Showing papers by "University of Texas Southwestern Medical Center published in 1972"
TL;DR: This model is based largely on transport characteristics obtained by perfusing isolated segments of rabbit nephrons in vitro, and allows the entire system to operate by passive diffusion of NaCl out of the thin ALH.
381 citations
TL;DR: In order to understand all the pathophysiological mechanisms involved in the effect of acid-base changes on the heart, the peripheral vessels, the lungs, and the diffusion of oxygen between air, blood, and tissues, it is necessary to understand the effects of changes in pH on each step in the chain.
251 citations
TL;DR: The temporal relationship demonstrated among the decreases in magnitude of binding spectra of hexobarbital, the increase in heme oxygenase activity, the decrease in measurable cytochrome P-450 content, and the reversal of these parameters during the recovery phase following a single injection of methemalbumin strongly indicates the involvement of the same components of the microsomal electron transport system in both the drug metabolism and hemeoxyase systems in liver.
248 citations
TL;DR: The evidence obtained indicates that in this model of chronic arthritis, the inducing antigen persists for long periods of time in the form of immune complexes in the surface layers of the intra-articular collagenous tissue.
Abstract: In an experimental arthritis induced by injection of bovine serum albumin or egg albumin into the joints of previously immunized animals, it has been demonstrated that the major portion of the radioactively labeled antigens injected was localized to avascular collagenous tissues in the joint, i.e., articular cartilage, menisci, and intra-articular ligaments. The antigens were partially eluted from the tissues with 5 M guanidine solution, but not with acid buffers or by 3 M magnesium chloride. The radioactive material eluted with guanidine was at least 80% precipitable by specific antisera. The radioactively labeled-inducing antigen was identified on the surface of articular collagenous tissues from arthritic joints by radioautography and immunofluorescence. Rabbit immunoglobulin and C3 were demonstrated in the same sites by immunofluorescence. The presence of specific antibody in collagenous tissues was demonstrated by the selective in vitro binding of 125I-labeled-inducing antigen to menisci from arthritic joints of immunized animals. The evidence obtained indicates that in this model of chronic arthritis, the inducing antigen persists for long periods of time in the form of immune complexes in the surface layers of the intra-articular collagenous tissue. The antigen retained in this form may be responsible for the chronicity of the synovitis by serving as a direct stimulus for the maintenance of prolonged antibody synthesis in the synovium and by providing a source of complement-fixing antigen-antibody complexes for the mediation of joint inflammation.
181 citations
TL;DR: This analysis excludes patients with joint involvement secondary to osteomyelitis except for the unique situation of septic hip in which it is difficult to determine whether joint infection or bone infection is the primary event.
Abstract: In 1966 we published our experience with 117 cases of septic arthritis seen on the pediatric services of Parkland Memorial Hospital and Children9s Medical Center in Dallas. That review brought to attention the hitherto unrecognized frequency of Hemophilus influenzae in this disease and, by emphasizing the wide variety of bacteria involved, tried to make the point that precise bacteriological diagnosis was essential to optimal therapy. This follow-up report of 221 patients adds the 104 patients treated from 1966 through 1970 to the previous series. The tabular material is arranged in the same manner as in the report covering the years 1955 through 1965 for easy comparison. (Tables I to IV) This analysis excludes patients with joint involvement secondary to osteomyelitis except for the unique situation of septic hip in which it is difficult to determine whether joint infection or bone infection is the primary event. The average number of cases per year has steadily risen but this appears to reflect mainly the even-enlarging medical population served rather than a real increase in frequency of septic arthritis. For example, total pediatric admissions rose by 32% from 1960 to 1970 while septic arthritis cases increased 46%. 1955-59: 6.4 cases per year 1960-65: 14.2 cases per year 1966-70: 20.8 cases per year A bacteriological diagnosis was established in 66.5% of cases overall (Table I) but the figure is higher during the past decade when the quality of diagnostic bacteriology was improved. 1955-59: 34% 1960-65: 71% 1966-77: 73% Part of the improved percentage of bacteriological diagnosis stems from better use of blood cultures.
173 citations
TL;DR: The results indicated the involvement of an β-adrenergic receptor mechanism and catecholamines (CA) in the transmission of the progesterone stimulus and drugs which modify brain CA levels were used to identify the CA involved.
