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D C Johnson

Publications and source records attributed to D C Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1991

Hydrazine sulfate protects D-galactosamine-sensitized mice against endotoxin and tumor necrosis factor/cachectin lethality: evidence of a role for the pituitary.

In previously published studies, we had demonstrated that hydrazine sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same hydrazine sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of hydrazine sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of hydrazine sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of hydrazine sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after hydrazine sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by hydrazine sulfate. Although hydrazine sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by hydrazine sulfate. We conclude that hydrazine sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the hydrazine sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.

Animals↗
PubMed1991

Identification of an immunodominant cytotoxic T-lymphocyte recognition site in glycoprotein B of herpes simplex virus by using recombinant adenovirus vectors and synthetic peptides.

Cytotoxic T-lymphocyte (CTL) responses to herpes simplex virus (HSV) polypeptides play an important role in recovery from infection and in preventing latency. We have previously shown that glycoprotein B (gB) is a major target recognized by HSV-specific CTLs in C57BL/6 (H-2b) and BALB/c (H-2d) mice but not in CBA/J (H-2k) mice (L. A. Witmer, K. L. Rosenthal, F. L. Graham, H. M. Friedman, A. Yee, and D. C. Johnson, J. Gen. Virol. 71:387-396, 1990). In this report, we utilize adenovirus vectors expressing gB with various deletions to localize an immunodominant site in gB, recognized by H-2b-restricted anti-HSV CTLs, to a region between residues 462 and 594. Overlapping peptides spanning this region were synthesized and used to further localize the immunodominant site to residues 489 to 515, a region highly conserved in HSV type 1 (HSV-1) and HSV-2 strains. The 11-amino-acid peptide was apparently associated exclusively with the Kb major histocompatibility complex gene product and not the Db gene product. In contrast, H-2d-restricted CTLs recognized an immunodominant site between residues 233 and 379.

Adenoviridae↗
PubMed1991

Sodium salicylate centrally augments ventilation through cholinergic mechanisms.

Several different stimuli, including hydrogen ions, may exert their effect on central ventilatory control through cholinergic mechanisms. Salicylates are known to be central respiratory stimulants. Therefore this study explored whether the ventilatory effect of sodium salicylate (SAL) is through cholinergic mechanisms. Ventriculocisternal perfusion was used in spontaneously breathing anesthetized (pentobarbital sodium, 30 mg/kg) mongrel dogs to study the effects of SAL (50 mM), atropine (ATR, 4.8 mM), and SAL-ATR on ventilation. After 15 min of perfusion with mock cerebrospinal fluid, each test agent was perfused for 15 min at a rate of 1 ml/min. Cardiovascular and ventilatory parameters were monitored. Values at 15 min of test agent perfusion were compared with values at 15 min of mock cerebrospinal fluid perfusion, with each animal used as its own control. Body temperature was kept between 37.5 and 39.0 degrees C. Perfusion with SAL increased minute ventilation (VE) by 54% (P less than 0.005) and respiratory frequency by 50% (P less than 0.005). Tidal volume was not changed, but mean inspiratory flow rate increased (P less than 0.05). Perfusion with ATR decreased VE by 22% (P less than 0.1), and perfusion with SAL-ATR decreased VE by 20% (P = 0.01). No significant cardiovascular changes were noted in any group. We conclude that SAL increases VE centrally, primarily by increasing respiratory frequency. Because ATR blocked this effect, cholinergic mechanisms are probably involved in the salicylates' central stimulation of ventilation.

Animals↗
PubMed1991

What is the best method for assessing the long-term outcome of surgery for accessory pathways and atrioventricular junctional reentrant tachycardias?

The success of surgery for supraventricular tachycardia (SVT) is evaluated by a variety of methods in different hospitals. Unfortunately, the predictive values of these methods are not known. We therefore compared the various methods in 261 patients undergoing surgery for SVT at Westmead Hospital since 1981. Surgical outcome was assessed by early tests during the first week after surgery (serial 12-lead electrocardiograms, telemetric monitoring of the electrocardiogram, and electrophysiological study performed using epicardial wires); later tests at 6 months after surgery (12-lead electrocardiograms and electrophysiological study); and symptomatic review done by telephone interview at a median of 34 months after surgery. Early tests were obtained in 97%, later tests were obtained in 76%, and symptomatic review was obtained in 98% of patients. All of the examined tests were inaccurate methods of surgical assessment compared with the late electrophysiological study. A large proportion of the patients proven to be surgical failures at the late electrophysiological study were not detected by early tests (83%), by later electrocardiograms (66%), or by symptomatic assessment (41%). Accurate assessment of surgical outcome requires a late electrophysiological study to permit comparison of surgical techniques. Late electrophysiological study also provides accurate information on the current risks and benefits of proposed surgery for communication to patients to enable them to make an informed decision on future treatment. Most patients are willing to have a late electrophysiological study and usually benefit from clarification of their true surgical outcome.

