All about asthma ... your queries answered.
Explore the source record for details and available documents.
Allergens↗
Biomedical subjects
J Hubbard
Publications and source records attributed to J Hubbard.
Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting.
The acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS) is a devastating complication of human immunodeficiency virus infection characterized by a disproportionate decrease in lean body mass. The pathogenesis of the AWS is unknown, but recent data suggest that endogenous secretion of the potent anabolic hormone, testosterone; is decreased in 30-50% of men with AIDS. However, it is unknown whether decreased androgen levels are associated with decreased lean body mass and/or functional decreases in muscle strength and aerobic capacity in hypogonadal men with the AWS. In addition, testosterone is known to have stimulatory effects on GH secretion, and the loss of these effects on the GH-insulin-like growth factor I (IGF-I) axis may be an additional mechanism of decreased lean body mass in this population. Twenty hypogonadal subjects (free-testosterone < 12 pg/mL) with weight loss > 10% of preillness weight or absolute weight < 90% ideal body weight (IBW) were enrolled in the study. None of the subjects were receiving Megace. Lean body mass and fat-free mass were determined by potassium-40 isotope analysis (40K) and dual-energy x-ray absorptiometry, respectively, and analyzed with respect to gonadal function by linear regression analysis. Muscle mass was determined by urinary creatinine excretion, and exercise functional capacity was assessed by a 6-min walk test, a sit-to-stand test, and a timed get-up-and-go test. Results also were compared with gonadal function by regression analysis. IGF-I and mean overnight GH levels, determined from frequent sampling (q20 min from 2000-0800 h), were compared with results obtained from age- and sex-matched normal controls. Subjects were 26-58 yr of age (39 +/- 7 yr, mean +/- SD) with a CD4 cell count of 150 +/- 186 cells/mm3. Serum levels of FSH were elevated in 30% of the subjects. Muscle mass was significantly reduced, compared with expected mass for height (23.3 +/- 5.5 vs. 29.3 +/- 1.7 kg, P = 0.0001) and was decreased disproportionately to weight (77% of expected value for muscle mass vs. 93% of expected value for weight). Free-testosterone levels were correlated with total body potassium (R = 0.45, P < 0.05) and muscle mass (R = 0.45, P < 0.05). Total-testosterone levels were correlated with exercise functional capacity (R = 0.64, P = 0.01 for the sit-to-stand test and R = 0.53, P < 0.05 for the 6-min walk test). Mean GH levels were significantly increased (3.03 +/- 1.76 vs. 0.90 +/- 0.37 ng/mL, P < 0.001) and IGF-I levels decreased (167 +/- 66 vs. 225 +/- 69 ng/mL, P < 0.01), compared with age- and sex-matched eugonadal controls. GH levels were inversely correlated with caloric intake (R = -0.60, P = 0.02) and percent fat mass by dual-energy x-ray absorptiometry (R = 0.58, P = 0.02). Six additional hypogonadal subjects receiving Megace for AIDS wasting were analyzed separately. Nutritional status and parameters of body composition were compared in the Megace and non-Megace-treated subjects. No significant differences in caloric intake, lean body mass, fat mass, or muscle mass were demonstrated. These data demonstrate that changes in body composition, including loss of lean body and muscle mass, and deterioration in exercise functional capacity are highly correlated with androgen levels in hypogonadal men with the AWS. Furthermore, our data demonstrate significantly increased GH levels and decreased IGF-I in association with low weight in this population. These data suggest that androgen deficiency combined with classical GH resistance may contribute to the critical loss of lean body and muscle mass in hypogonadal men with the AWS. These data are the first to link muscle and lean body wasting with progressive gonadal dysfunction among the large percentage of men with AIDS wasting who are hypogonadal. This demonstrates the need for additional studies to determine the efficacy of gonadal steroid replacement to increase lean body mass in this population.
Adult↗
Comorbidity of psychiatric diagnoses with posttraumatic stress disorder in survivors of childhood trauma.
