effects of hyperinsulinemia on renal hemodynamics in patients with iddm &niddm
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Publication
Journal: The American review of respiratory disease
November/29/1984
Abstract
Serial bronchoalveolar lavage (BAL) was performed prospectively on 10 normal control subjects, 20 Respiratory Distress Syndrome (RDS), and 11 Bronchopulmonary Dysplasia (BPD) newborn infants to evaluate the role of pulmonary inflammation in neonatal lung disease. Minimal inflammation was found in BAL at less than 24 h of life in all groups, but significant pulmonary polymorphonuclear leukocyte (PMN) influxes were noted at 96 h in RDS and BPD compared with control subjects. By 1 wk of life, BAL PMN counts returned to normal in RDS, but counts remained significantly elevated through 5 wk in BPD. Alveolar macrophage (AM) counts were significantly elevated at 96 h in RDS (p less than 0.05), but were significantly depressed in BPD at 4 and 5 wk (p less than 0.05). The BAL elastase/alpha 1-proteinase inhibitor (alpha 1Pi) ratios in RDS did not differ from those of normal control subjects; however, these ratios were significantly elevated from 1 through 4 wk of life in BPD, placing these infants at risk for proteolytic lung damage. Lavage elastase levels were elevated in both RDS and BPD, associated with a parallel increase in BAL alpha 1Pi in RDS and depressed BAL alpha 1Pi in BPD. These findings suggest that pulmonary inflammation, associated with a prolonged PMN influx and an imbalance between elastase and alpha 1Pi, may contribute to the development of the neonatal chronic lung disease, BPD.
Publication
Journal: Journal of Clinical Investigation
October/10/1990
Abstract
To examine the ability of the skeletal muscle of congestive heart failure (CHF) patients to adapt to chronic exercise, five patients performed localized nondominant wrist flexor training for 28 d. Inorganic phosphate (Pi) and phosphocreatine (PCr) were monitored by magnetic resonance spectroscopy in both forearms at rest and during submaximal wrist flexion exercise at 6, 12, 24, and 36 J.min-1 before and after exercise training. Simultaneous measurements of limb blood flow were made by plethysmography at 12, 24, and 36 J.min-1. Forearm muscle mass and endurance were measured by magnetic resonance imaging and wrist flexion exercise before and after training. The Pi/PCr ratio and pH were calculated from the measured Pi and PCr. Exercise cardiac output, heart rate, plasma norepinephrine, and lactate measured during training were not elevated above resting values, confirming that training was localized to the forearm flexor muscles. After training, muscle bioenergetics, as assessed by the slope of the regression line relating Pi/PCr to submaximal workloads, were improved in the trained forearm of each patient, although muscle mass, limb blood flow, and pH were unchanged. Forearm endurance increased by greater than 260% after training. In the dominant untrained forearm, none of the measured indices were affected. We conclude that localized forearm exercise training in CHF patients improves muscle energetics at submaximal workloads in the trained muscle, an effect which is independent of muscle mass, limb blood flow, or a central cardiovascular response during training. These findings indicate that peripheral muscle metabolic and functional abnormalities in CHF can be improved without altering cardiac performance.
Publication
Journal: Diabetes
August/20/1987
Abstract
This study addressed the controversial question of whether a negative-insulin-feedback loop exists in vivo. We utilized prehepatic insulin production, calculated by computerized deconvolution analysis of peripheral C-peptide concentration, as a measure of endogenous insulin secretion. Prehepatic insulin production was determined in 10 normal men who randomly underwent a control study and two additional studies involving different insulin infusion rates that achieved circulating insulin concentrations within the physiologic range during euglycemic clamps. The results demonstrate a dose-dependent suppression of prehepatic insulin production from 5.8 +/- 1.4 mU/min during the control study to 4.0 +/- 1.2 and 3.2 +/- 0.9 mU/min during plasma insulin levels of 34 +/- 4 and 61 +/- 6 microU/ml, respectively (P less than .05). Therefore, in contrast to recently reported results in vitro, insulin inhibits its own secretion in humans.
