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Biomedical subjects

D C Johnson

Publications and source records attributed to D C Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1993

Direct contact with herpes simplex virus-infected cells results in inhibition of lymphokine-activated killer cells because of cell-to-cell spread of virus.

Natural killer (NK) and lymphokine-activated killer (LAK) cells are disarmed after contact with herpes simplex virus (HSV)-infected cells. Cells infected with HSV-1 mutants that lack glycoproteins essential for viral entry into cells (gB, gD, gK, gH, and gL) did not inhibit LAK cells; cells infected with HSV-1 mutants that lack glycoproteins not required for virus entry into cells (gE, gI, gG, and gJ) inhibited lysis. LAK cells became infected after contact with target cells infected with wild-type HSV-1 but not with a gD-HSV-1, which cannot spread from cell to cell. Because LAK cells were inhibited only by very high concentrations of cell-free preparations of HSV and because neutralizing antibodies did not prevent infection of LAK cells in contact with infected cells, infection of LAK cells is probably greatly enhanced by the apposition of the effector and target cell membranes during target recognition. Disarming of immune effector cells by infection may be a general strategy for immune evasion by HSV.

Antigens, Viral↗
PubMed1993

Endogenous and exogenous glucocorticoids have different roles in modulating endotoxin lethality in D-galactosamine-sensitized mice.

Endotoxin sensitivity and dexamethasone protection have been assessed in mice that were adrenalectomized and also treated with D-galactosamine at the time of endotoxin challenge. Our data establish that adrenalectomy did not detectably alter the magnitude of the increased sensitivity induced by D-galactosamine alone. Furthermore, protection provided by acute exogenous glucocorticoid treatment was still demonstrable in these mice and was not influenced by chronic experimentally induced glucocorticoid deficiency. Our data confirm that the adrenalectomized mouse model of endotoxin lethality is characterized by increased sensitivity to endotoxin and establish that the magnitude of this sensitizing effect is more than 100-fold. We also show for the first time that adrenalectomy causes an appreciable kinetic shift in the endotoxic crisis and that dexamethasone, given at the time of endotoxin challenge, will significantly reverse the increased sensitivity to lethality. Our results indicate that the protective effects of corticosteroids may involve important chronic as well as acute responses. In particular, we conclude that endogenous glucocorticoid need not always increase host resistance to endotoxin, nor does such a circumstance eliminate the possibility for exogenous glucocorticoid-mediated protective effects.

Adrenalectomy↗
PubMed1993

A mutant herpes simplex virus type 1 unable to express glycoprotein L cannot enter cells, and its particles lack glycoprotein H.

Herpes simplex virus type 1 (HSV-1) glycoprotein H (gH) is essential for virus entry into cells and forms a hetero-oligomer with a newly described viral glycoprotein, gL. Normal folding, posttranslational processing, and intracellular transport of both gH and gL depend upon the coexpression of gH and gL in cells infected with vaccinia virus vectors (L. Hutchinson, H. Browne, V. Wargent, N. Davis-Poynter, S. Primorac, K. Goldsmith, A. C. Minson, and D. C. Johnson, J. Virol. 66:2240-2250, 1992). Homologs of gH and gL have been found in herpesviruses of all subgroups, and thus it appears likely that the gH-gL complex serves a highly conserved function during herpesvirus penetration into cells. To examine the role of gL in the infectious cycle of HSV-1, a mutant HSV-1 unable to express gL was constructed by inserting a lacZ gene cassette into the coding sequences of the UL1 (gL) gene. Because gL was found to be essential for virus replication, cell lines capable of expressing gL were constructed to complement the virus mutant. In the absence of gL, virus particles were produced, and these particles reached the cell surface; however, gL-negative particles purified from infected cells were also deficient in gH. Mutant virions lacking gH and gL were able to adsorb onto cells but were unable to enter cells and initiate an infection. Further, the role of gL in fusion of infected cells was reexamined. A mutation in HSV-1 (804) which produces the syncytial phenotype had previously been mapped to a region of the HSV-1 genome which includes the UL1 gene and no other open reading frame. However, in contrast to this previous report, we found that the syncytial mutation in 804 affects the UL53 gene, which encodes gK, a gene commonly mutated in syncytial viruses.

Adsorption↗
PubMed1993

Effects of temperature on muscle pHi and phosphate metabolites in newts and lungless salamanders.

