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Biomedical subjects

D E Johnston

Publications and source records attributed to D E Johnston.

At least 19 recordsLinked to original sources
PubMed1992

Sickle cell crisis and cocaine hepatotoxicity.

Hepatic dysfunction occurs in up to 10% of patients with sickle cell crisis; however, hepatic failure is quite unusual. Cocaine hepatotoxicity has recently been recognized in humans with liver biopsies showing varying patterns of necrosis. Most patients reported with cocaine intoxication have rhabdomyolysis with renal failure, and half of the cases have been fatal. A patient with concomitant sickle cell crisis and cocaine intoxication presented with hepatic failure, coagulopathy, and encephalopathy. Transjugular liver biopsy showed focal areas of confluent necrosis and large areas of collapse. Cocaine intoxication should be considered in the differential diagnosis of hepatic failure in patients with sickle cell anemia.

Adult↗
PubMed1991

Cirrhosis and portal hypertension in a patient with adult Niemann-Pick disease.

A woman with known Niemann-Pick disease, type B, presented at age 33 with upper gastrointestinal bleeding, ascites, and peripheral edema. Evaluation showed massive hepatosplenomegaly, infiltration of the liver with Niemann-Pick cells, cirrhosis, and evidence of portal hypertension. Chronic gastrointestinal bleeding, thrombocyctopenia, and platelet dysfunction were treated successfully by splenectomy. Cirrhosis and portal hypertension have not been reported previously in adult Niemann-Pick disease in the absence of some other cause.

Adult↗
PubMed1991

Synthesis and degradation of eicosanoids in primary rat hepatocyte cultures.

Arachidonic acid metabolites may play an important role in liver physiology, yet hepatocyte prostaglandin synthesis has not been characterized extensively. We used RIA to study production and clearance of several eicosanoids in confluent primary cultures of rat hepatocytes in serum-free, hormonally-defined medium. Under basal, unstimulated conditions 6-keto-PGF1 alpha (spontaneous breakdown product of prostacyclin) and 13,14-dihydro-15-keto-PGE (DHK-PGE, a metabolite of PGE) accumulated in the culture medium. Hepatocytes cleared 6-keto-PGF1 alpha, thromboxane B2, and DHK-PGE from the medium. Production of eicosanoids by primary cultures appeared resistant to indomethacin and several other cyclooxygenase inhibitors. This apparent resistance to indomethacin was not caused by rapid metabolism of indomethacin, by failure of the drug to enter hepatocytes, or by insensitivity of hepatocyte cyclooxygenase to the drug. Metabolism of PGE to DHK-PGE may be saturated under in vitro conditions. Hepatocytes can synthesize significant amounts of eicosanoids, although they are probably less active in this regard than are non-parenchymal cells.

Animals↗
PubMed1990

Wound healing in skin.

Wound healing in mammals occurs by a process of regeneration and scar tissue production. In particular, epithelium has marked regenerative capacity. Healing is an active process from the moment the wound is inflicted--a "lag" phase does not exist. In surgery the important factors affecting wound healing are protein deficiency, uremia, corticosteroids, and local tissue injury. Stimulants to wound healing are not available for clinical application.

Animals↗
PubMed1990

Care of accidental wounds.

In wound management, the first consideration is first aid, and the primary aim must be to minimize further tissue damage. Definitive care includes cleaning, debridement, and repair procedures. Saline solution is the key to cleaning; antibiotics and antiseptics are not always indicated. Debridement should be done surgically. The wound is then managed by primary closure or delayed primary closure, or it is left open to heal by contraction and epithelialization.

Animals↗
PubMed1990

Tension-relieving techniques.

Excess pressure by sutures in wound closure can lead to "cutting out" of sutures or to ischemia of tissue adjacent to the sutures. Excess pressure can be avoided by use of specific suture patterns or surgical procedures. The surgeon should select the simplest procedure and should consider, in order of preference, the use of subdermal sutures, tension-relieving sutures, and then surgical procedures, including undermining, relaxing incisions, and plasty procedures.

Animals↗
PubMed1990

Tissue expanders.

