Down-regulation of glial fibrillary acidic protein expression during acute lytic varicella-zoster virus infection of cultured human astrocytes

The effects of the varicella-zoster virus (VZV) OKA vaccine strain in producing morphologic and antigenic changes in dissociated cultures of human fetal brain was investigated. Cultures containing 80% glial acidic fibrillary protein (GFAP), GFAP+ (positive) astrocytes and 20% GFAP- (negative) fibroblastic-like cells were infected with cell-free VZV OKA at a multiplicity of infection of 0.1 plaque-forming units per cell. Cytopathic effects and significant viral antigen labeling with antibodies against VZV gpl and immediate-early (IE) protein 62 were first detected 6 to 7 days postinfection. Several observations indicated that astrocyte GFAP expression was altered and diminished as a result of VZV infection itself, thereby raising doubts about the utility of combining cell markers and viral antigenic labeling in assessing the susceptibility of neural cell types to viral infection. The down-regulation of GFAP expression by VZV appears to be mediated by early rather than late events in the viral replication cycle and may not be the result of virally induced global shut-off of host cell protein synthesis. Similar observations were made using VZV Ellen, a multipassaged, nonvaccine strain. These observations have potential in vivo implications related to histologic analysis of VZV-infected tissues and disease pathogenesis.     

Activity-dependent cortical target selection by thalamic axons

Connections in the developing nervous system are thought to be formed initially by an activity-independent process of axon pathfinding and target selection and subsequently refined by neural activity. Blockade of sodium action potentials by intracranial infusion of tetrodotoxin in cats during the early period when axons from the lateral geniculate nucleus (LGN) were in the process of selecting visual cortex as their target altered the pattern and precision of this thalamocortical projection. The majority of LGN neurons, rather than projecting to visual cortex, elaborated a significant projection within the subplate of cortical areas normally bypassed. Those axons that did project to their correct target were topographically disorganized. Thus, neural activity is required for initial targeting decisions made by thalamic axons as they traverse the subplate.     

Association of high plasma antioxidant capacity with new lesion formation in carotid atherosclerosis: a prospective study

BACKGROUND: In atherosclerosis, both reductions and elevations in plasma levels of antioxidants have been reported. This study investigated total antioxidant capacity of plasma from subjects with atherosclerotic disease. MATERIALS AND METHODS: The study population consisted of 48 men with or without carotid atherosclerosis. At baseline (1990) carotid arteries were evaluated by duplex sonography and plasma samples were obtained for testing antioxidant capacity by two different test systems. One assay system used neutrophils from healthy volunteers as a source of oxygen free radicals activating the non-fluorescent dichlorofluorescin diacetate in the presence of antioxidant containing plasma from study subjects. In the other test system, total plasma antioxidants were detected colorimetrically by using 2,2'-azino-di-(3-ethylbenzthiazoline sulphonate), metmyoglobin and superoxide in the presence of plasma. Carotid arteries were re-evaluated for the development of new plaques 5 years later (1995). RESULTS: Increased baseline total antioxidant capacity of plasma was significantly associated with the development of new atherosclerotic lesions during a period of 5 years. CONCLUSIONS: Endogenous antioxidant capacity of plasma is increased in patients with active atherosclerotic disease. As scavenging of oxygen free radicals is thought to protect from atherogenesis, elevated antioxidative capacity may represent an adaptive mechanism.     

A study of the lethal and sublethal toxicity of polyphase P-100, an antisapstain fungicide containing 3-iodo-2-propynyl butyl carbamate (IPBC), on fish and aquatic invertebrates

Since pneumotachograph masks are commonly used in studies of speech breathing, the purpose of this study was to measure the differences in respiratory volumetric and frequency measures during speech under two conditions: with and without a circumferentially vented pneumotachograph mask coupled to the face. Thus we sought to identify whether changes in breathing patterns occur with the use of a specific face mask, because these patterns are accepted as representative of normal speech breathing. Subjects were 10 normal-speaking women, each of whom produced a syllable train and a connected speech task, both at comfortable intensity levels. Respiratory measures were made using linearized magnetometers during speech production. The measurements included lung volume, rib cage volume, and abdominal volume at utterance initiation and termination, volume excursions during the utterance, and the number of breath groups during the speech task. There were no significant differences between the mask-on and mask-off conditions in volumetric and frequency measures. A significant task difference for abdominal initiation was found. It was concluded that the use of a circumferentially vented pneumotachograph mask does not alter the reliability of respiratory volume and frequency measures for studies of voice.     

Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo

Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis.     

Observer agreement on interpreting colposcopic images of CIN

The purpose of this work was to study intraobserver and interobserver variation in the interpretation of colposcopic images of cervical intraepithelial neoplasia (CIN). Twenty-three experienced colposcopists were asked to assess colposcopic images presented on slides and to select the biopsy site. Eleven cases were independently interpreted twice with an interval of 2-3 months by all observers. No information about the cytological classification was available. In each case the "majority assessment" was considered as the standard, being "no CIN" in 2 cases, CIN I in 4 cases, CIN II in 3 cases, and CIN III in 2 cases. Intraobserver concordance was 66.7%, the kappa value was 0.54. Interobserver agreement was found to be 52.4 and 51.0% in the first and second sessions, respectively, while the mean kappa values were 0.41 and 0.33, respectively. In selecting the site for biopsy, 77.4% of all observers agreed while the same site was selected in 85.3% of cases by the individual colposcopist in the two sessions. Overall, CIN I and II interpretations revealed lower levels of agreement than no CIN or CIN III interpretations. It is concluded that observer variability in interpreting colposcopic images and selecting the site for biopsy is in the same range as observer variation in other subjective diagnostic tests such as cytology and histopathology. This variation should be taken into account in the colposcopical management of patients with abnormal cytology.     

