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31.
Protective levels of diphtheria-neutralizing antibody induced in healthy volunteers by unilateral priming-boosting intranasal immunization associated with restricted ipsilateral mucosal secretory immunoglobulin a 总被引:6,自引:0,他引:6
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Mills KH Cosgrove C McNeela EA Sexton A Giemza R Jabbal-Gill I Church A Lin W Illum L Podda A Rappuoli R Pizza M Griffin GE Lewis DJ 《Infection and immunity》2003,71(2):726-732
Subunit intranasal vaccines offer the prospect of inducing combined systemic-mucosal immunity against mucosally transmitted infections such as human immunodeficiency virus. However, although human studies have demonstrated the induction of active immunity, secretory immunoglobulin A (sIgA) responses are variable, and no study has demonstrated protection by accepted vaccine-licensing criteria as measured by direct toxin-neutralizing activity. Using the genetically inactivated mutant diphtheria toxoid CRM(197) in a bioadhesive polycationic polysaccharide chitosan delivery system, we found that a single nasal immunization was well tolerated and boosted antitoxin neutralizing activity in healthy volunteers, which could be further boosted by a second immunization. The neutralizing activity far exceeded accepted protective levels and was equivalent to that induced by standard intramuscular vaccine and significantly greater than intranasal immunization with CRM(197) in the absence of chitosan. A striking but unexpected observation was that although unilateral intranasal immunization induced circulating antitoxin antibody-secreting cells, a nasal antitoxin sIgA response was seen only after the second immunization and only in the vaccinated nostril. If these data are reproduced in larger studies, an intranasal diphtheria vaccine based on CRM(197)-chitosan could be rapidly licensed for human use. However, a restricted sIgA response suggests that care must be taken in the priming-boosting strategy and clinical sampling techniques when evaluating such vaccines for the induction of local mucosal immunity. 相似文献
32.
Kim YH; de Kretser DM; Temple-Smith PD; Hearn MT; McFarlane JR 《Molecular human reproduction》1997,3(4):307-313
Using mechanical and chemical dissection methods, fibrous sheath was
isolated both from normal ejaculated human spermatozoa and from rabbit
cauda epididymal spermatozoa. The same techniques did not produce a pure
preparation of fibrous sheath from ejaculated rabbit spermatozoa,
suggesting that further cross-linking and stabilization of sperm structures
occurs in response to components of the seminal plasma. The isolation
procedures were monitored by phase contrast microscopy and the purity of
the fibrous sheath was verified by electron microscopy. Sodium dodecyl
sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of isolated human
fibrous sheath revealed at least 14 protein bands of which the most
intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5
kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which
the most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid
composition of the purified fibrous sheath from human and rabbit
spermatozoa was similar, being high in aspartic acid and/or asparagine and
glutamic acid and/or glutamine, serine, alanine, leucine, lysine and
glycine, but low in histidine, tyrosine and isoleucine. This composition is
similar to that reported for the rat and suggests that mammalian sperm tail
fibrous sheaths are composed of similar types of proteins, although there
are apparent differences in protein components between species.
相似文献
33.
Marjolein P de Vries Lisette van den Bemt Karen Aretz Bart PA Thoonen Jean WM Muris Arnold DM Kester Sonja Cloosterman CP Onno van Schayck 《The British journal of general practice》2007,57(536):184-190
BACKGROUND: The efficacy of bed covers that are impermeable to house dust mites has been disputed. AIM: The aim of the present study was to investigate whether the combination of 'house dust mite impermeable' covers and a self-management plan, based on peak flow values and symptoms, leads to reduced use of inhaled corticosteroids (ICS) than self-management alone. DESIGN OF STUDY: Prospective, randomised, double blind, placebo-controlled trial. SETTING: Primary care in a south-eastern region of the Netherlands. METHOD: Asthma patients aged between 16 and 60 years with a house dust mite allergy requiring ICS were randomised to intervention and placebo groups. They were trained to use a self-management plan based on peak flow and symptoms. After a 3-month training period, the intervention commenced using house dust mite impermeable and placebo bed covers. The follow-up period was 2 years. Primary outcome was the use of ICS; secondary outcomes were peak expiratory flow parameters, asthma control, and symptoms. RESULTS: One hundred and twenty-six patients started the intervention with house dust mite impermeable or placebo bed covers. After 1 and 2 years, significant differences in allergen exposure were found between the intervention and control groups (P<0.001). No significant difference between the intervention and control groups was found in the dose of ICS (P = 0.08), morning peak flow (P = 0.52), peak flow variability (P = 0.36), dyspnoea (P = 0.46), wheezing (P = 0.77), or coughing (P = 0.41). There was no difference in asthma control between the intervention and control groups. CONCLUSION: House dust mite impermeable bed covers combined with self-management do not lead to reduced use of ICS compared with self-management alone. 相似文献
34.
