Three novel germline BRCA1 mutations in early-onset breast and ovarian cancer families.
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Age of Onset↗
Biomedical subjects
D E Anderson
Publications and source records attributed to D E Anderson.
Cardiorenal effects of behavioral inhibition of breathing.
This article reviews evidence that mild, but sustained, inhibition of breathing can affect blood pressure regulation via effects of increased PCO2 on sodium regulation. Experiments with micropigs are summarized which show that anticipation of the onset of a familiar avoidance task is accompanied by sustained increases in PCO2, increases in plasma hydrogen and bicarbonate ion concentrations, decreases in hematocrit, and increases in circulating levels of sodium pump inhibitors that are sensitive to plasma volume. Observational studies with humans using an ambulatory respiration monitor characterize episodes of inhibited breathing occurring in the natural environment. Experimental studies with human subjects show that voluntary maintenance of end-tidal CO2 near the upper end of the normal range results in decreases in renal sodium excretion, increases in plasma sodium pump inhibitors and inhibition of sodium pump activity. Together, these studies are consistent with the view that behavioral stress can influence blood pressure regulation via sustained inhibition of respiration which acidifies the plasma and increases sodium/hydrogen exchange in kidneys and blood vessels.
Arousal↗
Comparison of various in vitro susceptibility methods for testing Stenotrophomonas maltophilia.
A total of 57 clinical isolates were screened by disk diffusion for a related pharmacodynamic study. Testing was performed using National Committee for Clinical Laboratory Standards guidelines, except that results were interpreted at 16 to 18 h and 48 h. Of the 57 isolates, 19 were randomly chosen for additional comparative susceptibility testing of five methods (disk diffusion, Etest, Alamar colorimetric broth microdilution, Vitek, and MicroScan) and an in-house broth microdilution method. The two diffusion methods (disk and Etest) had the closest correlation. The commercial broth microdilution methods and the in-house microdilution method generated inconsistent results for all agents except trimethoprim-sulfamethoxazole. Vitek compared poorly with both diffusion and microbroth dilution methods. The most significant discrepancies were evident with all methods when the incubation period was extended to 48 h. When results were interpreted at 48 h, the incidence of resistance for all bactericidal agents was approximately double the resistance observed at 16 to 18 h. The bacteriostatic agents, trimethoprim-sulfamethoxazole and doxycycline, demonstrated the greatest in vitro activity and were least influenced by extended incubation with diffusion methods. Because correlative in vivo and in vitro studies have not revealed an effective therapeutic regimen for serious S. maltophilia infections, susceptibility results with all testing methods should be interpreted with caution when choosing therapy for patients with life-threatening infections. Susceptibility testing for this heterogeneous group remains controversial and routine testing, with the possible exception of doxycycline (or minocycline) and trimethoprim-sulfamethoxazole, should be avoided. Our data support that if testing is done with bactericidal agents, consideration should be given to interpretation after 48-h incubation.
Anti-Bacterial Agents↗
Plasma marinobufagenin-like and ouabain-like immunoreactivity in adrenocorticotropin-treated rats.
Recently, an endogenous digitalis-like factor (EDLF) was shown to be stimulated in corticotropin (ACTH) hypertension in the rat. We have shown that mammalian plasma contains a vasoconstrictor Na,K-ATPase inhibitor, which cross-reacts with an antibody to amphibian EDLF, marinobufagenin. In the present experiment, the effect of 8 days of intramuscular ACTH treatment (0.5 mg/kg/day) of male Fisher 344 x NB rats on blood pressure, plasma ouabain-like and marinobufagenin-like immunoreactivity, and on the activity of Na,K-ATPase in aortic sarcolemma were studied. The ACTH treatment for 8 days resulted in increased systolic blood pressure (151 +/- 12.4 v 121 +/- 4.0 mm Hg, P < .01), inhibition of Na,K-ATPase in aortic sarcolemma (2.99 +/- 0.35 v 5.43 +/- 0.17 micromol ADP/mg(prot)/h), and increases in plasma concentration of marinobufagenin-like (0.44 +/- 0.06 v 0.21 +/- 0.05 nmol/L), but not ouabain-like (0.09 +/- 0.01 v 0.10 +/- 0.04 nmol/L) immunoreactivity. In dissociation enhanced lanthanide fluoroimmunoassay (DELFIA), serial dilutions of plasma from ACTH-treated rats extracted with 25% and 80% acetonitrile, respectively, demonstrated parallelism to the calibration curves of ouabain and marinobufagenin. These findings suggest that an endogenous bufodienolide Na,K-ATPase inhibitor, rather than an endogenous ouabain-like compound, is increased after 8 days of treatment of rats with ACTH.
