Biomedical subjects

P Yang

Publications and source records attributed to P Yang.

At least 19 recordsLinked to original sources

PubMed2000

Valproate modulates the expression of methylphenidate (ritalin) sensitization.

Repeated administration of amphetamine, cocaine, and methylphenidate (MPD) has been reported to elicit behavioral sensitization to their locomotor and stereotypic effects in rodents. GABAergic drugs have been shown to inhibit behavioral effects of stimulants. The objective of the present study was to determine whether single or multiple administration of sodium valproate, a GABA agonist, would prevent the expression of sensitization to the locomotor effect of MPD once it has developed. Twenty-eight male Sprague-Dawley rats were randomized into three treatment groups: a control group received only 2.5 mg/kg MPD during the 14-day cycle, a group received a single 50 mg/kg valproate injection on Day 9, and a group received multiple 50 mg/kg valproate injection on Days 9-13. Rats were housed in test cages and behavioral activities were recorded for 14 consecutive days. All injections were given between 12:00 h and 14:00 h. Multiple injection of MPD elicited sensitization to its locomotor and stereotypic effects. Single administration of valproate did not block the expression of sensitization in the four locomotor indices measured. However, multiple administration of valproate prevented MPD sensitization to horizontal activity, total distance and number of stereotypic movements.

Animals↗

PubMed2000

15-LOX-1: a novel molecular target of nonsteroidal anti-inflammatory drug-induced apoptosis in colorectal cancer cells.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to act via induction of apoptosis-programmed cell death-as potential colorectal cancer chemopreventive agents. NSAIDs can alter the production of different metabolites of polyunsaturated fatty acids (linoleic and arachidonic acids) through effects on lipoxygenases (LOXs) and cyclooxygenases. 15-LOX-1 is the main enzyme for metabolizing colonic linoleic acid to 13-S-hydroxyoctadecadienoic acid (13-S-HODE), which induces apoptosis. In human colorectal cancers, the expression of this enzyme is reduced. NSAIDs can increase 15-LOX enzymatic activity in normal leukocytes, but their effects on 15-LOX in neoplastic cells have been unknown. We tested the hypothesis that NSAIDs induce apoptosis in colorectal cancer cells by increasing the protein expression and enzymatic activity of 15-LOX-1. METHODS: We assessed 15-LOX-1 protein expression and enzymatic activity, 13-S-HODE levels, and 15-LOX-1 inhibition in association with cellular growth inhibition and apoptosis induced by NSAIDs (primarily sulindac and NS-398) in two colorectal cancer cell lines (RKO and HT-29). All P values are two-sided. RESULTS: Sulindac and NS-398 progressively increased 15-LOX-1 protein expression in RKO cells (at 24, 48, and 72 hours) in association with subsequent growth inhibition and apoptosis. Increased 13-S-HODE levels and the formation of 15-hydroxyeicosatetraenoic acid on incubation of the cells with the substrate arachidonic acid confirmed the enzymatic activity of 15-LOX-1. Inhibition of 15-LOX-1 in RKO cells by treatment with caffeic acid blocked NS-398-induced 13-S-HODE production, cellular growth inhibition, and apoptosis (P =. 007, P<.0001, and P<.0001, respectively); growth inhibition and apoptosis were restored by adding exogenous 13-S-HODE (P<.0001 for each) but not its parent compound, linoleic acid (P = 1.0 for each). Similar results occurred with other NSAIDs and in HT-29 cells. CONCLUSIONS: These data identify 15-LOX-1 as a novel molecular target of NSAIDs for inducing apoptosis in colorectal carcinogenesis.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Casein kinase I is anchored on axonemal doublet microtubules and regulates flagellar dynein phosphorylation and activity.

