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Biomedical subjects

J Chung

Publications and source records attributed to J Chung.

At least 145 records · Page 8Linked to original sources
PubMed1996

Prominent pigmented fungiform papillae of the tongue.

Prominent pigmented fungiform paillae of the tongue are characterized clinically by prominence and pigmentation confined to these papillae and histopathologically by melanophages in the lamina opriae. A 45-year-old Asian woman had dark erythematous papules exclusively involved with fungiform papillae on the anterior lateral dorsal aspect of the tongue and hyperpigmentation on the lip. Histologic examination revealed many melanophages in the subepidermal area within the fungiform papillae. Her skin lesions improved moderately following two months of treatment for anemia.

Anemia, Iron-Deficiency↗
PubMed1995

Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region.

A previously undescribed 62-kDa protein (p62) that does not contain phosphotyrosine but, nevertheless, binds specifically to the isolated src homology 2 (SH2) domain of p56lck has been identified. The additional presence of the unique N-terminal region of p56lck prevents p62 binding to the SH2 domain. However, phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62. Moreover, p62 is associated with a serine/threonine kinase activity and also binds to ras GTPase-activating protein, a negative regulator of the ras signaling pathway. Thus, phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation.

Amino Acid Sequence↗
PubMed1995

Long-term outcomes and modes of death of patients treated with nonthoracotomy implantable defibrillators.

Long-term outcomes of all patients who underwent nonthoracotomy implantable cardioverter-defibrillator (ICD) implantation at our institution from April 1991 to October 1994 were studied using the intention-to-treat analysis. Of 94 consecutive patients, 81 underwent nonthoracotomy ICD implantation and 13 underwent thoracotomy (for concomitant surgery in 11 and unavailability of nonthoracotomy leads in 2). Six of 81 patients had a high defibrillation threshold, 4 subsequently underwent thoracotomy, and 2 were treated with amiodarone. Surgical mortality was 0%. The duration of follow-up was 20 +/- 13 months, and was > 12 months in 74% of 67 living patients. Actuarial survival rates at 1 and 2 years were, respectively, 98% and 94% for sudden death and 91% and 83% for total mortality. Deaths during long-term follow-up were mostly due to nonsudden cardiac or noncardiac deaths. Two-year mortality rates were 12% and 25% in patients with ejection fraction > or = 30% and < 30%, respectively. Thus, instances of sudden death and surgical mortality are very few in patients with nonthoracotomy ICDs. Deaths during long-term follow-up are mostly due to nonsudden cardiac and noncardiac deaths. Therefore, ICD therapy may have greater impact on survival in patients with lower risks of nonsudden cardiac and cardiac death (e.g., younger patients with minimal heart disease) than in patients with severe cardiac or noncardiac disease. Prospective studies are needed to address this question.

Actuarial Analysis↗
PubMed1995

Distinct sequence motifs within the cytoplasmic domain of the human IL-4 receptor differentially regulate apoptosis inhibition and cell growth.

Hematopoietin receptors generally function as multimeric complexes composed of a unique ligand-binding chain and a second component often shared between several members of this receptor family. To better understand the signal transduction of the human IL-4 receptor (hIL4R), we analyzed the functionality of targeted mutations in two cytoplasmic regions of the ligand-binding hIL4R chain that we previously identified to be necessary for growth mediation in factor-dependent murine Ba/F3 cells. Here, we provide evidence that transient inhibition of apoptotic death of Ba/F3 cells and the competence to proliferate indefinitely depend on separated and distinct sequence motifs of the hIL4R. In particular, hIL4R constructs with a truncation of the recently described gp130 box1 from P242 to K264, or a deletion of the acidic region between S330 and S365, fail to stimulate growth or to mediate the inhibition of apoptosis. hIL4R bearing a point mutation within the gp130 box1 (P242S) is defective for growth stimulation but still signals the transient inhibition of apoptotic cell death and the induction of c-myc RNA. A third region required for IL4-mediated cell growth is localized between T462 and S476 and includes the sequence NPAY previously described to serve as interaction motif in signaling of epidermal growth factor and insulin receptors. Conversion of Y472 into F472 within the latter hIL4R motif affects the competence of stably transfected BA/F3 cells to proliferate indefinitely in the presence of hIL4. Sequences C-terminal of S476 are not essential for growth stimulation of BA/F3 transfectants.