The use of an inflatable bag to obtain skin for flaps is an exciting new reconstruction procedure in veterinary surgery. The silicone elastomer balloon is placed subcutaneously, adjacent to a defect, and slowly inflated over a period of several weeks. The resulting skin flap can be used to correct the defect or replace the skin loss. The use of this procedure is described in animals.

Animals↗
PubMed1989

Factors influencing the detachment of a polymer-associated Acinetobacter sp. from stainless steel.

The role of an extracellular polymer secreted by an Acinetobacter sp. attached to stainless steel was investigated. Parameters expected to influence polymer conformation, viz. temperature, pH, ionic strength and the concentration of calcium and magnesium ions, were altered and the resulting detached bacteria enumerated. Increasing both the temperature and pH resulted in increased numbers of bacteria detached. The effects of increasing the concentration of sodium chloride up to 100 mM and magnesium or calcium chloride up to 30 mM were small and, although statistically significant, were considered unlikely to have had major influence on the association of the bacteria with the stainless steel surfaces. Treatments including ultraviolet irradiation of surface-associated bacteria always resulted in removal of greater numbers of bacteria when compared to treatments where irradiation was not employed. The results indicate that an adhesive extracellular acidic polysaccharide may mediate the attachment of the Acinetobacter sp. to stainless steel.

Acinetobacter↗
PubMed1988

Correction of the genetic defect in hepatocytes from the Watanabe heritable hyperlipidemic rabbit.

Familial hypercholesterolemia is an inherited disease in humans that is caused by a defect in the receptor for low density lipoproteins (LDLR). The existence of an animal model for this disease, the Watanabe heritable hyperlipidemic (WHHL) rabbit, makes it an attractive candidate for developing new therapies that involve gene transfer into liver. As a first step toward the development of these therapies, we report the use of retrovirus-mediated gene transfer to correct the genetic defect in hepatocytes isolated from WHHL rabbits. A series of retroviral vectors that express the gene for human LDLR were constructed, each differing in the transcriptional elements used to drive LDLR expression. Helper-free amphotropic virus stocks representing each construct were then used to infect primary cultures of hepatocytes that were isolated from newborn WHHL rabbits. The efficiency of transduction, as measured by Southern analysis of integrated proviral sequences, ranged from 20% to 100%. Expression of human LDLR was analyzed by blot hybridization analysis of total cellular RNA and by biochemical and in situ analyses of transduced cultures for receptor function. The vector in which the expression of LDLR was driven by the viral long terminal repeat sequence produced the greatest quantity of LDLR RNA and protein in WHHL hepatocytes; LDLR activity approached normal levels in these cultures.

Animals↗
PubMed1988

Retrovirus-mediated transduction of adult hepatocytes.

Retrovirus-mediated gene transfer was used to develop a method for introducing genes into primary cultures of adult rat hepatocytes. Subconfluent monolayers of hepatocytes, cultured in hormonally defined media on different matrix substrata, were infected with helper-free stocks of a replication-defective retrovirus that constitutively expresses high levels of beta-galactosidase. Retrovirus-mediated transduction was measured by two methods: (i) an in situ cytochemical stain that specifically detects the expression of viral expressed beta-galactosidase, and (ii) Southern blot analysis, which measures the relative copy number of integrated provirus. Maximal transduction efficiency of approximately equal to 25% was achieved when the cells were infected after 3 days in culture; matrix had little effect on transduction efficiency. Enzyme cytochemical (catalase and glucose 6-phosphatase) and peroxidase immunocytochemical (asialoglycoprotein and UDP-glucuronosyltransferase) analyses of the cultures indicated that greater than 95% of cells were hepatocytes. The demonstration of hepatocyte-specific organelles in cells expressing the viral-directed beta-galactosidase provided unambiguous evidence for the transduction of hepatocytes. These methods should be useful in the development of liver-directed somatic gene therapy and in the study of liver-specific gene regulation.

Animals↗
PubMed1987

Histocompatibility antigens in primary biliary cirrhosis.