Publication
Journal: Breast Cancer Research and Treatment
February/9/2014
Abstract
Maintaining weight is important for better prognosis of breast cancer survivors. The associations between weight and cancer-related symptoms are not known. We examined associations among weight, weight change, inflammation, cancer-related symptoms, and health-related quality of life (HRQOL) in a cohort of stage 0-IIIA breast cancer survivors. Participants were recruited on average 6 months (2–12 months) after diagnosis. Height, weight, and C-reactive protein (CRP) were assessed at approximately 30 months post-diagnosis; cancer-related symptoms (chest wall and arm symptoms, vasomotor symptoms, urinary incontinence, vaginal symptoms, cognition/mood problems, sleep, sexual interest/function), and HRQOL (SF-36) were assessed at approximately 40 months post-diagnosis. Weight was measured at baseline in a subset. Data on 661 participants were evaluable for body mass index (BMI); 483 were evaluable for weight change. We assessed associations between BMI (<25.0, 25.0–29.9, ≥30.0 kg/m2), post-diagnosis weight change (lost ≥5 %, weight change <5 %, gained ≥5 %), and CRP (tertile) with cancer-related symptoms and HRQOL using analysis of covariance. Higher symptoms scores indicate more frequent or severe symptoms. Higher HRQOL scores indicate better HRQOL. Compared with those with BMI <25 kg/m2, women with BMI ≥30 kg/m2 had the following scores: increased for arm symptoms (+25.0 %), urinary incontinence (+40.0 %), tendency to nap (+18.9 %), and poorer physical functioning (−15.6 %, all p < 0.05). Obese women had lower scores in trouble falling asleep (−9.9 %; p < 0.05). Compared with weight change <5 %, participants with ≥5 % weight gain had lower scores in physical functioning (−7.2 %), role-physical (−15.5 %) and vitality (−11.2 %), and those with weight loss ≥5 % had lower chest wall (−33.0 %) and arm symptom scores (−35.5 %, all p < 0.05). Increasing CRP tertile was associated with worse scores for chest wall symptoms, urinary incontinence, physical functioning, role-physical, vitality and physical component summary scores (all P trend < 0.05). Future studies should examine whether interventions to maintain a healthy weight and reduce inflammation could alleviate cancer-related symptoms and improve HRQOL.
Publication
Journal: International Journal of Sports Medicine
December/5/1996
Abstract
The effects of glycerol ingestion (GEH) on hydration and subsequent cycle ergometer submaximal load exercise were examined in well conditioned subjects. We hypothesized that GEH would reduce physiologic strain and increase endurance. The purpose of Study I (n = 11) was to determine if pre-exercise GEH (1.2 gm/kg glycerol in 26 ml/kg solution) compared to pre-exercise placebo hydration (PH) (26 ml/kg of aspartame flavored water) lowered heart rate (HR), lowered rectal temperature (Tc), and prolonged endurance time (ET) during submaximal load cycle ergometry. The purpose of Study II (n = 7) was to determine if the same pre-exercise regimen followed by carbohydrate oral replacement solution (ORS) during exercise also lowered HR, Tc, and prolonged ET. Both studies were double-blind, randomized, crossover trials, performed at an ambient temperature of 23.5-24.5 degrees C, and humidity of 25-27%. Mean HR was lower by 2.8 +/- 0.4 beats/min (p = 0.05) after GEH in Study I and by 4.4 +/- 1.1 beats/min (p = 0.01) in Study II. Endurance time was prolonged after GEH in Study I (93.8 +/- 14 min vs. 77.4 +/- 9 min, p = 0.049) and in Study II (123.4 +/- 17 min vs. 99.0 +/- 11 min, p = 0.03). Rectal temperature did not differ between hydration regimens in both Study I and Study II. Thus, pre-exercise glycerol-enhanced hyperhydration lowers HR and prolongs ET even when combined with ORS during exercise. The regimens tested in this study could potentially be adapted for endurance activities.