Apoptosis↗
PubMed1995

Differential expression of HLA-DQB1 alleles in a heterozygous cell line.

Regulation of HLA class II transcription is complex, with both locus-specific and allele-specific polymorphisms associated with consensus regulatory region promoter elements. In order to evaluate the potential function of allele-specific elements, HLA-DQB1 transcripts and in vivo footprinting of the DQB1 promoter were studied in human cell lines inducible for HLA class II expression. In the heterozygous melanoma cell line Me9229/18, differential expression was observed for two DQB1 alleles. This variation was reflected in both steady-state and inducible transcripts, although methylation patterns of the promoter elements were similar for both alleles. This in vivo allelic difference expression, which correlates with previous studies of in vitro reporter gene transcription, indicates the potential for functionally important differences in tissue-specific and inducible expression attributable to promoter region polymorphism in HLA genes.

Alleles↗
PubMed1995

Antidiuretic hormone levels and polyuria in spinal cord injury. A preliminary report.

Chronic cervical spinal cord injury is characterized by defects in sodium and water homeostasis and defects of adaptive hormonal responses. The plasma osmolality is maintained in a relatively narrow range, the lower limit of which is determined by osmotic threshold for vasopressin release and the upper limit by the third threshold. Antidiuretic hormone as an important mediator of fluid and electrolyte balance was well investigated in able bodied children comparing children with normal voiding pattern and children with enuresis. The normal subjects were found to have higher plasma ADH at night, not detected in the group with enuresis. The findings were similar in elderly patients with increased diuresis at night, suggesting an important role of ADH in nocturnal decrease of urine output. Investigators studied the effect of rapid tilt on plasma ADH in tetraplegic compared with normal subjects, but there are no data available in the literature regarding ADH and its effects on water and electrolyte balance in healthy tetraplegic subjects with a normal lifestyle. We decided to undertake a pilot study to attempt to establish baseline ADH levels in this subject group, to better understand and manage tetraplegic patients with water and electrolyte dysregulation. Our preliminary data suggest that these individuals lack the normal diurnal variation of ADH, a phenomenon similar to that demonstrated in enuretic children and elderly, and furthermore appear to have generally depressed ADH levels.

Adult↗
PubMed1995

Activation of pp70/85 S6 kinases in interleukin-2-responsive lymphoid cells is mediated by phosphatidylinositol 3-kinase and inhibited by cyclic AMP.

Activation of phosphatidylinositol 3-kinase (PI3K) and activation of the 70/85-kDa S6 protein kinases (alpha II and alpha I isoforms, referred to collectively as pp70S6k) have been independently linked to the regulation of cell proliferation. We demonstrate that these kinases lie on the same signalling pathway and that PI3K mediates the activation of pp70 by the cytokine interleukin-2 (IL-2). We also show that the activation of pp70S6k can be blocked at different points along the signalling pathway by using specific inhibitors of T-cell proliferation. Inhibition of PI3K activity with structurally unrelated but highly specific PI3K inhibitors (wortmannin or LY294002) results in inhibition of IL-2-dependent but not phorbol ester (conventional protein kinase C [cPKC])-dependent pp70S6k activation. The T-cell immunosuppressant rapamycin potently antagonizes IL-2-(PI3K)- and phorbol ester (cPKC)-mediated activation of pp70S6k. Thus, wortmannin and rapamycin antagonize IL-2-mediated activation of pp70S6k at distinct points along the PI3K-regulated signalling pathway, or rapamycin antagonizes another pathway required for pp70S6k activity. Agents that raise the concentration of intracellular cyclic AMP (cAMP) and activate cAMP-dependent protein kinase (PKA) also inhibit IL-2-dependent activation of pp70S6k. In this case, inhibition appears to occur at least two points in this signalling path. Like rapamycin, PKA appears to act downstream of cPKC-mediated pp70S6k activation, and like wortmannin, PKA antagonizes IL-2-dependent activation of PI3K. The results with rapamycin and wortmannin are of added interest since the yeast and mammalian rapamycin targets resemble PI3K in the catalytic domain.

