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Biomedical subjects

D Li

Publications and source records attributed to D Li.

At least 289 records · Page 16Linked to original sources
PubMed2000

Mixed chimera converted into full donor chimera with powerful graft-versus-leukemia effects but no graft-versus-host disease after non T cell-depleted HLA-mismatched peripheral blood stem cell transplantation.

Instead of donor T cell depletion, we used CTLA4 and TJU103 (a small organic compound believed to block CD4 binding to MHC II molecule of APC) to block donor T lymphocyte activation in vitro before infusion, and mycophenolate mofetil to control the activity of lymphocytes of the recipient. We successfully treated a patient with an HLA-mismatched graft without donor T cell depletion. Mixed chimerism was observed 30 days and 60 days after transplantation. STR-PCR showed that 28% and 62% of blood mononuclear cells (MNC) were donor derived at day +30 and day +60, respectively. Mixed chimerism converted into full donor chimerism, when 99.7% of the MNC in the recipient were donor derived after three courses of DLI. A powerful GVL effect related to mixed chimerism was observed. No acute GVHD occurred, only grade II chronic GVHD occurred 6 months after transplant. Based on this case, we suggest that: (1) stable mixed chimerism can be intentionally established across HLA barriers without donor T cell depletion; (2) mixed chimerism can be converted into full donor chimerism by DLI; (3) mixed chimerism induced with this approach can be associated with a very powerful GVL effect, and these may be enhanced by DLI, without severe GVHD.

Adult↗
PubMed2000

Conversion of compatible plant-pathogen interactions into incompatible interactions by expression of the Pseudomonas syringae pv. syringae 61 hrmA gene in transgenic tobacco plants.

The hrmA gene from Pseudomonas syringae pv. syringae has previously been shown to confer avirulence on the virulent bacterium P. syringae pv. tabaci in all examined tobacco cultivars. We expressed this gene in tobacco plants under the control of the tobacco Delta0. 3 TobRB7 promoter, which is induced upon nematode infection in tobacco roots (Opperman et al. 1994, Science, 263, 221-223). A basal level of hrmA expression in leaves of transgenic plants activated the expression of pathogenesis-related genes, and the transgenic plants exhibited high levels of resistance to multiple pathogens: tobacco vein mottling virus, tobacco etch virus, black shank fungus Phytophthora parasitica, and wild fire bacterium Pseudomonas syringae pv. tabaci. However, the hrmA transgenic plants were not significantly more resistant to root-knot nematodes. Our results suggest a potential use of controlled low-level expression of bacterial avr genes, such as hrmA, in plants to generate broad-spectrum resistance to bacterial, fungal and viral pathogens.

Animals↗
PubMed2000

Detection of Listeria monocytogenes by polymerase chain reaction in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls.

BACKGROUND AND AIMS: Components of the intestinal microflora are believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD) in genetically susceptible hosts acting either as a non-specific antigenic stimulus or as a specific pathogen. Listeria monocytogenes has been suggested as an organism with the potential to cause IBD. The objective of the present study was to investigate the prevalence of L. monocytogenes DNA in intestinal biopsies from patients with IBD and from non-IBD controls by using nested polymerase chain reaction (PCR). METHODS: The DNA was extracted from 274 colonoscopic biopsies, which were obtained from 23 patients with Crohn's disease (CD), 28 with ulcerative colitis (UC) and 39 non-IBD control patients. Nested PCR amplification was used to detect the presence of the L. monocytogenes listeriolysin O (hly) gene. The sequences of positive PCR products were determined and compared with databases. RESULTS: The sensitivity of our nested PCR was 10 fg L. monocytogenes DNA. Overall, L. monocytogenes DNA was detected in 13.0% patients with CD, 17.9% patients with UC and 25.6% non-IBD control patients or in 29 of 274 (10.6%) endoscopic biopsies. Among them, L. monocytogenes DNA was detected in four of 67 (6%) biopsies from patients with CD, five of 94 (5.3%) biopsies from patients with UC and 20 of 113 biopsies (17.7%) from non-IBD control patients. Sequence analysis of positive PCR products demonstrated more than 95% similarity to the hly gene sequence of L. monocytogenes, confirming the authenticity of our PCR products. CONCLUSION: Listeria monocytogenes DNA was detected in the intestine of both patients with IBD and in non-IBD control patients, probably reflecting the widespread presence of this organism in the environment. The low yield of positive biopsies in our IBD patients (5-6%) and the fact that the detection rate of L. monocytogenes DNA was similar in endoscopic biopsies from IBD patients and non-IBD controls does not support a direct role for L. monocytogenes in the pathogenesis of IBD, at least in New Zealand patients.

