Estimation of aneuploidy for chromosomes 3, 7, 16, X and Y in spermatozoa from 10 normospermic men using fluorescence in-situ hybridization

Fluorescence in-situ hybridization (FISH) is a fast and efficient method of estimating aneuploidy in human spermatozoa. In this study, we have estimated baseline disomy frequencies in spermatozoa from a group of 10 normospermic men, using stringent scoring criteria. A triple-probe FISH procedure was used for chromosomes 3, X and Y, while a double-probe FISH method was used for chromosomes 7 and 16. A total of 101273 spermatozoa were scored for chromosomes 3, X and Y, resulting in 97.83% haploidy (3X or 3Y), 0.39% disomy (33X, 33Y, 3XX, 3YY or 3XY) and 0.35% diploidy (33XX, 33YY or 33XY). A total of 100760 spermatozoa were scored for chromosomes 7 and 16, giving 98.9% haploidy (716), 0.11% disomy (7716 or 71616) and 0.27% diploidy (771616). Disomy frequencies for individual chromosomes differed (chromosome 3, 0.20%; chromosome 7, 0.05%, chromosome 16, 0.06%; X + Y, 0.19%). The frequency of disomy 3 was significantly higher than disomy 7 (P = 0.019) and disomy 16 (P = 0.022), while the frequency of sex chromosome disomy was significantly higher than disomy 7 (P = 0.0058) and disomy 16 (P = 0.0067), but not disomy 3 (P = 0.73). The disomy and diploidy (0.27-0.35%) estimates obtained for this normospermic population were generally low and were similar to other recent reports.     

Comparison of the toxicity profiles of ISIS 1082 and ISIS 2105, phosphorothioate oligonucleotides, following subacute intradermal administration in Sprague-Dawley rats

The systemic toxicity of two phosphorothioate oligonucleotides specific for herpes simplex viruses (ISIS 1082) and human papiloma virus (ISIS 2105) were evaluated following repeated intradermal injections of vehicle control, 0.33, 2.17, or 21.7 mg/kg daily to Sprague-Dawley rats (10/sex/group) for 14 days. Animals were sacrificed 1 day after the last dose, except for a portion of the ISIS 1082-treated animals (5/sex/group) which were maintained for an additional 14-day recovery period. The profile of alterations noted for both compounds was very similar. Other than local signs of irritation at the site of injection, there were no clinical signs of toxicity or treatment-related mortality, but there was a slight decrease in body weight gain for the 21.7 mg/kg dose groups. Alterations in hematology parameters included dose-dependent thrombocytopenia and anemia. Alterations in serum chemistry parameters were suggestive of mild alterations in hepatic metabolism, with increases in liver transaminases and bilirubin, along with decreases in albumin and cholesterol. Both spleen and liver weights were significantly elevated in a dose-dependent fashion. Histopathological alterations noted in liver, kidney, lung, injection site skin, and spleen were characterized as perivascular and interstitial infiltrates of macrophages and monocytes. Additional microscopic alterations in the spleen included mild lymphoid hyperplasia (seen in lymph nodes as well), and extramedullary hematopoiesis. Treatment-related cytopenias were likely related to mild, focal hypocellularity in the bone marrow. Alterations in ISIS 1082-treated animals were only partially reversed following the 14-day treatment-free period. In conclusion, repeated intradermal administration of ISIS 1082 and ISIS 2105 produced a similar spectrum of toxicities, with liver, kidney, spleen, and bone marrow being identified as target tissues.     

Membrane currents induced in Xenopus oocytes by the C-terminal fragment of the beta-amyloid precursor protein

There is mounting evidence that at least some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the beta-amyloid precursor protein (beta APP). Most research has focused on the amyloid beta protein (A beta), which has been shown to possess ion channel activity. However, the possible role of other cleaved products of the beta APP is less clear. We have investigated the ability of various products of beta APP to induce membrane ion currents by applying them to Xenopus oocytes, a model system used extensively for investigating electrophysiological aspects of cellular, including neuronal, signalling. We focussed on the 105-amino-acid C-terminal fragment (CT105) (containing the full sequence A beta), which has previously been found to be toxic to cells, although little is known about its mode of action. We have found that CT105 is exceedingly potent, with a threshold concentration of 100-200 nM, in inducing nonselective ion currents when applied from either outside or inside the oocyte and is more effective than either beta APP or the A beta fragments, beta 25-35 or beta 1-40. The ion channel activity of CT105 was concentration dependent and blocked by a monoclonal antibody to A beta. These results suggest the possible involvement of CT105 in inducing the neural toxicity characteristic of AD.     