The effect of acute alterations in body temperature (BT) on intracellular pH (pHi) and phosphate metabolites was assessed in white skeletal muscle of intact newts and lungless red-backed salamanders using 31P-nuclear magnetic resonance spectroscopy. pHi decreased with increasing BT in the tail muscle of both newts and lungless red-backed salamanders. The change in pH with change in temperature from 10 to 30 degrees C was -0.018 U/degrees C in newts and -0.041 U/degrees C in red backs. The calculated alpha-imidazole for skeletal muscle cytosol did not change (0.56) in newts from 10 to 30 degrees C but fell from 0.69 to 0.43 in red-backed salamanders. Phosphocreatine (PCr)/Pi fell and Pi/beta-ATP rose with increasing temperature in both newts and red backs; however, the change was much greater in red backs. Providing the red backs with O2 at 30 degrees C led to higher pH and alpha-imidazole, comparable to that of newts, along with increased PCr/Pi and lower Pi/beta-ATP. Thus newts maintain white skeletal muscle cell cytosol alpha-imidazole constant with changes in BT, whereas red backs apparently do not. However, at the BT of preference, red backs and newts maintain similar muscle pHi and alpha-imidazole. The method of gas exchange appears to strongly influence the ability of an animal to maintain its acid-base status over a range of temperatures, and our results suggest that behavioral regulation of BT may involve alpha-imidazole regulation as well.

Acclimatization↗
PubMed1993

High resolution mapping of Koch's triangle using sixty electrodes in humans with atrioventricular junctional (AV nodal) reentrant tachycardia.

BACKGROUND: Recent evidence suggests that atrioventricular junctional reentrant tachycardia (AVJRT) uses a reentrant circuit that involves the atrioventricular (AV) node, the atrionodal connections, and perinodal atrial tissue. Electrogram morphology has been used to target the delivery of radiofrequency energy to the site of the "slow pathway," a component of this reentrant circuit. The aim of this study was to localize precisely the sites of atrionodal connections involved in AVJRT and to examine atrial electrogram morphologies and their spatial distribution over Koch's triangle. METHODS AND RESULTS: Electrical activation of Koch's triangle and the proximal coronary sinus was examined in 13 patients using a 60-point plaque electrode and computerized mapping system. Recordings were made during sinus rhythm (n = 12), left atrial pacing (n = 8), ventricular pacing (n = 12), and AVJRT (n = 12). During sinus rhythm electrical activation approached Koch's triangle and the AV node from the direction of the anterior limbus, activating the anterior part of the triangle before the posterior part. A zone of slow conduction during sinus rhythm was found within Koch's triangle in 64% of patients. The pattern of atrial activation in Koch's triangle during anterograde fast pathway conduction was similar to that seen during anterograde slow pathway conduction. Retrograde fast pathway conduction during ventricular pacing and during anterior (typical) AVJRT caused earliest atrial activation at the apex of Koch's triangle near the AV node-His bundle junction. In individual patients the site of earliest atrial activation was similar for both anterior AVJRT and retrograde fast pathway conduction during ventricular pacing. Retrograde slow pathway conduction during ventricular pacing and during posterior (uncommon or atypical) AVJRT caused earliest atrial activation posterior to the AV node near the orifice of the coronary sinus. This posterior or "slow pathway" exit site was 15 +/- 4 mm from the His bundle. In individual patients the site of earliest atrial activation was similar for both posterior AVJRT and retrograde slow pathway conduction during ventricular pacing. In one patient anterograde and retrograde conduction occurred via separate slow pathways during AVJRT: Complex atrial electrograms with two or more components were observed near the coronary sinus orifice and in the posterior part of Koch's triangle in all cases. These were categorized as either low or high frequency potentials according to the rapidity of the second component of the electrogram. Low frequency potentials were present at the site of earliest atrial excitation during retrograde slow pathway conduction in 5 of 5 cases (100%) and high frequency potentials in 4 of 5 cases (80%). However, both slow and high frequency potentials could be found at sites up to 16 mm from the site of earliest atrial excitation. CONCLUSIONS: At least two distinct groups of atrionodal connections exist. The site of earliest atrial activation during anterior AVJRT is similar to that of fast pathway conduction during ventricular pacing. This site is close to the His bundle-AV node junction. The site of earliest atrial activation during posterior AVJRT is similar to that of slow pathway conduction during ventricular pacing. This site is near the coronary sinus orifice, approximately 15 mm from the His bundle. The anterograde slow pathway appears to be different from the retrograde slow pathway in some patients. Double atrial electrograms are an imprecise guide to the site of earliest atrial excitation during retrograde slow pathway conduction.

