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Biomedical subjects

S J Yoon

Publications and source records attributed to S J Yoon.

At least 55 records · Page 3Linked to original sources

Expression of DAZ (deleted in azoospermia), DAZL1 (DAZ-like) and protamine-2 in testis and its application for diagnosis of spermatogenesis in non-obstructive azoospermia.

Spermatogenesis is regulated by hormones, local regulatory factors in the testes and specific gene expression of spermatogenic cells in humans. In this study, we have detected the expression of the deleted in azoospermia (DAZ), the DAZ-like autosome (DAZL1), and the protamine-2 genes in spermatogenic cells. Spermatogenesis in 38 male infertility patients was evaluated by the semen analysis and histological examination. Patients were diagnosed as Sertoli cell-only syndrome (n = 20), maturation arrest (n = 6), hypospermatogenesis (n = 6), and obstructive azoospermic patients with normal spermatogenesis (n = 6). After microscopic observation of the wet preparation of the testis tissues, seminiferous tubule contents were used for reverse transcription-polymerase chain reaction (RT-PCR) analysis of DAZ, DAZL1 and protamine-2. In cases with Sertoli-cell only syndrome, we found spermatogenic cells in 30% of patients (6/20) by the wet preparation method. There was no difference between the histology and the wet preparation results in maturation arrest and obstructive azoospermia; however, in one case of hypospermatogenesis, spermatozoa were not detectable by the wet preparation method. Using in-situ hybridization with DAZ and protamine-2 ribonuclear probes, we confirmed spermatogenic cell-specific expression of DAZ (spermatogonia/early spermatocyte) and protamine-2 (spermatid/spermatozoon). DAZ and protamine-2 expression can therefore be considered spermatogenic cell markers and could be useful in molecular diagnosis of spermatogenesis. In 13 patients with spermatozoa under the wet preparation, the expression of DAZ, DAZL1 and protamine-2 was detected in all the preparations. In one wet preparation showing only spermatogonia/spermatocyte, only DAZ and DAZL1 RNA were detected. In 14 wet preparations showing no spermatogenic cells, DAZ, DAZL1 and protamine-2 were not detected except in one preparation where DAZL1 expression was detected. In 10 wet preparations representing spermatogonia/spermatocyte to spermatids, but showing no spermaozoa, DAZ and DAZL1 were detected in eight and nine preparations respectively, and protamine-2 was detected in six preparations. These results of gene expression were similar to the wet preparation results. RT-PCR for DAZ, DAZL1 and protamine-2 was informative for the existence of germ cells, germ cell physiology and differentiation. From these results, we suggest that the analysis of DAZ, DAZL1 and protamine-2 expression by RT-PCR and wet preparation might offer a better method for finding the spermatogenic cells compared to the histological method.

Actins↗

Toxicities of 166Holmium-chitosan in mice.

166Holmium (166Ho) is a radionuclide of rare earth chemical and is known to have antitumor activity. Several chemicals were complexed with 166Ho to facilitate the transport of this radionuclide to the site of action. In this study, 166Ho was complexed to chitosan (Chit) which decreases the distribution of Ho into other tissues when applied intrahepatically. To investigate the single dose toxicity, mice were administered intravenously with 1 mCi/kg body weight of 166Ho-Chit (DW-166HC), Chit or nothing. Organ weights, hematological and histopathological studies were performed in 6 animals per group at 1, 3 and 14 days after administration. In 166Ho-Chit treated animals, a slight decrease of erythrocyte number was observed at day 14 and increases of relative liver and lung weights were found at day 3. Although marked multiple necrotic foci in the white pulp and depletion of marginal zone in the spleen were noted at day 1, these findings were decreased in severity and fully recovered at day 3 and day 14, respectively. Slightly decreased kidney weights were observed both in Chit and in 166Ho-Chit treated groups without histological alterations. Thus it is suggested that most effects of 166Ho-Chit observed at an early stage after administration are limited to rapidly dividing cells and reversible within 14 days.

Animals↗

In-vitro and in-vivo activities of DW-116, a new fluoroquinolone.

DW-116 is a novel fluoroquinolone that was two- to four-fold more active than rufloxacin and less active than sparfloxacin, ciprofloxacin and ofloxacin against Gram-positive bacteria in vitro. Against Gram-positive and Gram-negative bacteria, the in-vivo activity of DW-116 was similar or slightly greater than that of rufloxacin and less than that of sparfloxacin, ciprofloxacin and ofloxacin. ED50 (50% effective dose) values for DW-116 did not correlate with in-vitro MICs.

Animals↗

Characterization of human DSPG3, a small dermatan sulfate proteoglycan.

