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Showing papers by "University of Texas Southwestern Medical Center published in 1969"


Journal ArticleDOI
TL;DR: Observations indicate that choleragenicity and increased vascular permeability are intimately associated phenomena and may be manifestations of the same basic mechanism.
Abstract: Choleragen, a diarrheagenic protein enterotoxin elaborated by Vibrio cholerae, has been isolated from the supernate of fermenter cultures by steps involving ammonium sulfate precipitation, DEAE cellulose, Sephadex G-75, and Agarose A-5m chromatography. The resulting product appears to be pure according to immunoelectrophoretic, disc electrophoretic, ultracentrifugal, and immunologic criteria. Sephadex gel filtration and membrane filtration studies suggest a molecular size of 61,000. The isolated product is highly active in inducing experimental cholera in infant and adult rabbit models. It also elicits, in small dosage, an increased vascular permeability in skin. These observations indicate that choleragenicity and increased vascular permeability are intimately associated phenomena and may be manifestations of the same basic mechanism. An additional, antigenically identical, protein has also been isolated by the same procedures. The latter substance, termed "choleragenoid", lacks the permeability effect and choleragenicity of the choleragen moiety. Its size (estimated from Sephadex gel filtration at 42,000) is smaller than that of choleragen and it also differs in charge. Choleragenoid may prove useful as a nontoxic immunogen to protect against pathologic effects of V. cholerae infection.

310 citations


Journal ArticleDOI
TL;DR: Dihydrotestosterone formation was measurable in all of the immature prostates studied, including that from calf, and in a variety of other tissues known to be under androgenic control—duck preen gland, the comb and wattle of the chicken, and the preputial gland of rat and mouse.
Abstract: The conversion of testosterone-1,2-3H to dihydrotestosterone-3H has been measured under standardized conditions in slices of various tissues from 11 species. In the rat, the highest rates of this conversion were observed in prostate, epididymis, seminal vesicle, penis, preputial gland and scrotum, the other tissues exhibiting much lower values. When the rate of dihydrotestosterone formation was compared in prostate from 9 species, the values observed varied from 569±69 μμmoles/100 mg tissue in the rat to immeasurably low levels in the bull (4±3 μμmoles/100 mg/hr), whereas this conversion was demonstrable in all epididymal tissues studied. Furthermore, dihydrotestosterone formation was measurable in all of the immature prostates studied, including that from calf, and in a variety of other tissues known to be under androgenic control—duck preen gland, the comb and wattle of the chicken, and the preputial gland of rat and mouse. Dihydrotestosterone formation was not demonstrated in any muscle tested...

253 citations



Journal ArticleDOI
TL;DR: In vitro experiments were performed to determine if any of these agents, or epinephrine, might play a role in the regulation of LH release, and LH release was significantly enhanced when DA was added to the incubation medium in doses of 0.5–5.0 μg/ml.
Abstract: Recent evidence indicates the presence in the hypothalamus of neurons which contain dopamine (DA), norepinephrine (NE) and serotonin (5-HT). These in vitro experiments were performed to determine if any of these agents, or epinephrine (E), might play a role in the regulation of LH release. Doses of 0.5, 2.5 or 5.0 μg/ml of DA, NE or 5-HT failed to alter LH released from pituitaries incubated alone, whereas 5.0 μg/ml E enhanced LH release to some extent. DA at a 25.0 μg/ml dose significantly decreased assayable LH by inactivating it. When pituitaries were incubated in the presence of stalkmedian eminence (SME) tissue (2 SME/gland), LH release was stimulated by an average of 20.7% (p < .05). If the combined SME and pituitary tissue was incubated with 0.5–5.0 μg/ml of either NE or 5-HT, this basal release of LH was unaffected. LH release was significantly enhanced (p < .01) when DA was added to the incubation medium in doses of 0.5–5.0 μg/ml, and a dose response could be obtained. These results can only be e...

176 citations


Journal ArticleDOI
TL;DR: There is strong evidence that intramitochondrial malic enzyme activity is the major source of NADPH for 11β-hydroxylation in bovine adrenal cortex when either malate or succinate are the source of reducing equivalents.

