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Biomedical subjects

E Kim

Publications and source records attributed to E Kim.

At least 235 records · Page 13Linked to original sources

Localization of the human stem cell tyrosine kinase-1 gene (FLT3) to 13q12-->q13.

We have previously reported the cloning of stem cell tyrosine kinase-1 (STK-1, gene symbol FLT3), the human homolog of the mouse Flk2/Flt3 gene (Small et al., 1994). This growth factor receptor is expressed in CD34+ human bone marrow (stem/progenitor) cells. We have mapped the gene for STK-1 using PCR screening of a human-rodent somatic cell hybrid panel, and fluorescence in situ molecular hybridization (FISH) of STK-1 genomic probes to mitotic chromosomes of normal human lymphocytes. The results of both analyses show that the gene for STK-1 (FLT3) localizes to chromosome 13q12-->q13.

Animals↗

Cloning and analysis of the genes for polycyclic aromatic hydrocarbon degradation.

Bacterial degradation of polycyclic aromatic hydrocarbons initially proceeds through monooxygenase or dioxygenase attack on the aromatic ring. The dihydroxylated compounds formed are substrates for ring cleavage and further catabolism to tricarboxylic acid cycle intermediates. A number of microbial strains, both gram positive and gram negative, have been isolated that have the metabolic capability to degrade polycyclic aromatic hydrocarbons to carbon dioxide and water. In addition, many of these strains have the ability to cometabolize structurally similar aromatic compounds that may not normally serve as metabolic inducers or as carbon sources. The genes from several of these strains have been cloned for the purpose of analyzing in more detail their structure and function. The cloned genes were used to determine the range of substrates that can be metabolized by the genetically encoded pathway. For instance, the cloned genes from Pseudomonas sp. XPW-2 placed in E. coli encoded for the oxidation of such polycyclic aromatic hydrocarbons as naphthalene, biphenyl, anthracene, phenanthrene, acenaphthylene, fluorene, fluoranthene, chrysene, and pyrene. The cloned genes were also used as genetic probes to determine the degree of homology, if any, there is between different microbial strains capable of degrading polycyclic aromatic hydrocarbons. These experiments indicated significant homology among the class of terrestrial naphthalene and phenanthrene-degrading strains. Nevertheless, little homology was seen across species lines or among strains capable of degrading higher molecular weight polycyclic aromatic hydrocarbons. This indicates that there is a diversity of genetically distinct pathways for polycyclic aromatic hydrocarbon degradation.

Alcohol Oxidoreductases↗

All four known cyclic adducts formed in DNA by the vinyl chloride metabolite chloroacetaldehyde are released by a human DNA glycosylase.

We have previously reported that human cells and tissues contain a 1,N6-ethenoadenine (epsilon A) binding protein, which, through glycosylase activity, releases both 3-methyladenine (m3A) and epsilon A from DNA treated with methylating agents or the vinyl chloride metabolite chloroacetaldehyde, respectively. We now find that both the partially purified human epsilon A-binding protein and cell-free extracts containing the cloned human m3A-DNA glycosylase release all four cyclic etheno adducts--namely epsilon A, 3,N4-ethenocytosine (epsilon C), N2,3-ethenoguanine (N2,3-epsilon G), and 1,N2-ethenoguanine (1,N2-epsilon G). Base release was both time and protein concentration dependent. Both epsilon A and epsilon C were excised at similar rates, while 1,N2-epsilon G and N2,3-epsilon G were released much more slowly under identical conditions. The cleavage of glycosyl bonds of several heterocyclic adducts as well as those of simple methylated adducts by the same human glycosylase appears unusual in enzymology. This raises the question of how such a multiple, divergent activity evolved in humans and what may be its primary substrate.

Acetaldehyde↗

STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells.

We cloned the cDNA for stem cell tyrosine kinase 1 (STK-1), the human homolog of murine Flk-2/Flt-3, from a CD34+ hematopoietic stem cell-enriched library and investigated its expression in subsets of normal human bone marrow. The cDNA encodes a protein of 993 aa with 85% identity and 92% similarity to Flk-2/Flt-3. STK-1 is a member of the type III receptor tyrosine kinase family that includes KIT (steel factor receptor), FMS (colony-stimulating factor 1R), and platelet-derived growth factor receptor. STK-1 expression in human blood and marrow is restricted to CD34+ cells, a population greatly enriched for stem/progenitor cells. Anti-STK-1 antiserum recognizes polypeptides of 160 and 130 kDa in several STK-1-expressing cell lines and in 3T3 cells transfected with a STK-1 expression vector. Antisense oligonucleotides directed against STK-1 sequences inhibited hematopoietic colony formation, most strongly in long-term bone marrow cultures. These data suggest that STK-1 may function as a growth factor receptor on hematopoietic stem and/or progenitor cells.

Amino Acid Sequence↗

Effects of thyroid hormone on the calcium current and isoprenaline-induced background current in rabbit ventricular myocytes.

