A SINE element in the canine D2 dopamine receptor gene and its chromosomal location.
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Animals↗
Biomedical subjects
H Lee
Publications and source records attributed to H Lee.
Opposing functional effects of cyclic GMP and cyclic AMP may act through protein phosphorylation in rabbit cardiac myocytes.
1. We tested the hypothesis that the negative functional effects of cyclic GMP (cGMP) oppose the positive effects of cyclic AMP (cAMP) in cardiac myocytes through interaction at the level of their respective protein kinases. 2. Cell shortening was studied using a video-edge detector. The O2 consumption of a suspension of rabbit ventricular myocytes was measured using O2 electrodes. Protein phosphorylation was measured autoradiographically following SDS-PAGE. Data were collected with: (1) 8-bromo-cGMP (8-Br-cGMP) 10(-7) or 10(-5) M; (2) 8-bromo-cAMP (8-Br-cAMP) 10(-7) or 10(-5) M; (3) 8-Br-cAMP 10(-5) M followed by 8-Br-cGMP 10(-7) or 10(-5) M; (4) 8-Br-cGMP 10(-5) M followed by 8-Br-cAMP 10(-7) or 10(-5) M; (5) 8-Br-cGMP 10(-7) or 10(-5) M followed by KT 5720 (cAMP-dependent protein kinase inhibitor) or KT 5823 (cGMP-dependent protein kinase inhibitor) 10(-6) M; and (6) 8-Br-cAMP 10(-7) or 10(-5) M followed by KT 5720 or KT 5823 10(-6) M. 3. 8-Br-cGMP 10(-5) M decreased percent shortening (Pcs) from 6.3+/-0.6 to 3.6+/-0.4% and rate of shortening (Rs) from 66.7+/-4.4 to 41.8+/-4.2 microm s(-1). 8-Br-cAMP 10(-5) M increased Pcs (from 3.7+/-0.2 to 4.8+/-0.2) and Rs (from 50.0+/-3.0 to 60.0+/-3.1). With 8-Br-cAMP 10(-5) M, 8-Br-cGMP 10(-5) M decreased Pcs and Rs less. The positive functional effects of 8-Br-cAMP 10(-7) or 10(-5) M were also diminished with 8-Br-cGMP 10(-5) M. Following 8-Br-cGMP 10(-7) or 10(-5) M, KT 5720 10(-6) M further decreased Pcs to 2.5+/-0.3 and Rs to 30.0+/-4.1. KT 5823 10(-6) M returned Pcs to 4.7+/-0.4 and Rs to 61.3+/-5.3. Following 8-Br-cAMP 10(-7) or 10(-5) M, KT 5720 decreased the elevated Pcs and Rs significantly and KT 5823 10(-6) M further increased these parameters. 4. cGMP and cAMP phosphorylated the same five protein bands. With KT 5720 or KT 5823, all of the bands were lighter at the same concentration of 8-Br-cAMP and 8-Br-cGMP. 5. We conclude that, in rabbit ventricular myocytes, the opposing functional effects of cGMP and cAMP are related to the interaction at the level of their respective protein kinases.
Animals↗
Fungal cell wall phosphomannans facilitate the toxic activity of a plant PR-5 protein.
Osmotin is a plant PR-5 protein. It has a broad spectrum of antifungal activity, yet also exhibits specificity for certain fungal targets. The structural bases for this specificity remain unknown. We show here that full sensitivity of Saccharomyces cerevisiae cells to the PR-5 protein osmotin is dependent on the function of MNN2, MNN4 and MNN6. MNN2 is an alpha-1, 2-mannosyltransferase catalyzing the addition of the first mannose to the branches on the poly l,6-mannose backbone of the outer chain of cell wall N-linked mannans. MNN4 and MNN6 are required for the transfer of mannosylphosphate to cell wall mannans. Null mnn2, mnn4 or mnn6 mutants lack phosphomannans and are defective in binding osmotin to the fungal cell wall. Both antimannoprotein antibody and the cationic dye alcian blue protect cells against osmotin cytotoxicity. MNN1 is an alpha-1,3-mannosyltransferase that adds the terminal mannose to the outer chain branches of N-linked mannan, masking mannosylphosphate. Null mnn1 cells exhibit enhanced osmotin binding and sensitivity. Several cell wall mannoproteins can bind to immobilized osmotin, suggesting that their polysaccharide constituent determines osmotin binding. Our results demonstrating a causal relationship between cell surface phosphomannan and the susceptibility of a yeast strain to osmotin suggest that cell surface polysaccharides of invading pathogens control target specificity of plant PR-5 proteins.