Cardiac Pacing, Artificial↗
PubMed1991

Patients with two types of atrioventricular junctional (AV nodal) reentrant tachycardia. Evidence that a common pathway of nodal tissue is not present above the reentrant circuit.

BACKGROUND: The site of the reentrant circuit in atrioventricular (AV) junctional reentrant tachycardia has not been defined; in particular, the existence of a common pathway of AV nodal tissue above the reentrant circuit is controversial. METHODS AND RESULTS: Two types of AV junctional reentrant tachycardia were induced in each of three patients at electrophysiological study. In one type of tachycardia (anterior), the onset of atrial activity occurred from 0 to 12 msec before the onset of ventricular activation, and earliest atrial activity was recorded near the His bundle. In the second type of tachycardia (posterior), the ventriculoatrial intervals were longer (76-168 msec), and earliest atrial activity was recorded near the mouth of the coronary sinus. In individual patients, the two types of tachycardia had different cycle lengths. Posterior AV junctional reentrant tachycardia was not a fast-slow form of AV junctional reentry in at least two of the three patients. Surgical cure was attempted in two patients. In one patient, anterior AV junctional reentrant tachycardia was abolished by dissection of the anterior perinodal atrium, but posterior AV junctional reentrant tachycardia could still be induced. At reoperation 4 months later, dissection of the posterior perinodal atrium abolished posterior AV junctional reentrant tachycardia while preserving AV conduction. CONCLUSION: Differences in ventriculoatrial intervals and cycle lengths and the results of selective surgery suggest that the two types of AV junctional reentrant tachycardia used different reentrant circuits. These observations imply that a common pathway of AV nodal tissue is not present above the reentrant circuit and suggest that perinodal atrium is part of these circuits.

Adolescent↗
PubMed1991

Transition from exercise to rest. Ventilatory and arterial blood gas responses.

The mechanisms leading to rapid changes in arterial blood gas values soon after exercise ends have not been well established. To further study these phenomena, we exercised seven normal male volunteers to exhaustion on a cycle ergometer with a 25-W/min ramped protocol measuring arterial blood gas values, and breath-by-breath gas exchange from rest to exercise and through 15 minutes of recovery. Arterial PO2 (PaO2) increased from 108 mm Hg at peak exercise to 125 mm Hg at 2 minutes of recovery. There was a smaller rise in calculated alveolar PO2 (PAO2) from 121 to 128 mm Hg over the same period. Arterial PCO2 (PaCO2) fell from 35.0 mm Hg to 31.9 mm Hg. The gas exchange ratio R rose from 1.21 to 1.52, after having peaked at 1.68 at 1 minute. The alveolar-arterial O2 gradient (P[A-a]O2) fell from 12.3 mm Hg at peak exercise to 3.2 mm Hg at 2 minutes. Following exercise, the rise in R is related to a more rapid fall in O2 uptake than in CO2 output, and the fall in P(A-a)O2 is probably related to improved V/Q relationships and to a rise in mixed venous PO2. We conclude that the rise in PaO2 in the recovery period after progressive nonsteady state exercise is due to several factors, including a fall in P(A-a)O2 and a rise in PAO2 due primarily to an elevation of R and also to a fall in PaCO2.

Adult↗
PubMed1990

Antigenic and functional analysis of a neutralization site of HSV-1 glycoprotein D.

Herpes simplex virus glycoprotein D is a component of the virion envelope and appears to be involved in attachment, penetration, and cell fusion. Monoclonal antibodies (MAbs) against this protein can be arranged in groups, on the basis of a number of biological and biochemical properties. Group I antibodies are type-common, have high complement-independent neutralization titers, recognize discontinuous (conformational) epitopes, and block each other in a binding assay. The sum of their epitopes constitutes antigenic site I of gD. Using a panel of neutralization-resistant mutants, we previously found that group I MAbs can be divided into two subgroups, Ia and Ib, such that mutations selected with Ia antibodies have little or no effect on binding and neutralization by Ib antibodies, and vice versa. Antigenic site I therefore consists of two parts, Ia and Ib. We have now identified the point mutations which prevent neutralization. Two Ib MAbs (DL11 and 4S) selected a Ser to Asn change at residue 140; this alteration creates a new N-linked glycosylation site, which is used. A third Ib MAb (D2) selected a Gln to Leu change at 132. The mutation selected by the Ia MAb HD1 (Ser to Asn at residue 216) is identical to that selected by MAb LP2, another Ia antibody. By using oligonucleotide-directed mutagenesis, we have produced gD genes with combinations of the above mutations. Attempts to recombine these genes into the virus genome were unsuccessful, suggesting that the combinations are lethal. This was confirmed by a complementation assay which measures the ability of gD transiently expressed in transfected Vero cells to rescue the production of infectious virus by the gD-minus mutant F-gD beta.