Inhaled albuterol does not inhibit cellular influx or lung injury produced by segmental antigen challenge in humans

Many experimental protocols and published guidelines for performing bronchoscopy, bronchoalveolar lavage (BAL), bronchial biopsies, and segmental antigen challenge (SAC) of allergic asthmatic subjects recommend treating subjects with a beta-agonist prior to the procedure. However, the effect of beta-agonist pretreatment has not been reported. In a retrospective analysis of ragweed allergic subjects undergoing bronchoscopy, SAC, and BAL, we examined the effect of albuterol pretreatment on cellular influx and lung injury produced by antigen challenge. Forty-eight subjects, 17 who received no pretreatment and 31 who received four puffs of albuterol prior to bronchoscopy, comprised the study groups. No parameter monitored in BAL fluid 24 h after SAC (total cells, macrophages, neutrophils, eosinophils, lymphocytes, total protein, albumin, or eosinophil cationic protein) differed in subjects pretreated with albuterol when compared with subjects who were not pretreated. Although additional, prospective studies are warranted, we conclude that beta-agonist pretreatment of experimental subjects does not alter many aspects of the inflammatory response produced by SAC.     

Cytological characteristics, elemental composition of alveolar macrophages from bronchoalveolar lavage, lung pathology in liquidators of the consequences of the accident at the Chernobyl power plant

Tuberculosis is an ancient disease which has had a resurgence in the United States. Many elderly clients were exposed to tuberculosis as children and young adults and are still carrying the infection today. This article describes tuberculosis as it affects the elderly client in community and nursing home settings. The history, etiology, clinical manifestations, treatment, and prevention of tuberculosis infection and disease are presented. Because nurses can be very instrumental in controlling tuberculosis in the elderly, gerontological nursing implications are discussed.     

Evaluation of [11C]RTI-121 as a selective radioligand for PET studies of the dopamine transporter

The cocaine analogue RTI-121 (3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester), when labeled with carbon-11, was evaluated in rats as a potential PET ligand for the dopamine transporter. The compound gave in vivo striatum:cerebellum ratios that were similar to those obtained with the related ligand [11C]RTI-55 (2 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester) but showed a much greater selectivity for the dopamine compared with the 5-HT uptake site. The results indicate that [11C]RTI-121 could be used in preference to [11C]RTI-55 in man. Experimentally, [11C]RTI-121 has potential in the quantification of dopamine terminal function in rat models of disease, using a combination of autoradiography, postmortem sampling, and in vivo tomography.     

Closure of an iatrogenic femoral artery pseudoaneurysm by transcutaneous coil embolization

Pseudo-aneurysm following diagnostic or interventional procedures is a well-recognized complication. Ultrasound guided compression repair is routinely used to close an uncomplicated pseudo-aneurysm. We describe a patient with a femoral artery pseudo-aneurysm following iliac angioplasty and stenting in which ultrasound guided compression repair failed. Pseudoaneurysm was successfully closed by transcutaneous coil embolization technique.     

Invasive streptococcal infection as a complication of chickenpox

Two girls aged 11 months and 6 years, presented with an invasive group A streptococcal (GAS) infection during the course of primary varicella. The infant had severe cellulitis of the left arm and leg, fever and bacteraemia. She developed osteomyelitis of ulna and tibia. The 6-year-old girl had a fever > 38.5 degrees C, hypotension, an acute respiratory distress syndrome, liver function abnormalities, and positive cultures of blood and joints. Her clinical picture was compatible with a GAS-associated toxic shock syndrome. If during the course of primary varicella persistent fever, secondary fever or pain in one or more extremities occurs, invasive bacterial infection by GAS or Staphylococcus aureus should be considered, even in the absence of skin infection or cellulitis.