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Biomedical subjects

M Suda

Publications and source records attributed to M Suda.

At least 55 records · Page 3Linked to original sources
PubMed1999

The contribution of acute toxicity in animals to occupational exposure limits of chemical substances.

The correlations of lethal doses of various industrial chemicals for rats and mice with occupational exposure limit values were investigated. 50% lethal dose (LD50) values obtained by oral (p.o.) and intraperitoneal (i.p.) injection and 50% lethal concentration (LC50) values obtained by inhalation exposure were collected from Registry of Toxic Effects of Chemical Substances (RTECS). Threshold Limit Value (Time-Weighted Average) (TLVs-TWA) and Threshold Limit Value (Short Term Exposure Limit) (TLVs-STEL) recommended by American Conference of Governmental Industrial Hygienists (ACGIH) were used as exposure limits. TLVs-TWA or TLVs-STEL and LD50 or LC50 values obtained for the rats were plotted on logarithmic scales on the ordinate and abscissa, respectively. High correlations were obtained between these parameters. The order of correlations was: TLVs-STEL vs. LC50s > TLVs-TWA vs. LC50s > TLVs-TWA vs. LD50s i.p. > TLVs vs. LD50s p.o. The same calculations for the relationship between TLVs and lethal doses in mice were also performed. The order of the three types of correlations was same as that of the rats; however, correlation coefficients for TLVs-STEL vs. LC50s and for TLVs-TWA vs. LC50s obtained in mice were smaller than those in rats. TLVs-TWA are, therefore, well correlated with LC50 values rather than LD50 values, particularly with those in rats. High correlations between TLVs-STEL vs. LC50s were also obtained, as had been expected before calculation. The equation: TLV-TWA = 10b x (LC50)a can be obtained from these plottings, where the values a and b are taken from each linear regression line. TLV-TWA for each chemical can be calculated by using LC50 and the equation. The upper and lower 95% confidence limits for calculated TLV-TWA were TLV-TWA (calculated from LC50) x 22.9 and TLV-TWA (calculated)/22.9, respectively, where LC50 for rats expressed in ppm x hr was used.

Animals↗
PubMed1999

[Vimentin and neuroepithelial cell differentiation in the spinal cord of chick embryos: an immunohistochemical study].

Using vimentin immunohistochemical staining, the differentiation processes of neuroepithelium in the neural tube were examined in chick embryos from stages 8 through 28. At an early stage of the neural groove, stage 8, no morphological differences could be found among the neuroepithelial cells, but vimentin staining allowed us to identify four different regions in the groove wall. The epithelial cells in the ventral wall exhibited moderate staining of vimentin, and vimentin was detected in the basal and middle cytoplasmic areas. A weak staining limited to the basal cytoplasm was observed in the dorsal wall. In contrast, epithelial cells in the median hinge region and in the lateral edge of the neural groove had little vimentin. On the basis of this vimentin staining, four similar regions could also be observed in the neuroepithelium of the neural tube at stage 12; the ventral wall, dorsal wall, floor plate and roof plate. Prior to the morphological changes in the neuroepithelial cells, vimentin expression showed dramatic changes, and our immunohistochemical data suggest that cell differentiation into motor areas and sensory areas starts at an early stage of the neural groove.

Animals↗
PubMed1999

[A family of SCA1 with pigmentary macular dystrophy].

Pigmentary macular dystrophy (PMD) was detected in a 57-year-old Japanese man with SCA1, five years after the onset of ataxia. Family history revealed 7 other ataxic members in three generations. Among them, only his younger brother, who had already died, had developed central scotoma with normal peripheral fields, 15 years after the ataxia had appeared. None of the other family members, with or without ataxia, had visual disturbances. The numbers of CAG repeats in the patient's SCA1 gene were 27 and 47, the latter of which was within pathological range and belonged to mild to moderate CAG expansion in previously reported cases. The PMD seen in our patient could be one of the clinical features associated with SCA1, since patients with SCA1 often show various ocular changes. Although genetic analysis ruled out SCA7 in this patient, the phenotypic resemblance of this patient to SCA7 may reflect the necessity in the future, for genetic differentiation between SCA1 and SCA7 in patients with autosomal dominant cerebellar ataxia and PMD.

Adult↗
PubMed1998

Inhibitory effects of antioxidants on formation of heterocyclic amines.

