Comparison of the structure of human intervertebral discs in the cervical,thoracic and lumbar regions of the spine

Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc.     

Tissue fixation effects on immunohistochemical staining of caspase-3 in brain tissue.

Fixation methods for tissue often vary amongst clinical and research laboratories. To evaluate the effects of fixation method on studies of brain tissue, we examined immunohistochemical outcomes amongst 2 fixatives, 4 caspase-3 antibodies, and 2 species (human infants and piglets). Fixatives were 10% neutral buffered formalin (NBF) or 10% NBF and glacial acetic acid (FAA). Antibodies for caspase-3 were commercially obtained and included 2 for active caspase-3, and 2 for procaspase-3 (CASP3 and CPP32). Immunohistochemical staining of caspase-3 varied with fixation method, with the greatest effect of fixation method observed for the active caspase-3 antibodies and this effect was present in both species. In NBF-fixed tissue, active caspase-3 immunoreactivity was only visible microscopically, and was specific to neuronal cell bodies. In FAA-fixed tissue, active caspase-3 immunoreactivity was visible macroscopically, and predominantly present in fiber tracts and fasciculi compared with neuronal bodies. Fixation and species differences were also identified for the procaspase-3 antibodies, CASP3 and CPP32, where FAA-fixed pig tissue showed abundant staining of blood vessels that were not observed in the NBF-fixed pig tissue or in the human tissue. This study characterizes differences in immunohistochemical outcomes using commercially available antibodies for caspase-3, according to tissue fixation method and species.     

Skeletal muscle mitochondrial function and lean body mass in healthy exercising elderly

BACKGROUND: The decline in muscle mass (sarcopenia) with aging may be related to a decline in mitochondrial function. However, investigators have yet to reach a consensus as to whether a decline in mitochondrial function can be attenuated by physical activity has yet to reach a consensus. METHODS: Using dynamic 31PMRS to measure mitochondrial function, we measured baseline Phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiester (PDE), [ADP], pH and recovery times (t(1/2)) for PCr and [ADP] following exercise, in 45 older (73+/-4 years, SD), and 20 younger subjects (25+/-4 years, SD) who were matched for body mass across high and low activity levels and within age and sex groupings. RESULTS: Baseline PCr, and Pi, were lower, and PDE higher in the older subjects compared to younger subjects (all P<0.01). The t(1/2)(ADP) was longer in older subjects (P<0.001) controlling for age and sex in the low activity group (P=0.02). In the older low activity groups, t(1/2)(PCr) was longer than high activity groups. Higher PDE levels were positively correlated with longer t(1/2)(PCr) in the older low activity females (both P<0.05). CONCLUSIONS: Our data suggests that mitochondrial function declines with age in healthy, exercising elderly adults and that the decline appears to be influenced by the level of physical activity.     

Prognostic value of exercise testing soon after myocardial infarction.

The prognostic value of a limited treadmill exercises test performed one day before hospital discharge after acute myocardial infarction was studied in 210 consecutive patients who had no over heart failure and had been free of chest pain for at least four days. No complications occurred. During a one-year follow-up period 28 of 43 patients (65 per cent) who had chest pain during the test reported angina, as compared with 60 of 167 (36 per cent) who had no chest pain during test (P less than 0.001). The one-year mortality rates were 2.1 per cent (three of 146) in patients without changes in the S-T segment during exercise and 27 per cent (17 of 64) in those with depression of the S-T segment (P less than 0.001). Sudden death occurred in one of 146 (0.7 per cent) patients who showed no change in the S-T segment and in 10 of 64 (16 per cent) with depression of the segment (P less than 0.001). Thus, a limited treadmill exercise test performed before hospital discharge after acute myocardial infarction is safe and can predict mortality in the subsequent year.     

Leucine33-proline33 substitution in human platelet glycoprotein IIIa determines HLA-DRw52a (Dw24) association of the immune response against HPA-1a (Zwa/PIA1) and HPA-1b (Zwb/PIA2).

Alloantibody formation against HPA-1a (Zwa/PIA1) has, to date, only been found in HLA-DRw52(a+) (Dw24) individuals. Alloimmunization against the product of the other HPA-1 allele, HPA-1b, is rare. We have been able to evaluate ten cases of HPA-1b alloimmunization in Europe in order to study whether there is an association between HLA phenotype and anti-HPA-1b antibody formation. HLA typing of these patients was performed with particular attention to the DRw52a specificity using specific T-cell clones. No association with DRw52a or any other known HLA phenotype was found. This finding implies that the amino acid substitution leucine33-proline33 in GPIIIa, responsible for HPA-1a/b, is of primary importance for the association of anti-HPA-1a antibody formation with DRw52a. These data show that the amino acid polymorphism affects the presentation of the immunogenic oligopeptides of HPA-1a and -1b in the HLA class-II groove.     

