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Biomedical subjects

J Shin

Publications and source records attributed to J Shin.

At least 55 records · Page 3Linked to original sources
PubMed2000

New triterpenoid saponins from the sponge Melophlus isis.

Four new triterpenoid saponins were isolated, along with two known 30-norlanostane-type saponins- sarasinosides A(1) (1) and A(3) (2)-from the sponge Melophlus isis collected from Guam. The structures of these new compounds (3-6) proved to be 30-norlanosta-8(14),24-dien-23-ones bearing two hydroxyl groups or the corresponding methoxy groups at the 9alpha,15alpha- and 9alpha, 15beta-positions and the pentasaccharide portion identical with those of 1 and 2 at the 3beta position, by spectral, chemical, and GC analyses.

Animals↗
PubMed2000

Relationship between the tertiary structures of mastoparan B and its analogs and their lytic activities studied by NMR spectroscopy.

Mastoparan B (MP-B), an antimicrobial cationic tetradecapeptide amide isolated from the venom of the hornet Vespa basalis, is an amphiphilic alpha-helical peptide. MP-B possesses a variety of biological activities, such as mast cells degradation histamine release, erythrocyte lysis and inhibition of the growth of gram-positive and gram-negative bacteria. In order to study the relationship between the structure and the biological activity of MP-B, we used four analogs by replacing amino acids with alanine. Tertiary structures of MP-B and its analogs in 2,2,2-trifluoroethanol (TFE)-containing aqueous solution have been determined by NMR spectroscopy and molecular modeling. The results indicate that [Ala4]MP-B and [Ala12]MP-B with higher hydrophobicity adopt a higher content of amphiphilic helical structures, and have better antimicrobial and hemolytic activities than MP-B. However, [Ala3]MP-B and [Ala9]MP-B with lower hydrophobicity have disordered structures. [Ala3]MP-B and [Ala9]MP-B have low antimicrobial activity and much less hemolytic activity relative to MP-B. It is likely that tryptophan residue in MP-B and appropriate hydrophobicity of MP-B to induce alpha-helical structure is essential for the antibacterial and hemolytic activity of MP-B. This study can aid understanding of the structure-activity relationship of MP-B and to design peptides to possess lytic activity.

Alanine↗
PubMed2000

Complete congenital bony syngnathia in a case of oromandibular limb hypogenesis syndrome.

Congenital fusion of the maxilla and mandible (syngnathia) is rare and can present in a wide range of severity from single mucosal bands (synechiae) to complete bony fusion (synostosis). Congenital synostosis of the mandible and maxilla is even less common than synechiae, with only 19 cases reported in the literature. Most of them have presented as an incomplete, unilateral fusion. Only three of the reported cases showed more extensive but still incomplete, intermaxillary bony fusion. We present a case of complete bony fusion of the maxilla and mandible associated with a cleft palate, hypoglossia, micrognathia, unilateral choanal atresia, and limb abnormalities as a feature of oromandibular limb hypogenesis syndrome. Details of operative management are presented.

Choanal Atresia↗
PubMed2000

Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling.

Glucagon-like peptide-1 (GLP-1), a potent regulator of glucose homeostasis, is also produced in the central nervous system, where GLP-1 has been implicated in the neuroendocrine control of hypothalamic-pituitary function, food intake, and the response to stress. The finding that intracerebroventricular GLP-1 stimulates LH, TSH, corticosterone, and vasopressin secretion in rats prompted us to assess the neuroendocrine consequences of disrupting GLP-1 signaling in mice in vivo. Male GLP-1 receptor knockout (GLP-1R-/-) mice exhibit reduced gonadal weights, and females exhibit a slight delay in the onset of puberty; however, male and female GLP-1R-/- animals reproduce successfully and respond appropriately to fluid restriction. Although adrenal weights are reduced in GLP-1R-/- mice, hypothalamic CRH gene expression and circulating levels of corticosterone, thyroid hormone, testosterone, estradiol, and progesterone are normal in the absence of GLP-1R-/- signaling. Intriguingly, GLP-1R-/- mice exhibit paradoxically increased corticosterone responses to stress as well as abnormal responses to acoustic startle that are corrected by glucocorticoid treatment. These findings suggest that although GLP-1R signaling is not essential for development and basal function of the murine hypothalamic-pituitary-adrenal axis, abrogation of GLP-1 signaling is associated with impairment of the behavioral and neuroendocrine responses to stress.