HLA-A, -B, and -DR antigens were examined in 71 patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind trial of colchicine versus placebo. All patients had typical laboratory and histological features of PBC, except that six had a negative test for antimitochondrial antibody. Frequencies of these antigens were compared with the international Caucasian panel of the Eighth International Workshop and with a local Caucasian panel. Antigen frequencies were compared using the chi 2 test, with a correction for the number of antigens tested. The PBC patients had a significant excess of DR4 (29 of 70 typed, or 41.1%) compared to the international (804 of 3811, or 21.1%, corrected p value less than 0.05) but not the local panel (47 or 129, or 36.4%). Of PBC patients, 52.9% had only one DR antigen identified, compared to 67.5% for the international panel and 49.6% for the local panel. In past studies, the HLA antigen most strongly correlated with PBC was DR8, but this was not included in our panel of antisera. However, no significant relationship between HLA and PBC was found among the antigens screened.

Colchicine↗
PubMed1986

Evaluation of canine hyperadrenocorticism, using computed tomography.

Abdominal computed tomography was performed in 9 dogs with hyperadrenocorticism and in 2 healthy dogs. Both adrenal glands were identified in all dogs. Computed tomography allowed accurate identification of the sites of adrenal gland dysfunction, when interpreted in combination with a biochemical diagnosis of canine hyperadrenocorticism. This accuracy permitted the retroperitoneal approach to be used for all adrenalectomies. Use of contrast medium (although not essential) was helpful in the computed tomographic identification of blood vessels, kidneys, and other abdominal organs.

Adrenal Cortex Neoplasms↗
PubMed1986

Influence of plasticizer on soft polymer gelation.

An evaluation has been made of the soft polymer gel systems of the type used as prosthodontic short-term denture-lining materials. The purpose of the study was to determine the effect upon gel strength and gelation time produced by variations in the composition of the plasticizer liquids. Poly(ethylmethacrylate) co-polymers were mixed with combinations of ethyl alcohol and the esters dibutyl phthalate (DBP), butylphthalyl butylglycolate (BPBG), and benzyl salicylate (BS). The relative rate of gelation of plasticizer polymer compositions was obtained by means of a reciprocating rheometer. The gelation rate was found to increase rapidly with an increase in the ethyl alcohol content. Significantly shorter gelation times were also found with liquids containing the lower-molecular-weight esters. A linear relationship was found between the ethyl alcohol content and the log of the gelation time. The higher-molecular-weight esters produced the strongest gel. A linear relationship was found between the gelation (log) times and the seven-day puncture strength. The ratio of polymer to plasticizer liquid was found to have a very significant influence upon the puncture strength and gelation time. Molecular weight or molecular volume of the ester plasticizers was found to have a greater influence on gel formation than the cohesive energy parameter. The strong polar bonding of ethyl alcohol was found to have a significant influence on both the rate of gel formation and the subsequent gel strength. The data indicate that controlled variations in the characteristics of plasticity and gel strength of dental soft polymer systems can be made to suit different clinical prosthodontic requirements.

Chemical Phenomena↗
PubMed1978

A steady state assay for the RNA polymerase initiation reaction.

A new assay yielding mechanistic information on the initiation reaction of Escherichia coli RNA polymerase has been developed. It was found to be useful in characterizing the promoters of bacteriophage DNA templates. The binding of the first two triphosphates in an RNA sequence was determined to be equilibrium ordered with ATP binding first followed by UTP on the lambda promoters PL. and PR. The products resulting from phosphodiester bond formation, pppApU and PPi, dissociated rapidly in the absence of the other triphosphates required for RNA synthesis. The resulting steady state conversion of ATP and UTP into pppApU was the basis for the new assay. The rate-limiting step in the initiation reaction was not precisely determined, but it was argued not to be entirely the release of product. The Zn2+ chelator, 1,10-phenanthroline, was partially characterized and found to be an uncompetitive inhibitor of ATP in the reaction (Ki = 100 micrometer). The unique advantage of this steady state assay is that several steps in the RNA initiation process are amplified kinetically and thus can be examined separately with techniques applicable to any other two-substrate, two-product enzyme reaction.

Coliphages↗