Publication
Journal: Journal of the American Geriatrics Society
November/20/1984
Abstract
Folic acid and vitamin B12 nutritional status was examined in a group of 270 healthy elderly individuals using both dietary and biochemical measures. Of these 40 per cent had dietary intakes of folic acid that were less than half the recommended dietary allowance of 400 micrograms/day, and 13 per cent had intakes of less than half the recommended dietary allowance for vitamin B12 (3 micrograms/day). However, only 8 per cent had low plasma folates (less than 3.0 ng/ml) and only 3 per cent had RBC folates less than 140 ng/ml. Plasma true cobalamin levels less than 220 pg/ml were found in 3 per cent. None of these individuals showed any clinical signs of folate and/or vitamin B12 deficiency, and mean corpuscular volumes were not significantly greater than those for the entire population (90.8 +/- 4.1 fl). The correlations of intakes of folic acid and vitamin B12 with plasma or erythrocyte levels were moderate (about 0.5). It was also clear that those taking supplements had significantly greater blood levels than those not taking supplements, although the benefit of higher plasma or erythrocyte levels of these nutrients is not clear. The data indicate that folate and vitamin B12 status in free-living healthy elderly is not a major medical problem.
Publication
Journal: American Journal of Clinical Nutrition
September/9/1982
Abstract
Dietary and supplemental intakes were assessed from 3-day food records collected from 270 free-living, middle income and healthy men and women over 60 yr of age residing in the Albuquerque, NM vicinity. The 1980 Recommended Dietary Allowances (RDA) were used to assess adequacy of intake. Energy intake, as percentage of the RDA, was 90 +/- 23 (mean +/- SD) for men (n = 125) and 87 +/- 22 for women (n = 145). Mean daily protein intake was 83 g for men and 67 g for women and only 11% of men and 14% of women failed to receive at least 100% of the RDA for protein. Frequency and amount of vitamin and mineral supplementation was substantial. Approximately 60% of both men and women ingested one or more supplements; vitamins C and E were the most popular. In general, dietary intakes in this population appear to be adequate with the possible exception of vitamin D and calcium intakes in women.
Publication
Journal: Pediatrics
December/27/2005
Abstract
OBJECTIVE
Oxygen delivery through nasal cannulae to convalescent preterm infants is a common but largely unstudied practice. To learn more about current nasal cannula oxygen delivery practices, we examined the variations in oxygen delivery through nasal cannulae among the centers of the Neonatal Research Network, the frequency of prescription of low levels of oxygen, and the success of weaning to room air. We hypothesized that some infants treated with oxygen through nasal cannulae were receiving oxygen levels equivalent to those of room air.
METHODS
This was a descriptive, nested, cohort study of nasal cannula oxygen prescription among 187 infants with birth weights of <1250 g. All infants were studied at a postmenstrual age of 36 weeks, with a timed oxygen reduction challenge to establish their ability to be weaned to room air. The results of this challenge were compared with the fraction of inspired oxygen (FIO2) delivered, calculated as effective FIO2. Infants who maintained oxygen saturation values of>> or =90% during oxygen weaning and during a 30-minute period in room air were defined as passing the challenge.
RESULTS
Fifty-two infants (27.8%) were receiving oxygen concentrations and flow rates through nasal cannulae that delivered an effective FIO2 of <0.23, of whom 16 were receiving oxygen concentrations and flow rates that delivered an effective FIO2 of 0.21. In addition, 22 infants (11.8%) were prescribed room air through nasal cannulae intentionally. Seventy-two percent of those prescribed an effective FIO2 of <0.23 passed the room air challenge.
CONCLUSIONS
Prescription of oxygen with combinations of flow rates and oxygen concentrations that delivered a low effective FIO2 was common. We speculate that some of this, including the inadvertent prescription of an effective FIO2 equivalent to that of room air, is related to lack of knowledge of the effective FIO2. Routine calculation of effective FIO2 values may prompt earlier trials of room air and thus reduce unnecessary days of oxygen therapy.
Publication
Journal: Annals of Internal Medicine
February/15/1995
Abstract
OBJECTIVE
To determine whether asymptomatic retinal cholesterol embolism is a risk factor for vascular events.
METHODS
Cohort study with retrospectively selected controls.
METHODS
A Veterans Affairs medical center.
METHODS
70 consecutive patients with asymptomatic retinal cholesterol emboli on dilated ocular examination in an eye clinic and 70 controls without retinal emboli. Controls were matched to patients for sex; age; prevalence of hypertension, diabetes mellitus, and ischemic heart disease; serum cholesterol level; and smoking history.
METHODS
Stroke, myocardial infarction, and death.