It is important to search for effective antioxidants to suppress formation of mutagenic and carcinogenic heterocyclic amines (HCAs), like 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), because these HCAs are considered to be probable human carcinogens. The effects of various food-derived antioxidants on MeIQx formation were examined by their addition (0.2 mmol each) to mixtures of creatine (0.4 mmol), glycine (0.4 mmol) and glucose (0.2 mmol), and heating at 128 degreesC for 2 h. Glycine was replaced by l-phenylalanine in the case of PhIP formation. Among the 14 kinds of antioxidants tested, green tea catechins and the major component [(-)-epigallocatechin gallate], two flavonoids (luteolin and quercetin) and caffeic acid were found to clearly suppress the formation of both MeIQx and PhIP, being 3.2-75% of the level of the controls. These phenolic antioxidants also reduced the total mutagenicity of the heated mixtures. The results suggest that foodstuffs containing catechins, flavonoids and caffeic acid may suppress the formation of HCAs in cooked foods.

Animals↗
PubMed1998

Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway.

The natriuretic peptide family consists of three structurally related endogenous ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The biological actions of natriuretic peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The natriuretic peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-peptide GC-coupled natriuretic peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.

Animals↗
PubMed1998

Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide.

Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. Natriuretic peptides organize a family of three structurally related peptides: atrial natriuretic peptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide. Atrial natriuretic peptide and BNP are cardiac hormones that are produced predominantly by the atrium and ventricle, respectively. C-type natriuretic peptide occurs in a wide variety of tissues, where it acts as a local regulator. These peptides can influence body fluid homeostasis and blood pressure control through the activation of two guanylyl cyclase (GC)-coupled natriuretic peptide receptor subtypes-GC-A and GC-B. We report here marked skeletal overgrowth in transgenic mice that overexpress BNP. Transgenic mice with elevated plasma BNP concentrations exhibited deformed bony skeletons characterized by kyphosis, elongated limbs and paws, and crooked tails. Bone abnormalities resulted from a high turnover of endochondral ossification accompanied by overgrowth of the growth plate. Studies using an in vitro organ culture of embryonic mouse tibias revealed that BNP increases the height of cartilaginous primordium directly, thereby stimulating the total longitudinal bone growth. The present study demonstrates that natriuretic peptides can affect the process of endochondral ossification.

Aging↗
PubMed1998

Effects of colchicine on the enucleation of erythroid cells and macrophages in the liver of mouse embryos: ultrastructural and three-dimensional studies.

Enucleation is the last event in the development of a definitive erythroid line, and extruded nuclei are phagocytosed by macrophages. Both colchicine and cytochalasin have been known to exert a great influence on the enucleation process, but the relationship between enucleation and these agents has not yet been clearly revealed in vivo. Our aim was to clarify the significance of the enucleation in liver erythropoiesis and macrophage phagocytosis by colchicine and cytochalasin administration to embryonic mice. Pregnant mice were intraperitoneally injected with colchicine or cytochalasin at 13 days of gestation. Embryonic livers were removed at intervals of 3, 6 and 12 h after injection for processing for light and electron microscopy, and, to obtain three-dimensional morphology of erythroids at enucleation, computer-aided reconstructions were performed by light microscopy. Colchicine injections had cytolytic effects on hepatocytes and macrophages, and numerous erythroblasts were observed in the process of enucleation after colchicine injection. However, the extruding nuclei were irregularly shaped, and some erythroblasts at mitosis showed extreme peripheralization of their chromosomal masses and cell membrane constriction. Enucleation behavior could also be observed in immature erythroblasts. Liver macrophages engulfed extruded nuclei and erythroblasts in mitosis. Cytochalasin injections, on the other hand, had no significant effect on embryonic livers. The progress of erythroblast mitosis was clearly stopped by colchicine injection, and numerous erythroblasts at mitosis were extruding their nuclear compartment. Following colchicine injection, erythroid enucleation also took place in immature erythroblasts, and mitotic erythroids were phagocytosed. In enucleation, more attention should be paid to hematopoietic environmental factors than to hemopoietic cell factors.

Animals↗
PubMed1998

Prostaglandin E2 (PGE2) autoamplifies its production through EP1 subtype of PGE receptor in mouse osteoblastic MC3T3-E1 cells.

