Basal and infection-induced levels of heat shock proteins in human aging

Heat shock proteins (Hsp) are ubiquitously expressed proteins, which are highly inducible by a variety of stressful stimuli. As organisms age, various denatured proteins such as proteins modified by oxidation have been detected. Such abnormal proteins might serve as stress signals for the induction of Hsp, which plays indispensable roles in protecting proteins from denaturation. Although it is well known that the heat shock induced expression of Hsp decreases with age, little attention has been given to the unstimulated, basal levels of Hsp. Therefore, a study was performed to examine the expression pattern of various Hsp with aging, under normal physiological conditions in human peripheral blood cells. The basal levels of Hsp32, Hsp70 and Hsp90 increased significantly with age in controls but not patients. Moreover, the levels of Hsp32, Hsp70, Hsp90, but not Hsp27 correlated positively among each other, indicating both common and different regulatory mechanisms. Higher levels of Hsp32, Hsp70 and Hsp90 were noticed in patients with inflammation, a commonly occurring natural stimulant of Hsp production, compared to control subjects. The production of Hsp appeared to be related to the circulating levels of C-reactive protein and cytokines.     

A hat trick of ulcerating pathogens in a single genital lesion

We report on a patient from a London clinic, (a Jamaican heterosexual man known to have herpes) who has donovanosis and syphilis in a single genital ulcer. The case highlights the importance of careful clinical examination of genital ulcers.     

Psychological functioning and health-related quality of life in adulthood after preterm birth

The aim of this study was to determine if preterm birth is associated with socioeconomic status (SES), psychological functioning, and health-related quality of life (HRQoL) in adulthood. We used prospective follow-up of 192 adult offspring of mothers who took part in a randomized controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (66 born at term [33 males, 33 females] 126 born preterm [66 males, 60 females]). Cognitive functioning was assessed using the Wechsler Abbreviated Scale of Intelligence. Working memory and attention was assessed using the Benton Visual Retention Test, the Paced Auditory Serial Addition Test, and the Brown Attention Deficit Disorder Scale. Psychiatric morbidity was assessed using the Beck Depression Inventory II, the State-Trait Anxiety Inventory, and the Schizotypy Traits Questionnaire. Handedness was assessed using the Edinburgh Handedness Inventory. HRQoL was assessed using the Short Form-36 Health Survey. Moderately preterm birth (median gestation 34wks, mean birthweight 1946g [SD 463g]) was not related to later marital status, educational attainment, SES, cognitive functioning, working memory, attention, or symptoms of anxiety or schizotypy at 31 years of age. Preterm birth was associated with fewer symptoms of depression and higher levels of satisfaction in three of the eight HRQoL domains measured (bodily pain, general health perception, and social functioning). Adults who were born moderately preterm have SES, psychological functioning, and HRQoL consistent with those who were born at term. This good long-term outcome cannot be extrapolated to those with early childhood disability or very low birthweights.     

Brief Report: Brain Activation to Social Words in a Sedated Child with Autism

A functional magnetic resonance imaging (fMRI) study was performed on a 4-year-old girl with autism. While sedated, she listened to three utterances (numbers, hello, her own first name) played through headphones. Based on analyses of the fMRI data, the amount of total brain activation varied with the content of the utterance. The greatest volume of overall activation was in response to numbers, followed by the word ‘hello’, with the least activation to her name. Frontal cortex activation was greatest in response to her name, with less activation for numbers, and the least for the word ‘hello.’ These findings indicate that fMRI can identify and quantify the brain regions that are activated in response to words in children with autism under sedation.     

Age-dependent effects of environmental enrichment on spatial reference memory in male mice

Although environmental enrichment has been shown to improve various types of memory in young and aging mice, no study has directly compared the degree to which enrichment improves memory at different ages throughout the lifespan in male mice. Therefore, the present study investigated the effects of long-term continuous enrichment in young (3 months), middle-aged (15 months), and aged (21 months) male C57BL/6 mice. Spatial reference memory was tested in the Morris water maze. Results demonstrate that 24h/day environmental enrichment for approximately 6 weeks significantly improved spatial memory in the Morris water maze in aged males, but not in young or middle-aged males. These data also indicate that 24h exposure to complex enriched housing conditions increases the magnitude of enrichment-induced improvements in memory among aged mice relative to those previously reported by this lab and others.     

Rotavirus vaccines: opportunities and challenges

Each year rotavirus gastroenteritis episodes in young children cause more than 500,000 deaths and 2.4 million hospital admissions worldwide. Vaccine development became a priority when improved personal hygiene and living standards failed to significantly reduce this disease burden. Rotavirus vaccines were developed mimicking natural immunity by protecting against severe gastroenteritis in young children, which would otherwise lead to health-care attendance, hospitalization or even death. Licensed rotavirus vaccines appear safe and are well-tolerated. In high and middle-income countries they provide 80-100% protection against severe disease and 70-80% protection against rotavirus gastroenteritis of any severity, depending upon the population studied. However, rotavirus vaccines remain to be fully evaluated in low-income countries where reduced immunogenicity of oral vaccines, greater strain diversity and difficulties reaching target populations might decrease immunization program performance. Nevertheless, if these challenges are met, rotavirus vaccines should help reduce the 5% of all childhood deaths attributable to rotavirus gastroenteritis.     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.