Biomedical subjects

M Sniezek

Publications and source records attributed to M Sniezek.

At least 19 recordsLinked to original sources

PubMed1998

Computerised controllers for safety critical medical applications.

A novel design for a computer control system to be employed in safety critical applications, as found in medical environments, is presented. It features a low complexity, fault detecting hardware architecturally supporting a strictly cyclic operating mode, as known from programmable logic controllers, and a specification level, graphical programming technique based on the interconnection of application oriented standard software function modules. By design, there is no semantic gap between the programming and machine execution levels. Thus enabling the safety licensing of application software by an extremely simple but rigorous method, the software verification problem is satisfactorily solved for a large application area, where failures may cause hazards to, or even loss of, human safety and lives.

Computer Systems↗

PubMed1995

Influence of autonomic blockade and aging on AV conduction and responses to verapamil in the beagle.

BACKGROUND: Age-related differences in responses to verapamil have been noted in both intact humans and isolated denervated perfused rat hearts. The study was designed to determine the effects of aging on intracardiac conduction and pharmacodynamic responses to verapamil, and also to determine the potential role of autonomic responses in previously reported age-related differences in responses to verapamil. METHODS: After stability of measures was demonstrated in senescent animals, nine young (aged 3-4 years: 12.3 +/- 2.4 kg; 5 female, four male) and nine senescent (aged 8-11 years: 12.0 +/- 2.2 kg; 5 female, four male) beagles were randomized to undergo 60-minute verapamil infusions during pentobarbital anesthesia alone or after 1 mg/kg propranolol and 0.5 mg/kg atropine. RESULTS: In the nonblocked state, verapamil increased A-A intervals (p < .001), P-R (p < .001), A-H intervals (p < .001), and AV Wenckebach block cycle length (p < .0001) and decreased blood pressure (p < .001) without age-related differences in responses. After autonomic blockade, heart rate and blood pressure decreased (p < .0001) and AV conduction intervals (p < .05) and AV Wenckebach block cycle length increased (p < .006). A-A intervals, A-H intervals, and AV Wenckebach block cycle length were significantly longer in senescent vs young beagles (559 +/- 87 vs 471 +/- 42 msec, p < .002; 103 +/- 6 vs 89 +/- 14, p < .05), 273 +/- 21 vs 238 +/- 26, p < .006, respectively). Verapamil effects on heart rate (p < .001) and AV conduction intervals (p < .007) and diastolic blood pressure (p < .003) were enhanced in younger, but not senescent, beagles after propranolol and atropine. DISCUSSION: Verapamil produced similar effects on heart rate, blood pressure, and AV conduction in young and senescent beagles during barbiturate anesthesia. After double pharmacologic autonomic blockade, heart rate and AV conduction intervals and AV Wenckebach cycle length were significantly longer in senescent beagles when compared to younger beagles. Responses to verapamil after pharmacologic double autonomic blockade were enhanced only in younger beagles, suggesting greater contribution of reflex responses to results during verapamil infusions in the nonblocked state in younger animals.

Aging↗

PubMed1990

Altered release of eicosanoids by rat alveolar macrophages during granulomatous pulmonary inflammation.

Release of arachidonic acid metabolites (eicosanoids) by alveolar macrophages may be important in regulating pulmonary inflammatory reactions. The purpose of this study was to characterize eicosanoids released by rat alveolar macrophages during the evolution of experimentally induced pulmonary inflammation. Immunization with subcutaneous bacillus Calmette-Guerin (BCG) followed 2 wk later by intravenous BCG challenge resulted in mild granulomatous pulmonary inflammation for up to 30 days. At serial intervals, alveolar macrophages were lavaged from the BCG-treated rats as well as from control normal rats. Lavaged macrophages were cultured in vitro, and culture supernatants were assayed by radioimmunoassay for release of prostaglandin E2 (PGE2), Leukotriene B4 (LTB4), and thromboxane B2 (TXB2). Cells were cultured alone, or with added LPS or calcium ionophore A23187 to stimulate eicosanoid release. During BCG-induced inflammation, spontaneous release of PGE2 and LTB4 was unchanged, while spontaneous release of TXB2 was depressed acutely and then returned to control levels. The capacity of alveolar macrophages to release specific eicosanoids in response to an in vitro stimulus was dramatically altered during the course of BCG-induced inflammation. Stimulated release of PGE2 was transiently increased during acute lung injury, but stimulated release of LTB4 was significantly decreased at all stages of inflammation. Stimulated release of TXB2 was unchanged. These results indicate that during the course of granulomatous pulmonary inflammation there are dynamic changes in the profile of eicosanoids released by alveolar macrophages, both spontaneously and in response to in vitro stimulation. This alteration in the release of eicosanoids by alveolar macrophages may be an important factor in the resolution of pulmonary inflammation.

Animals↗

PubMed1989

Interferon-gamma increases alveolar macrophage Ia antigen expression despite oral administration of dexamethasone to rats.