Prostaglandin E2 (PGE2) is known to autoamplify its production in the osteoblasts through the induction of prostaglandin G/H synthase-2 (PGHS-2), which is the inducible form of the rate-limiting enzyme in PG synthesis, PGHS. To elucidate the cellular mechanism mediating this process, we have employed the PGE2 analogs, which are specific agonists for four subtypes of PGE receptor, and studied the potency of these analogs to induce PGHS-2 mRNA in mouse osteoblastic MC3T3-E1 cells. The induction was mainly observed by 17-phenyl-omega-trinor PGE2 (EP1 agonist) and sulprostone (EP3/EP1 agonist), but not by butaprost (EP2 agonist) or 11-deoxy PGE1 (EP4/EP2 agonist). Since EP3 subtype was undetectable in MC3T3-E1 cells, these data indicate that PGHS-2 mRNA induction is mediated through EP1 subtype of PGE receptor in MC3T3-E1 cells. PGE2 production determined by radioimmunoassay was also increased by 17-phenyl-omega-trinor PGE2 and sulprostone. The autoamplification of PGE2 production is considered to be important in elongating the otherwise short-lived PGE2 action in certain physiological conditions such as mechanical stress and fracture healing, as well as the pathological inflammatory bone loss. The observations in the present study provide us with the better understanding of these processes.

3T3 Cells↗
PubMed1998

Correlation of lethal doses of industrial chemicals between oral or intraperitoneal administration and inhalation exposure.

Correlations of lethal doses of industrial chemicals between oral or intraperitoneal administration and inhalation exposure in rats and mice were investigated. LC50 values for inhalation exposure and LD50 values for oral and intraperitoneal administration were obtained from the Registry of Toxic Effects of Chemical Substances. LC50 and LD50 values were plotted on ordinate and abscissa, respectively, using logarithmic scales. A correlation coefficient of r = 0.624 (n = 146, p < 0.001) was obtained for LC50 (ppm) and LD50 (mg/kg) values with oral administration (oral LD50) in rats. This correlation was improved by converting the units of LC50 from ppm to ppm h (cumulative dose), and by converting the units of LD50 from mg/kg to mmol/kg. The correlation coefficient was r = 0.742 when ppm*hr and mmol/kg were adopted for LC50 and LD50, respectively. A similar improvement in correlation coefficients by the same unit conversion was also observed between LC50 and LD50 with intraperitoneal (i.p.) administration (i.p. LD50) in rats. Correlations between LC50 and oral LD50 in mice were also improved by the same unit conversion. The correlations between LC50 and i.p. LD50 were higher than those between LC50 and oral LD50 both in rats and mice. In these correlations, coefficients obtained in rats were greater than corresponding coefficients in mice. We calculated equations to estimate LC50 values accompanied by confidence limits from oral or i.p. LD50 values.

Administration, Oral↗
PubMed1998

Treatment of a Brodie bite by lower lateral expansion: a case report and fourth year follow-up.

The patient was a 4 year 4 month old boy at the first visit. The chief complaint was chewing dysfunction. The intra-oral and facial films, study casts, cephalometrics, muscle-balance monitor, temporomandibular joint radiographs were analyzed. The patient presented with a Brodie bite or unilateral posterior cross bite. The upper dental arch was wider than other children of his age. The lower dental arch was significantly smaller than the upper dental arch. The lower dental arch was expanded using a Schwarz appliance. The period of treatment was one year and two months. The period of observation was four years and ten months. First the patient underwent chewing training and secondarily then was treated by lateral expansion. After this treatment the patient achieved good occlusion and muscle function, while the morphology and function of the temporomandibular joints were improved, as well.

Cephalometry↗
PubMed1997

Stretch-induced hypertrophic growth of cardiocytes and processing of brain-type natriuretic peptide are controlled by proprotein-processing endoprotease furin.

When hypertrophic growth is induced in neonatal rat cardiocytes by stretching, the cardiocytes express high levels of brain-type natriuretic peptide (BNP) and the proprotein-processing enzyme furin. A BNP precursor, gammaBNP, possesses a furin-cleavable Arg-X-X-Arg motif, which is cleaved when gammaBNP is processed to form BNP-45. The Arg-X-X-Arg motif is found in many precursors of growth factors and growth-related proteins. To determine if furin converts gammaBNP to BNP-45 as well as other unidentified growth-promoting protein precursors to their active form that may induce hypertrophic growth in cardiocytes, we used two protease inhibitor systems, synthetic peptidyl chloromethyl ketones (CMK) (dec-Arg-Val-Lys-Arg-CMK and dec-Phe-Ala-Lys-Arg-CMK; where dec is decanoyl) and vaccinia vector-integrated native and variant alpha1-antitrypsins. The furin-specific inhibitors, dec-Arg-Val-Lys-Arg-CMK and variant alpha1-antitrypsin with the inhibitory determinant Arg-X-X-Arg, suppressed the stretch-induced hypertrophic growth of cardiocytes as well as the processing of gammaBNP to BNP-45. The other serine protease inhibitors and variant alpha1-antitrypsin against elastase, or thrombin, however, neither suppressed the hypertrophic growth nor prevented the processing of gammaBNP to BNP-45. Thus, we suggest that furin catalyzes the conversion of gammaBNP to BNP-45 as well as growth-promoting proproteins to their active form, which might induce hypertrophic growth in cardiocytes.