132 citations


Journal ArticleDOI
01 Aug 1969-Science
TL;DR: The kinetics of repair suggest that, during the repair process, a transient, unstable cellular state occurs which prevents cell division in complete growth medium, and the capacity for repair appears to be dependent on cell age.
Abstract: Less than optimum conditions with regard to cell division after x-irradiation provide the necessary environment in which mammalian cells can repair potentially lethal radiation damage. The kinetics of repair suggest that, during the repair process, a transient, unstable cellular state occurs which prevents cell division in complete growth medium. The capacity for repair appears to be dependent on cell age.

130 citations



Journal ArticleDOI
TL;DR: It is concluded that metyrapone changes the equilibrium between two functionally different forms of cytochrome P-450 which exists in microsomes.

92 citations


Journal ArticleDOI
TL;DR: The relative sensitivities of the viruses to interferons were found to be characteristic for each of the species tested, with those closely related phylogenetically exhibiting similar patterns of relative interferon-induced virus resistance.
Abstract: Some viruses were found to be more sensitive than others to the action of interferons from certain species of animals but less sensitive to interferons from other species. Vaccinia virus was the most sensitive to mouse and hamster interferons of five viruses tested, but the least sensitive of these five viruses to human, rabbit, and bat interferons. The relative sensitivities of the viruses to interferons were found to be characteristic for each of the species tested, with those closely related phylogenetically exhibiting similar patterns of relative interferon-induced virus resistance. The amount of synthetic double-stranded polynucleotide polyinosinic acid-polycytidylic acid required to induce resistance to each of the viruses in each of the cell species correlated with the interferon sensitivities of the viruses.

88 citations


Journal ArticleDOI
TL;DR: Short-term incubations of rat anterior pituitary glands in Krebs-improved Ringer I (KR) media with varied concentrations of K+ showed that [K+] of 60 mm or more increased LH and FSH release from the glands, while with a [K +] of 30 mm the stimulatory effect was minimal.
Abstract: Short-term incubations of rat anterior pituitary glands in Krebs-improved Ringer I (KR) media with varied concentrations of K+ showed that [K+] of 60 mm or more increased LH and FSH release from the glands, while with a [K+] of 30 mm the stimulatory effect was minimal The effect of high [K+] on hormonal release was reversible, and there appeared to be an additive effect between high [K+] and releasing factors The action of high [K+] on LH and FSH release was completely abolished in Ca++-free media, while the effect of releasing factors was only partially inhibited EDTA-Na in Ca++-free media completely inhibited the effect of releasing factors EDTA had some inhibitory effect on the action of LRF by a mechanism other than by immobilization of Ca++ High concentrations of Mg++ also inhibited the action of both high [K+] media and releasing factors, while Mg++-free media enhanced their action very slightly, which supports the important role of Ca++ in the secretory mechanism Na-free Locke’s solution caus

88 citations



Journal ArticleDOI
TL;DR: Circular dichroic spectra of glucagon confirm that in dilute aqueous solutions about 10–15% α-helix is present which increases to about 35% α -helix at concentrations greater than 10 mg/ml.


Journal ArticleDOI
TL;DR: The finding that the low residual amounts of debrisoquin are sufficient to inhibit adrenergic neuronal monoamine oxidase (MAO) suggests that the antihypertensive action of debrisOquin and other neuronal blocking agents may lie, in part, in inhibition of neuronal MAO.


Journal ArticleDOI
TL;DR: Chicken liver citrate cleavage enzyme has an apparent optimum activity at pH 8.7, similar to the enzyme isolated from rat liver, and the loss of enzyme activity observed upon storage and its subsequent reactivation by dithiothreitol does not result from changes in aggregation and dissociation of the enzyme as judged by gel electrophoresis and ultracentrifugation.

Journal ArticleDOI
TL;DR: The results show that high levels of β-hydroxy-β-methylglutaryl coenzyme A synthase are unique to liver and the well differentiated hepatomas, and thus provide a biochemical basis for liver's role as the primary ketogenic organ.