RESULTS
During a mean follow-up of 3.4 years, stroke occurred at an annual rate of 8.5% among patients and 0.8% among controls (adjusted relative risk, 9.9; 95% CI, 2.3 to 43.1; P = 0.002). Nineteen strokes occurred, 17 in patients and 2 in controls; all were nonfatal cerebral infarctions. Twelve of the 17 that occurred in patients were in a carotid artery territory ipsilateral to the qualifying retinal cholesterol embolus and 5 were in another vascular territory. Ocular infarction or hemorrhagic stroke did not occur. Nonfatal myocardial infarction or vascular death occurred at an annual rate of 7.7% among patients and 4.9% among controls (adjusted relative risk, 1.4; 95% CI, 0.7 to 2.9; P = 0.39).
CONCLUSIONS
Asymptomatic retinal cholesterol embolism is an important risk factor for cerebral infarction independent of commonly recognized vascular risk factors.
Publication
Journal: SpringerPlus
September/30/2013
Abstract
OBJECTIVE
Here we assessed associations between null mutations in glutathione-S-transferase (GST)T1 and GSTM1 genes, and the rs1695 polymorphism in GSTP1 (Ile(105)Val), and risk of breast cancer-specific (n=45) and all-cause (n=99) mortality in a multiethnic, prospective cohort of 533 women diagnosed with stage I-IIIA breast cancer in 1995-1999, enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study.
METHODS
We measured the presence of the null mutation in GSTT1 and GSTM1, and the rs1695 polymorphism in GSTP1 by polymerase chain reaction. We assessed associations between breast-cancer specific and all-cause mortality using Cox proportional hazards models.
RESULTS
Participants with ER-negative tumors were more likely to be GSTT1 null (χ(2)=4.52; P=0.03), and African American women were more likely to be GSTM1 null (χ(2)=34.36; P<0.0001). Neither GSTM1 nor GSTT1 null mutations were associated with breast cancer-specific or all-cause mortality. In a model adjusted for body mass index, race/ethnicity, tumor stage and treatment received at diagnosis, the variant Val allele of rs1695 was associated with increased risk of all-cause (HR=1.81, 95% CI 1.16-2.82, P=0.008), but not breast cancer-specific mortality. The GSTT1 null mutation was associated with significantly higher levels of C-reactive protein.
CONCLUSIONS
GSTM1 and GSTT1 null genotypes had no effect on outcome; however the variant allele of rs1695 appears to confer increased risk for all-cause mortality in breast-cancer survivors. Given the limited sample size of most studies examining associations between GST polymorphisms with breast cancer survival, and the lack of women undergoing more contemporary treatment protocols (treated prior to 1999), it may be helpful to re-examine this issue among larger samples of women diagnosed after the late 1990s, who all received some form of chemotherapy or radiotherapy.
Publication
Journal: Transfusion
March/6/1985
Abstract
A pregnant 26-year-old woman with Devic's syndrome manifesting as paraplegia and visual loss was treated with multiple courses of lymphocytaplasmapheresis. Clinical improvement was temporally related to the lymphocytaplasmapheresis. She relapsed when treatment was stopped and improved with reinstitution of therapy. Thereafter, further treatments were not required and she delivered a normal infant.
Publication
Journal: Drug Metabolism and Disposition
January/26/1998
Abstract
Cytochrome P450 (CYP) 2E1 is implicated in a variety of chemically initiated hepatotoxicities, including alcoholic liver disease. These pathological conditions arise from increased production of reactive intermediates caused by elevated enzyme concentrations. Thus, the ability to detect enhanced CYP2E1 levels would aid in identifying individuals at high risk for xenobiotic-promoted liver injury. With this in mind, the present investigation assessed in vivo chlorzoxazone metabolism and compared pharmacokinetic parameters with CYP2E1 expression in blood. Twenty-two subjects were recruited and divided into two groups, control subjects and alcohol abusers, based on responses to two screening questionnaires. Those individuals with higher survey scores, i.e. those who consumed alcohol more frequently, exhibited higher rates of chlorzoxazone metabolism. Indeed, a correlation (r = 0.66, p < 0.01) was obtained when scores were compared with the pharmacokinetic parameter AUC for chlorzoxazone. Lymphocyte microsomes isolated from blood samples obtained from these same individuals were subjected to immunoblot analyses to detect CYP2E1 levels. That lymphocytes contained CYP2E1 was confirmed by reverse transcription-polymerase chain reaction and sequence analysis of the cDNA. Quantification of immunoreactive bands revealed that levels of this P450 were 2.3-fold higher in alcoholics than in control subjects. This increase in lymphocyte CYP2E1 content in alcoholic subjects coincided with a 2.1-fold increase in chlorzoxazone clearance and a 2-fold decrease in the AUC for chlorzoxazone. Importantly, a correlation (r = 0.62, p < 0.01) was observed between CYP2E1 content in lymphocytes and chlorzoxazone clearance rates. Thus, monitoring lymphocyte CYP2E1 expression may provide a substitute for estimating hepatic activity of this P450.