Adrenocorticotropic Hormone↗
Tick-borne relapsing fever in the northwestern United States and southwestern Canada.
Records from 182 cases of tick-borne relapsing fever (TBRF) were reviewed. In confirmed cases, there was febrile illness, and spirochetes were identified on peripheral blood preparations. In probable cases, there were clinical features of TBRF and either the same exposure as a confirmed case or serological (indirect fluorescent antibody test and western blotting [WB]) evidence of infection with Borrelia hermisii. Sera also were tested for antibody to Borrelia burgdorferi. We identified 133 confirmed and 49 probable cases of TBRF. A Jarisch-Herxheimer reaction was reported in 33 (54.1%) of 61 cases for which this information was available. Most patients who had antibodies to B. hermsii were serologically positive for B. burgdorferi, and WB demonstrated false positivity of testing for B. burgdorferi. Thirty-five (21%) of 166 cases were unreported to public health authorities. In 52 cases, there were more than two relapses before the diagnosis. This study demonstrates that TBRF is underrecognized and underreported and may be falsely identified as Lyme disease.
Adolescent↗
Sodium sensitivity in young adults with high resting end-tidal CO2.
BACKGROUND: Previous research with normotensive adults aged over 40 years ('older') found that sensitivity of blood pressure of subjects with high resting end-tidal partial pressures of CO2 to high sodium intake was greater than normal. OBJECTIVE: To test the hypothesis that the lesser sensitivity of blood pressure of young normotensive adults to high sodium intake is also a function of resting end-tidal partial pressure of CO2. DESIGN: Forty-eight Caucasian men and women (age 28.5 +/- 1.4 years) had a lower than normal dietary intake of sodium chloride for 4 days, and then ingested sodium chloride capsules for 7 days (an additional 190 mmol/day sodium chloride). Resting end-tidal partial pressure of CO2 and blood pressure, and 24 h ambulatory blood pressure, were measured before and after the high-sodium diet. Overnight urine samples were collected before and after the high-sodium diet to determine dietary compliance, and to assess changes in urinary excretion of endogenous digitalis-like factors (a ouabain-like factor, and a marinobufagenin-like factor) that covary with plasma volume. RESULTS: Subjects with high end-tidal partial pressures of CO2 had lower resting heart rates and lower urinary excretion of ouabain-like factor before sodium loading. Sodium loading decreased mean partial pressure of CO2 (by 0.8 +/- 0.2 mmHg) and increased only ambulatory systolic blood pressure (by 2.1 +/- 0.8 mmHg) for the whole group. However, the changes in resting systolic (r = 0.32, P < 0.025) and diastolic (r = 0.36, P < 0.01) blood pressures and in 24 h systolic (r = 0.28, P < 0.05) blood pressure after sodium loading were all positive functions of individual resting end-tidal partial pressures of CO2. Sodium loading increased urinary excretion of marinobufagenin-like factor (by 1.78 +/- 0.88 nmol) and the magnitude of the individual increase was a function of end-tidal partial pressure of CO2. CONCLUSIONS: The results indicate that a high resting partial pressure of CO2 augments the effects of high sodium intake on plasma volume, levels of endogenous digitalis-like factors, and blood pressure in young normotensive humans.
Adult↗
Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients.
