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31.
Zelinski-Wooten MB; Slayden OD; Chwalisz K; Hess DL; Brenner RM; Stouffer RL 《Human reproduction (Oxford, England)》1998,13(2):259-267
Large doses of antiprogestin typically disrupt menstrual cyclicity. A
chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which
permits continued menstrual cyclicity but alters gonadal- reproductive
tract activity, was established. Rhesus monkeys received vehicle (n = 6) or
0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight
daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and
gonadotrophin profiles were normal during cycles involving vehicle and 0.01
and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle
oestradiol and gonadotrophin surges, and subsequent progesterone
production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied
by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half
the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group
were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of
C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and
cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily
treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in
macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed
ovarian cyclicity, menstruation was disrupted in some animals. Increasing
the dose to 0.1 mg/kg antagonized pituitary function and resulted in
anovulation and amenorrhoea. A chronic low-dose regimen of the
antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity,
has potential as a contraceptive in women.
相似文献
32.
Epilepsy is a family of neurological disorders that result in seizure activity that is characterized by transient hypersynchronous activation of a large population of neurons. In animal models, focal tetanic electrical stimulation of sufficient duration and intensity, can elicit epileptiform activity, that if repeated results in progressive intensification of seizure activity known as kindling. Kindling serves as a model of partial as well as secondarily generalized temporal lobe epilepsy. We utilized hippocampal kindling to provide a means of evaluating the effect of sensory stimulation on the duration and severity of the induced seizure activity. Sensory stimuli targeted either the olfactory, auditory or somatosensory systems in an attempt to retard or suppress seizure activity. To that end, rats were chronically implanted with electrodes in the CA1 region of dorsal hippocampus and kindled once daily until the seizure behaviour was fully generalized. Kindling stimulation consisted of daily application of 1-s trains of biphasic square wave pulses applied at a frequency of 60Hz, at the afterdischarge (AD) threshold. Sensory stimulation was applied 6-8s after the kindling stimulation every third day. One group of rats received a different sensory stimulus (novel) every third day, while another group was presented with the same sensory stimulus (repeated) every third day. Kindling stimulation applied to the dorsal hippocampus resulted in progression of the AD characteristics and seizure behavior, which typically developed very slowly in the early stages. The application of both the novel and repeated sensory stimulation during partial seizures (stages 1 and 2) resulted in a reduction in the seizure severity but not in the afterdischarge duration. Sensory stimulation delivered during secondarily generalized seizures (stages 4 and 5) failed to affect either parameter. 相似文献
33.
M Parsons M Valentine J Deans G L Schieven J A Ledbetter 《Molecular and biochemical parasitology》1991,45(2):241-248
Regulation of tyrosine phosphorylation is a critical element in controlling growth and differentiation in higher eukaryotes. We have determined that the protozoan Trypanosoma brucei, which diverged early in the eukaryotic lineage, possesses multiple proteins which react with a specific anti-phosphotyrosine antiserum. Anti-phosphotyrosine immunoprecipitates of [32P]orthophosphate-labeled cells were shown to contain phosphotyrosine by two-dimensional electrophoresis. Western analysis of cells from different stages of the life cycle demonstrates the appearance of tyrosine-phosphorylated proteins at 40-42 kDa during the transition from slender to stumpy blood-forms. Growth of procyclic form cells in orthovanadate resulted in increased levels of specific tyrosine-phosphorylated proteins. The demonstration of phosphotyrosine-containing proteins in T. brucei and their differential regulation during the life cycle suggests that tyrosine kinases and phosphatases may play an important role in the biology of primitive protozoa. 相似文献
34.
Gonadotrophin-releasing hormone agonist dose-dependency of pituitary desensitization during controlled ovarian hyperstimulation in IVF 总被引:2,自引:2,他引:2
Janssens RM; Vermeiden JP; Lambalk CB; Schats R; Schoemaker J 《Human reproduction (Oxford, England)》1998,13(9):2386-2391
The aim of this study was to find the minimal effective daily s.c. dose of
the gonadotrophin-releasing hormone (GnRH) agonist, triptorelin acetate,
that suppresses the GnRH-induced release of luteinizing hormone (LH) at
time of human chorionic gonadotrophin (HCG) injection and thereby prevents
spontaneous LH surges during in-vitro fertilization (IVF) stimulation
cycles. Therefore, a double-blind, prospective and randomized titration
study was performed. A total of 48 IVF patients were divided into four
groups of 12 patients. Each group received a different dose of triptorelin
acetate, namely 5, 15, 50 or 100 microg s.c. daily. Standard ovarian
stimulation was carried out using urinary follicle stimulating hormone
(FSH) preparations. A 500 microg GnRH test was performed 90 min before the
HCG injection in order to measure the degree of pituitary desensitization.
Spontaneous LH surges were not detected in any of the groups, although
three patients in the 5 microg group had ovulated at the time of ovum
retrieval. The pituitary LH response to the GnRH test at time of HCG,
expressed as area under the curve (AUC), appeared to be dose-dependent.
Thus, a daily s.c. dose of 100 microg triptorelin acetate appears to be too
high, since adequate desensitization of the pituitary (i.e. no spontaneous
LH surge) can be achieved with doses as low as 15 and 50 microg.
相似文献
35.