Fuzzy-trace theory and false memory: new frontiers

We describe the origins of fuzzy-trace theory, including Piagetian, interference, information-processing, and judgment and decision-making influences. The contrasting properties of gist and verbatim memory serve as its foundation and, in recent models of spontaneous and implanted false memories, explain seemingly contradictory developmental trends, such as reverse developmental findings, differential time courses for true and false memories, and conflicting effects of trace strength. However, approaches that integrate fuzzy-trace theory with neurological, social, emotional, and motivational perspectives are needed. A method for accomplishing this integration, using the recent models, is introduced and new research that spans these perspectives is discussed. Relations to other contemporary theories, especially source-monitoring and dual-process theories, are also explained. We conclude by rejecting the notion that spontaneous false memories are actually "true" and distinguish gist and verbatim senses of the term "true" that have different consequences in real life.     

Temporal processing of the pitch of complex tones

The effect of tone duration on fundamental frequency (F0) discrimination is greater for complexes containing unresolved harmonics than for those containing resolved harmonics [Plack and Carlyon, J. Acoust. Soc. Am. 98, 1355-1364 (1995)]. Three experiments explored this effect further. The first experiment measured sensitivity (as d') to fundamental frequency (F0) differences for two complexes, both with an F0 of 250 Hz. The first complex was low-pass filtered at 1875 Hz to create a resolved complex and the second was bandpass filtered between 5500 and 7500 Hz to create an unresolved complex. The harmonics for the resolved complex were selected so that no two harmonics were the same between the two observation intervals. Performance for both complexes was measured for tone durations of 20, 40, 80, and 160 ms. For the unresolved complex, the effect of duration was greater than that for the resolved complex and greater than the predictions of a "multiple-looks" model assuming either peripheral (before sampling) or central (after combining samples) sources of variance. The second experiment replicated these results using an F0 of 62.5 Hz with the cutoff frequencies of the bandpass filters divided by four, confirming that the effect is related to resolvability and not to spectral region. In the final experiment, F0 discrimination for pairs of complexes separated by a temporal gap was measured relative to that for one complex. Performance for the resolved and unresolved complexes was similar: Very little effect of gap duration was observed and the results were consistent with the predictions of the peripheral-variance multiple-looks model. Taken together, the results suggest that the pitch mechanism for resolved harmonics uses a relatively short sampling window of around 20 ms, while the mechanism for unresolved harmonics may use a more complex strategy for optimizing the combination of information over time, perhaps involving a flexible integration time.     

The lactulose breath hydrogen test and small intestinal bacterial overgrowth

OBJECTIVES: To i) document the sensitivity and specificity of a combined scintigraphic/lactulose breath hydrogen test for small intestinal bacterial overgrowth and ii) investigate the validity of currently accepted definitions of an abnormal lactulose breath hydrogen test based on "double peaks" in breath hydrogen concentrations. METHODS: Twenty-eight subjects were investigated with culture of proximal small intestinal aspirate and a 10-g lactulose breath hydrogen test combined with scintigraphy. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of overgrowth flora to ferment lactulose were determined. RESULTS: Sensitivity (16.7%) and specificity (70.0%) of the lactulose breath hydrogen test alone for small intestinal bacterial overgrowth were poor. Combination with scintigraphy resulted in 100% specificity, because double peaks in serial breath hydrogen concentrations may occur as a result of lactulose fermentation by cecal bacteria. Sensitivity increased to 38.9% with scintigraphy, because a single rise in breath hydrogen concentrations, commencing before the test meal reaches the cecum, may occur in this disorder. Sensitivity remained suboptimal irrespective of the definition of small intestinal bacterial overgrowth used, the nature of the overgrowth flora, favorable luminal pH, the presence of concurrent gastric bacterial overgrowth, or the in vitro ability of the overgrowth flora to ferment lactulose. CONCLUSIONS: Definitions of an abnormal lactulose breath hydrogen test based on the occurrence of double peaks in breath hydrogen concentrations are inappropriate. Not even the addition of scintigraphy renders this test a clinically useful alternative to culture of aspirate for diagnosing small intestinal bacterial overgrowth.     

Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup

BACKGROUND & AIMS: Antineutrophil cytoplasmic antibodies (ANCA) have been consistently detected in a subgroup of patients with Crohn's disease (CD). This study was designed to determine whether serum ANCA expression in patients with CD characterizes an identifiable clinical subgroup. METHODS: The study population consisted of 69 consecutive patients with an established diagnosis of CD as determined by a combination of characteristic clinical, radiographic, endoscopic, and histopathologic criteria. Sera from the patients were analyzed for the presence of ANCAs using the fixed neutrophil enzyme-linked immunosorbent assay (ELISA) assay. Perinuclear ANCA (pANCA)-positive and cytoplasmic ANCA (cANCA)-positive results by ELISA were confirmed by indirect immunofluorescence staining. Clinical profiles of the ANCA-positive patients with CD were compared with those of patients with CD not expressing ANCA (ANCA-negative). RESULTS: pANCA-positive patients with CD have endoscopically and/or histopathologically documented left-sided colitis and symptoms of left-sided colonic inflammation, clinically reflected by rectal bleeding and mucus discharge, urgency, and treatment with topical agents. One hundred percent of patients with CD expressing pANCA had "UC-like" features. CONCLUSIONS: In patients with CD, serum pANCA expression characterizes a UC-like clinical phenotype. Stratification of CD by serum pANCA provides evidence of heterogeneity within CD and suggests a common intestinal mucosal inflammatory process among a definable subgroup of patients with CD and UC expressing this marker.