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.     

Tonsillitis and chronic psoriasis

Although the relationship between streptococcal tonsillitis and acute guttate psoriasis is well recognized, its relationship to chronic forms of psoriasis is less established. In order to explore this further, the authors questioned 35 patients with severe psoriasis and 35 age-matched eczema controls about their history of significant sore throats (i.e. requiring a GP visit) and any resultant worsening of the skin condition. A third of the psoriasis patients reported recurrent sore throats which worsened their skin condition. This was true of only one (3%) of the 35 eczema controls. The authors discuss these findings in the context of recent laboratory work on the association between streptococcal infection and psoriasis.     

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.      

Intrinsic connections in the caudal subdivision of the dorsolateral visual area (DL(C)) in squirrel monkeys

Patterns of intrinsic connections and features of individual intrinsic axons in the caudal subdivision of the dorsolateral visual area (DL(C)) were investigated in four squirrel monkeys (Saimiri) following extracellular injections of the tracers biocytin, biotinylated dextran amine, and wheat germ agglutinin conjugated to horseradish peroxidase. Injections were defined in DL(C) by reference to architectonic borders and patterns of connections with other cortical areas. Intrinsic connections extended up to 6 mm from an injection and were usually anisotropic, extending farther dorsoventrally than anteroposteriorly. Injections that involved the supragranular layers produced up to 20 mainly supragranular patches of projections that had a width of 285 +/- 8 microm (mean +/- standard error) and area of 0.125 +/- 0.016 mm(2). Seventy-four intrinsic axon segments with a total of 3,290 boutons were drawn and their bouton spacing measured. The sample included axons in layers 1, 2-3, 5, and multiple (>2) layers; horizontally and vertically oriented axons; and axons in an injection halo, patch, or nonpatch region of projections. There were no differences in bouton spacing for axons in halo, patch, or nonpatch regions. Layer 1 axons (n = 7) had a significantly sparser distribution of boutons (median interbouton interval of 45.2 +/- 17.8 microm) than the layers 2-3 (n = 35) and layer 5 axons (n = 26), which did not differ in bouton spacing (median interbouton intervals of 8.1 +/- 0.4 microm and 8.4 +/- 0.8 microm, respectively). Patterns of intrinsic connections in DL(C) are related to neural organization and properties reported for DL or visual area V4, and are compared to intrinsic connections of other areas.     

Misuse of anticholinergic drugs by people with serious mental illness

This study assessed misuse of anticholinergic drugs in a population of 50 patients with serious mental illness who were assertively managed by a community-based outreach team in Sydney, Australia. One-third of the subjects reported having misused anticholinergics over the previous month. All anticholinergics were misused, and trihexyphenidyl (benzhexol) was misused most frequently. Most subjects misused at least one other drug as well. On direct questioning, the reason given most frequently was "to get high"; on indirect questioning, reasons were related more to peer participation and feelings of futility. Marginalized patients living in the community are vulnerable to the misuse of anticholinergic drugs.     

Vitronectin and proliferative intraocular disorders. II. Expression of cell surface receptors for fibronectin and vitronectin in periretinal membranes

Several cell types participate in the formation of vitreoretinal traction membranes in proliferative intraocular disorders. The communication between these cells involves hormones, growth factors, and the interaction with extracellular matrix molecules. We have previously demonstrated a partial colocalisation of two potent mediators of cell attachment, fibronectin and vitronectin, in periretinal membranes from patients with proliferative vitreoretinopathy (PVR). We found a similar pattern of vitronectin and fibronectin deposition in proliferative diabetic retinopathy (PDR) (n = 6). Now we show the expression of the corresponding cell surface receptors, integrins, for fibronectin and vitronectin by proliferating cells in 22 periretinal membranes, including traumatic (n = 8) and idiopathic (n = 8) PVR as well as PDR membranes (n = 6). Integrins are membrane receptors for extracellular matrix macromolecules which are involved in such basic biological phenomena as embryogenesis and metastasis. Future studies on the pathogenesis of vitreoretinal proliferation will have to focus on the initiation, maintenance, and regulation of this intercellular communication network involving attachment proteins and integrins.