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Biomedical subjects

M Park

Publications and source records attributed to M Park.

At least 181 records · Page 10Linked to original sources
PubMed1993

Primary structure of neuropeptide Y from brains of the American alligator (Alligator mississippiensis).

The purification of NPY from brains of the American alligator (Alligator mississippiensis) was achieved using reverse-phase high performance liquid chromatography (HPLC). The amino acid sequence was determined using automated Edman degradation as Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu- Asp-Ala-Pro-Ala-Glu-Asp-Met-Ala-Arg-Tyr-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile- Asn-Leu - Ile-Thr-Arg-Gln-Arg-Tyr. Alligator NPY is the first non-mammalian vertebrate to have 100% sequence identity to human NPY. The conservation of alligator NPY suggests that serine in position 7 of chicken NPY evolved after the birds and reptiles diverged from a common Archosaurian ancestor. Furthermore, the sequence identity between alligator and human NPY suggests this sequence is the same as the ancestral amniote NPY.

Alligators and Crocodiles↗
PubMed1993

Expression of the met/hepatocyte growth factor/scatter factor receptor and its ligand during differentiation of murine P19 embryonal carcinoma cells.

The met proto-oncogene is a member of the family of tyrosine kinase growth factor receptors and was recently identified as a receptor for hepatocyte growth factor and scatter factor (HGF/SF). From Northern hybridization studies the met/HGF/SF receptor (R) is expressed in many adult and embryonic mouse tissues. To identify which specific differentiated cell types express the met/HGF/SFR and to investigate the biological function of this receptor and its ligand during early murine development, we chose to study the expression of the met/HGF/SFR and HGF/SF during differentiation of the pluripotent P19 murine embryonal carcinoma cell line in culture. In this paper we demonstrate that met/HGF/SFR mRNA, protein, and its ligand are expressed at a low level in undifferentiated P19 cells and that their expression is increased as P19 cells are induced to differentiate into neuroectodermal derivatives following treatment with retinoic acid (RA) and into mesodermal derivatives following treatment with dimethyl sulfoxide (DMSO). From in situ hybridization analyses, only a subpopulation of differentiating P19 cells treated with RA or DMSO expresses high levels of the met/HGF/SFR RNA. In cultures treated with RA and cytosine arabinoside, both met/HGF/SFR mRNA and protein can be localized specifically to nondividing neuronal cells. Expression of the met/HGF/SFR and its ligand, HGF/SF, in undifferentiated P19 cells and differentiated derivatives suggests that stimulation of this signal transduction pathway may be an important event for the control of cell differentiation, proliferation, or positioning during embryogenesis.

Animals↗
PubMed1993

Dimerization mediated through a leucine zipper activates the oncogenic potential of the met receptor tyrosine kinase.

Oncogenic activation of the met (hepatocyte growth factor/scatter factor) receptor tyrosine kinase involves a genomic rearrangement that generates a hybrid protein containing tpr-encoded sequences at its amino terminus fused directly to the met-encoded receptor kinase domain. Deletion of Tpr sequences abolishes the transforming ability of this protein, implicating this region in oncogenic activation. We demonstrate, by site-directed mutagenesis and coimmunoprecipitation experiments, that a leucine zipper motif within Tpr mediates dimerization of the tpr-met product and is essential for the transforming activity of the met oncogene. By analogy with ligand-stimulated activation of receptor tyrosine kinases, we propose that constitutive dimerization mediated by a leucine zipper motif within Tpr is responsible for oncogenic activation of the Met kinase. The possibility that this mechanism of activation represents a paradigm for a class of receptor tyrosine kinase oncogenes activated by DNA rearrangement is discussed.

3T3 Cells↗
PubMed1993

Intrinsic positive end-expiratory pressure in ambulatory patients with airways obstruction.

