Wernicke's encephalopathy in an autopsy material obtained over a one-year period

In a material comprising 279 consecutive autopsies obtained over a one-year period there were four cases of Wernicke's encephalopathy (WE), of which three were inactive (chronic) and one was active (acute). The latter was not related to chronic alcoholism. Our findings show that WE may be regularly present in a routine autopsy series. In only one case was WE suspected clinically and none of the cases revealed macroscopic brain changes indicative of WE. We therefore suggest that sections of the mammillary bodies should be taken routinely to detect all possible cases of WE.     

Utilisation of health services over a one-year period by an adolescent population with Down syndrome

The utilisation of health services during a one-year period by an adolescent population with Down Syndrome (DS) was surveyed and compared to controls of the same age-group and same geographical area. The probands comprised 28 males (65%) and 15 females (35%). The controls comprised 22 males (40%) and 33 females (60%). Mean age: 17.6 years for probands and 17.4 years for controls. Day of census, 31 December 1985. Chronic diseases or conditions were found to be significantly more frequent among probands than among controls. Controls visited their general practitioner significantly more frequently than the probands, who utilised the services of practising specialists significantly more frequently than controls. DS individuals received significantly more dental care than did controls. Altogether, probands utilise the secondary health services more frequently than controls. The question of sufficient secondary health services for DS-adolescents is discussed, but no conclusion can be drawn from the results of the present study.     

Utilisation of health services over a one-year period by an adult population with Down syndrome

The utilisation of health services over a one-year period by an adult population of 38 probands with Down Syndrome (DS) (23 males 60.5% and 15 females 39.5%) in the Danish County of Aarhus (CA) was surveyed. All patients were born between 1 January 1934 and 31 December 1943, mean age 45.7 years. Prevalence: 0.056% on day of census: 31 December 1984. Several additional diseases and handicaps were found, including four patients with seizures, three with endocrine dysfunctions, three with eye diseases and three with hearing disorders. This is in accordance with other papers, revealing such disorders among DS-probands. On the average, each patient sees his or her regular doctor six times a year. Various specialists are seen in private practice and out-patient clinics. The use of bed-days by the 38 probands is significantly higher than the non-DS-patients of the county, also with special conditions taken into consideration. Twenty-four patients (63%) received dental care during 1984. Patients living in an institution with its own dental clinic do not see a dentist more often than patients getting their dental care from dentists in private practice. It is concluded that the present study states minimum figures and that adults with DS utilise health services more frequently than the background population. This is due to the findings of many additional diseases and handicaps among this aging group.     

The temporal stability of electrodermal variables over a one-year period in patients with recent-onset schizophrenia and in normal subjects

Test-retest stability of electrodermal (EDA) variables indexing both general autonomic arousal (e.g., skin conductance level, number of nonspecific skin conductance responses) and attention to external stimuli (e.g., number of skin conductance orienting responses, electrodermal responder/nonresponder status) was assessed in 71 young, recent-onset schizophrenia patients and 36 demographically matched normal subjects. Significant stability over a 1-year period was found for both patients and normal subjects for most EDA variables and for responder/nonresponder status, with test-retest correlations generally being higher for normal subjects. The lower reliability for patients was not attributable to symptomatic fluctuations during the follow-up period and may reflect poorer arousal regulation among the patients. Among measures of responding to nontask stimuli, a simple count of the number of orienting responses occurring was more stable than was a traditional trials-to-habituation measure.     

Psychophysiological response specificities: a replication over a 12-month period

A sample of 58 students was subjected to four stress conditions (mental arithmetic, reaction time, free speech, cold-pressor test). Eight physiological variables (skin conductance, heart rate, pulse amplitude, Heather index, eye blinking, horizontal eye movements, respiration rate, blood pressure) and five psychological variables (self-rated anger, irritability, tenseness, motivation, indifference) were monitored. Proportions of variance in a three-factor ANOVA (subjects, situations, variables) accounted for by individual specific response patterns (ISR) amounted to 33-40% for physiological and 9-13% for psychological variables. Stimulus specific response patterns (SSR) accounted for 11-19% for physiological and 8-14% for psychological variables, and motivation specific response patterns (MSR) for 17% for physiological and 14-16% for psychological variables. About one-fourth of the subjects showed a rather stable ISR in physiological variables when tested again after two months, and about 14% when tested again after twelve months. Overall, the results replicated earlier findings from this laboratory.     

