A case of primary erythromelalgia improved by mexiletine.
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Adult↗
Biomedical subjects
C Oh
Publications and source records attributed to C Oh.
BOTOX delivery by iontophoresis.
We report two patients with severe palmar hyperhidrosis who responded to BOTOX delivered not by injection, the usual method of delivery, but by iontophoresis. The Botulinum molecule has been considered too large for delivery into the skin this way. However, other large peptides, both non-ionic and cationic, have been delivered successfully by this method, so we suspected that BOTOX could in fact be iontophoresed. Our saline-controlled treatment of these two patients with a small iontophoresis unit (Iomed Phoresor II) allowed small volumes of standard BOTOX dilutions to be used, and demonstrates that iontophoresis can indeed deliver BOTOX successfully. This has important therapeutic potential for the large number of patients with focal hyperhidrosis. They may be spared painful injections, and in more severe cases, invasive surgery.
Adult↗
Optimizing volatile fatty acid production in partial acidogenesis of swine wastewater.
This research has been conducted based on the fact that acetic and butyric acids are favorable substrates for methanogens, and that a low level of propionic acid production during acidogenesis minimizes the inhibition effect on methanogenic growth. Raw swine wastewater was pretreated with ammonia stripping to enhance acidogenesis. The ammonia nitrogen concentration of less than 1.2 g/L did not significantly affect the biochemical acidogenic potential of swine wastewater. For acidogenesis of swine wastewater, a set of experiments were carried out to produce short chain volatile fatty acids (VFA) in laboratory-scale continuously stirred tank reactors. The production of acetic, propionic, and butyric acids associated with simultaneous changes in hydraulic retention time (HRT) and temperature was investigated. Response surface methodology was successfully applied to approximate the responses of the VFA productions. The optimum physiological conditions where the maximum acetic and butyric acids production occurred were 2.4 days HRT at 34 degrees C and 2.1 days HRT at 35 degrees C, respectively. The propionic acid production linearly increased as both HRT and temperature increased.
Acetic Acid↗
Characterization, expression pattern and chromosomal localization of the spermatogenesis associated 6 gene (Spata6).
We report the cloning and characterization of the spermatogenesis associated 6 gene (Spata6) encoding a predicted protein of 488 amino acids. It exhibits similarity with the motor domain of kinesin related proteins and with the Caenorhabditis elegans neural calcium sensor protein (NCS-2). The gene encodes three mRNAs of approximately 2.6, approximately 1.8 and approximately 1.2 kb. The expression of the 2.6 kb mRNA is detected at low levels in testis, ovary, thymus and placenta, while the 1.8 and 1.2 kb transcripts are exclusively expressed in testis. The 1.8 and 1.2 kb transcripts are specifically expressed in haploid germ cells. Data from in situ hybridization experiments suggested that mRNA expression of Spata6 in spermatids is higher than in spermatocytes and spermatogonia. RT-PCR analysis and whole mount in situ hybridization demonstrate that the Spata6 transcript is expressed during embryonic development and is localized in neural tube, somites and limb buds of mouse embryo. The Spata6 gene consists of 15 exons ranging in size between 40 and 596 bp. The 2.6 and 1.8 kb transcripts have different 5' untranslated sequences but have the same translational initiation site and therefore may encode the same protein with a predicted molecular weight of 49.7 kDa. The 1.2 kb transcript is derived from a proximal promoter between exons 7 and 8, and contains a translation initiation codon AUG, which is in frame with initiator AUG codon of the 2.6 and 1.8 kb transcripts. Therefore, the 1.2 kb transcript may code for a truncated protein of 32 kDa. Western blot analysis with the antiserum raised against a synthetic peptide from the C-terminal of the deduced Spata6 protein detects only a single protein of 53 kDa in all tissues studied. The Spata6 gene was localized to chromosome 5, region q34-35 in the rat and to chromosome 1, region p32-35 in the human. In an effort to determine the function of Spata6, we inactivated the mouse gene in embryonic stem cells through homologous recombination. Although the heterozygous mutant cells were able to generate low coat colour chimeric mice, all chimeras did not transmit the targeted allele to their progeny suggesting that a high contribution of Spata6(+/-) cells lead to the lethality of the chimeric embryos.
