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Biomedical subjects

D J Johnson

Publications and source records attributed to D J Johnson.

At least 19 recordsLinked to original sources
PubMed1995

Factor VIIa and the extracellular domains of human tissue factor form a compact complex: a study by X-ray and neutron solution scattering.

The four-domain structure of human factor VIIa and the two-domain structure of tissue factor form a tight complex to initiate blood coagulation. By solution scattering, the mean X-ray and neutron radii of gyration RG (which determine macro-molecular elongation) were found to be 3.25 nm, 2.13 nm and 3.14 nm (+/- 0.13 nm) for factor VIIa, the extracellular region of tissue factor and their complex in that order. The mean cross-sectional radii of gyration RXS were 1.33 nm, 0.56 nm and 1.42 nm (+/- 0.13 nm) in that order. The mean lengths were 10.3 nm, 7.7 nm and 10.2 nm in that order. The data show that, in solution, the free proteins have extended domain structures, and the complex is formed by a compact side-by-side alignment of the two proteins along their long axes. The high binding affinity of tissue factor for factor VIIa may thus be accounted for by the occurrence of many intermolecular contacts in the complex.

Animals↗
PubMed1995

Protein-bound pyrroles in rat hair following subchronic intraperitoneal injections of 2,5-hexanedione.

Studies were initiated to ascertain whether body hair could be used to develop a biological marker for chronic exposure to industrial neurotoxicants that yield the metabolite 2,5-hexanedione (2,5-HD), that is, n-hexane and methyl n-butyl ketone. Rats were injected daily with a 50 mg/kg ip dose of 2,5-HD for 45 d. At intervals, body hair and individual vibrissae were removed (under general anesthesia) and tested for the presence of pyrrole substances with p-N,N-dimethylaminobenzaldehyde (DMAB, Ehrlich's reagent). Vibrissae and body hair were stained a reddish color that was distinctly different from that observed with the hair taken from control animals. Solubilized body hair protein from the treated animals gave a positive Ehrlich's test, while that from control animals was negative. Spectral analysis of the DMAB-treated hair from experimental animals disclosed a maximum absorbance at 530 nm, which indicated the presence of pyrrole substituents. Serial analysis of individual nose hairs taken during 2,5-HD administration showed a progression with time of the region staining positively for pyrroles, thus indicating that the process can proceed in growing hair. These findings suggest the potential utility of hair as an indicator for chronic exposure to this class of industrial chemicals possessing neurotoxicity potential. This could complement urinary analysis, which is now used to confirm recent exposure.

Animals↗
PubMed1995

Out-of-hospital ventilation: bag--valve device vs transport ventilator.

OBJECTIVE: To examine the patterns of out-of-hospital airway management and to compare the efficacy of bag-valve ventilation with that of the use of a transport ventilator for intubated patients. METHODS: A prospective, nonrandomized, convenience sample of 160 patients requiring airway management in the out-of-hospital urban setting was analyzed. A survey inquiring about airway and ventilatory management was completed by emergency medical services (EMS) personnel, and arterial blood gas (ABG) samples were obtained within 5 minutes of patient arrival in the ED. The ABG parameters were compared for patients grouped by different airway techniques and presence or absence of cardiac arrest (systolic blood pressure < 50 mm Hg) upon ED presentation. RESULTS: Over a one-year period, 160 surveys were returned. The majority (62%) of the patients were men; the population mean age was 61 +/- 19 years. Presenting ABGs were obtained for 76 patients; 17% (13/76) had systemic perfusion and 83% (63/76) were in cardiac arrest. There was no difference in ABG parameters between the intubated cardiac arrest patients ventilated with a transport ventilator (pH 7.17 +/- 0.17, PaCO2 37 +/- 20 torr, and PaO2 257 +/- 142 torr) and those ventilated with a bag-valve device (pH 7.20 +/- 0.16, PaCO2 42 +/- 21 torr, and PaO2 217 +/- 138 torr). The patients ventilated via an esophageal obturator airway (EOA) device had impaired gas exchange, compared with the groups who had endotracheal (ET) intubation (pH 7.09 +/- 0.13, PaCO2 76 +/- 30 torr, and PaO2 75 +/- 35 torr). The intubated patients not in cardiac arrest had similar ABG parameters whether ventilated manually with a bag-valve device or with a transport ventilator. Endotracheal intubation was successfully accomplished in 93% (123/132) of attempted cases. CONCLUSIONS: In this sample, ET intubation was the most frequently used airway by EMS providers. When ET intubation was accomplished, adequate ventilation could be achieved using either bag-valve ventilation or a transport ventilator. Ventilation via the EOA proved inadequate.