Abstract: Progesterone injected sc into spayed rats primed two days earlier with 5 μg estradiol benzoate increased plasma levels of LH and FSH 6 hr later as measured by radioimmunoassay (RIA). These peaks of plasma LH and FSH were abolished by prior treatment with phenoxybenzamine or haloperidol, while the P-adrenergic receptor blocker, propranolol, had no effect. The results indicated the involvement of an β-adrenergic receptor mechanism and catecholamines (CA) in the transmission of the progesterone stimulus. Drugs which modify brain CA levels were used to identify the CA involved. They were administered prior to the injection of progesterone. The expected peak levels of plasma LH and FSH failed to occur in rats treated with DL-β-methylp-tyrosine methyl ester HC1 (β-MPT) which lowers brain dopamine (DA) and norepinephrine (NE) levels. Sodium diethyldithiocarbamate (DDC) and l-phenyl-3-(2-thiazolyl)-2 thiourea (U-14,624), which are known to decrease NE levels without decreasing DA levels by inhibiting the activity...
148 citations
TL;DR: The present paper will be concerned with the factors involved in the generation and maintenance of metabolic alkalosis, andPhysiologic determinants will be explored and clinical derangements will be examined.
147 citations
TL;DR: From a clinical standpoint, newer studies relating to the treatment of diabetic ketoacidosis have been covered, with particular attention paid to the problems of late cerebral edema, paradoxical acidification of the cerebrospinal fluid during treatment, shifts of the oxygen dissociation curve due to 2,3-diphosphoglycerate depletion and initial hypokalemia.
Abstract: Recent studies of the regulation of ketogenesis are reviewed. Under circumstances of relative or absolute insulin deficiency there is a mobilization of free fatty acids from adipose tissue to the liver. While an increased delivery of fatty acids to this organ is important in providing substrate for ketone body formation, it is emphasized that enhanced uptake of fatty acids by the liver is not sufficient in itself to initiate maximal ketogenesis. It appears likely that a major determinant of the rate of ketogenesis is competition for the fatty acid substrate between the β-oxidative and triglyceride synthesizing pathways. While it is widely held that the rate of triglyceride synthesis is primary and that only those fatty acids not utilized for esterification become available for oxidation, evidence for the reverse sequence is presented. It is considered likely that fatty acids are utilized for triglyceride synthesis only insofar as they escape uptake and oxidation in the mitochondria. Regardless of the mechanism, fatty acid oxidation is increased in the ketotic state with the consequence that acetyl-CoA production is accelerated. Since the utilization of acetyl-CoA for fatty acid synthesis and, to a much lesser extent, its oxidation in the Krebs cycle is impaired, the synthesis of acetoacetate and β-hydroxybutyrate is stimulated to a remarkable degree. The hepatic overproduction of ketones appears to be coupled to a limited capacity for their utilization by peripheral tissues, the combined effect of which accounts for the life-threatening acidosis seen in diabetic coma. From a clinical standpoint, newer studies relating to the treatment of diabetic ketoacidosis have been covered, with particular attention paid to the problems of late cerebral edema, paradoxical acidification of the cerebrospinal fluid during treatment, shifts of the oxygen dissociation curve due to 2,3-diphosphoglycerate depletion and initial hypokalemia. Recommendations for therapy designed to minmize complications are presented.
136 citations
TL;DR: The chemical properties of two proteins, cholera enterotoxin ( choleragen) and a spontaneously formed toxoid (choleragenoid), have been studied and it is found that neither protein contains significant quantities of lipid or hexose.
132 citations
TL;DR: Evidence is presented that purified mitochondria have binding sites for the bound 80 S ribosomes; additional binding sites can be exposed by washing mitochondria with 2 mm EDTA, and at least two classes of binding sites with EDTA-washed mitochondria.
131 citations
TL;DR: The data indicate that the chronic synovial inflammatory response is associated with a chronic local immune response in which prolonged active synthesis of immunoglobulin and specific antibody directed against the locally retained inducing antigen takes place.
Abstract: Using the model described by Dumonde and Glynn in which a chronic synovitis is induced by the intraarticular injection of antigen in previously immunized rabbits, marked chronic local synthesis of immunoglobulin comparable to that of lymph nodes and spleen was found as long as 6 weeks after the arthritis was induced. Between 30 and 40% of this newly synthesized immunoglobulin was accounted for as specific antibody to the locally injected antigen. Very low levels of synthesis were found in the spleen, control synovia and regional lymph nodes not draining immunized sites. The circulating antibody levels at the time of induction showed a positive correlation (r = 0.66) with the severity of the subsequent histologic findings in the synovium. The fate of the intraarticular antigen was studied in arthritic and control animals. There was a selective local retention of antigen in animals previously immunized with the homologous antigen. The retained intraarticular antigen was eliminated very slowly, with a half-life of over 20 days. These data indicate that the chronic synovial inflammatory response is associated with a chronic local immune response in which prolonged active synthesis of immunoglobulin and specific antibody directed against the locally retained inducing antigen takes place.