Amino Acid Sequence↗
Defining the quantitative contribution of the melanocortin 1 receptor (MC1R) to variation in pigmentary phenotype.
The melanocortin 1 receptor (MC1R) is a key determinant of pigmentary phenotype. Several sequence variants of the MC1R have been described, many of which are associated with red hair and cutaneous sensitivity to ultraviolet radiation even in the absence of red hair. Red hair approximates to an autosomal recessive trait, and most people with red hair are compound heterozygote or homozygous for limited numbers of mutations that show impaired function in in vitro assays. There is a clear heterozygote effect on sun sensitivity (even in those without red hair) and with susceptibility to the most common forms of skin cancer.
Animals↗
Synthesis and biological properties of C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives as cyclin-dependent kinase inhibitors. Part II.
In this study, C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives were synthesized and their inhibitory effects on cyclin-dependent kinases (CDK2, 4) as well as their cytotoxicities were evaluated. The effects of substituents at the C-2, C-8, and N-9 positions of the substituted purine were investigated. Among the compounds tested, [6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9- isopropylpurine] (4h) was the most active inhibitor of CDK2 with IC50 of 0.3 microM, i.e. a two-fold increased inhibitory activity as compared to roscovitine. Results from structure-activity relationship studies should allow the design of more potent and selective CDK2 inhibitors, which may provide an effective therapy for cancer or other CDK-dependant diseases.
Antineoplastic Agents↗
Ovarian endodermal sinus tumor in a postmenopausal woman.
BACKGROUND: Ovarian endodermal sinus tumor is rare in postmenopausal women. CASE: We report the case of a 75-year-old woman with a pure endodermal sinus tumor of the ovary. CONCLUSION: We believe this to be the oldest patient reported with an ovarian endodermal sinus tumor. The histogenesis of this entity in older patients may be different than when it occurs in young women.
Age Factors↗
Molecular mechanism of activation and superactivation of Ret tyrosine kinases by ultraviolet light irradiation.
The catalytic activities of Ret tyrosine kinases as the products of oncogene RET with multiple endocrine neoplasia type 2A (Ret-MEN2A) or 2B (Ret-MEN2B) mutations and the hybrid gene from c-RET and RFP (Rfp-Ret) were higher than those of c-Ret. We demonstrated that ultraviolet light (UV) irradiation induced activation of c-Ret and superactivation of genetically mutated, and thereby constitutively activated, Ret-MEN2A, Ret-MEN2B, and Rfp-Ret. We found that small proportions of c-Ret and Ret-MEN2B and a large proportion of MEN2A were dimerized due to disulfide bonds and that high kinase activity resided in these fractions. The UV-induced activation of c-Ret and superactivation of Ret-MEN2A and Ret-MEN2B were then shown to be closely associated with promotion of the disulfide bond-mediated dimerization of the Ret proteins. Furthermore, we showed that a large proportion of Rfp-Ret was dimerized or polymerized and that almost all kinase activities resided in the highly polymerized but not dimerized fraction. The UV-induced superactivation of Rfp-Ret was also found to be closely associated with promotion of polymerization but not with dimerization of Rfp-Ret. Further experiments revealed that UV induced intracellular dimerization and activation of the extracellular domain-deleted mutant Ret (Ret-PTC-1). Most importantly, the levels of basal kinase activity and dimerization of Ret-TPC-1-C376A, in which cysteine 376 in the tyrosine kinase domain of Ret-TPC-1 was replaced with alanine, were low and were not increased by UV irradiation. These results suggest that the cysteine at this position works as the primary target of dimerization of Ret proteins inside the cell for both the maintenance of the basal kinase activity and its promotion by UV, possibly in co-operation with the cysteine(s) in the extracellular domain of Ret-MEN2A and Rfp-Ret, which is the target of dimerization and polymerization outside the cell. The potential biological significance of the UV-mediated superactivation of mutant Ret through the newly proposed mechanism in oncogenesis is discussed.