Adult↗
PubMed1995

Decreased elastin synthesis in normal development and in long-term aortic organ and cell cultures is related to rapid and selective destabilization of mRNA for elastin.

We have previously shown that aortic organ cultures from 1- to 3-day-old chickens initially mimic the high levels of elastin production seen in vivo. However, more prolonged incubation of these tissues results in decreased synthesis of elastin. In the present study, we demonstrate that decreased production of elastin in these aortic organ cultures is selective for elastin compared with collagen and is correlated with decreased steady state levels of mRNA for elastin. These decreases in steady state levels of elastin mRNA are due at least in part to a rapid and selective destabilization of mRNA for elastin, the half-life of which falls from approximately 25 hours in fresh aortic tissues to approximately 15 hours after incubation for only 8 hours. Destabilization of elastin mRNA can be prevented by incubation in the presence of blockers of DNA transcription (5,6-dichlorobenzimidazole riboside and actinomycin D) and mRNA translation (cycloheximide). Furthermore, the half-life of aortic elastin mRNA decreases from approximately 25 hours in the 1-day-old chicken to approximately 7 hours in the 8-week-old chicken, demonstrating that destabilization of mRNA is an important contributing factor in the decline in production of aortic elastin taking place during normal postnatal growth.

Age Factors↗
PubMed1992

Gut feeding and hepatic hemodynamics during PEEP ventilation for acute lung injury.

Mechanical ventilation with positive end-expiratory pressure (PEEP) limits hepatic blood flow (HBF) and oxygen delivery (HO2D). Early gut feeding may augment hepatic hemodynamics and avoid relative ischemia in this flow-limited environment. To examine these effects, canines were instrumented with arterial, pulmonary artery, portal, and hepatic vein catheters. Splenectomy and gastrostomy were performed and the hepatic artery and portal vein were encircled with flow probes. All animals underwent lung injury with oleic acid (0.08 ml/kg) followed by the addition of 10 cm H2O PEEP to correct shunt. One group (fed) was then given a bolus elemental feeding (1 kcal/ml, 10 ml/kg) and the Control group, sterile water. Cardiac index (CI), HBF, hepatic oxygen delivery (HO2D), and hepatic oxygen consumption (HO2C) were measured at baseline (T0), after PEEP (T1), and 1 (T2) and 2 hr (T3) after feeding. Data were tested for significant changes between time points in the same group by ANOVA and significant differences were subjected to t testing. PEEP significantly decreased CI, HBF, and HO2D compared to baseline. Subsequently, gut feeding increased HBF to baseline levels and improved HO2D. HO2C also increased but hepatic O2 extraction was unchanged. There was little change noted in the control group over this same period. We conclude that gut feeding augments HBF and HO2D in this flow-limited state and may preserve splanchnic integrity in critical illness.

Acute Disease↗
PubMed1992

Treatment of chloroquine-resistant malaria in monkeys with a drug combination that reverses resistance in vitro.

Compounds that inhibit the P-glycoprotein-related efflux mechanism of multidrug-resistant cells reverse chloroquine resistance in vitro. Hence, the co-administration of chloroquine and an efflux-blocking drug could potentially treat chloroquine-resistant malaria infections. We administered a drug combination (chloroquine and a tiapamil analogue), that has been shown to reverse chloroquine resistance in vitro, to Aotus monkeys but failed to safely clear experimentally-induced chloroquine-resistant Plasmodium falciparum parasitaemias.

Animals↗
PubMed1992

The effect of hypothermia on liver adenosine triphosphate (ATP) recovery following combined shock and ischemia.

