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Biomedical subjects

M Park

Publications and source records attributed to M Park.

At least 127 records · Page 7Linked to original sources
PubMed1997

The genetic basis of resistance to Ostertagia circumcincta in lambs.

The relationship between Ostertagia (Teladorsagia) circumcincta and sheep is one of the best understood host-parasite relationships in any species. The key components of resistance have been quantified, the extent of genetic control has been established for lambs, and methods now exist to breed lambs which will be both more resistant to worms and more productive than unselected lambs. A major gene for resistance has been identified within or around the major histocompatibility complex, and this gene appears to be the strongest yet identified for resistance to any parasite species. The most important mechanisms of resistance are local IgA responses which regulate worm fecundity and immediate hypersensitivity responses which regulate worm burdens. IgA responses develop before effective immediate hypersensitivity responses. Good simulation models now exist to predict, for example, outbreaks of disease and the response of sheep to selection. The challenge now is to use our improved understanding of the population biology to develop even better simulation models and to produce expert systems based on these models which can be used by veterinarians and others to determine optimal procedures for individual farms to control disease and reduce sub-clinical economic losses.

Animals↗
PubMed1997

A C. elegans E/Daughterless bHLH protein marks neuronal but not striated muscle development.

The E proteins of mammals, and the related Daughterless (DA) protein of Drosophila, are ubiquitously expressed helix-loop-helix (HLH) transcription factors that play a role in many developmental processes. We report here the characterization of a related C. elegans protein, CeE/DA, which has a dynamic and restricted distribution during development. CeE/DA is present embryonically in neuronal precursors, some of which are marked by promoter activity of a newly described Achaete-scute-like gene hlh-3. In contrast, we have been unable to detect CeE/DA in CeMyoD-positive striated muscle cells. In vitro gel mobility shift analysis detects dimerization of CeE/DA with HLH-3 while efficient interaction of CeE/DA with CeMyoD is not seen. These studies suggest multiple roles for CeE/DA in C. elegans development and provide evidence that both common and alternative strategies have evolved for the use of related HLH proteins in controlling cell fates in different species.

Amino Acid Sequence↗
PubMed1997

Evidence that gonadotropin-releasing hormone (GnRH) functions as a prolactin-releasing factor in a teleost fish (Oreochromis mossambicus) and primary structures for three native GnRH molecules.

Three forms of gonadotropin-releasing hormone (GnRH) are isolated and identified here by chemical sequence analysis for one species of tilapia, Oreochromis niloticus, and by HPLC elution position for a second species of tilapia, O. mossambicus. Of the three GnRH forms in O. mossambicus, chicken GnRH-II (cGnRH-II) and sea bream GnRH (sbGnRH) are present in greater abundance in the brain and pituitary than salmon GnRH (sGnRH). These three native forms of GnRH are shown to stimulate the release of prolactin (PRL) from the rostral pars distalis (RPD) of the pituitary of O. mossambicus in vitro with the following order of potency: cGnRH-II > sGnRH > sbGnRH. In addition, a mammalian GnRH analog stimulated the release of PRL from the pituitary RPD incubated in either iso-osmotic (320 mosmol/l) or hyperosmotic (355 mosmol/l) medium, the latter normally inhibiting PRL release. The response of the pituitary RPD to GnRH was augmented by co-incubation with testosterone or 17 beta-estradiol. The effects of GnRH on PRL release appear to be direct effects on PRL cells because the RPD of tilapia contains a nearly homogeneous mass of PRL cells without intermixing of gonadotrophs. Our data suggest that GnRH plays a broad role in fish, depending on the species, by affecting not only gonadotropins and growth hormone, but also PRL.

Amino Acid Sequence↗
PubMed1997

Ethnic differences in birthweight: the role of lifestyle and other factors.

OBJECTIVES: The purpose of this study was to expand the search for risk factors for low birthweight and to find new explanations for the ethnic-group disparities in birth outcomes. METHODS: The subjects were 1150 pregnant women from six ethnic groups (African American, Chinese, Dominican, Puerto Rican, Mexican, and White) who received prenatal care at clinics in New York and Chicago between December 1987 and December 1989. Two interviews were conducted during the second and third trimesters of pregnancy. RESULTS: The study, after controlling for poverty and other birthweight correlates, showed that living in public housing and believing that chance plays a major role in determining one's health status were negatively associated with birthweight. Having a stable residence was positively related to birthweight. Material hardship, social adversity, perceived racial discrimination, physical abuse, anxiety, and depression were not associated with birthweight. CONCLUSIONS: The negative role of an impoverished living environment and feelings of helplessness, as well as the positive role of having a stable form of social support, suggest new directions for research on the causes of low birthweight and the ethnic disparities in US birth outcomes.

