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L T Archer

Publications and source records attributed to L T Archer.

At least 19 recordsLinked to original sources
PubMed1990

Cellular F-actin levels as a marker for cellular transformation: relationship to cell division and differentiation.

Transformation is associated with profound structural and quantitative changes in the cytoskeleton. Herein we report studies using F-actin, a major cytoskeletal protein, as a quantitative marker for transformation cells, focusing on separating the effects of the cell cycle, cell differentiation, and transformation. The model system for these studies consisted of three lymphoblastic cell lines, one untransformed line (RPMI) and two transformed lines, one (HL-60) of which can be induced to differentiate and the other (Daudi) which cannot. The relation of F-actin levels to cell cycle was studied by flow cytometry with the use of fluorescein-phalloidin to label F-actin and propidium iodide to label DNA. F-actin levels in transformed Daudi and HL-60 lines were only two-thirds that of the untransformed RPMI cells. Histograms of the distribution of F-actin showed that the transformed lines consisted of two cell populations, one having an F-actin content near that of untransformed cells and the other having much less. Cell cycle analysis showed that F-actin in untransformed cells increased 10-15% as cells entered the S compartment, remaining approximately constant through G2 + M phases of the cell cycle, but in transformed cells the major increase in F-actin occurred during G2 + M phase. Double-label studies with rhodamine-phalloidin for F-actin and KI-67 monoclonal antibody for dividing cells (cells at late G1, S, G2, and M) measured with quantitative fluorescence image analysis showed that the mean F-actin content of dividing cells was twice that of nondividing cells. These results suggested that most of the cell division-related F-actin increase occurred during late G1 phase in untransformed cells. Differentiation of HL-60 cells with dimethyl sulfoxide or retinoic acid normalized the F-actin content of the nondividing cell population, but dimethyl sulfoxide and retinoic acid produced no detectable change in F-actin in the undifferentiable Daudi cells. A tumor promoter (12-O-tetradecanoylphorphol-13-acetate) inhibits differentiation of hematopoietic cells, resulted in a 32% decrease in the mean F-actin content of RPMI cells due to the appearance of a new subpopulation of low F-actin content. The 12-O-tetradecanoylphorbol-13-acetate-induced changes reversed slowly after removal of 12-O-tetradecanolyphorbol-13-acetate but more rapidly in the presence of retinoic acid. These results indicate that F-actin quantification can serve as a marker for cellular transformation and provides a tool for studying the mechanisms of cellular differentiation that may lead to a better understanding of the oncogenic process.

Actins↗
PubMed1988

Evaluation of naloxone therapy for Escherichia coli sepsis in the baboon.

This study evaluated the effects of naloxone hydrochloride in the treatment of Escherichia coli-induced shock in baboons. The baboons were studied for 12 hours and monitored for survival times. All baboons were intravenously infused for two hours with E coli and treated as follows: group 1, E coli (control); group 2, E coli plus naloxone hydrochloride, 0.5 mg/kg bolus plus 0.5 mg/kg/h for 9.5 hours; and group 3, E coli plus naloxone hydrochloride, 2.0 mg/kg bolus plus 2.0 mg/kg/h for 3.8 hours. Naloxone was administered after arterial pressure had reached the nadir (more than two hours following initiation of E coli infusion). Mean arterial pressure was supported by the lower dose of naloxone; however, sustained leukopenia and neutropenia were not reversed by its infusion. Naloxone prevented the increase in plasma beta-endorphin level and blunted the increase in plasma cortisol level. Despite these effects, naloxone did not prevent multiple-organ disease and did not decrease mortality.

Animals↗
PubMed1986

Treatment of LD100 Escherichia coli septic shock with netilmicin and methylprednisolone in baboons.

Treatment efficacy with netilmicin sulphate/methylprednisolone sodium succinate in a severe septic shock baboon model, using an LD100 of live Escherichia coli, was evaluated. All the animals treated with both netilmicin and methylprednisolone were permanent (greater than or equal to 7 days) survivors, whereas none of the untreated baboons lived more than 24 hours. These results indicate that, in a baboon model, netilmicin is an effective alternative to gentamicin (with methylprednisolone) in the treatment of severe septic shock.

Animals↗
PubMed1986

Tobramycin therapy for lethal sepsis in the dog.