Base Sequence↗
PubMed1990

Herpes simplex virus IgG Fc receptors induced using recombinant adenovirus vectors expressing glycoproteins E and I.

Evidence has been presented that herpes simplex virus (HSV) immunoglobulin (IgG) Fc receptors are composed of a complex of two glycoproteins, gE and gI. In previous studies, cells infected with HSV-1 mutants lacking either gE or gI bound lower levels of soluble IgG than cells infected with wild-type viruses suggesting that both gE and gI were required for IgG binding. We have reevaluated the Fc receptor activity of these mutants using a more sensitive assay involving IgG-coated erythrocytes and have found that cells infected with a gE- mutant HSV-1 did not bind IgG-coated erythrocytes whereas cells infected with a gI- mutant retained some Fc binding activity. To further study HSV-induced Fc receptors recombinant adenovirus vectors expressing gE or gI were constructed. Cells expressing gE alone bound both soluble IgG and IgG-coated red cells, although the binding was consistently lower than that observed with HSV-infected cells or cells expressing both gE and gI. Cells expressing only gI were unable to bind either soluble IgG or IgG-coated erythrocytes. These results support the conclusion that both gE and gI are required for full Fc receptor activity, although gE alone can bind IgG to a lesser extent.

Adenoviridae↗
PubMed1990

Cytotoxic T lymphocytes specific for herpes simplex virus (HSV) studied using adenovirus vectors expressing HSV glycoproteins.

In previous work, we observed that H-2k-restricted herpes simplex virus (HSV)-specific cytotoxic T lymphocytes (CTLs) were effectively able to lyse transfected target cells expressing HSV glycoprotein C (gC), but not cells expressing gB, gD or gE. To confirm and extend our observations on the specificity of anti-HSV CTLs, recombinant adenovirus (Ad) vectors able to express HSV-1 gB or gC (AdgB2 or AdgC) were constructed. Syngeneic target cells infected with AdgB2 were efficiently lysed by primary H-2b and H-2d, but not by H-2k-restricted HSV-specific CTL. Limiting dilution studies indicated that 4 to 10% of H-2b-restricted HSV-specific CTLs recognize gB. H-2k, H-2b and H-2d-restricted anti-HSV-1 CTLs were unable to lyse AdgC-infected syngeneic target cells. To examine the apparent discrepancy between the previous results involving transfected H-2k cells expressing gC and the present results involving AdgC-infected cells, gC-expressing cell lines used in previous experiments were subcloned and retested in CTL assays. DC2 cells which were lysed by HSV-specific CTLs in the previous experiments remained sensitive to anti-HSV CTLs but two other clones derived from the same transfection were not lysed. Further, L cells transfected with the gC or gD gene coupled to the mouse mammary tumour virus promoter and capable of expressing high levels of the glycoproteins following dexamethasone induction were not lysed by H-2k-restricted anti-HSV CTLs. These results suggest that HSV-specific CTLs do not recognize gC, at least when it is expressed using an Ad vector and in most transfected cell lines, whereas a significant proportion of anti-viral CTLs recognize gB presented in some but not all murine haplotypes.

Adenoviridae↗
PubMed1990

Deletions in herpes simplex virus glycoprotein D define nonessential and essential domains.

Herpes simplex virus glycoprotein D (gD) is a major component of the virion envelope and infected cell membranes and is essential for virus entry into cells. We have recently shown that gD interacts with a limited number of cell surface receptors which are required for virus penetration into cells. To define domains of gD which are required for aspects of virus replication including receptor binding, deletion mutations of 5 to 14 amino acids were constructed by using oligonucleotide-directed mutagenesis. Plasmids containing mutant genes for gD were assayed for the ability to rescue a recombinant virus, F-gD beta, in which beta-galactosidase sequences replace gD-coding sequences. Effects on global folding and posttranslational processing of the molecules were assessed by using a panel of monoclonal antibodies which recognize both continuous and discontinuous epitopes. A region near the amino terminus (residues 7 to 21) of gD which is recognized by monoclonal antibodies able to neutralize herpes simplex virus in the absence of complement was not essential for function. In addition, virtually all of the cytoplasmic domain of gD and an extracellular domain close to the membrane were dispensable. In contrast, deletion mutations in the central region of the molecule, save for one exception, led to alterations in global folding of the molecule and maturation of the protein was inhibited.