Amino Acid Sequence↗
Long-term clinical results after stent implantation in old obstructed saphenous vein grafts.
STUDY OBJECTIVE: To assess the long-term clinical outcome of treating patients with coronary artery disease and obstructed saphenous vein grafts (SVGs) with stents deployed by oversized balloon catheters. DESIGN: The study included 89 of 92 consecutive patients who had 121 SVG stent implants (average, 1.4 stents per patient). We aimed at achieving a negative stenosis using oversized balloons to achieve a catheter to artery ratio of 1.1:1, and a 100% follow-up at 24+/-14 months (range, 0 to 54 months) was achieved. PATIENTS: As 3 of 92 patients died during hospital admission, the study follow-up population consisted of 89 of 92 patients (mean age, 67+/-10 years). The age of the SVGs was 10+/-4 years. RESULTS: We implanted 118 Palmaz-Schatz and 3 Gianturco-Roubin stents. Procedural success was achieved in 87 of 92 patients (94.5%; < 50% stenosis, and no death, Q-wave acute myocardial infarction, or coronary artery bypass graft [CABG]). Mean SVG stenosis diameter was reduced from 80+/-13% to -11+/-12% (p<0.001) and mean luminal diameter increased from 0.6+/-0.5 mm to 3.3+/-0.8 mm (p<0.001). At follow-up, angina pectoris had developed in 42 of 89 patients (47%), acute myocardial infarction in 12 of 89 patients (14%), reperformed CABG in 12 of 89 patients (14%), cardiac death in 10 of 89 patients (11%), and unrelated death in 6 of 89 patients (7%). Coronary angiography was performed in 37 of 89 patients (42%), with restenosis in 16 of 37 patients (43%) and disease progression at other sites in 11 of 37 patients (30%). Only 25 of 89 patients (28%) experienced event-free survival at follow-up. CONCLUSIONS: Despite high procedural success and excellent angiographic results with oversized balloon catheters, the long-term clinical outcome of SVG stent implantation is suboptimal.
Aged↗
Sonographic demonstration, including color Doppler imaging, of recurrent sperm granuloma.
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Adult↗
Immediate and long-term results comparing coronary versus biliary tubular-slotted stents to treat old obstructed saphenous vein grafts.
Stenting of old obstructed saphenous vein grafts improves immediate angiographic results and long-term clinical outcome compared to standard balloon angioplasty. Comparison of results and long-term clinical outcome between different types of stents in the treatment of vein graft disease is scarce. The authors studied two matched groups of 33 patients each, receiving either coronary or biliary tubular-slotted stents in old vein graft lesions to compare immediate results and long-term clinical outcome. Patients in the two groups were matched for age and left ventricular function. Baseline angiographic characteristics, the minimal luminal diameter (MLD) (0.68 +/- 0.56 mm vs 0.61 +/- 0.51 mm, p = 0.9), and diameter stenosis (DS) (81 +/- 14% vs 82 +/- 15%) were similar between the groups. After stenting, the MLD (3.15 +/- 0.65 mm vs 3.37 +/- 0.63 mm, p = 0.9) and residual stenosis (-7 +/- 19% vs -11 +/- 21%) were also similar. The in-hospital major complications (myocardial infarction and death) (one vs eight, p = 0.01) and the combination of major and minor (bleeding and vascular) complications (eight vs 17, p = 0.02) were higher in the biliary stent group. At long-term follow-up, both groups of patients had high but comparable rates of major cardiovascular events (39% vs 45%, p = 0.62). Kaplan-Meier event-free survival analysis did not show any statistically significant difference in event-free survival (log-rank statistic 0.98). The authors conclude that patients receiving biliary stents had higher rates of immediate minor and major complications, but at long-term follow up, major cardiovascular event rates were comparable between the two groups of patients.
Aged↗
An hrcU-homologous gene mutant of Xanthomonas campestris pv. glycines 8ra that lost pathogenicity on the host plant but was able to elicit the hypersensitive response on nonhosts.