Flagellar dynein activity is regulated by phosphorylation. One critical phosphoprotein substrate in Chlamydomonas is the 138-kDa intermediate chain (IC138) of the inner arm dyneins (Habermacher, G., and Sale, W. S. (1997) J. Cell Biol. 136, 167-176). In this study, several approaches were used to determine that casein kinase I (CKI) is physically anchored in the flagellar axoneme and regulates IC138 phosphorylation and dynein activity. First, using a videomicroscopic motility assay, selective CKI inhibitors rescued dynein-driven microtubule sliding in axonemes isolated from paralyzed flagellar mutants lacking radial spokes. Rescue of dynein activity failed in axonemes isolated from these mutant cells lacking IC138. Second, CKI was unequivocally identified in salt extracts from isolated axonemes, whereas casein kinase II was excluded from the flagellar compartment. Third, Western blots indicate that within flagella, CKI is anchored exclusively to the axoneme. Analysis of multiple Chlamydomonas motility mutants suggests that the axonemal CKI is located on the outer doublet microtubules. Finally, CKI inhibitors that rescued dynein activity blocked phosphorylation of IC138. We propose that CKI is anchored on the outer doublet microtubules in position to regulate flagellar dynein.

Casein Kinases↗

PubMed2000

Myogenic stem cell function is impaired in mice lacking the forkhead/winged helix protein MNF.

Myocyte nuclear factor (MNF) is a winged helix transcription factor that is expressed selectively in myogenic stem cells (satellite cells) of adult animals. Using a gene knockout strategy to generate a functional null allele at the Mnf locus, we observed that mice lacking MNF are viable, but severely runted. Skeletal muscles of Mnf-/- animals are atrophic, and satellite cell function is impaired. Muscle regeneration after injury is delayed and incomplete, and the normal timing of expression of cell cycle regulators and myogenic determination genes is dysregulated. Mnf mutant mice were intercrossed with mdx mice that lack dystrophin and exhibit only a subtle myopathic phenotype. In contrast, mdx mice that also lack MNF die in the first few weeks of life with a severe myopathy. Haploinsufficiency at the Mnf locus (Mnf+/-) also exacerbates the mdx phenotype to more closely resemble Duchenne's muscular dystrophy in humans. We conclude that MNF acts to regulate genes that coordinate the proliferation and differentiation of myogenic stem cells after muscle injury. Animals deficient in MNF may prove useful for evaluation of potential therapeutic interventions to promote muscle regeneration for patients having Duchenne's muscular dystrophy.

Animals↗

PubMed2000

Diurnal differences in sensitization to methylphenidate.

Using a computerized monitoring system, we investigated the development of motor sensitization to methylphenidate (MPD) in the rat, and determined whether sensitization was dependent on the time of drug administration. Male Sprague-Dawley rats were housed in test cages and motor activity was recorded continuously for 16 days. The first 2 days served as baseline for each rat, and on day 3 each rat received a saline injection. The locomotor response to 0.6, 2.5, or 10 mg/kg of MPD was tested on day 4, followed by 5 days of single injections of 2.5 mg/kg MPD (days 5-9). After 5 days without injection (days 10-14) rats were re-challenged (day 15) with the same doses they received on day 4. There were three separate challenge doses and four different times of administration: 08:00, 14:00, 20:00, or 02:00 h. Horizontal activity, total distance, vertical activity, stereotypic activity, and number of stereotypic movements were recorded. Sensitization to MPD was dependent on the time of administration, the motor index studied, and the challenge dose used. It was more pronounced for forward ambulation than for rearing, with no augmented response to stereotypic effects. The expression of the sensitized response was dose-dependent and mainly observed with the 0.6 and 2.5 mg/kg challenge dose groups. The development of sensitization to MPD was also time-dependent with the most robust sensitization occurring during the light phase, while no sensitization was observed during the middle of the dark phase. In addition, repeated MPD administration caused a significant increase in the amount of nocturnal forward ambulation that persisted long after cessation of drug treatment.

