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Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome 总被引:3,自引:4,他引:3
Sirotkin H; Morrow B; DasGupta R; Goldberg R; Patanjali SR; Shi G; Cannizzaro L; Shprintzen R; Weissman SM; Kucherlapati R 《Human molecular genetics》1996,5(5):617-624
Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are
developmental disorders characterized by a spectrum of phenotypes including
velopharyngeal insufficiency, conotruncal heart defects and facial
dysmorphology among others. Eighty to eighty-five percent of VCFS/DGS
patients are hemizygous for a portion of chromosome 22. It is likely that
the genes encoded by this region play a role in the etiology of the
phenotypes associated with the disorders. Using a cDNA selection protocol,
we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS
minimally deleted interval. The cDNA encodes a protein of 1638 amino acids.
CLTD shares significant homology, but is not identical to the ubiquitously
expressed clathrin heavy chain gene. The CLTD gene also shows a unique
pattern of expression, having its maximal level of expression in skeletal
muscle. Velopharyngeal insufficiency and muscle weakness are common
features of VCFS patients. Based on the location and expression pattern of
CLTD, we suggest hemizygosity at this locus may play a role in the etiology
of one of the VCFS-associated phenotypes.
相似文献
17.
INTRODUCTION: Core biopsy of the breast has become the method of choice for tissue diagnosis of screen detected microcalcifications and some mass lesions in many breast assessment centres. Biopsy results are not available until the following day. Imprint cytology of fresh breast core samples allows same-day reporting and patient counselling.
AIM: To determine the accuracy of core imprint cytology when compared with core biopsy diagnosis when used in a breast assessment centre setting.
METHODS: Core imprints (CI) were prepared and reported on all fresh core biopsies (CB) performed at the Sir Charles Gairdner Hospital Breast Centre from May to December 2000. Fresh core samples were placed on a glass microscope slide. Core radiographs were taken for microcalcification lesions (MC). A laboratory technician gently and quickly rolled the cores on the slide with fine forceps. The cores were fixed in formalin, processed and reported next day. The imprint slide was air dried and stained with DiffQuik. CI were reported using four categories: Insufficient, Benign, Indeterminate and Malignant. Counselling and planning for management were possible on the same day in women with malignant diagnoses. Clinicians were advised not to discuss negative or indeterminate CI results with women and to defer to the final CB report.
RESULTS: Cores were performed on 381 lesions. There were 83 carcinomas (38 in MC and 45 in masses) and 56 were called malignant on CI (absolute sensitivity 67.5%; 78.9% for MC and 57.8% for masses). 3 malignancies on CB were negative on CI giving a false negative rate of 3.6%. There were no false positive diagnoses. The predictive value of a benign diagnosis was 95.3%. There were no adverse effects in the histology of CB.
CONCLUSION: CI was an accurate method of providing an immediate diagnosis of malignancy in two thirds of malignancies confirmed on CB. 相似文献
AIM: To determine the accuracy of core imprint cytology when compared with core biopsy diagnosis when used in a breast assessment centre setting.
METHODS: Core imprints (CI) were prepared and reported on all fresh core biopsies (CB) performed at the Sir Charles Gairdner Hospital Breast Centre from May to December 2000. Fresh core samples were placed on a glass microscope slide. Core radiographs were taken for microcalcification lesions (MC). A laboratory technician gently and quickly rolled the cores on the slide with fine forceps. The cores were fixed in formalin, processed and reported next day. The imprint slide was air dried and stained with DiffQuik. CI were reported using four categories: Insufficient, Benign, Indeterminate and Malignant. Counselling and planning for management were possible on the same day in women with malignant diagnoses. Clinicians were advised not to discuss negative or indeterminate CI results with women and to defer to the final CB report.
RESULTS: Cores were performed on 381 lesions. There were 83 carcinomas (38 in MC and 45 in masses) and 56 were called malignant on CI (absolute sensitivity 67.5%; 78.9% for MC and 57.8% for masses). 3 malignancies on CB were negative on CI giving a false negative rate of 3.6%. There were no false positive diagnoses. The predictive value of a benign diagnosis was 95.3%. There were no adverse effects in the histology of CB.