Adolescent↗
PubMed1993

A comparison of the effects of estradiol and 2- and 4-hydroxyestradiol on uterine ornithine decarboxylase activity in immature rats.

Effects of estradiol (E2) and catechol-estrogens (CEs: 2-OHE2 and 4-OHE2) on uterine ornithine decarboxylase (ODC) activity have been compared in immature rats. The intensity of their actions by s.c. (1 microgram) and intrauterine right-horn (i.u., 25 ng) injection was in the order of: 4-OHE2 > or = E2 > 2-OHE2. Although i.u. -injection of E2 caused an increase in ODC activity in the left (intact)-horn, which was about 60% that of the right-horn, the effects by CEs were limited only to the right-horn. The results are consistent with the previous view about the order of the potency of 4-OHE2 and 2-OHE2 and also suggest that locally produced CEs may play a role in the physiological functions of the production site.

Animals↗
PubMed1993

Embryo implantation in the rat uterus induced by epidermal growth factor.

The present study was undertaken to determine whether the mechanism of embryo transfer is a factor in the action of epidermal growth factor (EGF) in initiation of implantation. Unilateral intrauterine infusion of 3 microliters buffered saline, or saline containing 1.5 micrograms EGF, plus i.v. injection of 100 micrograms EGF 2 h later resulted in implantation sites in all animals within 48 h. In several animals implantation was also initiated in the non-injected uterine horn. Administration of indomethacin 1 h before the intrauterine injection completely blocked the effect of EGF but not that of 25 ng oestradiol. The results confirm that EGF can replace oestrogen for initiation of implantation provided that the uterine trauma associated with embryo transfer, that is puncture, is provided. The mechanisms involved remain to be resolved.

Animals↗
PubMed1993

Natural adrenocorticosteroids do not restore resistance to endotoxin in the adrenalectomized mouse.

Chronic loss of adrenocorticosteroid activity by adrenalectomy (10 days) or acute inhibition of glucocorticoid receptor function by injection of an anti-progestin (RU-38486) increased sensitivity to lipopolysaccharide about 200-fold, compared to that of control animals. Daily subcutaneous injection of a mixture of the natural glucocorticoid corticosterone and the mineralocorticoid deoxycorticosterone did not restore resistance to the endotoxin. The largest dose of steroid, 400 micrograms corticosterone + 200 micrograms deoxycorticosterone, provided only partial protection against 20 micrograms LPS, which was 10% of the LD50 for animals with adrenals. The mechanisms involved in lack of effectiveness of natural corticosteroids will require further experimentation.

Adrenal Cortex Hormones↗
PubMed1992

Cellular localization and factors controlling rat placental cytochrome P45017 alpha (CYP17): 17 alpha-hydroxylase/C17,20-lyase activity.

The junctional zone of the rat placenta, during the second half of gestation, contains cytochrome P45017 alpha (CYP17), the enzyme responsible for androgen synthesis. The present study was undertaken to 1) determine the cellular source of this enzyme and 2) examine the effect of various hormones upon the activity of the enzyme. An antiserum to a 15-amino-acid peptide, representing the carboxyl terminus of rat testicular CYP17, was raised in rabbits. This antiserum inhibited the activity of rat ovarian microsomal C17,20-lyase and reacted with a microsomal protein of about 55 kDa from ovarian and placental homogenates on Western immunoblots. When used for immunohistochemistry the antibody stained only the trophoblastic giant cells of the Day 15 (sperm-positive Day 1) rat placenta; not all giant cells were stained to the same extent and not all cells were stained. Removal of the hypophysis on Day 3 of pregnancy, and delay of implantation, resulted in increased placental C17,20-lyase activity in NIMR/AS dwarf--which lack only growth hormone--but not in normal Holtzman strain rats. Growth hormone, prolactin, testosterone propionate, excess progesterone, or withholding estrogen had no significant effect upon the specific activity of the placental enzyme. In contrast, increases in serum estradiol, produced endogenously by hCG or LH, or exogenously by silastic capsules containing diethylstilbestrol or estradiol-17 beta, significantly reduced enzyme activity. The results indicate that trophoblastic giant cells of the chorioallantoic and choriovitelline placentas contain the androgen-synthesizing enzyme system of the rat placenta and that this system is exquisitely sensitive to inhibition by estrogen.

Animals↗
PubMed1992

Identification and characterization of the virion-induced host shutoff product of herpes simplex virus gene UL41.

