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991.
Optically pure L-3(2-hydroxyphenyl) alanine(L-o-tyrosine ,Ⅲa,),L-3-(3-hydroxyphenyl) alanine(L-m-tyrosine,Ⅲb )and L-3-(4-hydroxyphenyl )alanine(L-p-tyrosine,Ⅲc )were synthesized by the stereocontrolled amination of corresponding hydroxycinnamic acld(Ⅱ)catalyzed by L-phenylalanine ammonia-lyase(PAL,EC4.3.1.5 )contained in Rhodoterula rubramycelium. The amination of compound Ⅱ was completed in aqueous ammonia solution( 6.4mol·L-1,pH10.5, 30℃) with the conversion of 74.9%(Ⅱa),21.1%(Ⅱb)and 20.6%(Ⅱc)respectively.The absolute configuration of the products Ⅲa~c were confirmed by circular dichroism(CD),and chiral high-performance ligand exchange chromatography(HPLEC)showed that productsⅢ were optically pure L-isomers. 相似文献
992.
Mark?JS?MillerEmail author Brian?K?Reuter John?L?Wallace Keith?A?Sharkey 《Journal of translational medicine》2008,6(1):3
Background
We examined the therapeutic potential of a proprietary Croton palanostigma extract (Zangrado®) in the management of emesis and itch.Methods
Emesis was induced in ferrets with morphine-6-glucuronide (0.05 mg/kg sc) in the presence of Zangrado (3 mg/kg, ip) and the cannabinoid receptor 1 antagonist, AM 251 (5 mg/kg, ip). Topical Zangrado (1%) was assessed for anti-pruretic actions in the 5-HT-induced scratching model in rats and evaluated in capsaicin-induced gastric hyperemia as measured by laser doppler flow. In the Apc Min mouse model of precancerous adenomatosis polyposis, mice received Zangrado (100 μg/ml in drinking water) from the age of 6 – 16 weeks for effects on polyp number. In RAW 264.7 cells Zangrado was examined for effects on lipopolysaccharide-induced nitrite production.Results
Zangrado was a highly effective anti-emetic, reducing morphine-induced vomiting and retching by 77%. These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism. Itch responses were blocked in both the morphine and 5-HT models. Zangrado did not exacerbate the Apc Min condition rather health was improved. Capsaicin-induced hyperemia was blocked by Zangrado, which also attenuated the production of nitric oxide by activated macrophages.Conclusion
Zangrado is an effective anti-emetic and anti-itch therapy that is devoid of common side-effects, cannabinoid-independent and broadly suppresses sensory afferent nerve activation. This complementary medicine represents a promising new approach to the management of nausea, itch and irritable bowel syndrome.993.
Mouse/human sequence divergence in a region with a paternal-specific methylation imprint at the human H19 locus 总被引:3,自引:2,他引:3
994.
995.
mdx muscle pathology is independent of nNOS perturbation 总被引:2,自引:0,他引:2
Crosbie RH; Straub V; Yun HY; Lee JC; Rafael JA; Chamberlain JS; Dawson VL; Dawson TM; Campbell KP 《Human molecular genetics》1998,7(5):823-829
In skeletal muscle, neuronal nitric oxide synthase (nNOS) is anchored to
the sarcolemma via the dystrophin-glycoprotein complex. When dystrophin is
absent, as in Duchenne muscular dystrophy patients and in mdx mice, nNOS is
mislocalized to the interior of the muscle fiber where it continues to
produce nitric oxide. This has led to the hypothesis that free radical
toxicity from mislocalized nNOS may contribute to mdx muscle pathology. To
test this hypothesis directly, we generated mice devoid of both nNOS and
dystrophin. Overall, the nNOS- dystrophin null mice maintained the
dystrophic characteristics of mdx mice. We evaluated the mice for several
features of the dystrophic phenotype, including membrane damage and muscle
morphology. Removal of nNOS did not alter the extent of sarcolemma damage,
which is a hallmark of the dystrophic phenotype. Furthermore, muscle from
nNOS-dystrophin null mice maintain the histological features of mdx
pathology. Our results demonstrate that relocalization of nNOS to the
cytosol does not contribute significantly to mdx pathogenesis.
相似文献
996.
Komal Mehta Jayesh Gala Surendra Bhasale Sattayasheel Naik Millind Modak Harshad Thakur Nivedita Deo Mark JS Miller 《BMC complementary and alternative medicine》2007,7(1):34
Background
The efficacy and safety of a dietary supplement derived from South American botanicals was compared to glucosamine sulfate in osteoarthritis subjects in a Mumbai-based multi-center, randomized, double-blind study. 相似文献997.
998.