Mahadevan MM; McIntosh Q; Miller MM; Breckinridge SM; Maris M; Moutos DM 《Human reproduction (Oxford, England)》1998,13(4):979-982
Cryopreservation of human zygotes and embryos has been routinely performed
by in-vitro fertilization clinics for many years. Karran and Legge (1996)
first reported that formaldehyde (FA) present in the cryoprotective
solutions can have a deleterious effect on mouse oocytes. FA is a
cytotoxic, carcinogenic and mutagenic chemical. The effect of FA on mouse
zygotes was investigated. In addition, the concentrations of FA in
propanediol (PROH) obtained from various sources were determined. Pooled
1-cell embryos were dispensed into droplets of modified Ham's F10 or human
tubal fluid containing various concentrations of FA. Since bovine serum
albumin (BSA) may minimize toxicity additional trials were done as above in
the absence of BSA. FA concentration in the standard 1.5 M PROH, from
different sources in water, was measured in the same assay using a standard
curve of 0-100 microM FA. FA in a complex medium had a significant
deleterious effect on embryo development and hatching but only at 1 mM
concentration (P < 0.000001; see Tables I-III). There was no significant
effect of FA at 100 microM. However, in a simple medium even 50 microM FA
decreased embryo hatching. FA was present in 1.5 M PROH from different
sources (range 1.0-35.3 microM concentration). It appears that FA
concentrations do not increase with storage because FA concentrations were
low even after opening and storage for 3 years on the shelf. This suggests
that FA is a contaminant during the manufacturing process and may vary from
manufacturer to manufacturer and batch to batch. Until further studies are
done to confirm the lack of toxicity to embryos during cryopreservation
(with or without FA scavengers) it may be prudent to screen all batches of
cryoprotectants for FA as part of quality control.
相似文献
35.
High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes 总被引:5,自引:0,他引:5
Shuber AP; Michalowsky LA; Nass GS; Skoletsky J; Hire LM; Kotsopoulos SK; Phipps MF; Barberio DM; Klinger KW 《Human molecular genetics》1997,6(3):337-347
As more mutations are identified in genes of known sequence, there is a
crucial need in the areas of medical genetics and genome analysis for
rapid, accurate and cost-effective methods of mutation detection. We have
developed a multiplex allele-specific diagnostic assay (MASDA) for analysis
of large numbers of samples (> 500) simultaneously for a large number of
known mutations (> 100) in a single assay. MASDA utilizes
oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA
samples are immobilized on a solid support and a single hybridization is
performed with a pool of allele-specific oligonucleotide (ASO) probes. Any
probes complementary to specific mutations present in a given sample are in
effect affinity purified from the pool by the target DNA. Sequence-specific
band patterns (fingerprints), generated by chemical or enzymatic sequencing
of the bound ASO(s), easily identify the specific mutation(s). Using this
design, in a single diagnostic assay, we tested samples for 66 cystic
fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell
anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations,
four mutations in Canavan disease, four mutations in Fanconi anemia, and
five mutations in BRCA1. Each mutation was correctly identified. Finally,
in a blinded study of 106 of these mutations in > 500 patients, all
mutations were properly identified. There were no false positives or false
negatives. The MASDA assay is capable of detecting point mutations as well
as small insertion or deletion mutations. This technology is amenable to
automation and is suitable for immediate utilization for high-throughput
genetic diagnostics in clinical and research laboratories.
相似文献
36.
Oocyte morphology predicts outcome of intracytoplasmic sperm injection 总被引:10,自引:14,他引:10
Serhal PF; Ranieri DM; Kinis A; Marchant S; Davies M; Khadum IM 《Human reproduction (Oxford, England)》1997,12(6):1267-1270
To examine the influence of cytoplasmic morphology on the success rate of
intracytoplasmic sperm injection (ICSI), the morphology of 837 metaphase II
oocytes was assessed after cumulus stripping. The main abnormalities
detected were excessive granularity, cytoplasmic inclusions such as
vacuoles, smooth endoplasmic reticulum clustering and refractile bodies.
Microinjection was performed in 538 oocytes with normal cytoplasm, 142 out
of 161 with excessive granularity and 112 out of 138 with cytoplasmic
inclusions. Very poor oocytes were not injected. No difference was found in
fertilization rate. The embryos achieved cleaved normally and a similar
number of good quality embryos among the three groups was noted. The
outcome of transfer of embryos derived solely from normal oocytes (group A:
72 patients, 183 embryos) was compared with those from oocytes with
cytoplasmic abnormalities (group B: 34 patients, 85 embryos). In group A,
17 clinical pregnancies (24% per patient, implantation rate 10%) were
established. In group B, only one clinical pregnancy (3% per patient,
implantation rate 1%) was established, from the transfer of embryos derived
from oocytes with homogeneous granularity of the cytoplasm. No pregnancy
resulted following the transfer of embryos from eggs with cytoplasmic
inclusions. The difference was statistically significant. The outcome of
ICSI is dependent on the quality of the oocytes retrieved. Normal
fertilization and early embryo development were achieved in oocytes with
abnormal cytoplasm morphology, but the resulting embryos failed to
demonstrate the same implantation potential as those derived from oocytes
with normal cytoplasm.
相似文献
37.
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Mucin was demonstrated in 11 of 16 carcinoid tumours of usual histological appearances. The mucin was characterized histochemically and shown to be similar to that which is produced in the gastrointestinal as well as the respiratory tract. This relative ubiquity of mucin in carinoid tumours has not hitherto been appreciated and more obviously "mixed" tumours have been regarded as rareties. The importance of these findings with respect to the neural crest theory of origin of enterochromaffin cells is discussed. 相似文献