In patients with severe expiratory airflow limitation, dynamic hyperinflation often occurs when inspiratory efforts are initiated at a thoracic volume above the relaxation point of the respiratory system. The result is intrinsic positive end-expiratory alveolar pressure (PEEPi). To determine whether PEEPi occurs in ambulatory patients, we measured alveolar pressure (Palv) noninvasively during tidal breathing in 8 normal subjects, 15 asthmatic subjects, and 19 patients with COPD, using a body plethysmographic technique that includes computerized corrections for nonlinear pneumotachometer output and for plethysmograph leakage. In all 8 normal subjects, 9 asthmatic subjects, and 3 COPD patients, Palv descended smoothly to zero at end expiration. In contrast, among each of the remaining 22 patients, there was an abrupt change in slope of the Palv tracing near end expiration, identifying the onset of the next inspiratory effort and indicating the presence of PEEPi, ranging from 0.2 to 9.5 cm H2O. PEEPi was significantly correlated with FRC (% of predicted); PEEPi = (0.040 x %FRC) - 3.65, r = 0.73, p < 0.001, and with the reciprocal of FEV1 (% of predicted), PEEPi = (138/%FEV1) - 1.34, r = 0.69, p < 0.001. PEEPi could be elicited in normal subjects by severe expiratory resistive loading but not by the increased expiratory muscle activity occurring during an MVV maneuver. We conclude that PEEPi is common in patients with airways obstruction, even without overt ventilatory failure, and that its severity is generally in proportion to the severity of the hyperinflation and the airways obstruction.

Adult↗
PubMed1993

Isoforms of the met receptor tyrosine kinase.

Hepatocyte growth factor/scatter factor (HGF-SF), a multifunctional cytokine, is the ligand for the met receptor tyrosine kinase. Multiple met mRNAs of 8, 7, 5, 3 and 1.6-kb in size have been identified in human cell lines and tissue. To investigate the biological function of these various isoforms we have isolated cDNA clones corresponding to some of the differentially spliced met mRNAs. Characterization of these cDNAs suggests that by alternative splicing and possibly by use of distinct transcription initiation sites the met HGF-SF receptor is expressed in various isoforms. We have demonstrated that there are two met 8-kb mRNAs that differ through alternative splicing of a 54-bp exon that maintains the open reading frame such that these proteins differ by only 18 aa in their extracellular domain. The -54-bp form corresponds to the most abundant 8-kb met RNA and encodes the p190 met alpha beta heterodimer. In contrast the +54-bp mRNA encodes a protein of 170 kd that is not cleaved yet is expressed at the cell surface and has in vitro kinase activity. The 7-kb mRNA differs by alternative splicing such that it encodes a protein with a distinct amino terminus. Unlike these met RNAs, the 1.6-kb mRNA has new 5' and 3' sequences and encodes a protein that shares homology with the extracellular domain of the met RTK but has a unique carboxy terminus. Thus multiple met RNAs encode proteins that differ in both the extracellular ligand binding domain and within the cytoplasmic domain suggesting that these different met isoforms may have distinct biological activities.

Alternative Splicing↗
PubMed1993

Hepatocyte growth factor/scatter factor is an autocrine factor for human normal bronchial epithelial and lung carcinoma cells.

Hepatocyte growth factor (HGF) or scatter factor (SF) has been considered primarily as an endocrine/paracrine factor. We report here that HGF/SF mRNA was expressed by cultured human normal bronchial epithelial cells and many non-small cell lung carcinoma cell lines. Scatter activity was detected in the culture media of these cells, and this activity was inhibited by a neutralizing anti-recombinant human HGF antiserum. Immunostaining confirmed the presence of immunoreactive human HGF-like protein in the cytoplasm of these cultured cells, and in ciliated columnar epithelium of normal human bronchus/bronchioles. The met/HGF/SF receptor of these cultured cells was constitutively phosphorylated on tyrosine residues. A neutralizing anti-recombinant human HGF antiserum decreased the phosphorylation of the receptor, inhibited the proliferation of 45% of the non-small cell lung carcinoma cell lines studied, and stimulated the proliferation of normal bronchial epithelial cells. Altogether, the data demonstrate that HGF/SF and/or HGF-like protein is an autocrine factor for normal and neoplastic human bronchial epithelial cells in culture.

Base Sequence↗
PubMed1992

Thoracic spinal calcinosis circumscripta causing cord compression in two German shepherd dog littermates.

Two young German shepherd dog littermates had progressive, painless, hindlimb ataxia. In both dogs plain radiography of the vertebral column revealed a solitary mineralised lesion on the dorsal laminae between the dorsal spines of the second and third thoracic vertebrae, and myelography with iopamidol demonstrated cord compression at the level of the lesions. The first dog died 18 hours after the myelography. A dorsal laminectomy performed in the second dog resulted in neurological improvement. A histopathological examination confirmed that both lesions were calcinosis circumscripta. The cause of the death of the first dog was meningitis.