The virion-induced host shutoff product of the herpes simplex virus UL41 gene is required for shutoff of host translation and degradation of cellular mRNAs. We employed a rabbit antipeptide antiserum to identify a 58K UL41-related phosphoprotein in infected cells. We also provide evidence that this protein is a component of the virus particle, consistent with its role in virion-induced shutoff.

Amino Acid Sequence↗
PubMed1992

The ICP4 binding sites in the herpes simplex virus type 1 glycoprotein D (gD) promoter are not essential for efficient gD transcription during virus infection.

Activation of the early and late genes of herpes simplex virus type 1 during infection in tissue culture requires functional immediate-early regulatory protein ICP4. ICP4 is a specific DNA-binding protein which recognizes a variety of DNA sequences, many of which contain the consensus ATCGTC. In general, mutations which impair the ability of ICP4 to bind to DNA also eliminate its ability to activate viral early and late promoters both in transfection assays and in the infected cell. However, the role of ICP4 binding sites in the viral genome is unclear; many early and late promoters do not contain consensus binding sites in their vicinity. The glycoprotein D (gD) gene contains two well-characterized ICP4 binding sites upstream of its promoter and a third downstream of the transcription start site. Multimerization of one of these sites has been shown to increase the response of the gD promoter to ICP4 in transfection assays, while their removal reduces stimulation of the gD promoter by ICP4 in vitro. To assess the role of these binding sites during virus infection, we have constructed a recombinant viral genome which has mutations affecting all three. Comparison of the amounts of gD RNA synthesized by the recombinant and wild-type viruses indicated that the mutations had little or no effect on the activity of the gD promoter. Therefore, either the sites have no essential role in gD promoter regulation in the presence of all of the herpes simplex virus type 1 IE polypeptides during a normal infection or they can be functionally substituted by other ICP4 binding sites elsewhere in the genome.

Animals↗
PubMed1992

A novel herpes simplex virus glycoprotein, gL, forms a complex with glycoprotein H (gH) and affects normal folding and surface expression of gH.

A glycoprotein encoded by the UL1 gene of herpes simplex virus type 1 (HSV-1) was detected in infected cells with antipeptide sera. The UL1 gene has previously been implicated in virus-induced cell fusion (S. Little and P. A. Schaffer, Virology 112:686-697, 1981). Two protein species, a 30-kDa precursor form and a 40-kDa mature form of the glycoprotein, both of which were modified with N-linked oligosaccharides, were observed. This novel glycoprotein is the 10th HSV-1 glycoprotein to be described and was named glycoprotein L (gL). A complex was formed between gL and gH, a glycoprotein known to be essential for entry of HSV-1 into cells and for virus-induced cell fusion. Previously, it had been reported that gH expressed in the absence of other viral proteins was antigenically abnormal, not processed, and not expressed at the cell surface (U.A. Gompels and A. C. Minson, J. Gen. Virol. 63:4744-4755, 1989; A. J. Forrester, V. Sullivan, A. Simmons, B. A. Blacklaws, G. L. Smith, A. A. Nash, and A. C. Minson, J. Gen. Virol. 72:369-375, 1991). However, gH coexpressed with gL by using vaccinia virus recombinants was antigenically normal, processed normally, and transported to the cell surface. Similarly, gL was dependent on gH for proper posttranslational processing and cell surface expression. These results suggest that it is a hetero-oligomer of gH and gL which is incorporated into virions and transported to the cell surface and which acts during entry of virus into cells.

Amino Acid Sequence↗
PubMed1992

Identification and characterization of a novel herpes simplex virus glycoprotein, gK, involved in cell fusion.

Antipeptide sera were used to identify a novel glycoprotein encoded by the UL53 gene of herpes simplex virus type 1 (HSV-1). The UL53 gene product is thought to play a central role in regulating membrane fusion because mutations giving rise to the syncytial phenotype, wherein cells are extensively fused, frequently map to this gene. A single 40-kDa protein, designated gK (the ninth HSV-1 glycoprotein to be described), was detected with antipeptide sera in cells infected with both wild-type and syncytial strains of HSV-1 which were labelled with [35S]methionine and [35S]cysteine or with [3H]glucosamine, and this protein was sensitive to treatment of cells with tunicamycin. With all other HSV glycoproteins studied to date, at least two glycosylated species, often differing substantially in electrophoretic mobility, have been observed in infected cells; thus, gK is unusual in this respect. The 40-kDa gK protein was also immunoprecipitated from cells infected with a recombinant adenovirus vector carrying the UL53 gene. Two glycosylated species of 39 and 41 kDa were produced when UL53 mRNA was translated in vitro in the presence of microsomes, and these proteins differed from gK produced in infected cells not only because they possessed different electrophoretic mobilities but also because they were unable to enter gels after being heated. In addition, a 36-kDa protein was detected in extracts from cells infected with HSV-2 with use of these sera.