The majority of previous studies have been performed to explain the effects of thyroid hormone on the heart in chronic hyperthyroidism that was usually induced by eight to 10 daily injections of thyroid hormones. However, it is unclear whether or not the electrophysiological effects result from the chronic manifestations of hyperthyroidism and whether thyroid hormone acts directly or indirectly on cardiac myocytes to alter cardiac electrophysiological properties. In order to examine the acute term electrophysiological effects of thyroid hormone applied in vitro and the mechanisms responsible for some of these effects, we investigated the modulatory effects of thyroid hormone on the calcium current and isoprenaline-induced background current in L-triiodothyronine-treated ventricular myocytes of the rabbit. The major findings were as follows. Over 5 h (range, 5-24 h) after treatment of L-triiodothyronine (1 microM) in vitro, the calcium current was increased significantly. Isoprenaline (1 microM) and cyclic AMP (100 microM) caused an increase in the calcium current in both euthyroid and hyperthyroid myocytes. The hyperthyroid myocytes were more sensitive to the effect of beta-adrenergic stimulation on the calcium current and isoprenaline-activated background current. In euthyroid myocytes, acetylcholine (1 microM) produced no or little changes in the amplitude of the calcium current. In hyperthyroid myocytes, acetylcholine markedly reduced the calcium current, however, acetylcholine was ineffective in the presence of sufficient intracellular cyclic AMP (100 microM). Our results suggest that thyroid hormone can affect the cardiac myocytes directly. Furthermore, our results demonstrate that thyroid hormone affects the calcium current and isoprenaline-activated background current. These electrophysiological changes may explain, at least in part, the occurrence of positive inotropy and cardiac arrhythmias that is associated with hyperthyroidism.

Acetylcholine↗

"Normal" control subjects are hard to find: a model for centralized recruitment.

A central program for recruiting "normal" control subjects is examined by considering the yield of subjects who meet criteria for "healthy" as defined by their personal and family histories of mental disorders. Of the 267 applicants, 30.3% have no lifetime diagnoses, 41.2% are currently healthy with a history of mental illness, and 27.7% are currently mentally ill. Only 16.1% met Research Diagnostic Criteria for "never mentally ill" and reported no family history of mental disorders. Benefits of a central recruitment program for studies of mental disorders include increased information on a large subject pool and decreased volunteer bias.

Adult↗

Increased production of paired helical filament epitopes in a cell culture system reduces the turnover of tau.

To investigate the regulation of posttranslational modifications of tau that might be pertinent to the production of the paired helical filament (PHF) of Alzheimer's disease, we incubated human neuroblastoma cells with the protein phosphatase inhibitor okadaic acid. This treatment results in increased immunoreactivity of tau with the monoclonal antibodies Alz-50, PHF-1, T3P, and NP8, a reduction in Tau-1 immunoreactivity, and an elevation in apparent molecular weight of tau. Moreover, our data demonstrate that accumulation of phosphates in tau leads to a decrease in the turnover rate of tau in the neuroblastoma cells. It is suggested that similar build-up of hyperphosphorylated tau in the neuronal perikarya may represent an early event in PHF formation. The present system facilitates the investigation of regulatory mechanisms governing the occurrence of PHF epitopes, their effects on neuronal cell metabolism, and possible pharmacological intervention.

Alkaline Phosphatase↗

Scintigraphic appearance of albuterol-induced inhibition of hypoxic pulmonary vasoconstriction.

Alveolar hypoxia is known to result in localized pulmonary arterial vasoconstriction. As a consequence, blood is diverted from poorly ventilated alveoli, maintaining ventilation-perfusion (V/Q) matching and thereby reducing the deleterious effects on gas exchange. An incomplete alveolar hypoxic vasoconstrictive response can be easily demonstrated by radionuclide V/Q lung scanning. A case of albuterol-induced inhibition of hypoxic pulmonary vasoconstriction is described in a patient with steroid-dependent asthma. The utility of V/Q lung scanning as a simple, noninvasive test to detect this phenomenon in patients with primary airway disorders who deteriorate despite appropriate therapy is also briefly discussed.

Administration, Inhalation↗

Outcome of extremely low-birth-weight infants: 1980-1990.

Neonatal and follow-up data of infants from the special care nursery whose birth weights were < 750 g, born between 1980 and 1990, were reviewed. There was a 20% relative improvement in the odds of surviving the neonatal period, a 16% improvement in the odds of being discharged and a 19% improvement in the odds of surviving until 2 years of age with each consecutive year. Home oxygen use increased significantly over the study period. The neurodevelopmental outcomes of infants were similar over the 11-year period, with 53% being classified as neurologically normal, with a mean developmental index of 83 at 1 to 2 years of age. We conclude that there has been an improved survival of infants with birth weights < 750 g in our institution, and that the overall incidence of serious neurodevelopmental deficits among survivors has remained stable.

Birth Weight↗

Treatment of organic bipolar mood disorders in Parkinson's disease.

