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PubMed2004

123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia.

RATIONALE: The dopamine hypothesis for schizophrenia postulates overactivity of dopamine transmission in the basal ganglia. Most effective antipsychotic drugs block postsynaptic dopamine receptors, but in-vivo imaging studies have not been able to show changes in these receptors in drug-naive schizophrenics. OBJECTIVES: The presynaptic dopamine transporter (DAT) is thought to be an important regulator of synaptic dopamine concentration. We have used SPECT with (123)I-beta-CIT, which has a high affinity for DAT, in order to further examine the dopamine hypothesis for schizophrenia. METHODS: Six patients with chronic schizophrenia treated with classic dopamine D(2)-receptor blocking neuroleptics were investigated. The number of DAT binding sites in the basal ganglia was calculated and compared with five healthy volunteers and ten parkinsonian patients. RESULTS: The schizophrenic patients showed a 36-63% increase in DAT binding sites compared with the volunteers, whereas the parkinsonian patients showed a 57-96% decrease. The differences between the groups were highly significant (even after correction for different age composition within the groups). CONCLUSIONS: There was an increased number of DAT binding sites in the schizophrenic patients treated with dopamine D(2)-receptor blocking neuroleptics. This fits well with several recent reports that have shown increased volumes of basal ganglia in this patient category. It thus appears that there is an increased number of presynaptic dopamine releasing nerve terminals in the basal ganglia, possibly as a biological adaptation to counteract the postsynaptic dopamine D(2)-receptor blockade.

Adult↗
PubMed2000

Hormonal responses to whole-body vibration in men.

The aim of this study was to evaluate the acute responses of blood hormone concentrations and neuromuscular performance following whole-body vibration (WBV) treatment. Fourteen male subjects [mean (SD) age 25 (4.6) years] were exposed to vertical sinusoidal WBV, 10 times for 60 s, with 60 s rest between the vibration sets (a rest period lasting 6 min was allowed after 5 vibration sets). Neuromuscular performance tests consisting of counter-movement jumps and maximal dynamic leg presses on a slide machine, performed with an extra load of 160% of the subjects body mass, and with both legs were administered before and immediately after the WBV treatment. The average velocity, acceleration, average force, and power were calculated and the root mean square electromyogram (EMGrms) were recorded from the vastus lateralis and rectus femoris muscles simultaneously during the leg-press measurement. Blood samples were also collected, and plasma concentrations of testosterone (T), growth hormone (GH) and cortisol (C) were measured. The results showed a significant increase in the plasma concentration of T and GH, whereas C levels decreased. An increase in the mechanical power output of the leg extensor muscles was observed together with a reduction in EMGrms activity. Neuromuscular efficiency improved, as indicated by the decrease in the ratio between EMGrms and power. Jumping performance, which was measured using the counter-movement jump test, was also enhanced. Thus, it can be argued that the biological mechanism produced by vibration is similar to the effect produced by explosive power training (jumping and bouncing). The enhancement of explosive power could have been induced by an increase in the synchronisation activity of the motor units, and/or improved co-ordination of the synergistic muscles and increased inhibition of the antagonists. These results suggest that WBV treatment leads to acute responses of hormonal profile and neuromuscular performance. It is therefore likely that the effect of WBV treatment elicited a biological adaptation that is connected to a neural potentiation effect, similar to those reported to occur following resistance and explosive power training. In conclusion, it is suggested that WBV influences proprioceptive feedback mechanisms and specific neural components, leading to an improvement of neuromuscular performance. Moreover, since the hormonal responses, characterised by an increase in T and GH concentration and a decrease in C concentration, and the increase in neuromuscular effectiveness were simultaneous but independent, it is speculated that the two phenomena might have common underlying mechanisms.

Adult↗
PubMed2000

Molecular analysis of alpha-thalassemia in Nepal: correlation with malaria endemicity.