Adolescent↗
PubMed2000

Inhibition of arterial thrombogenesis by quinapril but not losartan.

The cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors and angiotensin type I (AT1) receptor blockers may relate to their antithrombotic effect. We determined the differential effects of the ACE inhibitor quinapril and the AT1 receptor blocker losartan on arterial thrombus formation in the rat. Sprague-Dawley rats were fed regular chow or chow mixed with low-dose quinapril (0. 6 mg/kg/day), high-dose quinapril (1.2 mg/kg/day), or losartan (10 mg/kg/day) for 15 days. Abdominal aorta was exposed and wrapped with Whatman paper impregnated with 29% FeCl(3) (ferric chloride). Time to occlusive thrombus formation and weight of the thrombus were recorded. Aortic superoxide anion generation, platelet aggregation, plasma angiotensin II levels, and morphology of the thrombus were also examined. Both losartan and quinapril caused similar reductions in arterial pressure. Losartan did not affect the time to thrombus formation, whereas quinapril (both low and high doses) delayed the time to thrombus formation (P<.01 vs control). Weight of the thrombus was similar in all groups of rats. Platelet aggregation was inhibited by approximately 50 in both quinapril- and losartan-treated rats. The high-dose quinapril-treated rats showed markedly reduced vascular superoxide anion generation compared with the control rats (P<.05). Plasma angiotensin II levels were unaffected by quinapril treatment but were elevated 7-fold in losartan-treated rats (P <.001 vs. control rats). The thrombi in the control rats consisted of platelet aggregates, fibrin, and red blood cells. The intravascular platelet aggregates were much smaller in the quinapril-treated rats (P<.05 vs. control), but were similar in control and losartan-treated rats. In conclusion, quinapril but not losartan prolongs time to arterial thrombus formation and results in smaller platelet aggregates in the thrombus. Both quinapril and losartan decrease platelet aggregation, but only quinapril decreases superoxide anion generation. This effect on superoxide anion generation as well as mechanisms other than AT1 receptor blockade may underlie the salutary effect of quinapril on arterial thrombogenesis.

Angiotensin II↗
PubMed2000

Isolation and identification of the group B streptococcal toxin CM101 from infants with sepsis.

OBJECTIVE: To determine whether the group B streptococcal (GBS) polysaccharide exotoxin CM101, which induces a complement-activated cytokine-driven inflammatory response, is present in body fluids of infants with GBS disease. STUDY DESIGN: With a sandwich enzyme-linked immunosorbent assay, CM101 was measured in plasma, urine, and cerebrospinal fluid from newborn infants who were evaluated for possible infection and from older infants with culture-confirmed GBS disease. RESULTS: Urine from 11 newborn infants with culture-confirmed early-onset disease contained large amounts of CM101 (1.0 to 5.5 mg/48 h). Plasma concentrations were 62.6 +/- 10.5 microg/mL in these infants and were 69.0 +/- 21.2 microg/mL in 4 older infants with late-onset disease. Plasma CM101 concentrations did not correlate with indexes of illness severity, leukocyte counts, or interleukin-6 or interleukin-8 plasma concentrations. CM101 was present in cerebrospinal fluid of 5 infants with meningitis (8.4 +/- 1.6 microg/mL). CM101 was not found in control samples. CM101 isolated from urine had molecular weight and sugar composition similar to those obtained from GBS culture media, and they both elicited a comparable pathophysiologic response when infused intravenously in lambs. CONCLUSIONS: CM101 is present in infants with GBS disease, and it appears to be the same as CM101 obtained from GBS culture media.

Animals↗
PubMed2000

The locus of a novel gene responsible for arrhythmogenic right-ventricular dysplasia characterized by early onset and high penetrance maps to chromosome 10p12-p14.