Transposon mutagenesis was used to isolate nonpathogenic mutants of Xanthomonas campestris pv. glycines 8ra, which causes bacterial pustule disease in soybean. A 6.1-kb DNA region in which a mutation gave loss of pathogenicity was isolated and found to carry six open reading frames (ORFs). Four ORFs had homology with hrcU, hrcV, hrcR, and hrcS genes of Ralstonia solanacearum and X. campestris pv. vesicatoria. One nonpathogenic mutant, X. campestris pv. glycines H80, lost pathogenicity on soybean but was able to elicit the hypersensitive response (HR) on nonhost pepper and tomato plants. This mutant still multiplied as well as the wild type in the leaves or cotyledons of soybean. Although the DNA and amino acid sequences showed high homology with known hrp genes, the hrcU-homolog ORF is not required for HR induction on nonhost plants, pepper and tomato, or for the multiplication of bacteria in the host plant. This gene was only required for the pathogenic symptoms of X. campestris pv. glycines 8ra on soybean.
Amino Acid Sequence↗
Induction of T lymphocyte apoptosis by treatment with glycyrrhizin.
The effect of glycyrrhizin (GL), a Chinese herbal drug extracted from licolice roots, on murine lymphocytes for inducing apoptotic cell death was studied. Addition of GL (25-400 micrograms/ml) to cultured splenocytes and thymocytes from BALB/c mice definitely promoted DNA fragmentation. A single injection of GL (100 micrograms/mouse) into BALB/c mice did not cause any detectable DNA fragmentation or cell death of splenocytes and thymocytes. Cytofluorometric analysis of these cells, however, demonstrated a reduction in mitochondrial transmembrane potentials (delta psi m). Repeated injections of GL (100 micrograms/mouse/day) into mice for 7 days actually resulted in induction of low grade DNA fragmentation selectively in splenocytes. Cell population analysis of viable lymphocytes suggested that both CD4+ Th lymphocytes and CD8+ Tc lymphocytes may have been relatively more sensitive than B220+ B lymphocytes for the apoptotic cell death. We concluded from these results that GL acts as a rather selective inducer of mature T lymphocyte apoptosis with a reduction in delta psi m potentially preceding lymphocyte death.
Animals↗
Results of saphenous vein graft stent implantation: single center results from use of oversized balloon catheters.
The results and complications of a single-center experience of stent implantation in old saphenous vein grafts (SVGs) need to be defined. The authors studied their initial consecutive 92 patients (125 stents, 1.4 stents/per patient) with a mean age of 67+/-9 years. The patients' mean saphenous vein graft (SVG) age was 10+/-4 years, and the mean left ventricular ejection fraction was 46%+/-15. Patient population included unstable angina (65%), stable angina (10%), myocardial infarction (21%), and silent ischemia (4%). The authors implanted 122 Palmaz-Schatz/biliary and three Gianturco-Roubin stents. They aimed at a balloon-artery ratio of 1.1/1.0. Procedural success, defined as stent deployment with <50% stenosis without death/Q-wave myocardial infarction/coronary artery bypass grafting (MI/CABG) was 95%. The mean luminal diameter (MLD) increased from 0.6+/-0.5 to 3.3+/-0.8 mm (p<0.001) and mean SVG stenosis diameter was decreased from 80%+/-14 to -10%+/-11 (p<0.001). Angiographic SVG lesions exhibited thrombus (17%), ulceration (38%), and plaque rupture (28%). Sixty-two patients were treated with warfarin and aspirin and 30 with ticlid and aspirin. Complications included death in three patients (3.3%) who sustained subacute stent thrombosis, and two of three had Q-wave MI. Distal embolization occurred in seven patients (8%); six of seven sustained a non Q-wave acute myocardial infarction (AMI); and one of seven a Q-wave MI. Eight (9%) patients had major groin hematoma, two had pseudoaneurysm (2.2%), one had arteriovenous (A-V) fistula (1.1%), two had vascular surgery (2.2%), nine had blood transfusion (9.8%), and three had stent migration (3.3%). Single-center experience with stents in SVGs indicates a highly successful procedural and angiographic immediate result. However, it was complicated by significant risk of non Q-wave MI due to distal coronary embolization which may affect prognosis.