Animals↗

PubMed2000

Mirrorless lasing from mesostructured waveguides patterned by soft lithography

Mesostructured silica waveguide arrays were fabricated with a combination of acidic sol-gel block copolymer templating chemistry and soft lithography. Waveguiding was enabled by the use of a low-refractive index (1.15) mesoporous silica thin film support. When the mesostructure was doped with the laser dye rhodamine 6G, amplified spontaneous emission was observed with a low pumping threshold of 10 kilowatts per square centimeter, attributed to the mesostructure's ability to prevent aggregation of the dye molecules even at relatively high loadings within the organized high-surface area mesochannels of the waveguides. These highly processible, self-assembling mesostructured host media and claddings may have potential for the fabrication of integrated optical circuits.

Journal Article↗

PubMed2000

Analysis of the human KCNH2(HERG) gene: identification and characterization of a novel mutation Y667X associated with long QT syndrome and a non-pathological 9 bp insertion.

Long QT (LQT) syndrome is a potentially life-threatening disorder, characterized by a distinct cardiac arrhythmia known as torsades de pointes. Mutations within a number of genes linked to the familial form, including that coding for a cardiac potassium channel called KCNH2 (HERG), have been described based on the characterized genomic organization. A standardized method was developed to screen the entire gene for gene variants. We report a single base pair substitution, introducing a premature STOP codon at codon 667 of the gene in a healthy individual with an extended QTc interval (460 msec). In vitro expression of the codon Y667X variant in Xenopus oocyte suggests that the autosomal dominant variant does not function in a dominant/negative manner and cannot co-assemble to form a channel, resulting in a reduction of the KCNH2 current, and an extension of the QT interval. This indicates that pathogenic LQT gene variants exist in the apparently normal population, the prognosis and clinical consequences of which remain to be determined. The assays described should facilitate future studies into this area.

Animals↗

PubMed2000

Hydrostatic pressure stimulates synthesis of elastin in cultured optic nerve head astrocytes.

Elastin is a major component of the extracellular matrix (ECM) of the lamina cribrosa in the optic nerve head in humans and nonhuman primates. The lamina cribrosa appears to be the site of damage to the retinal ganglion cell axons in glaucomatous optic neuropathy, characterized in many patients by elevated intraocular pressure (IOP). Type 1B astrocytes are the major cell type in the lamina, synthesize elastic fibers during development, express increased elastin mRNA, and synthesize abnormal elastin in glaucoma. In this study, we determined the effect of elevated hydrostatic pressure on the synthesis of elastin by type 1B astrocytes in culture. Type 1B astrocytes were exposed to gradients of hydrostatic pressure and tested for proliferation, morphology, synthesis, and deposition of elastin. Trichloroacetic acid (TCA) and immunoprecipitation of radiolabeled protein determined total new protein and elastin synthesis. Proteins from the conditioned media were analyzed by Western blot. Levels of elastin mRNA were determined by in situ hybridization. Cell proliferation increased approximately 2-fold after exposure to pressure for one day, approximately 5-fold after 3 and 5 days of exposure to pressure. Confocal and electron microscopic cytochemistry showed a marked increase in intracellular elastin in astrocytes exposed to pressure, as compared with controls. Intracellular elastin was associated with the RER-Golgi region and with the cytoskeleton. Total protein and elastin synthesis increased significantly (P < 0.05) at 3- and 5-day exposure to pressure, as well as the level of elastin mRNA. Elastin protein in the media increased with the level of pressure. These results indicate that hydrostatic pressure stimulates type 1B astrocytes to synthesize and secrete soluble elastin into the media. In glaucoma, type 1B astrocytes may respond to IOP-related stress with increased expression of elastin and formation of elastotic fibers leading to loss of elasticity and tissue remodeling.

Adolescent↗

PubMed2000

Gene therapy that inhibits nuclear translocation of nuclear factor kappaB results in tumor necrosis factor alpha-induced apoptosis of human synovial fibroblasts.

OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) increases the survival and proliferation of human rheumatoid arthritis (RA) cell lines. These experiments were designed to determine if inhibition of nuclear factor kappaB (NF-kappaB) nuclear translocation leads to increased apoptosis of TNFalpha-treated human RA cell lines. METHODS: We constructed an inhibitor of nuclear factor kappaB(IkappaB) dominant-negative adenovirus (AdCMVIkappaB-DN) and an X-linked inhibitor of apoptosis (XIAP) antisense adenovirus (AdCMVXIAP-AS). Primary RA synovial fibroblast (RASF) cell lines were transfected in vitro, and SV40-transformed RA synovial cell lines in SCID mice were transfected in vivo. Cells were treated with TNFalpha and analyzed for apoptosis. RESULTS: There was no apoptosis of primary RASF transfected in vitro with AdCMVIkappaB-DN alone. In contrast, there was apoptosis of >85% of cells treated with AdCMVIkappaB-DN plus TNFalpha. Primary RASF in SCID mice also exhibited high levels of apoptosis after in vivo transfection with AdCMVIkappaB-DN followed by treatment with TNFalpha. There was no apoptosis after treatment with AdCMVIkappaB-DN in the absence of TNFalpha. XIAP is an inhibitor of apoptosis which was up-regulated by TNFalpha, and this up-regulation was inhibited by AdCMVIkappaB-DN plus TNFalpha. Transfection of an AdCMVXIAP-AS gene therapy resulted in increased TNFa-induced apoptosis. CONCLUSION: AdCMVIkappaB-DN gene therapy greatly enhances apoptosis due to inhibition of an NF-kappaB-mediated antiapoptosis signaling pathway, and XIAP is a TNFalpha-inducible specific inhibitor of apoptosis in RA synovial cell lines. This and other modulators of TNF receptor or the Fas apoptosis pathway may be therapeutically beneficial in facilitating apoptosis of synovial tissue in patients with RA.

Animals↗

PubMed2000

Intravascular ultrasound predictors of major adverse cardiac events in patients with unstable angina.

BACKGROUND: Intravascular ultrasound (IVUS) predictors of native culprit lesion morphology for occurrence of major adverse cardiac events (MACE) have not been reported. Moreover, the published data on IVUS predictors of restenosis include patients with stable and unstable angina, although the development and progression of atherosclerosis related to unstable coronary syndrome is different from that of stable angina. HYPOTHESIS: This study investigated whether IVUS-derived qualitative and quantitative parameters of native (preangioplastic) plaque morphologic features can predict major adverse cardiac events in patients with unstable angina. METHODS: Clinical (age, gender, coronary risk factors), qualitative and quantitative angiographic (lesion localization, morphology, pre- and postangioplastic minimal lumen diameter, reference diameter, and percent diameter stenosis), and IVUS variables (soft/fibrocalcific plaque, calcification, presence of thrombus or plaque disruption, different types of arterial remodeling, pre- or postangioplastic minimal lumen, external elastic membrane and plaque cross-sectional area, and plaque burden of the target lesion and reference segments) were analyzed by regression analyses using the Cox model, assuming proportional hazards. RESULTS: Of 60 consecutively enrolled patients, 21 suffered from MACE, while 39 remained event-free during the followup period. Multivariate regression analyses revealed that the presence of adaptive remodeling [p = 0.0177, risk ratio (RR) = 3.108, with 95% confidence interval (CI) = 1.371-8.289] and the preangioplastic lumen cross-sectional area (p = 0.0130, RR = 0.869, with 95% CI = 0.667-0.913) are independent predictors of MACE during follow-up, as is postangioplastic angiographic minimal lumen diameter (p = 0.0330, RR = 0.715 with 95% CI = 0.678-0.812). CONCLUSIONS: Adaptive remodeling and preangioplastic lumen cross-sectional area determined by IVUS and postangioplastic minimal lumen diameter calculated by quantitative angiography are significant independent predictors of time-dependent MACE in patients with unstable angina.

Angina, Unstable↗

PubMed2000

Longitudinal straightening effect of stents is an additional predictor for major adverse cardiac events. Austrian Wiktor Stent Study Group and European Paragon Stent Investigators.