Publication
Journal: Pediatric Research
January/21/2013
Abstract
BACKGROUND
Information on cytokine profiles in fungal sepsis (FS), an important cause of mortality in extremely low birthweight (ELBW) infants, is lacking. We hypothesized that cytokine profiles in the first 21 d of life in ELBW infants with FS differ from those with bacterial sepsis (BS) or no sepsis (NS).
METHODS
In a secondary analysis of the National Institute of Child Health and Human Development Cytokine study, three groups were defined-FS (≥1 episode of FS), BS (≥1 episode of BS without FS), and NS. Association between 11 cytokines assayed in dried blood spots obtained on days 0-1, 3 ± 1, 7 ± 2, 14 ± 3, and 21 ± 3 and sepsis group was explored.
RESULTS
Of 1,066 infants, 89 had FS and 368 had BS. As compared with BS, FS was more likely to be associated with lower birthweight, vaginal delivery, patent ductus arteriosus, postnatal steroids, multiple central lines, longer respiratory support and hospital stay, and higher mortality (P < 0.05). Analyses controlling for covariates showed significant group differences over time for interferon-γ (IFN-γ), interleukin (IL)-10, IL-18, transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) (P < 0.05).
CONCLUSIONS
Significant differences in profiles for IFN-γ, IL-10, IL-18, TGF-β, and TNF-α in FS, BS, or NS in this hypothesis-generating secondary study require validation in rigorously designed prospective studies and may have implications for diagnosis and treatment.
Publication
Journal: Archives of general psychiatry
July/26/1989
Abstract
We studied pituitary corticotropin response to exogenous corticotropin-releasing hormone infusion and attempted to control for the confounding effect of variable serum cortisol levels between depressed and control subjects. If metyrapone was given during the time of day when hypothalamic pituitary adrenal activity was otherwise low, the relative increase in the corticotropin concentration was small. Pituitary response to exogenous corticotropin-releasing hormone can be defined under conditions in which the amount of glucocorticoid-mediated negative feedback present at the level of the pituitary gland is equal in all subjects. When the ambient cortisol level was equalized (and suppressed) in all subjects at the time of study with a threshold dosage of corticotropin-releasing hormone, we found an augmented response to corticotropin-releasing hormone in depressives. This raises the possibility that either increased pituitary sensitivity to corticotropin-releasing hormone or an increased intracellular pool of corticotropin is available for release in subjects with major depressive illness.
Publication
Journal: Journal of Clinical Endocrinology and Metabolism
June/20/1996
Abstract
To evaluate the relative usefulness of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) in screening for GH status, GH stimulation (arginine-insulin/L-DOPA) tests and overnight GH studies (every 20 min sampling) were performed in 104 healthy short children (32 girls), aged 3-16 yr (height, -1.8 or more SD). IGFBP-3 had no advantage over IGF-I in screening sensitivity or specificity. IGF-I correlated with mean nighttime GH. Both IGF-I and IGFBP-3 correlated with peak stimulated GH. To identify more than 90% of children with GH deficiency (GHD) and borderline GHD, the mean values for age for IGF-I and IGFBP-3 were required as the cut-off criterion. However, at this criterion, 70% or more of idiopathic short stature (ISS) children would have to undergo testing to identify 90% of GHD or borderline GHD. More stringent criteria (-1.0, -1.64, and -2.0 SD) were more specific, but lost sensitivity. A practical application is suggested. Screening use of IGF-I with criterion of -1.0 SD would identify a subgroup that includes 88% of GHD, 71% of borderline GHD, and 46% of ISS. Both IGF-I and IGF-BP-3 higher than -1.0 SD would accurately identify 68% of ISS as not needing GH testing. Evaluation of growth velocity would identify the remaining children requiring definitive testing. Thus, combined screening for GHD using both IGF-I and IGFBP-3 has no better sensitivity than either test alone. However, such combined screening will improve the specificity and thus decrease the number of normal but short children who might otherwise undergo unnecessary testing.
