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Biomedical subjects

T Abel

Publications and source records attributed to T Abel.

At least 37 records · Page 2Linked to original sources

Fear conditioning in inbred mouse strains: an analysis of the time course of memory.

Three mouse strains were examined for short- and long-term memory for Pavlovian fear conditioning measured 1 hr and 24 hr after conditioning. Both DBA/2J and CBA/J mice exhibit reduced long-term memory for contextual fear conditioning compared with C57BL/6J mice. In cued fear conditioning, however, DBA/2J mice show reduced short- and long-term memory compared with C57BL/6J mice, whereas CBA/J mice exhibit reductions only in short-term memory. These results underscore the importance of examining the time course of memory retention, and they suggest that inbred mouse strains may provide a diversity of phenotypes. The results also suggest that the processes of short- and long-term memory storage as well as contextual and cued fear conditioning are dissociable and are mediated by genetically distinct neurobiological mechanisms.

Animals↗

Self reported physical activity, public health, and perceived environment: results from a comparative European study.

STUDY OBJECTIVE: The focus of physical activity promotion is moving from methods for increasing health enhancing physical activity on the individual level to higher level strategies including environmental and policy approaches. Scientific inquiry, traditionally related to individual-based strategies, requires adaptation and refinement when environmental and policy changes become more relevant. The objective of this study is to investigate the significance for behaviour and health of community-based environments that encourage physical activity. DESIGN AND SETTING: The article presents data and results from a cross sectional comparative survey of the general population in six European countries (Belgium, Finland, Germany (East and West), Netherlands, Spain, Switzerland). Specifically, the relation between perceived community-based opportunities for physical activity, self reported physical activity, and self rated health status is investigated. PARTICIPANTS: Representative samples of general populations (adults 18 years or older). Overall response rate: 53.5%. Sample sizes realised: Belgium: n = 389; Finland: n = 400; Germany (East): n = 913; Germany (West): n = 489; Netherlands: n = 366; Spain: n = 380; Switzerland: n =406. MAIN RESULTS: Analyses show that best opportunities are reported by people who are lightly to moderately physically active. People's self rated health is moderately, but significantly associated with both perceived opportunities, and physical activity itself. These predictors interact in that especially for women, the health impact of physical activity is more pronounced in case of good opportunities. CONCLUSIONS: The paper shows the potential of opportunities within residential and community environments with regard to physical activity, both for behaviour and health. Opportunities may enable the population, especially women, to develop an active lifestyle, and thus improve their health. Future studies with objective indicators for physical activity related environments should test the findings that are based on perceptions.

Adolescent↗

Cadaveric fibula, locking plate, and allogeneic bone matrix for anterior cervical fusions after cervical discectomy for radiculopathy or myelopathy.

OBJECT: The authors have previously reported that the results of using cadaveric fibula and locking plate (CF/LP) fusion following anterior cervical discectomy (ACD) for cervical spondylotic radiculopathy and myelopathy are superior to those obtained using autologous iliac crest (AIC) grafts in the short term. The long-term results of using this construct are important in substantiating this improvement. The authors report on 246 consecutive patients (54% smokers) who underwent ACD with CF/LP fusion (175 with allogeneic bone matrix [ABM]) and compare them with 111 consecutive patients in whom AIC fusions (49% smokers) were performed by the same surgeons. METHODS: The study is a retrospective nonrandomized analysis, and chi-square statistics were used. Bone densitometric studies of AIC grafts and CF grafts were performed. A paired t-test was used for statistical analysis of the results. Disease in the group of patients undergoing CF/LP fusion included soft-disc herniation with radiculopathy in 14, soft-disc hemiation with myelopathy in seven, cervical spondylotic radiculopathy in 144, cervical spondylotic myelopathy in 75, AIC graft collapse pseudarthrosis in five, and ACD with no fusion collapse/kyphosis in one. Operations consisted of single-level CF/LP fusion in 142 patients and multilevel CF/LP fusion in 104. Perioperative complications in the CF/LP group included three cases of transient hoarseness. There were no transfusions, infections, neurological injuries, or deaths. The mean hospital length of stay was 1.2 days (28% outpatient and 66% 23-hour stay). The mean follow-up period was 60 months (range 12-94 months). Ten patients were lost to follow up after 1 year. Long-term complications included one traumatic plate fracture and one symptomatic pseudarthrosis with plate fracture. At 1 year and beyond, in 245 (99.6%) of 246 patients radiographically documented fusion with no motion at the fused level on flexion-extension films was demonstrated. There was no kyphosis, no symptomatic screw plate backout, and no CF/LP graft collapse (100% in the ABM group). In the 111 consecutive patients with AIC fusions, however, there was a 17% graft-related complication rate. There were significantly fewer graft-related complications in the CF/LP group (p < 0.001). There was no difference in neurological outcome for any of the groups. In the groups undergoing single-level ACD there was a significantly greater chance of complete relief of neck pain CF/LP fusion compared with those undergoing AIC fusion (p < 0.02). There was a significantly greater chance of AIC collapse with the passage of time compared with CF graft (p < 0.02). Time until return to work was shorter for the CF/LP group by 5 to 6 weeks (p < 0.02). There was a higher rate of radiographically documented pseudarthrosis in the AIC group (p < 0.006). The mean bone densitometry for the CF/LP group was 0.7 g/cm2, significantly greater than that of the AIC group, which was 0.2 g/cm2 (paired t-test p < 0.001). CONCLUSIONS: When fusion is necessary following ACD, the results of CF/LP fusion are significantly superior in the first 5 years after surgery compared with those for AIC fusions. It remains to be determined if demineralized ABM has a significant effect in enhancing fusion.

