It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.
Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI])?=?0.64 [0.47–0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value?=?0.003). OS did not differ significantly, with a HR of 0.82 [0.54–1.27] for ceritinib compared to crizotinib.
Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC. 相似文献
Stroke produces a wide range of mental and emotional disorders. Neuropsychiatric complications associated with stroke may have negative effects on the social functioning, overall quality of life and the recovery of motor functioning of stroke survivors.
Objective
To determine the prevalence and nature of psychiatric morbidity among stroke patients attending neurology outpatient clinic of the University of Ilorin Teaching Hospital (UITH), Ilorin-Nigeria.
Methods
All patients with stroke aged 18 years and above at an outpatient neurology clinic in Ilorin, Nigeria were assessed for mental and emotional disorders using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) over one year (March 2009 to February 2010).
Results
Overall prevalence of psychiatric morbidity was 36.0% (30/83) among 83 patients who constituted the study population. Specific diagnoses recorded were depression (19.2%), generalised anxiety disorder (9.6%), harmful alcohol use (2.4%); dementia, somatoform disorder, phobia and delusional disorder each had a prevalence of 1.2%. Clinical and sociodemographic variables were not significantly associated with psychiatric morbidity.
Conclusion
Psychiatric disorders are often associated with stroke. Identifying and treating stroke patients with these psychiatric co-morbidities could thus help to improve the overall quality of life of these patients. 相似文献
We developed a model of herpetic orchitis in guinea pigs. Intratesticular inoculation of type 2 herpes simplex virus suspension
results in infection of the testicular spermatocytes and spermatides. The possibility of viral infection dissemination from
infected into intact testis is proven.
__________
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 7, pp. 79–83, July, 2007 相似文献
Prion disease is a neurodegenerative malady, which is believed to be transmitted via a prion protein in its abnormal conformation
(PrPSc). Previous studies have failed to demonstrate that prion disease could be induced in wild-type animals using recombinant
prion protein (rPrP) produced in Escherichia coli. Here, we report that prion infectivity was generated in Syrian hamsters after inoculating full-length rPrP that had been
converted into the cross-β-sheet amyloid form and subjected to annealing. Serial transmission gave rise to a disease phenotype
with highly unique clinical and neuropathological features. Among them were the deposition of large PrPSc plaques in subpial and subependymal areas in brain and spinal cord, very minor lesioning of the hippocampus and cerebellum,
and a very slow progression of disease after onset of clinical signs despite the accumulation of large amounts of PrPSc in the brain. The length of the clinical duration is more typical of human and large animal prion diseases, than those of
rodents. Our studies establish that transmissible prion disease can be induced in wild-type animals by inoculation of rPrP
and introduce a valuable new model of prion diseases. 相似文献
Summary Using an indirect lymphokin-assay, the leucocyte-migration-inhibition-test (LMI-test), the cellular sensitization of fertile
and infertile patients before and after homologous and heterologous intrauterine insemination (IUI) was investigated. In this
assay several preparations of spermatozoa (“washed”-, “swim-up”- and “pellet”-spermatozoa) in different concentrations (1,
5 and 10×106 sperms/ml culture medium) and seminal plasma were tested as antigen. In all investigated groups a cellular immune response
against spermatic antigen was demonstrable and seemed to be dose dependent. In contrast to fertile women who reacted with
an enhancement of the macrophage migration for low concentrations the same concentration of antigen induced an inhibition
of macrophage migration in fertile patients. For high concentrations of spermatic antigens there was a difference in the intensity
of cell-mediated immune response between fertile and infertile women. Since infertile patients demonstrated an increased level
of cell-mediated immune response it is possible that infertility may be caused by this altered immunological reaction. This
response changes after multiple IUI-treatment and that change might be caused by the high concentration of spermatic antigens
as there was a difference in the intensity of cell-mediated immune response between fertile and infertile women. Since infertile
patients demonstrated an increased level of cell-mediated immune response it is possible that infertility may be caused by
this altered immunological reaction. This response changes after multiple IUI-treatment and that change might be caused by
the high concentration of spermatozoa. The immunological response of infertile patients seems to be similar in those receiving
husband and donor IUI. 相似文献