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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 361 records · Page 20Linked to original sources

Sexual dimorphism in the tooth crown dimensions of the second deciduous and first permanent molars of Taiwan Chinese.

Sexual dimorphism in the crown components in the second deciduous molar (dm2) and the first permanent molar (M1) of the dental casts taken from Chinese living in Kaohsiung (Taiwan) was investigated. Mesiodistal and buccolingual crown diameters, and 4 main-cusp sizes in the maxillary molars and mesiodistal diameters of the trigonid and talonid in the mandibular molars were measured using a digital caliper (0.01 mm). Percentage sexual differences were calculated. With the exception of trigonid mesiodistal diameters, the mean values of males were larger than females. In both of dm2 and M1 the mean values of the trigonid mesiodistal diameters were slightly larger in females than in males, but the differences were not significant. Percentage sexual dimorphism was smaller in the mesiodistal diameters than in the buccolingual in both dm2 and M1. The crown components showed larger sexual difference in dm2 than in M1, while in the maxilla the external crown size showed larger sexual difference in M1 than in dm2. The buccal cusps showed larger sexual difference than the lingual in the maxillary molars and the talonid showed larger sexual difference than the trigonid in the mandibular. Sexual dimorphism of dm2 and M1 in their crown components displayed similar pattern, although the different degree was noted. This result is thought to relate to the fact these molars belong to the first dentition embryologically.

China↗

Antagonist effect of insulin-like growth factor I on protein kinase inhibitor-mediated apoptosis in human glioblastoma cells in association with bcl-2 and bcl-xL.

OBJECT: Tamoxifen (TAM) has been found to be effective in inhibiting proliferation of glioblastoma cells in vitro, but clinical studies have been disappointing. The purpose of this study was to determine whether insulin-like growth factor I (IGF-I), a potential autocrine/paracrine mitogen produced by glioblastomas, interferes with the antimitogenic actions of TAM. METHODS: Human glioblastoma cells were treated with or without TAM and/or IGF-I in vitro and evaluated for: viability by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide cleavage assay; apoptosis by histochemical analysis of nuclear morphology and 3'-OH DNA fragments; and expression of the IGF-I receptor, and the bcl-2, bcl-xL, and bax proteins by immunoblot analysis. In addition, p53 status was determined by DNA sequencing and by transient transfection with luciferase reporter plasmids containing wild-type or mutant p53. Results indicated that after 72 hours of exposure to 2 mg/ml TAM in vitro, 56.3% of WITG3 and 43.8% of U87-MG glioblastoma cells contained apoptotic nuclei (p < 0.01 compared with untreated cells). Apoptosis was independent of the presence of p53 because the WITG3 cells, in contrast to the U87-MG cells, expressed a mutant, nonfunctional p53. The WITG3 cells expressed IGF-I receptor proteins and demonstrated IGF-I binding. Exogenous IGF-I stimulated WITG3 cell proliferation and significantly (p < 0.05) antagonized the cytotoxic effects of TAM in a dose-dependent fashion; IGF-I, but not TAM, enhanced expression of bcl-2 and bcl-xL proteins; however, bax protein expression was unchanged by either treatment. CONCLUSIONS: Because many gliomas secrete large amounts of IGF-I in autocrine/paracrine growth pathways, these data may, in part, explain the failure of TAM to achieve clinical results as dramatic as those in vitro.

Antineoplastic Agents, Hormonal↗

Synthesis and activity of 3-epi-actinobolin.

3-epi-Actinobolin was synthesized by the chemical transformation of actinobolin involving a key step of the reconstruction of fused delta-lacton skeleton via intramolecular acylation reaction. The analogue with low toxicity weakly inhibits Gram-positive and Gram-negative bacteria.

Anti-Bacterial Agents↗

The novel enzymatic 3''-N-acetylation of arbekacin by an aminoglycoside 3-N-acetyltransferase of Streptomyces origin and the resulting activity.

