Search PubMed⌕ Search

Biomedical subjects

D J Johnson

Publications and source records attributed to D J Johnson.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1989

Substance P receptor binding sites are expressed by glia in vivo after neuronal injury.

In vitro studies have demonstrated that glia can express functional receptors for a variety of neurotransmitters. To determine whether similar neurotransmitter receptors are also expressed by glia in vivo, we examined the glial scar in the transected optic nerve of the albino rabbit by quantitative receptor autoradiography. Receptor binding sites for radiolabeled calcitonin gene-related peptide, cholecystokinin, galanin, glutamate, somatostatin, substance P, and vasoactive intestinal peptide were examined. Specific receptor binding sites for each of these neurotransmitters were identified in the rabbit forebrain but were not detected in the normal optic nerve or tract. In the transected optic nerve and tract, only receptor binding sites for substance P were expressed at detectable levels. The density of substance P receptor binding sites observed in this glial scar is among the highest observed in the rabbit forebrain. Ligand displacement and saturation experiments indicate that the substance P receptor binding site expressed by the glial scar has pharmacological characteristics similar to those of substance P receptors in the rabbit striatum, rat brain, and rat and canine gut. The present study demonstrates that glial cells in vivo express high concentrations of substance P receptor binding sites after transection of retinal ganglion cell axons. Because substance P has been shown to regulate inflammatory and immune responses in peripheral tissues, substance P may also, by analogy, be involved in regulating the glial response to injury in the central nervous system.

Animals↗
PubMed1988

Electron microscope study of the association between hypothalamic blood vessels and oxytocin-like immunoreactive neurons.

An association between oxytocin-like immunoreactive neurons and hypothalamic blood vessels has been observed with the light microscope. Recently, it has been demonstrated that oxytocin stimulates vascular smooth muscle contraction in vitro. A hypothesis has thus been proposed that oxytocin may play a role in modulating blood flow in certain brain regions. In a study on the golden-mantled ground squirrel (Spermophilus lateralis) we noted the association at the light microscope level between oxytocin-like immunoreactive neurons and blood vessels in preoptic and paraventricular nuclei of the hypothalamus. To determine if these neurons were associated with hypothalamic capillaries, transverse 30 micron immunostained hypothalamic sections were prepared for thin sectioning and observation by transmission electron microscopy. Oxytocin-like immunoreactive neurons were observed to lie within 77 nm of the edge of the lumen of capillary blood vessels. One neuronal cell body was observed approximately 380 nm from the edge of a capillary lumen and what appears to be an output region of a neuron was observed to terminate on the basement membrane of a capillary blood vessel.

Animals↗
PubMed1988

The abdomen as a source of occult sepsis.

When a patient presents with sepsis and no clear etiology, the abdomen can hide a focus of infection and must be considered in the course of the evaluation (Fig. 1). There are certain groups of patients who do not exhibit the usual signs and symptoms of intra-abdominal infection and therefore constitute the population at risk for occult abdominal sepsis. These patients, for one reason or another, have an unreliable history or physical exam. Once intra-abdominal infection is suspected, certain basic laboratory and radiographic evaluations should be undertaken. Treatment delays are not tolerated and the performance of diagnostic tests when a laparotomy appears inevitable is not indicated. CT of the abdomen should not be used as a screening exam and should be reserved for those cases potentially having an infected fluid collection. If a thorough evaluation of the abdomen reveals a possible source, a measured medical and surgical approach can be undertaken, depending on the etiology. If no source is found, the question of a diagnostic laparotomy arises in certain cases (Fig. 2). This procedure should be reserved for those patients having some type of underlying abdominal surgery or pathology. Without a previous history of abdominal surgery or pathology, and with no other clinical evidence of intra-abdominal infection, a nondirected laparotomy can be safely performed when organ failure is not present but usually will not reveal a treatable lesion. Multiple organ failure may indicate the presence of a hidden abdominal source of infection; however, the window for successful surgical intervention may have already passed. Multiple organ failure does not mandate laparotomy when there is no clinical or radiographic basis for suspecting an abdominal source of infection. This is especially true if an alternative source of sepsis has been defined.

Abdomen↗
PubMed1988

Altered elastin and collagen synthesis associated with progressive pulmonary hypertension induced by monocrotaline. A biochemical and ultrastructural study.