A blood culture cohort study investigating issues related to isolation of coagulase-negative staphylococci (CoNS) and other skin microflora is reported. Data were collected over 12 weeks to determine the incidence of significant CoNS bacteremia versus that of pseudobacteremia (contaminants) and to evaluate drug therapy in patients with cultures positive for CoNS. In addition, the effectiveness of 0.2% chlorine peroxide as a bactericidal disinfectant was compared to that of 10% providone iodine. A total of 3,276 cultures of blood from 1,433 patients were evaluated in the study. Eighty-nine cultures were positive for skin flora, with 81 of 89 (91%) involving CoNS. The incidence of significant CoNS bacteremia was 20 of 81 (24.7%), that of indeterminate bacteremia was 10 of 81 (12.3%), and that of contamination was 59 of 81 (72.8%). The incidence of significant bacteremia involving CoNS was double the 10 to 12% rate based on previous estimations at our institutions. In tests with the two bactericidal disinfectants, 22 of 1,639 cultures (1.3%) in the chlorine peroxide group versus 37 of 1,637 (2.3%) in the providone iodine group were considered contaminated (P = 0.065). Rates of contamination for venipuncture versus catheter collection were not significantly different (P = 0.46). The overall contamination rate was 59 of 3,276 (1.8%), which is consistent with the lower end of published quality assurance benchmark standards. The low rate was believed to be due to the professional phlebotomy staff in our institutions. There was excellent agreement between retrospective analysis by reviewers, when formal criteria were used, and the attending physicians' intuitive clinical impressions in the classification of significant bloodstream infections (100% agreement) or contamination (95% agreement). However, physicians still used antimicrobial agents to treat nearly one-half of the patients with contaminated blood cultures, with vancomycin being misused in 34% of patients. In addition, 10% of patients with significant bacteremia were treated with inappropriate agents. There were no significant adverse events or prolonged hospital stays due to the unnecessary use of vancomycin; however, the additional costs of treating patients whose cultures contained CoNS contaminants was estimated to be $1,000 per patient. Measures to limit the unnecessary use of vancomycin (and other agents) are important.
Adult↗
Reference values for selected hematologic and biochemical variables in Holstein bulls of various ages.
OBJECTIVE: To determine reference ranges for hematologic and serum biochemical variables of bulls residing at an artificial insemination center. ANIMALS: 225 healthy Holstein bulls categorized by age into yearling, intermediate age, and adult groups. PROCEDURE: Hematologic and serum biochemical analyses were performed on 1 blood and 1 serum sample from each bull. RESULTS: Significant differences associated with age were identified for 25 of 33 variables. Serum creatinine concentration for clinically normal adult bulls (2.44+/-0.33 mg/dl) was higher than previously reported reference values for adult cattle. There was a reversal of the segmented neutrophil-to-lymphocyte ratio between yearling (0.85:1) and adult (2.6:1) bulls. This was associated with a significant and marked decrease in absolute numbers of lymphocytes per microliter between yearling (5,801+/-1,683) and adult (1,307+/-509) bulls. CLINICAL RELEVANCE: Reference values for selected clinicopathologic variables were generated from the data.
Aging↗
Expression of a hypoglycosylated form of CD86 (B7-2) on human T cells with altered binding properties to CD28 and CTLA-4.
CD80 (B7-1) and CD86 (B7-2) on APC provide a major costimulatory signal through interactions with CD28 on T cells. Absent from resting human T cells, CD86 is up-regulated early upon T cell activation, whereas CD80 expression appears later. Whereas T cell expression of CD80 has been implicated in costimulation, the functional significance of CD86 expression on T cells is unclear. We now demonstrate that CD86 expressed on human CD4+ T cell clones does not provide a costimulatory signal for other CD4+ T cell clones. Binding studies using CD28-Ig and CTLA-4-Ig fusion proteins demonstrate that CD86 expressed on T cells has significantly reduced binding affinity for CTLA-4 and no detectable binding to CD28. Biochemical analysis demonstrates that post-translational modifications of CD86 in human T cells are different from those of CD86-transfected Chinese hamster ovary cells or EBV-transformed B cells, in that T cells express a hypoglycosylated form of CD86 on the surface membrane. Thus, our results suggest that while CD86 is expressed on a number of different cell types, its costimulatory function and affinity for its ligands may be regulated by cell type-specific post-translational modifications.
Abatacept↗
Weak peptide agonists reveal functional differences in B7-1 and B7-2 costimulation of human T cell clones.