OBJECTIVES: The aim of this study was to perform an investigation of the effects of the longitudinal straightening of coronary arteries by stents and the possible association with major adverse cardiac events (MACE) (primary end point) and angiographic restenosis (secondary end point). BACKGROUND: Stent deployment straightens a tortuous artery, and any consequent arterial longitudinal stretch may contribute to MACE and stent restenosis severity. METHODS: Clinical, qualitative and quantitative angiographic data on 404 patients with single stent implantation were subjected to multivariate nominal logistic regression analysis for the prediction of MACE. The predictive accuracy, sensitivity and specificity values and cut-off points of the continuous variables were determined via receiver operating characteristics curves. The longitudinal straightening effect of stents was characterized through the changes in vessel angle (defined by the tangents to the proximal and distal parts of the stenoses/stents). RESULTS: Follow-up angiography on 354 patients revealed 73 cases of stent restenosis (> or =50% diameter stenosis). Coronary bypass surgery was performed in 4 patients and repeated percutaneous transluminal coronary angioplasty in 56 patients; acute myocardial infarction (AMI) occurred in 2 patients, and 4 patients died during the follow-up. The overall incidence of MACE (death, AMI and revascularization) was 16.3% (66 patients). The best predictive accuracies and sensitivities/specificities of factors indicative of MACE were found for the minimal lumen diameter (MLD) at follow-up (predictive accuracy: 0.9305, sensitivity/specificity: 86.6%), the post-stent MLD (0.773, 77.2%), the percent diameter stenosis (%DS) at follow-up (0.9432, 87.1%), the prestent vessel angulation (0.6797, 68.2%) and the poststent changes in vessel angulation (0.6279, 62.2%). Multivariate nominal logistic regression analysis demonstrated that a poststent MLD < or =2.63 mm (p = 0.0017, odds ratio [OR] = 17.961, 95% confidence interval [CI] = 17.45-20.428), an MLD at follow-up < or =1.7 mm (p = 0.0059, OR = 11.880, 95% CI = 11.490-14.093), a %DS at follow-up > or =42.2% (p = 0.0000, OR = 49.553, 95% CI = 48.024-53.507), a prestent vessel angulation > or =33.5 degrees (p = 0.0477, OR = 5.404, 95% CI = 5.382-7.142) and poststent changes in vessel angulation > or =9.1 degrees (p = 0.0026, OR = 19.161, 95% CI = 18.562-21.750) were significant predictors for MACE. Multiple linear regression revealed that the poststent MLD (multivariate p = 0.0001), the MLD at follow-up (p = 0.0000), the prestent vessel angulation (p = 0.0431) and the changes in vessel angulation after stent implantation (p = 0.0316) were significant independent variables predicting angiographic stent restenosis severity. CONCLUSIONS: The longitudinal straightening effect of coronary artery stents contributes significantly to the occurrence of MACE and angiographic restenosis, and this finding may have an impact on future stent design.

Aged↗

PubMed2000

Abnormal turning behavior in Drosophila larvae. Identification and molecular analysis of scribbler (sbb).

Our genetic dissection of behavior has isolated scribbler (sbb), a vital gene that encodes a novel protein expressed in the embryonic and larval nervous systems and in the imaginal discs. Larvae with mutations in sbb exhibit abnormally high amounts of turning behavior in the absence of food. sbb is a large gene spanning >50 kb of genomic DNA with four major developmentally regulated transcripts. Transgenic rescue of scribbler behavior was demonstrated by targeting expression of a normal sbb transgene (sbb(+)) expressing one of the major transcripts to the nervous system. The vital function of sbb was restored by ubiquitous expression of this transgene throughout development.

Amino Acid Sequence↗

PubMed2000

Identification of occupational cancer risks in British Columbia. A population-based case-control study of 995 incident breast cancer cases by menopausal status, controlling for confounding factors.