The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response

An essential part of the cellular response to environmental stress is a reversible translational suppression, taking place in dynamic cytoplasmic structures called stress granules (SGs). We discovered that HDAC6, a cytoplasmic deacetylase that acts on tubulin and HSP90 and also binds ubiquitinated proteins with high affinity, is a novel critical SG component. We found that HDAC6 interacts with another SG protein, G3BP (Ras-GTPase-activating protein SH3 domain-binding protein 1), and localizes to SGs under all stress conditions tested. We show that pharmacological inhibition or genetic ablation of HDAC6 abolishes SG formation. Intriguingly, we found that the ubiquitin-binding domain of HDAC6 is essential and that SGs are strongly positive for ubiquitin. Moreover, disruption of microtubule arrays or impairment of motor proteins also prevents formation of SGs. These findings identify HDAC6 as a central component of the stress response, and suggest that it coordinates the formation of SGs by mediating the motor-protein-driven movement of individual SG components along microtubules.     

Benefit of endurance training in elderly people over a short period is reversible

 The present study assessed daily activity, physical capacity and body composition in 11 initially sedentary healthy subjects [5 men and 6 women, mean age 62.8 (SD 2.7) years] before training (T_o), after completion of 7 (T_7w) and 14 (T_14w) weeks of training, and again 6 (T_6m) and 12 (T_12m) months after training. The mean daily activity index decreased from T_7w to T_12m reaching a lower level than at T_o [T_12m − T_o = −1.5 (SD 4.6) units, P = 0.18]. Mean maximal oxygen uptake (V˙O_2max) and its corresponding mean power output (W˙ _max) were increased by 12.5 (SD 6.6)% (P = 0.003) and 22.8 (SD 12.8)% (P = 0.003), respectively, at T_14w, and returned to their T_o levels within 1 year. Mean body mass (m _b) remained stable until T_6m but increased significantly by 2.6 (SD 3.7)% from T_6m to T_12m (P < 0.05). Mean fat mass (m _f, from bioelectrical impedance analysis measurements) tended to decrease [−2.0 (SD 4.2)%, P = 0.10] during the training period but increased by 7.8 (SD 10.9)% between T_6m and T_12m (P < 0.05). The mean fat free mass did not vary during the study period (P = 0.81) but magnetic resonance imaging (MRI) showed that mean thigh muscle volume decreased between T_7w and T_12m to less than at T_o [T_12m − T_o = −2.3 (SD 3.6)%, P = 0.05]. Therefore, this study confirmed the favourable effects of endurance training on the physical capacity and body composition of elderly people, but demonstrated that the training programme would have to be continued to maintain the training-related benefits (i.e. increased V˙O_2max and W˙ _max) which would otherwise be lost within 1 year. After training, m _b and m _f were found to be increased. Furthermore, a fast and reproducible MRI protocol was validated for study of small intra-individual variations in tissue volumes in longitudinal studies. Accepted: 7 September 1999     

The measurement of plasma catecholamine and lactate thresholds: a comparison of methods

Plasma lactate and catecholamine thresholds were calculated using three different variations of linear regression, an algorithmic linear regression method, a log-log transformation method and a semi-log method. A group of 18 male sports science students undertook an incremental test to exhaustion on a cycle ergometer. A 5-ml blood sample was drawn at rest, after 4 min of exercise and every 2 min thereafter until the cessation of the test. Lactate, adrenaline and noradrenaline concentrations were measured. Lactate threshold (Th_la), adrenaline threshold (Th_A) and noradrenaline threshold (Th_NA) were calculated using each of the three methods. The best fits of the methods were examined by comparing their standard error of estimates (SEEs). The algorithmic method demonstrated a higher SEE than the other two methods, but only for Th_la and Th_NA. The power output for which each method calculated the thresholds demonstrated a main effect for method. Tukey post hoc tests showed that the algorithmic method produced significantly higher outputs than the other two methods, which did not differ significantly from one another. Comparison of these power outputs showed that Th_la and Th_A differed significantly, regardless of method, there were no other significant differences. Plasma concentrations of lactate, adrenaline and noradrenaline showed that the values of Th_la and Th_NA calculated by the algorithmic method were significantly higher than those calculated using the other two methods, which did not differ significantly from one another. The only significant difference for Th_A was between the algorithmic and semi-log methods. Correlations between the power outputs at which each method calculated the thresholds varied greatly between methods, and were at best only moderate (r=0.63). It was concluded that the algorithmic method was less powerful than the other two methods, and that Th_la, Th_A and Th_NA are not highly correlated. Accepted: 15 March 2000     