Kanamycin group antibiotics were subjected to enzymatic acetylation by a cell free extract containing an aminoglycoside 3-N-acetyltransferase, AAC(3)-X, derived from Streptomyces griseus SS-1198PR. Characterization of the incubated reaction mixtures by TLC and antibiotic assay revealed that a product retaining activity was specifically formed from arbekacin, an anti-MRSA semisynthetic aminoglycoside. The structural determination demonstrated that acetylation occurred at the 3"-amino group in arbekacin and amikacin, and at the 3-amino group in dibekacin as in the case of kanamycin. These results should reflected the effect of the (S)-4-amino-2-hydroxybutyryl side chain which is present in arbekacin and amikacin, but absent in dibekacin and kanamycin. The 3"-N-acetylation is the first finding in the enzymatic modifications of aminoglycoside antibiotics. 3"-N-Acetylarbekacin showed antibiotic activity as high as that of 2'-N-acetylarbekacin reported previously, whereas 3"-N-acetylamikacin showed no substantial activity. Thus, our results illuminated a novel aspect of arbekacin distinct from the other aminoglycosides.

Acetylation↗

High production of nondisjunction mutants in the offspring of Drosophila melanogaster females exposed to carbon dioxide at meiosis I.

Drosophila melanogaster females homozygous for X-linked recessive markers, y and wi, were exposed to CO2 and mated with y+ w+/Y males. The progeny were sampled and inspected for y wi/y wi/Y (XXY) and y+ w+/O (XO) mutants. The frequency of nondisjunction XXY mutants after a 90-min exposure to CO2 increased 100-fold above the control level in the first-day brood but did not increase above the control level in the second to sixth broods, showing that CO2 is an extremely potent inducer of nondisjunction in mature oocytes during meiotic metaphase I but is not harmful to immature oocytes. Nondisjunction-causing damage induced by CO2 in mature oocytes disappeared completely within one day after CO2 treatment, as evidenced by a reduction of the number of XXY mutants to the control level when the mating of CO2-treated females was delayed by one day. CO2-induced nondisjunction is probably due to damage to spindle microtubules in mature oocytes at metaphase I. N2 is a less potent inducer of nondisjunction than CO2. Maternal X-irradiation with 4 Gy did not induce XXY mutants, showing that medium-level radiation does not induce nondisjunction. The results support Gaulden's hypothesis that oxygen deficits and CO2 increases in the microenvironment of mature oocytes can be potent inducers of nondisjunction. The possible relationship to the cluster of Down syndrome seen in Berlin shortly after the Chernobyl accident is discussed.

Aneuploidy↗

Lipodystrophia centrifugalis abdominalis infantilis.

AIM: To describe the clinical features of lipodystrophia centrifugalis abdominalis infantilis (LCAI) with special attention to the erythema which is seen around the depressed lesion. BACKGROUND: LCAI is a rare disorder which occurs mainly in Asian people, particularly in Japanese; it usually begins as an erythematous macule which subsequently expands centrifugally and leaves a central depression. However, the erythema has been seldom documented in detail. We here report a case of LCAI observed from its early stage and review the literature. CASE REPORT: A 2-year-old Japanese girl was brought to our out-patient clinic. Clinical examination revealed a slight depression surrounded by faint erythema that mimicked morphea on her left inguinum, but there was no hardening of the skin. The erythema disappeared 5 months after onset. Thereafter, the lipodystrophy expanded irrespective of the treatment to her right inguinum and lower abdomen. CONCLUSIONS: The depression continues to grow without the erythema in most patients. This suggests that the erythema is not necessary for enlargement of the depression although it precedes the depression in most patients.

Anti-Inflammatory Agents↗

Involvement of interleukin-1beta-converting enzyme in apoptosis of irradiated retinoblastomas.

PURPOSE: To investigate whether interleukin-1beta-converting enzyme (ICE), a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, is involved in gamma-irradiation-induced apoptosis (programmed cell death) of human retinoblastoma cells. METHODS: The induction of apoptotic cell death in human retinoblastoma cell lines WERI-Rb-1 and Y79 by gamma-irradiation was determined with a modified 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide colorimetric assay and the DNA-binding fluorochrome bis (benzimide) trihydro-chloride (Hoechst 33258) staining. The change of ICE protein level in tumor cells during apoptosis was determined by immunoblotting assay. Whether the specific tetrapeptide ICE inhibitor Ac-YVAD-CMK affected gamma-irradiation-induced apoptosis in tumor cells was also examined. The effect of ICE overexpression on tumor cells was evaluated by a transient transfection assay using ICE expression vector. RESULTS: Gamma-irradiation inhibited the cell viability of WERI-Rb-1 and Y79 cells in a dose-dependent manner and induced apoptosis. The protein level of ICE was remarkably enhanced after the treatment. The apoptotic cell death induced by gamma-irradiation was suppressed by the tetrapeptide ICE inhibitor Ac-YVAD-CMK. Moreover, overexpression of ICE induced apoptosis in tumor cells. CONCLUSIONS: These findings suggest that ICE may play an important role in gamma-irradiation-induced apoptosis in retinoblastoma cells. Transfer of the ICE gene induces apoptosis in these cells without gamma-irradiation.