Animals↗
PubMed1990

Soluble forms of herpes simplex virus glycoprotein D bind to a limited number of cell surface receptors and inhibit virus entry into cells.

Herpes simplex virus type 1 (HSV-1) and HSV-2 plaque production was inhibited by treating cells with soluble forms of HSV-1 glycoprotein D (gD-1t) and HSV-2 glycoprotein D (gD-2t). Both glycoproteins inhibited entry of HSV-1 and HSV-2 without affecting virus adsorption. In contrast, a soluble form of HSV-2 glycoprotein B had no effect on virus entry into cells. Specific binding of gD-1t and gD-2t to cells was saturable, and approximately 4 x 10(5) to 5 x 10(5) molecules bound per cell. Binding of gD-1t was markedly reduced by treating cells with certain proteases but was unaffected when cell surface heparan sulfate glycosaminoglycans were enzymatically removed or when the binding was carried out in the presence of heparin. Together, these results suggest that gD binds to a limited set of cell surface receptors which may be proteins and that these interactions are essential for subsequent virus entry into cells. However, binding of gD to its receptors is not required for the initial adsorption of virus to the cell surface, which involves more numerous sites (probably including heparan sulfate) than those which mediate gD binding.

Adsorption↗
PubMed1990

Effects of passive smoking on the pulmonary function of adults.

The effects of exposure to environmental tobacco smoke (passive smoking) on pulmonary function of non-smoking, healthy Iranian men (n = 167) and women (n = 108) were investigated. There were significant reductions in % predicted FEV1 (5.7%), forced vital capacity (FVC, 4.6%) and forced expiratory flow 25-75% (FEF25-75, 9.9%) among men exposed to cigarette smoke (n = 78). The adverse effect of passive smoking was greatest among men exposed at the workplace (reduction in % predicted FEV1 9.4%, FVC 7.6%, and FEF25-75 15.3%). No significant difference in pulmonary function was found among the 54 women exposed to passive smoke, but only eight women had smoke exposure at work. It is concluded that exposure to environmental tobacco smoke, particularly at the workplace, adversely affects the pulmonary function of adults.

Adult↗
PubMed1990

Adrenergic and cholinergic interaction in central ventilatory control.

The ventrolateral medulla, which functions as integrator of cardiorespiratory control, contains cholinergic and adrenergic neurons. Exogenously administered cholinergic and adrenergic agents affect both ventilation and circulation. It is not clear whether these agents act in an independent or coordinate manner. beta-Adrenergic and alpha 2-adrenergic agents stimulate and depress the cardiorespiratory system, respectively. beta-Adrenergic and alpha 2-adrenergic agents stimulate and depress the production of adenosine 3',5'-cyclic monophosphate (cAMP), respectively. Increased intracellular cAMP may facilitate the release of acetylcholine (ACh). This work seeks to answer the following questions: 1) Are the cardiorespiratory effects of adrenergic agents secondary to possible changes in ACh release? 2) Does cAMP production have an intermediate role? By means of ventriculocisternal perfusion in anesthetized (pentobarbital sodium, 30 mg/kg) spontaneously breathing dogs, isoproterenol (ISO) increased ventilation (VE) 75% (P less than 0.05); heart rate and cardiac output were also increased (P less than 0.05). Esmolol (a beta-antagonist) blocked both the cardiovascular and ventilatory effects of ISO. Atropine (a cholinergic antagonist) blocked the ventilatory effects of ISO, but the circulatory changes persisted. Forskolin (a direct activator of adenylate cyclase) increased VE 51% (P less than 0.05), and its effect was also blocked by atropine. Clonidine decreased VE 42% (P less than 0.05); heart rate and cardiac output were also decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

The cytochrome P450(17) alpha (17 alpha-hydroxylase/C17,20-lyase) activity of the junctional zone of the rat placenta.