Arrhythmogenic right-ventricular dysplasia (ARVD), a cardiomyopathy inherited as an autosomal-dominant disease, is characterized by fibro-fatty infiltration of the right-ventricular myocardium. Four loci for ARVD have been mapped in the Italian population, and recently the first locus was mapped in inhabitants of North America. None of the genes have been identified. We have now identified another North American family with early onset of ARVD and high penetrance. All of the children with the disease haplotype had pathological or clinical evidence of the disease at age <10 years. The family spans five generations, having 10 living and 2 dead affected individuals, with ARVD segregating as an autosomal-dominant disorder. Genetic linkage analysis excluded known loci, and a novel locus was identified on chromosome 10p12-p14. A peak two-point LOD score of 3.92 was obtained with marker D10S1664, at a recombination fraction of 0. Additional genotyping and haplotype analysis identified a shared region of 10.6 cM between marker D10S547 and D10S1653. Thus, a novel gene responsible for ARVD resides on the short arm of chromosome 10. This disease is intriguing, since it initiates exclusively in the right ventricle and exhibits pathological features of apoptosis. Chromosomal localization of the ARVD gene is the first step in identification of the genetic defect and the unraveling of the molecular basis responsible for the pathogenesis of the disease.

Adult↗
PubMed2000

Propofol stimulates ciliary motility via the nitric oxide-cyclic GMP pathway in cultured rat tracheal epithelial cells.

BACKGROUND: Airway ciliary motility is impaired by inhaled anesthetics. Recent reports show that nitric oxide (NO) induces upregulation in ciliary beat frequency (CBF), and others report that propofol, an intravenous anesthetic, stimulates NO release; this raises the possibility that propofol increases CBF by stimulating the NO-cyclic guanosine monophosphate (cGMP) signal pathway. In this study, the authors investigated the effects of propofol on CBF and its relation with the NO-cGMP pathway using the pharmacologic blockers NG-monomethyl-l-arginine (l-NMMA), an NO synthase inhibitor; 1H-[1,2,4]oxidazole[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor; and KT5823, a cGMP-dependent protein kinase inhibitor, in cultured rat tracheal epithelial cells. METHODS: Rat tracheal tissues were explanted and cultured for 3-5 days. Images of ciliated cells were videotaped using a phase-contrast microscope. Baseline CBF and CBF 25 min after exposure to propofol or blocker were measured using video analysis. RESULTS: Vehicle (0.1% dimethyl sulfoxide; n = 11) increased CBF by 0.2 +/- 1.7% (mean +/- SD) from baseline. Propofol stimulated CBF significantly (P < 0.01) and dose dependently (1 microM, 2.0 +/- 1. 9%, n = 6; 10 microM, 8.2 +/- 6.7%, n = 9; 100 microM, 14.0 +/- 4.7%, n = 10). Intralipid (0.05%), the clinical vehicle of propofol, did not affect CBF (-0.2 +/- 2.2%; n = 5). The enhancement of CBF with use of 100 microm propofol was abolished (P < 0.01) by coadministration of 10 mmicroM l-NMMA (2.4 +/- 3.6%; n = 5), 100 microM ODQ (-0.3 +/- 2.2%; n = 6) or 30 microM KT5823 (-0.1 +/- 4. 1%; n = 8). l-NMMA, ODQ, or KT5823 alone did not change CBF. CONCLUSIONS: These results show that propofol stimulates CBF viathe NO-cGMP pathway in rat tracheal epithelial cells, suggesting a possible advantage of propofol in decreasing respiratory risk.

Anesthetics, Intravenous↗
PubMed2000

Effects of alpha-tocopherol on ox-LDL-mediated degradation of IkappaB and apoptosis in cultured human coronary artery endothelial cells.

Experimental studies have demonstrated that vitamin E (alpha-tocopherol) may provide significant cytoprotection during cell injury. In this study, we examined the effects of alpha-tocopherol on oxidized low-density lipoprotein (ox-LDL)-induced apoptosis in human coronary artery endothelial cells (HCAECs). In addition, we examined the activation of NF-kappaB pathway in this process. Cultured HCAECs were treated with ox-LDL for 24 h. Incubation of HCAECs with ox-LDL resulted in apoptosis of HCAECs in a concentration-dependent manner, as determined by TUNEL and DNA laddering. Ox-LDL degraded IkappaB and activated NF-kappaB in HCAECs, as determined by Western blot analysis. Treatment with alpha-tocopherol (10 and 50 microM) decreased ox-LDL-mediated apoptosis as well as degradation of IkappaB and activation of NF-kappaB in HCAECs. High concentration of alpha-tocopherol (50 microM) was more effective than the low concentration of alpha-tocopherol (10 microM). Thus, ox-LDL induces apoptosis of HCAECs, in concurrence with degradation of IkappaB and activation of NF-kappaB. Alpha-tocopherol markedly decreases ox-LDL-induced effects.