Antimicrobial effectiveness and effect on survival of single-dose vs. multiple-dose aminoglycoside antibiotic therapy (with and without steroid) for lethal sepsis were evaluated. Adult dogs of either sex were anesthetized, divided into five groups, and infused iv for one hour with Escherichia coli. Group A was given no drug. Group B was given a 45-mg/kg, 10-min iv injection of tobramycin (TOB) at 65 min. Group C was given a 3-mg/kg, 10-min TOB injection at 65 min, followed by an 8.25-mg/kg iv infusion for 285 min, and three 11.25-mg/kg intramuscular injections at 6, 12, and 18 h (total 45 mg/kg). Group D was given the same TOB regimen as B, plus a 30-mg/kg iv injection and 30-mg/kg iv infusion of methylprednisolone sodium succinate (MPSS) from 15 to 360 min. Group E was given the same TOB regimen as C, plus the same MPSS regimen as D. Treated dogs also received 11.25 mg/kg of TOB daily for 4 days. The percent surviving more than 7 days was 0, 0, 17%, 83%, and 83%, for groups A through E, respectively. By 4 h, TOB-treated groups had significantly (p less than .05) lower E. coli blood levels than group A. Also E. coli levels in group B were significantly (p less than .05) lower than those in groups C, D, or E. High trough serum TOB concentrations were associated with death and very low levels with recovery. Serum urea nitrogen and creatinine concentrations increased in all groups, but returned to normal by 7 days in survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of prior administration of steroids upon recovery from lethal sepsis.

The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study. Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight. All dogs in group 1 (n equals six) not given steroid died within 25 hours. Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days). All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours. Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid. Thirty-three per cent of the dogs in group 4 permanently survived. One or two daily large doses of steroid did not detrimentally affect survival of the dogs. Eight days of steroid administration suppressed endogenous cortisol production. When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited.

Adrenal Cortex Hormones↗
PubMed1985

Myocardial dysfunction in endotoxin- and E. coli-induced shock: pathophysiological mechanisms.

Experimental studies have documented that myocardial dysfunction is precipitated between 3 and 6 hr after endotoxin or E. coli. This finding has now been confirmed in human septic shock. A "Hinshaw-modified" isolated working left ventricle preparation has been used to document and assess the degree of failure. It was found that the failure is often severe and reversible only temporarily by adrenergic agents but reversible by digoxin or insulin. The cause of the failure has not been identified, but evidence is presented against a myocardial depressant factor (MDF) being the causative factor. Hearts subjected to a 2-4 hr period of hypotension on the threshold of failure show no signs of failure when subjected to blood circulating from an animal in splanchnic arterial occlusion shock. Hearts from pancreatectomized animals subjected to endotoxin shock with their source of MDF removed demonstrate the typical failure in 4-6 hr. Other factors are suggested that contribute to myocardial dysfunction: hypotension or nonuniform perfusion of subendocardial regions of the heart, depressed responsiveness to inotropic and chronotropic stimuli, intracardiac ionic and fluid disturbances, and increases in heart chamber and muscle stiffness. Since steroid/antibiotic therapy increases the probability (p less than 0.05) that an animal will survive lethal sepsis, investigating the effect of this therapy on myocardial function may aid in determining whether or not this degree of heart failure contributes in the animal to irreversible shock and death.

Animals↗
PubMed1985

Corticosteroid/antibiotic treatment of adrenalectomized dogs challenged with lethal E. coli.

Adrenalectomized animals are extremely sensitive to endotoxin and die quickly when given small doses. A six hour administration of the corticosteroid, methylprednisolone sodium succinate (MPSS), combined with the antibiotic, gentamicin sulfate (GS), promotes complete recovery of dogs with intact adrenals administered LD100 E. coli. The aim of the present study was to determine if this early administered treatment would protect adrenalectomized dogs from overwhelming lethal doses of E. coli. Dogs were infused with MPSS from fifteen minutes to six hours after the onset of E. coli administration and with GS after administration of all E. coli. Animals given only E. coli died in 2.6 (+/- 0.3) hours, while those given no E. coli, or E. coli plus steroid/antibiotic, survived longer than 100 hours. Arterial pressure, pH, pO2, hematocrit, lactate, and glucose concentrations were maintained near control values in animals receiving steroid/antibiotic infusions. Adrenalectomized dogs infused with corticosteroid/antibiotic recovered completely from shock even though the treatment period was limited to the first 6 hours after lethal E. coli infusion. Findings indicate that animals treated with MPSS/GS after E. coli ultimately succumbed to adrenal insufficiency rather than from the E. coli insult and thus recovery from shock itself was complete.

Adrenal Cortex Hormones↗
PubMed1979

Prolonged shock in the monkey following live E coli organism infusion.

Responses of the rhesus monkey to the administration of live Escherichia coli organisms during an observation of 0--27 hours were studied. Nine monkeys were infused for 30 minutes with live E coli organisms, the dose ranging between 7.6 X 10(9) and 3.0 X 10(11) organisms/kg. Three of nine animals survived for 24 hours or longer. Nonsurvivors demonstrated significant hypotension, hypoglycemia, and hypoinsulinemia, while survivors showed lesser degrees of physiologic derangement. Findings were hepatic sinusoidal fibrin thrombi and hepatocellular damage accompanied by elevated serum enzymes. The kidney did not show glomerular fibrin thrombi; however, tubular lesions were clearly evident and increases in blood urea nitrogen levels and endogenous creatinine were documented. Lungs of animals surviving longer contained fewer polymorphonuclear leukocytes and platelets than were seen in acute shock studies. This study emphasizes the importance of monitoring the nonhuman primate during an extended time period, since many significant pathophysiologic responses occur after eight hours of observation.

