Replication of the human hepatitis delta virus genome Is initiated in mouse hepatocytes following intravenous injection of naked DNA or RNA sequences.

As early as 5 days after DNA copies of the hepatitis delta virus (HDV) genome or even in vitro-transcribed HDV RNA sequences were injected into the mouse tail vein using the hydrodynamics-based transfection procedure of F. Liu et al. (Gene Ther. 6:1258-1266, 1999), it was possible to detect in the liver by Northern analyses of RNA, immunoblots of protein, and immunostaining of liver sections what were considered typical features of HDV genome replication. This transfection strategy should have valuable applications for in vivo studies of HDV replication and pathogenesis and may also be useful for studies of other hepatotropic viruses.

Cardiopulmonary exercise response in patients with left ventricular dysfunction or heart failure: a noninvasive study by gas exchange and impedance cardiography monitoring.

We investigated the upright bicycle exercise cardiopulmonary response in 20 patients with left ventricular dysfunction (LVD, secondary to previous myocardial infarction, left ventricular ejection fraction range 18-44%). Ten patients (48 +/- 7 years) asymptomatic (I NYHA class) without drug treatment (LVD group). The others (n = 10) (50 +/- 1 years) complained of dyspnea and/or fatigue despite therapy (NYHA II-III). They represented the heart failure (HF) group. Eight sedentary men (40 +/- 10 years) served as controls. Controls and patients performed stress testings under drug treatment, when administered. Anaerobic ventilatory threshold (ATge) was considered as an index of submaximal exercise while peak exercise VO2 (Peak VO2) was considered the maximal volitional exercise capacity. The ratio between minute ventilation (VE) to carbon dioxide release (VCO2) (VE/VCO2) was assessed to evaluate the ventilatory response during exercise. We coupled gas exchange assessment (2001, MGC) with noninvasive monitoring of stroke volume (SV) by impedance cardiography (NCCOM3, BOMED) and total systemic vascular resistances (TSVR; by auscultatory blood pressure measurement). In controls VO2 increase during exercise was related to higher heart rate (HR) and SV both from resting to ATge and from this point to the peak. TSVR declined during both steps. In patients with HF VO2 rose from resting to ATge (by faster HR and unchanged SV). VO2 increased slightly from this point to Peak VO2. This result was related to flat HR increase and unchanged SV as well as TSVR. In patients with LVD VO2 increased similarly to controls from resting to ATge and less above the threshold. In these patients both HR and SV increased during submaximal exercise. From ATge to Peak VO2 only HR increased. TSVR declined significantly similarly to controls. The VE/VCO2 ratio was higher at peak exercise in patients with HF compared to controls. Different determinants were demonstrated in patients with left ventricular dysfunction with mild or symptomatic chronic heart failure (CHF). These findings and the increased ventilatory response in patients with CHF can explain different changes of VO2 in these patients during submaximal and maximal voluntary exercise and contribute to explain exercise-induced exertion in these subjects.

[In vitro mucociliary clearance: observations in subjects exposed to acute inhalation of nitrous vapors]. / La clearance mucociliare in vitro: osservazioni su soggetti esposti ad inalazione acuta di vapori nitrosi.

Acute inhalation of nitrous vapours did not cause any damage to the respiratory apparatus detectable via spirometric or X-ray tests in the four workers who were actually exposed and kept under observation during the two months following the explosion of a tank containing nitric acid. However, measurement of the coefficient of relative transport speed in vitro of tracheo-bronchial secretions revealed alterations of the mucus related to specific situations, such as during acute inhalation of nitrous vapours and upon resuming work. The coefficient of relative speed, obtained with the in vitro technique on the palate of the frog, thus proved to be reliable in monitoring irritation of the mucus secreting apparatus of workers accidentally exposed to acute inhalation of nitrous vapours.

[Total and partial O2 and CO2 ductances in workers exposed to inhalation of cement-asbestos]. / Misura delle duttanze globali e parziali ad O2 e CO2 in lavoratori esposti ad inalazione di cemento-amianto.

The aim of the study was to assess the efficiency of the respiratory system in ensuring the correct dynamics of respiratory gases in subjects chronically exposed to the inhalation of asbestos-cement dust but not yet suffering from parenchymal asbestosis, via measurement of total and partial O2 and CO2 ductance coefficients (Du). Two groups of male workers of working age were selected, the first consisting of 22 workers employed on the manufacture of asbestos-cement products, the second consisting of 26 workers who had never been exposed to the inhalation of significant concentrations of occupational respiratory irritants. The two groups were comparable for age, smoking, and normal spirometric parameters for FVC, FEV1 and PEF, and were free of any type on interstitial lung disease according to ILO standards. In the exposed group, all O2 and CO2 ductance coefficients were significantly lower than in the non-exposed, except DuBCO2 (alveolar-capillary ductance for CO2). Measurement of O2 and CO2 lung ductances at rest thus revealed an impairment of the diffusion and of the interpulmonary exchange of blood and air in subjects chronically exposed to the inhalation of asbestos-cement dust. In the sample under study, such impairment preceded lung damage detectable by spirometric and radiological tests and was an obstacle not only to oxygen intake but also to the elimination of carbon dioxide.

Outbreaks of Pneumocystis carinii pneumonia in colonies of immunodeficient mice.

Outbreaks of Pneumocystis carinii pneumonia occurred in colonies of nu/nu and scid/scid mice at four different institutions. The disease, which was characterized by chronic wasting and respiratory insufficiency, was more severe in older mice and in animals housed in cages with special protective tops. Histopathologic features included alveolar filling with the typical foamy honeycomb material and a mild, nonspecific host inflammatory response. Immunofluorescence and immunoblotting studies suggested the P. carinii isolate was of mouse rather than of rat or human origin, and the outbreaks could be related to each other by common vendor or source of breeding animals. Once P. carinii became established in a mouse colony, the organism tended to persist for long periods of time. The principal control measure was depopulation of the colony, although limited experience with the administration of trimethoprim-sulfamethoxazole was encouraging. Thus, outbreaks of pneumocystosis are a serious problem among colonies of immunodeficient mice, with important implications for the use of these animals in biomedical research. Data obtained by studying these outbreaks should enhance understanding of the pathogenesis of P. carinii pneumonia and be helpful in formulating improved methods of detection and control.

Peptido polysaccharide antigens from Trichophyton mentagrophytes var. granulosum.

Two highly purified peptido polysaccharide antigens have been isolated from surface-grown cultures of Trichophyton mentagrophytes var. granulosum. Trichloroacetic acid extraction and ethanol precipitation yielded a mixture containing high-molecular-weight components which were first separated on Sephadex G-200. Subsequent fractionation by ion-exchange chromatography on DE-52-cellulose (borate form) yielded the two peptido polysaccharides. Both of the peptido polysaccharides reacted with rabbit antiserum to T. mentagrophytes var. granulosum. The two peptido polysaccharides contain 73.2% hexoses (mannose-galactose-glucose, 7.5:0.7:1), 8.6% amino acids and 1.8% amino sugars and 77.4% hexoses (mannose-galactose-glucose, 9:0.3:1), 6.2% amino acids, and 0.4% amino sugars, respectively. Each contains 16 different amino acids, threonine, proline, and serine predominating.