The cytochrome P450 responsible for androgen synthesis by the placenta during the second half of pregnancy in the rat was studied in intact and hypophysectomized animals. The two activities of P450(17) alpha, 17 alpha-hydroxylase and C17,20-lyase, were limited to the junctional zone. C17,20-Lyase activity was greater with progesterone than with 17-hydroxyprogesterone as substrate. Although the apparent Michaelis constants were similar, progesterone had a higher maximum velocity than 17-hydroxyprogesterone. Regardless of substrate, C17,20-lyase activity was greater with NADPH than with NADH as an electron donor, and there was no additive effect using both cofactors. Administration of human chorionic gonadotrophin (hCG; 10 IU at 09.00 and 21.00 h on days 13 and 14 and at 09.00 h on day 15) to intact females resulted in more than a 50% reduction of enzyme activity when measured on day 15. The same dose of hCG given to hypophysectomized animals with delayed implantation, i.e. pituitary removal on day 3 and implantation induced by oestrone 5 days later, had no effect on placental enzyme activity, but increased that in the ovary. Administration of ovine LH by osmotic minipump (days 11-15) to intact females resulted in abortion in all animals. The same treatment to animals hypophysectomized on day 11 produced abortion in three of four rats; enzyme activity was greatly reduced in the single animal with placentas. In contrast, infusion of LH into hypophysectomized animals with delayed implantation increased placental enzyme activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMed1990

Initiation of embryo implantation and maintenance of early pregnancy in the rat by chlordecone (Kepone).

The effect of chlordecone (Kepone), an insecticide/fungicide with reproductive toxicity, on the early stages of pregnancy in the rat was studied. Intraperitoneal injection of chlordecone into adult virgin female Holtzman strain rats before mating, in doses as high as 80 mg/kg, did not prevent fertilization, early development of the embryo to the blastocyst stage, transport of the embryo through the oviduct, or its implantation into the uterus. However, a single dose of 60 or 80 mg/kg, but not 20 or 40 mg/kg, before mating significantly reduced the concentration of progesterone in the serum of rats undergoing normal embryo implantation 5 days later. A dose of 80 mg/kg of chlordecone reduced progesterone levels in the serum by more than 50% within 48 hr in ovariectomized rats with Silastic tubing implants containing crystalline progesterone. This dose of chlordecone induced deciduomata formation in progesterone-primed ovariectomized rats to the same extent as 1 microgram of estradiol benzoate. The minimal effective single dose of chlordecone to initiate implantation of blastocysts in the uteri of hypophysectomized progesterone-primed rats, and to maintain embryo development for at least 5 days, was 50 mg/kg. Daily doses of 20 mg/kg for 3 or 5 days were effective at initiating implantation but did not maintain pregnancy. The latter treatment, however, did not prevent initiation of implantation or embryo development induced by subsequent administration of estrone. The results are consistent with the view that chlordecone is a weak estrogen that has both nongenomic and genomic estrogenic actions.

Animals↗
PubMed1990

Use of desmopressin in the management of aspirin-related and intractable haemorrhage after cardiopulmonary bypass.

Desmopressin (DDAVP) has been used both prophylactically and therapeutically in the management of excessive bleeding after cardiopulmonary bypass. A series of four consecutive cases is presented in which DDAVP was used to treat excessive bleeding, associated with aspirin antiplatelet therapy in three cases and after all other measures had failed in one. The therapeutic use of DDAVP in aspirin-related bleeding after bypass has not been reported previously. There was no measured haemodynamic effect of the regimen used. Bleeding ceased promptly after administration of DDAVP in all cases. No morbidity was observed in any of the patients. The indications for use of DDAVP and postulated mechanisms of action are discussed.

Adult↗
PubMed1989

Comparison of pulsed coulometric detection and potential-sweep pulsed coulometric detection for underivatized amino acids in liquid chromatography.

Pulsed coulometric detection (PCD) and potential-sweep pulsed coulometric detection (PS-PCD) are applied to the direct detection of amino acids in protein hydrolyzates. The detection mechanisms are based upon surface-catalyzed oxidation of the amine functionalities activated by the transient formation of surface oxide on Au electrodes. PCD uses a triple-step potential waveform in which the integration of electrode current at a constant potential is followed by anodic and cathodic polarizations to clean and reactivate the electrode surface. PS-PCD incorporates a cyclic potential sweep into the triple-step waveform which proceeds through the formation and subsequent removal of the surface oxide with simultaneous current integration. Reactions catalyzed by the formation of the noble metal oxide can be monitored in PS-PCD with the automatic rejection of the surface oxide background. A significant decrease is obtained also in the fluctuation and drift in the base line resulting from gradient elution and variations of the electrode surface. PCD and PS-PCD following gradient elution chromatography are demonstrated to allow for the direct detection of 20 amino acids including secondary amino acids. Detection limits for lysine are ca. 220 ppb (11 ng, 75 pmol) by PCD and 60 ppb (3 ng, 19 pmol) by PS-PCD applied at gold electrodes.

Amino Acids↗