Depressive Symptoms, Perceived Stress, and Cortisol in School-Age Children With Type 1 Diabetes: A Pilot Study.

Despite adequate insulin regimens and concurrent treatments for Type 1 diabetes (T1D), many children have trouble achieving glycemic control, as evidenced by elevated HbA1c levels. Maternal and child depressive symptoms, as well as child perceived stress, are associated with less optimal glycemic control. Cortisol, a stress hormone, may mediate the relationships among depressive symptoms, perceived stress, and glycemic control. The purposes of this pilot study were to (1) examine the feasibility of collecting salivary samples to measure cortisol change in prepubertal school-age children diagnosed with T1D and (2) determine effect sizes for the relationships among maternal depressive symptoms and child depressive symptoms, perceived stress, cortisol levels, and glycemic control. Participants were recruited using convenience sampling from a pediatric endocrinology clinic in the southeastern United States. All data, including surveys, salivary samples, HbA1c, height, and weight, were collected the same day as a clinic visit. The study included 30 children, ages 6.9-12.2 years, and their mothers. Most children were female (70%) and Caucasian (76.7%), but the sample was socioeconomically diverse. HbA1c values ranged from 6.1% to 12.2%. Of the children, 18 showed normal declines in cortisol over 3 hr, while 12 had increases in cortisol. Results show recruitment, participation, and data collection are feasible in school-age children with T1D. Examination of relevancy thresholds for effect sizes between variables of interest supports the need for future research in a larger, more representative sample on research questions that include the role cortisol plays as a potential mediator among examined variables.

Partial support for the central-marginal hypothesis within a population: reduced genetic diversity but not increased differentiation at the range edge of an island endemic bird.

Large-scale population comparisons have contributed to our understanding of the evolution of geographic range limits and species boundaries, as well as the conservation value of populations at range margins. The central-marginal hypothesis (CMH) predicts a decline in genetic diversity and an increase in genetic differentiation toward the periphery of species' ranges due to spatial variation in genetic drift and gene flow. Empirical studies on a diverse array of taxa have demonstrated support for the CMH. However, nearly all such studies come from widely distributed species, and have not considered if the same processes can be scaled down to single populations. Here, we test the CMH on a species composed of a single population: the Island Scrub-Jay (Aphelocoma insularis), endemic to a 250 km2 island. We examined microsatellite data from a quarter of the total population and found that homozygosity increased toward the island's periphery. However, peripheral portions of the island did not exhibit higher genetic differentiation. Simulations revealed that highly localized dispersal and small total population size, but not spatial variation in population density, were critical for generating fine-scale variation in homozygosity. Collectively, these results demonstrate that microevolutionary processes driving spatial variation in genetic diversity among populations can also be important for generating spatial variation in genetic diversity within populations.

Compression garments do not alter cerebrovascular responses to orthostatic stress after mild passive heating.

Whole-body heating increases the likelihood of syncope, whereas utilizing lower-body compression garments may reduce syncope risk. We hypothesized that graded compression garments would reduce the typically observed large postural reductions in arterial blood pressure and middle cerebral artery velocity, in normothermia and especially once passively heat stressed. Fifteen men (age: 27 ± 4 years, aerobic fitness range: 30-75 mL/kg(/) min) completed a supine-to-stand orthostatic challenge for 3 min at normothermia and after passive heating (esophageal temperature, +0.5 °C from baseline) on two occasions (> 7 days): once wearing commercially available compression trousers and once wearing low-compression placebo trousers (randomized order). Blood flow velocity in the middle cerebral artery (transcranial Doppler), mean arterial blood pressure (mean BP: Finometer) and end-tidal carbon dioxide pressure were measured continuously. During normothermia, compression, garments did not alter the magnitude of the postural changes in mean BP or middle cerebral artery velocity. After passive heating, although the magnitudes of these changes were exaggerated, they were not significantly affected by compression garments. Compression garments did not attenuate the initial or sustained orthostatic hypotension associated with posture change, either during normothermia or following passive heat stress.

Using the Spinal Cord Independence Measure III to measure functional recovery in a post-acute spinal cord injury program.

