Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Actuarial survival in the premature infant less than 30 weeks' gestation

OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants.     

Antisense RNA-mediated reduction of p53 induces malignant phenotype in nontumorigenic rat urothelial cells

p53 mutation is commonly associated with high-grade, high-stage human urothelial carcinomas. Recent studies suggest that p53 mutation in low- grade, low-stage bladder carcinomas may be correlated with the progression of the disease. In the present study, we used antisense RNA methodology in vitro to evaluate the significance of the loss of p53 function at an early stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA in antisense orientation. The transfection resulted in a significant reduction in p53 mRNA expression and protein synthesis, in stimulation of anchorage- dependent growth, and in acquisition of anchorage-independent growth potential. Three such clones, when tested in athymic nude mice, all formed muscle-invasive, high-grade transitional cell carcinomas at s.c. injection sites. When cells were inoculated into an orthotopic site (urinary bladder), one of two antisense transfectants tested formed bulky tumors in the bladder in all seven nude mice and metastases to lungs in three of the seven mice. Analysis of these cells revealed a decrease in the expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene product. Phosphorylation of Rb protein was not inhibited when the cells were starved. No significant difference was observed in the expression of p16 protein. In cell cycle analysis, all antisense transfectants tested escaped from G1 arrest by starvation. Furthermore, secretion of interleukin (IL)-6 into culture medium was increased significantly. Treatment with anti-IL-6 antibody suppressed anchorage-dependent growth. This study directly demonstrates that the loss of p53 function at an early stage of urothelial carcinogenesis may result in acquisition of a malignant phenotype by regulating IL-6 production as well as cell cycle related genes.      

Prevalence of Galen's anastomosis: an anatomical and comparative study

An anatomical study of 50 fresh adult human cadavers was performed in order to verify prevalence of Galen's anastomosis (GA) and to evaluate whether factors such as gender, ethnicity, side of the neck, and individual stature may interfere with GA prevalence. The results were analysed using the Chi-square test, Student t-test, and F-Snedecor test. GA was observed in 87 of 100 dissections. There was no statistically significant difference regarding GA prevalence between groups separated by ethnicity (p = 0.853), gender (p = 0.198), side of the neck (p = 0.766), or individual height (p = 0.199). Therefore, the GA was a frequent anatomical finding, and this result was not influenced by any studied factor. Comparing our data with previous studies, we also concluded that the GA seems to play an important role in the innervation of the larynx, even though its function remains unclear. Also, it is reasonable to consider GA a constant anatomical constituent.     

Study of immunohistochemical expression of insulin-like growth factor I and proliferating cell nuclear antigen in thyroid gland papillary carcinoma and its metastasis

BACKGROUND: Several tumor factors are associated with papillary thyroid cancer. Most studies do not compare the expressions of these factors in the primary tumors and in their associated cervical metastasis. METHODS: Paraffin sections of 20 patients with papillary carcinoma of the thyroid gland with lymph node metastasis were studied. The presence and distribution of insulin-like growth factor I (IGF-I) and proliferating cell nuclear antigen (PCNA) was analyzed, through immunohistochemical technique, in both primaries and lymph node metastasis. The results were correlated with clinical-pathologic data (sex, age, size of primary, multicentricity, thyroid capsule invasion, lymphatic and blood vessels invasion, development of distant metastasis, and associated thyroid diseases). RESULTS: The qualitative analysis showed the reaction for IGF-I was present in more than 90% of the neoplastic cells in both primaries and lymph node metastasis. No correlation with the clinical-pathological features was observed. Regarding the PCNA, the mean percentage of nuclei stained showed no statistical difference between primaries and metastasis (p = 0.598). Except for age, clinicopathologic data had no influence on the mean percentage of nuclei stained. A correlation was verified between the percentage of cells stained by PCNA in primary tumors and the patients' age (p < 0. 01). CONCLUSIONS: The expressions of these tumor factors are equally intense for both primary and metastatic tissue in papillary thyroid cancer. Despite the small size of the sample, the expressions of IGF-I and PCNA could not be associated to clinical-pathologic features, except for the age. As patients over 40 years old had higher expression of PCNA, this marker may have prognostic significance for patients with papillary thyroid cancer.     

Simplified estimates of ion-activity products of calcium oxalate and calcium phosphate in mouse urine

This study aimed at formulating simplified estimates of ion-activity products of calcium oxalate (AP(CaOx)) and calcium phosphate (AP(CaP)) in mouse urineto find the most important determinants in order to limit the analytical work-up. Literature data on mouse urine composition was used to determine the relative effect of each urine variable on the two ion-activity products. AP(CaOx) and AP(CaP) were calculated by iterative approximation with the EQUIL2 computerized program. The most important determinants for AP(CaOx) were calcium, oxalate and citrate and for AP(CaP) calcium, phosphate, citrate, magnesium and pH. Urine concentrations of the variables were used. A simplified estimate of AP(CaOx) (AP(CaOx)-index(MOUSE)) that numerically approximately corresponded to 10(8) × AP(CaOx) was given the following expression:[Formula: see text]For a series of urine samples with various composition the coefficient of correlation between AP(CaOx)-index(MOUSE) and 10(8) × AP(CaOx) was 0.99 (p = 0.00000). A similar estimate of AP(CaP) (AP(CaP)-index(MOUSE)) was formulated so that it approximately would correspond numerically to 10(14) × AP(CaP) taking the following form:[Formula: see text]For a series of variations in urine composition the coefficient of correlation was 0.95 (p = 0.00000). The two approximate estimates shown in this article are simplified expressions of AP(CaOx) and AP(CaP). The intention of these theoretical calculations was not to get methods for accurate information on the saturation levels in urine, but to have mathematical tools useful for rough conclusions on the outcome of different experimental situations in mice. It needs to be emphasized that the accuracy will be negatively influenced if urine variables not included in the formulas differ very much from basic concentrations.     

BKCa Channel Activation Attenuates the Pathophysiological Progression of Monocrotaline-Induced Pulmonary Arterial Hypertension in Wistar Rats

Cardiovascular Drugs and Therapy - In the present study, the therapeutic efficacy of a selective BKCa channel opener (compound X) in the treatment of monocrotaline (MCT)-induced pulmonary arterial...     

First report and molecular characterization of hepatitis E virus infection in renal transplant recipients in Brazil

Hepatitis E virus (HEV) causes acute and chronic hepatitis in organ transplant recipients. Serological evidence for HEV infection has been discovered in various population groups in Brazil, and a single acute case has been confirmed. To date, however, no cases of HEV infection in immunocompromised patients have been reported in Brazil. This study aimed to identify and characterize hepatitis E cases in renal transplant recipients in Brazil. A retrospective study was performed on 96 serum samples from renal transplant recipients with unexplained liver enzymes elevation. Three confirmed cases of HEV infection were identified that lacked seroconversion to HEV IgG antibodies. The prevalence of HEV in these patients was 3.1%. Using a sequence analysis of a 304‐nucleotide fragment within ORF2, the strains were classified as genotype 3 with a low percent identity to previously characterized strains. This is the first report of hepatitis E infection in renal transplant recipients in Brazil, and the data indicate that a novel genotype 3 subvariant may be present and that further investigation is necessary to characterize the circulating HEV strains. In this setting, HEV infection should be considered as a potential cause of abnormal liver tests of unknown origin. J. Med. Virol. 85:615–619, 2013. © 2013 Wiley Periodicals, Inc.