Animals↗
PubMed1979

Extracorporeal perfusion without anticoagulation and the response to endotoxin.

The results of this study show that an extracorporeal perfusion system without anticoagulation can be established in the dog under certain conditions. The exact mechanisms merit further investigation. It also points to a model to study the effects of endotoxin without heparin interference and as another model for studying the canine blood coagulation system.

Animals↗
PubMed1979

Effects of methylprednisolone sodium succinate on clearance of live E coli from the peripheral blood of dogs.

Corticosteroids have been reported to potentiate infections, and yet recent clinical and experimental studies have documented their therapeutic effectiveness in both septic and endotoxin shock. This study was designed to determine if methylprednisolone sodium succinate (MP) affects the clearance of live E coli organisms from peripheral blood of dogs. The experimental group was pretreated with 30 mg/kg of MP, and controls received equal volumes of saline. Both control and MP-pretreated dogs significantly reduced the number of E coli in peripheral blood by almost two orders of magnitude; however, there was no significant difference in clearance of E coli organisms between the two groups. An initial leukopenia occurred in both groups after E coli injections; however, the subsequent development of leukocytosis in the MP group was significantly greater at +6 hours. Rectal temperatures were higher in the MP group from +1 through +4 hours than in the controls. Hyperglycemia developed initially in both groups, followed by a progressive hypoglycemia, with survivors returning to near normal blood glucose concentrations. Hemoconcentration occurred in both groups, with higher hematocrits being associated with mortality. Results support the view that methylprednisolone sodium succinate does not affect the clearance of live E coli organisms.

Animals↗
PubMed1979

Recovery from endotoxin shock after extracorporeal perfusion without anticoagulation.

The purpose of this study was to determine the effect of an extracorporeal nonanticoagulated perfusion system on survival from endotoxin shock in anesthetized closed-chest dogs. Dogs weighing approximately 18 kg were perfused four hours or used as nonperfused controls. In the perfused animals, blood was diverted from the distal aorta via plastic tubing at 1,000 ml/min into a reservoir and returned by means of a roller-type pump to the femoral veins. Whole blood clotting times increased from a control value of seven minutes to greater than 24 hours within 45 minutes of perfusion in the absence of exogenous anticoagulation. After blood became incoagulable, animals were infused with 3 mg/kg Escherichia coli endotoxin during a 30-minute period. Systemic pressures declined during the initial period but returned to base-line values; glucose remained at normal levels and all six dogs thus treated remained healthy survivors after seven days. On the other hand, animals infused with endotoxin without extracorporeal perfusion demonstrated hypotension, hypoglycemia, and diarrhea, and five of six dogs died within 36 hours.

Animals↗
PubMed1978

Reversal of myocardial dysfunction in endotoxin shock with insulin.

Recent data reported from this laboratory have documented myocardial functional depression in endotoxin shock. The purpose of the present study was to determine the effects of insulin on the dysfunctioning canine myocardium subjected to lethal endotoxin shock. Experiments were conducted on isolated working left ventricular preparations in which LD90-100 endotoxin was administered prior to, or following, isolation of the heart. Determinations of myocardial performance were conducted under the conditions of controlled mean aortic pressure and cardiac output. Myocardial dysfunction occurred between 2 and 6 h postendotoxin, as evidenced by significantly increased left ventricular end-diastolic pressure, decreased power, and depressed negative dP/dt, although blood glucose concentrations were maintained at control values. Intraatrial infusions of insulin at rates of 6 U/min reversed all signs of myocardial dysfunction. During insulin infusion, heart rates decreased (p less than 0.02) and myocardial lactate uptake increased (p less than 0.02), while oxygen uptake and coronary blood flow were insignificantly altered.

Animals↗
PubMed1978

Escherichia coli shock in the baboon and the response to adrenocorticosteroid treatment.

Results of recent studies from this laboratory have demonstrated that methylprednisolone sodium succinate increases the survival rate of dogs given LD100 Escherichia coli endotoxin. This study was undertaken to determine the effects of methylprednisolone on the baboon infused with live Escherichia coli organisms. Awake baboons were paired by infusing intravenously comparable doses of Escherichia coli during a five hour period. Baboons given methylprednisolone received bolus injections of 30 milligrams per kilogram at 15 minutes after beginning the infusion of Escherichia coli and two hour infusions of 15 milligrams per kilogram at two hour intervals until death or for a 24 hour period. The mortality was unaltered by methylprednisolone. Six of seven baboons that were dying became progressively hypoglycemic, while hypoinsulinemia occurred in all baboons within six hours and was sustained until death. Systemic hypotension was observed. although pressures were variable. Potassium and lactate concentrations increased, while pH remained relatively constant in most baboons. Serum glutamic-pyruvic transaminase and arginase concentrations rose in most baboons dying with 18 hours. Results of morphologic studies revealed the presence of fibrin thrombi in the liver, kidney and adrenal tissue in most baboons. No significant differences in physiologic, metabolic, hematologic or morphologic parameters were observed between treated and untreated baboons.

Animals↗