Corticosteroids have multiple effects on immune and inflammatory responses and decrease host resistance to a broad range of microorganisms. Resident tissue macrophages have been proposed as a target for the immunosuppressive effects of corticosteroids and are important in host defense against infections. During infection-induced immune responses, macrophages are activated after exposure to interferon-gamma (IFN-gamma), and class II major histocompatibility (Ia) antigens on their surface are increased. We investigated the effect of orally administered corticosteroids on alveolar macrophages, the resident macrophages of the lung parenchyma. We hypothesized that corticosteroids would inhibit the activation of alveolar macrophages and measured induction by IFN-gamma of Ia antigens as a marker of cell activation. Alveolar macrophages from normal and corticosteroid-treated rats were exposed to recombinant murine IFN-gamma (rMuIFN-gamma) in vitro and assayed for Ia transcription and surface Ia expression. Ia mRNA accumulation was induced in alveolar macrophages from normal and corticosteroid-treated rats after exposure in vitro to rMuIFN-gamma. Furthermore, rMuIFN-gamma increased surface expression of Ia proteins on alveolar macrophages from corticosteroid-treated rats, although to a lesser extent than on cells from control rats. Finally, surface Ia expression could also be increased in vivo by exposure of corticosteroid-treated rats to an aerosol containing rMuIFN-gamma. These results demonstrate that administration of oral corticosteroids, while establishing a state of immunosuppression in rats, does not abolish responsiveness of rat alveolar macrophages to rMuIFN-gamma. We speculate that IFN-gamma-induced augmentation of phagocytic cell function may constitute an important therapeutic modality to treat complications of immunodeficiency.

Administration, Oral↗

PubMed1988

Cellular influx and activation increase macrophage cytotoxicity and interleukin-1 elaboration during pulmonary inflammation in rats.

This study was undertaken to investigate the effects of pulmonary inflammation induced by bacillus Calmette-Guérin (BCG) on the density distribution of lavaged alveolar macrophages. We sought to determine macrophage cytotoxicity and interleukin-1 elaboration in density-defined subpopulations of macrophages during tissue inflammation. At all time points after intravenously administered BCG, lavaged alveolar macrophages contained increased percentages of higher density cells. Alveolar macrophage cytotoxicity against the rat sarcoma cell line XC increased maximally 2 to 6 days after intravenous administration of BCG before declining on Day 13. Macrophage interleukin-1 elaboration increased maximally 14 days after administration of BCG before declining on Day 23. Additionally, macrophage cytotoxicity and interleukin-1 elaboration were increased above normal in cells from each of five density fractions. We conclude that a subpopulation of higher density macrophages, probably recently derived from blood monocytes, accumulates in inflammatory sites. Cellular activation increases the cytotoxicity and interleukin-1 elaboration by macrophages in all density-defined subpopulations and obscures the relationship between cellular density and function that is present in normal animals.

Animals↗

PubMed1987

Acquisition of peroxidase activity by rat alveolar macrophages during pulmonary inflammation.

The authors investigated the ability of rat alveolar macrophages to acquire peroxidase activity in the course of pulmonary inflammation. Granulomatous pulmonary inflammation was induced in bacille Calmette-Guérin (BCG)-immunized rats by intravenous injection of BCG in mineral oil. In contrast to normal alveolar macrophages, which are peroxidase-negative, alveolar macrophages lavaged from the BCG-treated rats showed significant peroxidase activity in large cytoplasmic inclusions compatible with internalized exogenous material. Alveolar macrophage uptake of intact peroxidase-positive neutrophils was also observed. Maximal numbers of peroxidase-positive alveolar macrophages were observed after the initial influx of neutrophils into the lungs, and peroxidase activity could be demonstrated in cell-free lavage fluid during the acute phase of lung injury. Normal alveolar macrophages acquired peroxidase activity after incubation with peritoneal exudate neutrophils, with purified soluble human myeloperoxidase, and with opsonized erythrocytes. It is concluded that alveolar macrophages acquire peroxidase activity from multiple sources during pulmonary inflammation. Internalization of peroxidase by the alveolar macrophage may serve to clear a potentially toxic enzyme(s) from the alveolar space and contribute to the resolution of pulmonary inflammation.

Animals↗

PubMed1987

Endogenous peroxidase activity as a marker of macrophage renewal during BCG-induced inflammation in the rat lung.

To determine whether the cytochemical localization of peroxidase activity could be used as a marker of monocyte influx into the lung during an inflammatory response, the authors studied the peroxidase phenotypes of lavaged alveolar macrophages from rats with bacille Calmette-Guérin (BCG)-induced pulmonary inflammation. Rats were immunized subcutaneously and 2 weeks later intravenously with BCG. During the early phase of pulmonary inflammation, an increase was observed in the numbers of alveolar macrophages with no peroxidase activity in the endoplasmic reticulum. These cells appeared to reflect monocyte influx into the injured lung. The later stages of inflammation were characterized by increased numbers of alveolar macrophages with peroxidase-positive endoplasmic reticulum, probably due to activation of enzymatic activity in situ. During the early phase, peroxidase activity was also observed within macrophage cytoplasmic inclusions, probably representing both primary monocyte lysosomes and internalized myeloperoxidase from inflammatory neutrophils. Serial observations indicated that the peroxidase-positive cytoplasmic inclusions became negative with time. It is concluded that inflammation-induced modulation of peroxidase activity in the endoplasmic reticulum and in cytoplasmic inclusions makes the alveolar macrophage peroxidase phenotype no more than a rough marker of monocyte influx into the inflamed lung.

Animals↗

PubMed1981