OBJECTIVE: This study examines posttraumatic stress disorder (PTSD) symptoms, trauma exposure, gender, and diagnostic comorbidity in a sample of 59 Cambodian young adults (29 male and 30 female) who survived massive trauma as children. METHOD: Psychiatric diagnoses were made using the Structured Clinical Interview for DSM-III-R-Non-Patient version, a structured diagnostic interview, and trauma exposure was measured with a Traumatic Life Events Questionnaire. RESULTS: A significant number of those with PTSD (59%) had one or more additional DSM-III-R Axis I disorders. Major depression and generalized anxiety disorder were the most common comorbid disorders. Somatoform pain disorder was also found to coexist with PTSD but only among females. Women were also found to have higher levels of both current and lifetime PTSD symptoms. CONCLUSION: Trauma symptoms were related to exposure and exposure was related to age, but age was not related to symptoms. The findings suggest that the significant levels of comorbid diagnoses previously found to exist with PTSD in people traumatized as adults can be found among survivors of massive childhood trauma. Also, the rate of PTSD diagnoses found in this sample 15 years after the trauma of Pol Pot is comparable to findings previously reported in studies of Cambodian youths and shows that the effects of trauma experienced in childhood persist into early adulthood.
Adaptation, Psychological↗
Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins.
The initial rolling interaction of leukocytes with the blood vessel wall during leukocyte trafficking has been postulated to rely on members of the selectin family of adhesion molecules. Two selectins, E-selectin and P-selectin, have been identified that are expressed on activated endothelial cells. Mice deficient in E-selectin expression have been produced in order to examine the role of this selectin in leukocyte trafficking. Mice homozygous for an E-selectin null mutation were viable and exhibited no obvious developmental alterations. E-selectin-deficient mice displayed no significant change in the trafficking of neutrophils in several models of inflammation. However, blocking both endothelial selectins by treatment of the E-selectin-deficient animals with an anti-murine P-selectin antibody, 5H1, significantly inhibited neutrophil emigration in two distinct models of inflammation. While neutrophil accumulation at early times during thioglycollate-induced peritonitis was dependent on P-selectin, neutrophil accumulation at later time points was blocked by 5H1 only in E-selectin-deficient mice but not in wild-type mice. Similarly, edema as well as leukocyte accumulation in a model of delayed-type hypersensitivity in the skin was almost completely prevented by blockade of P-selectin function with 5H1 in the E-selectin-deficient mice while the same treatment had no effect in wild-type mice. These data demonstrate that the majority of neutrophil migration in both models requires an endothelial selectin but that E-selectin and P-selectin are functionally redundant. These data have important implications in the use of selectin antagonists in the treatment of inflammatory disease.
Animals↗
A performance study of the Loma Linda proton medical accelerator.
More than three years have passed since Loma Linda treated the first cancer patient with the world's first proton accelerator dedicated to radiation therapy. Since that time, over 1000 patients have completed treatments and the facility currently treats more than 45 patients per day. With a typical intensity of 3 x 10(10) protons per pulse and 27 pulses per minute, dose rates of 90-100 cGy/min are easily achieved on a 20-cm diameter field. In most cases, patient treatment times are 2 min, much less than the patient alignment time required before each treatment. Nevertheless, there is considerable medical interest in increasing field sizes up to 40-cm diameter while keeping dose rates high and treatment times low. In this article, beam measurements relevant to intensity studies are presented and possible accelerator modifications for upgrades are proposed. It is shown that nearly all intensity losses can be ascribed to the large momentum spread of the injected beam and occur at or near the injection energy of 2 MeV. The agreement between calculations and measurements appears quite good. In addition, optimum beam characteristics for a new injector are discussed based upon the momentum acceptance and space charge limits of the Loma Linda synchrotron.
Biophysical Phenomena↗
Evidence that facilitative glucose transporters may fold as beta-barrels.