Acoustic Stimulation↗
PubMed2000

Pregnancy in cystic fibrosis. Fetal and maternal outcome.

OBJECTIVE: To assess the effect of pregnancy on pulmonary function and survival in women with cystic fibrosis (CF) and to assess the fetal outcome. DESIGN: Cohort study. The data analyzed were collected from the Toronto CF database, chart review, and patient questionnaire. SETTING: Tertiary-care center. PATIENTS: All women with CF who, at the time of diagnosis or pregnancy, attended the Toronto Cystic Fibrosis Clinics between 1961 and 1998. RESULTS: From 1963 to 1998, there were 92 pregnancies in 54 women. There were 11 miscarriages and 7 therapeutic abortions. Forty-nine women gave birth to 74 children. The mean follow-up time was 11 +/- 8 years. One patient was lost to follow-up shortly after delivery, and one was lost after 12 years. The overall mortality rate was 19% (9 of 48 patients). Absence of Burkholderia cepacia (p < 0.001), pancreatic sufficiency (p = 0.01), and prepregnancy FEV(1) > 50% predicted (p = 0.03) were associated with better survival rates. When adjusted for the same parameters, pregnancy did not affect survival compared to the entire adult female CF population. The decline in FEV(1) was comparable to that in the total CF population. Three women had diabetes mellitus, and seven developed gestational diabetes. There were six preterm infants and one neonatal death. CF was diagnosed in two children. CONCLUSIONS: The maternal and fetal outcome is good for most women with CF. Risk factors for mortality are similar to those for the nonpregnant CF population. Pregnancies should be planned so that there is opportunity for counseling and optimization of the medical condition. Good communication between the CF team and the obstetrician is important.

Adolescent↗
PubMed1999

Adaptive neural coding dependent on the time-varying statistics of the somatic input current.

It is generally assumed that nerve cells optimize their performance to reflect the statistics of their input. Electronic circuit analogs of neurons require similar methods of self-optimization for stable and autonomous operation. We here describe and demonstrate a biologically plausible adaptive algorithm that enables a neuron to adapt the current threshold and the slope (or gain) of its current-frequency relationship to match the man (or dc offset) and variance (or dynamic range or contrast) of the time-varying somatic input current. The adaptation algorithm estimates the somatic current signal from the spike train by way of the intracellular somatic calcium concentration, thereby continuously adjusting the neurons' firing dynamics. This principle is shown to work in an analog VLSI-designed silicon neuron.

Adaptation, Physiological↗
PubMed1999

Molecular responses of macrophages to porcine reproductive and respiratory syndrome virus infection.

The detailed mechanism(s) by which porcine reproductive and respiratory syndrome virus (PRRSV) impairs alveolar Mo homeostasis and function remains to be elucidated. We used differential display reverse-transcription PCR (DDRT-PCR) to identify molecular genetic changes within PRRSV-infected Mo over a 24 h post infection period. From over 4000 DDRT-PCR amplicons examined, 19 porcine-derived DDRT-PCR products induced by PRRSV were identified and cloned. Northern blot analysis confirmed that four gene transcripts were induced during PRRSV infection. PRRSV attachment and penetration alone did not induce these gene transcripts. DNA sequence revealed that one PRRSV-induced expressed sequence tag (EST) encoded porcine Mx1, while the remaining 3 clones represented novel ESTs. A full-length cDNA clone for EST G3V16 was obtained from a porcine blood cDNA library. Sequence data suggests that it encodes an ubiquitin-specific protease (UBP) that regulates protein trafficking and degradation. In pigs infected in vivo, upregulated transcript levels were observed for Mx1 and Ubp in lung and tonsils, and for Mx1 in tracheobronchial lymph node (TBLN). These tissues correspond to sites for PRRSV persistence, suggesting that the Mx1 and Ubp genes may play important roles in clinical disease during PRRSV infection.