Adult↗

An immediate-shock freezing deficit with discrete cues: a possible role for unconditioned stimulus processing mechanisms.

Five experiments with C57BL/6 mice (Mus musculus) investigated whether failures in shock processing might contribute to deficits in freezing that occur after an animal receives a shock immediately on exposure to a conditioning context. Experiment 1 found that more contextual freezing resulted from delayed shocks than from immediate shocks across 4 shock intensities. Experiment 2 extended the immediate-shock freezing deficit to discrete stimuli. Experiment 3 found that preexposure to the to-be-conditioned cue did not facilitate immediate cued conditioning. Experiment 4 found that context preexposure enhanced context-evoked fear after an immediate shock. Experiment 5 found that context preexposure also enhanced immediate cued conditioning. These findings are problematic for current theories of the immediate-shock freezing deficit that focus exclusively on processing of the conditioned stimulus, and they suggest that failures in shock processing may contribute to the deficit.

Animals↗

Parallel instabilities of long-term potentiation, place cells, and learning caused by decreased protein kinase A activity.

To further elucidate the links among synaptic plasticity, hippocampal place cells, and spatial memory, place cells were recorded from wild-type mice and transgenic "R(AB)" mice with reduced forebrain protein kinase A (PKA) activity after introduction into a novel environment. Place cells in both strains were similar during the first exposure and were equally stable for recording sessions separated by 1 hr. Place cell stability in wild-type mice was unchanged for sessions separated by 24 hr but was reduced in R(AB) mice over the longer interval. This stability pattern parallels both the reduced late-phase long-term potentiation in hippocampal slices from R(AB) mice and the amnesia for context fear conditioning seen in R(AB) mice 24 but not 1 hr after training. The similar time courses of synaptic, network, and behavioral instability suggest that the genetic reduction of PKA activity is responsible for the defects at each level and support the idea that hippocampal synaptic plasticity is important in spatial memory.

Action Potentials↗

Self-rated health, life satisfaction and personal characteristics of post-menopausal women under estrogen replacement therapy.

OBJECTIVES: To describe the prevalence of oestrogen replacement therapy (ERT)-use among post-menopausal women in relation with personal and socio-economic characteristics and to examine the association of ERT-use with self-rated health and selected aspects of life satisfaction. METHODS: Population survey data were derived from a cohort study of 511 Bernese women, aged 55-65 years. Data were collected by means of telephone interviews. Overall prevalence of ERT-use, and selected associations with personal and socio-economic characteristics were investigated using descriptive statistical methods and logistic regression. The relations of ERT-use with five self-reported health measures were explored using Spearman's correlation coefficients. The associations of ERT-use with six dichotomous variables on satisfaction with various aspects of life were tested with chi-square tests in cross tabulations. RESULTS: The overall prevalence of self reported ERT-use was 17.6%. ERT was more prevalent women younger than 61 years than in women in the older age group. Women with a body mass index (BMI) under 25 reported ERT-use significantly more frequently than women with higher BMI (OR=3.16, CI 1.87-5.34). ERT-use was more prevalent in women with relatively high education: OR=2.01, CI 1.18-4.00. The self-reported health measures and the satisfaction items were not significantly associated with ERT-use. CONCLUSIONS: ERT-use among post-menopausal women was found to be associated with higher educational level and lower BMI. ERT-users did not report better health or life-satisfaction.