Black or African American↗
PubMed1997

CNS innervation of the urinary bladder demonstrated by immunohistochemical study for c-fos and pseudorabies virus.

The aim of the present study is to verify the functional and anatomical neural pathways which innervate the urinary bladder in the central nervous system of the rat. To identify the functional neural pathway, the urinary bladder was stimulated by infusing formalin for 2 h. Then, brain and spinal cord were dissected out and immunohistochemistry was done by using anti-c-fos antibody. Many c-fos immunoreactive (IR) neurons were identified in the telencephalic cortical areas and in several brainstem nuclei, which are known mostly to be related with urinary bladder. In the spinal cord, a number of c-fos IR neurons were found in the lamina I, IIo, dorsal gray commissure, sacral parasympathetic nucleus. To identify the anatomical neural pathway of the urinary bladder, Pseudorabies virus (PRV) was injected into the wall of urinary bladder and was identified with anti-PRV by using immunohistochemistry. Most PRV labeled neurons were found where c-fos IR neurons were identified and few of them were also in the areas where c-fos IR neurons were not found, e.g., prefrontal cortex, agranular insular cortex, and subfornical organ. In the spinal cord, PRV labeled cells were found all over the gray matter. The present study presents morphological evidence demonstrating the supraspinal areas are related with the neural control of the urinary bladder and most functional neural pathway of the urinary bladder is well consistent with the anatomical neural pathway except in some telencephalic cortical areas.

Animals↗
PubMed1997

[Ultrasound biomicroscopic observation of the anterior eye segment in a sclerocornea and a microcornea].

We observed the anterior segment of eyes in one case of sclerocornea and one case of microcornea using an ultrasound biomicroscope. The sclerocornea was the peripheral type. The contrast in the image of ultrasound biomicroscopy changes from low to high density in proportion to the optical opacity at the peripheral portion of the cornea. There was no abnormality in the anatomical figures of the anterior chamber angle in ultrasound biomicroscopic findings, which gave significant information in the cataract surgery. The patient with microcornea had horizontal nystagmus, partial coloboma of the iris, choroidal coloboma, and cataract in both eyes. We observed the iris tissue in all the meridians in the ultrasound biomicroscopic pictures. Ultrasound biomicroscopy is a promising procedure for examining the anterior segment of eyes with corneal opacity.

Adult↗
PubMed1997

Inhibition of junction assembly in cultured epithelial cells by hepatocyte growth factor/scatter factor is concomitant with increased stability and altered phosphorylation of the soluble junctional molecules.

Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived glycoprotein with a strong scattering effect on epithelial cells. A receptor tyrosine kinase encoded by the met proto-oncogene has been identified as the cellular receptor for HGF/SF. Following stimulation with HGF/SF, cell scattering occurs concurrent with decreased cell-cell adhesion and disassembly of junctional components. In culture, junction formation is cell-cell contact dependent and can be regulated by modulating the Ca2+ concentrations of the growth media. Decreasing the Ca2+ concentrations below 50 microM causes rapid disassembly of junctions, whereas increasing the Ca2+ concentrations to 1.8 mM induces cell-cell contact and junction assembly. Although associated with decreased cell-cell adhesion and disassembly of the junctional complex, HGF/SF-induced scattering occurs under high extracellular Ca2+ concentrations. To gain insight into the mechanisms of HGF/SF-induced scattering of epithelial cells, we have studied the effect(s) of HGF/SF on junction assembly by examining the solubility, stability, phosphorylation, and subcellular localization of the major components of the adhering junctions, plakoglobin (Pg) and E-cadherin, in Madin-Darby canine kidney (MDCK) epithelial cells and in a MDCK cell line expressing an exogenous chimeric met receptor (CSF-MET) that scatters in response to colony-stimulating factor 1 (CSF-1). The results have shown that in HGF/SF-stimulated MDCK cells, adhering junctions were not assembled upon induction of cell-cell contact. Immunofluorescence analyses showed that larger amounts of Pg and E-cadherin were Triton X-100 extractable, and more significantly, these proteins were homogeneously distributed along the membrane and were not concentrated at the areas of cell-cell contact. Similar results were obtained for CSF-MET expressing MDCK cells in response to CSF-1. In contrast, none of the above effects were detected in MDCK cells expressing a mutant CSF-MET chimera containing a phenylalanine substitution at tyrosine 1356 in met, which fails to scatter in response to CSF-1. When compared with the unstimulated cells, the inhibition of cell adhesion promoted by HGF/SF correlated with an increased stability of the newly synthesized soluble E-cadherin and Pg and an altered phosphorylation pattern of E-cadherin, as determined by partial proteolytic peptide mapping.