PG-Lb is a small dermatan sulfate proteoglycan that has been previously characterized in chicken. In the developing limb, chick PG-Lb appears to be exclusively expressed in the zone of flattened chondrocytes. We have cloned and sequenced the human homolog to chick PG-Lb from two human chondrocyte cDNA libraries and a human chondrocyte RNA sample. The human homolog has been named DSPG3, as it is the third member of the small dermatan sulfate proteoglycan family to be identified and characterized along with biglycan (PG-I) and decorin (PG-II). DSPG3 maps to chromosome 12q21 and is composed of 1515 nucleotides of cDNA that code for a 322-amino-acid protein. The protein contains three potential glycosaminoglycan attachment sites, two N-glycosylation sites, a poly- glutamic acid stretch, and six cysteines. By Northern analysis, we have demonstrated that DSPG3 is expressed in cartilage, as well as ligament and placental tissues.

Amino Acid Sequence↗

Glucocorticoid regulation of androgen binding protein expression in primary Sertoli cell cultures from rats.

Glucocorticoids are known to inhibit testicular function, and its receptor is also localized in the Sertoli cells. To evaluate possible role of glucocorticoid in Sertoli cells, the effects of dexamethasone on the expression of androgen binding protein (ABP) have been investigated in primary Sertoli cell cultures. Dexamethasone increased ABP mRNA levels, with maximal stimulation reached at 36 hr. The induction of ABP mRNA was dependent on the low concentration (10(-8) and 10(-7) M) of dexamethasone but gradually reduced in the cells treated with high concentration (10(-6) and 10(-5) M). Dexamethasone-induced ABP mRNA level was no change in the cells after addition of cycloheximide but almost reduced by actinomycin-D pretreatment. Steady-state levels of ABP mRNA gradually increased in the Sertoli cells prepared from 14- and 21-days of age corresponding to rat puberty, and ABP mRNA was induced by dexamethasone. These results suggest that ABP gene is transcriptionally regulated by dexamethasone in primary Sertoli cell cultures.

Age Factors↗

Translocation breakpoints upstream of the HMGIC gene in uterine leiomyomata suggest dysregulation of this gene by a mechanism different from that in lipomas.

Uterine leiomyomata are the most common pelvic tumors in women and are the indication for more than 200,000 hysterectomies annually in the United States. Rearrangement of chromosome 12 in bands q14-q15 is characteristic of uterine leiomyomata and other benign mesenchymal tumors, and we identified a yeast artificial chromosome (YAC) spanning chromosome 12 translocation breakpoints in a uterine leiomyoma, a pulmonary chondroid hamartoma, and a lipoma. Recently, we demonstrated that HMGIC, which is an architectural factor mapping within the YAC, is disrupted in lipomas, resulting in novel fusion transcripts. Here, we report on the localization of translocation breakpoints in seven uterine leiomyomata from 10 to > 100 kb upstream of HMGIC by use of fluorescence in situ hybridization. Our findings suggest a different pathobiologic mechanism in uterine leiomyomata from that in lipomas. HMGIC is the first gene identified in chromosomal rearrangements in uterine leiomyomata and has important implications for an understanding of benign mesenchymal proliferation and differentiation.

Chromosomes, Human, Pair 12↗

Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2.

Hereditary haemorrhagic telangiectasia, or Osler-Rendu-Weber (ORW) syndrome, is an autosomal dominant vascular dysplasia. So far, two loci have been demonstrated for ORW. Linkage studies established an ORW locus at chromosome 9q3; endoglin was subsequently identified as the ORW1 gene. A second locus, designated ORW2, was mapped to chromosome 12. Here we report a new 4 cM interval for ORW2 that does not overlap with any previously defined. A 1.38-Mb YAC contig spans the entire interval. It includes the activin receptor like kinase 1 gene (ACVRLK1 or ALK1), a member of the serine-threonine kinase receptor family expressed in endothelium. We report three mutations in the coding sequence of the ALK1 gene in those families which show linkage of the ORW phenotype to chromosome 12. Our data suggest a critical role for ALK1 in the control of blood vessel development or repair.

Activin Receptors↗

Physical mapping of the human ELA1 gene between D12S361 and D12S347 on chromosome 12q13.

ELA1, the pancreatic elastase 1 gene, is conserved in mammalian genomes. ELA1 was previously mapped to chromosome 12 using a panel of mouse-human somatic cell hybrids. We now report the physical and cytogenetic localization of the ELA1 gene. On the physical map, ELA1 is adjacent to the polymorphic marker AFMa283yg1 and between D12S361 and D12S347. Using fluorescence in situ hybridization, we determined that ELA1 maps to 12q13.

Animals↗

A second-generation YAC contig map of human chromosome 12.