Changes in elastin and collagen synthesis in the pulmonary artery wall, assessed both biochemically and ultrastructurally, were related to the development of progressive pulmonary hypertension induced by the toxin monocrotaline. Male Sprague-Dawley rats (200 to 225 gm) were injected subcutaneously in the hind flank with either monocrotaline (60 mg/kg) or an equivalent volume of saline and studied 8, 16 and 28 days later. At each time point, the right ventricle and left ventricle with septum were separated and weighed to follow the development of right ventricular hypertrophy. The hilar pulmonary artery was assessed by light microscopy for medial hypertrophy and by electron microscopy for changes in the endothelium, subendothelium and media. The mainstem pulmonary artery was used to determine synthesis of elastin and collagen by in vitro incorporation of [14C]proline into nonelastin, [14C]hydroxyproline into collagen, and [3H]valine into cyanogen bromide-insoluble elastin. In addition, total content of insoluble elastin was determined by weight of the residue after cyanogen bromide digestion and of collagen by total hydroxyproline content in sodium dodecyl sulfate and cyanogen bromide extracts. Eight days after monocrotaline injection, there was pulmonary artery endothelial swelling and a significant decrease in the number of myoendothelial junctions (p less than 0.05) associated with a decreased proportion of amorphous elastin in the media (p less than 0.01). Sixteen days after monocrotaline injection, a decrease in the proportion of elastin in the media was still evident (p less than 0.01) despite an apparent increase in insoluble elastin synthesis. Moreover, the amorphous elastin was distributed preferentially in small islands rather than in laminae (p less than 0.05). Twenty-eight days after monocrotaline injection, medial and right ventricular hypertrophy had developed (p less than 0.05 and p less than 0.01, respectively). At the same time, there was a striking increase in both insoluble elastin synthesis and total insoluble elastin content (p less than 0.01 for both) and an increase in collagen synthesis and total collagen content (p less than 0.05 for both). In addition, the ratio of insoluble elastin synthesis to collagen synthesis was greater than in controls (p less than 0.01), whereas the ratio of total insoluble elastin to total collagen did not change. On ultrastructural analysis, the proportion of amorphous elastin in the vessel wall relative to other elements remained low (p less than 0.01) and was distributed throughout the media as increased numbers of small islands (p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Age differences in the effect of hydrocortisone on the synthesis of insoluble elastin in aortic tissue of growing chicks.

Glucocorticoids have been shown by others to increase the synthesis of elastin both in aortic tissue of embryo chicks and in cells derived from fetal ligamentum nuchae. This report describes the effects of hydrocortisone on the production of elastin in aortic tissue of developing chick embryos and chicks. While the effect of hydrocortisone on elastin synthesis is stimulatory in the 14 day chick embryo and the day-old chick, the same dose of this glucocorticoid has no effect on elastin production in the 7 day old chick and significantly inhibits synthesis of elastin in the 14 day old chick. These age-related alterations in elastin production in response to hydrocortisone cannot be attributed to an effect of the steroid on the pool size of the radioactively labelled amino acid used to measure elastin synthesis.

Aging↗
PubMed1986

Hypothermic anesthesia attenuates postoperative proteolysis.

The catabolic response that commonly occurs after major operation is characterized by net skeletal muscle proteolysis and accelerated nitrogen excretion. This response was absent in patients undergoing cardiac surgical procedures associated with the combination of cardiopulmonary bypass, narcotic anesthesia, neuromuscular blockade, and hypothermia. Forearm nitrogen release was 422 +/- 492 nmol/100 ml X min on the first postoperative day, approximately 25% of preoperative values (1677 +/- 411, p less than 0.05). Nitrogen excretion and the degree of negative nitrogen balance were comparable to levels observed in nonstressed, fasting subjects. The potential role of hypothermia, high-dose fentanyl anesthesia, and neuromuscular blockade in modifying the catabolic response to laparotomy and retroperitoneal dissection was further evaluated in animal studies. Six hours after operation, amino acid nitrogen release from the hindquarter was 84% less than control values (p less than 0.05). Nitrogen excretion and urea production were also reduced compared to normothermic controls. It is concluded that the combination of hypothermia, narcotic anesthesia, and neuromuscular blockade attenuates the catabolic response to injury and thus may be useful in the care of critically ill surgical patients.

Amino Acids↗
PubMed1986

Branched chain amino acid uptake and muscle free amino acid concentrations predict postoperative muscle nitrogen balance.

Amino acid solutions rich in branched chain amino acids (BCAA) are commonly utilized both clinically and in experimental protocols in an attempt to reduce skeletal muscle and whole body protein catabolism. To investigate the effectiveness of BCAA infusion, amino acid formulas containing varying concentrations of BCAA were given during operation in this study to three groups of dogs undergoing a standard laparotomy and retroperitoneal dissection. A fourth group was given saline alone. With the use of previously described hindquarter flux techniques, individual and total amino acid nitrogen exchange rates were measured and utilized in estimating skeletal muscle protein catabolism. Intracellular free amino acid concentrations were measured in percutaneous muscle biopsy samples. Although there was no relationship with the rate of BCAA infusion, there was a significant correlation between the rate of BCAA uptake by muscle and diminished total nitrogen release from hindquarter skeletal muscle after operation. There was also a significant relationship between muscle nitrogen balance and the postoperative change in the muscle concentration of either total amino acids or the single amino acid glutamine. When combined in a single equation, BCAA uptake and the change in muscle free amino acid concentration predict skeletal muscle nitrogen release with an r = 0.86. Thus, the rate of BCAA uptake and the free glutamine or total amino acid concentration in muscle appear to be independent predictors of muscle nitrogen balance. The nitrogen-sparing effect of BCAA in skeletal muscle is unrelated to infusion concentration or rate of infusion.

Amino Acids↗
PubMed1986

The effect of developing hypertension on the synthesis and accumulation of elastin in the aorta of the rat.

