Inhibition of acute cardiac allograft rejection in immunoglobulin-deficient mice.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
Z Qian
Publications and source records attributed to Z Qian.
Recirculation-type Amplatz clot macerator: determination of particle size and distribution.
PURPOSE: A high-speed mechanical clot macerator was tested in vitro, and the distributions and sizes of residual particles produced by this device were determined. MATERIALS AND METHODS: Human thrombi aged for 4 days and 10 days were macerated using a recirculation-type Amplatz thrombectomy device with an 8-F, high-speed screw propeller. The device was activated for 15, 30, and 60 seconds. Two different methods of particle measurement were used to determine overall particle distribution and to determine the size and number of large particles. RESULTS: The recirculation device liquefied 99.2% of 4-day-old and 98.8% of 10-day-old thrombi, producing particles ranging in size from 13 to 1,000 microns; all particles were smaller than 1,000 microns. Particle size and distribution results were identical for the 30-second and 60-second activation times. CONCLUSION: The recirculation-type thrombectomy device appears to perform well as a method of macerating human thrombi. Clinical trials need to be conducted to test the device further and to determine if it can be used safely on venous as well as arterial occlusions.
Humans↗
Hemolytic effect of the Amplatz thrombectomy device.
PURPOSE: The hemolytic effect of the Amplatz thrombectomy device (ATD) was evaluated in nine dogs and in nine patients. MATERIALS AND METHODS: The device was activated for 1-2 minutes in the abdominal aorta, inferior vena cava, or femoral artery of nine dogs. The device was activated for 1-4 minutes in the nine patients in occluded lower extremity bypass grafts (n = 5), native superficial femoral artery (n = 1), a pulmonary artery embolus (n = 1), a portocaval shunt (n = 1), and an iliac vein stent (n = 1). Patients were examined for laboratory evidence of hemolysis following mechanical thrombectomy. RESULTS: In all dogs haptoglobin level decreased, free hemoglobin level in the plasma increased, and hemoglobinuria was present. There was no change in renal function. The level of haptoglobin decreased and the level of plasma free hemoglobin increased in eight patients, with hemoglobinuria detected in one. More hemolysis was observed in the animals than in the patients. CONCLUSION: The ATD has a definite transient hemolytic effect. Until further studied, it should not be used in children and should be used with caution in patients who are anemic, hypoxemic, or have potentially reversible renal insufficiency. Activation time should be monitored closely because hemolysis probably increases with increasing activation time.
Animals↗
In vitro and in vivo experimental evaluation of a new vena caval filter.
PURPOSE: A new stainless steel (MP35N alloy) vena cava filter without a central stasis point was evaluated in vitro and in vivo. MATERIALS AND METHODS: The clot-trapping efficiency and hemodynamic flow pattern of the filter were assessed in a flow model and were compared with those of currently available commercial filters including the Vena Tech-LGM, Simon nitinol, Greenfield, and Bird's Nest filters. The new filter was placed in the inferior vena cava (IVC) of 31 dogs; 21 of the 31 dogs were followed up with cavography for up to 3 months. At the termination of the study, the filters and IVCs were examined grossly and histologically. An in vivo clot-trapping test was carried out in five dogs. RESULTS: The least turbulence was noted with the new filter and the titanium Greenfield filter. The stainless steel Greenfield and Simon nitinol filters caused major flow disturbances. Migration within 5 cm of initial placement occurred in two animals (9.5%). There were no IVC thromboses, perforations, or filter embolizations. An in vivo clot-trapping study showed an 80% efficiency for small thrombi (3 x 20 mm) and 100% efficiency for large thrombi (6 x 20 mm) with the new filter. The Simon and the new filter had the best clot-trapping capabilities. The Vena Tech-LGM and Bird's Nest filters were slightly inferior and the Greenfield filter demonstrated by far the lowest trapping capacity. CONCLUSION: The new vena cava filter is easily introduced percutaneously through a 12-F sheath and appears to be very promising due to its high filtering capability, low turbulence, nonmagnetic properties, good mechanical stability, and hypothrombogenicity. Clinical trials are warranted.
Alloys↗
Ethanol inhibits sphincter of Oddi motility.