During both hemorrhagic shock and ischemia, adenosine triphosphate (ATP) concentrations fall in liver tissue. Incomplete recovery of ATP correlates with cell death and subsequent organ dysfunction. Changes in liver ATP levels were evaluated in paired groups of rats subjected to combined hemorrhagic shock and ischemia. A second set of paired animals was studied over time with shock alone. One animal in each pair was maintained at 28 degrees C and the other at 37 degrees C. Ischemia was produced by occluding inflow to the left half of the liver, and tissue was obtained from this area in all animals studied. Adenosine triphosphate levels fell in warm and cold animals subjected to both shock and 60 minutes of ischemia but recovered more completely during reperfusion in the cold animals. Shock alone caused a steady fall in ATP levels in the warm, but not the cold rats. These biochemical changes may indicate a beneficial effect of moderate hypothermia in the management of severe liver hemorrhage requiring temporary occlusion of blood flow.

Adenosine Triphosphate↗
PubMed1992

Monoethylglycinexylidide production parallels changes in hepatic blood flow and oxygen delivery in lung injury managed with positive end-expiratory pressure.

Mechanical ventilation with high levels of positive end-expiratory pressure (PEEP) decreases hepatic blood flow (HBF) and hepatic oxygen delivery (HO2D). Noninvasive methods of detecting decreased HBF might prevent hepatic ischemia and dysfunction. Monoethylglycinexylidide (MEGX) is a hepatic metabolite of lidocaine, used clinically to determine graft function following hepatic transplantation. In order to test the hypothesis that MEGX production would be affected by changes in hepatic hemodynamics associated with lung injury, 12 dogs were instrumented with femoral and pulmonary artery catheters. Splenectomy was performed and the portal and hepatic veins cannulated. The hepatic artery and portal vein were encircled with flow probes. Lung injury was induced in six animals (INJURED group) with oleic acid (0.08 mL/kg) and 10 cm H2O PEEP was added to correct subsequent shunt. Levels of MEGX were measured 15 minutes after injection of intravenous lidocaine (1 mg/kg). Levels of HBF, HO2D, and MEGX were measured at BASELINE, after lung injury (INJURY time point), and after addition of PEEP (PEEP time point). CONTROL animals (n = 6) were studied at the same time points but without lung injury or PEEP. Hepatic blood flow and hepatic oxygen delivery were significantly decreased after lung injury and further decreased after PEEP. Levels of MEGX were unchanged in the CONTROL group but were significantly reduced by lung injury and PEEP in the INJURED group. Decreased MEGX production may be a useful clinical indicator of reduced hepatic flow and oxygen supply in critical illness.

Animals↗
PubMed1992

Cost and complications during in-hospital transport of critically ill patients: a prospective cohort study.

We prospectively studied transport of a group of 100 surgery/trauma patients and a matched control group in the ICU. APACHE II scores for the two groups were 23 +/- 6 and 20 +/- 8. During transport both groups had ECG, heart rate, blood pressure, and oxygen saturation continuously monitored. We also determined the cost and results of transport for those patients requiring diagnostic testing. There were six diagnostic tests performed: CT scan of the abdomen (39%), CT scan of the head (31%), CT scan of the chest (8%), CT scan of the cervical spine (4%), angiography (14%), and tomography (4%). Average transport time was 74 +/- 16 minutes with a range of 20-225 minutes. Physiologic changes defined as a BP +/- 20 mm Hg, heart rate +/- 20 beats/min, respiratory rate +/- 5 breaths/min, or oxygen saturation +/- 5% for 5 minutes duration occurred in 66% of transported patients and 60% of ICU patients. There were no differences in arterial blood gas levels before and during transport. In 39% of transports, the results of diagnostic testing produced a change in patient management within 48 hours. Abdominal CT scanning and angiography were associated with the highest percentage of tests leading to a management change (51% and 57%). The average charge to the patient was $612.00 and the average cost to the hospital $452.00. Our results suggest that while physiologic changes are frequent during transport, they are also frequent in ICU patients as a consequence of the severity of illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The effect of low dose dopamine on gut hemodynamics during PEEP ventilation for acute lung injury.

