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H G Kim

Publications and source records attributed to H G Kim.

86 records · Page 5Linked to original sources
PubMed1991

A novel cyclin encoded by a bcl1-linked candidate oncogene.

We have previously identified a candidate oncogene (PRAD1 or D11S287E) on chromosome 11q13 which is clonally rearranged with the parathyroid hormone locus in a subset of benign parathyroid tumours. We now report that a cloned human placental PRAD1 complementary DNA encodes a protein of 295 amino acids with sequence similarities to the cyclins. Cyclins can form a complex with and activate p34cdc2 protein kinase, thereby regulating progress through the cell cycle. PRAD 1 messenger RNA levels vary dramatically across the cell cycle in HeLa cells. Addition of the PRAD1 protein to interphase clam embryo lysates containing inactive p34cdc2 kinase and lacking endogenous cyclins allows it to be isolated using beads bearing p13suc1, a yeast protein that binds cdc2 and related kinases with high affinity and coprecipitates kinase-associated proteins. Addition of PRAD1 also induces phosphorylation of histone H1, a preferred substrate of cdc2. These data suggest that PRAD1 encodes a novel cyclin whose overexpression may play an important part in the development of various tumours with abnormalities in 11q13.

Adenoma↗
PubMed1991

Rods and cones activate different excitatory amino acid receptors on the mudpuppy retinal horizontal cell.

We have studied rod and cone neurotransmission onto horizontal cells (HCs) of the mudpuppy retina by: (1) dual whole-cell recordings from synaptically connected pairs in a superfused retinal slice preparation, and (2) intracellular recordings from HCs in a superfused retina-eyecup preparation. In the presence of relatively weak concentrations of broad spectrum excitatory amino acid antagonists, HC recordings show that cone-mediated responses were significantly more attenuated than those mediated by rods. These observations suggest that the HC postsynaptic receptors for rods and cones are pharmacologically different. One advantage of having distinct rod- and cone-activated receptors on second-order neurons may be to preserve different rod and cone functions under varying levels of light stimulation and provide separate means of regulating rod and cone neurotransmission onto the second-order cells.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Rearrangement and overexpression of D11S287E, a candidate oncogene on chromosome 11q13 in benign parathyroid tumors.

We report the detailed molecular characterization of a human parathyroid adenoma with a clonal parathyroid hormone gene rearrangement. This rearrangement is similar to one we characterized recently in an independent adenoma. In these two, plus a third partially characterized adenoma, one allele of the PTH gene, on 11p15, is rearranged with DNA from the D11S287 region on 11q13. This region contains a transcribed sequence, D11S287E, distinct from known 11q13 oncogenes, that is expressed in all parathyroid tissues examined, but is overexpressed dramatically in all three tumours with PTH gene-D11S287 rearrangements. These findings suggest that overexpression of D11S287E, perhaps driven by the misplaced PTH gene's regulatory elements, contributed to the development of these benign tumors. D11S287E is a new candidate oncogene with potential importance in parathyroid adenomas and perhaps other tumors with 11q13 abnormalities.

Adenoma↗
PubMed1989

Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma.

Parathyroid adenomas are common benign neoplasms for which no chromosomal defects have been described. We recently found two parathyroid adenomas bearing clonal restriction fragment abnormalities involving the PTH locus, and now show that in one of these tumors: (a) a DNA rearrangement occurred at the PTH locus; (b) the rearrangement separated the PTH gene's 5' flanking region from its coding exons, conceivably placing a newly adjacent gene under the influence of PTH regulatory elements; (c) the DNA that recombined with PTH normally maps to 11q13, the known chromosomal location of several oncogenes and the gene for multiple endocrine neoplasia type I; and (d) the rearrangement was a reciprocal, conservative recombination of the locus on 11q13 (Human Gene Mapping Library assignment D11S287) with PTH (on 11p15). These data provide molecular cytogenetic evidence for the clonal occurrence of a major chromosome 11 aberrancy in this benign parathyroid tumor. The D11S287 clone could prove useful in genetic linkage analyses, in determining precise 11q13 breakpoints in other neoplasms, and in identifying a gene on chromosome 11 that may participate in parathyroid tumor development.

Adenoma↗
PubMed1989

Clonal loss of one chromosome 11 in a parathyroid adenoma.