A widely accepted model for the structure of the facilitative glucose transporters (GLUTs) predicts that they form 12 transmembrane alpha-helices and that the highly conserved sequence Ile-386-Ala-405 in GLUT1 is intracellular. We raised a polyclonal antibody against a synthetic peptide encompassing this conserved sequence and found that antibody treatment increased 2-deoxy-D-glucose (DOG) uptake in Xe-nopus oocytes expressing GLUT1, GLUT2, or GLUT4 only when applied to the extracellular side. This effect was dose dependent and was specifically blocked by competition with the peptide Ile-386-Ala-405; it was due to a decrease in the Km for the transport of DOG. To ascertain GLUT orientation, we raised anti-peptide antibodies against the last 21 and 25 C-terminal amino acids of GLUT1 and GLUT4, respectively, which were previously shown to be intracellular. These antibodies increased DOG uptake when injected into oocytes expressing GLUT1 and GLUT4, but not when added extracellularly. Prompted by the noted discrepancy, we found sequence similarity between GLUTs and porins, two of which are known from crystallography to form 16-stranded transmembrane antiparallel beta-barrels. Analysis of the hydrophobicity, amphiphilicity, and turn propensity of GLUT1 leads us to propose that GLUTs fold as porin-like transmembrane beta-barrels. This model is consistent with the results of the present antibody studies and also with previously published experimental evidence inconsistent with the 12-helix model.
Amino Acid Sequence↗
Managing cultural diversity in the workplace.
Cultural diversity is a strength of the American work force. Due to the increasing cultural diversity in the workplace, organizations find it in their best interest to move beyond affirmative action to effective management to achieve higher employee retention and develops an employee cultural mix that better matches the mix of the available labor force and customer base. To manage a diverse work force, managers need to have the proper tools, training and evaluation and monitoring programs. Important initiatives to successful management of cultural diversity include eliciting support and commitment from the board of directors, the CEO and other top management; organizing subcommittees to research and monitor demographic changes to determine what the organization's goals should be and to decide what changes are to be made. Employees must be trained to be aware of prejudices and how to manage their own actions.
Administrative Personnel↗
The effects of althesin on luteinizing hormone release cannot be explained by actions of the GABAA receptor alone.
Althesin and pentobarbitone are anaesthetics which act by prolonging the open time of the chloride channels of the GABA(A) receptor. To explain why luteinizing hormone (LH) release is less depressed by Althesin anaesthesia than by pentobarbitone anaesthesia we suggest that either Althesin is a less potent anaesthetic in the preoptic area or that Althesin as well as stimulating GABA(A) receptors has some other action, perhaps stimulation of GABA(B) receptors, which may facilitate LH release. To investigate the relative potency of the anaesthetics in the preoptic area nine cats were anaesthetised, six with Althesin and three with pentobarbitone, mounted in a stereotaxic frame and prepared for extracellular recording and stimulation of spontaneously active units in the preoptic region. When cats anaesthetised with Althesin were compared with cats anaesthetised with pentobarbitone there were significantly fewer of these units for the number of tracks made. These units also had a significantly lower frequency and a distribution significantly skewed toward lower frequencies. Electrical stimulation of the fornix and of sites in the medial basal hypothalamus and medial forebrain bundle inhibited about 50% of the units and the median duration of the inhibitory pause was significantly longer following stimulation at all three sites in cats anaesthetised with Althesin. We conclude that Althesin is a more potent anaesthetic than pentobarbitone in the preoptic region and that its effects on LH release cannot be explained by its effects on the GABA(A) receptor alone.
Action Potentials↗
Birth order and its relationship to depression, anxiety, and self-concept test scores in children.
Children (N = 404), 7 to 12 years old, were given the Children's Depression Inventory, the State-Trait Anxiety Inventory for Children, and the Piers-Harris Self-Concept Scale. First-born children scored significantly lower on depression than second-, third-, fourth-born, and youngest children. First borns showed significantly less trait anxiety than third-born children. First-born children also showed significantly higher levels of self-esteem than second-born and youngest children. Girls in this study showed significantly more trait anxiety than boys.