STUDY DESIGN: A prospective design was conducted using admission and discharge Spinal Cord Independence Measure III (SCIM-III) data for persons discharged from a post-acute rehabilitation program. OBJECTIVE: The purpose of this study is to analyze the functional gains as measured by the SCIM-III that occur during a post-acute rehabilitation program. SETTING: Shepherd Center, Atlanta, GA, USA. METHODS: Participants were included if they had a motor complete spinal cord injury (SCI), were within 12 months from the date of injury and completed the recommended length of stay. Median SCIM-III changes between admission and discharge were calculated by subgroups (C1-4, C5, C6, C7-8, T1-6 and T7-12) based on the American Spinal Injury Association motor injury levels. Ceiling and floor effects were examined by item and the percentage of participants showing change between admission and discharge were calculated. RESULTS: In all, 114 participants were included in the analysis. The median total SCIM-III score at admission was 42 (range 13-68), whereas the median total SCIM-III score at discharge was 50 (range 16-72). The median improvement of 5 points in total SCIM-III score between admission and discharge was statistically significant. Significant improvements were also observed between admission and discharge across all subgroups except C1-4. Ceiling and floor effects were noted in some subgroups. CONCLUSIONS: The SCIM-III seems to be an effective measure for functional assessment of persons with SCI in a post-acute rehabilitation program. There are some ceiling and floor effects noted; however, the SCIM-III seems to be sensitive enough to capture functional changes during a post-acute rehabilitation program.

Nitrogen enrichment modifies plant community structure via changes to plant-soil feedback.

We tested the hypothesis that N enrichment modifies plant-soil feedback relationships, resulting in changes to plant community composition. This was done in a two-phase glasshouse experiment. In the first phase, we grew eight annual plant species in monoculture at two levels of N addition. Plants were harvested at senescence and the effect of each species on a range of soil properties was measured. In the second phase, the eight plant species were grown in multi-species mixtures in the eight soils conditioned by the species in the first phase, at both levels of N addition. At senescence, species performance was measured as aboveground biomass. We found that in the first phase, plant species identity strongly influenced several soil properties, including microbial and protist biomass, soil moisture content and the availability of several soil nutrients. Species effects on the soil were mostly independent of N addition and several were strongly correlated with plant biomass. In the second phase, both the performance of individual species and overall community structure were influenced by the interacting effects of the species identity of the previous soil occupant and the rate of N addition. This indicates that N enrichment modified plant-soil feedback. The performance of two species correlated with differences in soil N availability that were generated by the species formerly occupying the soil. However, negative feedback (poorer performance on the soil of conspecifics relative to that of heterospecifics) was only observed for one species. In conclusion, we provide evidence that N enrichment modifies plant-soil feedback relationships and that these modifications may affect plant community composition. Field testing and further investigations into which mechanisms dominate feedback are required before we fully understand how and when feedback processes determine plant community responses to N enrichment.

Quantitative model for prediction of hydrodynamic size of nonionic reverse micelles.

The sizes of nonionic reverse micelles were investigated as a function of the molecular structure of the surfactant, the type of oil, the total concentration of surfactant [NP], the ratio of surfactant to total surfactant (r), the water to surfactant molar ratio (omega), temperature, salt concentration, and polar phase. The basis of our investigation was a mixture of nonylphenol polyethoxylates--NP4 and NP7, various polar phases, and several oils. Micelle sizes were determined using dynamic light scattering (DLS). A central composite experimental design was used to quantitatively model micelle size as a function of omega, surfactant concentration, and r. The model has demonstrated the capability of predicting the mean diameter of micelles from 4 to 13 with a precision of +/-2 nm as measured by DLS. This quantitative correlation between the size of reverse micelles and the synthetic variables provides the foundation for choosing experimental conditions to control reverse micelle size. In turn, this allows control of the size of nanoparticles synthesized within them.

Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination.

We treated a cohort of 38 HIV-infected individuals with a therapeutic vaccine (REMUNE, HIV-1 Immunogen) in an open label study. We then determined whether baseline parameters, such as CD4 cell count, viral load and IgG levels, were predictive of the magnitude of the HIV-specific lymphocyte proliferative responses (LPRs). We demonstrate herein that there is a significant enhancement from baseline for both HIV and p24 antigen-stimulated LPRs after immunization. Using a responder definition of a stimulation index of >5 on at least two post-immunization time-points, 29/38 (76%) responded to HIV-1 antigen while 27/38 (71%) responded to native p24 antigen. Viral load and total IgG were negatively correlated, while CD4 cell counts were positively associated with the magnitude of the HIV antigen LPR. In a multivariable analysis, baseline CD4 was the best predictor of HIV antigen LPR post-immunization.