The influence of costimulation on the T cell response to altered peptide ligands that act as either partial or weak agonists for human CD4+ T cell clones was examined. Using stable Chinese hamster ovary (CHO) cell transfectants expressing DR2 (DRB1*1501) and human B7-1 or B7-2 as APC, presentation of native myelin basic protein (MBP) p85-99 peptide Ag or a partial agonist of MBP p85-99 induced equivalent T cell activation as measured by [3H]TdR incorporation and cytokine secretion. In marked contrast, presentation of cross-reactive peptides of MBP p85-99 that act as weak agonists with B7-1, but not B7-2, costimulation resulted in significant T cell activation as measured by [3H]TdR incorporation and cytokine secretion. These data suggest that decreasing the strength of the signal provided to the TCR allows differences in B7-1 and B7-2 signaling to be observed. Thus, the costimulatory environment during T cell activation may be a mechanism of regulating T cell cross-reactivity in the periphery.
Amino Acid Sequence↗
Multifocal polyostotic aneurysmal bone cysts in a llama.
A 3.3-year-old 125-kg castrated male llama was evaluated because of acute non-weight-bearing lameness on the left hind limb. Physical examination revealed crepitus in the midportion of the femur. On radiographs, a comminuted middiaphyseal fracture was seen. There was also a region of bone lysis with cortical thinning and expansion in the distal metaphysis and epiphysis of the left femur. Multiple small circular lesions were observed in the proximal metaphysis of the left femur, and the proximal portion of the left tibia appeared irregular. The owner elected to pursue treatment, and the fracture was repaired with 2 compression plates. Multiple bone biopsy specimens were obtained and submitted for bacterial culture and histologic examination. Cultures yielded neither bacteria nor fungi. Histologic examination revealed fibrous connective tissue, normal appearing cortical bone, and an absence of medullary structures. The llama was maintained in a hind-limb sling for 14 days after surgery, at which time follow-up radiography revealed a comminuted fracture of the proximal portion of the femur. The llama was euthanatized, and multifocal polyostotic aneurysmal bone cysts were found in the proximal and distal metaphyses of the left femur and tibia. Cysts were lined by fibroblasts or endothelial-like cells.
Animals↗
Fascia lata autograft for treatment of congenital cranial cruciate ligament deficiency in a llama.
An 11.4-kg female llama that had been born without assistance while its dam was under observation at the veterinary teaching hospital was observed to ambulate abnormally on its right hind limb. A cranial drawer sign could be elicited in the right stifle. Cranial displacement of the tibia relative to the femur and dysplasia of the proximal end of the tibia were seen on radiographs. When the cria was 10 days old, the joint was stabilized with a fascia lata autograft. At the time of surgery, a segment of thin, loose tissue was found where the cranial cruciate ligament would have been. Three years after surgery, the llama gave birth to a normal cria and was 60 days pregnant with a second cria. To our knowledge, congenital cranial cruciate ligament deficiency with tibial dysplasia has not been reported in llamas. The heritability of these defects is unknown.
Animals↗
The characterization of composite agarose/hydroxyethylcellulose matrices for the separation of DNA fragments using capillary electrophoresis.
Mixtures of the polysaccharide derivatives, 19% hydroxyethylated SeaPrep agarose (SP-AG) and hydroxyethylcellulose (HEC), in aqueous buffer solutions are applied for the first time to the separation of DNA fragments using capillary electrophoresis (CE). These matrices form unique size-sieving networks that allow the separation of a wide size range of DNA fragments in a single analysis. Relative to their homogeneous counterparts, the composite separation matrices provide enhanced selectivity properties of DNA fragments, especially for fragments greater than 1000 base pairs (bp) in length. Additionally, the effects on separation performance of capillary temperature, the incorporation of a DNA intercalator, and applied field strength are demonstrated. Solution viscosity measurements of the homogeneous and composite matrix solutions were made in order to establish the entanglement threshold concentrations for the unique size-sieving solutions. The relatively low solution viscosities of the composite separation matrices allow reproducible replacement of the separation matrix between analyses. The mechanism of separation of DNA fragments for the composite matrices is proposed.
Buffers↗
Influence of pH on the antimicrobial activity of clarithromycin and 14-hydroxyclarithromycin against Haemophilus influenzae using an in vitro pharmacodynamic model.