Antioxidants↗
PubMed2000

A mitogen-activated protein kinase kinase required for induction of cytokinesis and appressorium formation by host signals in the conidia of Colletotrichum gloeosporioides.

Differentiation of fungal conidia of phytopathogens into the infection structure, appressorium, requires contact with a hard surface and host signals. The molecular signaling involved in the induction of this differentiation is poorly understood. We report the cloning of a mitogen-activated protein kinase kinase (MEK), CgMEK, from Colletotrichum gloeosporioides and its role in the induction of these developmental processes involved in pathogenesis. Disruption of CgMEK1 resulted in the loss of its ability to form appressoria in response to the host's signals and a loss of virulence. Results of confocal microscopic examination of germinating conidia of the gene-disrupted mutants were similar to those for wild-type conidia treated with an MEK inhibitor, suggesting that CgMEK1 is involved in two developmental processes in the differentiation into appressorium: (1) polarized cell division, with the preferential increase in F-actin in one of the daughter nuclei after nuclear division and the formation of septum; and (2) differentiation of the germ tube into an appressorium. CgMEK1 is required for the differentiation.

Actins↗
PubMed2000

Quantifying coevolution of nonstationary biomedical signals using time-varying phase spectra.

We present a novel time-varying phase spectrum (TVPS) method to quantify the dynamics of coevolution of two persistent nonstationary coupled signals. Based on the TVPS, an instantaneous intersignal phase shift is defined within the primary frequency range in which the two signals are highly correlated. The TVPS is estimated using a fixed-window method or an adaptive-window method. In the latter method, the window length changes dynamically and automatically as a function of change in frequency of the signals. The effects of altering window types and lengths on the accuracy of the estimation of the primary phase shift is assessed by analyzing synthesized linear chirp signals with decaying amplitude and constant relative phase shift or decaying amplitude and changing relative phase shifts. The methods developed are also used for determining the evolution of the primary phase shift among ventral root activities during fictive locomotion in an in vitro rat spinal cord preparation. The analyses indicate that the TVPS method in conjunction with the determination of the primary frequency range, allows determination of both the evolution of the coupling strength and the evolution of the phase shift between two persistent nonstationary rhythmic signals in the joint time-frequency domain. An adaptive window reduces the estimation bias and the estimation variability.

Algorithms↗
PubMed2000

Epicardial suction: a new approach to mechanical testing of the passive ventricular wall.

The lack of an appropriate three-dimensional constitutive relation for stress in passive ventricular myocardium currently limits the utility of existing mathematical models for experimental and clinical applications. Previous experiments used to estimate parameters in three-dimensional constitutive relations, such as biaxial testing of excised myocardial sheets or passive inflation of the isolated arrested heart, have not included significant transverse shear deformation or in-plane compression. Therefore, a new approach has been developed in which suction is applied locally to the ventricular epicardium to introduce a complex deformation in the region of interest, with transmural variations in the magnitude and sign of nearly all six strain components. The resulting deformation is measured throughout the region of interest using magnetic resonance tagging. A nonlinear, three-dimensional, finite element model is used to predict these measurements at several suction pressures. Parameters defining the material properties of this model are optimized by comparing the measured and predicted myocardial deformations. We used this technique to estimate material parameters of the intact passive canine left ventricular free wall using an exponential, transversely isotropic constitutive relation. We tested two possible models of the heart wall: first, that it was homogeneous myocardium, and second, that the myocardium was covered with a thin epicardium with different material properties. For both models, in agreement with previous studies, we found that myocardium was nonlinear and anisotropic with greater stiffness in the fiber direction. We obtained closer agreement to previously published strain data from passive filling when the ventricular wall was modeled as having a separate, isotropic epicardium. These results suggest that epicardium may play a significant role in passive ventricular mechanics.

