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41.
Reference ranges for serum C4 concentrations in subjects with and without C4 null alleles. 总被引:4,自引:0,他引:4
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Serum C4 concentrations were measured in 102 healthy subjects and 90 subjects with type I diabetes mellitus. A wide range was observed in the group as a whole (0.08-0.67 g/l; mean = 0.26 g/l; SEM = 0.01 g/l). After C4 allotyping it was possible to subgroup 134 of these subjects according to the number of C4 null alleles present. C4 concentrations in the group with two null alleles were lower than in the group without null alleles (mean 0.2 v 0.37 g/l; p less than 0.001). C4 concentrations in the group with one C4 null allele were intermediate and significantly different from those of the group without null alleles (mean 0.24 v 0.37 g/l; p less than 0.001). Appropriate analysis has defined reference ranges for serum C4 concentrations in subjects with two, one, or zero C4 null alleles. Interpretation of low serum C4 concentrations should take account of the number of C4 null alleles present. 相似文献
42.
J T Yarrington D J Sprinkle D E Loudy K A Diekema P P McCann J P Gibson 《Experimental and molecular pathology》1983,39(3):300-316
Subacute (2 week) oral or intravenous administration of DL-alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), caused diarrhea and frequent emesis as early as 4 to 5 days in dogs (dose greater than or equal to 200 mg/kg/day). Diarrhea also occurred in monkeys after 1 week of treatment with an intravenous dose of 1000 mg/kg/day. Especially evident in the treated dogs with diarrhea were fluid loss, hemoconcentration, and decreased serum sodium and chloride which were findings totally reversible about 2 weeks after cessation of dosing. As a result of treatment with the highest intravenous dosage (1000 mg/kg/day), villous atrophy of the mucosa was observed by light and scanning electron microscopy in the canine small intestine. Transmission electron microscopy demonstrated that the most significant alterations of the canine intestinal tract involved the microvilli of epithelial cells which became shorter and were frequently less numerous or absent along focal areas of the plasma membrane. Intestinal mucosal levels of putrescine, especially in the duodenum and jejunum, were decreased as demonstrated in the monkeys following intravenous treatment with 100, 300, or 1000 mg/kg/day of DFMO. The results of this investigation are consistent with the hypothesis that the inhibition of ODC activity and subsequent altered polyamine metabolism may lead to delayed maturation of the intestinal epithelial cells and the impaired development of their microvilli, causing fluid loss due to reduced absorptive surface area. 相似文献
43.
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
44.
The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene 总被引:4,自引:2,他引:4
45.
Mahadevaiah SK; Odorisio T; Elliott DJ; Rattigan A; Szot M; Laval SH; Washburn LL; McCarrey JR; Cattanach BM; Lovell-Badge R; Burgoyne PS 《Human molecular genetics》1998,7(4):715-727
An RNA-binding motif (RBM) gene family has been identified on the human Y
chromosome that maps to the same deletion interval as the 'azoospermia
factor' (AZF). We have identified the homologous gene family (Rbm) on the
mouse Y with a view to investigating the proposal that this gene family
plays a role in spermatogenesis. At least 25 and probably >50 copies of
Rbm are present on the mouse Y chromosome short arm located between Sry and
the centromere. As in the human, a role in spermatogenesis is indicated by
a germ cell-specific pattern of expression in the testis, but there are
distinct differences in the pattern of expression between the two species.
Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are
female due to a position effect resulting in non-expression of Sry ;
sex-reversing such mice with an Sry transgene produces males with a high
incidence of abnormal sperm, making this the third deletion interval on the
mouse Y that affects some aspect of spermatogenesis. Most of the copies of
Rbm map to this deletion interval, and the Yd1males have markedly reduced
Rbm expression, suggesting that RBM deficiency may be responsible for, or
contribute to, the abnormal sperm development. In man, deletion of the
functional copies of RBM is associated with meiotic arrest rather than
sperm anomalies; however, the different effects of deletion are consistent
with the differences in expression between the two species.
相似文献
46.
47.
Murphy M Mabruk MJ Lenane P Liew A McCann P Buckley A O Flatharta C Hevey D Billet P Robertson W Javed S Leader M Kay E Murphy GM 《Journal of clinical pathology》2002,55(11):829-833
AIM: Ultraviolet light (UV) is known to cause DNA damage in the epidermis. The damaged DNA is repaired or deleted by apoptosis to prevent the generation of cancer. It has been suggested that a deficient apoptotic mechanism may predispose individuals to skin cancer. Therefore, the response of normal controls and patients with basal cell carcinoma (BCC) to UV irradiation was investigated. METHODS: The buttock skin from normal volunteers and patients with BCC was irradiated using solar simulated radiation (SSR). SSR mimics the effect of natural sunlight. Skin biopsies were excised and examined for p53, p21, and Bax protein expression and for the induction of apoptosis. RESULTS: At 33 hours after UV irradiation, the induction of apoptosis was significantly higher (p = 0.04) in patients with BCC than in normal volunteers (Mann Whitney test). A trend towards higher p21 expression was found at 33 hours in patients with BCC (mean, 18.69 positive cells/field) than in normal volunteers (mean, 9.89), although this difference was not significant (p = 0.05 positive cells/field). CONCLUSION: These results may imply that patients with BCC have enhanced sensitivity to UV irradiation or that there is some defect in the cell arrest or repair pathways, which results in damaged cells been pushed into apoptosis rather than repair. 相似文献
48.
L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns 总被引:8,自引:3,他引:8
Fransen E; D'Hooge R; Van Camp G; Verhoye M; Sijbers J; Reyniers E; Soriano P; Kamiguchi H; Willemsen R; Koekkoek SK; De Zeeuw CI; De Deyn PP; Van der Linden A; Lemmon V; Kooy RF; Willems PJ 《Human molecular genetics》1998,7(6):999-1009
L1 is a neural cell adhesion molecule mainly involved in axon guidance and
neuronal migration during brain development. Mutations in the human L1 gene
give rise to a complex clinical picture, with mental retardation,
neurologic abnormalities and a variable degree of hydrocephalus. Recently,
a transgenic mouse model with a targeted null mutation in the L1 gene was
generated. These knockout (KO) mice show hypoplasia of the corticospinal
tract. Here we have performed further studies of these KO mice including
magnetic resonance imaging of the brain, neuropathological analysis and
behavioral testing. The ventricular system was shown to be abnormal with
dilatation of the lateral ventricles and the 4th ventricle, and an altered
shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the
KO mice is hypoplastic. Their exploratory behavior is characterized by
stereotype peripheral circling reminiscent of that of rodents with induced
cerebellar lesions.
相似文献
49.
This study provides the first psychophysiological analysis of narcissism by measuring autonomic responses during active and passive anticipatory coping in 40 undergraduate men who scored high or low on the Narcissistic Personality Inventory (NPI). Compared to the low NPI group, the high NPI group showed greater preejection period (PEP) shortening, cardiac deceleration, and skin conductance response (SCR) habituation during anticipation of an aversive stimulus (p < .02). As expected, SCR and PEP reactivity were greater during active than passive coping. In the case of PEP, this effect emerged only in the low NPI group; the high NPI group showed the greatest PEP reactivity during the first task, regardless of coping demands. These data support hypothesized relationships among narcissism, psychopathy, and psychological predictors of cardiovascular disease, and suggest that a psychobiological dimension may underlie important features of narcissism. 相似文献
50.