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Biomedical subjects

B H Johnson

Publications and source records attributed to B H Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1993

Actions and interactions of glucocorticoids and transforming growth factor beta on two related human myeloma cell lines.

To evaluate possible involvement of a paracrine/autocrine inhibitory growth factor in myeloma cell growth, we studied the expression and actions of two forms of transforming growth factor beta (TGF-beta 1 and TGF-beta 2) on two closely related myeloma cell lines, OPM-1 and OPM-2. Earlier studies showed that both cell lines contain glucocorticoid receptors, but only OPM-2 cells are growth inhibited by dexamethasone (Dex). We found that OPM-2 growth was inhibited by TGF-beta, with TGF-beta 1 exerting a greater effect than TGF-beta 2, and Dex plus TGF-beta 1 acting synergistically. In OPM-1 (Dex insensitive), TGF-beta mRNA was not expressed, whereas it was induced by Dex in OPM-2. It was also possible to block partially the growth inhibition of Dex in OPM-2 cells by the addition of anti-TGF-beta 1 antibodies. These data suggest that the glucocorticoid effect(s) on myeloma cells may be mediated at least in part through modulation of internal and/or external levels of TGF-beta 1.

Dexamethasone↗
PubMed1992

Effects of sexual experience, season, and mating stimuli on endocrine concentrations in the adult ram.

Two behavioral trials were conducted to determine the endocrine response of cortisol (C), luteinizing hormone (LH), testosterone (T), prolactin (PRL), and growth hormone (GH) in adult rams during exposure to estrous ewes during the breeding and nonbreeding seasons. One-half of the rams in each season were sexually experienced (SE) and the remainder were sexually inexperienced (SI). All SE rams (100%) achieved at least one ejaculation, but only 33% (summer) and 67% (fall) SI rams achieved ejaculation. In the fall, mean C, T, and GH concentrations were elevated (P less than .001) compared to values measured in the summer, whereas LH and PRL levels were higher (P less than .01) in the summer. Overall levels of C, LH, T, and PRL were higher (P less than .05) in SE rams than in SI rams. Mean GH concentration was higher (P less than .10) in SI than in SE rams during restricted and complete access to estrous ewes. In general, LH, PRL, and GH responses were similar during restricted and complete access to females for both SE and SI rams. Cortisol levels were higher (P less than .06) during periods of mating and T levels were higher (P less than .001) during periods where activity was limited to courtship behavior (nasogenital investigation). Correlations of hormones to reproductive behaviors indicated that mounting and intromission were associated with elevations in C and PRL, whereas elevated LH and T tended to be associated with courtship behaviors. Correlations between GH and behaviors were inconsistent. However, there was an increased coincidence between time of female exposure and hormonal response that occurred in the fall; brief exposure to estrous ewes resulted in increases in concentrations of all hormones examined. The most consistent response was observed in sexually experienced rams during restricted access to females during the breeding season. These results provide new information on the effects of season and level of sexual experience upon hormonal and behavioral characteristics of the ram during mating activity.

Animals↗
PubMed1992

Glucocorticoid, interleukin-2, and prostaglandin interactions in a clonal human leukemic T-cell line.

We have studied the growth effects of conditioned media, interleukin-2 and PGE prostaglandin analogs on the glucocorticoid-sensitive human leukemic T-cell clone, CEM-C7. After 4 days, the glucocorticoid dexamethasone at approximately 10 nM kills 50% of CEM-C7 cells. To test the hypothesis that glucocorticoid-mediated lymphocytolysis was due to suppression of lymphokine expression only, we attempted to protect CEM-C7 cells from lysis by provision of lymphokine(s). Conditioned media from interleukin-2 secreting Jurkat T-cells as well as the glucocorticoid-insensitive, but receptor positive clone, CEM-C1, failed to prevent lymphocytolysis; exogenous interleukin-2 also did not provide protection. There were complex, biphasic interactions between dexamethasone and the synthetic PGEs, enisoprost and enisoprost free acid. Low doses of enisoprost alone (0.01 to 1 microgram/ml) stimulated growth, and in combinations completely reversed the growth inhibitory effects of 10 nM dexamethasone. Higher concentrations of enisoprost were inherently lethal and were additive to the steroid effect. Thus the glucocorticoid-induced lymphocytolysis in this human leukemic T-cell line may be modified biphasically by PGE prostaglandins, depending on their concentration. However, interleukin-2 or components in the conditioned media assayed had no effect in ameliorating the lethal response to glucocorticoid.