Carbohydrate Conformation↗
Sleep disturbance and nonmalignant chronic pain: a comprehensive review of the literature.
Sleep disturbance is an important clinical complaint for individuals with nonmalignant pain conditions. This review is a broad introduction to the literature on sleep disturbance and chronic pain conditions. The article critically reviews studies of sleep disturbance in musculoskeletal pain, arthritis, headache, and fibromyalgia. Current neurobiological hypotheses regarding the pathogenesis of sleep disturbance and chronic pain, common comorbid disorders, and pharmacologic and non-pharmacologic treatments for sleep disturbance are reviewed.
Journal Article↗
Prehospital delay with myocardial infarction: the interactive effect of clinical symptoms and race.
This study examined prehospital delays and clinical symptoms of myocardial infarction (MI) in blacks and whites and the relationship between longer delays and types of clinical symptoms. The convenience sample included 128 patients, admitted consecutively, with acute MI. Data on types of clinical symptoms of MI and treatment-seeking behavior were collected on day 2 or 3 after admission, using face-to-face semistructured interviews. The total mean delay time differed significantly between blacks and whites (16 hours vs. 8.8 hours, p < .05). Although the frequency of chest pain was similar in both blacks and whites (78% vs. 77%), more than twice as many blacks as whites presented with symptoms of dyspnea (56% vs. 24%, p < .01) and fatigue (32% vs. 17%, p < .05). There was an interactive effect of race-ethnicity and types of symptoms on delay (p < .05) was present. Delay times for whites with chest pain were shorter than for whites without chest pain. Delay times for blacks with dyspnea were significantly shorter than for blacks without dyspnea, although delay times did not differ between whites with and without dyspnea.
Black or African American↗
Altered electrophysiological responses to mechanical stimulation and abnormal signalling through alpha5beta1 integrin in chondrocytes from osteoarthritic cartilage.
OBJECTIVE: To establish whether chondrocytes from normal and osteoarthritic human articular cartilage recognize and respond to pressure induced mechanical strain in a similar manner. DESIGN: Chondrocytes, extracted from macroscopically normal and osteoarthritic human articular cartilage obtained from knee joints at autopsy, were grown in monolayer culture and subjected to cyclical pressure-induced strain (PIS) in the absence or presence of anti-integrin antibodies, agents known to block ion channels and inhibitors of key molecules involved in the integrin-associated signalling pathways. The response of the cells to mechanical stimulation was assessed by measuring changes in membrane potential. RESULTS: Unlike chondrocytes from normal articular cartilage, which showed a membrane hyperpolarization response to PIS, chondrocytes from osteoarthritic cartilage responded by membrane depolarization. The mechanotransduction pathway involves alpha5beta1 integrins, stretch-activated ion channels, tyrosine kinases and phospholipase C but the actin cytoskeleton and protein kinase C, which are important in the membrane hyperpolarization response in normal chondrocytes, are not necessary for membrane depolarization in osteoarthritic chondrocytes in response to PIS. CONCLUSION: Chondrocytes derived from osteoarthritic cartilage show a different signalling pathway via alpha5beta1 integrin in response to mechanical stimulation which may be of importance in the production of phenotypic changes recognized to be present in diseased cartilage.
Aged↗
Arthroscopic reduction of a high condylar process fracture: a case report.
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Adolescent↗
Association of CYP1A1 and microsomal epoxide hydrolase polymorphisms with lung squamous cell carcinoma.
Lung cancer is the leading cause of death among cancers in Taiwan. Although the etiology of lung cancer has yet to be defined, genetic variability in activities of metabolic enzymes has been correlated with lung cancer. In the present study, the possibility of association of CYP1A1 and microsomal epoxide hydrolase (HYL1) genetic polymorphisms with lung cancer was examined among 132 lung cancer patients and 259 controls in Taiwan. No significant association was observed for either CYP1A1 or HYL1 polymorphism alone and the overall incidence of lung cancer after adjusting for age, gender and smoking status. When cases were stratified according to histological type, there was significant association between CYP1A1*2A homozygote and squamous cell carcinoma (SCC) (odds ratio (OR) 2.86; 95% confidence interval (CI) 1.33-6.12). Similarly, the proportion of HYL1 genotypes corresponding to high or normal enzyme activities was higher in SCC than in controls (OR 1.96; 95% CI 1.04-3.70). A combination of susceptible CYP1A1 and HYL1 genotypes was found to be highly associated with lung cancer, especially with SCC (OR 6.76; 95% CI 2.29-19.10). Our results suggest that the combination of CYP1A1 and HYL1 polymorphisms is an important risk factor for lung SCC.