Amino Acid Sequence↗
PubMed1999

Detecting interactions between gene, site, and environmental variables using GAP.

Regressive models that incorporate measured variables and assumed genetic parameters were used to detect interactions between gene, research site, and environmental variables in GAW11 Problem 2. Replicates 1 to 5 were used in the analyses. Significant three-way gene x environment x site interactions were seen for all models, regardless of what assumptions were made about genetic transmission. Therefore, regressive models within each of the four sites were examined for significant gene x environment interactions. At one site, there was a pattern of gene x environment interaction that was consistent in most of the genetic models assumed. Joint and separate segregation and linkage analyses were compared in this site. No patterns of gene x environment interaction were seen in the other sites. Results from this analysis show that regressive modeling can identify complex interactions in data from heterogeneous populations even when ascertainment assumptions are violated.

Chromosome Mapping↗
PubMed1999

Evaluation of the contribution of environmental factors.

For the simulated data of GAW11, the roles of two environmental factors, E1 and E2, were investigated. Logistic regression analyses measuring the association between outcome (either mild or severe disease versus no disease) and E1 and E2 exposure indicated that E1 was a risk factor for disease (either mild or severe) but that E2 was not associated with outcome. Linkage analyses were performed for strata defined by E1 and E2 exposure. A specific disease locus was identified in these stratified analyses where this locus would not have been identified with an unstratified linkage analysis. Finally, stratified generalized transmission disequilibrium test analyses yielded several false positive results.

Environment↗
PubMed1999

Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar.

OBJECTIVES: With the use of clinical data from a large international cohort, we evaluated and compared affected siblings and isolated cases. STUDY DESIGN: Data from 116 families were collected, and patients conforming to our predetermined diagnostic criteria were analyzed. Phenotypic manifestations of affected siblings and singletons were compared with the use of t tests, Wilcoxon scores, and chi2 analysis. RESULTS: Eighty-eight patients (33 female, 55 male; median age 5.20 years) fulfilled our predetermined diagnostic criteria for Shwachman syndrome; 63 patients were isolated cases, and 25 affected siblings were from 12 multiplex families. Steatorrhea was present in 86% (57 of 66), and 91% (78 of 86) displayed a low serum trypsinogen concentration. Patients older than 4 years more often had pancreatic sufficiency. Neutropenia occurred in 98%, anemia in 42%, and thrombocytopenia in 34%. Myelodysplasia or cytogenetic abnormalities were reported in 7 patients. Short stature with normal nutritional status was a prominent feature. CONCLUSIONS: Clinical features among patients with Shwachman syndrome varied between patients and with age. Similarities in phenotype between isolated cases and affected sibling sets support the hypothesis that Shwachman syndrome is a single disease entity.

Bacterial Infections↗
PubMed1999

New acetylenic enol ethers of glycerol from the sponge Petrosia sp.

Ten acetylenic enol ethers of glycerols, including six new compounds (1-6) and a linear acetylenic alcohol (7), have been isolated from a sponge of the genus Petrosia. The structures of the novel compounds were elucidated by spectroscopic methods. The absolute stereochemistry of 1-7 was determined by chemical transformations and the Mosher method. Some of these compounds exhibited weak cytotoxicity against a human leukemia cell-line (K-562).

Acetylene↗
PubMed1999

New Bis(Indole) alkaloids of the topsentin class from the sponge spongosorites genitrix

Four bis(indole) alkaloids of the topsentin class, including two new brominated compounds (1 and 2), have been isolated from the sponge Spongosorites genitrix collected from Jaeju Island, Korea. The structures of the novel compounds were determined by spectroscopic methods. These compounds exhibited moderate cytotoxicity against a human leukemia cell-line (K-562).