Monitoring exercise stress by changes in metabolic and hormonal responses over a 24-h period

Summary Metabolic and endocrine responses of 14 subjects of varying levels of fitness to an intensive anaerobic interval training session were assessed before exercise and at 2 h, 4 h, 8 h and 24 h postexercise. The endocrine response of the same subjects to a control day, where they were required not to exercise, was also assessed and compared with the values obtained on the interval training day. Uric acid, urea, and creatine phosphokinase concentrations still remained elevated above pre-exercise values 24 h postexercise. Lactate, creatinine, testosterone and cortisol concentrations were significantly elevated above pre-exercise values immediately postexercise but these had reversed by 2 h postexercise. Over the remainder of the recovery period testosterone concentrations remained significantly lower than values measured at similar times on the control day. This was shown to be due directly to a change in testosterone as sex hormone binding globulin concentration remained constant throughout the recovery period. The data indicate that when comparisons of data were made to control (rest) days, imbalances in homeostasis, due to intensive training, are not totally reversed within the next 24-h. The data also demonstrate that the parameters measured undergo the same variations in subjects with a wide range of physical fitness, indicating that these parameters could be used to monitor exercise stress and recovery in athletes of a wide range of abilities. The more acute responses to exercise could be mistaken for overtraining if insufficient recovery time were not permitted between the final exercise session and taking blood samples, further emphasising the need to be able to recognise the difference between the fatigue associated with acute exercise and a state of chronic fatigue that may result from too little regeneration time within the training programme.     

The Batten disease gene CLN3 is required for the response to oxidative stress

Mutations in the CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early onset neurodegenerative disorder. JNCL is the most common of the NCLs, a group of disorders with infant or childhood onset that are caused by single gene mutations. The NCLs, although relatively rare, share many pathological and clinical similarities with the more common late-onset neurodegenerative disorders, while their simple genetic basis makes them an excellent paradigm. The early onset and rapid disease progression in the NCLs suggests that one or more key cellular processes are severely compromised. To identify the functional pathways compromised in JNCL, we have performed a gain-of-function modifier screen in Drosophila. We find that CLN3 interacts genetically with the core stress signalling pathways and components of stress granules, suggesting a function in stress responses. In support of this, we find that Drosophila lacking CLN3 function are hypersensitive to oxidative stress yet they respond normally to other physiological stresses. Overexpression of CLN3 is sufficient to confer increased resistance to oxidative stress. We find that CLN3 mutant flies perceive conditions of increased oxidative stress correctly but are unable to detoxify reactive oxygen species, suggesting that their ability to respond is compromised. Together, our data suggest that the lack of CLN3 function leads to a failure to manage the response to oxidative stress and this may be the key deficit in JNCL that leads to neuronal degeneration.     

The metabolic dynamics of cartilage explants over a long-term culture period

INTRODUCTION:

Although previous studies have been performed on cartilage explant cultures, the generalized dynamics of cartilage metabolism after extraction from the host are still poorly understood due to differences in the experimental setups across studies, which in turn prevent building a complete picture.

METHODS:

In this study, we investigated the response of cartilage to the trauma sustained during extraction and determined the time needed for the cartilage to stabilize. Explants were extracted aseptically from bovine metacarpal-phalangeal joints and cultured for up to 17 days.

RESULTS:

The cell viability, cell number, proteoglycan content, and collagen content of the harvested explants were analyzed at 0, 2, 10, and 17 days after explantation. A high percentage of the cartilage explants were found to be viable. The cell density initially increased significantly but stabilized after two days. The proteoglycan content decreased gradually over time, but it did not decrease to a significant level due to leakage through the distorted peripheral collagen network and into the bathing medium. The collagen content remained stable for most of the culture period until it dropped abruptly on day 17.