Mechanical ventilation with positive end-expiratory pressure (PEEP) diminishes gut and hepatic blood flow and redistributes cardiac output away from the splanchnic circulation. This flow-limited environment can aggravate underlying hypoperfusion and ischemia in the postinjury setting. To examine the effects of low dose dopamine on a lung injury PEEP model of gut hypoperfusion, six anesthetized, splenectomized canines were instrumented with arterial, pulmonary artery, portal vein, and hepatic vein catheters. Electromagnetic flow probes were placed around the hepatic artery and portal vein for continuous flow measurements. Gut and hepatic blood flow, oxygen delivery, oxygen consumption, and extraction ratio were calculated at four time points: baseline, 1 hr after lung injury with oleic acid, 1 hr after ventilation with 10 cm H2O PEEP, and 1 hr after the continuous infusion of dopamine. Portal flow and gut oxygen delivery fell significantly with the infusion of PEEP. These values returned to near baseline levels with the addition of dopamine. Gut oxygen extraction increased from 16 +/- 2% to 35 +/- 3% with PEEP but returned to near baseline with dopamine (20 +/- 4%, P less than 0.01 compared to PEEP). We conclude that dopamine improves blood flow and oxygen delivery to the gut in this flow-limited model. This may preserve splanchnic physiology during PEEP ventilation for acute lung injury.

Animals↗
PubMed1990

Pattern of accumulation of elastin and the level of mRNA for elastin in aortic tissue of growing chickens.

Synthesis and accumulation of elastin in many elastic tissues begins in the last third of fetal development, reaches a maximum shortly after birth, and then declines rapidly. For the aorta of the chick and the pig and the ligamentum nuchae and lung of the sheep, it has been shown that increased levels of elastin production with fetal development are correlated with increased levels of elastin mRNA in the tissue, measured both by cell-free translation and by hybridization to cDNA probes. In this study we examine the relationship between insoluble elastin accumulation and message levels for tropoelastin in aortic tissue of chickens during posthatching development and growth. Whether evaluated by cell-free translation or by dot blot hybridization, steady state levels of tropoelastin message increase to a maximum at 2 weeks after hatching, and then fall rapidly with further development and growth. This pattern correlates well with production of insoluble elastin by the aorta, determined either by direct measurements of synthesis or by rate of accumulation of insoluble elastin. The data indicate that the major site of regulation of elastin production is pretranslational throughout the entire period of development and growth of the chicken aorta.

Animals↗
PubMed1990

Toward cultural/ecological perspectives on schooling and achievement in African- and Asian-American children.

The review acknowledges that research on the family and its contribution to achievement in ethnic minority children is important. Past research and theorizing suggest the need for new directions, however. For example, research in educational achievement predicts educational failure for African-American students and educational success for Asian-American students. Little differentiation is made either among African-Americans or among Asian-Americans of different cultural, language, immigration, and economic backgrounds. The theory and design of research on family and educational achievement have been influenced by prevailing societal stereotypes. Research and policy implications of this review include the need to move toward cultural/ecological theories of achievement socialization and development.

Achievement↗
PubMed1990

Alterations in elastin and collagen related to the mechanism of progressive pulmonary venous obstruction in a piglet model. A hemodynamic, ultrastructural, and biochemical study.

We created an animal model to understand better the pathogenesis and underlying mechanism of progressive central pulmonary venous (PV) obstruction, a condition not amenable to current therapy. Twenty piglets underwent banding of their PVs, 18 had a sham operation, and 12 were nonoperated controls. After 1, 3, and 6 weeks hemodynamic data were obtained and correlated with ventricular weights, PV and pulmonary artery (PA) distensibilities (at 1 week), morphometric structural and ultrastructural analyses, and biochemical assessment of elastin determined gravimetrically (and by desmosine level at 1 week), collagen, and elastase activity. At 1 week, PV banding was associated with increased PV compliance (p less than 0.05). At 3 weeks, an increased PA pressure (Ppa) (p less than 0.05) was observed, unaccompanied by a rise in PV pressure (Pcw). In the PV, however, there was breakdown of the internal elastic lamina with apparent migration of smooth muscle cells from media to subendothelium. At 6 weeks, a rise in Pcw (p less than 0.01), a further rise in Ppa (p less than 0.01), and right ventricular hypertrophy (p less than 0.005) were observed. We also observed mild PV intimal thickening (p less than 0.01), complete degradation of elastic laminae (p less than 0.05), and an increase in collagen assessed morphometrically (p less than 0.01). The banding procedure resulted in an overall increase in PV elastin synthesis and in the proportion of elastin determined gravimetrically (p less than 0.05 for both) but not by desmosine level, suggesting the possibility of poor cross-linking of elastin, which might account for the early increased distensibility of the PV. However, our assay could not detect an increase in elastase activity associated with either the increased distensibility or the ultrastructural changes of elastin degradation. The increased Ppa was not associated with significant PA biochemical or structural changes. We speculate that in response to distal venous obstruction, early remodeling of the PVs increases distensibility, protecting the lung from venous congestion and blunting a rise in Pcw. PA hypertension precedes the rise in Pcw, likely because of reflex vasoconstriction. The subsequent modest rise in Pcw is already associated with extensive fibrosis of the PV, suggesting a reason for unsuccessful current therapy and a need for consideration of earlier assessment and intervention.