B lymphocytes secreting IgG linked to latent transforming growth factor- beta prevent primary cytolytic T lymphocyte responses 总被引:3,自引:0,他引:3
B lymphocytes secreting IgG linked to latent transforming growth factor
(TGF)-beta (IgG-TGF-beta) prevent cytolytic T lymphocyte (CTL) responses to
unrelated antigens in mixed lymphocyte cultures (MLC) so long as resting
resident macrophages and functional Fc receptors are present. This was
shown using IgG-secreting plaque-forming cells (PFC) to sheep erythrocytes
(SRBC) obtained from popliteal lymph nodes of mice injected repeatedly in
foot pads with SRBC. Remarkably, as few as approximately 300 PFC prevented
CTL responses of 5 x 10(5) normal syngeneic spleen cells in MLC.
Supranatants of short-term cultures of PFC also prevented CTL responses,
and suppression was prevented by eliminating or dissociating IgG and
TGF-beta present in supranatants or by antibody against active TGF-beta.
Furthermore, the latency- associated peptide of latent TGF-beta was
detected in approximately 10% of foci of IgG captured from single PFC,
indicating that at least some B lymphocytes secrete IgG-TGF-beta as a
complex. Resting resident macrophages (which do not produce latent
TGF-beta) and functional Fc receptors were required for suppression,
consistent with idea that IgG- TGF-beta is taken up through Fc receptors
for IgG and that active TGF- beta, cleaved from latent TGF-beta of the
complex, is delivered directly to potentially responding CTL. If CTL
responses in man are similarly regulated by B lymphocytes, then an ongoing
B cell response in patients with chronic viral infections or bearing
immunogenic cancers may prevent effective therapeutic vaccination.
相似文献
36.
37.
D Proud R M Naclerio D A Meyers A Kagey-Sobotka L M Lichtenstein M D Valentine 《International archives of allergy and applied immunology》1990,93(2-3):165-170
We performed a double-blind, placebo-controlled, crossover study using 12 subjects to determine the effects of a single 50-mg dose of captopril on the response to nasal challenge with increasing doses of allergen. Levels of kinins, histamine and N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity were measured in nasal lavages, and symptom scores and the number of sneezes were recorded. Captopril had no significant effects on histamine, TAME-esterase, sneezing or symptom scores. Peak postchallenge kinin levels, however, were significantly elevated (p less than 0.05) compared to placebo, while an increase in the magnitude of the dose-response curve was of marginal significance (p = 0.058). Thus, captopril causes increases in the kinin levels in nasal secretions during the allergic response. If increased kinin levels persist or worsen with chronic therapy, it is possible that they could exacerbate allergic symptoms during repeated seasonal exposure. 相似文献
38.
Synergistic effect of mutations in invA and lpfC on the ability of Salmonella typhimurium to cause murine typhoid. 总被引:4,自引:0,他引:4
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A J Bumler R M Tsolis P J Valentine T A Ficht F Heffron 《Infection and immunity》1997,65(6):2254-2259
Penetration of the intestinal mucosa at areas of Peyer's patches is an important first step for Salmonella typhimurium to produce lethal systemic disease in mice. However, mutations in genes that are important for intestinal invasion result in only moderately decreased virulence of S. typhimurium for mice. Here we report that combining mutations in invA and lpfC, two genes necessary for entry into Peyer's patches, results in a much stronger attenuation of S. typhimurium than inactivation of either of these genes alone. An S. typhimurium invA lpfC mutant was 150-fold attenuated by the oral route of infection but was fully virulent when the intestine was bypassed by intraperitoneal challenge of mice. During mixed-infection experiments, the S. typhimurium invA lpfC mutant showed a strong defect in colonizing Peyer's patches and mesenteric lymph nodes. These data suggest that mutations in invA and lpfC deactivate distinct pathways for intestinal penetration and colonization of Peyer's patches. While the inv-mediated pathway is widely distributed, the lpf operon is absent from many phylogenetic groups within the genus Salmonella. To investigate how acquisition of the lpf-mediated pathway for mucosal penetration contributed to evolution of virulence, we studied the relationship between the presence of the lpf operon and the pathogenicity for mice of 18 isolates representing 14 Salmonella serotypes. Only strains possessing the lpf operon were able to cause lethal infection in mice. These data show that both the invA- and lpfC-mediated pathways of intestinal perforation are conserved in mouse virulent Salmonella serotypes. 相似文献
39.
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
40.
C. Y. W. Tong C. Valentine O. P. Arya 《European journal of clinical microbiology & infectious diseases》1996,15(4):336-340
Endourethral swabs and first-pass urine (FPU) samples from 148 male patients were tested forChlamydia trachomatis by an automated enzyme immunoassay (EIA) (Vidas; bioMérieux, France), a direct fluorescent antibody (DFA) test (MicroTrak; Syva, USA) and two polymerase chain reaction (PCR) methods.Chlamydia trachomatis was considered present if a specimen was positive by at least two methods. This expanded criterion identified 27 patients (18%) as truly infected. One of the PCR methods was most sensitive for both types of specimen. When the recommended cut-off value of Vidas was reduced by 50%, its sensitivity on endourethral swabs was comparable to that of the DFA test, but the DFA test performed better with FPU. In general, FPU was suitable only for PCR. 相似文献