Base Sequence↗
Discoplasty with autogenous superficial musculoaponeurotic system (SMAS) flap in reconstruction of the temporomandibular joint combined with cervicofacial rhytidectomy.
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Facial Muscles↗
Submandibular gland mucocele: diagnosis and management.
Mucoceles originating from the submandibular gland are extremely rare. A review of the English literature resulted in identification of only 5 such cases. We have diagnosed and treated 2 submandibular mucoceles. Both lesions were removed in continuity with the submandibular and sublingual glands. No complications and no recurrences have occurred to date. The diagnosis of these lesions is complicated because of the lack of specific clinical diagnostic criteria and the similarity between submandibular mucoceles and plunging or cervical ranulas. Computerized tomography and specifically the presence of a so-called "tail" sign is pathognomonic for plunging ranula. This sign is absent in mucoceles originating in the submandibular glands. The treatment strategies vary as well. A diagnostic algorithm and a surgical rationale for treatment of submandibular mucoceles are presented.
Adolescent↗
College binge drinking in the 1990s: a continuing problem. Results of the Harvard School of Public Health 1999 College Alcohol Study.
In 1999, the Harvard School of Public Health College Alcohol Study resurveyed colleges that participated in the 1993 and 1997 surveys. Responses to mail questionnaires from more than 14,000 students at 119 nationally representative 4-year colleges in 39 states were compared with responses received in 1997 and 1993. Two of 5 students (44%) were binge drinkers in 1999, the same rate as in 1993. However, both abstention and frequent binge-drinking rates increased significantly. In 1999, 19% were abstainers, and 23% were frequent binge drinkers. As before, binge drinkers, and particularly frequent binge drinkers, were more likely than other students to experience alcohol-related problems. At colleges with high binge-drinking rates, students who did not binge drink continued to be at higher risk of encountering the second-hand effects of others' heavy drinking. The continuing high level of binge drinking is discussed in the context of the heightened attention and increased actions at colleges. Although it may take more time for interventions to take effect, the actions college health providers have undertaken thus far may not be a sufficient response.
Adult↗
Enhancing initial release of peptide from poly(d,l-lactide-co-glycolide) (PLGA) microspheres by addition of a porosigen and increasing drug load.
The objective of this study was to evaluate formulation variables such as drug load and addition of a porosigen in achieving an increased initial release of peptide from poly(d,l-lactide-co-glycolide) (PLGA) microspheres by altering carrier characteristics. Leuprolide acetate-loaded PLGA microspheres were prepared by a solvent-extraction-evaporation process and were characterized for their drug load (HPLC assay), bulk density (tapping method), size distribution (dynamic light scattering), specific surface area (Brunauer-Emmett-Teller [BET] analysis), surface morphology (scanning electron microscopy), in vitro drug release (at 37 degrees C), and in vivo efficacy (suppression of rat serum testosterone). Increasing the drug load, and adding various amounts of calcium chloride to organic and aqueous phases of the emulsion during processing yielded particles with increased porosity, lower bulk density, higher specific surface area, and accordingly higher initial release. In an animal model, these formulations showed a faster onset of testosterone suppression compared to microspheres without higher drug load or calcium chloride. The approaches employed in this study were found to be effective in avoiding the therapeutic lag phase usually observed with microencapsulated macromolecular drugs.
Animals↗
Genomic structure and promoter analysis of the mouse EphA8 receptor tyrosine kinase gene.
The gene encoding the mouse EphA8 receptor tyrosine kinase has been isolated from a mouse genomic library, and its complete genomic structure has been determined. This gene spans approximately 28 kb and consists of 17 exons. This gene structure is similar to the structure of the chick EphB2 (Cek5) gene, except for one intron present between the first two exons encoding the EphA8 kinase domain. This difference may reflect an evolutionary divergence of the catalytic domain between EphA and EphB subgroup receptors. The site for transcription initiation has been mapped to the 19th nucleotide upstream from the translation start codon ATG. A feature of this gene is an unmethylated CpG island spanning exon 1 and the flanking sequence. The putative promoter of the EphA8 gene lacks a TATA box and contains multiple copies of the sequence GGGCGG, the core sequence of the putative Sp1-binding site. The 3.5-kb upstream genomic region containing part of the first exon showed strong promoter activity in NG108-15 neuroblastoma cells but much less in 293T cells, suggesting that this fragment is sufficient for neural cell-directed promoter activity. By deleting the genomic region containing the five GC boxes, it was shown that the minimal promoter region is primarily comprised of five copies of the Sp1-binding site located upstream from the transcription initiation site. Finally, in situ RNA hybridization studies revealed a very specific pattern of EphA8 gene expression restricted to the rostral region of midbrain tectum during embryonic development. Isolation of a functional promoter for the EphA8 gene is a first step in understanding how expression of this gene is controlled at the molecular level.