Anti-F(ab')2 antibody in HIV type 1 infection: relationship to hypergammaglobulinemia and to antibody specific to the V3 loop region of glycoprotein 120.

As HIV infection and autoimmune disease share certain similarities, it has been suggested that HIV may disrupt control of humoral immunity by the antiidiotype network, and that this may be evident as increased IgG antibody to F(ab')2. When anti-F(ab')2 was quantified by ELISA in sera of randomly chosen HIV-infected versus uninfected donors, some HIV-infected sera did contain increased anti-F(ab')2, resulting in a median amount twofold higher than in uninfected sera. Moreover, when data were grouped by blood CD4 lymphocyte count, anti-F(ab')2 in HIV+ groups appeared to rise as CD4 lymphocytes declined. However, increased anti-F(ab')2 mirrored the elevation in serum IgG closely, and normalization of anti-F(ab')2 to serum IgG concentration equalized the groups so that no relationship to CD4 lymphocytes remained. Hypergammaglobulinemia is therefore strongly implicated as a cause of variation in anti-F(ab')2. After dissociation of immune complexes, anti-F(ab')2 activity per microgram of monomeric IgG was slightly increased over normal only in the HIV-infected group with fewest CD4 lymphocytes, without statistical significance. In contrast, the proportion of IgG antibody to the V3-neutralizing determinant in HIV-1 decreased significantly as disease advanced. The same was true for 12 HIV+ individuals studied longitudinally for 500-1300 days. The data suggest that measuring serum anti-F(ab')2 is misleading when immune complexes are present: apparent increases as disease progresses are due to increased IgG and, possibly, to related technical artifacts. During HIV infection, the proportion of antiidiotypic IgG in fact remains unaltered or falls, making this an unlikely cause of suppressed humoral immunity to HIV-1.

Impairment of phagosome-lysosome fusion in HIV-1-infected macrophages.

Phagosome-lysosome fusion is critical for intracellular killing of most organisms and is inhibited by some viruses, notably influenza. We explored the effects of infection in vitro with HIV-1 (IIIB or Ada-M) on phagosome-lysosome fusion in blood monocyte-derived macrophages. After 8 days of infection, fusion was assessed from the fluorescence change occurring up to 2 h after labeling the lysosome compartment with acridine orange and loading of phagosomes with opsonized yeast. Compared with mock-infected control macrophages, the proportion of cells showing fusion after infection was reduced from a mean of 70% to a mean of 47% (p = 0.0001). Inhibition was seen with heat-killed HIV-1 IIIB but not virus-free filtrate. It was mimicked by recombinant gp 120 and blocked by soluble CD4 or antibody to CD4 but not by a neutralizing antibody to the V3 loop of gp 120. The inhibitory effect was seen 8 days after the original, transient exposure to gp 120. These results suggest that a lasting abnormality of phagosome-lysosome fusion results from interaction between gp 120 and CD4, contributing, perhaps, to the increased susceptibility to opportunistic infections of people infected with HIV.

A role for urokinase-type plasminogen activator in human immunodeficiency virus type 1 infection of macrophages.

Urokinase-type plasminogen activator (uPA), a proteinase which activates plasminogen by cleaving at -CPGR(arrow downward)V-, was shown to cleave the V3 loop in recombinant gp120 of human immunodeficiency virus type 1 (HIV-1) IIIB and MN strains, as well as a synthetic, cyclized peptide representing the clade B consensus sequence of V3. Proteolysis occurred at the homologous -GPGR(arrow downward)A-, an important neutralizing determinant of HIV-1. It required soluble CD4 and was prevented by inhibitors of uPA but not by inhibitors of likely contaminating plasma proteinases. It was accelerated by heparin, a known cofactor for plasminogen activation. In immune capture experiments, tight binding of uPA to viral particles, which did not depend on CD4, was also demonstrated. Active site-directed inhibitors or uPA diminished this binding, as did a neutralizing antibody to V3. Addition of exogenous uPA to the laboratory-adapted IIIB strain of HIV-1, the macrophage-tropic field strains JR-CSF and SF-162, or a fresh patient isolate of indeterminate tropism, followed by infection of macrophages with the various treated viruses, resulted in severalfold increases in subsequent viral replication, as judged by yields of reverse transcriptase activity and p24 antigen, as well as incorporation, as judged by PCR in situ. These responses were reversible by inhibitors or antibodies targeting the proteinase active site or the V3 loop. We propose that uPA, a transcriptionally regulated proteinase which is upregulated when macrophages are HIV infected, can be bound and utilized by the virus to aid in fusion and may be an endogenous component that is critical to the infection of macrophages by HIV-1.

