gamma-producing capacities decreased with the progress of tumor-bearing stages. This was parallel to the levels of IL-2 and IFN-gamma mRNAs expressed by cultured spleen cells. In contrast, comparable levels of TNF mRNA were expressed by all groups of cultured cells. However, large amounts of TNF were secreted by the cells from early but not from late tumor-bearing mice. TNF was produced mainly by the non-T cell fraction upon stimulation with CD4+ T cell-derived IFN-gamma. Therefore, the reduced TNF production by whole spleen cells from late tumor-bearing mice was restored by addition of rIFN-gamma to their cultures. Reciprocally to the progressive decrease in the production of IFN-gamma/TNF, the capacities of tumor-bearing mice to produce TGF-beta and IL-6 increased along with tumor growth. TGF-beta suppressed production of IL-2, IFN-gamma, and TNF, but not of IL-6. Moreover, IFN-gamma/TNF production was negatively regulated by IL-6. Taken together with the fact that the growth of CSA1 M cells is completely inhibited by the combination of TNF and IFN-gamma, these results demonstrate that the tumor-bearing state induces an abnormal cytokine network under which the production of antitumor cytokines is negatively regulated.

Animals

Oxidized cholesterol modulates age-related change in lipid metabolism in rats.

For three weeks, male Sprague-Dawley rats at either four weeks (young) or eight months (adult) of age were pair-fed one of the purified diets free of or containing either 0.2% of oxidized cholesterol mixture (cholesterol oxidation products) or 0.2% of cholesterol. Although the food intake was similar, dietary oxidized cholesterol lowered body weight gain in young rats, but did not increase relative liver weight, in contrast to the enlargement seen with dietary cholesterol. Oxidized cholesterol, compared to cholesterol, tended to reduce the activity of hepatic 3-hydroxy-3-methylglutaryl CoA reductase and cholesterol 7 alpha-hydroxylase, particularly the latter in aged rats, and prevented the rise in the concentration of liver cholesterol at both ages. It also tended to increase the activity of hepatic delta 6 desaturase, particularly in young rats. Moreover, oxidized cholesterol in relation to cholesterol influenced liver and serum lipid concentrations in different ways, and increased lipid peroxidation at both ages. The ratio of splenic CD4+/CD8+ T-lymphocytes increased with age, but the influence of cholesterol and oxidized cholesterol was comparable. Thus, oxidized cholesterol may specifically disturb growth and age-related changes in the lipid metabolism in rats.

Aging

Holmium: yttrium-aluminum-garnet laser for endoscopic lithotripsy.

OBJECTIVES: To evaluate the holmium:yttrium-aluminum-garnet (Ho:YAG) laser for endoscopic lithotripsy on patients diagnosed with urinary tract calculi. METHODS: Thirty-eight procedures utilizing transurethral ureterolithotripsy or percutaneous nephroureteral lithotripsy were evaluated: 5 renal calculi, 31 ureteral calculi (most in the upper ureter), 1 ureteropelvic junction calculus, and 1 bladder calculus. These were mainly in cases that, after being treated with extracorporeal shock-wave lithotripsy (ESWL), were contraindicated for further ESWL. Laser parameters included energy of 0.5 to 1.0 J/pulse and pulse rate of 5 to 10 Hz. RESULTS: Composition of calculi was determined in 26 procedures. The Ho:YAG laser was effective for fragmenting all types of calculi. Patient outcome evaluated at 6 weeks after treatment showed that 33 of 38 procedures (87%) were effective. Residual calculi in 4 of the 5 unsuccessful procedures were less than 5 mm in size and judged to be able to pass spontaneously. In the remaining procedure, the calculus was passed spontaneously 3 months after treatment. No severe damage to tissues or adverse effects to the body were observed due to the Ho:YAG laser. CONCLUSIONS: On the basis of these results, we determine that this wavelength is effective for lithotripsy in addition to its previously reported usefulness for soft tissue applications, and, thus, is a cost-effective and highly useful clinical device.

Adult

Cervical cytology and conservative management of cervical neoplasias during pregnancy.