Aged↗

Patterns of health-related behaviour and their cross-cultural validity--a comparative study on two populations of young people.

The study aimed at exploring health-related behaviour patterns among young people. The approach was cross-cultural and the study was focused on identifying culturally valid behaviour patterns in two countries, Finland (F) and Switzerland (CH). Data came from two surveys and included 16- and 18-year-old respondents (F: study year 1993, n = 280, CH: study year 1992/3, n = 272). Three intake behaviours--eating, drinking and smoking--were analysed by means of cluster and logistic regression analyses. Three cross-culturally valid behaviour clusters emerged: a healthy, an unhealthy and a mixed pattern where unhealthy eating behaviours were combined with non-smoking and low alcohol use. The determinants of the patterns were tested by comparing the two countries in relation to the socio-demographic characteristics of the young people that belonged in the same cluster. In both countries the structure of the determinants was almost identically indicating high cross-cultural stability. The study suggests that among young people of this age there is clear and cross-culturally consistent patterning of health-related behaviours.

Adolescent↗

Genetic and pharmacological demonstration of differential recruitment of cAMP-dependent protein kinases by synaptic activity.

cAMP-dependent protein kinase (PKA) is believed to play a critical role in the expression of long-lasting forms of hippocampal long-term potentiation (LTP). Can distinct patterns of synaptic activity induce forms of LTP that require different isoforms of PKA? To address this question, we used transgenic mice that have genetically reduced hippocampal PKA activity, and a specific pharmacological inhibitor of PKA, Rp-cAMPS. Transgenic mice [R(AB) mice] that express an inhibitory form of a particular type of regulatory subunit of PKA (type-Ialpha) showed significantly reduced LTP in area CA1 of hippocampal slices as compared with slices from wild-type mice. This impairment of LTP expression was evident when LTP was induced by applying repeated, temporally spaced stimulation (4 1-s bursts of 100-Hz applied once every 5 min). In contrast, LTP induced by applying just 60 pulses in a theta-burst pattern was normal in slices from R(AB) mice as compared with slices from wild-type mice. We found that Rp-cAMPS blocked the expression of LTP induced by both spaced tetra-burst and compressed theta-burst stimulation in hippocampal slices of wild-type and R(AB) mice, respectively. Since Rp-cAMPS is a PKA inhibitor that is not selective for any particular isoform of PKA and these R(AB) mice show reduced hippocampal PKA activity resulting from genetic manipulation of a single isoform of PKA regulatory subunit, our data support the idea that distinct patterns of synaptic activity can produce different forms of LTP that significantly engage different isoforms of PKA. In particular, theta-burst LTP significantly recruits isoforms of PKA containing regulatory subunits other than the mutant RIalpha subunit, whereas tetra-burst LTP requires PKA isoforms containing the mutant RIalpha subunit. Thus, altering both the total amount of imposed synaptic activity and the temporal spacing between bursts of imposed activity may subtly modulate the PKA dependence of hippocampal LTP by engaging distinct isoforms of PKA. In a broader context, our findings suggest that synaptic plasticity in the mammalian brain might be importantly regulated by activity-dependent recruitment of different isoforms of key signal transduction molecules.

Animals↗

Memory suppressor genes: enhancing the relationship between synaptic plasticity and memory storage.