Detection of precursor Th cells in mesenteric lymph nodes after oral immunization with protein antigen and cholera toxin 总被引:2,自引:0,他引:2
We have characterized the earliest antigen-specific Th cells in murine
mesenteric lymph nodes (MLN), following oral immunization with the hen egg
lysozyme (HEL) as antigen and cholera toxin (CT) as adjuvant. We did this
by analyzing in vitro proliferation and cytokine production in response to
HEL by the MLN T cells. MLN cells taken 5 days after a single oral
immunization with HEL and CT provided the earliest source of proliferating
HEL-specific T cells. This proliferation was completely inhibited by
anti-IL-2, but not inhibited by anti-IL-4 antibody. IL-2 protein was
detected in culture supernatants but not IL- 4 using ELISA or bioassays.
IL-4 mRNA was not found in responding cells using RT-PCR. Some of the day 5
MLN cultures produced IFN-gamma in response to HEL, but isolated T cells
from the same MLN did not. Exogenous IL-4 alone did not stimulate day 5 MLN
T cells, but IL-4 did synergize with HEL to induce a large proliferative
response. The data indicate that the HEL-specific CD4 T cell pool in MLN 5
days after oral immunization is composed of undifferentiated precursor Th
cells. These cells have the potential for IL-2 production and IL-4R
expression upon re-stimulation in vitro.
相似文献
999.
Human neutrophil dysfunction with giant granules and defective activation of the respiratory burst 总被引:1,自引:0,他引:1
Newburger PE; Robinson JM; Pryzwansky KB; Rosoff PM; Greenberger JS; Tauber AI 《Blood》1983,61(6):1247-1257
We describe a patient whose peripheral blood neutrophils and bone marrow precursors (beyond promyelocytes) contained multiple large azurophilic granules. There were also giant granules in eosinophils, basophils, melanocytes, renal tubules, thyroid, and neurones, but not lymphocytes or monocytes. His clinical course included recurrent (ultimately fatal) infections and severe neurologic impairment. Immunofluorescent staining with fluoroscein- and rhodamine-conjugated antisera to primary and secondary granule markers showed virtually all of the granulocyte granules and rare monocyte granules to be fusion products containing both markers. Electron microscopy showed the granules to be large peroxidase-containing lysosomes. Only rare normal primary and secondary granules were present. Superoxide generation in response to opsonized zymosan was 7.3 nmole/min/10(6) cells (control 8.9); but in response to phorbol myristate acetate, only 2.2 (control 9.4). Nitroblue tetrazolium slides showed 3+ dye reduction in response to opsonized zymosan by 90% of granulocytes (control 91%) and to phorbol myristate acetate by 22% (control 99%), with 71% producing only a minimal 1+ response. Cellular contents of myeloperoxidase and beta- glucuronidase were elevated, but the percent release during exocytic degranulation was equivalent to control. Ingestion of complement- opsonized Staphylococcus aureus and zymosan was also normal. Killing of Staphylococcus aureus was 60% at 90-min incubation (control 92%). Granulocyte cyclic adenosine monophosphate (AMP) content was 4 pmole/10(7) cells (control 3.1). In order to determine whether these characteristics derived from the cells' genetic program or their environment, the patient's bone marrow was grown in long-term culture. Granulocytes produced in vitro demonstrated the same morphology, same defect in activation of nitroblue tetrazolium reduction, and same normal cyclic AMP level as those harvested from peripheral blood. These studies describe a new disorder of granulocytes; the structural similarity to, but biochemical differences from, Chediak-Higashi disease indicate the probable heterogeneity of mechanisms for the same morphological abnormality. 相似文献
1000.
The integrin alpha IIb beta 3, a calcium-dependent heterodimer, plays a critical role in platelet aggregation. The alpha IIb subunit of the heterodimer contains four highly conserved putative calcium-binding domains in its extracellular portion. During studies of the molecular basis of Glanzmann thrombasthenia in a child of mixed Caucasian background whose platelets expressed little alpha IIb beta 3 on their surface, we found the patient heterozygous for a two amino acid deletion in the fourth alpha IIb calcium-binding domain. When this alpha IIb mutant was expressed in COS-1 cells, we found that the deletion did not interfere with the assembly of alpha IIb beta 3 heterodimers, but altered their conformation such that they were neither recognized by the heterodimer-specific antibody A2A9 nor able to undergo further intracellular processing or transport to the cell surface. These results suggest that the calcium-binding domains in alpha IIb play an important role maintaining the overall conformation of alpha IIb beta 3. To confirm this suggestion, we deleted each of the four 12 amino acid calcium-binding domains in alpha IIb by in vitro mutagenesis and expressed the mutants along with beta 3 in COS-1 cells. Each construct formed a heterodimer with beta 3, but none of the heterodimers interacted with A2A9 or underwent further intracellular processing. These data indicate that the calcium-binding domains in alpha IIb are not involved in alpha IIb beta 3 heterodimer formation, but their presence is required for the intracellular transport of alpha IIb beta 3 to the cell surface. 相似文献