Alprostadil↗
PubMed1992

Glucocorticoids in malignant lymphoid cells: gene regulation and the minimum receptor fragment for lysis.

We have examined clones of human malignant lymphoid cells for markers that correlate with glucocorticoid-mediated cell lysis. In glucocorticoid-sensitive clones of CEM, a human T-cell lymphoblastic leukemia line, two genes correlate with glucocorticoid-induced cell lysis. The glucocorticoid receptor (GR) itself is induced by standard glucocorticoids in sensitive clones and not in insensitive clones. The phenylpyrazolo-glucocorticoid cortivazol (CVZ) is capable of lysing several clones resistant to high concentrations of standard potent glucocorticoids. When these clones were tested for cortivazol responses, they were not only lysed by cortivazol but also showed induction of GR mRNA. Thus receptor induction appears to correlate with the lysis function of receptor in these cells. To determine what parts of the GR are required for lysis, we have mapped this function by transfecting and expressing GR and GR fragment genes in a GR-deficient CEM clone. Our results indicate that none of the known trans-activation regions of the GR are required. Removal of the steroid binding domain gives a fragment that is fully constitutive. Only one and one-half "Zn fingers" of the DNA binding region are required. We also find in CEM cells rapid suppression of the c-myc protooncogene, preceding growth arrest and cell lysis by glucocorticoids. This occurs only in clones possessing both intact receptors and lysis function. Thus the simple presence of GR alone is not sufficient to guarantee c-myc down-regulation. Introduction into the cells of c-myc driven by a promoter that does not permit suppression by glucocorticoids confers resistance to steroids. Furthermore, suppression of c-myc by antisense oligonucleotides also kills the cells. Therefore, c-myc appears to be a pivotal gene related both to ability of steroid to kill and to cell viability.

Cell Line↗
PubMed1991

Effects of pretreatment with adrenocorticotropin on endocrine and behavioral responses of bulls to sexual activity.

Peripheral concentrations of cortisol, growth hormone and testosterone were determined in two experiments which examined the endocrine and behavioral responses of sexually mature Angus bulls to an estrous female (Experiment 1) and to female exposure 5 hours following an adrenocorticotropin (ACTH) injection (Experiment 2). Sexual activity of bulls in Experiment 1 significantly increased levels of cortisol when compared with concentrations before exposure to a female. Administration of ACTH in Experiment 2 consistently elevated levels of cortisol by 30-fold (P<0.01) when compared with pre-ACTH concentrations. This heightened level of cortisol persisted throughout the period of exposure to an estrous cow, although a gradual decline in cortisol concentrations occurred over time (P<0.05). In Experiment 1, growth hormone profiles tended to increase in response to sexual activity (P<0.10), whereas in Experiment 2, growth hormone increased in response to ACTH administration (P<0.01) and to female exposure (P<0.01). Concentrations of testosterone were unaffected (P>0.10) by mating activity in Experiment 1. In Experiment 2, acute suppression (P<0.01) in testosterone concentrations 5 hours after ACTH administration coincided with the exposure period to the estrous female. Frequencies of mounting behavious (penis extension, mounting, intromission and ejaculation) exhibited by ACTH-treated bulls were significantly lower compared with the frequencies two days earlier. Exogenous ACTH administration suppressed reproductive behaviors of bulls and altered secretion of cortisol, growth hormone and testosterone. Furthermore, these data provide evidence that specific mating behaviors of the bull can be influenced by circulating steroids.

Journal Article↗
PubMed1991

Survival of early preimplantation porcine embryos after co-culture with cells producing an avian retrovirus.