Memory suppressor genes encode proteins that act as inhibitory constraints to impede memory storage. The study of memory suppressor genes is important not only for understanding the link between synaptic plasticity and learning but also for identifying potential targets for future pharmaceuticals to treat memory disorders. This article first reviews the evidence for proteins that impede memory storage from work in invertebrates and then explores recent evidence for the existence of memory suppressor genes in vertebrates in the context of hippocampus-dependent forms of memory. In Aplysia, memory suppressor gene products act at each step in long-term facilitation: in the cytoplasm to regulate kinase activity, in the nucleus to alter the activity of transcriptional regulatory proteins, and on the cell surface to modulate cell-cell interactions. Studies of genetically modified Drosophila have provided behavioral evidence for the existence of memory suppressor genes. One of the best candidates for a neuronal mechanism underlying learning is long-term potentiation (LTP), which has been extensively studied in the mammalian hippocampus. Recent work has identified a number of putative memory suppressor gene products that act in the hippocampus at the levels of LTP induction, regulation of intracellular signaling cascades, and transcriptional control. Using these gene products as tools to study enhancements rather than deficits in LTP and learning may generate more precise information about the relationship between synaptic plasticity and behavioral learning. The study of mammalian memory suppressor genes may provide insights into alleviating the learning and memory deficits that accompany both normal aging and a variety of human disorders.

Animals↗

The Berne-Munich Lifestyle Panel. Background and baseline results from a longitudinal health lifestyle survey.

The Berne-Munich Lifestyle Panel (BMLP) studies health relevant lifestyles among some 2000 adults in Switzerland and Germany. This paper introduces the theoretical background and empirical concept of the BMLP. Sociological theory provided the guidelines for the development of an empirical model that measures structures and dynamics of health lifestyles. Health lifestyles are explained as the product of the complex interplay between health related behaviours, orientations and social resources. Residents of Berne (Switzerland) and Munich (Germany) in the age between 55 and 65 years were contacted in 12 months periods and interviewed by telephone (CATI). The questionnaire comprised some 200 questions on selected aspects of health lifestyles and health status. Interviews were conducted in two waves in Munich (1996 and 1997) and three waves in Berne (1996/97/98). The paper reports findings from baseline data analysis and explores cultural differentiations with respect to the distribution of 1. health relevant behaviours, orientations and social resources, 2. triggers of lifestyle change (life events), 3. mediating factors (Health Locus of Control, Sense of Coherence). Initial results from the search for patterns of health behaviours are also reported. The findings show considerable differences but also impressive similarities in health lifestyle elements across the two samples. There is also preliminary evidence for meaningful patterns of health behaviours in the cohort under investigation. Moreover, the findings clearly demonstrate the need for a gender specific approach in the analysis of cultural differences in health behaviours and lifestyles.

Adult↗

Outcome of 51 cases of unilateral locked cervical facets: interspinous braided cable for lateral mass plate fusion compared with interspinous wire and facet wiring with iliac crest.

OBJECT: To increase knowledge about unilateral facet dislocation, including presentation, radiological findings, management, and outcome, the authors reviewed the cases of 51 consecutive patients with unilateral locked facets of the cervical spine who underwent treatment over an 11-year period. With the development of internal fixation devices, the authors compared the procedure of using interspinous wire and facet wiring of iliac crest to fix unilateral locked facets with that in which interspinous braided cable and lateral mass plates were used. METHODS: Thirty-seven patients (73%) presented with radiculopathy, eight (16%) with neck pain only, and six (12%) with spinal cord injuries (SCIs). Plain x-ray films demonstrated subluxation in only 44 (86%) of 51 cases. All patients underwent cervical computerized tomography (CT) scanning, and in all patients with SCI, a magnetic resonance (MR) image was obtained. Fracture in addition to facet locking was seen on 24 (47%) of 51 CT scans. Disc disruption with cord compression was seen in five cases (10%). Based on CT and/or MR imaging findings, a closed reduction procedure was believed to be contraindicated in 11 cases (22%). Of the remaining 40 patients, 13 (33%) underwent closed reduction procedures. Two patients who underwent a closed reduction procedure were placed in a halo brace but experienced resubluxation. Thus, all cases were surgically treated. Forty-six patients underwent posterior reduction and/or internal fixation alone (in 24 cases spinous process fixation with facet wiring was connected to struts of iliac crest, and in 22 cases interspinous braided cable for lateral mass plating was used). Initial surgery, regardless of technique, was successful in 45 (98%) of 46 cases. One patient experienced a resubluxation and underwent reoperation in which anterior cervical fusion and plating were performed. Four of six patients with SCI underwent an emergency combined anterior-posterior decompressive procedure in which internal fixation was performed, and the patients experienced immediate neurological improvement. Overall there were no cases of neurological worsening or death, and there were three cases of wound infection. At 1 year postsurgery, all deficits had improved. Of 37 cases of radiculopathy, three patients (8%) experienced persistent 4/5 weakness, and the remaining patients were normal, including four patients in whom diagnosis was delayed. The six patients with SCI all improved significantly by 1 year. Persistent neck pain was seen in nine cases (18%). Although the lateral mass plates and interspinous cable are stronger, easier to place, and significantly lessened the amount of resultant kyphosis (p < 0.02), the results of chi-square analysis demonstrated only a slight trend for improved clinical outcome compared with the use of wire and iliac crest (p = 0.1). CONCLUSIONS: Cervical CT and MR imaging provide information that aids in the diagnosis and management of patients with unilateral locked facets of the cervical spine. The authors' experience strongly suggests that a reduction procedure in which internal fixation and bone fusion are performed will be the most successful treatment for this injury.