Lifetime occupational histories as well as information on known and suspected breast cancer risk factors were collected by means of a self-administered questionnaire from 1018 women with incident breast cancer ascertained from the British Columbia Cancer Registry, and from 1020 population controls. A matched case-control study design was used. Conditional logistic regression for matched sets data and the likelihood ratio were used in a two-step procedure and were performed separately for pre-menopausal women, post-menopausal women, and for all cases combined. Excess risk was noted for several white-collar occupations. Significantly increased risk was observed: (1) among pre-menopausal women: in electronic data-processing operators; barbers and hairdressers; in sales and material processing occupations; and in the food, clothing, chemical and transportation industries; (2) among post-menopausal women: in schoolteaching; in medicine, health, and nursing occupations; in laundry and dry-cleaning occupations; and in the aircraft and automotive, including gasoline service station, industries. Several significant associations were also seen in the combined group of pre- and post-menopausal women, particularly in crop farmers and in the fruit and vegetable, publishing and printing, and motor vehicle repair industries. The results of this study suggest excess breast cancer risk in a number of occupations and industries, notably those that entail exposure to solvents and pesticides.

Adolescent↗

PubMed2000

Histone-histone interactions and centromere function.

Cse4p is a structural component of the core centromere of Saccharomyces cerevisiae and is a member of the conserved CENP-A family of specialized histone H3 variants. The histone H4 allele hhf1-20 confers defects in core centromere chromatin structure and mitotic chromosome transmission. We have proposed that Cse4p and histone H4 interact through their respective histone fold domains to assemble a nucleosome-like structure at centromeric DNA. To test this model, we targeted random mutations to the Cse4p histone fold domain and isolated three temperature-sensitive cse4 alleles in an unbiased genetic screen. Two of the cse4 alleles contain mutations at the Cse4p-H4 interface. One of these requires two widely separated mutations demonstrating long-range cooperative interactions in the structure. The third cse4 allele is mutated at its helix 2-helix 3 interface, a region required for homotypic H3 fold dimerization. Overexpression of wild-type Cse4p and histone H4 confer reciprocal allele-specific suppression of cse4 and hhf1 mutations, providing strong evidence for Cse4p-H4 protein interaction. Overexpression of histone H3 is dosage lethal in cse4 mutants, suggesting that histone H3 competes with Cse4p for histone H4 binding. However, the relative resistance of the Cse4p-H4 pathway to H3 interference argues that centromere chromatin assembly must be highly regulated.

Centromere↗

PubMed2000

Antigen presenting cells expressing Fas ligand down-modulate chronic inflammatory disease in Fas ligand-deficient mice.

We assessed the effect of modified antigen presenting cells (APCs) expressing high levels of Fas ligand (APC-FasL) on post-viral chronic inflammatory disease. FasL-deficient B6-gld/gld mice infected with murine cytomegalovirus (MCMV) cleared the virus from their lungs, kidneys, and livers within 2 weeks of infection. However, inflammation persisted in these organs for more than 8 weeks, with a chronically increased T-cell response to MCMV-infected APCs and production of autoantibodies. Administration of APC-AdFasL at 4 weeks suppressed this inflammation and diminished the T-cell response and autoantibody production. APC-AdFasL that had been transfected with ultraviolet-irradiated MCMV were more effective than uninfected APC-AdFasL in ameliorating the chronic inflammation. APC-AdFasL migrated preferentially to the spleen, where they triggered apoptosis of lymphocytes in the marginal zone of the spleen. These results confirm that Fas-mediated apoptosis is not required for clearance of virus, but is required for down-modulation of the virally induced chronic inflammatory response. This organwide effect of APC-AdFasL appears to be mediated by elimination of activated T lymphocytes in the spleen before their emigration to the target organs.

Adenoviridae↗

PubMed2000

Protein phosphatases PP1 and PP2A are located in distinct positions in the Chlamydomonas flagellar axoneme.