To determine the relative survival of porcine embryos after co-culture with cells producing an avian retrovirus, four-cell stage embryos were obtained from sows following synchronization with altrenogest and superovulation with gonadotropins. These embryos were randomly assigned to the following treatments: no manipulation (zona-intact); zona removed with acidified Tyrode's solution (zona-free); and zona removed followed by co-culture with D-17 canine cells producing an avian retrovirus vector derived from spleen necrosis virus (zona-free + co-culture). The survival rates of four-cell stage embryos to morulae or early blastocysts during a 48-h culture period were 93.3, 80.0 and 57.7% in zona-intact, zona-free and zona-free + co-culture groups, respectively. Following embryo transfer, the development of embryos to fetuses at six weeks of gestation was 37.5, 30.0 and 11.7% in zona-intact, zona-free and zona-free + co-culture groups. These results indicate that early preimplantation porcine embryos can develop to apparently normal fetuses following co-culture with cells producing a retrovirus, and the feasibility of this method for retrovirus-mediated gene transfer in pigs was demonstrated.

Journal Article↗
PubMed1991

Percutaneous loss of desflurane, isoflurane, and halothane in humans.

We studied the percutaneous losses of the new inhaled anesthetic, desflurane (I-653), and of isoflurane and halothane during anesthetic administration and elimination in seven healthy male volunteers. Anesthesia was induced and maintained with midazolam, thiopental, and fentanyl. We administered 70% N2O for 30 min, and then administered 2% desflurane, 0.4% isoflurane, and 0.2% halothane concurrently with 65% N2O for 30 min. Inspired, end-tidal, and mixed-expired gas samples were collected during administration of the volatile agents and for 5-7 days of elimination. The right arm and hand of each subject was enclosed in a sealed glass cylinder having a port at each end, one for sampling and both for flushing with N2 after anesthetic administration and every 15 min thereafter. We sampled gases from the cylinder during administration and for the 150 min of elimination and analyzed their anesthetic concentrations by gas chromatography. The surface area of the enclosed portion of the arm was measured, and the total body surface area was calculated. All values were normalized to (i.e., divided by) the end-tidal (alveolar) concentration at the end of administration. During administration, percutaneous loss of halothane was 3.5 times that of desflurane and 2 times that of isoflurane. During elimination, the loss of halothane was 6 times and 2 times greater than the loss of desflurane and isoflurane, respectively. Percutaneous loss of halothane significantly exceeded that of isoflurane. The elimination values included an estimate of elimination after 150 min. The percutaneous loss of each anesthetic was 2- to 3-fold greater during elimination than administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Kinetics of desflurane, isoflurane, and halothane in humans.

The low solubility of desflurane in blood and tissues suggests that the partial pressures of this agent in blood and tissues should approach the inspired partial pressure more rapidly than would the blood and tissue partial pressures of other potent inhaled anesthetics. We tested this prediction, comparing the pharmacokinetics of desflurane with those of isoflurane, halothane, and nitrous oxide in eight volunteers. We measured the rate at which the alveolar (endtidal) (FA) concentration of nitrous oxide increased towards an inspired (FI) concentration of 65-70%, and then measured the concurrent increase in FA and mixed expired concentrations (FM) of desflurane, isoflurane, and halothane at respective FI values of 2.0%, 0.4%, 0.2%. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. The potent vapors were administered for 30 min; administration of nitrous oxide continued throughout the period of anesthesia. For the potent agents, we also measured VE, FA, and FM for 5-7 days of elimination. We used FA/FI and FA/FA0 (FA0 = the last FA during the administration of each anesthetic) to define the rate of increase of anesthetic in the lungs and the rate of elimination of anesthetic, respectively. FA/FI values at 30 min of administration were: (mean +/- SD) nitrous oxide 0.99 +/- 0.01, desflurane 0.90 +/- 0.01, isoflurane 0.73 +/- 0.03, and halothane 0.58 +/- 0.04. FA/FA0 values after 5 min of elimination were: desflurane 0.14 +/- 0.02, isoflurane 0.22 +/- 0.02, and halothane 0.25 +/- 0.02. Recovery (volume of anesthetic recovered during elimination per volume taken up) of desflurane (105 +/- 25%) equalled recovery of isoflurane (102 +/- 13%) and exceeded recovery of halothane (64 +/- 9%). Time constants for a five-compartment mammillary model for halothane and isoflurane differed for the lungs, fat group, and hepatic metabolism, and exceeded those for desflurane for all compartments. In summary, we found that FA/FI of desflurane increases more rapidly and that FA/FA0 decreases more rapidly in humans than do these variables with other available potent anesthetics. We also found that desflurane resists biodegradation in humans and so may have little or no toxic potential.