Journal ArticleDOI
17 Oct 1969-Science
TL;DR: Pituitary halves incubated in pituitary stalk plasma release more luteinizing hormone than their opposite halves incubation in plasma from peripheral blood, and the secretion of lute inizing hormone-releasing factor may be controlled by a dopaminergic mechanism.
Abstract: Pituitary halves incubated in pituitary stalk plasma release more luteinizing hormone than their opposite halves incubated in plasma from peripheral blood. Glands incubated in stalk plasma from dopamine-treated rats release more luteinizing hormone than glands incubated in stalk plasma from untreated controls. Luteinizing hormone-releasing activity in stalk plasma may be due to the luteinizing hormone-releasing factor, and the secretion of luteinizing hormone-releasing factor may be controlled by a dopaminergic mechanism.


Journal ArticleDOI
TL;DR: The first inhibitor selected for study, cyclo-heximide, prevented or delayed the onset of choleragen-induced edema in the rat foot test and also prevented the development of choleraic diarrhea in the infant rabbit assay, but it did not alter the course of the established lesion in theRat foot.
Abstract: SummaryThis preliminary study suggests that the rat foot edema test may provide a useful means of screening pharmacological agents potentially capable of preventing or reversing the specific metabolic lesions induced by cholera enterotoxin (choleragen). The first inhibitor selected for study, cyclo-heximide, prevented or delayed the onset of choleragen-induced edema in the rat foot test and also prevented the development of choleraic diarrhea in the infant rabbit assay. However, it did not alter the course of the established lesion in the rat foot. These observations suggest that a choleragen-induced, host-produced protein mediator may be involved. Additional studies, involving this model, directed toward understanding the pathogenic mechanism of cholera toxin and to develop potentially more effective methods of treatment of cholera patients, are in progress.We wish to thank Miss Mary Knoohuizen for her assistance in helping to set up these assays. Support was provided by a grant, 1 R22 AI08877-01, from t...

Journal ArticleDOI
TL;DR: The temporal course of depolarizing potentials of cortical glial cells and their relationship to neural activity were investigated to provide information about the mechanisms producing glialdepolarization and the possible contribution of glial depolarization to slow potentials recorded from the surface of the cortex.

Journal ArticleDOI
TL;DR: The concentration of norepinephrine remaining in heart 18 hr after the administration of small doses of reserpine was inversely related to the concentration of persisting drug and the correlation was highly significant.

Journal ArticleDOI
TL;DR: The results can be explained in terms of the existence of two spectrally distinguishable forms of cytochrome P-450, which can associate with various substrates to form complexes which are spectRally similar to, but not necessarily identical to, one or the other of these forms.

Journal ArticleDOI
TL;DR: Dopamine is a potent stimulator of coronary blood flow and myocardial contractility, and the fact that the increased coronary flow was proportional to increases inMyocardial oxygen consumption indicates that the induced coronary vasodilation is secondary to increased myocardian oxygen demands, rather than the result of primary coronary vasODilation.
Abstract: The effect of intravenous infusions of dopamine on left circumflex coronary blood flow and myocardial oxygen consumption in doses ranging from 5 to 100 µg/kg/min was studied in 17 open-chest dogs anesthetized with chloralose. Flow was measured with an electromagnetic flowmeter. Dopamine caused a progressive and linear increase of coronary flow that was proportional to increases in myocardial oxygen consumption up to a dose of 80 µg/kg/min; at this dose, the increase over control was 365% (28 to 129 ml/min). These changes accompanied marked increases in stroke volume, left ventricular dP/dt, and mean systolic ejection rate. Mean aortic pressure and heart rate changed little at doses below 10 µg/kg/min, but increased steadily with doses over the range of 15 to 40 µg/kg/min. Dopamine is a potent stimulator of coronary blood flow and myocardial contractility. The fact that the increased coronary flow was proportional to increases in myocardial oxygen consumption indicates that the induced coronary vasodilation is secondary to increased myocardial oxygen demands, rather than the result of primary coronary vasodilation.

Journal ArticleDOI
TL;DR: Citrate cleavage enzyme was phosphorylated with γ-32P-ATP and the isolated compound behaved chromatographically and electrophoretically like phosphohistidine.