Clarithromycin activity can be influenced by the pH of the surrounding environment. Evidence supports a reduced pH of middle ear fluid (MEF) and lung tissues in patients with otitis media and pneumonia, respectively. To evaluate the influence of pH on clarithromycin activity, an in vitro pharmacodynamic chamber model (PDCM) was used to generate bacterial time-kill curves for clarithromycin and a 2:1 ratio of clarithromycin and 14-hydroxyclarithromycin (HC) against Haemophilus influenzae at three different pH values: 7.2, 6.8, 6.4. Concentrations observed in MEF and lung tissues were simulated for clarithromycin alone and clarithromycin plus HC. Differences in activity at each pH were identified by comparing initial kill curve slopes and total log reduction. Experiments with amoxicillin-clavulanate were conducted as a reference. In simulated MEF regimens at pH 7.2, activity of clarithromycin alone improved by adding HC (additional 2 log10 reduction at 8 h); however, at pH values of 6.8 and 6.4, kill curves resembled growth controls. In simulated lung regimens, differences between clarithromycin alone and clarithromycin plus HC were insignificant; both produced a 2 log10 reduction at pH 7.2, and activity dramatically dropped to < 0.4 log10 as pH declined. In contrast, amoxicillin-clavulanate consistently produced a 3 log10 reduction over each pH value with more rapid initial kill relative to all clarithromycin regimens. These findings suggest the activity of clarithromycin against H. influenzae may be significantly compromised in respiratory tract infections involving a reduced pH. Trials with emphasis on clinical outcomes analysis will assist further in determining the significance of these experimental findings.
Clarithromycin↗
Surgery of the respiratory system.
Diseases affecting the respiratory tract are common in cattle; however, surgery required for treatment of these diseases is infrequent. Therefore, veterinarians may be reluctant to perform these surgical procedures. Familiarity with the variety and complexity involved in various surgical procedures should reduce this anxiety. When used, surgery of the respiratory tract can offer significant benefit to the patient and profitable returns to the owner.
Animals↗
Identification and molecular cloning of a gene encoding a fibronectin-binding protein (CadF) from Campylobacter jejuni.
Campylobacter jejuni, a Gram-negative bacterium, is a common cause of gastrointestinal disease. By analogy with other enteric pathogens such as Salmonella and Shigella, the ability of C. jejuni to bind to host cells is thought to be essential in the pathogenesis of enteritis. Scanning electron microscopy of infected INT407 cells suggested that C. jejuni bound to a component of the extracellular matrix. Binding assays using immobilized extracellular matrix proteins and soluble fibronectin showed specific and saturable binding of fibronectin to C. jejuni. Ligand immunoblot assays using 125I-labelled fibronectin revealed specific binding to an outer membrane protein with an apparent molecular mass of 37 kDa. A rabbit antiserum, raised against the gel-purified protein, reacted with a 37 kDa protein in all C. jejuni isolates (n = 15) as tested by immunoblot analysis. Antibodies present in convalescent serum from C. jejuni-infected individuals also recognized a 37 kDa protein. The gene encoding the immunoreactive 37kDa protein was cloned and sequenced. Sequencing of overlapping DNA fragments revealed an open reading frame (ORF) that encodes a protein of 326 amino acids with a calculated molecular mass of 36872Da. The deduced amino acid sequence of the ORF exhibited 52% similarity and 28% identity to the root adhesin protein from Pseudomonas fluorescens. Isogenic C. jejuni mutants which lack the 37 kDa outer membrane protein, which we have termed CadF, displayed significantly reduced binding to fibronectin. Biotinylated fibronectin bound to a protein with an apparent molecular mass of 37 kDa in the outer membrane protein extracts from wild-type C. jejuni as judged by ligand-binding blots. These results indicate that the binding of C. jejuni to fibronectin is mediated by the 37 kDa outer membrane protein which is conserved among C. jejuni isolates.
Adhesins, Bacterial↗
Facilitated ankylosis for treatment of septic arthritis of the distal interphalangeal joint in a llama.
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Animals↗
Use of a multifenestrated indwelling lavage system for treatment of septic digital tenosynovitis in cattle.
Septic tenosynovitis was diagnosed in seven cattle on the basis of history, physical examination, radiographs, cytological examination of tendon sheath fluids, and microbial culture. A commercially available indwelling multifenestrated silicone rubber drain was used to perform frequent lavage of the flexor tendon sheaths. The sepsis resolved in all cattle. Five of six cattle for which long-term (> 1 year) follow-up information was available were clinically sound on the affected limb and had remained productive members of the herd.
Animals↗