Enhancement of porcine circovirus 2 replication in porcine cell lines by IFN-gamma before and after treatment and by IFN-alpha after treatment.

Stimulation of the porcine immune system causes increased replication of porcine circovirus 2 (PCV2) in vivo. In the present study, we investigated whether various cytokines (interleukin-1 [IL-1], IL-6, IL-10, tumor necrosis factor-alpha [TNF-alpha], interferon-alpha [IFN-alpha], and IFN-gamma) are able to influence PCV2 infection in vitro. No changes were observed in IL-1, IL-6, TNF-alpha, or IL-10-treated cells. However, it was demonstrated that IFN- alpha and IFN-gamma influenced PCV2 infection in porcine kidney cells (PK-15) and porcine monocytic cells (3D4/31). IFN-gamma added to the culture medium before, during, or after inoculation increased the number of PCV2 antigen- positive cells, respectively, by 418%, 171%, and 691% in PK-15 cells and by 706%, 114%, and 423% in 3D4/31 cells. IFN-alpha pretreatment decreased the number of infected PK-15 cells. When it was added after inoculation, IFN-alpha enhanced PCV2 infection by 529% in PK-15 cells and by 308% in 3D4/31 cells. The effect of both IFNs on PCV2 infection was dose dependent and could be blocked with IFN-alpha or IFN-gamma neutralizing antibodies. Leukocyte-derived porcine IFN-gamma induced a similar effect on PCV2 infection. Treatment of PK- 15 cultures with IFN-gamma caused a 20 times higher production of progeny virus. Confocal microscopy studies showed that the enhancing effect of IFN-gamma on PCV2 infection was achieved by increased internalization of PCV2 virionlike particles (VLPs). Binding of the VLPs to the cell or expression kinetics of PCV2 proteins in infected cells were not altered by IFN-gamma treatment. To our knowledge, this study reports the first enhancement of a viral infection by treatment with type I or type II IFNs.     

Dyspepsie und Helicobacter-pylori-Infektion bei Besch?ftigten eines gro?en Industrieunternehmens Ergebnisse der prospektiven BASF-Helicobacter-pylori-Vorsorgeaktion