Anxiety↗
Modulation of glucocorticoid receptor from development to aging.
Explore the source record for details and available documents.
Aging↗
CA125 as a serum marker for poor prognosis in ovarian malignancies.
In cancer of the ovary, a tumor marker is much needed to assist the conventional methods for monitoring the disease course. All published reports of the CA125 serum immunoassay to date have indicated that rising or falling CA125 levels correlated with disease progression or regression in patients with ovarian malignancies. Our experience with CA125 at the University of Alabama at Birmingham shows that rising CA125 levels are highly suggestive of progressive disease. However, the significance of our findings with CA125 is that, contrary to other reports, falling CA125 levels are not a reliable indicator for regressive disease. Thus, falling CA125 levels are not clinically useful whereas rising CA125 levels may be interpreted as indicative of poor tumor response to therapy, and of the presence of persistent or recurrent disease either prior to second-look laparotomy or during post-treatment follow-up.
Antigens, Neoplasm↗
The risk of deep venous thrombosis: a computerized epidemiologic approach.
The appropriate use of prophylactic measures to prevent deep venous thrombosis is dependent on the ability of physicians to identify high-risk patients. This problem has been the subject of numerous epidemiologic reports compiled during the last several decades. Described herein is a computerized technique to condense the literature on this subject into a form better suited for practical application. This technique comprises an interactive program that calculates a patient's relative risk of developing a thrombus on the basis of a comparative evaluation of his medical profile. The computer then reports the patient's calculated relative risk along with other information that may pertain to his risk of deep venous thrombosis.
Computers↗
Building owners find alternatives to asbestos removal, replacement.
Explore the source record for details and available documents.
Asbestos↗
Chemotherapy of cervix cancer with doxorubicin and cisplatin. A phase I pilot study of the Gynecologic Oncology Group.
Twelve women with previously irradiated advanced pelvic cancer were treated with doxorubicin and cisplatin to determine a maximum tolerable dose. Response was not an objective of this phase I study, but one partial response was seen in four cases of cervix cancer with measurable lesions. Hematologic toxicity was frequent and severe at the starting doses (doxorubicin 30 mg/M2 and cisplatin 100 mg/M2 every 3 weeks), but was acceptable when cisplatin was used at 75 mg/M2. Further evaluation of this combination in squamous carcinoma of the cervix is not recommended.
Adult↗
Antiarrhythmic and electrophysiologic effects of oral propafenone.
Twenty-six patients had ventricular tachycardia initiated at control electrophysiologic study and had a repeat study during oral propafenone therapy. Ten patients had had sustained ventricular tachycardia, 6 cardiac arrest and 10 symptomatic, nonsustained ventricular tachycardia. Twenty-two patients had heart disease, 18 of whom had coronary artery disease. During propafenone therapy, ventricular tachycardia could not be initiated during programmed ventricular stimulation in 5 patients, and in 21 patients the cycle length of induced ventricular tachycardia increased from 246 +/- 42 ms at control to 355 +/- 96 ms (p less than 0.001). Seventeen patients were discharged with propafenone therapy and have been followed for a mean of 11 months. No symptomatic ventricular tachycardia recurred in the 5 patients without inducible ventricular tachycardia during drug treatment. Six of 12 patients with inducible ventricular tachycardia during the drug study have remained asymptomatic. In conclusion, propafenone substantially prolongs the cycle length of ventricular tachycardia, and initiation of ventricular tachycardia by programmed ventricular stimulation at drug study does not preclude a favorable clinical outcome.
Adult↗
Propafenone treatment of recurrent ventricular tachycardia: comparison of continuous electrocardiographic recording and electrophysiologic study in predicting drug efficacy.