Animals↗
PubMed1997

Origin of the central cells of erythroblastic islands in fetal mouse liver: ultrahistochemical studies of membrane-bound glycoconjugates.

To clarify the origin of the central cells in hepatic erythroblastic islands, glycoconjugates on the surface of cellular constituents in fetal mice liver were ultrahistochemically examined using lectin staining. At 11 days of gestation, the cells derived from mesenchyme in fetal liver, including sinusoidal macrophages, endothelial cells, and erythropoietic cells, bound Griffonia simplicifolia isoagglutinin I-B4 (GS-I-B4), but hepatocytes lacked binding sites for the isolectin. Scavenger macrophages in the hepatic cords at 13 days of gestation and the central cells in the erythroblastic islands at 15 days of gestation also bound GS-I-B4. Hepatocytes, however, exhibited no GS-I-B4 binding site at any gestational day. At 11 days of gestation, none of the cells in fetal liver had binding sites for soybean agglutinin (SBA), but cells derived from mesenchyme acquired these binding sites at 13 days of gestation. The central cells in the erythroblastic islands also bound SBA, but hepatocytes did not bind the lectin at all. The central cells in the erythroblastic islands can be considered to belong to a mesenchymal cell lineage, and primitive sinusoidal macrophages at 11 days of gestation are possible precursors of these central cells.

Animals↗
PubMed1997

Prolonged resolution of hemophagocytic lymphohistiocytosis following myeloablative chemotherapy and subsequent autologous peripheral blood stem cell transplantation.

A 30-month-old boy with hemophagocytic lymphohistiocytosis (HLH) received an autologous peripheral blood stem cell transplant (PBSCT) following high-dose chemotherapy. He presented with hemophagocytic syndrome (HPS) at 6 months of age, but relapsed despite the repeated administration of prednisolone, VP-16, cyclosporin A (CsA), and other cytotoxic agents. PBSC were obtained using combination chemotherapy with etoposide (VP16, 450 mg/m2), doxorubicin (70 mg/m2), vincristine (2 mg/m2) and cyclophosphamide (CY, 1200 mg/m2). 2.7 x 10(5)/kg CFU-GM PBSC were transplanted after similar high-dose VP16 preconditioning used for allogeneic BMT for HLH. The boy continues to remain in complete remission 30 months after PBSCT while receiving low-dose PSL/CsA therapy. High-dose chemotherapy followed by PBSCT may be an optional therapeutic approach for patients with HLH.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Adult-onset type II citrullinemia: clinical pictures before and after liver transplantation.

In a 25-year-old man with adult-onset type II citrullinemia, liver transplantation resulted in elimination of hyperammonemia and amino acid abnormalities associated with the disease. Postoperatively, a high intensity area in the right cingulate gyrus on a T2-weighted brain magnetic resonance imaging (MRI) also disappeared, suggesting that it reflected an early reversible lesion due to the hyperammonemia. Moreover, the serum level of pancreatic secretory trypsin inhibitor (PSTI), which had been elevated, was normalized. Since the levels of PSTI mRNA and PSTI have been reported to be increased in the livers of type II citrullinemia patients, measurement of serum PSTI levels could aid in the diagnosis of this disease.

Adult↗
PubMed1997

Proprotein-processing endoprotease furin controls growth of pancreatic beta-cells.