Androstadienes↗
PubMed1994

PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase.

Platelet-derived growth factor receptor (PDGF-R) phosphorylation at tyrosines 740/751 and insulin receptor phosphorylation of insulin receptor substrate-1 effects the recruitment and activation of phosphatidylinositol-3-OH kinase (PI(3)K). Changes in PI(3)K activity correlate with cell growth but its downstream signal transducers are unknown. Activation of the 70/85K S6 kinases (pp70S6k) by serine phosphorylation results in 40S ribosomal protein S6 phosphorylation and is important for G1 cell-cycle transition in a variety of cells. Although receptor tyrosine kinases activate the microtubule-associated protein kinase cascade through SH2-/SH3-adaptor proteins, Sos and c-Ras, it is unclear how tyrosine kinases are coupled to the pp70S6k phosphorylation cascade. Here we report that PI(3)K mediates PDGF or insulin receptor signalling to pp70S6k. PI(3)K-mediated activation of pp70S6k is independent of conventional protein kinase C isoforms. Additionally, rapamycin blocks pp70S6k activation by all mitogens, without inhibiting PI(3)K, and acts downstream in this signalling system.

3T3 Cells↗
PubMed1994

Relationship between multiple biologic effects of rapamycin and the inhibition of pp70S6 protein kinase activity. Analysis in mutant clones of a T cell lymphoma.

Rapamycin (RAP) inhibits several biologic responses in the YAC-1 T cell lymphoma, including the serum-driven proliferation and cyclin A mRNA expression, the induction of Ly-6E Ag expression by IFN, and the induction of IFN-gamma production by IL-1. RAP also suppresses the enzymatic activity of the 70 kDa S6 protein kinase (pp70s6k). To define the mechanistic relationship between these multiple effects of RAP, we have generated stable somatic mutants with altered sensitivities to this drug. A first series of mutants, represented by the R19, 4R16, and 10R13 clones, showed markedly reduced sensitivity to the inhibitory effect of RAP on all biologic responses tested and on pp70s6k activity. Two other mutant types, R103 and R125, were both highly sensitive to RAP-mediated suppression of proliferation, of IL-1-induced IFN-gamma production, and of pp70s6k activity but differed in their Ly-6E response. This response was not affected by RAP in the R125 clone and was enhanced in the R103 clone. Therefore, the inhibitory effects of RAP on proliferation and IL-1-mediated IFN-gamma induction both appear associated with the inhibition of pp70s6k activity, whereas the modulation of Ly-6E induction is independent from the latter. Moreover, the cellular binding of [3H]dihydro-FK-506 was found to be blocked by RAP in all mutant types to the same extent as in wild-type YAC-1 cells, suggesting that the altered sensitivity to the effects of RAP in these mutants is not due to an inability of the drug to enter the cells or to interact with FKBP. Further biochemical characterization of the mutant cells described here is expected to help clarify the mechanisms of RAP action.

Animals↗
PubMed1994

Retrospective population-based analysis of the dose-response (fecal fat excretion) relationship of orlistat in normal and obese volunteers.

Orlistat, an inhibitor of gastrointestinal lipases, limits the absorption of ingested fat and could become a potential treatment for obesity. This analysis was performed to elucidate the relationship between orlistat dose and intensity of inhibition of dietary fat absorption (assessed by measuring fecal fat excretion). In 11 phase I double-blind, placebo-controlled, parallel-group randomized studies, a total of 171 subjects received oral daily doses that ranged from 30 to 1200 mg orlistat or matching placebo three times a day for 9 to 10 days. The results of the daily mean fecal fat excretion percentage (relative to ingested fat) were correlated to the orlistat daily dose. A simple maximum-effect model that included a basal value was used to fit the dose-response relationship for all evaluable subjects. The mean maximum percentage of ingested fat excreted in the feces was approximately 32% during orlistat administration compared with 5% during placebo administration. The orlistat daily dose that produced 50% of the maximum effect was 98 mg/day. The model-fitting suggests the existence of a steep portion of the dose-response curve up to approximately 400 mg/day, with a subsequent tendency to plateau at higher doses. Such an analysis was instrumental in identifying appropriate doses to be used in therapeutic trials for weight loss in obese patients.