Propafenone was administered to 29 patients who had multiple episodes of recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) despite previous antiarrhythmic therapy. All patients had 24-hour continuous electrocardiographic recording and electrophysiologic study in a drug-free control state and while receiving maximum doses of propafenone. During propafenone treatment, the mean frequency of ventricular premature complexes (VPCs) decreased 74% (p less than 0.05). There was more than an 83% decrease in VPC frequency in 17 of 29 patients, and 11 patients had 99 to 100% decreases. Propafenone prevented VT induction at electrophysiologic study in 6 patients, whereas another 12 patients were judged to have satisfactory electrophysiologic responses on the basis of slower VT rates and absence of hemodynamic compromise during VT. After long-term treatment from 2 to 26 months, 9 patients continued propafenone without evidence of recurrent arrhythmia. Six of these 9 patients had not VT induction at electrophysiologic study while receiving propafenone. The decrease in VPC frequency produced by propafenone was a poor predictor of a successful electrophysiologic study and of long-term therapy. In conclusion, propafenone has potential as an effective antiarrhythmic agent, but better methods to stratify risk for recurrence of VT and VF are needed.
Adult↗
Stabilization of glucocorticoid receptors in vitro using divalent cations plus cation chelators.
The specific glucocorticoid receptor binding of rat liver cytosol was very unstable in vitro at 25 and 4 degrees C. However, 5 mM CaCl2 added with 5 mM EDTA to cytosol prior to incubation markedly stabilized unbound glucocorticoid receptors at both temperatures. Optimal effectiveness was achieved using equimolar (5 mM) amounts of CaCl2 and EDTA. On the other hand, 5 mM CaCl2 (added alone) further destabilized the unbound glucocorticoid receptor, while 5 mM EDTA (added alone) had no effect at 25 degrees C. EGTA (in lieu of EDTA) added with CaCl2 stabilized hepatic receptor binding at 25 degrees C. On the other hand, citrate added with calcium was ineffective in stabilizing the hepatic glucocorticoid receptor. MgCl2 effectively replaced CaCl2 as a stabilizing agent at 25 degrees C if added with 5 mM EDTA. When added alone, MgCl2 slightly destabilized the unbound receptor. Sucrose density gradient analysis (in low salt) revealed that CaCl2 plus EDTA enhanced the steroid-receptor complex sedimentation coefficient from 7 S to about 10 S. Unlike molybdate, CaCl2 plus EDTA had no apparent effect on steroid-receptor complex thermal transformation into a nuclear binding form, while MgCl2 plus EDTA partially reduced transformation. These results suggest a novel means to chemically stabilize unbound hepatic glucocorticoid receptors in vitro which may be of particular importance for receptor purification studies.
Animals↗
Alteration of hepatic glucocorticoid receptor stability and nuclear binding in vitro by citrate.
Citrate greatly stabilized rat hepatic unbound glucocorticoid receptors in cell-free conditions at 4 degrees C with optimal effectiveness at 5-15 mM. Control receptors were inactivated at 4 degrees C with a half-life of less than 12 h. However, in the presence of 10 mM-citrate, unbound receptors were almost completely stabilized for 48 h at 4 degrees C. Citrate at a concentration of 1-2 mM yielded half-maximal stabilization. The stabilizing effect of citrate was rather specific, as succinate, alpha-oxoglutarate, oxaloacetate, malate and pyruvate had no apparent stabilizing action. Citrate stabilized receptors over a wide range of H+ concentrations, with complete protection between pH 6.5 and 8.5. In addition, citrate appeared to have a significant effect on glucocorticoid-receptor complex activation into a nuclear binding form. Thus 5-10 mM-citrate enhanced nuclear binding, with optimal activation achieved at 10 mM concentration. As analysed by sucrose-density-gradient centrifugation and DEAE-cellulose chromatography, no apparent change was observed in the physical characteristics of the glucocorticoid receptor in the presence of citrate.
Animals↗