Journal Article↗
PubMed1999

Prevalence of vitamin K deficiency in cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) are at risk of developing vitamin K deficiency because of pancreatic insufficiency, hepatobiliary disease, or both. OBJECTIVE: Our objective was to determine the prevalence of vitamin K deficiency in unsupplemented patients with CF and to identify risk factors that might be associated with the deficiency. DESIGN: Ninety-eight patients with CF-83 who were pancreatic insufficient (age: 15.2 +/- 10.7 y; range: 0.6-45.8 y), 15 who were pancreatic sufficient (age: 26.2 +/- 11.6 y; range: 6.5-45.3 y), and 62 healthy individuals (age: 16.2 +/- 12. 8 y; range: 1-45 y)-were studied prospectively. None had taken vitamin K supplements. Eight pancreatic-insufficient patients had advanced CF-associated liver disease. Plasma prothrombin in vitamin K absence (PIVKA-II) was measured by immunoassay. All control subjects had PIVKA-II concentrations <3 microg/L. RESULTS: Seventy-eight percent of pancreatic-insufficient patients had PIVKA-II concentrations >/=3 microg/L (22.8 +/- 35.7 microg/L). All patients with CF-associated liver disease had abnormal PIVKA-II concentrations. The mean PIVKA-II concentration of pancreatic-insufficient patients with liver disease was greater than that of those without liver disease (46.6 +/- 65.3 compared with 15. 3 +/- 26.1 microg/L; P < 0.05). Five pancreatic-sufficient patients had mildly elevated PIVKA-II concentrations. Six (7%) pancreatic insufficient patients (3 with CF-associated liver disease) had mildly prolonged prothrombin time but no clinical bleeding. There was no correlation between PIVKA-II concentrations and severity of fat malabsorption or antibiotic use. CONCLUSIONS: Vitamin K deficiency is common in unsupplemented patients with CF and pancreatic insufficiency and routine supplementation should be considered in all of these patients.

Adolescent↗
PubMed1998

Immediate early response of the p62 gene encoding a non-proteasomal multiubiquitin chain binding protein.

p62 is a cytoplasmic ubiquitin chain binding protein. Upon a variety of extracellular signals, both transcript and protein levels of p62 were rapidly increased. These signals include phorbol 12-myristate 13-acetate (PMA) and calcium ionomycin for peripheral blood mononuclear cells, serum or PDGF for serum-starved NIH3T3 cells, IL-3 for the G1 arrested pre-B cell line Ba/F3, and PMA for a human promyelocyte line U937. The elevation of p62 transcript level is due to temporal stabilization of mRNA and rapid activation of the p62 gene. Cycloheximide-induced enhanced transcription suggests the immediate early response of the p62 gene. The rapid induction of p62 indicates the presence of a novel ubiquitination-mediated regulatory mechanism during cell proliferation and differentiation.

3T3 Cells↗
PubMed1998

Genomic structure and promoter analysis of the p62 gene encoding a non-proteasomal multiubiquitin chain binding protein.

p62 is a novel immediate early response gene encoding a ubiquitin chain binding protein. To investigate the mechanism of p62 gene expression, we isolated and characterized the 20 kb long human p62 gene. The p62 gene contains seven introns and eight exons. The splice sites conformed to the GT/AG rule, except introns 6 and 7 which used the unusual GC dinucleotides. The p62 promoter is TATA-less, and 357 nucleotides of the 5'-flanking region contain basic machineries for transcription. A reporter gene linked to 1800 nucleotides of the 5'-flanking region was rapidly activated by various extracellular signals. The presence of a CpG island as well as multiple binding sites for SP-1, AP-1, NF-kappaB, and Ets-1 family in the promoter region supports the regulated activation of the p62 gene.

Amino Acid Sequence↗
PubMed1998

P62 and the sequestosome, a novel mechanism for protein metabolism.

In addition to selecting proteins for degradation by the 26S proteasome, ubiqitination appears to serve other regulatory functions, including for endosomal/lysosomal targeting, protein translocation, and enzyme modification. Currently, little is known how multiubiquitin chains are recognized by these cellular mechanisms. Within the 26S proteasome, one subunit (Mcb1/S5a) has been identified that has affinity for multiubiquitin chains and may function as a ubiquitin receptor. We recently found that a non-proteasomal protein p62 also preferentially binds multiubiquitin chains and forms a novel cytoplasmic structure "sequestosome" which serves as a storage place for ubiquitinated proteins. In the present manuscript, the role and regulation of p62 in relation to the sequestosomal function will be reviewed.

Adenosine Triphosphatases↗