Animals↗
PubMed2000

Evaluation of sound propagation models used in bottom volume scattering studies

The proper evaluation of sound propagation between sources/receivers and scatterers is important in characterizing bottom volume scattering. In this article, several sound propagation models used in bottom volume scattering studies are evaluated and their results compared to the exact solution obtained through a numerical wave number integration technique. It is found that Hines' approach [J. Acoust. Soc. Am. 88, 324-334 (1990)] works well for the two isovelocity half-space case except when the grazing angle is close to the critical angle. The far-field approximation, given by Ivakin [Sov. Phys. Acoust. 32(6), 492-496 (1986)] and Mourad and Jackson [J. Acoust. Soc. Am. 94, 344-358 (1993)], has a performance depending upon the sound speed structure in the sediment. For an isovelocity slow bottom, it agrees well with the exact solution. However, discrepancies arise for an isovelocity fast bottom or a bottom with a complex sound speed structure. In addition, the appropriateness of using the equivalent surface scattering strength as a function of grazing angle in volume scattering characterizations is studied. In conclusion, precautions need to be taken in modeling both the propagation effects and the scattering mechanisms associated with the bottom volume scattering process.

Journal Article↗
PubMed2000

Two novel genes induced by hard-surface contact of Colletotrichum gloeosporioides conidia.

Germinating conidia of many phytopathogenic fungi must differentiate into an infection structure called the appressorium in order to penetrate into their hosts. This differentiation is known to require contact with a hard surface. However, the molecular basis for this requirement is not known. Induction of this differentiation in the avocado pathogen, Colletotrichum gloeosporioides, by chemical signals such as the host's surface wax or the fruit-ripening hormone, ethylene, requires contact of the conidia with a hard surface for about 2 h. To study molecular events triggered by hard-surface contact, we isolated several genes expressed during the early stage of hard-surface treatment by a differential-display method. The genes that encode Colletotrichum hard-surface induced proteins are designated chip genes. In this study, we report the characterization of CHIP2 and CHIP3 genes that would encode proteins with molecular masses of 65 and 64 kDa, respectively, that have no homology to any known proteins. The CHIP2 product would contain a putative nuclear localization signal, a leucine zipper motif, and a heptad repeat region which might dimerize into coiled-coil structure. The CHIP3 product would be a nine-transmembrane-domain-containing protein. RNA blots showed that CHIP2 and CHIP3 are induced by a 2-h hard-surface contact. However, disruption of these genes did not affect the appressorium-forming ability and did not cause a significant decrease in virulence on avocado or tomato fruits suggesting that C. gloeosporioides might have genes functionally redundant to CHIP2 and CHIP3 or that these genes induced by hard-surface contact control processes not directly involved in pathogenesis.

Amino Acid Sequence↗
PubMed2000

Pathogenicity of Hantaan virus in newborn mice: genetic reassortant study demonstrating that a single amino acid change in glycoprotein G1 is related to virulence.

Two Hantaan virus strains, clone 1 (cl-1), which is virulent in newborn mice, and its attenuated mutant (mu11E10), were used to examine the pathogenesis of Hantaan virus infection in a mouse model and identify virus factors relating to virulence. After subcutaneous inoculation of newborn BALB/c mice, cl-1 caused fatal disease with high viral multiplication in peripheral organs, but mu11E10 produced nonfatal infection with a low level of virus multiplication. Intracerebral inoculation of either strain caused fatal disease. Histopathological changes in the dead animals were prominent in the brain, indicating that the brain is the target organ and produces the fatal outcome. These results indicate that mu11E10 has a generally less virulent phenotype, and because of decreased multiplication in peripheral tissues, neuroinvasiveness is also decreased. An experiment with genetic reassortant viruses showed that in newborn mice the M segment is the most related to virulence and the L segment is partly related. Sequence comparison detected a single deduced amino acid change (cl-1 Ile to mu11E10 Thr) at amino acid number 515 in glycoprotein G1. One nucleotide change, but no amino acid substitution, was observed in the noncoding region of the L segment. In mouse brain microvascular endothelial cells in vitro, viruses possessing a cl-1-derived M segment grew more rapidly than viruses containing a mu11E10-derived M segment. These results suggest that the single amino acid change in the glycoprotein alters peripheral growth, which affects invasion of the central nervous system in mice.