Adenoviridae↗
PubMed1992

Environmental tobacco smoke and cardiovascular disease. A position paper from the Council on Cardiopulmonary and Critical Care, American Heart Association.

Although the number of cardiovascular deaths associated with environmental tobacco smoke cannot be predicted with absolute certainty, the available evidence indicates that environmental tobacco smoke increases the risk of heart disease. The effects of environmental tobacco smoke on cardiovascular function, platelet function, neutrophil function, and plaque formation are the probable mechanisms leading to heart disease. The risk of death due to heart disease is increased by about 30% among those exposed to environmental tobacco smoke at home and could be much higher in those exposed at the workplace, where higher levels of environmental tobacco smoke may be present. Even though considerable uncertainty is a part of any analysis on the health affects of environmental tobacco smoke because of the difficulty of conducting long-term studies and selecting sample populations, an estimated 35,000-40,000 cardiovascular disease-related deaths and 3,000-5,000 lung cancer deaths due to environmental tobacco smoke exposure have been predicted to occur each year. The AHA's Council on Cardiopulmonary and Critical Care has concluded that environmental tobacco smoke is a major preventable cause of cardiovascular disease and death. The council strongly supports efforts to eliminate all exposure of nonsmokers to environmental tobacco smoke. This requires that environmental tobacco smoke be treated as an environmental toxin, and ways to protect workers and the public from this health hazard should be developed. According to a 1989 Gallup survey commissioned by the American Lung Association, 86% of nonsmokers think that environmental tobacco smoke is harmful and 77% believe that smokers should abstain in the presence of nonsmokers.(ABSTRACT TRUNCATED AT 250 WORDS)

American Heart Association↗
PubMed1992

Differential effects of dichlorodiphenyltrichloroethane analogs, chlordecone, and 2,3,7,8-tetrachlorodibenzo-p-dioxin on establishment of pregnancy in the hypophysectomized rat.

Many of the organochlorine pesticides have been shown to elicit estrogenic responses in laboratory animals. Two estrogenic actions, initiation of implantation and maintenance of pregnancy, were examined in progesterone-primed, delayed-implanting, hypophysectomized rats exposed to several polychlorinated hydrocarbons. The insecticide P,P'-dichlorodiphenyltrichloroethane (DDT) was nearly devoid of estrogenic activity for initiating implantation, as was a dichloro analog, 1,1-dichloro-2-[p-chlorophenyl],2-[o-chlorophenyl]ethane (O,P'-DDD), but another such analog, 1,1-dichloro-2-(p-chlorophenyl),2-(o-chlorophenyl)ethylene (O,P'-DDE), was nearly as estrogenic as the O,P'-DDT isomer of DDT and the methoxylated analog methoxychlor. The latter three compounds not only initiated implantation, but maintained pregnancy when given in large (200 mg/kg) and repeated doses. Another insecticide, chlordecone (Kepone) was more estrogenic than any of the DDT analogs and maintained pregnancy with a single dose of 50 mg/kg. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a toxic contaminant of herbicide production, did not induce implantation at a dose of 125 micrograms/kg, but inhibited the implantation initiated by estrone in 35% of the animals. The mechanism of this antiestrogenicity is unknown but most probably does not involve direct action via the classical estrogen receptor. The possible interference with the normal blastocyst-uterine interactions of these polychlorinated xenobiotics may be an important factor in their being considered reproductive toxins.

Animals↗
PubMed1992

Acute renal failure and glomerulopathy caused by nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs are now one of the most common causes of acute renal failure (ARF). To define more clearly the magnitude of the problem, we reviewed all cases of ARF in the Reno (Nev) area from 1972 through 1986. Twenty-seven cases of ARF and seven cases of glomerulopathy were identified, primarily during the last 5 years of the study period. Twenty-three of the cases of ARF and six of the cases of glomerulopathy cleared an average of 23 and 118 days, respectively, after treatment with the nonsteroidal anti-inflammatory drug was stopped. Two cases of ARF persisted, and two patients died. Proteinuria, hematuria, and casts were prominent in both ARF and glomerulopathy but were more pronounced in the glomerulopathies. The treatment of choice is to stop the use of the nonsteroidal anti-inflammatory drug. The role of steroids has not been evaluated.

Acute Kidney Injury↗