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81.
82.
Vilarinho L Cardoso ML Gaspar P Barbot C Azevedo L Diogo L Santos M Carrilho I Fineza I Kok F Chorão R Alegria P Martins E Teixeira J Cabral Fernandes H Verhoeven NM Salomons GS Santorelli FM Cabral P Amorim A Jakobs C 《Human mutation》2005,26(4):395-396
We studied 21 patients, from 18 families, with L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic disorder with a homogeneous presentation: progressive neurodegeneration with extrapyramidal and cerebellar signs, seizures, and subcortical leukoencephalopathy. Increased levels of L-2-hydroxyglutaric acid in body fluids proved the diagnosis of L-2-HGA in all 21 patients. We analyzed the L-2-HGA gene (L2HGDH), recently found to be mutated in consanguineous families with L-2-HGA, and identified seven novel mutations in 15 families. Three mutations appeared to be particularly prevalent in this Portuguese panel: a frameshift mutation (c.529delC) was detected in 12 out of 30 mutant alleles (40%), a nonsense mutation (c.208C>T; p.Arg70X) in 7/30 alleles (23%), and a missense mutation (c.293A>G; p.His98Arg) in four out of 30 mutant alleles (13%), suggesting that common origin may exist. Furthermore, two novel missense (c.169G>A; p.Gly57Arg, c.1301A>C; p.His434Pro) and two splice error (c.257-2A>G, c.907-2A>G) mutations were found. All the mutations presumably lead to loss-of-function with no relationship between clinical signs, progression of the disease, levels of L-2-HGA and site of the mutation. In the three remaining families, no pathogenic mutations in the L-2-HGA were found, which suggests either alterations in regulatory regions of the gene or of its intervening sequences, compound heterozygosity for large genomic deletion and, or further genetic heterogeneity. 相似文献
83.
Lopata AL Jeebhay MF Reese G Fernandes J Swoboda I Robins TG Lehrer SB 《International archives of allergy and immunology》2005,138(1):21-28
BACKGROUND: Aerosolization of fish proteins during seafood processing has been identified as a potential route for allergic sensitization and occupational asthma among workers involved in high-risk activities. The aim of this study was to develop immunological assays for the quantification of aerosolized fish antigens in a fish-processing factory. METHODS: Polyclonal antibodies to the main fish species processed in the factory (anchovy and pilchard) were generated in rabbits and compared by ELISA inhibition assay and immunoblotting. These antisera were utilized to develop ELISA assays for the detection of fish antigens. The ELISA inhibition assays were evaluated by analyzing environmental air samples collected from three areas in a fish-processing factory: pilchard canning, fish meal production and lobster processing. RESULTS: By immunoblotting, the rabbit polyclonal antibodies demonstrated IgG antibody binding patterns comparable with IgE antibodies of fish-sensitized patients, particularly in regard to the major fish allergens parvalbumins. The sensitivity of the fish-specific ELISA assays developed was 0.5 microg/ml. The ELISA inhibition assays were able to differentiate between the two different fish species of interest but did not recognize a crustacean species. Notable differences in exposure levels to canned pilchard and anchovy antigens were demonstrated in the three different working areas of the factory, with assays having a detection limit as low as 105 ng/m(3). CONCLUSION: These ELISA-based assays are sensitive and specific to quantify differential exposure levels to fish antigens produced during fish processing, making it possible to investigate exposure-disease response relationships among workers in this industry. 相似文献
84.
Middle cerebral artery blood velocity during exercise with beta-1 adrenergic and unilateral stellate ganglion blockade in humans 总被引:5,自引:0,他引:5
Ide K Boushel R Sørensen HM Fernandes A Cai Y Pott F Secher NH 《Acta physiologica Scandinavica》2000,170(1):33-38
A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA V(mean)) is attenuated during cycling with beta-1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocaine; 8 mL; n=8) affects the attenuated exercise - MCA V(mean following cardio-selective beta-1 adrenergic blockade (0.15 mg kg(-1) metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V(mean) were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA V(mean) increased to the same extent (11.4 +/- 1.9 vs. 11.1 +/- 1.9 cm s(-1)). With the pharmacological intervention the exercise CO (10 +/- 1 vs. 12 +/- 1 L min(-1); n=5), HR (115 +/- 4 vs. 134 +/- 4 beats min(-1)) and delta MCA V(mean) (8.7 +/- 2.2 vs. 11.4 +/- 1.9 cm s(-1) were reduced, and MAP was increased (100 +/- 5 vs. 86 +/- 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the beta-1 blockade induced attenuation in delta MCA V(mean) (10.2 +/- 2.5 cm s(-1)). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system. 相似文献
85.
