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排序方式: 共有426条查询结果,搜索用时 15 毫秒
1.
可逆性胆硷酯酶抑制剂二甲氨基甲酸-5-二氢吲哚酯的合成 总被引:1,自引:0,他引:1
为了深入研究催醒宁类化合物的结构与抑酶活性的关系,设计合成了-系列1-,3-或5-位不同取代的二氢吲哚类衍生物(中间体和终产物共24个新化合物)。中间体1,3-二甲基-5-烷氧基-2-二氢吲哚酮(A)的C3烷化。采用相转移催化方法进行;反应中还分离到三个副产物(Ⅶ~Ⅸ)。初筛结果表明:这些化合物大多有较强的抑酶活性;1,3-或5-位取代基的改变均明显影响其活性。 相似文献
2.
Braffman BH; Coleman BG; Ramchandani P; Arger PH; Nodine CF; Dinsmore BJ; Louie A; Betsch SE 《Radiology》1994,190(3):797
3.
This study was designed to determine whether the somatostatin analogue,
octreotide, could prevent embryonic loss by normalizing increased uterine
insulin-like growth factor-I (IGF-I) action related to hyperoestrogenaemia
following superovulation. Superovulated immature and
oestradiol-17beta-treated adult rats were infused with 100 or 300 microg/ml
of octreotide respectively, or injected daily with 1 or 10 microg of
octreotide from day 1 to day 3 of pregnancy. On day 3, embryos were
collected from the oviducts and uteri. Uterine luminal fluid was subjected
to embryo culture. The amounts of uterine IGF-I and IGF binding proteins
(IGFBP) were determined by radioimmunoassay and ligand binding assay
respectively. Octreotide infusion normalized uterine IGF-I action following
superovulatory and oestradiol-17beta treatment, by reducing IGF-I
concentrations and increasing IGFBP concentrations. Octreotide infusion
increased the number of normal embryos by 2.7-fold and 1.7-fold in
superovulated and oestradiol-17beta- treated rats respectively, and
reversed the detrimental effects of uterine luminal fluid on embryonic
development caused by superovulatory and oestradiol-17beta treatment. Daily
injections with octreotide had similar but reduced effects in all
parameters examined in both treatment groups. In conclusion, octreotide may
reduce embryonic loss, at least in part, by normalizing IGF-I action
following superovulation.
相似文献
4.
W Kiess S Malozowski M Gelato O Butenand H Doerr B Crisp E Eisl A Maluish B H Belohradsky 《Clinical immunology and immunopathology》1988,48(1):85-94
Natural killer (NK) cell activity was assessed in the peripheral blood of 20 patients with growth hormone (GH) deficiency due to a hypothalamic deficit of GH-releasing hormone (GHRH). All patients failed to respond to at least two provocative tests of GH secretion (GH below 7 ng/ml) but responded to a single GHRH iv bolus injection (1 microgram/kg body wt). In 14 of the 20 patients (20 determinations), lymphocyte subsets were also measured; in all patients the distribution of lymphocyte subsets was within the normal range. More importantly, NK cell activity in the 20 patients was significantly lower than in controls (P less than 0.01). To assess the in vivo effect of GH and GHRH on NK activity and lymphocyte subset distribution, immunologic tests were performed (i) before and after a single iv bolus injection of GHRH (1 microgram/kg body wt) in six patients; (ii) before and after 3 weeks of GHRH treatment (3-9 micrograms/kg body wt, one to four times daily) in five patients; and (iii) after 6 weeks of GH treatment (5 IU sc every alternate day) in one patient. Neither NK activity nor the distribution of lymphocyte subsets was altered during short-term GHRH administration. In conclusion, low NK activity is found in GH-deficient patients, and short-term administration of GH or GHRH fails to restore this immunological abnormality. This result suggests that the hypothalamus may be a regulator of NK activity in the human and that patients with hypothalamic deficiencies should be monitored for the development of discrete immunodeficiencies. 相似文献
5.