Animals↗
PubMed1992

Tumor necrosis factor-alpha activates nuclear factor kappa B and induces manganous superoxide dismutase and phosphodiesterase mRNA in human papillary thyroid carcinoma cells.

Human papillary thyroid carcinoma (PTC) has a relatively benign prognosis despite a high frequency of lymphatic metastasis. This suggests that local anticancer factors, generated in lymph nodes, control PTC progression. The cytokine, tumor necrosis factor-alpha (TNF-alpha), may be one such factor. We have previously shown that a human PTC cell line (NP-PTC) has high affinity TNF-alpha receptors. We now report on the action of TNF-alpha in these cells. TNF-alpha decreased [3H]thymidine incorporation as well as cellular DNA content and cell number in a dose-dependent manner. The abundance of phosphodiesterase and manganous superoxide dismutase mRNA species was increased in a time- and dose-dependent manner in the NP-PTC cells after TNF-alpha treatment. TNF-alpha activated NF-kappa B, a nuclear factor thought to mediate multiple actions of TNF-alpha, in these cells with a maximum effect observed after 30 min of treatment. Thus, TNF-alpha has an antiproliferative action on NP-PTC cells, despite its ability to induce the accumulation of mRNA that encodes an enzyme (manganous superoxide dismutase), thought to be cytoprotective. The net antiproliferative effect must therefore be explained by a balance of protective and tumoricidal or static effects that ultimately result in control of tumor spread. These antiproliferative effects may be in part mediated by NF-kappa B and PDE.

Base Sequence↗
PubMed1992

Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor.

The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). It was previously shown that, like the oncogenic tpr-met, the mouse met proto-oncogene transforms NIH 3T3 cells. We have established NIH 3T3 cells stably expressing both human (Methu) and mouse (Metmu) met proto-oncogene products. The protein products are properly processed and appear on the cell surface. NIH 3T3 cells express endogenous mouse HGF/SF mRNA, suggesting an autocrine activation mechanism for transformation by Metmu. However, the tumor-forming activity of Methu in NIH 3T3 cells is very low compared with that of Metmu, but efficient tumorigenesis occurs when Methu and HGF/SFhu are coexpressed. These results are consistent with an autocrine transformation mechanism and suggest further that the endogenous murine factor inefficiently activates the tumorigenic potential of Methu. The tumorigenicity observed with reciprocal chimeric human and mouse receptors that exchange external ligand-binding domains supports this conclusion. We also show that HGF/SFhu expressed in NIH 3T3 cells produces tumors in nude mice.

3T3 Cells↗
PubMed1992

Transforming growth factor-beta blocks protein kinase-A-mediated iodide transport and protein kinase-C-mediated DNA synthesis in FRTL-5 rat thyroid cells.

Recent studies have shown that transforming growth factor-beta (TGF beta) alters DNA synthesis and iodide metabolism in human, porcine, and rat thyroid cells. In the present work we studied the mechanism of TGF beta action in FRTL-5 rat thyroid cells. The cells were treated with TGF beta in the presence of TSH, growth factors, and cellular modulators for various periods of time; then, [3H]thymidine incorporation and DNA content were measured as indicators of DNA synthesis, and [125I]iodide uptake was measured to assess cell function. TGF beta (10 ng/ml) inhibited TSH-induced DNA synthesis and iodide uptake. TGF beta also inhibited DNA synthesis induced by insulin-like growth factor-I, fibroblast growth factor, and endothelial cell growth factor. The protein kinase-A (PKA) activator 8-bromo-cAMP increased both iodide uptake and DNA synthesis; TGF beta inhibited 8-bromo-cAMP-induced [125I]iodide uptake, but not [3H]thymidine incorporation. The protein kinase-C (PKC) activator phorbol 12-myristate 13-acetate increased [3H]thymidine incorporation, and TGF beta inhibited this action of phorbol 12-myristate 13-acetate. The results show that activation of PKA or PKC increases DNA synthesis. TGF beta inhibited PKC-mediated, but not PKA-mediated, DNA synthesis in these cells. The results also show that TGF beta selectively inhibits PKA-mediated iodide uptake, but not PKA-mediated DNA synthesis. These findings suggest that TGF beta is a strong inhibitor of the proliferation and function of thyroid cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

The development of a decision support system for diagnosing nasal allergy.