Adult↗

Memory suppressor genes: inhibitory constraints on the storage of long-term memory.

Synaptic plasticity, the ability of neurons to alter the strength of their synaptic connections with activity and experience, is thought to play a critical role in memory storage. Molecular studies of gene expression during long-lasting synaptic plasticity related to memory storage initially focused on the identification of positive regulators. More recent work has revealed that the establishment of long-lasting synaptic plasticity and long-term memory also requires the removal of inhibitory constraints. By analogy to tumor suppressor genes, which restrain cell proliferation, we propose that these inhibitory constraints of memory storage, which restrain synapse growth, be termed memory suppressor genes.

Activating Transcription Factor 2↗

Positive and negative regulatory mechanisms that mediate long-term memory storage.

The protein kinase A pathway and the cyclic AMP-response element binding protein (CREB) appear to play a critical role in the consolidation of short-term changes in neuronal activity into long-term memory storage in a variety of systems ranging from the gill and siphon withdrawal reflex in Aplysia to olfactory conditioning in Drosophila to spatial and contextual learning in mice. In this review we describe the molecular machinery that mediates memory consolidation in each of these systems. One of the surprising findings to emerge, particularly from studies of long-term facilitation in Aplysia, is that memory storage is mediated by not only positive but also negative regulatory mechanisms, in much the same way as cell division is controlled by the proteins encoded by oncogenes and tumor suppressor genes. This suggests the interesting possibility that there are memory suppressor genes whose protein products impede memory storage.

Animals↗

Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory.

To explore the role of protein kinase A (PKA) in the late phase of long-term potentiation (L-LTP) and memory, we generated transgenic mice that express R(AB), an inhibitory form of the regulatory subunit of PKA, only in the hippocampus and other forebrain regions by using the promoter from the gene encoding Ca2+/ calmodulin protein kinase IIalpha. In these R(AB) transgenic mice, hippocampal PKA activity was reduced, and L-LTP was significantly decreased in area CA1, without affecting basal synaptic transmission or the early phase of LTP. Moreover, the L-LTP deficit was paralleled by behavioral deficits in spatial memory and in long-term but not short-term memory for contextual fear conditioning. These deficits in long-term memory were similar to those produced by protein synthesis inhibition. Thus, PKA plays a critical role in the consolidation of long-term memory.

Amygdala↗

Risk equalization, competition, and choice: a preliminary assessment of the 1993 German health reforms.

Risk adjustment and/or equalization has become a central issue in the health care reform initiatives of many countries, including Germany, Switzerland, the Netherlands, Israel, the U.K. and the U.S. Risk adjustment is widely seen as essential to prevent cream skimming and to promote fair competition. In this vein, the 1993 German health reforms require implementation of a risk-based contribution rate equalization scheme by 1996. This paper provides a preliminary assessment of the risk equalization methodology currently proposed for Germany. Recent research in the U.S. and the Netherlands is used to examine whether the sociodemographic factors being used in Germany are likely to be effective. Research findings from both countries indicate that risk formulas based only on socio-demographic factors predict only one-tenth to one-fourth of the maximum possible explainable variance. If the current formula is used, sickness funds with higher concentrations of high risk groups are likely to be substantially under compensated, and to face serious enrollment and financial problems. The authors conclude that improvements in the formula through measures based on diagnosis and prior hospitalization, disability status, and regional variations in utilization and cost are urgently needed before the system is implemented. The German experience is also relevant to other countries that have relied to date on socio-demographic measures for risk adjustment.

Financing, Organized↗