Adult↗
PubMed1994

Rudimentary polydactyly.

A case of rudimentary polydactyly on the radial aspect of the thumb of a 4-year-old male was examined. Histologic examination revealed hyperkeratosis and acanthosis in the epidermis and large numbers of nerve bundles in the dermis. With immunoperoxidase staining for S-100 protein, the nerve corpuscles were positively stained. We think that rudimentary polydactyly is a kind of congenital traumatic neuroma and that the possible cause may be intrauterine amputation.

Child, Preschool↗
PubMed1994

HAEMOLYMPH AND TISSUE TITRES OF ACHETAKININS IN THE HOUSE CRICKET ACHETA DOMESTICUS: EFFECT OF STARVATION AND DEHYDRATION

Achetakinin-like immunoreactive material in tissues and haemolymph of adult male crickets was quantified by radioimmunoassay. Achetakinin-like material was found in the brain, suboesophageal ganglia and the thoracic and abdominal ganglia, but the largest amount was within the retrocerebral complex. A Ca2+-dependent release of achetakinin-like immunoreactive material was demonstrated from retrocerebral complexes incubated in vitro in saline containing a high concentration of K+. The concentration of achetakinin-like material in haemolymph from fed crickets was estimated to be 2.8 nmol l-1 and increased more than 10-fold in insects starved for 48 h without access to water. The presence of achetakinin-like material in haemolymph suggests that these peptides are released in vivo and function as circulating neurohormones.

Journal Article↗
PubMed1994

Endodermal sinus tumor: immunophenotypic expression of a carcinoma.

A series of five endodermal sinus tumors was studied for their cytoskeletal and other phenotypic markers. They included 2 ovarian, 2 testicular, and 1 inguinal tumors. The cytoskeletal expression was also studied by gel electrophoresis and immunoblotting. Every tumor was diffusely and strongly immunostained for cytokeratin. By SDS-PAGE and immunoblotting, cytokeratins 8 & 18 were detected. Vimentin was focally coexpressed in 4 cases. The stroma was diffusely immunostained for vimentin. None of them expressed desmin, neurofilament, or glial filament protein. Desmoplakin was expressed only in one ovarian tumor. Alpha-fetoprotein and S-100 protein were also diffusely positive among the neoplastic cells; intracytoplasmic globules were especially strongly immunostained. These findings suggest that endodermal sinus tumors represent a group of pure malignant epithelial neoplasms, and may be regarded as primitive carcinomas.

Adult↗
PubMed1993

Analysis of differential HLA-DQB expression in autologous B cell lines.

Class II major histocompatibility complex genes are differentially expressed during cellular activation and differentiation, often in a locus-specific manner. We investigated the differential expression of the HLA-DQB gene, using B cell lines LAZ221 and LAZ388: LAZ221, derived from an early B cell leukemia, expresses HLA-DR but not HLA-DQ: LAZ388, the autologous Epstein-Barr virus-transformed B cell line, expresses both DR and DQ. Transfection experiments demonstrate differential function of class II gene upstream regulatory regions in the two lines, which correlates with differential class II gene expression. Using gel retardation and DNase I footprint assays, we demonstrate that absence of DQB gene expression is associated with characteristic nuclear protein-binding interactions in the proximal DQB gene upstream regulatory region. These interactions are visualized as DNA-protein complexes that are seen with nuclear proteins from the DQ-negative cell line, LAZ221, and involve consensus promoter Y box and W box elements, as well as novel upstream sites. Transcriptional regulatory proteins that differ in these autologous B cell lines may be stage-specific factors involved in the developmental regulation of HLA genes.

Animals↗