Adult↗
PubMed1991

Age affects the pharmacokinetics of inhaled anesthetics in humans.

To define the effect of aging on the pharmacokinetics of volatile anesthetics, we determined the end-tidal and mixed expired anesthetic concentrations of isoflurane, enflurane, halothane, and methoxyflurane during 30 min of simultaneous administration and for 5-12 days of elimination in seven healthy young patients (31 +/- 1.8 yr [mean +/- SEM]) and in 11 healthy aged patients (73.2 +/- 3.1 yr [mean +/- SEM]). A five-compartment mammillary function was fit to the end-tidal and mixed expired anesthetic elimination data simultaneously using ordinary least-squares analysis. We assumed the compartments to represent the following tissue groups: lungs and pulmonary capillary blood (V1), vessel-rich tissues (i.e., liver, heart, kidneys, and brain) muscle, an unidentified fourth compartment, perhaps fat adjacent to well-perfused tissues, and fat tissues. The tissue volumes and perfusions estimated for these compartments approximated values from the literature. In general, the volume of the fourth and fifth compartments increased with age, and perfusion to the second and fifth compartments decreased with age. Aging delayed anesthetic elimination and increased the apparent volume of distribution at steady state. These observations are compatible with decreased tissue perfusion and an increase in the ratio of fat/lean body weight in the elderly. Our mammillary analysis described the behavior of less soluble anesthetics such as isoflurane well, but that of highly soluble anesthetics such as methoxyflurane less well.

Adipose Tissue↗
PubMed1991

Effect of insulin-like growth factor-I on protein synthesis in porcine embryonic discs cultured in vitro.

Porcine embryos at Day 13 (Day 0 = first day of oestrus) were collected surgically and embryonic discs were isolated microsurgically. The discs were washed and cultured in Dulbecco's modified Eagle's medium without serum, with either 14C-leucine alone or 14C-leucine plus insulin-like growth factor-I (IGF-I) (100 ng/ml) at 37 degrees C for 48 h in 5% CO2 in air. After incubation, discs were morphologically evaluated, frozen in liquid nitrogen and stored at -70 degrees C. No statistical differences in morphology were observed between embryonic discs cultured in medium with IGF-I and those cultured in medium alone (control). Although more radioactivity was incorporated by embryonic discs in the presence of IGF-I than by those cultured in medium without the growth factor, the difference between the two groups was not significant. From two-dimensional gel electrophoresis, it was observed that IGF-I selectively stimulated the synthesis of four new proteins with Mr of 24,000, 70,000, 77,000 and 95,000, respectively and pI between 5.5 and 6.5. At least 90% of the other proteins in the gels was synthesized in greater amount by embryonic discs cultured in the presence of IGF-I than in the controls. These results show that IGF-I can stimulate protein synthesis in pig embryonic discs cultured in vitro and suggest that this growth factor may play an important role in regulating early development.

Animals↗
PubMed1991

Cortisol, growth hormone, and testosterone concentrations during mating behavior in the bull and boar.

Two experiments were conducted to evaluate peripheral concentrations of cortisol (C), growth hormone (GH), and testosterone (T) in bulls and boars during mating and to correlate mating behaviors with endocrine secretion in the presence of an estrous female. In Exp. 1, six sexually inexperienced mature bulls were bled every 15 min for 2 h before and 2 h after a 30-min exposure to a single, restrained, estrous cow; sampling occurred every 5 min during exposure. In Exp. 2, six sexually experienced boars were bled similarly before and after exposure to a sow and every 5 min during a 15-min exposure to a freely moving, estrous sow. Behavioral events recorded during exposure to a female included the following: flehmen responses (bulls only), mounts, penis extensions, intromissions, ejaculations, and time to first mount and first ejaculation. Of the six bulls, four completed at least one service (intromission + ejaculation), and three of six mounted the estrous cow eight or more times. Completion of one or more services resulted in significant elevations in serum C and GH concentrations, but not T concentrations, during the exposure period. Bulls mounting eight or more times also experienced significant elevations in C concentrations during exposure. Three of six boars completed at least one service. Servicing and mounting the sow fewer than five times were both associated with significant elevations in serum C concentrations. Serum concentrations of T were also elevated as a result of exposure to an estrous sow. Collectively, these data support the suggestion that specific events during natural mating activity can alter endocrine secretions of C and GH in bulls and C and T in boars.