This paper deals with the problem of improving the capability of the medical decision support system (MDSS) for diagnosing nasal allergy by integrating the previously developed expert system with the neural network approach. Three knowledge acquisition methods were used to develop the expert system: statistical, rule-based, and the combined approach. Among the three, a combined approach showed the best prediction rate based on discriminant analysis. Using the results of a combined approach as input values, the neural network was developed using back-propagation method. Unlike the expert system, the neural network system provides the resulting allergy status in probabilistic terms. Managerial as well as legal issues were also discussed in this paper.

Decision Support Techniques↗
PubMed1992

Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and nonsurgical blood loss.

The hemostatic dysfunction induced by cardiopulmonary bypass is due, in part, to a platelet dysfunction evidenced by a postoperative extension of the bleeding time; it leads to increased postoperative blood loss and morbidity. This study, which was conducted in 85 patients undergoing cardiopulmonary bypass, was designed to characterize the hematologic changes during and after cardiopulmonary bypass and to elucidate the relationships between these changes, the extension of the bleeding time, and the magnitude of the postoperative nonsurgical blood loss. Variables were measured before, during, and 2, 24, 48, and 72 hours after cardiopulmonary bypass. Univariate and multivariate analyses were performed with either the 2-hour postbypass bleeding time or the 4-hour postbypass blood loss as the dependent variables. The reversal of the extension of the bleeding time in the postoperative period was accompanied by a significant increase in the mean platelet volume and by a significant increase in the level of thromboxane B2 measured in the blood shed from the site of the bleeding time determination. The postoperative bleeding time correlated with the postoperative blood loss, and both parameters were dependent on the duration of cardiopulmonary bypass. In addition, the postoperative bleeding time correlated with the skin temperature and the plasma level of D-dimer, while the postoperative blood loss also correlated with temperature and the plasma levels of C3. These data establish a direct relationship between the postoperative bleeding time, the postoperative blood loss, and temperature. They indicate that the reversal of the postoperative extension of the bleeding time is due in part to rewarming and to the release of larger platelets into the circulation, and they suggest that hyperfibrinolysis and complement activation may play an important role in the cardiopulmonary bypass-induced platelet dysfunction.

Bleeding Time↗
PubMed1992

Overexpression of c-met proto-oncogene but not epidermal growth factor receptor or c-erbB-2 in primary human colorectal carcinomas.

The epidermal growth factor receptor (EGFR) and the protein products of c-erbB-2 and c-met proto-oncogenes belong to a family of growth factor receptors with tyrosine kinase activity. In human colonic carcinomas, the expression of the EGFR and c-erbB-2 have been studied at the protein level only, while c-met expression has not been reported. We have examined the mRNA expression of these genes in human normal colorectal mucosa and primary carcinomas. The results demonstrate that the normal mucosa shows highly variable levels of EGFR and c-erbB-2 mRNAs, but expresses consistently low amounts of c-met mRNA. Colorectal carcinomas did not express significantly higher levels of the EGFR and c-erbB-2 mRNAs than the normal mucosa. In contrast, c-met was consistently and significantly overexpressed (mean sixfold) in carcinomas as compared with normal mucosa. Seventy percent of paired normal-tumor specimens showed a tumor to normal c-met mRNA ratio of greater than 4. The expression of c-met mRNA was also enhanced in the adenomas, suggesting that over-expression of this proto-oncogene may have mechanistic significance in the early stages of human colorectal carcinogenesis.

Colorectal Neoplasms↗
PubMed1991

Primary structure of two forms of gonadotropin-releasing hormone from brains of the American alligator (Alligator mississippiensis).

Two forms of gonadotropin-releasing hormone (GnRH) have been purified from brains of the American alligator, Alligator mississippiensis, using reverse-phase high-pressure liquid chromatography (HPLC). The concentration of total GnRH was 8.8 ng/g of frozen brain tissue or 21.1 ng per brain. The amino acid sequence of each form of GnRH was determined using automated Edman degradation. The presence of the N-terminal pGlu residue was established by digestion studies with bovine pyroglutamyl aminopeptidase and coelution with synthetic forms of the native peptide. The primary structure of alligator GnRH I is pGlu-His-Trp-Ser-Tyr-Gly-Leu-Gln-Pro-Gly-NH2 and alligator GnRH II is pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2.

Alligators and Crocodiles↗