CONCLUSION:

Overall, the tested cartilage explants were sustainable over long-term culture. They were most stable from day 2 to day 10. The degradation of the collagen on day 17 did not reach diseased levels, but it indicated the potential of the cultures to develop into degenerated cartilage. These findings have implications for the application of cartilage explants in pathophysiological fields.     

The free-run period is not the best Zeitgeber period for the house mouse

Two light cycles were presented simultaneously to house mice. One cycle had a period of 23.7 hr, the free-run period of the activity cycle in constant darkness, and the other a period of 24.0 hr. The activity cycles of all 31 subjects synchronized temporarily with the 24.0 hr light cycle. In contrast, only 10 mice also showed temporary synchronization with the 23.7 hr light cycle and only 2 of these spent more time synchronized with the 23.7 than the 24.0 hr light cycle. The results suggest that a relaxation oscillator is not an adequate model of the mouse circadian activity cycle. The results may have practical significance for the design of human temporal environments.     

The stress response: a new perspective.

A theory of the response to chronic intermittent stress, intergating many diverse studies, is presented. Chronic intermittent stress is presumed to be the type of stress most frequently encountered and most likely to cause physiological changes which predispose an organism to tissue damage. The theory states that all organisms are genetically predisposed to adapt to stress and that the physiological pattern of adaptation is similar across species. This pattern consists of a conditioned endocrine response before the stressor is presented accompanied by a decrease in arousal during the stress. These changes occur because the organism is predisposed to learn cues predictive of stress and to assess the threat potential of the stressor. This pattern is adaptive because it conserves resources and promotes homeostasis. Maladaptation is discussed in terms of failure to learn situational expectancies and appropriate responses. Implications of this theoretical perspective are examined.     

ZRANB3 is a structure-specific ATP-dependent endonuclease involved in replication stress response

To efficiently duplicate their genomic content, cells must overcome DNA lesions that interfere with processive DNA replication. These lesions may be removed and repaired, rather than just tolerated, to allow continuity of DNA replication on an undamaged DNA template. However, it is unclear how this is achieved at a molecular level. Here we identify a new replication-associated factor, ZRANB3 (zinc finger, RAN-binding domain containing 3), and propose its role in the repair of replication-blocking lesions. ZRANB3 has a unique structure-specific endonuclease activity, which is coupled to ATP hydrolysis. It cleaves branched DNA structures with unusual polarity, generating an accessible 3'-OH group in the template of the leading strand. Furthermore, ZRANB3 localizes to DNA replication sites and interacts with the components of the replication machinery. It is recruited to damaged replication forks via multiple mechanisms, which involve interactions with PCNA, K63-polyubiquitin chains, and branched DNA structures. Collectively, our data support a role for ZRANB3 in the replication stress response and suggest new insights into how DNA repair is coordinated with DNA replication to maintain genome stability.     

The stability of the Parental Bonding Instrument over a 20-year period

BACKGROUND: The Parental Bonding Instrument (PBI) measures the perception of being parented to the age of 16 years. Low scores on the care dimension and high scores on the overprotection dimension are considered to be risk factors of depression. While the PBI has been shown to be a reliable and valid instrument, the stability of the PBI over extended periods (taking into account individual characteristics and life experience) needs to be demonstrated. METHOD: The PBI was measured in a non-clinical cohort on four waves between 1978 and 1998, along with a series of self-report measures including state depression and neuroticism. Differences in PBI change over time were examined by gender, lifetime major depression diagnosis, and life event variables, as well as by scores on neuroticism and state depression. RESULTS: Acceptable retest coefficients on PBI scores over the 20-year study were found for the cohort. No differences were found in PBI scores over time on the variables examined, including sex and depression measures. CONCLUSIONS:The results indicate long-term stability of the PBI over time. The influences of mood state and life experience appear to have little effect on the stability of the perception of parenting as measured by the PBI. The present study increases confidence in the PBI as a valid measure of perceived parenting over extended time periods.