Pumeechockchai W Bevitt D Agarwal K Petropoulou T Langer BC Belohradsky B Bassendine MF Toms GL 《Journal of medical virology》2002,68(3):335-342
The purpose of this study was to analyse the influence of the humoral immune response on the generation and clearance of hepatitis C virus (HCV) RNA containing particles in the blood of chronically infected patients. Blood samples were fractionated by sequential flotation ultracentrifugation and HCV RNA was recovered in three fractions: low density of < 1.063 g/ml, intermediate density of 1.063-1.21 g/ml, and high density of > 1.21 g/ml. Serum low-density lipoproteins co-fractionated with the low-density particles, and high-density lipoproteins co-fractionated with the intermediate-density particles. Immunoglobulins were found exclusively in the high-density fractions. In patients with congenital immunodeficiencies, with no or low serum antibodies to the virus, mean HCV RNA titres were equal in each fraction, at approximately 10(5) IU/ml. In antibody-positive, immunocompetent patients, however, virus titres in the low-density fraction and those in the high-density fraction were reduced or absent in most patients, suggesting that virus particles in these fractions are subject to antibody-mediated clearance. Particles of intermediate density were approximately equal in titre in both patient groups, suggesting that these particles are neither generated by, nor cleared, as a result of the humoral immune response. Immunoprecipitation experiments indicated that particles of intermediate density were not complexed with either high-density lipoprotein or immunoglobulins. Elucidation of the mechanisms by which these particles are generated and maintained in the blood may provide valuable insight into the mechanism of virus persistence. 相似文献
6.
Wijmenga C Hansen RS Gimelli G Björck EJ Davies EG Valentine D Belohradsky BH van Dongen JJ Smeets DF van den Heuvel LP Luyten JA Strengman E Weemaes C Pearson PL 《Human mutation》2000,16(6):509-517
ICF syndrome is a rare autosomal recessive immunoglobulin deficiency, sometimes combined with defective cellular immunity. Other features that are frequently observed in ICF syndrome patients include facial dysmorphism, developmental delay, and recurrent infections. The most diagnostic feature of ICF syndrome is the branching of chromosomes 1, 9, and 16 due to pericentromeric instability. Positional candidate cloning recently discovered the de novo DNA methyltransferase 3B (DNMT3B) as the responsible gene by identifying seven different mutations in nine ICF patients. DNMT3B specifically methylates repeat sequences adjacent to the centromeres of chromosome 1, 9, and 16. Our panel of 14 ICF patients was subjected to mutation analysis in the DNMT3B gene. Mutations in DNMT3B were discovered in only nine of our 14 ICF patients. Moreover, two ICF patients from consanguineous families who did not show autozygosity (i.e. homozygosity by descent) for the DNMT3B locus did not reveal DNMT3B mutations, suggesting genetic heterogeneity for this disease. Mutation analysis revealed 11 different mutations, including seven novel ones: eight different missense mutations, two different nonsense mutations, and a splice-site mutation leading to the insertion of three aa's. The missense mutations occurred in or near the catalytic domain of DNMT3B protein, indicating a possible interference with the normal functioning of the enzyme. However, none of the ICF patients was homozygous for a nonsense allele, suggesting that absence of this enzyme is not compatible with life. Compound heterozygosity for a missense and a nonsense mutation did not seem to correlate with a more severe phenotype. 相似文献
7.
S Bydder NA Spry DRH Christie D Roos BH Burmeister H Krawitz S Davis DJ Joseph M Poulsen M Berry 《Journal of Medical Imaging and Radiation Oncology》2003,47(3):284-288
The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty‐eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty‐two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high‐dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53?66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well‐tolerated treatment achieves useful palliation. 相似文献
8.
U. Wintergerst N. Rümmelein B. H. Belohradsky 《Monatsschrift für Kinderheilkunde》1998,146(4):315-322
Zusammenfassung
Fragestellung: Retrospektive Auswertung der Erkrankungen HIV-infizierter Kinder (<18 Jahre) an einer Pneumocystis-carinii-Pneumonie. Erfa?t wurden Prophylaxesituation, Krankheitsverlauf und Prognose.
Methode: Ein Fragebogen wurde an alle 16 p?diatrischen Zentren in Deutschland, die HIV-infizierte Kinder betreuen, verschickt und
deskriptiv ausgewertet.