Animals↗
PubMed1996

Detailed deletion mapping with a refined physical map of 7q31 localizes a putative tumor suppressor gene for breast cancer in the region of MET.

In breast cancer, loss of heterozygosity (LOH) has been described on the long arm of chromosome 7 at band q31, suggesting the presence of a tumor suppressor gene in this region. To define the deleted region, we analysed 73 cases of breast cancer and matched normal DNAs with 17 polymorphic markers. A minimal area of LOH was identified as the chromosomal interval flanked by markers D7S687 and metH, spanning a segment of 2 Mb on chromosome 7q31. Of the 73 breast cancer patients studied, all were informative for at least one marker in this region and nine patients showed LOH at one or more loci (12.3%). To define the physical size of the deletion and to ensure the correct interpretation of the LOH deletion studies, we redefined the physical map of markers within this region of 7q31. We present a new physical order for markers at 7q31. More significantly, we have mapped the minimum deletion of 7q31 in the breast cancers studied to date to a physical distance of 1000 kb, contained on a single YAC clone, which includes the MET receptor tyrosine kinase but no other known genes.

Breast Neoplasms↗
PubMed1996

Two new forms of gonadotropin-releasing hormone in a protochordate and the evolutionary implications.

The neuropeptide gonadotropin-releasing hormone (GnRH) is the major regulator of reproduction in vertebrates. Our goal was to determine whether GnRH could be isolated and identified by primary structure in a protochordate and to examine its location by immunocytochemistry. The primary structure of two novel decapeptides from the tunicate Chelyosoma productum (class Ascidiacea) was determined. Both show significant identity with vertebrate GnRH. Tunicate GnRH-I (pGlu-His-Trp-Ser-Asp-Tyr-Phe-Lys-Pro-Gly-NH2) has 60% of its residues conserved, compared with mammalian GnRH, whereas tunicate GnRH-II (pGlu-His-Trp-Ser-Leu-Cys-His-Ala-Pro-Gly-NH2) is unusual in that it was isolated as a disulfide-linked dimer. Numerous immunoreactive GnRH neurons lie within blood sinuses close to the gonoducts and gonads in both juveniles and adults, implying that the neuropeptide is released into the bloodstream. It is suggested that in ancestral chordates, before the evolution of the pituitary, the hormone was released into the bloodstream and acted directly on the gonads.

Amino Acid Sequence↗
PubMed1996

Branching tubulogenesis but not scatter of madin-darby canine kidney cells requires a functional Grb2 binding site in the Met receptor tyrosine kinase.

Hepatocyte growth factor is a multifunctional cytokine that induces mitogenesis, motility, invasion, and branching tubulogenesis of several epithelial and endothelial cell lines in culture. The receptor for hepatocyte growth factor has been identified as the Met tyrosine kinase. To investigate the signaling pathways that are involved in these events, we have generated chimeric receptors containing the colony stimulating factor-1 receptor fused to the transmembrane and intracellular domains of the Met receptor. Madin-Darby canine kidney epithelial cells expressing the Met chimera dissociate scatter and form branching tubules in response to colony stimulating factor-1. From structure-function analyses, tyrosine residue 1356 within the carboxyl terminus of the Met receptor is critical for these events. The amino acid sequence downstream from tyrosine 1356 represents a consensus binding site for the Grb2 adaptor protein and forms a multisubstrate binding site for the p85 subunit of phosphatidylinositol 3-kinase, phospholipase Cgamma, and the Shc adaptor protein. To distinguish which of these signaling pathways are required, we generated a mutant receptor that selectively fails to associate with the Grb2 adaptor protein. Cells expressing this mutant receptor scattered but were unable to form branching tubules, indicating that a Grb2 binding site in the Met receptor is critical for morphogenic responses.