Traditional cytogenetic approaches have been unsuccessful in the study of parathyroid adenomas. We now describe one parathyroid adenoma in which a molecular cytogenetic approach revealed clonal loss of one chromosome 11. Restriction fragment length polymorphism analysis of the patient's normal leukocyte DNA demonstrated heterozygosity at four loci (PTH, INT2, APOA1, and ETS1) that span the length of chromosome 11. However, the adenoma DNA showed clonal deletion of one allele, i.e. loss of heterozygosity, at each locus. Use of five nonpolymorphic probes from chromosome 11 was consistent with 50% loss of total chromosome 11 DNA in the adenoma. No tumor-specific loss of heterozygosity was observed when restriction fragment length polymorphisms from five other autosomes (no. 1, 5, 6, 7, and 12) were analyzed, and an X-chromosome probe also showed no tumor DNA loss. We have demonstrated tumor-specific chromosome loss in a parathyroid adenoma; such a lesion has been described only rarely in benign tumors. Our finding adds to the evidence for monoclonality in parathyroid adenomatosis, indicates that only one PTH gene copy is sufficient for hyperparathyroid tumor function, and raises the possibility that a tumor-suppressor gene important in the development of nonfamilial parathyroid neoplasia is located on chromosome 11.

Adenoma↗
PubMed1989

Correlation of magnetic resonance imaging and surgical findings in patients with meniscal perforation.

Advancement of surgical techniques has made it necessary to accurately diagnose internal derangements. Arthrography and computerized tomography have been used to diagnose the majority of temporomandibular joint disorders; however, these methods have had their disadvantages. Magnetic resonance imaging utilizing surface coils has greatly improved the ability to diagnose meniscus abnormalities without using interarticular injections or ionizing radiation. Ninety-two patients (184 joints) were evaluated by means of magnetic resonance imaging (MRI). Thirty-one patients (39 joints) were diagnosed as having meniscus perforation. Retrospective reviews of 15 patients (20 joints) with a perforated meniscus diagnosed by magnetic resonance imaging preoperatively demonstrated a 65% correlation between the radiographic diagnosis and the surgical findings.

Adult↗
PubMed1988

Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas.

Previous work based on the relative tissue content of glucose-6-phosphate dehydrogenase isoenzymes suggested that parathyroid adenomas, like primary hyperplasia, may be multicellular (not clonal) in origin. We have reexamined this issue by using two independent molecular genetic methods. We report tumor-cell-specific restriction-fragment-length alterations involving the parathyroid hormone gene from two human parathyroid adenomas. These abnormal restriction fragments indicate that in each case a clonal proliferation of cells was present and also suggest that DNA alterations involving the parathyroid hormone locus may be important in the tumorigenesis or clonal evolution of some parathyroid adenomas. In addition, we used a restriction-fragment-length polymorphism in an X-linked gene (hypoxanthine phosphoribosyltransferase) to examine the clonality of eight parathyroid adenomas in women. Of these eight adenomas, six had the DNA hybridization pattern of monoclonality, and two had an equivocal pattern. None of five hyperplastic parathyroid glands had a monoclonal pattern. We conclude that some (and perhaps many) single parathyroid adenomas are monoclonal neoplasms. Our observations suggest that there is a fundamental biologic difference between parathyroid adenomas and primary hyperplasia--a difference that could prove useful in distinguishing these entities clinically.

Adenoma↗
PubMed1979

Procainamide-induced sinus node dysfunction in patients with chronic renal failure.

Two patients with chronic renal failure developed transient sinus node dysfunction requiring insertion of a temporary pacemaker while receiving procainamide to control ventricular arrhythmias. Blood levels of procainamide were found to be elevated, although at these levels, sinus node dysfunction has not previously been reported. Following discontinuance of procainamide, sinus rhythm returned. A combination of factors, including elevated levels of N-acetyl procainamide, the metabolite of procainamide with anti-arrhythmic properties, are suggested as possible contributory causes for the ECG findings. Thus, procainamide may produce electrophysiologic features of "sick sinus syndrome" in patients with chronic renal failure even when blood levels of this substance are being monitored.

Acecainide↗
PubMedDate not supplied

Properties of excitatory synaptic events in neurons of primary somatosensory cortex of neonatal rats.