Animals↗
PubMed1991

Cardiovascular actions of desflurane in normocarbic volunteers.

The cardiovascular actions of three concentrations of desflurane (formerly I-653), a new inhalation anesthetic, were examined in 12 unmedicated normocapnic, normothermic male volunteers. We compared the effects of 0.83, 1.24, and 1.66 MAC desflurane with measurements obtained while the same men were conscious. Desflurane caused a dose-dependent increase in right-heart filling pressure and a decrease in systemic vascular resistance and mean systemic arterial blood pressure. As measured by echocardiography, left ventricular end-diastolic area did not change except for a small increase at 1.66 MAC desflurane, and systolic wall stress was less at all concentrations of desflurane than during the conscious state. Desflurane did not change cardiac index or left ventricular ejection fraction. Heart rate did not change at 0.83 MAC, but progressively increased with deeper desflurane anesthesia. Stroke volume index was less at all concentrations of desflurane than while the men were conscious, but desflurane did not alter the velocity of ventricular circumferential fiber shortening. Mixed venous blood PO2 and oxyhemoglobin saturation were higher during all concentrations of desflurane anesthesia than during the conscious state. No volunteer developed a metabolic acidosis. We conclude that desflurane with controlled ventilation and constant PaCO2 causes cardiovascular depression, as indicated by the increased cardiac filling pressure and decreased stroke volume index and by no change in the velocity of circumferential fiber shortening in the presence of decreased systolic wall stress. However, cardiac output is well maintained, and heart rate does not increase at light levels of anesthesia. The cardiovascular actions of 0.83 and 1.66 MAC desflurane were also reexamined in 6 of the 12 men during the seventh hour of anesthesia. Prolonged desflurane anesthesia resulted in lesser cardiovascular depression than was evidenced during the first 90 min. The measures of cardiac filling (central venous pressure and left ventricular end-diastolic cross-sectional area) did not differ between the early and late periods of anesthesia. Systemic vascular resistance decreased further during the late period, but systolic wall stress did not differ between the two time periods. During the seventh hour of desflurane anesthesia, heart rate and cardiac index were higher at both anesthetic concentrations than during the first 90 min of anesthesia. Left ventricular ejection fraction and velocity of fiber shortening did not change with duration of desflurane anesthesia. Oxygen consumption, oxygen transport, the ratio of the two, mixed venous PO2, and mixed venous oxyhemoglobin saturation (SO2) increased late in the anesthetic in comparison with the first 90 min.

Adult↗
PubMed1990

Single-lumen vs double-lumen catheters for total parenteral nutrition. A randomized, prospective trial.

Multilumen catheters have been condemned for hyperalimentation based on reports of infection rates between 10% and 25% in uncontrolled studies. Because of the potential usefulness of multilumen catheters, we studied infection rates in a prospective, randomized trial. All patients requiring total parenteral nutrition were randomized to either single- or double-lumen catheters. Single-lumen catheters were used for dextrose-amino acids only. Medications or fat emulsions were given either by another central line or peripherally. Double-lumen catheters were used for dextrose-amino acid solutions, compatible medications, and fat emulsions. Catheters were cultured (48 single lumen and 53 double lumen) from 112 patients who successfully completed the study. No patients in either group developed catheter sepsis. We concluded that parenteral nutrition can be given as safely via double-lumen catheters as single-lumen catheters when strict protocols are established and followed.

Bacterial Infections↗
PubMed1990

Increased glucocorticoid responsiveness of CD4+ T-cell clonal lines grown in serum-free media.