Patients with alcohol-induced liver disease are at increased risk for pigment gallstones, which are known to be particularly associated with biliary stasis. Although the effects of ethanol on the sphincter of Oddi are thought to contribute to alcoholic pancreatitis, the precise effects of ethanol on the biliary component of the sphincter of Oddi are unclear. In the prairie dog the common bile and pancreatic ducts enter the duodenum separately, facilitating pressure measurement in the sphincter choledochus in isolation. We therefore used this model to test the hypothesis that ethanol administration alters sphincter of Oddi motility. Twenty-six male prairie dogs fed a nonlithogenic diet were studied. With the animals under alpha-chloralose anesthesia, a side-hole pressure-monitored perfusion catheter was positioned in the sphincter of Oddi and femoral arterial and venous catheters were placed. Sphincter of Oddi phasic wave frequency (F), amplitude (A), and motility index (MI = F x A) and arterial blood pressure were monitored at 10-minute intervals before (baseline), during 20-minute intravenous infusions of 15 mg/kg (n = 9), 150 mg/kg (n = 10), and 1.5 g/kg (n = 7) ethanol and for 20 minutes after ethanol infusion. The 15 mg/kg dose of ethanol had no effect, the 150 mg/kg dose tended to reduce sphincter of Oddi motility, and significant reductions in sphincter of Oddi amplitude and motility index were seen at the 1.5 g/kg dose. These data demonstrate that ethanol infusion inhibits both sphincter of Oddi amplitude and motility index and that this effect persists for at least 20 minutes following ethanol infusion. Ethanol may contribute to gallstone formation by altering biliary sphincter motility.
Animals↗
Long-term ambient air pollution levels in four Chinese cities: inter-city and intra-city concentration gradients for epidemiological studies.
The field data collection of an air pollution epidemiologic study was carried out from 1993 to 1996 in four Chinese cities of Lanzhou, Chongqing, Wuhan, and Guangzhou. In each city, an urban district and a suburban district were selected. Ambient concentrations of total suspended particles (TSP), size-fractionated particulate matter including PM2.5, PM2.5-10, and PM10, sulfur dioxide (SO2), and oxides of nitrogen (NOx) were measured in these districts. The results indicate the presence of wide inter-city and intra-city gradients in long-term ambient levels of these measured pollutants. Across the eight districts, the 1993-1996 4-year means of TSP, SO2, and NOx ranged from 198 to 659 microg/m3, from 14.6 to 331 microg/m3, and from 31.5 to 239 microg/m3, respectively, and the 1995-1996 2-year means of PM2.5, PM2.5-10, and PM10 ranged from 51.5 to 142 microg/m3, from 29.2 to 107 microg/m3, and from 80.7 to 232 microg/m3, respectively. These pollution ranges substantially extended the upper end of the pollution ranges of previous air pollution epidemiologic studies conducted in North America and Europe. In each district, significant correlations among the measured pollutants were observed for daily concentrations. However, the gradient patterns in long-term means of different pollutants were different across the eight districts. (e.g., PM2.5-10 and TSP were highest in the Lanzhou urban district, PM2.5 and PM10 were highest in the Guangzhou urban district, SO2 was highest in the Chongqing urban district, and NOx was highest in the Guangzhou urban district). In general, seasonal variations were present in the ambient concentrations with high levels often occurring in winter months. The eight districts may be classified into four district clusters based on integrated levels of all measured pollutants. These features of the ambient air pollution have important implications for epidemiological studies and may provide unique opportunities to study exposure-effects relationships in the four Chinese cities.
Air Pollutants↗
Effects of air pollution on children's respiratory health in three Chinese cities.
During the winter of 1988-1989, parents of 2,789 elementary-school students completed standardized questionnaires. The students were 5-14 y of age and were from three urban districts and one suburban district of three large Chinese cities. The 4-y average ambient levels of total suspended particles in the three cities differed greatly during the period 1985-1988: Lanzhou, 1,067 microg/m3; urban Wuhan, 406 microg/m3; Guangzhou, 296 microg/m3; and suburban Wuhan, 191 microg/m3. The authors constructed unconditional logistic-regression models to calculate odds ratios and 95% confidence intervals for prevalences of several respiratory symptoms and illnesses, adjusted for district, use of coal in the home, and parental smoking status. There was a positive and significant association between total suspended particle levels and the adjusted odds ratios for cough, phlegm, hospitalization for diseases, and pneumonia. This association was derived from only the 1,784 urban children and, therefore, the authors were unable to extrapolate it to the suburban children. The results also indicated that parental smoking status was associated with cough and phlegm, and use of coal in the home was associated only with cough prevalence (alpha = 0.05).
Adolescent↗
Effects of air pollution on respiratory health of adults in three Chinese cities.
The authors examined potential associations between air-pollution exposures and respiratory symptoms and illnesses of 4,108 adults who resided in 4 districts of 3 large, distinct Chinese cities. Data on respiratory health outcomes and relevant risk factors for parents and children were obtained via standardized questionnaires in the winter of 1988. (The effects in children were described previously.) The yearly averages of ambient levels of total suspended particles in the 4 districts for the years 1985-1988 differed greatly. The authors constructed logistic-regression models to assess the respiratory health parameters of parents of the children. The results revealed significant and strong effects, by district, on prevalence rates of cough, phlegm, persistent cough and phlegm, and wheeze for both the mothers and the fathers. In addition, the odds ratios increased as ambient total suspended particle concentration increased across the 3 urban districts. Other local within-city risk factors, however, may have confounded the total suspended particles-effects association, especially for asthma prevalence. Findings for adults were similar to those found for their children. A strong adverse effect of active tobacco smoking on the fathers' respiratory health was observed. The children appeared to be more strongly affected by passive smoking exposure received in their homes than their mothers.