Zusammenfassung Hintergrund: Die Assoziation zwischen Helicobacter-pylori-(H.-pylori-)Infektion und Dyspepsie wird kontrovers diskutiert. Im Rahmen der BASF-H.-pylori-Vorsorgeaktion wurde u. a. die Prävalenz von Dyspepsie bei arbeitsfähigen Personen ermittelt sowie der Zusammenhang mit der H.-pylori-Infektion und der Erfolg einer Eradikationstherapie untersucht. Probanden und Methodik: 6 132 Beschäftigte der BASF wurden untersucht und im Rahmen einer standardisierten Anamnese u. a. zu dyspeptischen Beschwerden befragt. Diese wurden entsprechend der führenden Symptomatik den Dyspepsiesubtypen vom Ulkustyp, Dysmotilitätstyp, Refluxtyp und unspezifischen Typ zugeordnet. Bei allen Beschäftigten wurde die Seroprävalenz (IgG-ELISA) der H.-pylori-Infektion bestimmt. Allen H.-pylori-positiven Personen mit Dyspepsie wurde weitere Diagnostik in Form einer Ösophagogastroduodenoskopie und einer Sonographie des Abdomens bei Fachärzten empfohlen und eine H.-pylori-Eradikationstherapie (Italian-Triple-Therapie) angeboten. In einer Untergruppe endoskopisch untersuchter Beschäftigter mit peptischer Ulkuskrankheit (PUD, n = 37) bzw. Non-Ulcer-Dyspepsie (NUD; n = 39) wurde der prognostische Wert der im Western Blot ermittelten Antikörper gegen CagA und VacA untersucht. Ergebnisse: 1 255 der 6 143 Beschäftigten (20,4%) berichteten über Dyspepsie. 492 Personen mit Dyspepsie (39,2%) waren gleichzeitig H.-pylori-positiv. Bei Personen ohne dyspeptische Symptome betrug die H.-pylori-Prävalenz 35,8%. Personen mit unterschiedlichen Dyspepsiesubtypen unterschieden sich nicht hinsichtlich der H.-pylori-Prävalenz. Personen, die häufige und intensive dyspeptische Beschwerden angaben, waren allerdings signifikant häufiger H.-pylori-positiv (OR 2,09, CI 1,43-3,05). Die Seroprävalenz von CagA und VacA bei Personen mit PUD unterschied sich nicht signifikant von derjenigen bei Personen mit NUD. 458 H.-pylori-positiven Personen wurde die Eradikation empfohlen. 330 Personen (72,1%) folgten der Empfehlung. 128 (27,9%) ließen sich nicht behandeln. An der Nachkontrolle nach 12 Monaten nahmen 402 Personen (87,8%) teil, davon waren 300 behandelt, 102 nicht. Der serologisch analysierte Eradikationserfolg lag bei 81,5%. 42,8% der erfolgreich behandelten Personen berichteten über Besserung ihrer Beschwerden, 33,2% über Beschwerdefreiheit. Bei den nicht behandelten Personen war dies nur in 16,7% bzw. in 37,3% der Fall. Vermehrte Refluxbeschwerden traten nach erfolgreicher Eradikation nicht auf. Schlussfolgerung: Wir konnten keinen generellen Zusammenhang zwischen Dyspepsie und H.-pylori-Infektion in einem großen Kollektiv arbeitsfähiger Personen erkennen. Häufige und intensive dyspeptische Symptome scheinen allerdings ein prädikativer Faktor für die H.-pylori-Seropositivität zu sein. Die serologisch bestimmbaren Virulenzfaktoren tragen nicht zur Unterscheidung PUD oder NUD bei. Die Eradikationstherapie führte nach 1 Jahr zwar häufiger zur Besserung, aber nicht häufiger zu Beschwerdefreiheit bei Beschäftigten mit dyspeptischen Beschwerden im Vergleich zu unbehandelten Personen. Abstract Background: The role of Helicobacter pylori (H. pylori) infection in dyspepsia is controversial. In the course of a health initiative within a large industrial corporation, we investigated the prevalence of both dyspepsia and positive H. pylori serology and the outcome of eradication therapy in symptomatic H. pylori positive employees. Test Persons and Methods: H. pylori serology (IgG ELISA) was determined in 6,143 employees of BASF AG Ludwigshafen/Germany who were also asked to complete a standardized health history administered by a physician. Peptic ulcer disease (PUD) and dyspepsia subgroups were defined based on past medical history and symptom profiles using the criteria of Heading. Upper GI endoscopy, abdominal ultrasound and eradication therapy (Italian Triple Therapy) was recommended for symptomatic H. pylori positive individuals. The prognostic value of antibodies against CagA and VacA was evaluated in 37 and 39 employees with PUD and non-ulcer dyspepsia (NUD) confirmed by endoscopy, respectively. Results: Of 6,143 employees, 1,255 (20.4%) were classified as dyspeptic, 492 (39.2%) of whom were H. pylori positive. The seroprevalence of H. pylori in asymptomatic employees was 35.8%. There were no significant differences in H. pylori seroprevalence among dyspepsia subgroups (reflux only, dysmotility only, reflux/dysmotility, ulcer-like and non-specific). However, individuals reporting severe dyspeptic symptoms were significantly more likely to be H. pylori positive (OR 2.09, CI 1.43-3.05). The seroprevalence of CagA and VacA was not significantly different among employees with NUD compared to referents or among employees with NUD compared to those with PUD. 330 (72%) of 458 employees with dyspepsia received eradication therapy, 128 persons refused therapy. Based on a 12-month follow-up of 402 individuals (300 of whom had received therapy), eradication success was 81.5% as judged by serology. Of the successfully treated employees, 33.2% reported a total absence and 42.8% reported a decrease in symptoms. Among the employees who refused therapy, the corresponding percentages were 37.3% and 16.7%, respectively. An increase in reflux complaints was not observed among treated employees. Conclusion: In a large active employee population, at most a very weak association was observed between the prevalence of H. pylori seropositivity and dyspepsia. Frequent and severe dyspeptic symptoms were associated with an increased rate of H. pylori seropositivity. The analysis of the virulence factors is not particularly helpful in discriminating PUD or NUD. Eradication of H. pylori infection leads to a decrease in dyspeptic symptoms after 12 months, but not more often to their complete absence compared to untreated individuals.     