Amino Acid Substitution↗
PubMed2000

Basic mechanisms of atrial fibrillation--very new insights into very old ideas.

Atrial fibrillation (AF) was recognized and studied extensively in the early twentieth century, but many fundamental aspects of the arrhythmia were poorly understood until quite recently. It is now recognized that AF can be initiated by a variety of mechanisms that share the ability to cause extremely rapid, irregular atrial electrical activity. Once initiated, AF causes alterations in atrial electrical properties (electrical remodeling), including both rapid functional changes and slower alterations in ion channel gene expression, which promote the maintenance of AF and facilitate reinitiation of the arrhythmia should it terminate. Electrical remodeling decreases the atrial refractory period in a heterogeneous way, thus decreasing the size and stability of potential functional atrial reentry waves and promoting multiple-circuit reentry. Whatever the initial cause of AF, electrical remodeling is likely to be a final common pathway that ultimately supervenes. Recent advances in understanding ion channel function, regulation, and remodeling at the molecular level have allowed for a much more detailed appreciation of the basic determinants of AF. Improvements in the clinical management of AF will inevitably follow the recent advances in our understanding of its detailed pathophysiology.

Animals↗
PubMed2000

eNOS-deficient mice show reduced pulmonary vascular proliferation and remodeling to chronic hypoxia.

Pulmonary hypertension is characterized by structural and morphological changes to the lung vasculature. To determine the potential role of nitric oxide in the vascular remodeling induced by hypoxia, we exposed wild-type [WT(+/+)] and endothelial nitric oxide synthase (eNOS)-deficient [(-/-)] mice to normoxia or hypoxia (10% O(2)) for 2, 4, and 6 days or for 3 wk. Smooth muscle alpha-actin and von Willebrand factor immunohistochemistry revealed significantly less muscularization of small vessels in hypoxic eNOS(-/-) mouse lungs than in WT(+/+) mouse lungs at early time points, a finding that correlated with decreases in proliferating vascular cells (5-bromo-2'-deoxyuridine positive) at 4 and 6 days of hypoxia in the eNOS(-/-) mice. After 3 wk of hypoxia, both mouse types exhibited similar percentages of muscularized small vessels; however, only the WT(+/+) mice exhibited an increase in the percentage of fully muscularized vessels and increased vessel wall thickness. eNOS protein expression was increased in hypoxic WT(+/+) mouse lung homogenates at all time points examined, with significantly increased percentages of small vessels expressing eNOS protein after 3 wk. These results indicate that eNOS deficiency causes decreased muscularization of small pulmonary vessels in hypoxia, likely attributable to the decrease in vascular cell proliferation observed in these mice.

Actins↗
PubMed2000

Arachidonic acid metabolic pathways regulating activity of renal Na(+)-K(+)-ATPase are age dependent.

Locally formed arachidonic acid (AA) metabolites are important as modulators of many aspects of renal tubular function, including regulation of the activity of tubular Na(+)-K(+)-ATPase. Here we examined the ontogeny of the AA metabolic pathways regulating proximal convoluted tubular (PCT) Na(+)-K(+)-ATPase activity in infant and adult rats. Eicosatetraynoic acid, an inhibitor of all AA-metabolizing pathways, abolished this effect. AA inhibition of PCT Na(+)-K(+)-ATPase was blocked by the 12-lipoxygenase inhibitor baicalein in infant but not in adult rats and by the specific cytochrome P-450 fatty acid omega-hydroxylase inhibitor 17-octadecynoic acid in adult but not in infant rats. The lipoxygenase metabolite 12(S)-hydroxyeicosatetraenoic acid (HETE) and the cytochrome P-450 metabolite 20-HETE both inhibited PCT Na(+)-K(+)-ATPase in a protein kinase C-dependent manner, but the effect was significantly more pronounced in infant PCT. Lipoxygenase mRNA was only detected in infant cortex. Expression of renal isoforms of cytochrome P-450 mRNA was more prominent in adult cortex. In summary, the AA metabolic pathways that modulated the activity of rat renal proximal tubular Na(+)-K(+)-ATPase are age dependent.

5,8,11,14-Eicosatetraynoic Acid↗