Two patients with long-standing idiopathic Parkinson's disease (PD), without individual or family histories of affective disorders, developed bipolar mood disorders. Both were treated with lithium and clozapine, and one responded favorably. These may be the first reported cases in which mania was treated with clozapine in PD patients.

Bipolar Disorder↗

Antithetical actions of mitoxantrone and doxorubicin on ryanodine-sensitive Ca++ release channels of rat cardiac sarcoplasmic reticulum: evidence for a competitive mechanism.

The anthracenedione mitoxantrone (MTX) is examined for activity toward ryanodine-sensitive Ca++ release channels (i.e., ryanodine receptors; RyR) from rat cardiac SR singly or in combination with doxorubicin (DXR). MTX and DXR exhibit antithetical activities toward RyR. Under conditions promoting channel closure, DXR enhances the binding of [3H]ryanodine (EC50 = 44 microM), whereas MTX has higher affinity (EC50 = 25 microM) but > 10-fold lower activity towards activating RyR. Unlike DXR, MTX assayed under conditions promoting channel activation inhibits the binding of [3H]ryanodine (IC50 = 3.3 microM) and does not alter the potency with which Ca++ activates RyR in the presence or absence of Mg++. In the presence of Mg++, MTX does not alter kobs and slows k-1 for [3H]ryanodine binding, whereas DXR accelerates kobs with little change in k-1. The antithetical behavior of MTX and DXR at the RyR raises the possibility that MTX antagonizes the ability of DXR to activate the RyR when the drugs are present in combination. In consonance with this hypothesis, MTX inhibits DXR (60 microM)-sensitized [3H]ryanodine-binding sites in a dose-dependent manner (IC50 = 8.4 microM) and shifts the EC50 for DXR-activated [3H]ryanodine-binding without reducing the maximum occupancy attained at high DXR concentration, revealing the competitive nature of the interaction of DXR and MTX. MTX singly does not alter active Ca++ accumulation by SR but is shown to fully inhibit DXR-induced Ca++ release. The results suggest that MTX antagonizes DXR-activated RyR by binding to mutually exclusive sites and may provide a rational basis for combination therapy aimed at extending the current dose limits of DXR.

Animals↗

Comparison of the effects of the dopamine D2 agonist quinelorane on tuberoinfundibular dopaminergic neuronal activity in male and female rats.

The purpose of the present study was to examine the effects of quinelorane (LY163502), a potent and selective D2 dopaminergic (DA) receptor agonist, on the activity of tuberoinfundibular DA neurons in male and female rats as estimated by determining the concentration of the primary metabolite of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), in terminals of these neurons in the median eminence (ME). In males, quinelorane produced dose- and time-related increases in the concentration of DOPAC in the Me which was blocked by the D2 receptor antagonist raclopride. The activity of tuberoinfundibular neurons in female rats is higher than it is in males because circulating levels of prolactin tonically stimulate these neurons in the female. In female rats, quinelorane markedly lowered plasma concentrations of prolactin but failed to alter DOPAC concentrations in the ME. Pretreatment of female rats with prolactin antiserum induced hypoprolactinemia and reduced DOPAC concentrations in the ME; in these animals quinelorane increased ME DOPAC concentrations. These results indicate that by acting on D2 receptors quinelorane is able to stimulate tuberoinfundibular DA neurons in both male and female rats, but in female rats the ability of quinelorane to reduce circulating levels of prolactin indirectly reduces the activity of tuberoinfundibular DA neurons and thereby masks the stimulatory action of this drug on these neurons.

3,4-Dihydroxyphenylacetic Acid↗

Gene organization and primary structure of a ribosomal RNA gene cluster from Streptomyces griseus subsp. griseus.

The Streptomyces griseus subsp. griseus KCTC 9080 genome contains six rRNA-encoding gene (rDNA) clusters. One rDNA cluster (rrnE), contained in an 8.7-kb BamHI fragment, was cloned and sequenced. The rDNA were arranged in the order 16S-23S-5S, and separated by small intergenic spacers. No tRNA-encoding sequences were found in the spacer regions. The lengths of the mature 16S, 23S and 5S rRNAs were 1528, 3120 and 120 nucleotides (nt), respectively. The G + C content of the gene cluster was lower than that of the chromosomal DNA. In general, the primary and secondary structures of the three rRNAs showed good agreement with those from other Streptomyces species. However, in comparison with Escherichia coli, two noticeable changes (mismatches and deletions) and two large insertions were identified in the 16S and 23S rRNAs, respectively. On the other hand, regions showing considerable heterogeneity, even within the genus Streptomyces, were found in both rRNAs. Putative primers and processing signals showing high sequence similarity to those from other Streptomyces species were located in the region upstream from the 5' end of the mature 16S rRNA. A potential hairpin loop structure reminiscent of a Rho-independent terminator was located just downstream from the 5S rRNA. A considerable degree of sequence conservation and variation within rDNA gene clusters was revealed in this study, both at the infra- and suprageneric levels.

Base Sequence↗