Dibucaine elicits platelet procoagulant activity in factor VIII and factor X activation by a mechanism involving a sulfhydryl-dependent enzyme.

Dibucaine, a potent inhibitor of platelet aggregation and platelet release, was found to enhance the ability of fresh gel-filtered or washed human platelets to support factor VIII activation and factor X activation. Dibucaine-treated platelets increased the peak of factor VIII clotting activity by 2-fold compared to activity with untreated platelets. Similarly platelets optimally stimulated by dibucaine (1.0-1.5 mM for 5 min at 37 degrees C) supported as much factor X activation by factors IXa and VIII (measured in a chromogenic assay) as platelets optimally stimulated by ionophore A23187 (15 microM). An assay of platelet calcium-dependent sulfhydryl proteases was devised and used to test the effect of various inhibitors on these platelet proteases. The membrane-permeable sulfhydryl inhibitor Thiolyte MB inhibited platelet calcium-dependent protease activity; whereas, membrane-impermeable Thiolyte MQ did not. Thiolyte MB also blocked the ability of dibucaine-stimulated platelets to support factor X activation. Incubation of fresh, gel-filtered platelets with calpain inhibitor II (N-Ac-L-L-Normethioninal) completely inhibited the calcium-dependent sulfhydryl protease activity of these platelets but did not affect their ability to support factor X activation after subsequent incubation with dibucaine. These data support the interpretation that an intracellular SH-dependent enzyme, which may not be calpain, is involved in the expression of platelet procoagulant activity in dibucaine-treated platelets.

Effect of breed and body weight on echocardiographic values in four breeds of dogs of differing somatotype.

Eighty normal dogs of four morphologically disparate breeds (Pembroke Welsh Corgi, Miniature Poodle, Afghan Hound, Golden Retriever) (twenty of each breed), were studied by echocardiography to determine the importance of breed and weight in establishing normal echocardiographic reference ranges. Echocardiographic measurements included left-ventricular chamber dimension at systole and end-diastole, right-ventricular chamber dimension at end-diastole, interventricular septal thickness at systole and end-diastole, left-ventricular free wall thickness at systole and end-diastole, E-point septal separation, aortic root dimension at end-diastole, left atrial dimension, and fractional shortening. Analyses of covariance indicated that for all measurements except right-ventricular chamber dimension, the means were significantly different among breeds, after the differences in weight were taken into account. Echocardiographic measurements are variable even within the same breed. Breed must be considered in establishing echocardiographic measurement reference ranges. Echocardiographic values for each breed are presented.

Acromegaly in 14 cats.

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).

Airline deregulation and public policy.

An assessment of the effects of airline deregulation on travelers and carriers indicates that deregulation has provided travelers and carriers with $14.9 billion of annual benefits (1988 dollars). Airport congestion, airline safety, airline bankruptcy, and mergers are also analyzed and found in most cases to have reduced benefits. But, these costs should not be attributed to deregulation per se, but to failures by the government to pursue appropriate policies in these areas. Pursuit of policies that promote airline competition and efficient use of airport capacity would significantly increase the benefits from deregulation and would provide valuable guidance for other industries undergoing the transition to deregulation.

The presence of Campylobacter pylori in nonsteroidal antiinflammatory drug associated gastritis.

Although Campylobacter pylori has recently been causally linked to active chronic gastritis and peptic ulcer disease, its relationship to nonsteroidal antiinflammatory drug (NSAID) associated gastritis is unclear. We performed a case-control study of 100 patients who had undergone gastritis biopsy. Blinded review of Giemsa stained slides demonstrated the presence of C. pylori in 32% of 19 NSAID treated cases with active chronic gastritis vs 3% of 36 controls with chronic gastritis not taking NSAID, and 69% of 45 "positive" controls with active chronic gastritis not taking NSAID (p less than 0.001). Our results suggest a possible multifactorial etiology of NSAID associated gastritis.