TL;DR: The new spectral species is interpreted to be an oxygenated form of cytochrome P-450, presumably a ternary complex of oxygen, camphor, and ferrous cyto Chrome, and undergoes slow decomposition to the ferric form of the hemoprotein and is most stable in the pH range 7–8 and at temperatures below 10 °.
TL;DR: The results demonstrate that careful use of the described method yields accurate measurement of unidirectional uptake rates of lipids across the brush border that are of critical importance in defining the characteristics of membrane penetration and the rate-limiting steps in fat and sterol absorption.
TL;DR: The fact that the simplest of these reactions, that catalyzed by citrate lyase, occurs in the most primitive organisms and that the most complex, the ATP citrate Lyase reaction, occursIn the most recently evolved organisms, suggests a possible evolutionary relation between these enzymes.
Abstract: Publisher Summary The enzymes that catalyze lyase reactions on citrate to yield a C 2 and a C 4 unit are: citrate lyase, citrate synthase, and adenosine triphosphate (ATP) citrate lyase. Citrate lyase has been reported only in certain bacteria, citrate synthase has been found in all cells examined for it, and ATP citrate lyase has been found only in eukaryotic cells. The reaction catalyzed in common by these three enzymes is an aldol type, that is the reversible formation of a C—H bond from a C—C bond. It is possible that there exist some catalytic similarities in the three enzymatic reactions so that comparison of the results obtained with each enzyme might be useful in understanding the others. The citrate enzymes comprise a unique biological system in which three enzymes catalyze the same bond-breaking-making reaction. The fact that the simplest of these reactions, that catalyzed by citrate lyase, occurs in the most primitive organisms and that the most complex, the ATP citrate lyase reaction, occurs in the most recently evolved organisms, suggests a possible evolutionary relation between these enzymes.
TL;DR: Two lines of evidence are presented in support of the view that thyroid peroxidase plays a role in T4 formation beyond that of simply providing the DIT precursor for the coupling reaction.
Abstract: When thyroglobulin and other proteins are incubated with iodide in the presence of purified thyroid peroxidase and glucose plus glucose oxidase, the iodotyrosines MIT and DIT are formed by iodination of tyrosyl residues, and significant amounts of T4 are also produced. Formation of T4 is greatest when goiter thyroglobulin is the iodine acceptor. The present study was designed to determine whether thyroid peroxidase plays a catalytic role in the coupling reaction to form T4, or whether it serves only to form the precursor of T4, diiodotyrosine, which might then couple non-enzymatically to form T4. Two lines of evidence are presented in support of the view that thyroid peroxidase plays a role in T4 formation beyond that of simply providing the DIT precursor for the coupling reaction. In one group of experiments, thyroglobulin, casein, and fibrinogen were iodinated chemically with molecular iodine and enzymatically with thyroid peroxidase. At any given level of iodination the number of DIT and MIT residues p...
TL;DR: Rat hepatoma cells are able to adhere to many surfaces of diverse chemical compositions, but inhibition of adhesion by p -mercuribenozate and arsenite was reversible; inhibition by HgCl 2, iodoacetate and N -ethylmaleimide was not reversible.
TL;DR: It was concluded that the 5α-reductase in prostatic nuclei is located in a nuclear membrane and in the isolation of this nuclear membrane fraction a 90-fold purification of the enzyme has been achieved.
TL;DR: The effect of intensive physical exercise upon plasma levels of pancreatic glucagon was investigated in dogs and in man and glucose rose in parallel from a pre-exercise value to 124 mg/100 ml during recovery.
Abstract: The effect of intensive physical exercise upon plasma levels of pancreatic glucagon was investigated in dogs and in man. In 7 dogs, treadmill exercise until collapse was invariably associated with a rise in plasma glucagon, which at the time of collapse averaged 426 pg/ml (sem ± 71), more than 4 times the baseline average of 111 pg/ml (sem ± 26) (p < 0.005). Glucose rose in parallel from 88 mg/100 ml prior to exercise (sem ± 2) to a peak of 105 mg/100 ml (sem ± 4) at collapse (p < 0.01). Hypoglycemia did not occur in any dog. Insulin remained unchanged but rose briefly soon after collapse. In 4 human volunteers exercised to exhaustion on a stationary bicycle glucagon rose from 68 pg/ml (sem ± 17) to 116 pg/ml (sem ± 14) 10 min after the exhaustion point (p < 0.02), and again glucose rose in parallel from a pre-exercise value of 93 mg/100 ml (sem ± 3) to 124 mg/100 ml (sem ± 8) during recovery. Insulin also rose during recovery. When dogs were exercised to collapse during a 15 mg/kg/min intravenou...