86.
Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro fertilization and embryo transfer cycle 总被引:1,自引:1,他引:1
Balasch J; Creus M; Fabregues F; Civico S; Reverter JC; Carmona F; Tassies D; Vanrell JA 《Human reproduction (Oxford, England)》1998,13(5):1180-1183
Increased antiphospholipid antibody prevalence has been demonstrated by a
number of recent studies in in-vitro fertilization (IVF) patients but the
potential effects of antiphospholipid antibodies on the different
components of the reproductive process and the consideration of whether to
test IVF patients for antiphospholipid antibodies are controversial. The
present study was undertaken to investigate the possible association
between the presence of circulating antiphospholipid antibodies (namely the
lupus anticoagulant and anticardiolipin antibodies), among a series of 21
consecutive IVF patients having a clinical spontaneous abortion after their
first embryo transfer. As a control group (n=42), the nearest IVF cycle
resulting in an ongoing pregnancy before and after each miscarried IVF
cycle (i.e. the closest cycles in temporal relationship to the index cycle)
was used. One patient (4.8%) in the study group and two women (4.8%) among
controls were seropositive for antiphospholipid antibodies. These low and
similar seropositivity rates found in the two groups studied lead us to
conclude that antiphospholipid antibodies testing in IVF patients should be
considered only in those women having repeated failures of
implantation/clinical abortion after embryo transfer but not in an
infertile general population reaching an IVF programme.
相似文献
87.
Boesel LF Fernandes MH Reis RL 《Journal of biomedical materials research. Part B, Applied biomaterials》2004,70(2):368-377
Composite bone cements were formulated with bioactive glass (MgO--SiO(2)--3CaO. P(2)O(5)) as the filler and hydrophilic matrix. The matrix was composed of a starch/cellulose acetate blend (SCA) as the solid component and a mixture of methylmethacrylate/acrylic acid (MMA/AA) as the liquid component. The curing parameters, mechanical properties, and bioactive behavior of these composite cements were determined. The addition of up to 30 wt % of glass improved both compressive modulus and yield strength and kept the maximum curing temperature at the same value presented by a typical acrylic-based commercial formulation. The lack of a strongly bonded interface (because no coupling agent was used) had important effects on the swelling and mechanical properties of the novel bone cements. However, bone cements containing AA did not show a bioactive behavior, because of the deleterious effect of this monomer on the calcium phosphate precipitation on the polymeric surfaces. Formulations without AA were prepared with MMA or 2-hydroxyethyl methacrylate (HEMA) as the liquid component. Only these formulations could form an apatite-like layer on their surface. These systems, therefore, are very promising: They are bioactive, hydrophilic, partially degradable, and present interesting mechanical properties. This combination of properties could facilitate the release of bioactive agents from the cement, allow bone ingrowth in the cement, and induce a press-fitting effect, improving the interfaces with both the prosthesis and the bone. 相似文献
88.
Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen,but not by the LACK antigen,are protective against experimental Leishmania (Leishmania) amazonensis infection
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Coelho EA Tavares CA Carvalho FA Chaves KF Teixeira KN Rodrigues RC Charest H Matlashewski G Gazzinelli RT Fernandes AP 《Infection and immunity》2003,71(7):3988-3994
Leishmania amazonensis is one of the major etiologic agents of a broad spectrum of clinical forms of leishmaniasis and has a wide geographical distribution in the Americas, which overlaps with the areas of transmission of many other Leishmania species. The LACK and A2 antigens are shared by various Leishmania species. A2 was previously shown to induce a potent Th1 immune response and protection against L. donovani infection in BALB/c mice. LACK is effective against L. major infection, but no significant protection against L. donovani infection was observed, in spite of the induction of a potent Th1 immune response. In an attempt to select candidate antigens for an American leishmaniasis vaccine, we investigated the protective effect of these recombinant antigens (rLACK and rA2) and recombinant interleukin-12 (rIL-12) against L. amazonensis infection in BALB/c mice. As expected, immunization with either rA2-rIL-12 or rLACK-rIL-12 induced a robust Th1 response prior to infection. However, only the BALB/c mice immunized with rA2-rIL-12 were protected against infection. Sustained gamma interferon (IFN-gamma) production, high levels of anti-A2 antibodies, and low levels of parasite-specific antibodies were detected in these mice after infection. In contrast, mice immunized with rLACK-rIL-12 displayed decreased levels of IFN-gamma and high levels of both anti-LACK and parasite-specific antibodies. Curiously, the association between rA2 and rLACK antigens in the same vaccine completely inhibited the rA2-specific IFN-gamma and humoral responses and, consequently, the protective effect of the rA2 antigen against L. amazonensis infection. We concluded that A2, but not LACK, fits the requirements for a safe vaccine against American leishmaniasis. 相似文献
89.
Huisman JA; Paulussen RJ; Geurts TB; Odink J; Rekers H 《Human reproduction (Oxford, England)》1997,12(1):34-38
The objective was to demonstrate bioequivalence between s.c. and i.m.
administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio
3:1). In two randomized, single-centre, cross-over studies, 18 healthy
volunteers on each formulation were assigned to one of the two
administration sequences. Subjects were given single doses of one of the
above gonadotrophins after endogenous gonadotrophin production had first
been suppressed using high-dose oral contraceptive. Subsequently, rate
(Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone
(FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax
and AUC, analysis of variance (ANOVA) was performed on log-transformed data
and for tmax ANOVA was performed on ranks. Intramuscular and s.c.
injections of Humegon were bioequivalent with respect to the main
pharmacokinetic parameters, being AUC and Cmax of FSH absorption.
Intramuscular and s.c. injections of Normegon were bioequivalent with
respect to the AUC of FSH and not bioequivalent with respect to the Cmax of
FSH. For tmax of FSH as well as for most LH variables of both preparations,
bioequivalence could not be proven due to the high intra- and
interindividual variability and/or concentrations being close to the
detection limit. Thus, the main pharmacokinetic FSH variables after i.m.
and s.c. administration of Humegon and Normegon were bioequivalent.
相似文献
90.
Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx? 总被引:4,自引:7,他引:4
Sowter MC; Akande VA; Williams JA; Hull MG 《Human reproduction (Oxford, England)》1997,12(10):2147-2150
A pilot study was designed to examine whether the outcome of embryo
transfer in women with a hydrosalpinx might be improved by surgical
drainage of the hydrosalpinx at the time of oocyte collection for in- vitro
fertilization treatment. A comparative, controlled but retrospective
analysis of the results was performed of all women with infective tubal
damage aged <40 years old, who had ovulatory cycles, a normal uterus and
a partner with normal spermatozoa. A standardized treatment regimen was
used. A maximum of three embryos were transferred. Hydrosalpinx was defined
by prior hysterosalpingography and/or laparoscopy with transcervical dye
injection. A total of 237 embryo transfer cycles in women with
hydrosalpinges (tubal distension not visible in 151, visible but not
drained in 30 and drained in 56) were compared with 705 embryo transfer
cycles in women with tubal disease but no hydrosalpinx. Results were
analysed in the first three cycles but also separately in the first cycle
to check for bias. Success rates were higher in the first cycle, but did
not significantly influence overall differences. Implantation rates were
significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2%
for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup
without evident tubal distension and 7.5% (not significant) in the drained
hydrosalpinx group. This study shows that tubal damage with distal
occlusion is associated with a marked reduction in embryo implantation,
even in the absence of obvious fluid distension. Surgical drainage of
distended hydrosalpinges appears to offer no benefit.
相似文献