Amino Acid Chloromethyl Ketones↗

[Value of paraaortic lymphadenectomy for gallbladder carcinoma].

Seven reports of paraaortic lymphadenectomy for advanced carcinoma of the gallbladder were reviewed and positive paraaortic nodes were found in 20-40% of the resected patients and 10-15% of those with subserosal cancer invasion. The rate of patients with positive paraaortic nodes/all patients with positive nodes was 30-50%. Paraaortic lymphadenectomy did not improve the surgical outcome, and most of the patients with positive paraaortic nodes died within 1 year even after aggressive surgery with extensive lymph node dissection. Therefore it is important to clarify the value of paraaortic lymph node dissection for patients with possibly positive paraaortic node metastasis and those with histologically positive nodes excluding the paraaortic area. Although pancreatoduodenectomy for prophylactic lymphadenectomy around the head of the pancreas has been carried out in some institutions, the procedure does not seem to be effective because the main lymphatic route from the gallbladder has a direct connection with the paraaortic nodes via the pericholedochal, periportal, and/or the posterior nodes along the common hepatic artery. The present authors recommend a D2 plus paraaortic lymph node dissection (ext D2) as a standard surgical strategy for carcinoma of the gallbladder.

Aorta↗

Depressed Langerhans cell migration and reduced contact hypersensitivity response in mice lacking TNF receptor p75.

Epidermal Langerhans cells (LC) belong to the dendritic cell family and represent the major APC within the skin. LC capture epicutaneous Ag, migrate into regional lymph nodes, and present Ag to T cells, thereby initiating primary immune response. The migratory properties of LC are an essential component of their function. The molecular mechanisms responsible for LC migration are far less defined. However, evidence has been accumulating to suggest that TNF-alpha, a major proinflammatory cytokine, plays an important role in promoting DC migration. To confirm the role of TNF-alpha in LC migration and to examine which type of TNF receptor signaling is involved in such an event, we utilized gene-targeted knockout mice lacking TNF receptor p55 or p75. The migration of LC was assessed by examining the frequency of hapten-bearing cells in draining lymph nodes following hapten FITC painting, and the accumulation of dendritic cells in draining lymph nodes after intradermal injection of TNF-alpha. While LC migration was normal in p55-deficient mice, the migration was markedly depressed in p75-deficient mice. Receptor p75-deficient mice also demonstrated a hyporesponsiveness in allergen-induced contact dermatitis, but a normal responsiveness in irritant-induced contact dermatitis. These results suggest that p75-dependent signaling plays a crucial role in the migration of LC and in the initiation of cutaneous immune responses.

Administration, Cutaneous↗

The membrane-bound form of heparin-binding epidermal growth factor-like growth factor promotes survival of cultured renal epithelial cells.