Publication
Journal: American Journal of Clinical Nutrition
October/27/1985
Abstract
A double-blind study was done giving 10 mg of copper/day as copper gluconate or placebo capsules for 12 wk. The seven subjects receiving copper gluconate had no change in the level of copper in the serum, urine, or hair. There was also no change in the levels of zinc or magnesium. There was also no significant change in levels of hematocrit, triglyceride, SGOT, GGT, LDH, cholesterol, or alkaline phosphatase. The side effects of nausea, diarrhea, and heartburn were the same in the subjects receiving copper gluconate and subjects receiving placebo capsules.
Publication
Journal: Clinical immunology and immunopathology
October/27/1983
Abstract
The pathogenetic mechanisms responsible for the impaired immunoglobulin production in common variable hypogammaglobulinemia (CVH) are diverse with abnormalities in both B cells and immunoregulatory T cells. Production of IgG, IgM, and IgM-rheumatoid factor (IgM-RF) was measured in pokeweed mitogen (PWM) or Epstein-Barr virus (EBV)-stimulated cultures using various combinations of CVH, cord blood mononuclear cells (CBMC), and normal adult control B and T cells. The following results were obtained. First, the proportion of OKT3+ and OKT8+ cells were increased in CVH patients. Second, the T cells from four CVH patients and CBMC suppressed PWM-induced IgG, IgM, and IgM-RF production by normal B cells. Furthermore, major suppressor activity was found in the OKT8+ T-cell subpopulations in CBMC and three out of four CVH patients. There was no significant difference in relative suppression by OKT8+ cells from normal adults, CVH patients, or CBMC. However, in one CVH patient suppressor T cells were found in both OKT4+ as well as OKT8+ fractions. In the CVH patient with OKT4+ suppressor cells, X irradiation (1250 rads) abrogated suppressor activity and restored helper activity in the OKT4+ T-cell fraction. Irradiation of normal OKT4+ cells did not increase helper activity. When non-E-rosetting cells from normal subjects, CVH, and CBMC were stimulated with EBV it was observed that normal adult B cells could be induced to secrete IgG, IgM, and Ig-RF whereas CVH and CBMC could only produce IgM and IgM-RF but not IgG. The present study demonstrates for the first time that a radiosensitive OKT4+ suppressor cell is present in some CVH patients.
Publication
Journal: Journal of Perinatology
January/24/2012
Abstract
OBJECTIVE
For infants born with extremely low birth weight (ELBW), we examined the (1) correlation between results on the Ages and Stages Questionnaire (ASQ) and the Bayley Scales of Infant Development-II (BSID-II) at 18 to 22 months corrected age; (2) degree to which earlier ASQ assessments predict later BSID-II results; (3) impact of ASQ use on follow-up study return rates.
METHODS
ASQ data were collected at 4, 8, 12 and 18 to 22 months corrected age. The BSID-II was completed at 18 to 22 months corrected age. ASQ and BSID-II 18 to 22 month sensitivity and specificity were examined. Ability of earlier ASQs to predict later BSID-II scores was examined through linear regression analyses.
RESULTS
ASQ sensitivity and specificity at 18 to 22 months were 73 and 65%, respectively. Moderate correlation existed between earlier ASQ and later BSID-II results.
CONCLUSIONS
For extremely low birth weight infant assessment, the ASQ cannot substitute for the BSID-II, but seems to improve tracking success.