Late ultrastructural changes in the retina of the rat following low-dose X-irradiation

This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3–12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glia1 cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss.     

Ankle-brachial index and extent of atherothrombosis in 8891 patients with or at risk of vascular disease: results of the international AGATHA study.

AIMS: AGATHA (a Global Atherothrombosis Assessment) was designed to assess the extent of atherothrombosis and the use of the ankle-brachial index (ABI) in vascular patients. The principal hypotheses were that (1) in diseased patients, a low ABI was related to the number and site of vascular beds affected and (2) in at-risk patients without disease, a low ABI was related to the number of risk factors present. METHODS AND RESULTS: Patients were recruited consecutively by 482 clinicians in 24 countries and the ABI measurement was performed at a single visit. Of 8891 patients recruited, 1792 were defined as at risk and 7099 as with disease. Of the with-disease patients, 65.2% had one arterial bed affected, 27.6% two and 7.1% all three. Abnormal ABI (< or =0.9) was present in 30.9% of at-risk and 40.5% of with-disease patients. A lower ABI was weakly associated with an increasing number of risk factors in at-risk patients (r=-0.056, P=0.02) and with the site and number of arterial beds affected in with-disease patients (P<0.001). CONCLUSION: This large international study confirms that atherothrombotic disease often occurs at more than one site. The ABI is related to the risk factor profile and to the site and extent of atherothrombosis.     

The use of magnetic resonance imaging and spectroscopy in the assessment of patients with head and neck and other superficial human malignancies

The proper demarcation of diseased tissue is important for radiation therapy planning and treatment. The volume to be irradiated is usually identified on radiographs or on x-ray computed tomography (CT) sections. Magnetic resonance (MR)-derived images of the proton T2 relaxation times in small pixel elements, typically 0.5 mm2 or less, provide significantly sharper differentiation between normal and diseased tissue. The T2 values in tissue depend on the tissue composition, histologic condition, and physiologic environment within the tumor. Furthermore, for many tumors the histogram of T2 values has a clear biphasic distribution suggesting that T2 maps may be useful for the identification of necrotic or hypoxic regions within tumors. The distribution of T2 values within the tumor bed shows the general pattern that the T2 values are elevated with a range greater than that seen in normal muscle. Elevated T2 values are not by themselves diagnostic of malignancy; however, they demonstrate the heterogeneity of the microenvironment present within a tumor. The spatial distribution of T2 values is being explored as a method for computer assistance in the delineation of the target volume for treatment planning. In addition, MR P-31 spectroscopic examinations were performed on 30 patients with squamous cell carcinomas of the head and neck. Although hampered by muscle contamination in some P-31 spectra obtained with surface coil profile localization techniques, significant trends can still be appreciated in our data. These trends include the following: (1) the P-31 spectra from malignant tissue have well-resolved spectral lines in the upfield region that correspond to Pi, phosphomonoester (PME), and phosphodiester (PDE) not usually seen in normal muscle; (2) the PDE/B-ATP and PME/B-ATP ratios are greater than unity in all cases; and (3) most of the tumors have higher PME peaks than PDE peaks. The P-31 spectra from patients treated with ionizing radiation changed during and after therapy. Some of the changes could be associated with alteration of the tumor metabolic activity or synthesis and breakdown of lipoproteins. These studies suggest that magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) studies may be useful for both radiotherapy treatment planning and the noninvasive monitoring of patients both before and during treatment.     

Virtual real-time digital processing of hemodynamic data

At present, the majority of cardiac catheterization laboratories acquire and store hemo-dynamic data in analog form. To examine the possibility of performing complex analysis of digital data during the catheterization procedure, we examined whether virtual realtime digital (fast Fourier) analysis improves the accuracy of clinical data. We compared digital filtering of fluid manometry during right heart catheterization with 10-Hz and 250-Hz analog filters. Using the simultaneously acquired micromanometry as the “gold standard,” we found that analog filtering is associated with a greater error and time delay than digital filtering. This study demonstrates that digital hemodynamic data analysis performed during cardiac catheterization can improve the quality of data obtained during right heart catheterization, with the results available within seconds. More extensive use of computers in the cardiac catheterization laboratory may be useful for both clinical and research purposes. © 1992 Wiley-Liss, Inc.     