Ergebnisse: Von Januar 1989 bis Dezember 1995 wurden aus 6 klinischen Zentren 21 Patienten mit Pneumocystis-carinii-Pneumonie mitgeteilt (1–5 Erkrankungen pro Jahr). In den übrigen 10 Zentren wurden in diesem Zeitraum keine Patienten mit
Pneumocystis-carinii-Pneumonie behandelt. 17 Kinder erwarben die HIV-Infektion pr?- und perinatal, 4 Kinder durch Blut oder
Blutprodukte. Das Alter der vertikal infizierten Kinder betrug im Median 5 Monate. 15/21 Kindern erhielten keine Pneumocystis-carinii-Prophylaxe. Davon wurden 10 Patienten zum Zeitpunkt der Diagnosestellung nicht durch die aktuell geltenden Prophylaxerichtlinien
der Centers for disease control erfa?t, und bei 5 Kindern wurde die HIV-Exposition erst mit Diagnosestellung der Pneumocystis-carinii-Pneumonie bekannt. Die akute Letalit?t betrug 29%, die Letalit?t der beatmeten Kinder 71%. Bis Juni 1996 betrug die mittlere
überlebenszeit aller Patienten 20,3±19,1 Monate. Die überlebenszeit der bereits im 1. Lebensjahr erkrankten Kinder war mit
14,8±18,4 Monaten deutlich, aber nicht signifikant kürzer als diejenige der sp?ter erkrankten Kinder (27,6±18,5 Monate). Die
nach Kaplan-Meier gesch?tzte 1-Jahres-überlebenszeit betrug 66%.
Schlu?folgerungen: Die Pneumocystis-carinii-Pneumonie bei HIV-infizierten Kindern ist in Deutschland eine seltene Erkrankung mit ernster Prognose. Obwohl eine effektive
Prophylaxe zur Verfügung steht, treten immer wieder Pneumocystis-carinii-Pneumonien auf, insbesondere bei Kindern, deren HIV-Exposition nicht rechtzeitig erkannt wurde. Die in dieser Umfrage ermittelten
überlebenszeiten sind im internationalen Vergleich eher günstig.
相似文献
9.
Dr. A. Jansson U. Wintergerst S. Bechtold B. H. Belohradsky 《Monatsschrift für Kinderheilkunde》2006,154(10):990-995
Systemic lupus erythematosus (SLE) is an autoimmune disorder which can affect every organ. Its etiopathogenesis is not fully understood, but animal models have demonstrated that B lymphocytes play an important role in the pathogenesis of affected organs. Severely ill patients may not respond to conventional immunosuppressive therapies. In such cases therapeutic options such as plasmapheresis, newer experimental therapies, or autologous stem cell therapy are applied with variable success. Especially for severely affected children safe therapeutic options are desperately needed. We report two children with therapy-refractory SLE who responded to rituximab – a genetically engineered monoclonal CD20 antibody. B-cell depletion with rituximab seems to be a promising therapy for refractory SLE. Compared to the severe side effects of immunosuppressive drugs, rituximab appears to be safer and should be considered for children with severe SLE. Controlled studies are needed. 相似文献
10.
Stojanov S Lohse P McDermott MF Renner ED Kéry A Mirakian R Hammond LJ Aganna E Hoffmann F Zellerer S Belohradsky BH 《Rheumatology (Oxford, England)》2004,43(4):526-527
SIR, The hereditary periodic fever syndromes are characterizedby recurrent episodes of fever due to multisystemic inflammation.In the case of autosomal dominantly inherited tumour necrosisfactor (TNF) receptor-associated periodic syndrome (TRAPS),these attacks are associated with severe abdominal pain, localizedmyalgia, painful migratory erythematous skin rash, conjunctivitisand/or periorbital oedema. TRAPS is caused by sequence alterationsin the TNFRSF1A gene, which encodes the 55-kDa TNF receptor[1]. Familial Mediterranean fever (FMF) is the most common autosomalrecessively inherited periodic fever syndrome. Attacks of FMFare of 13 days 相似文献