The role of upstream U3 sequences in the pathogenesis of simian immunodeficiency virus-induced AIDS in rhesus monkeys

The nef reading frame overlaps about 70% of the U3 region of the 3' long terminal repeat (LTR) in primate lentiviruses. We investigated the functional role of these overlapping U3 sequences by analyzing the properties of three mutant forms of the pathogenic SIVmac239 clone. In mutant UScon, 90 of 275 bp in the upstream sequences (US) of U3 were changed in a conservative fashion without changing the predicted nef coding sequence. In mutant USnon, 101 of 275 bp in this region were changed in a nonconservative fashion, again without changing the predicted nef coding sequence. In mutant delta US, 275 bp in this region were deleted. Full-size, immunoreactive nef protein was synthesized in cells infected with the UScon and USnon mutants. The USnon and delta US mutants replicated with similar kinetics and to similar extents as wild-type, parental SIVmac239 in primary rhesus monkey peripheral blood mononuclear cell (PBMC) cultures. The UScon mutant replicated with slightly delayed kinetics in rhesus monkey PBMC cultures. In the CEMx174 cell line, the delta US mutant replicated similarly to the wild type, but the UScon and USnon mutants replicated with significantly delayed kinetics. Analysis of LTR-driven chloramphenicol acetyltransferase (CAT) activity and the effects of 5-azacytidine on virus replication suggested that the growth defect of the point mutants in CEMx174 cells was due in whole or in part to the introduction of multiple CG methylation sites in proviral DNA. Rhesus monkeys were experimentally infected with the UScon and USnon mutants, and the characteristics of the infection were compared with those of the parental SIVmac239. Analysis of the levels of plasma antigenemia, virus load, and CD4+ cells in PBMC revealed no decreased virulence of the mutant viruses. Analysis of lymph node biopsies taken from animals that received mutant viruses revealed histologic changes and levels of virus expression indistinguishable from those of the wild type. Furthermore, the wild-type behavior of the mutant viruses in rhesus monkeys occurred without any specific reversional events through at least 20 weeks of infection. These results, and the recent results of Kirchhoff et al. (F. Kirchoff, H. W. Kestler III, and R. C. Desrosiers, J. Virol. 68:2031-2037, 1994), suggest that these upstream sequences in U3 are primarily or exclusively nef coding sequence.     

Impact of cross-phase modulation for WDM systems over positive andnegative dispersion NZ-DSF and methods for its suppression

The impact of cross-phase modulation (XPM) is measured on positive and negative dispersion fibre. The exponential build-up of XPM over positive dispersion fibre indicates amplification due to modulation instability. Methods for suppressing XPM crosstalk are also demonstrated     

The spontaneous aortocaval fistula: a complication of the abdominal aortic aneurysm. Case report and review of the literature

AIMS: (i) to compare Helicobacter pylori serology in two 70-year-old cohorts in Gothenburg, Sweden, born 21 years apart, (ii) to study H. pylori serology in a 70-year-old cohort over 20 years. POPULATION AND METHOD: H. pylori serology at the age of 70 was investigated in 98 men and 132 women born in 1901/02 and in 77 men and 113 women born in 1922. In 21 men and 40 women Helicobacter serology was monitored longitudinally with examinations at 70, 81, and 90 years of age. The analyses were performed on frozen samples by use of an in-house enzyme immunoassay with a sensitivity of 0.99, specificity of 1.00 and positive and negative predictive values of 0.96 and 1.00, respectively. Absorbance values <0.500 were interpreted as negative; values of > or = 0.700 were interpreted as positive, and values in between as inconclusive. RESULTS: The 70-year-old cohort, born in 1922, showed a significantly lower proportion of subjects with positive H. pylori serology in both men (57.1% vs 80.6%) and women (48.7% vs 75.8%) compared with 70-year-olds born in 1901/02. There were no significant sex differences in either cohort. No longitudinal increase or decrease could be demonstrated in those who were examined at 70, 81 and 90 years of age. CONCLUSIONS: The difference in H. pylori prevalence between the two cohorts may reflect a rapid change in socio-economic conditions in Sweden during this 20-year period.     

A non-pungent resiniferatoxin analogue, phorbol 12-phenylacetate 13 acetate 20-homovanillate, reveals vanilloid receptor subtypes on rat trigeminal ganglion neurons