TL;DR: It is established unequivocally that mitochondria undergo energy-linked ultrastructural transformation between the condensed and the orthodox configurations which are thus natural structural states related to the metabolic activity of the mitochondrion.
Abstract: An investigation was carried out in which microsamples of isolated rat liver mitochondria and freshly prepared mitoplasts in defined energy states were freeze-cleaved. Parallel microsamples were fixed with osmium tetroxide and with glutaraldehyde followed by osmium tetroxide as previously used in this laboratory for the preservation of energy-linked mitochondrial configurations. The details of the orthodox configuration of energized mitochondria and the condensed configuration of de-energized mitochondria, as revealed previously by chemical fixation, are confirmed in this report for nonfixed, freeze-cleaved mitochondria. The precise agreement in preservation of configuration obtained by the physical fixation of rapid freezing and by chemical fixation establishes unequivocally that mitochondria undergo energy-linked ultrastructural transformation between the condensed and the orthodox configurations which are thus natural structural states related to the metabolic activity of the mitochondrion. Configurations observed by freeze-cleaving and by chemical fixation reveal that mitoplasts also undergo a specific and dramatic ultrastructural transformation with the induction of oxidative phosphorylation. The transformation appears to be isovolumetric and therefore is thought to be mediated through energized conformational activity in the surface electron-transport membrane of the mitoplast. Passively swollen, spherical, osmotically active mitoplasts could not be fixed rapidly enough by chemical fixatives as normally used without altering the spherical form. In this special case preservation of configurational form required rapid freezing or chemical fixatives of low osmolar concentration.
TL;DR: It is concluded that stress can induce a rapid release of pituitary FSH and LH as well as prolactin in the rat, and the effect of Nembutal is thought to be on the CNS.
Abstract: The stress of etherization and bleeding produced an elevation within 2 min in the plasma levels of prolactin, LH, and FSH in ovariectomized rats. Quantitatively the elevation was greatest in the case of prolactin, less for LH, and least for FSH. A second exposure to ether and bleeding one hour later produced a further elevation in prolactin and no further change in LH and FSH. The levels of prolactin and LH but not FSH had declined to control, nonstress (decapitated) levels within one hr. Nembutal blocked the stressinduced elevations of plasma prolactin and LH but did not affect the levels of FSH. The effect of Nembutal is thought to be on the CNS since the Nembutalized rats responded to hypothalamic extract or ovine LRF with dramatic elevations in plasma LH, indicating that the pituitary was still responsive to releasing factors. It is concluded that stress can induce a rapid release of pituitary FSH and LH as well as prolactin in the rat. (Endocrinology 90: 707, 1972)
TL;DR: The clinical characteristics, diagnosis, and treatment of obstructive and inflammatory diseases of the major salivary glands are discussed in this article.
TL;DR: It is concluded that median eminence lesions may initially lead to release of stored releasing factors from the damaged tissues and that this is followed by a profound decrease in release of gonadotropins which is more pronounced for LH than for FSH.
Abstract: Plasma gonadotropins and prolactin were measured by radioimmunoassay before and after placement of direct current or radiofrequency lesions in the hypothalamus in intact and castrated rats of either sex. Following median eminence lesions, there was a rapid increase in the levels of plasma prolactin, LH and FSH. In general the response was greatest for LH, slightly less for prolactin and minimal for FSH. In the case of FSH and LH, this was followed by a decline to subnormal levels. The decline was much more pronounced in castrate than in intact animals. It is concluded that median eminence lesions may initially lead to release of stored releasing factors from the damaged tissues and that this is followed by a profound decrease in release of gonadotropins which is more pronounced for LH than for FSH. The initial rise in prolactin may be caused by release of prolactin—releasing factor. The maintained secretion of prolactin is presumably caused by withdrawal of tonic inhibitory hypothalamic influences. The el...
TL;DR: The injection of either saline or contrast medium results in an immediate alteration in left ventricular function secondary to an increased volume load (the Frank-Starling mechanism), an effect possibly resulting from changes in osmolality.