Adult↗
Temporal and spatial regulation of the expression of BAD2, a MAP kinase phosphatase, during seizure, kindling, and long-term potentiation.
Recent studies indicate that stimulation of NMDA receptors in cultured hippocampal cells activates MAP kinase. Although the pathway whereby MAP kinase is activated has been been characterized, little is known about the mechanisms that shut off MAP kinase. In the course of analyzing several immediate-early genes identified previously by differential screen as inducible by seizure activity, we found that one of them, BAD2, encodes dual purpose, threonine/tyrosine phosphates with specific activity directed against MAP kinase (MKP-1). In situ hybridization of BAD2 demonstrates that stimuli that produce seizure, kindling, and long-term potentiation cause a rapid increase in BAD2 mRNA (within 0.5-1 hr after stimulation) that has, in each case, a distinctive pattern of expression in the brain. In these regions, the induction of a MAP kinase-specific phosphatase may provide a negative feedback control associated with long-term synaptic changes.
Amino Acid Sequence↗
Urinary 6 beta-hydroxycortisol/cortisol ratios measured by high-performance liquid chromatography for use as a biomarker for the human cytochrome P-450 3A4.
Cortisol is metabolized to 6 beta-hydroxycortisol by the human cytochrome P-450 3A4, an enzyme implicated in the critical epoxidation reactions of aflatoxin B1 and certain polycyclic aromatic hydrocarbons. A method has been developed to measure the 6 beta-hydroxycortisol:cortisol ratio in human urine by reverse-phase high-performance liquid chromatography using diode-array detection. This method permits measurement of both cortisols in a single chromatographic run and has the potential to measure other metabolites useful for the determination of other human cytochrome P-450 activities. Using the 6 beta-hydroxycortisol:cortisol ratio as a marker of cytochrome P-450 3A4 activity adjusts for the circadian fluctuation in cortisol levels, providing a determination that is consistent over a 24-h period, obviating the need for 24-h urine collections. This high-performance liquid chromatography technique was used for the analysis of 14 different human urines and a range of ratios of 1.6 to 21.7 (mean +/- SE, 6.2 +/- 1.6) was found. These values are consistent with those reported in the literature. This method should be useful in molecular epidemiological studies investigating relationships between the susceptibility from environmental carcinogen exposure and cancer risk.
Biomarkers↗
Inhibition of neutrophil adhesion and the membrane attack complex of complement synergistically prolongs cardiac xenograft survival.
BACKGROUND: Hyperacute xenograft rejection is affected by activation of the complement cascade. Split products of early complement components influence the localization, activation, and effector function of platelets, granulocytes, and lymphocytes, whereas the formation of the membrane attack complex (C5b-9) leads to direct cellular injury. In a unique strain of PVG rats deficient in the C6 component of complement, the terminal membrane attack complex is not formed. However, production of the chemotactic and vasoactive components C3a and C5a proceeds normally. Guinea pig cardiac xenografts in these C6-deficient rats have prolonged survival, and at the time of rejection the inflammatory infiltrate is composed primarily of neutrophils. NPC 15669, a member of a class of antiinflammatory agents called leumedins, is known to inhibit neutrophil adhesion. The purpose of this study was to determine whether inhibition of neutrophil recruitment in animals incapable of membrane attack complex formation would prolong cardiac xenograft survival. METHODS: Cardiac xenografts from male Hartley guinea pigs were heterotopically grafted into PVG (C-) and PVG (C+) male rats. Experimental animals received 20 mg/kg of NPC 15669 i.v. before cross-clamp release and 10 mg/kg of NPC 15669 intravenously on postoperative day 1. Control animals received intravenous saline solution only. RESULTS: Complement sufficient PVG (C+) rats rejected cardiac xenografts hyperacutely despite mode of treatment: PVG (C+) rats which received saline solution (n = 5) rejected their xenografts at 10.8 +/- 2.6 minutes, and those receiving NPC 15669 (n = 5) rejected at 13.9 +/- 5.3 minutes. Histologic examination showed edema, platelet aggregation, and hemorrhage but no cellular inflammatory infiltrate. As expected, complement-deficient PVG (C-) rats had markedly longer xenograft survival in the saline solution-treated group (n = 5) with graft function being sustained 14.7 +/- 6.1 hours. NPC 15669 treatment (n = 4) further prolonged graft function to 61.0 +/- 4.7 hours. In addition to edema, platelet aggregation, and hemorrhage, histologic analysis of these grafts at the time of rejection was characterized by an infiltration of neutrophils. CONCLUSIONS: We conclude that neutrophils play a critical role in cardiac xenograft rejection when complement activation is restricted. Combined inhibition of complement and neutrophil adhesion prolongs xenograft survival longer than inhibition of either component alone.
Animals↗