Journal ArticleDOI
TL;DR: The results indicated that endogenous CRF-induced ACTH secretion is a corticosteroid-sensitive process, and that the anterior pituitary may be a cortICosteroid feedback point, and the effect of intrapituitary dexamethasone on the ACTH release induced by exogenous ovine CRF was studied.
Abstract: Dexamethasone phosphate in doses ranging from 0 (vehicle control) to 2 μg/rat was injected into both lobes of the anterior pituitary, or into the median eminence or septa region of the brain. Endogenous CRF release was provoked by scald. Dexamethasone bilaterally in the anterior pituitary inhibited ACTH release after scald in doses of 100 ng/lobe or greater. These doses of dexamethasone were ineffective against scald when given intravenously. These results indicated that endogenous CRF-induced ACTH secretion is a corticosteroid-sensitive process, and that the anterior pituitary may be a corticosteroid feedback point. To test this conclusion further, we studied the effect of intrapituitary dexamethasone on the ACTH release induced by exogenous ovine CRF. Intrapituitary dexamethasone was again effective in preventing ACTH release. When similar small doses of dexamethasone were placed in the anterior medial basal hypothalamus, they were effective in stopping the adrenocortical response both to scald and to e...

Journal ArticleDOI
01 Nov 1969-Nature
TL;DR: In this paper, it was shown that the neutralization of protons by NH3 has precedence as a biological phenomenon, which may also serve to regulate the acidity of sweat.
Abstract: THE mechanism for the formation of CO32−, the reacting species in CaCO3 formation in biological systems which deposit CaCO3, is not known. The involvement of carbonic anhydrase in the biological formation of CaCO3 (refs. 1 and 2) suggests that CO32− arises from the dissociation of HCO3−. Hodges and Lorcher3,4 have summarized the major questions concerning the origin of CO32− in the avian eggshell-forming system and have outlined a model, originally proposed by Diamantstein5, in which the CO32− of eggshell CaCO3 arises in the shell gland lumen from HCO3− which is produced intracellularly by shell gland carbonic anhydrase. As emphasized by Hodges and Lorcher and also recently by Simkiss6, a major question remaining with the mechanism of CO32− formation is the fate of the proton formed by HCO3− dissociation. We propose that this proton may be neutralized by the reaction, NH3 + H+⇌NH4+. We also feel that NH3 acts in this manner in CaCO3 deposition by certain land snails7,8. The neutralization of protons by NH3 has precedence as a biological phenomenon. For example, protons are neutralized by NH3 in the mammalian kidney during metabolic acidosis9 and this reaction may also serve to regulate the acidity of sweat10. The effect of NH3 in the biological deposition of CaCO3 is summarized by the equation: This overall reaction has also been considered as a model for the geochemical deposition of CaCO3 in certain circumstances11.

Journal ArticleDOI
TL;DR: Although early or solitary metastasis to the jaws is uncommon, its occurrence, as evidenced by three of the seven cases reported here, makes it essential to include this entity in the differential diagnosis of jaw lesions.

Journal ArticleDOI
TL;DR: The antibiotic susceptibility results reported here provide guidelines for selection of antibacterial therapy and all rattlesnake bites are potentially contaminated with Clostridia and a wide variety of aerobic bacteria.
Abstract: Venom from 100 rattlesnakes and swabs of the fangs of 50 of these snakes were cultured for aerobic and anaerobic bacteria. Agar-dilution antibiotic susceptibilities for 170 of 207 aerobes and disc susceptibilities for 65 of 113 Clostridia were determined. Clostridia were isolated from 48% of venom and 86% of fang specimens. Histotoxic species were found in 50% of the snakes. Ninety- seven strains of gram-positive cocci were isolated, but no coagulase-positive staphylococci. Of 110 strains of gram-negative rods, Aerobacter, Proteus, and Pseudomonas genera were most common. Four salmonella strains were found. All rattlesnake bites are potentially contaminated with Clostridia and a wide variety of aerobic bacteria. Inflammation and necrosis secondary to envenomation provide a favorable setting for proliferation of organisms. The antibiotic susceptibility results reported here provide guidelines for selection of antibacterial therapy.