TL;DR: It is suggested that specific adsorption of toxin to the brush-border membrane is the initial step in the pathogenesis of cholera, but that an additional process, stimulated by toxin but not toxoid, is essential, which could be activation of adenyl cyclase.
Abstract: Immunohistochemical techniques, done with fluorescein- and horseradish peroxidase-labeled antibodies specifically purified by immunoadsorption, were used to show cholera-toxin antigen in intestinal tissues from adult mice injected intraluminally with highly purified cholera toxin. The toxin (choleragen) and natural toxoid (choleragenoid), but not formalin-inactivated toxoids, were specifically and selectively adsorbed uniformly to the entire mucosal surface of the villi and crypt areas. No penetration of toxin into the epithelium or the lamina propria was observed. Ultrastructural localization studies, using the peroxidase-antibody method, revealed the toxin to be on the membranes of the microvilli. Autoradiography with highly purified, tritium-labeled toxin confirmed these observations. It is suggested that specific adsorption of toxin to the brush-border membrane is the initial step in the pathogenesis of cholera, but that an additional process, stimulated by toxin but not toxoid, is essential. This could be activation of adenyl cyclase. The possibility that amounts of toxin or toxin fragments below the limits of detection by the systems used could penetrate cannot be excluded. Since there is a systemic antitoxin response in cholera, this is likely to occur but may not actually be important in the pathogenesis of the diarrhea of cholera.
TL;DR: It was observed that orally administered toxin causes experimental cholera in mice, and this may be a useful means of bioassay of the toxin, although it is difficult to demonstrate intestinal immunity to a bolus toxin challenge.
Abstract: Mice fed single, moderate doses of highly purified, relatively nontoxic antigenic equivalents of the enterotoxin (exotoxin) of Vibrio cholerae developed serum antibodies and became resistant to intraintestinal challenge with live vibrios and to the lethal effect of cholera toxin administered iv. The same antigens--choleragenoid, procholeragenoid, and formalin toxoid-were also effective when administered parenterally, but there were inversions of the relative activity of the antigens depending on the route of challenge; furthermore, the antigens may have side effects. The study clearly suggests that it may prove feasible and advantageous to immunize man against cholera by the oral route. It was also observed that orally administered toxin causes experimental cholera in mice. This may be a useful means of bioassay of the toxin, although it is difficult to demonstrate intestinal immunity to a bolus toxin challenge.
TL;DR: Differences in the rate of formation of the piperonyl butoxide metabolite-cytochrome P-450 complex in liver microsomes from rats and mice can account for the greater sensitivity of mice to piperonies butoxide inhibition of drug metabolism.
TL;DR: In this paper, the authors examined the influence of distal sodium delivery upon glomerular hydrostatic pressure utilizing a servo null pressure device in Wistar rats with surface glomeruli on normal NaCl diet and during saline diuresis.
TL;DR: The mechanisms which determine the response of stroke volume to mild, moderate, and severe exercise were compared in nine dogs running on a level treadmill and it was concluded that, despite extremely high heart rates, stroke volume increased during exercise.
Abstract: The mechanisms which determine the response of stroke volume to mild, moderate, and severe exercise were compared in nine dogs running on a level treadmill. The dogs ran for 3-minute periods at 3-4 mph (mild exercise), 6-8 mph (moderate exercise), and 10-14 mph (severe exercise). Heart rate increased from a standing control value of 107 ± 6 beats/min to 191 ± 10 beats/min in mild, 221 ± 8 beats/min in moderate, and 263 ± 9 beats/min in severe exercise. Stroke volume increased 14%, 19%, and 15% for mild, moderate, and severe exercise, respectively. During mild exercise, left ventricular internal diameter decreased at end-systole but was unchanged at end-diastole. During moderate and severe exercise, end-diastolic diameter increased consistently as did left ventricular end-diastolic pressure. It was concluded that, despite extremely high heart rates, stroke volume increased during exercise. The augmentation in stroke volume was due to the combined effects of an increase in contractility, caused by increased sympathetic nervous system activity, and the operation of the Frank-Starling mechanism.
TL;DR: The presence of the AB (hybrid) band demonstrates that both X-linked G6PD alleles are functional in the maturing human oocyte.
TL;DR: Experiments with inhibitors of protein synthesis are consistent with a translational site for heme repression, and a mechanism whereby drugs may induce δ-aminolevulinic acid synthetase by interfering with heme synthesis is demonstrated.