Adaptor Proteins, Signal Transducing↗
PubMed1996

The wingless signaling pathway is directly involved in Drosophila heart development.

Heart development in both vertebrates and Drosophila is initiated by bilaterally symmetrical primordia that may be of equivalent embryological origin: the anterior lateral plate mesoderm in vertebrates and the dorsal-most mesoderm in arthropods. These mesodermal progenitors then merge into a heart tube at the ventral midline (vertebrates) or the dorsal midline (Drosophila). These observations suggest that there may be similarities between vertebrate and invertebrate heart development. The homeobox gene, tinman, is required for heart as well as visceral mesoderm formation in Drosophila, and at least one of several vertebrate genes with similarities in protein sequence and cardiac expression to tinman is crucial for heart development in vertebrates. Inductive signals are also required for Drosophila heart development: The secreted gene product of wingless (wg) is critical for heart development during a time period distinct from its function in segmentation and neurogenesis. Here, we show that wg is epistatic to hedgehog (hh), another secreted segmentation gene product, in its requirement for heart formation. We also provide evidence show that downstream of wg in the signal transduction cascade, dishevelled (dsh, a pioneer protein) and armadillo (arm, beta-catenin homolog) are mediating the cardiogenic Wg signal. In particular, overexpression of dsh can restore heart formation in the absence of wg function. We discuss the possibility that Wg signaling is part of a combinatorial mechanism to specify the cardiac mesoderm.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Pathways downstream of Shc and Grb2 are required for cell transformation by the tpr-Met oncoprotein.

The Tpr-Met oncoprotein, which is a member of a family of tyrosine kinase oncoproteins generated following genomic rearrangement, consists of the catalytic kinase domain of the hepatocyte growth factor/scatter factor receptor tyrosine kinase (Met) fused downstream from sequences encoded by the tpr gene. We have previously demonstrated that a single tyrosine residue in the carboxyl terminus, Tyr489, is highly phosphorylated and is essential for efficient transformation of Fr3T3 fibroblasts by Tpr-Met and for the association of Tpr-Met with the Grb2 adaptor protein and phosphatidylinositol 3'-kinase. We show here that Tyr489 is also required for association of Tpr-Met with phospholipase Cgamma and the tyrosine phosphatase, SHPTP2/Syp. To distinguish which of these substrates are required for cell transformation by the Tpr-Met oncoprotein, we generated a novel Tpr-Met mutant that selectively fails to associate with the Grb2 adaptor protein. Utilizing this mutant, together with additional Tpr-Met mutants containing Tyr to Phe substitutions, we have demonstrated that transformation of Fr3T3 fibroblasts by the Tpr-Met oncoprotein is dependent upon pathways downstream of Shc and Grb2 and that pathways downstream of phosphatidylinositol 3'-kinase, phospholipase Cgamma, and SHPTP2/Syp are insufficient for transformation.

3T3 Cells↗
PubMed1996

Identification of the proteolytic enzyme which cleaves human p75 TNF receptor in vitro.

The extracellular domains of the human 55 and 75 kD TNF receptors (p55 and p75 TNF-R) are proteolytically cleaved to produce 30 and 40 kD soluble fragments, respectively. In this study, the enzymatic activity involved in the cleavage of human p75 TNF-R, named TNF-R releasing enzyme (TRRE), was identified in the culture supernatant of PMA-stimulated THP-1 cells using an activity assay system established by our group. When THP-1 cells were stimulated with PMA, TRRE was released rapidly into the supernatant, reaching maximal activity within 3 hours. The release of TRRE into the culture supernatant depended on the concentration of PMA and FCS. TRRE activity was partially inhibited by chelating agents, suggesting that TRRE may be a metallo-protease-like enzyme. This is the first successful attempt to establish a stable TRRE source with a reliable assay system.

Animals↗
PubMed1996

Characterization of a sheep brain corticotropin releasing factor binding protein.