Amino Acid Sequence↗
Modulation of estrogen production and 17beta-hydroxysteroid dehydrogenase-type 1, cytochrome P450 aromatase, c-met, and protein kinase Balpha messenger ribonucleic acid content in rat ovarian granulosa cells by hepatocyte growth factor and follicle-stimulating hormone.
Hepatocyte growth factor (HGF) suppresses FSH-dependent estradiol-17beta (E(2)) production in ovarian granulosa cells (GC). The mechanisms of action for HGF in GC are unknown; however, activation of the HGF receptor, c-Met, can induce c-Akt/protein kinase B (PKB)-mediated signal transduction in nonovarian cells. Using immature rat GC, the present study investigated the effects of HGF within the estrogen biosynthetic pathway, concomitant with changes in c-Met and PKBalpha mRNA expression. Granulosa cells were incubated with androstenedione and FSH, HGF, and/or dibutyryl-cAMP (Bu(2)-cAMP). Follicle-stimulating hormone and Bu(2)-cAMP each stimulated estrone (E(1)) and E(2) synthesis at 48 h. Hepatocyte growth factor suppressed FSH-dependent E(2), but not E(1), synthesis. Semiquantitative reverse transcription-polymerase chain reaction showed that HGF impaired FSH-supported 17beta-hydroxysteroid dehydrogenase type-1 (17beta-HSD) and cytochrome P450 aromatase (P450arom) mRNA levels. Hepatocyte growth factor did not reduce E(2) synthesis or 17beta-HSD and P450arom mRNA expression in the presence of Bu(2)-cAMP at 48 h. The FSH and HGF each down-modulated c-Met mRNA accumulation, whereas Bu(2)-cAMP increased c-Met mRNA content. Between 0 and 48 h a biphasic change in PKBalpha mRNA content occurred with either FSH or HGF; however, PKBalpha mRNA accumulation was augmented by HGF. Collectively, results suggest that HGF can suppress E(2) production in GC by disrupting cAMP-dependent 17beta-HSD and P450arom. Changes in c-Met and PKBalpha mRNA content provide a potential link between HGF signaling and the FSH-dependent mechanisms that control the steroidogenic differentiation of GC.
17-Hydroxysteroid Dehydrogenases↗
Recombinant kringle 1-3 of plasminogen inhibits rabbit corneal angiogenesis induced by angiogenin.
PURPOSE: Angiostatin is a potent angiogenesis inhibitor that has been identified as a cryptic fragment of plasminogen molecule containing the first four kringle domain. Angiogenin, a 14-kDa monomeric protein, a potent blood vessel inducer, is expressed in tumors and present in mammalian plasma. The purpose of this study was to determine whether recombinant kringle 1-3 (rKI-3) of human plasminogen could interfere with angiogenesis induced by angiogenin and to evaluate the role of angiogenin in corneal angiogenesis in rabbit. METHODS: A Hydron polymer pellet containing 2.0 microg of angiogenin was implanted intrastromally into the superior cornea of each of 44 rabbit eyes. All eyes received an intrastromal pellet and were randomized into either one group treated with 12.5 microg of rKI-3 (n = 25) or the other group treated with phosphate-buffered saline (PBS; n = 19). Both pellets were positioned in parallel at the site 1.2 mm from the superior limbus. Two masked observers kept the angiogenesis score daily, based on the number and the length of new vessels. The corneas with induced angiogenesis also were examined histologically. RESULTS: On the third day of the angiogenin pellets implantation, the eye treated with rKI-3 had less angiogenesis (mean score, 4.2 +/- 6.6) than eye treated with PBS (mean score, 16.1 +/- 17.1; p < 0.05, Mann-Whitney U test). The cornea treated with PBS also showed much more leukocyte adhesion than the cornea treated with rKI-3. CONCLUSION: Recombinant kringle 1-3 appears to inhibit angiogenin-induced angiogenesis in a rabbit corneal pocket assay. Recombinant kringle 1-3 may have therapeutic potential as an antiangiogenic agent.
Angiogenesis Inducing Agents↗
Combined antitumor effects of an adenoviral cytosine deaminase/thymidine kinase fusion gene in rat C6 glioma.
