Genetic studies on murine susceptibility to herpes simplex keratitis

We studied the influence of lgh-linked genes on the development of keratopathy after corneal inoculation with herpes simplex virus (HSV). Using congenic strains of mice, we found that the lgh-1 gene locus, or genes closely linked to it, influence the clinical expression of HSV infection. Mice with the lgh-1e or lgh-1d allotype routinely developed severe keratopathy after HSV corneal inoculation, whereas congenic strains with lgh-1a or lgh-1b allotype were less susceptible. Cell-mediated immune responses to HSV also differed between susceptible and resistant murine strains. We interpret our results to imply a genetic influence on cell-mediated, acquired immune responses to HSV infection.     

Correlates of body image dissatisfaction among overweight women seeking weight loss

Predictors of body image dissatisfaction (BID) among obese people are poorly understood. In 79 obese women seeking weight reduction, associations with BID of self-esteem, youth teasing, adult teasing, and internalization of sociocultural appearance standards (ISAS) were studied. Analyses revealed that only self-esteem, adult teasing, and ISAS predicted BID. Results highlight the importance of adulthood self-esteem and interpersonal-cultural context--rather than childhood experiences--in predicting adulthood BID.     

Invasive electrophysiological evaluation of patients with sleep apnoea-associated ventricular asystole—methods and preliminary results

SUMMARY  Twelve patients (aged 48 ± 12 y) with ventricular asystole of >3s due to complete atrioventricular (AV) block ( n = 8), sinoatrial (SA) block or sinus node arrest ( n = 3) or both ( n = 1) associated with obstructive sleep apnoea underwent invasive electrophysiological evaluation of sinus node function and AV conduction properties before and after administration of atropine (0.02 mg kg^-1). Ventricular asystole lasted for 5.9 ± 2.8 s (range 3.1–13 s). Sinus node function was assessed by measurement of sinus node recovery time, sinoatrial conduction time, and the response of sinus rate to atropine. Parameters of AV-conduction assessment included AH- and HV-intervals, AV- and VA-Wenckebach periods, and effective refractory period of the AV node before and after atropine. Sinus node function was normal in 11 of the 12 study patients and moderately abnormal in 1 patient. AV-nodal function was normal in 8 patients and moderately abnormal in 4 patients. A slightly prolonged HV-interval (59–63 ms) was present in 6 patients. Intra- or infra His block was not observed in any patient. In conclusion, normal or only moderately abnormal electrophysiological findings in patients with sleep apnoea-associated ventricular asystole suggest that a neurally mediated cardioinhibitory reflex may cause ventricular asystole in these patients. This sleep apnoea-triggered 'vasovagal' reflex may unmask pre-existing mild to moderate structural abnormalities of the AV conduction system.     

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responses

Cytokines and their receptors represent key targets for therapeutic intervention. Ligands are being used to supplement cell numbers that become depleted as a result of disease (organ failure, infection) or subsequent disease treatments (i.e. chemotherapy). Conversely, the inhibition of target cell binding by cytokines is an established strategy for abrogating pathologic cellular activities common to many immunological diseases. Considerable effort in biomedical research is being focused on the cytokine families that play a dominant role in regulating immunity and then prioritizing each member for its therapeutic potential. Currently, the interleukin-2 (IL-2) family of cytokines is widely recognized for its central involvement in controlling lymphocyte function and is the most explored for medical utility. Collectively, these proteins (or their antagonists) are either marketed drugs or have received advanced testing for an impressive array of indications including cancer, infectious disease, transplantation, inflammation and allergic asthma. Here we review the current understanding of IL-21, the most recent member of this cytokine family to be discovered. As will be discussed, IL-21 shares many of the same attributes as its relatives in that it has broad immunoregulatory activity and can modulate both humoral and cell-mediated responses. Its ability to stimulate durable anti-tumour responses in mice defines one therapeutic indication that merits clinical development.     

Dielectric properties of low-water-content tissues

The dielectric properties of two low-water-content tissues, bone marrow and adipose tissue, were measured from 1 kHz to 1 GHz. From 1 kHz to 13 MHz, the measurements were performed using a parallel-plate capacitor method. From 10 MHz to 1 GHz, a reflection coefficient technique using an open-ended coaxial transmission line was employed. The tissue water contents ranged from 1 to almost 70% by weight. The dielectric properties correlate well with the values predicted by mixture theory. Comparison with previous results from high-water-content tissues suggests that bone marrow and adipose tissues contain less motionally altered water per unit dry volume than do the previously studied tissues with lower lipid fractions. The high degree of structural heterogeneity of these tissues was reflected in the large scatter of the data, a source of uncertainty that should be considered in practical applications of the present data.     

The effect of elevated intracranial pressure on the vibrational response of the ovine head

Although potentially fatal increases in intracranial pressure (ICP) can occur in a number of pathological conditions, there is no reliable and noninvasive procedure to detect ICP elevation and quantitatively monitor changes over time. In this experimental study, the relationships between ICP elevation and the vibrational response of the head were determined. An ovine animal model was employed in which incremental increases in ICP were elicited and directly measured through intraventricular cannulae. At each ICP increment, a vibration source elicited a flexural response of the animal's head that was measured at four locations on the skull using accelerometers. Spectral analysis of the responses showed changes in proportion to ICP change up to roughly 20 cm H₂O (15 mm Hg) above normal; a clinically significant range. Both magnitude and phase changes at frequencies between 4 and 7 kHz correlated well (γ>0.92) with ICP across the study group. These findings suggest that the vibrational response of the head can be used to monitor changes in ICP noninvasively.     

Impedance-gradient electrode reduces skin irritation induced by transthoracic defibrillation

A new type of disposable external defibrillation electrode has been developed to reduce the skin irritation commonly associated with defibrillation and synchronised cardioversion. This design employs an impedance gradient to reduce the proportion of current delivered to the electrode periphery. The temperature distribution under the new electrode was compared with that of four other types of commercially available electrodes after repeated high-energy biphasic defibrillation discharges to domestic swine. Skin temperature distributions were acquired using non-invasive thermography. Measurements of the maximum temperature rise at each electrode site, taken 3.6s after the fifth defibrillation discharge, demonstrated that the new impedance-gradient electrode produced 50–60% less skin heating than two of the three uniform-impedance electrode designs. Histological examination of erythematous sites excised 24h after defibrillation quantified the associated skin damage using a scoring protocol developed for this study. In contrast to previous studies, histological examinations demonstrated second-degree skin burns following defibrillation. The new electrode design, however, induced 44–46% less skin damage than two of the traditional uniform-impedance electrodes.