Publication
Journal: Journal of Immunology
September/14/1981
Abstract
Physical stress is associated with depressed cellular immune function. We have found that lymphocytes from subjects undergoing either of 2 stressful events, cardiac surgery or childbirth, are more sensitive to inhibition by PGE2. For example, the concentration of PGE2 required for 50% inhibition of 3H-thymidine incorporation (ID50) into phytohemagglutinin-stimulated lymphocytes from patients undergoing cardiac surgery went from 1.5 X 10(-8) M on the day before surgery to 3 X 10(-9) M on the day after surgery. This increase in sensitivity to PGE2 was accompanied by a significantly decreased lymphocyte proliferative response (27 to 68% of control, depending on mitogen dose) and a 50% increase in the percentage of E rosette-positive cells with receptors for the Fc portion of IgG. The increased sensitivity to PGE and the depressed mitogen responses returned to preoperative values by day 10. The depressed mitogen responses of the postoperative patients were completely restored to normal by removal of glass-adherent cells before culture. In addition, the responses of the postoperative patients and the women in labor were partially restored by the addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures. Thus it would appear that physical stress causes lymphocytes to become more sensitive to prostaglandin E2, and the increased sensitivity to inhibition by this immunomodulator is responsible in part for the depressed cellular immune function after physical stress.
Publication
Journal: American Journal of Psychiatry
June/28/1984
Abstract
The scores of 14 women with hyperprolactinemia on the Symptom Rating Test and the Symptom Questionnaire were compared with those of nonpsychotic women attending a psychiatric clinic, women attending a family practice clinic, and female nonpatient employees. The scores of the hyperprolactinemic women were similar to those of the psychiatric patients. Hyperprolactinemic patients were significantly more hostile, depressed, and anxious and had more feelings of inadequacy than family practice patients and nonpatient employees. The authors recommend measuring the serum prolactin levels of women with depression, hostility, anxiety, and symptoms or signs suggestive of hyperprolactinemia.
Publication
Journal: Journal of Experimental Medicine
August/13/1982
Abstract
We showed that sera from normal subjects after antigenic challenge with intradermal PPD or Candida antigens or with subcutaneous tetanus vaccine contain a factor that blocks the binding of mouse monoclonal anti-Ia antibody to Ia-positive T cells or to B35 M cells, an Ia-positive human B cell line. The blocking activity appears 48 to 72 h after antigenic challenge and is gone by day 7. The appearance of the anti-Ia blocking activity coincided with a drop in the percentage of Ia-positive T cells and non-T cells in the peripheral blood of these subjects and also with a decrease in the density of surface Ia on the non-T cell population. The blocking was not genetically restricted; that is, serum from a given subject blocked anti-Ia binding to Ia-positive T cells of subjects with different DR haplotypes. The blocking activity was contained in the IgM fraction of the sera. The blocking activity of the sera was eliminated after absorption of the sera with Ia-positive but not with Ia-negative human cell lines. It would appear, therefore, that the blocking of monoclonal anti-Ia binding is caused by an IgM anti-Ia antibody that appears in normals after in vivo antigenic challenge.
Publication
Journal: Metabolism: Clinical and Experimental
July/28/1988
Abstract
To determine the effects of age on nocturnal fuel regulation, we measured spontaneous plasma glucose and free fatty acid (FFA) levels as well as counterregulatory hormones in healthy young (n = 9, mean age 26 +/- 3 years) and old (n = 10, mean age 69 +/- 3 years) men from midnight to 8 AM. FFA levels rose from midnight (660 +/- 80 mEq/L for young subjects, 545 +/- 55 mEq/L for old) to a peak mean level of 866 +/- 110 mEq/L at 3 AM in young and 713 +/- 120 mEq/L at 1:30 AM in old (P less than .05). FFA levels declined thereafter for both groups. FFA levels were lower in older subjects (P less than .05) but integrated glucose (P less than .05) and insulin (P less than .05) levels were higher. FFA levels were inversely related to integrated insulin (r = -0.46, P less than .05) and glucose concentrations (r = -0.66, P less than .05). Integrated insulin levels were significantly higher in older subjects, which may explain the lower FFA levels as may lower growth hormone levels in the older subjects. While fasting glucose responsivity to endogenous insulin is impaired in healthy older men, the FFA response appears to be preserved.