OBJECTIVE: In this study, we investigated the feasibility of a double-suicide gene/prodrug therapy, involving direct introduction of the herpes simplex virus Type 1 thymidine kinase (TK) gene and the Escherichia coli cytosine deaminase (CD) gene, via a recombinant adenoviral vector, and ganciclovir (GCV) and/or 5-fluorocytosine (5-FC) treatment, in a rat C6 glioma model. METHODS: Efficient gene transfer and transduction of C6 glioma cells via a recombinant adenovirus were evaluated by infecting cells with adenovirus bearing the beta-galactosidase gene and then staining cells with X-5-bromo-4-chloro-3-indolyl-13-D-galactoside. CD/TK expression in cells infected with adenovirus bearing the CD/TK gene (ad-CD/TK) was examined by immunoblotting analysis. For in vitro cytotoxicity experiments, the cells were infected with ad-CD/TK or ad-deltaE1 (as a control). After the addition of a variety of concentrations of GCV and 5-FC, either separately or in combination, cell viability was determined by staining the cells with crystal violet solution 6 days after infection. For in vivo antitumor experiments, 1x10(5) cells were stereotactically injected into the right caudate-putamen of female Wistar rat brains. At 3 days after implantation, 1x10(8) plaque-forming units of ad-CD/TK or ad-deltaE1 (as a control) were stereotactically injected into the tumors and GCV (25 mg/kg) and 5-FC (250 mg/kg), alone or in combination, were intraperitoneally administered. Animals were then killed, and tumor volumes were measured by determining the tumor area in every fifth section, using a light microscope. RESULTS: C6 glioma cells were efficiently transduced with recombinant adenoviral vector at multiplicities of infection of 200 or more. In vitro cytotoxicity of GCV and/or 5-FC, either alone or in combination, was exclusively observed in the cells transduced with ad-CD/TK. Obvious cytotoxicity (>50% inhibition) was observed in the presence of 5-FC at concentrations greater than 30 microg/ml or GCV at concentrations greater than 0.3 microg/ml at a multiplicity of infection of 100. Additionally, cytotoxicity in the presence of both GCV and 5-FC was greater than that after single-prodrug treatments, indicating additive effects of the prodrug treatments. In in vivo experiments, the tumor volumes of the rats treated with GCV or 5-FC alone after ad-CD/TK injection (59.1+/-4.6 and 57.4+/-7.1 mm3, respectively) were significantly smaller than that of the control rats (157+/-8.9 mm3, P<0.05). Furthermore, the tumor volume of the rats treated with GCV and 5-FC in combination was 14.7+/-1.8 mm3. CONCLUSION: These results demonstrated the efficient transduction of C6 glioma cells with a recombinant adenovirus and the additive effects of CD/TK fusion gene/GCV/5-FC treatment, compared with single-gene therapy with the TK or CD gene. Therefore, our data suggest that the direct administration of a double-suicide gene/prodrug therapy has great potential in the treatment of brain tumors.
Adenoviridae↗
High-resolution transcript map of the region spanning D12S1629 and D12S312 at chromosome 12q13: triple A syndrome-linked region.
For those searching for human disease-causing genes, information on the position of genes with respect to genetic markers is essential. The physical map composed of ESTs and genetic markers provides the positional information of these markers as well as the starting point of gene identification in the form of genomic clones containing exons. To facilitate the effort of identification of genes in the region spanning D12S1629 and D12S312, we constructed a high-resolution transcript map with PAC/BAC/cosmid clones. The strategy for the construction of such a map involved utilization of STSs for the screening of the large insert bacterial chromosome libraries and a chromosome 12-specific cosmid library by hybridization. The contig was constructed based on the STS contents of the clones. The resulting high-resolution transcript map of the region between P273P14/SP6 and D12S312 spans 4.4 cM from 66.8 to 71.2 cM of the Généthon genetic map and represents approximately 2.4 Mb. It was composed of 81 BAC, 45 PAC, and 91 cosmid clones with a minimal tiling path consisting of 16 BAC and 4 PAC clones. These clones are being used to sequence this part of chromosome 12. We determined the order of 135 STSs including 74 genes and ESTs in the map. Among these, 115 STSs were unambiguously ordered, resulting in one ordered marker per 21 kb. The order of keratin type II locus genes was determined. This map would greatly enhance the positional cloning effort of the responsible genes for those diseases that are linked to this region, including male germ cell tumor as well as palmoplantar keratoderma, Bothnian-type, and triple A syndrome. This transcript map was localized at human chromosome 12q13.
Addison Disease↗
Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.
Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.
Acetates↗