Capsaicin, the vanilloid responsible for the pungent taste of hot peppers, binds to receptors found primarily in polymodal nociceptors. Capsaicin initially stimulates polymodal nociceptors and subsequently inhibits them from responding to a variety of stimuli. This property makes it useful clinically as an analgesic and anti-inflammatory compound. There is mounting, albeit indirect, evidence for the existence of several subtypes of vanilloid receptors. One such piece of evidence comes from studying analogues of capsaicin, such as phorbol 12-phenylacetate 13 acetate 20-homovanillate. This compound binds to (capsaicin) vanilloid receptors on sensory neurons, but unlike capsaicin it is non-pungent and does not produce hypothermia. To determine how sensory neurons respond to phorbol 12-phenylacetate 13 acetate 20-homovanillate, and to compare these responses with those evoked by capsaicin, whole-cell patch-clamp measurements were performed on cultured rat trigeminal ganglion neurons. It was found that 63% of the neurons held at -60 mV were activated by 3 microM, phorbol 12-phenylacetate 13 acetate 20-homovanillate, and 87% of these were also activated by 1 microM capsaicin. In a given neuron, phorbol 12-phenylacetate 13 acetate 20-homovanillate, like capsaicin, could activate kinetically distinct inward currents. The current-voltage curves characterizing phorbol 12-phenylacetate 13 acetate 20-homovanillate responses were asymmetric and had reversal potentials at -5.8 +/- 6.0 mV and 10.4 +/- 4 mV. The averaged dose-response curves for phorbol 12-phenylacetate 13 acetate 20-homovanillate were fit to the Hill equation and had binding constants (K(1/2)s) of 2.73 microM and 0.96 microM and Hill coefficients (ns) of approximately 1 for a rapidly- and slowly-activating current, respectively. These parameters are consistent with those obtained from binding experiments and calcium-influx experiments on sensory nerves. Repeated applications of phorbol 12-phenylacetate 13 acetate 20-homovanillate every 3 min caused a complete reduction in the rapidly-activating currents leaving only a reduced slowly-activating current. This provides strong evidence for the independence of these currents and the existence of subtypes of vanilloid receptors. Additional evidence for the existence of receptor subtypes is that 10 microM capsazepine, a specific and competitive inhibitor of capsaicin-evoked responses, did not inhibit the phorbol 12-phenylacetate 13 acetate 20-homovanillate-induced currents in some neurons and partially inhibited them in other neurons. Thus, there are capsazepine-sensitive and capsazepine-insensitive subtypes of vanilloid receptors. In summary, we have obtained electrophysiological and pharmacological evidence for distinct subtypes of vanilloid receptors.     

Visual size processing in spatial neglect

Evidence from the use of the landmark task and from two size-matching tasks shows that many patients with left-sided neglect systematically under-perceive visual extent in leftward parts of space. This perceptual distortion of size serves to explain the occurrence of rightward line-bisection errors in most neglect patients. One possibility is that attentional biases of a chronic nature might underlie these perceptual changes seen in neglect patients. But contrary to this idea, we have found that attentional cueing in the landmark task causes changes in neglect patients exactly opposite to those seen in healthy subjects. The distortions of size perception seen in neglect could instead be caused by a high-level alteration of visual processing rather than by an attentional bias. In order to explore which visual stream of cortical processing might be compromised in such a disorder, we have begun to examine neglect patients on visuomotor as well as perceptual tasks. We have found clear evidence in one patient for intact grip scaling for object size in the neglected half of space, despite gross perceptual underestimations of the same objects. This result suggests that neglect can occur without major disruption of the dorsal stream, and may result instead from damage to a cortical system whose predominant visual input comes from the ventral stream.     

Sonographic features of mammary oil cysts

Mammographic lesions that are pathognomonic for oil cysts require no further evaluation. Oil cysts, however, may first be discovered by ultrasonography. Between 1988 and 1995, we performed sonography of 26 oil cysts in 15 patients. Sonography was used to evaluate a palpable finding when an oil cyst was not initially perceived on the mammogram (47%) or as an initial evaluation of a palpable lump (33%); in addition, oil cysts were identified incidentally in 20% of cases. Retrospective review showed that the sonographic appearance of oil cysts is highly variable; only 8% mimic simple apocrine cysts. Twelve percent mimic an intracystic mass. Most have smooth walls (88%), are hypoechoic (65%), and have neither enhancement or shadowing (50%). The sonographic appearance of oil cysts can be suggestive of a pathologic lesion such as an intracystic carcinoma. Unnecessary biopsy can be avoided using directed mammography.     

Further measurements of the 14C-content of fermentation alcohol in dependence of growth times and location of the fermentation material (author's transl)]

The carbon-14 content of ethanol obtained from material (mostly potatoes) grown in the years 1964--1973 is compared with that of material of the vegetation periods 1956--1966 determined by other laboratories. Six ethanol samples from material grown 1973 in different parts of Europe show no significant differences. The average value is 19.3 dpm/g carbon. Furthermore no significant difference was found in ethanol from potatoes cultivated 50--800 m east and west of a freeway with very heavy traffic. The same is true also for ethanol from potatoes grown near a large industrial area and others grown far from such an area.     

Pragmatic Testing Protocols to Measure Software Reliability

This paper investigates four different test protocols based upon the Jelinski-Moranda model of software reliability growth. The main task is to estimate the number of remaining errors in a system at the time of system release. These four protocols are: 1) testing is discontinued after some number of errors has been observed; 2) testing is discontinued at the end of a prescribed period of time; 3) testing is discontinued when a specified amount of time is observed to be completely error free; 4) error checking and debugging is done only by a prespecified time schedule. Two examples with actual failure data illustrate the estimation procedures under different protocols.