Human chromosome 12 constitutes approximately 4.5% of the human genome and has an estimated size of 135 million base pairs (Mb). We have started to construct a high-resolution physical map of chromosome 12 as overlapping yeast artificial chromosomes (YACs), using as a foundation the first-generation physical map of this chromosome covers nearly 102 Mb of DNA and includes 426 highly polymorphic, monomorphic and gene-based markers. We also mapped 119 of the YACs, most of which are part of the physical map, by cytogenetic methods. Thus the map integrates genetic, physical and cytogenetic data and provides information about the organization of this chromosome and will help in the localization and cloning of disease-related genes. The strategy used here to generate the chromosome-12 map could be applied for the rapid construction of physical and expression maps for other human chromosomes.

Base Sequence↗

Identification of a YAC spanning the translocation breakpoints in uterine leiomyomata, pulmonary chondroid hamartoma, and lipoma: physical mapping of the 12q14-q15 breakpoint region in uterine leiomyomata.

Uterine leiomyomata are the most common tumors in women and can cause abnormal uterine bleeding, pelvic pain, and infertility. Approximately 200,000 hysterectomies are performed annually in the U.S. to relieve patients of the medical sequelae of these benign neoplasms. Our efforts have focused on cloning the t(12;14)(q14-q15;q23-q24) breakpoint in uterine leiomyoma to further our understanding of the biology of these tumors. Thirty-nine YACs and six cosmids mapping to 12q14-q15 have been mapped by fluorescence in situ hybridization to tumor metaphase chromosomes containing a t(12;14). One YAC spanned the translocation breakpoint and was mapped to tumor metaphases from a pulmonary chondroid hamartoma containing a t(12;14)(q14-q15;q23-q24) and a lipoma containing a t(12;15)(q15;q24); this YAC also spanned the breakpoint in these two tumors, suggesting that the same gene on chromosome 12 may be involved in the pathobiology of these distinct benign neoplasms.

Base Sequence↗

Organization of the human keratin type II gene cluster at 12q13.

Keratin proteins constitute intermediate filaments and are the major differentiation products of mammalian epithelial cells. The epithelial keratins are classified into two groups, type I and type II, and one member of each group is expressed in a given epithelial cell differentiation stage. Mutations in type I and type II keratin genes have now been implicated in three different human genetic disorders, epidermolysis bullosa simplex, epidermolytic hyperkeratosis, and epidermolytic palmoplantar keratoderma. Members of the type I keratins are mapped to human chromosome 17, and the type II keratin genes are mapped to chromosome 12. To understand the organization of the type II keratin genes on chromosome 12, we isolated several yeast artificial chromosomes carrying these keratin genes and examined them in detail. We show that eight already known type II keratin genes are located in a cluster at 12q13, and their relative organization reflects their evolutionary relationship. We also determined that a type I keratin gene, KRT18, is located next to its partner, KRT8, in this cluster. Careful examination of the cluster also revealed that there may be a number of additional keratin genes at this locus that have not been described previously.

Amino Acid Sequence↗

High glucose can induce lipid peroxidation in the isolated rat glomeruli.

The present study examined the effect of elevated glucose on glomerular cell membrane lipid peroxidation. Glomeruli were isolated from male Sprague-Dawley rat kidneys utilizing a standard sieving method and incubated in medium containing different concentrations of glucose at 37 degrees C for one and 48 hours. The levels of lipid peroxides (LPO) in the glomeruli were quantitated by malondialdehyde-thiobarbituric acid adduct formation. The levels of LPO in the glomeruli were significantly increased after one hour of exposure to high glucose (HG; 30 mM) medium, and this increase was sustained after 48 hours of exposure to HG. In contrast, osmotic control media containing either L-glucose or mannitol did not increase glomerular LPO. Dimethylthiourea (20 mM), a hydroxyl radical scavenger, completely blocked the increase of LPO in the glomeruli exposed to HG not only for one hour but also for 48 hours without altering LPO levels in the glomeruli exposed to control glucose. This provides evidence that oxidative stress can be induced by high ambient concentrations of glucose. Pretreatment with PKC antagonists, either 500 microM H-7 or 100 nM staurosporine, prevented the increase of LPO in the glomeruli exposed to HG for one hour but not in glomeruli exposed for 48 hours. These data suggest that (i) elevated glucose levels per se can cause oxidative stress and augment membrane lipid peroxidation of glomeruli, and (ii) activation of PKC may play a role in early phase of glucose-induced glomerular lipid peroxidation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Organization of the human skeletal myosin heavy chain gene cluster.