This report describes an investigation of the effects of developing hypertension on the synthesis and accumulation of insoluble elastin in the thoracic aorta of young rats. Uninephrectomized male rats were made hypertensive by administration of deoxycorticosterone acetate and addition of 1% NaCl to their drinking water. Divergence of systolic blood pressures between treated and control animals and hypertrophy of the vessel began after about 2 weeks of treatment. Coincident with the appearance of hypertrophy, there was an increased accumulation of insoluble elastin in the aorta and a large increase in the capacity of the aortic tissue to synthesize elastin. However, in spite of continued increases in blood pressure and vessel hypertrophy, this effect on elastin synthesis and accumulation was transient. The results of this study suggest that synthesis of elastin in aortic tissue of young rats is highly sensitive to alterations in blood pressure.

Animals↗
PubMed1985

The effect of induced atherosclerosis on the synthesis of elastin in chick aortic tissue.

Atherosclerosis was induced in growing chickens by the administration of a diet containing elevated levels of cholesterol and vitamin D3. The effect of this diet on the accumulation of insoluble elastin and the synthesis of soluble and insoluble elastin in the thoracic aortas of these animals was measured. Although the diet resulted in significant increases in levels of cholesterol, 25-OH vitamin D3 and calcium in plasma, increased levels of cholesterol and calcium in aortic tissue, and histological evidence of aortic lipid deposition, there were no detectable differences between experimental and control animals in either the rate or the time course of accumulation of total insoluble elastin in the thoracic aorta, or in the rate and time course of synthesis of soluble and insoluble elastin. These data suggest that, at least in this model, any effect of atherosclerosis on aortic elastin production must be either small or so localized as to be not measurable by the methods used.

Animals↗
PubMed1985

Measurement of hepatic blood flow.

Measurement of hepatic blood flow is fundamental to understanding hepatic physiology and biochemistry, quantitating drugs metabolized in the liver, and describing pathophysiologic states such as portal hypertension. However, the dual blood supply, altered handling of labels during disease states, and the relative inaccessibility of the portal system have made precise measurements of hepatic blood flow difficult. A variety of techniques can be utilized in both laboratory animals and patients; the more invasive techniques are generally available for animal studies, while semi-invasive and noninvasive methodologies yield information from patients. Each method has its inherent strengths and weaknesses, and may be utilized in a particular circumstance to accurately assess hepatic blood flow. It is therefore critical to select a measurement technique which yields the desired accuracy without interfering with the physiologic conditions under study. The methodology is presently available to achieve this end.

Animals↗
PubMed1985

Hormonal blockade modifies post-traumatic protein catabolism.

Protein catabolism following injury is associated with elevated levels of the stress hormones cortisol, glucagon, and the catecholamines. To study the effect of hormonal blockade on catabolic responses to surgery, 16 dogs underwent general anesthesia, a standard abdominal operation, and implantation of aortic and caval catheters. Five received phentolamine and propranolol continuously, at doses which block catecholamine effects. To prevent the rise in both catecholamines and cortisol, 6 received a high epidural anesthetic (T4-S3), started preoperatively and continued for 24 hr. Five dogs served as controls. Hindquarter amino acid flux was measured at 6 and 24 hr post-op. Pre- and post-op skeletal muscle biopsies were analyzed for amino acids. Urinary nitrogen was measured over 24 hr. Urinary nitrogen excretion was unaffected by treatment, but urinary creatinine fell from 0.039 +/- 0.002 g/24 hr X kg for controls to 0.03 +/- 0.002 for the epidural group and 0.031 +/- 0.001 for alpha and beta blockade (P less than 0.05). Hindquarter amino acid nitrogen efflux was decreased from -19.05 +/- 4.06 mumole/min X kg in controls to -8.98 +/- 0.86 in the epidural and -6.89 +/- 1.21 in the alpha- and beta-blockade groups (P less than 0.05). The urinary nitrogen loss, glutamine efflux, and fall in muscle glutamine produced by the operation were not prevented by either form of hormonal blockade, but hindquarter nitrogen efflux was diminished. Hormonal blockade inhibits net skeletal muscle protein catabolism without altering whole-body nitrogen loss. Hormones and other factors must be responsible for the increased ureagenesis that occurs following injury.

Adrenergic alpha-Antagonists↗
PubMed1985

Limited effects of prostaglandin inhibitors in Escherichia coli sepsis.

Responses to bacteremia include fever, leukocytosis, elaboration of acute-phase proteins, hypoferremia, and increased protein catabolism. To evaluate the role of prostaglandins in the mediation of these responses, the effects of intravenous ibuprofen (12.5 mg/kg X dose) were studied in eight dogs infused with live Escherichia coli. Thirteen dogs served as noninfected controls. Two of the eight animals that received ibuprofen died during the study, whereas all control animals with sepsis survived. Prostaglandin inhibition prevented the rise in temperature resulting from sepsis, while alterations in white cell count, C-reactive protein, and serum iron levels were unaffected. In addition, protein catabolism appeared to be similar in both groups. This minimal metabolic effect coupled with observed renal side effects makes the use of nonsteroidal, anti-inflammatory agents in sepsis of questionable benefit.

Acute Disease↗