We have characterized the development of synaptic responses from neurons of rat parietal cortex. Whole-cell recording was used in slice preparations in vitro. Neurons were stained with biocytin to allow their identification, and the sample included pyramidal neurons and Cajal-Retzius cells. Dye-coupling of 3-12 cells was frequently observed from the day of birth (P0) to P3. On average, when recorded with Cs(+)-filled electrodes, the input resistances of neonatal cells were large (mean = 1.1 G omega) and resting membrane potentials were relatively depolarized (mean = -45 mV) when compared to mature neocortical neurons. The application of an NMDA receptor antagonist usually hyperpolarized cells by 5-10 mV and increased their input resistance (mean increase = 83%), suggesting that immature neurons are tonically activated by excitatory amino acids (EAA) in our preparation. Excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) could be obtained from animals as young as P0 by brief stimulation of the subplate. Synaptic responses at these early ages had long durations, often lasting over hundreds of milliseconds, they reversed polarity around 0 mV, and they were blocked by tetrodotoxin and EAA antagonists. Pharmacology and current-voltage relationships demonstrated the presence of both NMDA receptor- and non-NMDA receptor-dependent components in most EPSPs. Unlike synaptic responses of mature neurons, neonatal synaptic responses were composed largely of NMDA receptor-dependent components. We did not observe inhibitory synaptic inputs before P6. In some neurons, single shocks to the subplate region initiated spontaneous EPSPs that lasted > 1 min. This study clearly demonstrates functional synapses in the neocortex of rats on the day of birth. Large NMDA receptor-mediated EPSPs with long duration could have a major influence on the development of cortical circuits in the neonate.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMedDate not supplied

Nrs1, a repetitive element linked to pisatin demethylase genes on a dispensable chromosome of Nectria haematococca.

We have identified a repetitive DNA element in Nectria haematococca mating population VI, isolate T-2. This repetitive sequence has been called Nrs1. DNA hybridization analysis indicates the sequence is found in several isolates of the fungus pathogenic to Pisum sativum. A 2,027-bp clone containing the Nrs1-2 allele contains a long polyA sequence, imperfect RNA polymerase III promoter sequences, multiple inverted repeats, and the potential for extensive secondary structure similar to known RNA polymerase III transcripts and related retroelements. Ten of the 11 HindIII restriction fragments from isolate T-2 DNA that hybridize to Nrs1-2 segregate in a manner consistent with a 1:1 ratio for random ascospore progeny. The 10 restriction fragment length polymorphism (RFLP) loci define three linkage groups and correspond to three chromosome-sized DNAs from T-2 separated by pulsed field gel electrophoresis. Three RFLP loci defined by hybridization to the gene for pisatin demethylase and localized on the 1.6 million base pair (Mb) chromosome were genetically linked to each other and to several Nrs1 loci. These sequences recombined despite the fact that no obvious homolog exists for the 1.6-Mb chromosome in one parent strain. Allelic RFLPs corresponding to the gene sequence of cutinase were unlinked to Nrs1 loci.

Base Sequence↗
PubMedDate not supplied

Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3'-Kinase/Akt signal transduction pathway.

Angiopoietin-1 (Ang1) is a strong apoptosis survival factor for endothelial cells. In this study, the receptor/second messenger signal transduction pathway for the antiapoptotic effect of Ang1 on human umbilical vein endothelial cells was examined. Pretreatment with soluble Tie2 receptor, but not Tie1 receptor, blocked the Ang1-induced antiapoptotic effect. Ang1 induced phosphorylation of Tie2 and the p85 subunit of phosphatidylinositol 3'-kinase (PI 3'-kinase) and increased PI 3'-kinase activity in a dose-dependent manner. The PI 3'-kinase-specific inhibitors wortmannin and LY294002 blocked the Ang1-induced antiapoptotic effect. Ang1 induced phosphorylation of the serine-threonine kinase Akt at Ser473 in a PI 3'-kinase-dependent manner. Expression of a dominant-negative form of Akt reversed the Ang1-induced antiapoptotic effect. Ang1 mRNA and protein were present in vascular smooth muscle cells but not in endothelial cells. Cultured vascular smooth muscle cells, but not human umbilical vein endothelial cells, secreted Ang1. These findings indicate that the Tie2 receptor, PI 3'-kinase, and Akt are crucial elements in the signal transduction pathway leading to endothelial cell survival induced by the paracrine activity of Ang1.

Angiopoietin-1↗
PubMedDate not supplied

Treatment of internal carotid artery dissections with endovascular stent placement: report of two cases.

Extracranial carotid artery dissection may manifest as arterial stenosis or occlusion, or as dissecting aneurysm formation. Anticoagulation and/or antiplatelet therapy is the first-line treatment, but because it is effective and less invasive than other procedures, endovascular treatment of carotid artery dissection has recently attracted interest. We encountered two consecutive cases of trauma-related extracranial internal carotid artery dissection, one in the suprabulbar portion and one in the subpetrosal portion. We managed the patient with suprabulbar dissection using a self-expandable metallic stent and managed the patient with subpetrosal dissection using a balloon-expandable metallic stent. In both patients the dissecting aneurysm disappeared, and at follow-up improved luminal patency was observed.

Adult↗