We postulated that microcystin-sensitive protein phosphatases are integral components of the Chlamydomonas flagellar axoneme, positioned to regulate inner arm dynein activity. To test this, we took a direct biochemical approach. Microcystin-Sepharose affinity purification revealed a prominent 35-kDa axonemal protein, predicted to be the catalytic subunit of type-1 protein phosphatase (PP1c). We cloned the Chlamydomonas PP1c and produced specific polyclonal peptide antibodies. Based on western blot analysis, the 35-kDa PP1c is anchored in the axoneme. Moreover, analysis of flagella and axonemes from mutant strains revealed that PP1c is primarily, but not exclusively, anchored in the central pair apparatus, associated with the C1 microtubule. Thus, PP1 is part of the central pair mechanism that controls flagellar motility. Two additional axonemal proteins of 62 and 37 kDa were also isolated using microcystin-Sepharose affinity. Based on direct peptide sequence and western blots, these proteins are the A- and C-subunits of type 2A protein phosphatase (PP2A). The axonemal PP2A is not one of the previously identified components of the central pair apparatus, outer arm dynein, inner arm dynein, dynein regulatory complex or the radial spokes. We postulate PP2A is anchored on the doublet microtubules, possibly in position to directly control inner arm dynein activity.

Amino Acid Sequence↗

PubMed2000

Effects of third ventricle injection of norepinephrine analogue on LH secretion of the non-laying SIJI goose.

The effect of norepinephrine analogue (NA) and norepinephrine antagonists on luteinizing hormone releasing hormone (LHRH) secretion in geese was investigated by monitoring serum levels of LH. Twenty non-laying geese were selected and randomly assigned to 4 groups of 5 each. The geese received a single intraventricular injection of saline (control), NA (12 microg/6 microl), phentolamine (1 microg/6l) plus NA or yohimbine (10 microg/6 microl). Phentolamine, a non-selective adrenoreceptor blocker was given 5 min before NA, but yohimbine, an alpha2-adrenoreceptor blocker, was delivered without NA injection. The results showed that serum levels of LH began to increase 20 min after injection of NA, and that high serum levels of LH were maintained until 105 min, followed by a decline to the basal level 125 min later. Significantly high levels of serum LH were observed at 50 and 105 min after the injection as compared with the respective control. Treatment with phentolamine completely blocked the stimulatory effect of NA on serum levels of LH in NA treated geese. Serum levels of LH increased by yohimbine treatment 5 min after the injection and the high levels of serum LH were maintained until 125 min later. Five out of 8 points were significantly high as compared with their respective control values. The present study also suggested that there is presynaptic modulation in the a-noradrenergic neural pathways which mediate the release of LHRH, and that this modulation may be carried out by alpha2-adrenoreceptor blocker.

Adrenergic alpha-Agonists↗

PubMed2000

Alpha1-antitrypsin deficiency and inflammatory bowel diseases.

OBJECTIVE: To evaluate a possible etiologic role of alpha1-antitrypsin deficiency (alpha1AD), most frequently caused by a Z allele mutation, in ulcerative colitis (UC) and Crohn disease (CD). PATIENTS AND METHODS: This retrospective study included 10 patients diagnosed with and/or treated for inflammatory bowel disease (IBD) between 1976 and 1997 and identified from the Mayo Clinic Medical Index System. All 10 patients had either alpha1AD and CD or alpha1AD and UC. The alpha1-antitrypsin (alpha1AT) types and levels were determined with isoelectric focusing testing. The allele types, representing genotypes, were designated PiZZ (or ZZ) for homozygotes and PiMZ (or MZ) for heterozygotes. RESULTS: Seven patients had UC: 4 were genotype ZZ and 3 MZ. Four of these 7 patients had emphysema, 2 had asthma, and 1 had chronic bronchitis. Five were cigarette smokers, but only 1 had smoked coincident with activity of her UC. Two of the UC patients never smoked, and 1 of these 2 had asthma. Three of the 10 patients had CD, 2 genotype ZZ and 1 MZ. Two of the 3 patients were long-term cigarette smokers, and both had emphysema. Nine of the 10 patients with UC and alpha1AD required surgery. CONCLUSIONS: The need for surgery in patients with UC and alpha1-AD may point to a unique phenotypic subgroup of patients with alpha1AD and severe UC. Further studies are required to substantiate the etiologic role of alpha1AD in IBD. Our observations, if confirmed by future studies, suggest that in patients with both IBD and chronic obstructive pulmonary disease, alpha1AD testing should be considered.

Adult↗