CONCLUSION: CI was an accurate method of providing an immediate diagnosis of malignancy in two thirds of malignancies confirmed on CB. 相似文献
18.
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
19.
The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction 总被引:10,自引:3,他引:10
Herrmann SM; Ricard S; Nicaud V; Mallet C; Evans A; Ruidavets JB; Arveiler D; Luc G; Cambien F 《Human molecular genetics》1998,7(8):1277-1284
P-selectin is an adhesion molecule, expressed at the surface of activated
cells, that mediates the interaction of activated endothelial cells or
platelets with leukocytes. P-selectin expression is increased in
atherosclerotic plaques, and high plasma levels of this molecule have been
observed in patients with unstable angina. We investigated the P-selectin
gene as a possible candidate for myocardial infarction (MI). The P-selectin
gene is situated on chromosome 1q21-q24, spans >50 kb and contains 17
exons. The sequences of the 5'-flanking region and exons of 40 alleles from
patients with MI were screened for polymorphisms using polymerase chain
reaction/single-strand conformation polymorphism (PCR-SSCP) and sequencing.
Thirteen polymorphisms were identified: five in the 5'-flanking and eight
in the exonic sequences. Four polymorphisms (Ser290Asn, Asn562Asp,
Leu599Val and Thr715Pro) predicted a change in the amino acid sequence of
the P- selectin protein. All P-selectin polymorphisms as well as a common
E- selectin polymorphism, Ser128Arg which has been reported as being
associated with an increased risk of premature coronary heart disease
(CHD), and is in tight linkage disequilibrium with several P-selectin
polymorphisms, were investigated in 647 patients with MI and 758 control
subjects from four regions of France and Northern Ireland (the ECTIM
study). The entire set of P-selectin polymorphisms provided a
heterozygosity of 91%. The polymorphisms were tightly associated with one
another and displayed patterns of linkage disequilibrium suggesting the
existence of highly conserved ancestral haplotypes. The five polymorphisms
in the 5'-flanking region of the gene were unrelated to MI or any relevant
phenotype measured in the ECTIM study. We inferred that the four missense
variants identified in the coding region predicted eight common forms of
the P-selectin protein. The Pro715 allele which characterizes one of these
forms was less frequent in France than in Northern Ireland ( P < 0.002)
and in cases than in controls ( P < 0.002; P < 0.02 after correction
for the number of tests). We conclude that the P-selectin gene is highly
polymorphic and hypothesize that the Pro715 variant may be protective for
MI. Whether this variant affects the properties of the P-selectin protein
in a way which is compatible with this hypothesis needs to be checked
experimentally.
相似文献
20.
Glycoproteins present in human follicular fluid that inhibit the zona- binding capacity of spermatozoa 总被引:1,自引:0,他引:1
Previous studies have suggested that human follicular fluid contains
factors that reduce the zona-binding capacity of spermatozoa. The present
study provides further evidence of the existence of such factors. Using the
hemizona binding assay (HZA), we have shown that the inhibitory effect of
human follicular fluid on the zona-binding capacity of spermatozoa is
concentration-dependent, an inhibitory effect being detected when the
concentration of human follicular fluid was > or = 10%. A 1%
concentration of human follicular fluid did not possess this inhibitory
activity. Heating human follicular fluid at 56 degrees C for 30 min did not
affect its inhibitory properties; treatment with proteinase-K abolished
such inhibition. Human follicular fluid was fractionated sequentially by
concanavalin-A affinity chromatography, Mono Q ion-exchange chromatography
and Superose-12 gel filtration. The zona binding inhibitory activity
resided in the fraction which bound to the lectin and Mono Q column and
contained molecules with native molecular weights of 32 and 192 kDa. Sodium
dodecyl sulphate-polyacrylamide gel electrophoresis analysis suggested that
the 192 kDa glycoprotein was a tetramer, while the 32 kDa glycoprotein
remained as a single molecular species under denaturing conditions. We
conclude that two glycoproteins were responsible for the zona binding
inhibitory activity of human follicular fluid. The physiological role of
these factors remains unclear.
相似文献