Myosin is an important structural and enzymatic component of skeletal muscle. Multiple myosin isoforms are encoded by a multigene family and are expressed in different developmental stages and fiber types. In humans and mice, skeletal myosin heavy chain (MYH) genes are clustered on a single chromosome (17p and 11, respectively). Since the structural organization of the gene cluster may affect its expression as well as shed light on MYH genetic alterations, a physical map of the human MYH gene cluster was constructed. Nine yeast artificial chromosomes containing MYH genes were isolated and used to construct a contiguous set (contig) of overlapping yeast artificial chromosomes. This contig encompasses a genetic marker mapped to 17p13.1. Six MYH genes were located within a 500-kilobase segment of human DNA. The order of the genes within this cluster does not correspond to the developmental pattern of expression of individual members.

Base Sequence↗

Atypical clinical manifestations of amebic colitis.

Amebic colitis is a disease revealing diverse clinical manifestations and endoscopic gross features and often confused with other types of colitis. In case of misdiagnosis as an idiopathic inflammatory bowel disease or delayed recognition of intestinal amebiasis, an undesirable outcome may occur resulting from erroneous administration of steroids or delayed antiamebic treatment. To demonstrate the pitfalls in the diagnosis and treatment of intestinal amebiasis, 3 cases of amebic colitis with atypical clinical manifestations are presented in this paper. In conclusion, despite the low sensitivities of routine stool examination for parasite and histopathologic confirmation in biopsy specimen, every effort must be made to find amebic trophozoites either in fresh stool or biopsy specimens for prompt and correct diagnosis of amebic colitis when we manage patients with chronic intestinal ulcerations, even though their clinical course and endoscopic findings are not typical of amebiasis. Moreover, following initial successful anti-amebic therapy, more careful clinical, endoscopical, and parasitological follow-up should be done for the early detection of recurrence.

Adult↗

IgA related disorders in rheumatoid arthritis.

Serum monomeric and polymeric IgA, IgA rheumatoid factor (IgA-RF) and IgA containing circulating immune complexes (IgA-CIC) were studied in 192 patients with rheumatoid arthritis (RA) to explore the relationships among IgA related abnormalities and to investigate their potential associations with disease activity, immunoregulatory disorders and effect of treatments. Total serum IgA and polymeric IgA (p-IgA) levels were elevated in 23 and 11% of patients with RA, respectively. Their respective mean concentrations in serum were significantly elevated compared to normal values (p less than 0.001 and p less than 0.004). A preferential increase in polymeric rather than monomeric IgA was observed. IgA-RF, detected by a solid phase ELISA, was found in 71% and was associated with decreased grip strength (p less than 0.005), active disease (p less than 0.05), increased p-IgA level (p less than 0.001), elevated p-IgA:total IgA ratio (p less than 0.05), the presence of IgA-CIC (p less than 0.005) and IgM-RF (p less than 0.005). Complement fixing IgA-CIC were detected in 40% of patients by IgA specific conglutinin and anti-C3 binding solid phase ELISA. High molecular weight IgA species precipitated by 2.5% polyethylene glycol from RA sera positive for IgA-CIC were shown to be IgA-RF complexed to IgG. Taken together, our results suggest that IgA-RF are essentially polymeric in nature and circulate as IgA-RF-IgG immune complexes. Although the presence of IgA-CIC was not associated with disease activity, IgA-CIC activated C3 and thus are potentially pathogenic.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗

Circulating immune complexes in rheumatoid arthritis: a prospective study using five immunoassays.

We evaluated 257 patients with rheumatoid arthritis (RA) to determine the frequency of circulating immune complexes (CIC) in the serum, relationships between the presence of CIC, clinical indices of disease activity and other laboratory features, and relationships between changes in CIC levels and changes in disease activity. CIC were detected by fluid phase Clq binding activity, conglutinin binding activity, anti-C3 assay, staphylococci protein A binding assay and the precipitation of cryoglobulins. CIC in the serum were found to correlate with indices of disease activity, extraarticular features and the presence of rheumatoid factor. A change in Clq binding activity correlated with a parallel change in the joint count.

Antibodies, Antinuclear↗

Evaluation of clinical and prognostic significance of T cell regulatory subsets in rheumatoid arthritis.

Phenotypic analysis of circulating lymphocytes and T cell subsets using monoclonal antibodies was performed on 60 patients with rheumatoid arthritis (RA). A significant lymphopenia was observed in RA patients and correlated with the use of disease suppressant drugs (p less than 0.0001). A significant decrease in the number of suppressor/cytotoxic T cells resulted in an increase in the TH/TS ratio in 40% of RA patients. This elevated ratio did not correlate with disease activity, the presence of extraarticular features, autoantibody production or immune complex formation. We conclude that the evaluation of the TH/TS ratio has no diagnostic or prognostic value.

Arthritis, Rheumatoid↗