Hypersomatotropism and insulin-resistant diabetes mellitus in a cat.

In this report, we described the clinical, radiographic, and echocardiographic findings in a cat with hypersomatotropism and insulin-resistant diabetes mellitus. Growth hormone determinations were made because of persistent hyperglycemia despite insulin requirements exceeding 2.2 U/kg of body weight, and the acromegalic features of the cat. Also, the results of a therapeutic trial in which a long-acting analogue of somatostatin was used are discussed.

Biofeedback to facilitate unassisted ventilation in individuals with high-level quadriplegia. A case report.

The purpose of this case report is to discuss the effectiveness of electromyographic biofeedback in reeducating and strengthening the accessory breathing muscles in an individual with high-level (C1) complete quadriplegia. Six unassisted breathing sessions were performed with EMG biofeedback intervention. Six unassisted breathing sessions without EMG biofeedback intervention were also performed. In both conditions, the subject's vital capacity and the amount of time of unassisted ventilation were recorded. The study results indicated that EMG biofeedback may be a helpful modality in training accessory breathing muscles to enable an individual with high-level quadriplegia to become independent of mechanical ventilation for varying amounts of time.

Effect of limited modification of amino groups on the reactivity of human factor Xa.

The basis of the specificity of human coagulation factor Xa has been probed with a reagent that reacts with nucleophiles, N-succinimidylpropionate. At pH 8.0 and 0.25 mM N-succinimidylpropionate, 0.4 microM factor Xa lost approx. 90% of its activity toward prothrombin in 4 min. The decay was first-order, k = 0.64 min-1, which increased to 0.98 min-1 in 1 mM Ca2+, and the dependence of k upon pH was consistent with primary amines being the target. The rate of modification was unaffected by the presence of a tetrapeptide substrate during modification; likewise, activity toward a tripeptide p-nitroanilide was unaltered during exposure of factor Xa to N-succinimidylpropionate with or without Ca2+. In addition, inhibition by antithrombin III was retained with a somewhat enhanced rate after modification; however, the acceleration of this by heparin was significantly less. Kinetic determination of the number of residues modified gave a reaction order of 2.0, while reaction with N-succinimidyl[3H]propionate yielded labeled factor Xa containing 1.0 mol N-succinimidylpropionate/mol factor Xa and 50% normal clotting activity, or 2.0 mol N-succinimidylpropionate/mol and 1% activity, respectively. Thus, one nucleophilic group is required for the reaction of factor Xa with prothrombin but not for the hydrolysis of peptides or recognition of antithrombin III. The decay of clotting activity of the factor X zymogen in N-succinimidylpropionate was much slower though still Ca2+-dependent. Conversely, the reaction of a related compound--N-succinimidyl(4-hydroxyphenyl)propionate or Bolton-Hunter reagent--with factor Xa broadly resembled that of N-succinimidylpropionate but the decay curves indicated more complex kinetics. Therefore, the target groups vary in their accessibility to modification according to the structural characteristics of both the protein and the reagent.

Origin of a fluorescence increase accompanying the limited proteolysis of fluorescein-labeled human prothrombin by Factor Xa.

In a search for a probe which would report its proteolysis to thrombin, the human blood coagulation zymogen prothrombin was covalently labeled with fluorescein. Fluorescein isothiocyanate (FITC) and dichlorotriazinylaminofluorescein (DCTAF) both introduced approximately 1 molecule of dye, but labeling occurred at different locations, as FITC had no effect on clotting activity whereas DCTAF caused 95% inactivation. At pH 9.0 DCTAF, but not FITC, could induce labeling up to 4 mol/mol. All derivatives were activated normally by prothrombinase (the activating complex of Factor Xa, Factor V(a), Ca2+ and phospholipids), as indicated by the pattern of bands on SDS gel electrophoresis and an unaltered yield of activity toward a chromogenic substrate for thrombin. Upon undergoing this limited proteolysis, the most heavily labeled derivative showed a 40% increase in fluorescence of the fluorescein at 520 nm (lambda ex 480 nm). In contrast, the fluorescence of lightly labeled forms was more intense but increased by only 0-5% upon activation. The data suggest that the lower fluorescence of the most labeled form is due to an intramolecular quenching effect between the dye molecules on individual polypeptide chains that is partly relieved when activation occurs.