We have previously reported that in the well-differentiated beta-cell line MIN6 cells, the beta-cell-specific differentiated characteristics, such as insulin content, expression of prohormone convertases PC2 and PC3, and glucose-regulated insulin secretion, diminished when the proprotein-processing endoprotease furin was highly expressed. Since furin converts many growth-related protein precursors to their bioactive forms, we compared the four pancreatic islet cell lines RINm5F, betaTC3, betaHC9, and MIN6 with respect to cell growth rate, furin expression, endoprotease activity, and insulin content. RINm5F cells exhibited the strongest furin expression, higher furin-type endoprotease activity, and the fastest cell growth, but had the least insulin content. In contrast, MIN6 cells exhibited only a weak furin expression, little furin-type endoprotease activity, and the slowest cell growth, but had the highest insulin content. To test whether furin-expressing cells secrete growth-promoting factors cleaved by furin, we prepared conditioned media from RINm5F and furin cDNA-introduced MIN6 (MIN6-F) cells. The conditioned media from RINm5F and MIN6-F induced increased DNA synthesis and promoted the growth of normal MIN6 cells, compared with the medium from the empty vector-introduced MIN6-0 cells. We then examined the effect of the protease inhibitors alpha1-antitrypsin and its variants by infecting their vaccinia recombinants to the four cell lines. All conditioned media from each cell line expressing the furin-specific alpha1-antitrypsin variant exhibited the least DNA synthetic capacity on normal MIN6 cells. Furthermore, all three sublines of MIN6-F grew faster than MIN6-0 and MIN6. Thus, we suggest that the islet cells with higher furin expression may induce increased production of growth factors, which result in an increase in cell growth, through an autocrine/paracrine mechanism.

Animals↗
PubMed1997

Changes in plasma lipoproteins as toxicity markers for carbon tetrachloride, chloroform, and dichloromethane.

Effects of single intraperitoneal (i.p.) administration of carbon tetrachloride (CCl4), chloroform (CHCl3), and dichloromethane (CH2Cl2) on lipoproteins in plasma and liver were investigated in rats. Changes in lipoproteins caused by these solvents were compared with changes in traditional hepatotoxicity markers such as GPT (ALT). Following the administration, concentrations of lipoproteins (VLDL, LDL, HDL), triglyceride, cholesterol, and GPT activity in plasma were determined through changes in liver weight, liver content of triglyceride, malon dialdehyde (MDA), and glutathione (GSH). Time-course study revealed that changes in plasma and liver reached their peaks at 19 or 32 hr following the administration of CCl4 or CHCl3. Peaks of changes were observed at 8 or 19 hr following the administration of CH2Cl2. Dose dependency of these changes was investigated at dosages of 3, 30, and 300 mg/kg of CCl4 or CHCl3, and 300, and 1,000 mg/kg of CH2Cl2. Significant decreases in triglyceride and apolipoproteins in VLDL fraction were observed at 3 mg/kg of CCl4. Such VLDL components decreased at 30 mg/kg of CHCl3. HDL decreased significantly at 300 mg/kg of CH2Cl2 and marked increase in LDL occurred at 1,000 mg/kg of the solvent. Liver weight and liver content of triglyceride and MDA significantly increased at 30 mg/kg of CCl4, while significant increase in GPT activity was observed at 300 mg/kg of CCl4 and CHCl3. GPT increased significantly at 1,000 mg/kg of CH2Cl2. These results revealed that changes in plasma lipoproteins can serve as sensitive and simple markers for liver disorders caused by chlorinated hydrocarbon solvents such as CCl4, CHCl3, or CH2Cl2.

Analysis of Variance↗
PubMed1997

Death process of primitive erythrocytes and phagocytosis by liver macrophages of the mouse embryo.

Primitive erythrocytes from the yolk sac are nucleated cells which have a short life span of several days in the embryonic circulation of the mouse. The death process of primitive erythrocytes was ultrastructurally investigated in embryonic mice. At 12 days of gestation, primitive erythrocytes accounted for 96.1% of the circulating erythrocytes. The percentages in 13-, 14-, 15- and 18-day-embryos were 43.8%, 15.4%, 7.7% and 0.0%, respectively. Between 13 and 15 days, anucleate primitive erythrocytes made up from 1.5% to 5.9% of circulating erythrocytes. During the gestational period, the nuclei of primitive erythrocytes markedly decreased in volume, and the chromatin underwent condensation and marginated to crescents along the nuclear envelope. Following nuclear fragmentation and dissolution of condensed chromatin, nuclear residues were finally formed in aging primitive erythrocytes. Formation of annulate lamellae was also observed, associated with the nuclear shrinkage. The nuclei had an apoptotic-like appearance, but TUNEL-positive reactions could not be identified in any nuclei of the primitive erythrocytes. Dying erythrocytes with nuclear residues were phagocytosed in toto by hepatic macrophages and disposed of from embryonic circulation without enucleation.

Animals↗