We report here the identification, purification and cDNA cloning of a corticotropin releasing factor (CRF) binding protein(s) (CRF-BP) from sheep brain. Native sheep and rat brain CRF-BP and recombinant rat CRF-BP were shown to be N-glycosylated. Two membrane associated forms of brain CRF-BPs of 33 and 35 kDa were purified from sheep brain homogenates after solubilization in the presence of detergent. N-Terminal sequence analysis revealed that the 35 kDa protein is proteolytically cleaved near the N-terminus giving rise to an 18 amino acid peptide and a 33 kDa CRF-BP. Both the purified 33 and 35 kDa ovine CRF-BPs could be specifically cross linked to ovine [125I]CRF and human [125I]CRF. In contrast, recombinant rat CRF-BP can only be cross-linked to human [125I]CRF. A 1.7 kb cDNA clone (Basil 7) encoding an open reading frame for a 324 amino acid CRF-BP precursor was cloned from a sheep brain lambda gtlO cDNA library and was shown to have 85% and 87% amino acid homology to the rat and human proteins, respectively. Competitive binding analysis of the recombinant sheep CRF-BP (Basil 7) expressed in CHO cells revealed that it binds human and ovine CRF with high affinity. However, the recombinant sheep CRF-BP (Basil 7) had approximately 50-fold higher affinity for human CRF than for the ovine peptide. These data present the first biochemical proof that CRF-BP is in the brain and provides evidence for the existence of different forms of CRF-BP which have evolved across species to regulate CRF.

Amino Acid Sequence↗
PubMed1996

Identification of tyrosine 489 in the carboxy terminus of the Tpr-Met oncoprotein as a major site of autophosphorylation.

The Met receptor tyrosine kinase is the receptor for hepatocyte growth factor/scatter factor. HGF/SF is a multifunctional cytokine that can stimulate proliferation, motility, and morphogenesis in epithelial and endothelial cells. Oncogenic activation of the Met receptor occurs through a genomic rearrangement that generates a hybrid protein in which tpr sequences are directly fused amino terminal to the met receptor kinase domain. The resultant Tpr-Met hybrid protein possesses tyrosine kinase activity, is constitutively phosphorylated on tyrosine residues in vivo, and transforms fibroblasts in culture. We have identified two tyrosine residues within the catalytic domain of the Tpr-Met oncoprotein (Y365, Y366) and Met receptor (Y1234, Y1235) that are phosphorylated and essential for both the catalytic and biological activity of the oncoprotein and receptor. However, a detailed analysis of phosphorylation in these proteins has not been undertaken. In order to determine the sites of tyrosine phosphorylation in the Tpr-Met oncoprotein, in vitro mutagenesis, phosphopeptide mapping, and dephosphorylation protection assays were performed. Here we identify that a single tyrosine (Y489) in the carboxy terminus of the Tpr-Met oncoprotein is highly phosphorylated and is essential for biological activity. In contrast, additional tyrosines (Y482, Y498) located in the carboxy terminus are not phosphorylated at detectable levels and are not essential for the biological activity of the oncoprotein.

Animals↗
PubMed1996

Determining factors for the outcome of peripheral blood progenitor cells harvests.

This is a pilot retrospective study to investigate the factors that may affect the collection of peripheral blood progenitor cells (PBPC). Sixty-nine PBPC harvests in 18 cancer patients (median age 39.5; 8 males and 10 females) were performed during marrow recovery after chemotherapy and hematopoietic growth factors. Median number of nucleated cells (MNC) collected were 13.3 (range 2.3-44.5) x 10(9) per session. Median CFU-GM was 362 colonies (range 63-1,720) per 500,000 MNC. Neither sex, body weight, diagnosis, nor the number of days into leukapheresis was significantly associated with MNC and CFU-GM. Older patients tend to have higher CFU-GM in the PBPC harvests (P = .0437). Higher WBC on the day of harvest is significantly associated with higher yield of MNC after leukapheresis (P < .0001). Patients without any evidence of disease have significantly higher yield of MNC than those having local/distant metastases with or without marrow involvement (P = .0302 and .0446). For patients with metastatic disease, those with bone marrow involvement tend to have higher CFU-GM than those without bone marrow involvement although the difference is not statistically significant (P = .0559). Those patients who have received only one, or three and more chemotherapy regimens have a higher yield of MNC than those who have only two previous chemotherapy regimens (P = .036 and .0324). The mechanism of PBPC mobilization is also discussed. In view of the limited patient number in this study, the results should be confirmed by larger studies.

Adolescent↗