Animals↗
PubMed1990

Factors affecting the production of insoluble elastin in aortic organ cultures.

Aortic organ and cell culture systems have made important contributions to the understanding of the synthesis and accumulation of elastin in arterial tissues. However, methods used to quantitate production of elastin have been diverse, and evaluations of different culture conditions have not been made. In this study we describe a convenient and reproducible organ culture system for the assay of insoluble elastin synthesis. Under optimum incubation conditions, insoluble elastin is produced in organ culture at rates approximating in vivo accumulation rates. The assay is stable under a wide variety of incubation conditions, although elastin production is sensitively inhibited by acidification of the incubation medium. Alterations in intracellular calcium concentration had little effect on elastin production. In contrast, manipulations of sodium ion concentration, including treatment with ouabain or monensin, depressed elastin production. Except at high doses, pharmacological or humoral agents, including non-steroidal anti-inflammatory agents, alpha and beta adrenergic agonists, cyclic nucleotides, theophylline or aminophylline, and histamine, generally had only small effects on elastin production in this organ culture system.

Animals↗
PubMed1990

Fluid volume deficit: validating the indicators. The Research Committee, Greater Milwaukee Area Chapter of the American Association of Critical-Care Nurses.

A validation of the nursing diagnosis "fluid volume deficit related to active isotonic loss" was completed by using the diagnostic content validity method. A validation tool containing 72 clinical indicators was mailed to a national sample of critical care experts. The study sample rated the clinical indicators on a scale from one to five, evaluating their relevancy to this diagnosis. The Delphi survey technique was used. Of the 72 clinical indicators on the validation tool, 17 were categorized as critical indicators and 29 were categorized as defining characteristics.

Dehydration↗
PubMed1990

Studies of cobalamin as a vehicle for the renal excretion of cyanide anion.

To examine the ability of hydroxocobalamin (vitamin B12a, HO-Cbl) to counteract the toxicity of cyanide by promoting the renal excretion of cyanide anion, we studied the pharmacokinetics of HO-Cbl and cyanocobalamin (vitamin B12, CN-Cbl) given in high doses to dogs. After administration of intravenous bolus doses of HO-Cbl and CN-Cbl (5, 10, 25 mg/kg) to female foxhounds, peak plasma concentrations were attained within 1 minute, after which the cobalamins disappeared from plasma in a manner consistent with two-phase distribution and elimination kinetics. While mean t1/2 measurements for the initial distribution phase were similar for HO-Cbl and CN-Cbl, the secondary excretion phase was more prolonged for HO-Cbl than for CN-Cbl (t1/2, 94.75 minutes vs 62.64 minutes, respectively). Pharmacokinetic data permitted the design of a HO-Cbl infusion schedule that resulted in stable plasma concentrations in test animals. When NaCN was then given intravenously to animals preloaded with HO-Cbl (20 micrograms/ml plasma), conversion of HO-Cbl to CN-Cbl in vivo, was documented by both thin-layer and high-performance liquid chromatographic analysis of successive urine samples. Moreover, in dogs preloaded with HO-Cbl (20 micrograms/ml plasma), up to 10% of the cyanide administered as NaCN infusions was recovered in urine as CN-Cbl by 60 minutes, compared with less than 0.3% in dogs not treated with HO-Cbl. In addition, under these conditions of HO-Cbl loading, the minimum doses of NaCN required to produce sublethal signs of cyanide toxicity (hypotension, tachypnea, tachycardia) were found to be increased to levels that in some cases exceeded normally lethal doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