The effect of aging on IgD receptor expression by T cells and its functional implications

Summary: Exposure to oligomeric or aggregated (a), but not to mono-merle (m), IgD causes a rapid (within 1 h) upregulation of IgD-R expression on CD4⁺ T cells from young, but not from aged, mice and on both CD4⁺ and CD8⁺ T cells from all young and from =65% of aged humans. In normal young (but not in IgD^−/-) mice, this increase in IgD-R expression is associated with a marked increase in primary and secondary antibody responses, transferable to both aged and young mice with T cells from aIgD pretreated donors. In both species, immunization causes a rise in the IgDR⁺ expression in vivo in the young. In mice, mIgD abolishes both the Induction of IgD-R expression and augmentation of immune responses, suggesting that interaction between IgD-R⁺ T and IgD⁺ B cells is needed. In aged humans, the ability of peripheral blood lymphocytes to exhibit IgD-R expression in response to aIgD in vitro or to influenza vaccine in vivo is strongly correlated to the individual's ability to produce antibody. In T cells from aged mice, but not from aged IgD-non-responder humans, IgD-R are able to come to the cell surface if an additional signal has been supplied, such as by (ionomycin/thapsigargin + aIgD). Agents which induce IgD-R and augmentation of antibody production in aged and young mice include phosphatidylcholine and dehydroepiandrosterone sulfate. The immunoaugmenting effect of pretreatment with these agents appears Indeed due to IgD-R⁺ T cells, because it is abolished by mIgD.     

The Phenotypic Consequences of CFTR Mutations

Cystic fibrosis is a common autosomal recessive disorder that primarily affects the epithelial cells in the intestine, respiratory system, pancreas, gall bladder and sweat glands. Over one thousand mutations have currently been identified in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that are associated with CF disease. There have been many studies on the correlation of the CFTR genotype and CF disease phenotype; however, this relationship is still not well understood. A connection between CFTR genotype and disease manifested in the pancreas has been well described, but pulmonary disease appears to be highly variable even between individuals with the same genotype. This review describes the current classification of CFTR mutation classes and resulting CF disease phenotypes. Complex disease alleles and modifier genes are discussed along with alternative disorders, such as disseminated bronchiectasis and pancreatitis, which are also thought to result from CFTR mutations.     

Mycobacterium chelonae causing otitis media in an ear-nose-and-throat practice

Seventeen cases of otitis media caused by Mycobacterium chelonae were detected among patients seen at a single ear-nose-and-throat (ENT) office (Office A) in Louisiana between May 5 and September 15, 1987. All the patients had a tympanotomy tube or tubes in place or had one or more tympanic-membrane perforations, with chronic otorrhea that was unresponsive to standard therapy with antimicrobial agents. Middle-ear exploration in six patients revealed abundant granulation tissue; multiple granulomas and acid-fast bacilli were demonstrated on a section of tissue from one patient with a nonhealing mastoidectomy incision. Thirteen of the 14 ear isolates obtained from patients seen in Office A had the same unusual pattern of high-level resistance to aminoglycosides. M. chelonae and other nontuberculous mycobacteria were recovered from several sources of water in Office A, as well as in another ENT office (Office B) in a neighboring city that was visited by the index patient. Only one additional case was detected in Office B during the same period. Otologic instruments in Office A were cleaned in an ultrasonic bath with tap water and a liquid detergent; the contents of the bath were changed only once weekly. Instruments in Office B were placed in boiling water between patient examinations. This outbreak establishes M. chelonae as an agent of otitis media and underscores the need for high-level disinfection or sterilization of ENT instruments between examinations to prevent the transmission of this organism to patients in the office setting.     

Neutrophil mobilization and clearance in the bone marrow

The bone marrow is the site of neutrophil production, a process that is regulated by the cytokine granulocyte colony‐stimulating factor (G‐CSF). Mature neutrophils are continually released into the circulation, with an estimated 10 11 neutrophils exiting the bone marrow daily under basal conditions. These leucocytes have a short half‐life in the blood of ～6·5 hr, and are subsequently destroyed in the spleen, liver and indeed the bone marrow itself. Additionally, mature neutrophils are retained in the bone marrow by the stromal cell‐derived factor (SDF‐1α)/chemokine (C‐X‐C motif) receptor 4 (CXCR4) chemokine axis and form the bone marrow reserve. Following infection or inflammatory insult, neutrophil release from the bone marrow reserve is substantially elevated and this process is mediated by the co‐ordinated actions of cytokines and chemokines. In this review we discuss the factors and molecular mechanisms regulating the neutrophil mobilization and consider the mechanisms and functional significance of neutrophil clearance via the bone marrow.     

Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

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Brain responses associated with the Valsalva maneuver revealed by functional magnetic resonance imaging

The Valsalva maneuver, a test frequently used to evaluate autonomic function, recruits discrete neural sites. The time courses of neural recruitment relative to accompanying cardiovascular and breathing patterns are unknown. We examined functional magnetic resonance imaging signal changes within the brain to repeated Valsalva maneuvers and correlated these changes with physiological trends. In 12 healthy subjects (age, 30-58 yr), a series of 25 volumes (20 gradient echo echo-planar image slices per volume) was collected using a 1.5-Tesla scanner during a 60-s baseline and 90-s challenge period consisting of three Valsalva maneuvers. Regions of interest were examined for signal intensity changes over baseline and challenge conditions in cardiorespiratory-related regions. In addition, whole brain correlations between signal intensity and heart rate and airway load pressure were performed on a voxel-by-voxel basis. Significant signal changes, correlated with the time course of load pressure and heart rate, emerged within multiple areas, including the amygdala and hippocampus, insular and lateral frontal cortices, dorsal pons, dorsal medulla, lentiform nucleus, and fastigial and dentate nuclei of the cerebellum. Signal intensities peaked early in the Valsalva maneuver within the hippocampus and amygdala, later within the dorsal medulla, pons and midbrain, and deep cerebellar nuclei, and last within the lentiform nuclei and the lateral prefrontal cortex. The ventral pontine signals increased during the challenge, but not in a fashion correlated to load pressure or heart rate. Sites showing little or no correlation included the vermis and medial prefrontal cortex. These data suggest an initiating component arising in rostral brain areas, a later contribution from cerebellar nuclei, basal ganglia, and lateral prefrontal cortex, and a role for the ventral pons in mediating longer term processes.     

Folate-related genes and omphalocele

Women who take folic acid in the periconceptional period greatly reduce their chances of having a child with a neural tube defect (NTD). Using multivitamins may also reduce the risk of having a child with an omphalocele. In this study, we tested single nucleotide polymorphisms in folate-related enzyme genes for association with omphalocele. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (MTHFD1), the reduced folate carrier (SLC19A1), and transcobalamin II (TCN2) were examined in 25 children with euploid omphalocele and 59 matched controls. Omphalocele cases were significantly more likely to carry the T allele of MTHFR 677C-->T, a known risk factor for NTDs (odds ratio 3.50, 95% confidence interval 1.07-11.47, P=0.035). The MTHFD1 R653Q, SLC19A1 R27H, and TCN2 P259R polymorphisms showed no significant association with omphalocele. In this small study, the thermolabile variant of MTHFR, 677C-->T, was associated with an increased risk for omphalocele. This variant causes reduced enzyme activity, thus suggesting a mechanism by which multivitamins with folic acid might prevent omphalocele. Additional investigation is required.     

Prevalence of antibody to human immunodeficiency virus and hepatitis B surface antigen in blood samples submitted to a hospital laboratory. Implications for handling specimens

The prevalence of hepatitis B surface antigen (HBsAg) and antibody to human immunodeficiency virus (HIV) was determined in serum or plasma specimens of 506 patients submitted to the clinical chemistry laboratory of an urban teaching hospital, and the results were correlated with "biohazard" warning labels on the specimens. Hepatitis B surface antigen, HIV antibody, or either of these were present in 32 (6.3%), 15 (3.0%), and 44 specimens (8.7%), respectively. Ten (67%) of 15 specimens with HIV antibody and nine (28%) of 32 with HBsAg bore biohazard labels. Among 473 unlabeled specimens, HIV antibody was present in five (1.1%), HBsAg was present in 23 (4.9%), and 27 (5.7%) contained either or both of these markers. All clinical and laboratory personnel should be vaccinated against hepatitis B and should handle all blood specimens as if they were infected, regardless of biohazard labeling. By fostering complacency in handling unlabeled specimens, the use of biohazard labels may paradoxically increase the risk that health care workers will be exposed to HIV and hepatitis B virus.     

Quality of life profiles and their association with clinical and demographic characteristics and physical activity in people with a stoma: a latent profile analysis

Quality of Life Research - Quality of life can be negatively impacted by the formation of a stoma and is influenced by a number of factors. Research to date treats people with a stoma as a...