CEM-C7, a human leukemic CD4+ T-lymphocyte cell line and three of its subclones, CEM-4R4, CEM-3R43, and ICR-27, previously cultured in a medium supplemented with 5 to 10% fetal bovine serum, have been adapted to serum-free media. The best medium of those tested was RPMI 1640 supplemented with 5 micrograms/ml each transferrin and insulin + 5 ng/ml sodium selenite +/- 0.1% bovine serum albumin. While growing either with or without albumin, the several clonal lines of CEM cells displayed growth similar to serum-supplemented cultures. Cell proliferation of CEM-C7 cells cultured in both serum-free media has been sustained for 3 mo. with culture doubling times of about 25 h for both serum-supplemented and serum-free cultures (viability greater than or equal to 90%). Cell morphology remained essentially the same in serum-free or serum containing media. The expression of CD4, a marker for T-derived lymphoid cells, was not significantly different in serum-free medium. When grown in serum-free medium, CEM-C7 cells exhibited increased steroid responsiveness as evidenced by increased glucocorticoid receptor binding sites, increased induction of glutamine synthetase, and cell lysis at lower concentrations of steroid. Receptor mutant subclones of CEM-C7, which are proven to be completely unresponsive to micromolar concentrations of dexamethasone when grown in serum-supplemented medium, become partially sensitive to the hormone after growth in defined medium. The increased sensitivity of CEM-C7 cells and its subclones to dexamethasone in serum-free medium returned to previous levels when these cells were recultured in serum-containing medium. Our results suggest that substances in serum influence steroid effects on these cells and that the molecular details of glucocorticoid hormone action may be pursued more precisely in a clearly defined culture medium.

CD4 Antigens↗
PubMed1990

Three-phase study of phlebitis in patients receiving peripheral intravenous hyperalimentation.

We found clinical phlebitis in 57 of 88 patients with peripheral hyperalimentation (65%). To determine if this was a problem common to all intravenous fluid therapy at our hospital, we performed a point-prevalence study. The prevalence of phlebitis in nonhyperalimentation intravenous patients was 18% (84 of 456 patients). We then performed a randomized, prospective, double-blind trial of sham versus standard in-line filters to determine if bacteria or filterable particulate matter was responsible for phlebitis in the peripheral hyperalimentation group. The standard-filter group had a phlebitis rate of 74% compared with 64% in the sham-filter group. We then eliminated in-line filters and replaced the standard glucose-based solution with a glycerol-based peripheral hyperalimentation solution. The phlebitis rate decreased from 68% to 27% (p less than 0.001). In conclusion, phlebitis in peripheral hyperalimentation patients was probably due to chemical properties of the peripheral hyperalimentation solution rather than bacteria or particulates.

Amino Acids↗
PubMed1990

Biotransformation and hepato-renal function in volunteers after exposure to desflurane (I-653).

Ten healthy unpremedicated male volunteers were exposed to an average inspired concentration of 3.6% desflurane (I-653) in oxygen for 89 (SD 17) min. Standard haematological and biochemical tests were performed before (control) and immediately after exposure and at 4, 24, 72 and 192 h. Liver function was assessed at these times by determining total and unconjugated (indirect) bilirubin, and plasma concentrations of aspartate amino transferase, alanine amino transferase, gamma-glutamyl transpeptidase and alkaline phosphatase. Renal function was assessed by examining the urine microscopically for leucocytes, red blood cells, casts and crystals at these times, and creatinine clearance and urine concentrating ability were determined before and 24 and 72 h after exposure. Two additional and sensitive tests of renal integrity were performed before and 4 and 24 h after anaesthesia: measurement of urinary retinol-binding protein and beta-N-acetyl-D-glucosaminidase. Serum inorganic fluoride was determined immediately before and 1, 4, 24, 48, 72 and 192 h after anaesthesia. Urinary inorganic and organic fluoride concentration and excretion rate were determined before and 24, 48, and 72 h after anaesthesia. There were no significant changes in any measured haematological or biochemical variable (other than an increase in total white cell count from 5.9 (1.3) to 8.3 (1.1) x 10(9) litre-1 immediately after exposure) nor in liver or renal function tests. There was no increase in serum or urinary inorganic fluoride or urinary non-volatile organic fluoride concentrations.

Anesthetics↗