Exercise induced vasodepressor syncope.

Five cases of exercise induced pure vasodepressor syncope in patients without significant structural heart disease are reported. Hypotension and symptoms of syncope or pre-syncope were induced by treadmill exercise testing and in each case limited exercise performance. Evidence of inappropriate peripheral vasodilation, probably as a consequence of ventricular mechanoreceptor stimulation, was shown in all five patients. Head up tilt testing resulted in hypotension in four patients and isoprenaline infusion in the supine position resulted in hypotension in the fifth. These patients had a new condition of exercise induced neurally mediated (vasodepressor) syncope without appreciable structural cardiac abnormalities.     

The roles of ionic processes in muscular fatigue during intense exercise.

Muscular fatigue is manifested by a decline in force- or power-generating capacity and may be prominent in both submaximal and maximal contractions. Disturbances in muscle electrolytes play an important role in the development of muscular fatigue. Intense muscular contraction is accompanied by an increased muscle water content, distributed in both intracellular and extracellular spaces. This water influx will modify ionic changes in both compartments. Changes in muscle intracellular electrolyte concentrations with intense contraction may be summarised as including decreases in potassium (6 to 20%) and in creatine phosphate (up to 70 to 100%) and increases in lactate (more than 10-fold), sodium (2-fold) and small, variable increases in chloride. The net result of these intracellular ionic concentration changes with exercise will be a reduction in the intracellular strong ion difference, with a consequent marked rise in intracellular hydrogen ion concentration. This intracellular acidosis has been linked with fatigue via impairment of regulatory and contractile protein function, calcium regulation and metabolism. Potassium efflux from the contracting muscle cell dramatically decreases the intracellular to extracellular potassium ratio, leading to depolarisation of sarcolemmal and t-tubular membranes. Surprisingly little research has investigated the effects of intense exercise training on electrolyte regulation and fatigue.     

Early pathological changes in progressive multifocal leukoencephalopathy: a report of two asymptomatic cases occurring prior to the AIDS epidemic

Serial sections of formalin-fixed, paraffinembedded blocks from two asymptomatic, non-AIDS cases of progressive multifocal leukoencephalopathy (PML) were stained with a double-label immunocytochemical method for detection of glial fibrillary acidic protein and JC virus (JCV) capsid proteins and with luxol fast blue/hematoxylin-eosin. In case 1 small, rounded lesions of about 1-mm diameter were seen within a restricted area in the posterior part of the superior frontal gyrus of both cerebral hemispheres, suggesting an early manifestation of the disease. Fully developed demyelinated lesions of the classical type with JCV-infected oligodendrocytes appeared in the white matter and along its border with the cortex. Lesswell-developed lesions, believed to be precursors to the fully developed ones, were seen in the gray and white matter. Of special interest were areas which contained small collections of enlarged, glial fibrillary acidic protein (GFAP)-positive astrocytes without capsid antigen and which seemed to lack destruction of myelin as judged from the appearance of matching serial sections stained for myelin. Large lesions in the brain of case 2 showed the well-known features of advanced PML. The close relation between some astrocytes and oligodendrocytes with viral antigen raises the possibility of early intercellular passage of virus. Vacuolation, seen within or near lesions in both cases, has previously been noted in the CNS infected by HIV, but not in PML. It is suggested that PML, a disease of both oligodendrocytes and astrocytes, may actually begin in astroglial cells which, under the influence of a restricted JCV infection, become reactive, express GFAP and pass on virus to the more highly susceptible oligodendrocytes with which they are in contact.Supported in part by a grant N.S.07596 from the National Institute of Neurological Disorders and Stroke. The work was carried out in the Laboratory of Experimental Neurophathology, NINDS, and in the Department of Pathology II, Karolinska Institute, Stockholm