To understand whether expression of membrane-anchored heparin binding epidermal growth factor (proHB-EGF) is involved in renal epithelial cell survival, rat membrane-bound HB-EGF precursor was stably transfected into a renal epithelial cell line, NRK 52E cells (NRKproHB-EGF). When exposed to 10% fetal calf serum (FCS), there were no differences in growth rates among wild-type (WT), vector-transfected (NRKvector), and NRKproHB-EGF. However, when cells were grown in the presence of 1% FCS, the growth rate of NRKproHB-EGF was 65% faster. When confluent cell monolayers were exposed to H2O2 or etoposide, WT or NRKvector exhibited significant apoptotic bodies and DNA laddering; in contrast, NRKproHB-EGF were resistant to both stimuli, as indicated by increased cell viability and marked decrease of apoptotic bodies and DNA laddering. When plated at high density onto plastic dishes without FCS, WT and NRKvector formed few attachments, did not proliferate, and underwent apoptosis. By day 3, no cells survived. Addition of exogenous recombinant HB-EGF (10(-8) M) to WT or NRKvector increased cell survival by <10% and incubation with conditioned media of NRKproHB-EGF had no effect. In contrast, NRKproHB-EGF attached and formed epithelial colonies, although they did not proliferate. After 3 days, cell viability was 84% of the initial cell number plated, and no evidence of apoptosis was present. When plated in 10% FCS, NRKproHB-EGF attachment to plastic substratum at 1, 2, and 3 h was 250% greater than that of WT or NRKvector. Addition of exogenous recombinant human HB-EGF to WT or NRKvector increased attachment by <50%. When grown on poly(2-hydroxyethyl methacrylate) or in the presence of the integrin receptor-blocking peptide GRGDTP, neither WT nor NRKvector attached to the substratum or formed cell-cell attachments. Compared with WT or NRKvector, NRKproHB-EGF exhibited 300% greater cell viability on either poly(2-hydroxyethyl methacrylate)-coated dishes or in the presence of GRGDTP and formed cell clusters. When plated at low density (1 x 10(3) cells/1.5-cm dish) or at high density in the presence of an anti-HB-EGF blocking antibody, NRKproHB-EGF failed to form epithelial colonies. Addition of formalin fixed NRKproHB-EGF promoted EGF receptor tyrosine phosphorylation in quiescent A431 cells and stimulated DNA synthesis and prevented H2O2-induced apoptosis in renal epithelial cells. These results indicate that membrane-bound HB-EGF promotes renal epithelial cell survival, possibly by promoting cell-matrix and cell-cell interactions. The failure of either conditioned media or exogenous HB-EGF to reproduce these findings suggests that juxtacrine or tightly coupled paracrine interactions underlie this cytoprotection.

Animals↗

Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress.

A cDNA library of human umbilical vein endothelial cells exposed to fluid shear stress was constructed to search for functional endothelial genes expressed under flow conditions, and cDNAs encoding members of the G protein-coupled receptor (GPCR) family were cloned by a polymerase chain reaction (PCR) method using degenerate oligonucleotide primers. One of the two GPCR clones obtained was edg-1, and the other clone is a novel gene named FEG-1 that encodes a 375-amino acid protein similar to the receptors for both angiotensin II and chemokines. Reverse transcriptase-PCR showed that the FEG-1 and edg-1 mRNA levels in endothelial cells increased markedly in response to fluid flow. This suggests that FEG-1 and edg-1 may be receptor genes that play important roles in the regulation of endothelial function under physiological blood flow conditions.

Amino Acid Sequence↗

Involvement of p53 and WAF1/CIP1 in gamma-irradiation-induced apoptosis of retinoblastoma cells.

Retinoblastoma is an intraocular malignancy of childhood, which is very radiosensitive. gamma-irradiation, however, induces side effects, and the precise mechanisms of tumor cell death after the treatment remain unknown. In this study, we demonstrated that gamma-irradiation induced apoptosis (programmed cell death) in human retinoblastoma cell lines Y79 and WERI-Rb-1. The expression levels of p53, tumor suppressor gene product, and its-associated protein, WAF1/CIP1, were both up-regulated, and function of p53 was remarkably activated after the treatment. Moreover, apoptosis was induced in the absence of gamma-irradiation by overexpression of the WAF1/CIP1 gene in both retinoblastoma cells. These results indicate that the transfer of the WAF1/CIP1 gene may have potential for the treatment of human retinoblastomas instead of gamma-irradiation.

Apoptosis↗

A 1.2-megabase BAC/PAC contig spanning the 14q13 breakpoint of t(2; 14) in a mirror-image polydactyly patient.

We previously assigned a 14q13 breakpoint of t(2; 14) in a patient with mirror-image polydactyly to a segment between two loci, AFM200ZH4 and D14S306, within a genetic distance of 0.6 cM. In the present study, we constructed a 1.2-Mb high-resolution physical map with a contig composed of 16 bacterial artificial chromosomes (BACs) and 6 P1-derived artificial chromosomes (PACs) at a region around the breakpoint, extending from D14S75 to D14S728 loci. Thirty-four novel sequence-tagged sites (STSs) were also characterized at this region. Of nine ESTs that had been mapped between D14S75 and D14S288, T99065 was confirmed to be in two BAC clones, B102 and B319. This BAC/PAC contig with STSs is useful for further genomic sequencing, for construction of a transcription map, and for the isolation of the putative gene for mirror-image polydactyly.