Histological and immunohistochemical study of hepatitis B virus in human immunodeficiency virus infection

Because the risk factors for human immunodeficiency virus (HIV) infection and hepatitis B (HBV) are similar and therefore coinfection is not uncommon, a detailed histological and immunohistochemical study of chronic hepatitis B infection in a group of 20 HIV positive Caucasian males (who did not have AIDS) and 30 HIV negative controls were undertaken. Using both the conventional histological classification and the Knodell histological activity index it was shown that HIV negative patients were more likely to have active disease and also more scarring than HIV positive patients. Hepatitis B surface antigen (HBsAg) expression was not significantly different between the two groups but expression of hepatitis Be antigen (HBeAg) and HBV-DNA polymerase was greater in those who were HIV positive. HIV positive patients are therefore more likely to have immunohistochemical markers of active viral replication, although histologically, liver disease is less severe. These findings have important implications for assessing the biopsy specimens in this group of patients and for treatment strategies aimed at improving their immune function.     

Detailed mapping of a congenital heart disease gene in chromosome 3p25

Distal deletion of chromosome 3p25-pter (3p− syndrome) produces a distinct clinical syndrome characterised by low birth weight, mental retardation, telecanthus, ptosis, and micrognathia. Congenital heart disease (CHD), typically atrioventricular septal defect (AVSD), occurs in about a third of patients. In total, approximately 25 cases of 3p− syndrome have been reported world wide. We previously analysed five cases and showed that (1) the 3p25-pter deletions were variable and (2) the presence of CHD correlated with the proximal extent of the deletion, mapping a CHD gene centromeric to D3S18. To define the molecular pathology of the 3p− syndrome further, we have now proceeded to analyse the deletion region in a total of 10 patients (five with CHD), using a combination of FISH analysis and polymorphic markers, for up to 21 loci from 3p25-p26. These additional investigations further supported the location of an AVSD locus within 3p25 and refined its localisation. Thus, the critical region was reduced to an interval between D3S1263 and D3S3594. Candidate 3p25 CHD genes, such as PMCA2 (ATP2B2), fibulin 2, TIMP4, and Sec13R, were shown to map outside the target interval. Additionally, the critical region for the phenotypic features of the 3p− phenotype was mapped to D3S1317 to D3S17 (19-21 cM). These findings will accelerate the identification of the 3p25 CHD susceptibility locus and facilitate investigations of the role of this locus in non-syndromic AVSDs, which are a common form of familial and isolated CHD.


Keywords: congenital heart disease; chromosome 3p25     

Behavioral and hypnotic treatments for insomnia subtypes

This investigation compared progressive muscle relaxation plus cognitive distraction (PMR/CD), hypothesized to better improve sleep onset, versus sleep restriction and stimulus control (SR/SC), hypothesized to better improve sleep maintenance, versus a flurazepam (Dalmane) positive contrast condition (MED) and a sleep hygiene education minimal treatment control condition (SHE). Participants with chronic insomnia (N = 53), completed 2 baseline weeks of sleep diaries, and were randomly assigned to a treatment group for 2 more weeks. In the second phase, PMR/CD participants were assigned to 2 weeks of PMR/CD + SR/SC + SHE while SHE participants continued SHE. Results indicated that PMR/CD had greater effect upon sleep onset than SR/SC and SHE, SR/SC had greater effect on sleep maintenance than PMR/CD, and MED was better than the other treatments. In the second phase, the treatment package produced modest additional improvements and SHE performed superior to expectations.     

Repeated Habituation and Overhabituation of the Orienting Response

This investigation was designed to test (a) whether stimuli presented in the form of repeated blocks of habituation trials, as opposed to.1 single continuous series of stimuli, would produce a progressive decline. in amount of spontaneous recovery and trials to rehabituation of the skin conductance component of the orienting response; and (b) whether 30 or 50 post-habituation trials would produce a return of the orienting response which could be related In sensitization effects. Results showed that repeated habituations strengthened habituation as reflected in progressively decreasing spontaneous recovery across blocks, but not in speed of habituations. Further, neither 30 nor 50 post-habituation trials produced a return of the orienting response, although 30 such trials did result in increased skin conductance level. Discussion centers on whether habituation beyond asymptotic levels (‘below-zero’) within sessions was unambiguously obtained; relationships among stimulus intensity, frequency, and the return of the orienting response; and factors affecting measures of retention of habituation within sessions.