Publication
Journal: The open allergy journal
February/19/2017
Abstract
The role of basophils, the rarest of blood granulocytes, in the pathophysiology of allergic asthma is still incompletely understood. Indirect evidence generated over many decades is consistent with a role for basophils in disease promotion. Recent improvements in procedures to purify and analyze very small numbers of human cells have generally supported this view, but have also revealed new complexities. This chapter focuses on our analyses of Fcε R1 function in basophils in the context of understanding and treating human allergic asthma. In long-term studies, we demonstrated that asthmatic subjects have higher circulating numbers of basophils than non-atopic non-asthmatic subjects and that their basophils show higher rates of both basal and anti-IgE or antigen-stimulated histamine release. These results hint at a direct role for basophils in promoting asthma. Supporting this interpretation, the non-releaser phenotype that we linked to the excessive proteolysis of Syk via the ubiquitin/proteasomal pathway is less common in basophils from asthmatic than non-asthmatic donors. The discovery of a basophil-specific pathway regulating Syk levels presents a clear opportunity for therapy. Another route to therapy was revealed by evidence that basophil FcεRI signaling can be downregulated by co-crosslinking the ITAM-containing IgE receptor, FcγRI, to the ITIM-containing IgG receptor, FcγRIIB. Based on this discovery, hybrid co-crosslinking fusion proteins are being engineered as potential therapies targeting basophils. A third distinguishing property of human basophils is their high dependence on IgE binding to stabilize membrane FcεRI. The circulating IgE scavenging mAb, Omalizumab, reduces FcεRI expression in basophils from asthmatics by over 95% and produces a substantial impairment of IL-4, IL-8 and IL-13 production in response to the crosslinking of residual cell surface IgE-FcεRI. A search for small molecule inhibitors that similarly impair high affinity IgE binding to basophils may yield reagents that mimic Omalizumab's therapeutic benefits without the potential for immune side effects. Although studies on allergen and FcεRI-mediated basophil activation all point to a role in promoting disease, a case can also be made for an alternative or additional role of basophil FcεRI in protection against allergic asthma. Human basophils have high affinities for IgE, they upregulate receptor levels over a >100-fold range as circulating IgE levels increase and they have short half-lives in the circulation. Thus, when allergen is absent, basophil FcεRI could serve as scavengers of serum IgE and therefore protectors against mast cell IgE-mediated inflammatory responses. Further studies are clearly needed to determine if FcεR-expressing basophils play pathogenic or protective roles - or both - in human allergic asthma and other IgE-mediated inflammatory disorders.
Publication
Journal: BMC Cancer
July/11/2013
Abstract
BACKGROUND
C-reactive protein (CRP) and Serum amyloid A protein (SAA) increases with systemic inflammation and are related to worse survival for breast cancer survivors. This study examines the association between percent body fat and SAA and CRP and the potential interaction with NSAID use and weight change.
METHODS
Participants included 134 non-Hispanic white and Hispanic breast cancer survivors from the Health, Eating, Activity, and Lifestyle Study. Body fat percentage, measured with Dual Energy X-ray Absorptiometer (DEXA), and circulating levels of CRP and SAA were obtained 30 months after breast cancer diagnosis.
RESULTS
Circulating concentrations of CRP and SAA were associated with increased adiposity as measured by DEXA after adjustment for age at 24-months, race/ethnicity, dietary energy intake, weight change, and NSAID use. Survivors with higher body fat ≥35% had significantly higher concentrations of CRP (2.01 mg/l vs. 0.85 mg/l) and SAA (6.21 mg/l vs. 4.21 mg/l) compared to non-obese (body fat < 35%). Women who had gained more than 5% of their body weight since breast cancer diagnosis had non-statistically significant higher geometric mean levels of CRP and SAA. Mean levels of CRP and SAA were higher among obese women who were non-users of NSAIDs compared to current users; the association with SAA reached statistical significance (Mean SAA = 7.24, 95%CI 6.13-8.56 for non-NSAID; vs. 4.87; 95%CI 3.95-6.0 for NSAID users respectively).
CONCLUSIONS
Breast cancer survivors with higher body fat had higher mean concentrations of CRP and SAA than women with lower body fat. Further assessment of NSAID use and weight control in reducing circulating inflammatory markers among survivors may be worthwhile to investigate in randomized intervention trials as higher inflammatory markers are associated with worse survival.
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