Aged↗
Localization of atrial natriuretic peptide receptors in the rat tongue and hard palate.
Atrial natriuretic peptide (ANP) receptors were characterized in rat oral mucosa using quantitative in vitro autoradiography and activation of particulate guanylyl cyclase (GC) by natriuretic peptides. Competition-binding analysis performed by quantitative in vitro autoradiography demonstrated specific [125I]rANP(1-28) binding sites in the tongue and hard palate. The precise location of this binding was revealed on the basal and parabasal cells of the epithelia by microautoradiography. The dissociation constant (Kd) and maximal binding capacity (Bmax) of these sites were 3.34+/-1.35 nM and 2.71+/-2.21 fmol/mm2 on the epithelium of the tongue, and 4.09+/-1.52 nM and 3.45+/-3.01 fmol/mm2 on the epithelium of the hard palate, respectively. Receptor subtypes were characterized by competition with des [Gln18, Ser19, Gly20, Leu21, Gly22] ANP(4-23) (C-ANP), a specific ligand for the clearance receptor (NPR-C). These binding sites were displaced by C-ANP with inhibition constant (Ki) of 8.96+/-3.18 nM and Bmax of 2.89+/-2.45 fmol/mm2 on the epithelium of the tongue, and Ki of 9.12+/-2.71 nM and Bmax of 3.08+/-2.94 fmol/mm2 on the epithelium of the hard palate, respectively. Production of cyclic GMP by particulate GC in the epithelial membranes of the tongue and hard palate was stimulated by rANP(1-28), porcine brain natriuretic peptide (BNP)(1-26), and C-type natriuretic peptide (CNP)(1-22) in a dose-dependent manner. These results indicate that ANP-binding sites in the epithelium of the tongue and hard palate are mainly clearance receptors (NPR-C) but biological receptors (NPR-A and/or NPR-B) with GC activity are also present, and suggest that ANP may have a role in the proliferation of the oral epithelial cells, especially in the tongue and hard palate.
Analysis of Variance↗
The Effect of Overlap between Monomers on the Determination of Fractal Cluster Morphology
Diffusion limited cluster aggregate (DLCA) morphology is studied as a function of monomeric particle overlap for finite sized clusters. The morphology is parameterized by both the fractal dimension D and the prefactor k0. For clusters created on a three-dimensional cubic lattice we find D = 1.80 ± 0.03 and k0 = 1.30 ± 0.07 when the spherical monomers are in point contact. Both these values increase as overlap increases. Also presented is an analysis of the two-dimensional projection of these clusters in order to facilitate electron micrograph images of real clusters. Quantitative relations between actual three-dimensional cluster parameters such as cluster radius of gyration, fractal dimension and number of monomers per aggregate, and measurable two-dimensional quantities such as longest lengths and projected area are given as a function of monomer overlap. Relationships between lengths can be explained only by use of the proper density correlation function and accounting for cluster anisotropy. Finally, we make an unsuccessful attempt to find the source of recent experimental discrepancies in the prefactor k0 in terms of a possible unknown degree of overlap. Copyright 1997Academic Press
Journal Article↗
Mitochondrial acyl carrier protein is involved in lipoic acid synthesis in Saccharomyces cerevisiae.
The yeast gene, ACP1, encoding the mitochondrial acyl carrier protein, was deleted by gene replacement. The resulting acp1-deficient mutants had only 5-10% of the wild-type lipoic acid content remaining, and exhibited a respiratory-deficient phenotype. Upon meiosis, the lipoate deficiency co-segregated with the acp1 deletion. The role of ACP1 in long-chain fatty acid synthesis was studied in fast and fas2 null mutants completely lacking cytoplasmic fatty acid synthase. When grown on odd-chain (13:0 and 15:0) fatty acids, these cells showed less than 1% of C-16 and C-18 acids in their total lipids. Mitochondrial ACP is therefore suggested to be involved with the biosynthesis of octanoate, a precursor to lipoic acid.
Acyl Carrier Protein↗
Successful treatment of steroid-resistant chorea associated with lupus by use of valproic acid and clonidine-HCL patch.
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Administration, Oral↗