To elucidate the clinical significance of cervical cytology during pregnancy, 7,725 pregnant women were examined. Abnormal cytologic findings were recorded in 65 cases (0.8%). Colposcopically directed punch biopsies revealed cervical dysplasia and carcinoma in 27 cases (0.35%). The incidences in a massive examination for 714,119 women in Osaka Prefecture were 1.1% and 0.25%, respectively. Cytologic findings of the patients with cervical neoplasia during pregnancy agreed well (76%) with their histologic findings. Colposcopically, the squamo-columnar junction was visible in many cases, and white epithelium was most commonly observed during pregnancy. Pre- and postpartum follow-up study revealed that progression from dysplasia was seen only in two (20%) of 20 cases. Laser conization was performed on six women during pregnancy, and four were microinvasive carcinoma, all of which underwent normal vaginal delivery without any complication from conization. These results suggest that routine cervical cytology must be performed during pregnancy, and cytologic and colposcopic diagnosis may supply enough data to avoid unnecessary biopsies. Moreover, laser conization is recommended as an excellent diagnostic and therapeutic procedure for women with microinvasive carcinoma during pregnancy.

Adolescent

Do structural changes of T cell receptor complex occur in tumor-bearing state?

T cells in tumor-bearing mice and cancer patients were recently shown to be devoid of CD3-zeta chain, a signal-transducing invariant chain in T cell receptor (TCR) complex, and p56lck tyrosine kinase. In the present study, we investigated the structure and function of TCR complex in T cells from BALB/c mice bearing CSA1M fibrosarcoma. The expressions of TCR chains and p56lck in a T cell-enriched population from spleen were analyzed. Almost complete loss of CD3-zeta and p56lck was observed in the preparation from tumor-bearing mice as assessed by immunoblotting analysis using whole cell lysates, whereas the amounts of other TCR chains were relatively unchanged. However, these changes were due to the increase of contaminating Mac-1+ cells in the spleen of tumor-bearing mice because: 1) the removal of Mac-1+ cells led to the restoration of CD3-zeta and p56lck; and 2) CD3-zeta was clearly present when the preparation was solubilized with ionic detergent. Fc receptor gamma chain detected in the preparation from tumor-bearing mice disappeared along with the removal of Mac-1+ cells. These observations were further supported by the finding that addition of Mac-1+ cells from tumor-bearing mice to normal T cells resulted in loss of CD3-zeta, leaving CD3-epsilon largely intact. When T cells from tumor-bearing mice were highly purified by depletion of Mac-1+ cells, these T cells contained normal amounts of CD3-zeta at mRNA, protein, and surface levels, and expressed the properly assembled TCR complex on their cell surface. Moreover, stimulation of the TCR in these T cells by anti-TCR antibodies resulted in a comparable Ca2+ mobilization to that observed in normal T cells. These results suggest that no structural changes occur in TCR complex in our tumor-bearing mice, and that complete depletion of Mac-1+ cells in important to assess the structure of TCR complex.

Animals

Retinopathy and subconjunctival haemorrhage in patients with chronic viral hepatitis receiving interferon alfa.

A total of 43 patients (86 eyes) with chronic viral hepatitis were examined prospectively before and after the start of interferon therapy. Of 37 non-diabetic patients, 23 (group A1) did not have retinopathy or subconjunctival haemorrhage, 11 (group A2) developed retinopathy, and three (group A3) exhibited subconjunctival haemorrhage during the treatment. In most eyes, the retinopathy disappeared after therapy was stopped. Of six diabetic patients, three (group B1) developed retinopathy and three (group B2) showed progression of existing retinopathy. Thrombocytopenia was not associated with the retinopathy in any patient. The patients' good visual acuity remained unchanged, even after retinal changes appeared. Ophthalmologists should be aware that retinopathy and subconjunctival haemorrhage may develop in patients with chronic viral hepatitis receiving interferon therapy.

Adult

Recurrent subconjunctival hemorrhages in patients with Fuchs' heterochromic iridocyclitis.

We examined two women who had keratic precipitates, minimal intracameral cells and flare, diffuse iris stromal atrophy, posterior subcapsular cataract, and vitreous opacities in their left eyes. No ocular pain, photophobia, or posterior synechia was noted. Their right irises appeared brown. Heterochromia was evident in both patients. Recurrent subconjunctival hemorrhages were also in their affected left eyes. It is possible that subconjunctival hemorrhages in our patients may be associated with Fuchs' heterochromic iridocyclitis.

Atrophy

A case of mitral regurgitation whose nocturnal periodic breathing was improved after mitral valve replacement.

Nocturnal periodic breathing (PB) is often observed in patients with congestive heart failure (CHF). We investigated the sleep architecture polysomnographically in a 54-year-old man with CHF due to mitral regurgitation before and after surgical treatment. We found that the overnight frequency of central dominant sleep apnea decreased from 154 to 56, and the lowest nocturnal oxygen saturation increased from 66% to 85% postoperatively. These improvements in the manifestations of PB might be attributed to the improved hemodynamics after successful valve replacement.

Cheyne-Stokes Respiration