Comparison of the hybrid capture tube test and PCR for detection of human papillomavirus DNA in cervical specimens.

The strong association of human papillomavirus (HPV) and cervical cancer makes it important to study HPV detection methods that may play a role in cervical cancer screening. We compared two DNA methods that are commonly used for HPV research in the United States: the MY09/MY11 L1 consensus primer PCR-based test and the first-generation Hybrid Capture tube method (HCT). Laboratory assays by each method were performed with 596 cervicovaginal specimens collected from participants in a large cohort study conducted in Portland, Oreg. Included were 499 specimens from women whose cytology was normal and 97 specimens from women with squamous intraepithelial lesions (SILs). The overall HPV DNA positivity for known types was 22.5% by PCR compared to 13.6% by HCT. When the analysis was restricted to the 14 HPV types detectable by both methods, the sensitivity of HCT, with PCR used as the standard for HPV status, was higher for specimens from women with concurrent SILs (81.0%) than for specimens from women with normal cytology (46.7%). Among specimens testing positive by both methods, 97.2% of the time the two methods agreed on whether specimens were positive for cancer-associated HPV types. Both of these HPV test methods provide information that supplements the information provided by the Pap smear. The PCR method has higher analytic sensitivity than HCT in detecting HPV, but HCT may be helpful in identifying women with concurrent SILs.     

The glucocorticoid receptor recognizes a specific nucleotide sequence in hepatitis B virus DNA causing increased activity of the HBV enhancer

The hepatitis B virus (HBV) genome contains a specific DNA binding site for the glucocorticoid receptor. Using DNase I footprinting, this binding site was localized at HBV map positions 341-370 clockwise from the EcoRI site. The DNA sequence protected in the footprint contains two tandem copies of the GRE core hexanucleotide 5'-TGTTCCT-3'. Deletion analysis and reconstruction experiments in plasmid expression vectors demonstrated that this glucocorticoid receptor binding sequence serves as a signal for augmenting glucocorticoid-dependent activity of the HBV enhancer, which is located approximately 730 nucleotides downstream in the HBV genome. Even though it does not serve as an independent enhancer element, the HBV glucocorticoid receptor domain can therefore be categorized as a functional GRE.     

Increased Sensitivity of Lymphocytes from Atopic Individuals to Histamine-Induced Suppression

Histamine depressed lymphocyte reactivity to phytohemagglutinin and, to a lesser degree, concanavalin A, when administered simultaneously with mitogen to lymphocyte cultures. Addition of histamine at later times to the cultures appeared to have a slightly enhancing effect on the lymphocyte response. Stimulation of lymphocytes with pokeweed mitogen was in some cases enhanced, even by high concentrations of histamine. Lymphocytes from atopic individuals were more sensitive to the inhibitory effect of histamine than lymphocytes from nonatopic individuals. The sensitivity appeared age-dependent, but within each age group histamine evoked significantly more suppression on lymphocytes from atopic than from nonatopic individuals. The possibility that the altered reactivity of lymphocytes to histamine, which appears to be associated with atopic allergy, is of pathogenic importance, is discussed, and a hypothesis for the development of atopic disease is proposed.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

1.5-T surface-coil MRI of the knee

Five normal knees and 20 knees with suspected abnormalities involving the menisci or articular surfaces were examined with high-resolution surface-coil MRI. Surgical correlation was available in 15 cases. Signal-to-noise ratios were optimized using a field strength of 1.5 T and a round 7.6-cm surface coil. Spatial resolution was maximized by using fields of view reduced to as small as 8 cm. Separate examinations of the medial and lateral joint compartments were performed with the surface coil positioned vertically adjacent to the meniscus of interest. Ten meniscal tears were identified using sagittal and coronal images. T1-weighted images were adequate to detect most meniscal tears, and T2-weighted images were useful for providing an "arthrogram effect" in the presence of a joint effusion. Extrameniscal lesions that were examined included osteonecrosis of the femoral condyle, subchondral cysts, rheumatoid arthritis, degenerative arthritis, and anterior cruciate ligament tears. MRI was useful in determining the integrity of articular cartilage overlying defects in the subchondral bone and in detecting gross cartilage lesions in arthritis, but was less sensitive than arthroscopy in evaluating moderate changes in the hyaline cartilage.     

Choice of the physiologic implantation site for artificial lenses

The consideration for the choice of intracapsular lens-implantation are presented, and the surgical technique of the implantation of the new Binkhorst "all in the bag" lens is described in detail.