Chromosome Mapping↗

Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome.

KIF (kinesin superfamily) proteins are microtubule-dependent molecular motors that play important roles in intracellular transport and cell division. The extent to which KIFs are involved in various transporting phenomena, as well as their regulation mechanism, are unknown. The identification of 16 new KIFs in this report doubles the existing number of KIFs known in the mouse. Conserved nucleotide sequences in the motor domain were amplified by PCR using cDNAs of mouse nervous tissue, kidney, and small intestine as templates. The new KIFs were studied with respect to their expression patterns in different tissues, chromosomal location, and molecular evolution. Our results suggest that (i) there is no apparent tendency among related subclasses of KIFs of cosegregation in chromosomal mapping, and (ii) according to their tissue distribution patterns, KIFs can be divided into two classes-i.e., ubiquitous and specific tissue-dominant. Further characterization of KIFs may elucidate unknown fundamental phenomena underlying intracellular transport. Finally, we propose a straightforward nomenclature system for the members of the mouse kinesin superfamily.

Amino Acid Sequence↗

Synthesis and antimetastatic activity of L-iduronic acid-type 1-N-iminosugars.

L-Iduronic acid-type 1-N-iminosugars, (3R,4S,5R,6R)- and (3R,4S,5S,6R)-6-acetamido-4-amino-5-hydroxypiperidine-3-carboxylic acid (6 and 7, respectively), (3R,4S,5R,6R)-6-acetamido-4- guanidino-5-hydroxypiperidine-3-carboxylic acid (8), and (3R,4S,5R,6R)-4-amino- and -guanidino-5-hydroxy-6-(trifluoroacetamido) piperidine-3-carboxylic acid (9 and 10, respectively), were synthesized from siastatin B (1), isolated from Streptomyces culture, by the intramolecular Michael addition of O-imidate to its alpha,beta-unsaturated ester through cis oxiamination as a key step. Preincubation of B16 BL6 cells with these compounds inhibited invasion of the cells through reconstituted basement membranes. Pulmonary metastasis of B16 BL6 cells in mice was remarkably inhibited by pretreatment of the cells with these compounds in culture.

Animals↗

The CDK inhibitor, p27Kip1, is required for IL-4 regulation of astrocyte proliferation.

IL-4 is a pleiotrophic cytokine that has been shown to affect cells of the central nervous system. We have demonstrated that IL-4 inhibits DNA synthesis and proliferation in human astroglia expressing IL-4 receptors. In this study, we sought to identify mechanisms that could account for the antimitogenic effects of IL-4. Epidermal growth factor (EGF)-stimulated human astroglia were arrested in G1 phase by IL-4, even though IL-4 stimulated levels of the G1 cyclins, D1 and E. Histone H1 kinase activity of cdk2 immunoprecipitates, however, was sharply reduced by IL-4; impairment of kinase activity was also evident in cyclin E immunoprecipitates, which contained evidence of hypophosphorylated (inactive) cdk2 product. Reduced cyclin E-associated cdk2 activity was not due to impaired cyclin-dependent kinase-activating kinase (CAK) activity, which was unaffected by IL-4. Inactive cyclin E/cdk2 complexes from IL-4 + EGF-treated cells contained, however, strikingly elevated p27Kip1 cdk inhibitor. Elevated p27 was also detectable in whole cell lysates after 24 and 48 h of IL-4 treatment; by 72 h, p27 was no longer elevated. Pretreatment with antisense but not mismatch p27 oligonucleotides attenuated the inhibitory effects of IL-4 on DNA synthesis and histone kinase activity of cyclin E/cdk2 complexes. Antisense p27 also abrogated IL-4-mediated elevation of p27 in whole cell lysates and cyclin E/cdk2 complexes. These findings demonstrate that IL-4 regulates the cell cycle machinery of astroglial cells via a p27Kip1 braking mechanism.

Antigens, CD↗