Thalassemia is a prevalent hereditary disorder characterized by impaired synthesis of globin chains. It has been suggested that the high frequency of thalassemia might reflect heterozygote advantage due to reduced susceptibility to malaria. In Nepal, malaria has often occurred in places below the altitude of 1,200m. We carried out a microepidemiological study on thalassemia in two neighboring populations in Nepal, the Danuwar and the Tamang. Settlements of the Danuwar are located below the limit of the malarial zone (1,200m in altitude), whereas those of the Tamang are found in malaria-free uplands. Three heterozygotes for hemoglobin E (HbE) were observed in the Danuwars. We detected one type (-alpha3.71) of alpha+-thalassemia that involves a deletion of 3.7kb, leading to a loss of one of two alpha-globin genes, in the Danuwars, at a high gene frequency of 63%, while the gene frequency in the Tamangs was only 5%. Analysis of the alpha-globin gene cluster revealed that four different haplotypes were associated with the type of alpha+-thalassemia in the Danuwars. Nucleotide sequences of the D-loop region in the mitochondrial DNA of the two populations indicated a similar nucleotide diversity in each population. The fixation index, FST, representing the degree of genetic differentiation estimated from mitochondrial DNA diversities (FST, 0.05), was smaller than that obtained from the gene frequencies of alpha-thalassemia (FST, 0.55). If we assume neutral molecular evolution in the D-loop region of mitochondrial DNA, these results suggest that the high frequency of alpha+-thalassemia may be due to biological adaptation to the malarial environment rather than to events such as a bottleneck.

DNA, Mitochondrial↗
PubMed2006

Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival.

Peripheral benzodiazepine receptors (PBR) are widely distributed in peripheral tissues, astrocytes, and microglia of the brain. They are involved in apoptosis, proliferation, and many other processes, such as steroidogenesis in adrenal glands, male and female gonads, biological adaptation to stress, etc. It has been established that the expression of PBR in astrocytomas is higher than in the normal brain. The goal of this study was to explore the correlation of the immunohistochemical expression of PBR in astrocytomas with the grade of malignancy and rates of apoptosis, proliferation and survival. In 130 cases of astrocytomas (25 grade I, 25 grade II, 20 grade III, 60 grade IV), paraffin sections were stained immunohistochemically for PBR and MIB-1(Ki-67). TUNEL assay was used for evaluation of apoptosis. It was found that the intensity and extent of staining for PBR had a strong direct correlation with the grade of malignancy of the tumor, along with proliferative and apoptotic indices. The highest expression of PBR was in glioblastomas grade IV, especially around areas of necrosis. There was a strong negative correlation between PBR expression and survival. The results of this study may be applied in the pathological diagnosis of astrocytomas as an additional clue in establishing tumor grade; they may be used in the imaging of astrocytomas, both for diagnosis and follow-up, by the application of positron emission tomography scanning with PBR specific ligands. Targeting of PBR in high-grade gliomas may be a promising approach, achieving more specific anti-tumor effect.

Analysis of Variance↗
PubMed1999

Recent advances in the biology of addiction.

Recent research into the biologic basis of drug addiction continues to offer considerable promise for understanding how neurochemistry, pharmacology, and molecular biology relate to the reinforcing effects of abused drugs. One area of research is the development and pharmacologic and neurochemical characterization of cocaine and opiate polydrug abuse, a growing subset of the drug abuse population. Considerable advances have also been made in understanding how chronic and persistent drug use induces biochemical and molecular biologic adaptations in brain regions related to drug reinforcement.

Animals↗
PubMed1988

Deviations in brain development of F2 generation on caloric undernutrition and scope of their prevention by rehabilitation: alterations in dendritic spine production and pruning of pyramidal neurons of lower laminae of motor cortex and visual cortex.

This is a report of comparison of developmental changes of spine densities on the different categories of dendrites of neocortical pyramidal neurons (V and VI layers of motor and visual areas) of Wistar rat, during 11-150 days of age, under conditions of normal nutrition and under chronic caloric but not protein deprivation. The studied animals were of F2 generation born to parents undernourished to a degree that their weights were only 40-50% of normal control. At such a level they would be active, reproduce, and not morbid. Similar level of undernutrition also continued in the F2 group studied. A group of undernourished animals was also, for rehabilitation, put on normal diet from 21 days of age. Visual and motor cortical area pieces were impregnated by Stensaas' rapid Golgi method. Spines were counted on successive 20-micron segments (I-IV) of both apical and basal dendritic main shafts as well as primary and secondary branches. The spine count per segment (density) in the normal population reached exuberant values by 26-50 days of age and later underwent a progressive decline or pruning by 30-50% or more by 150 days of age. The degrees of exuberance and pruning varied in different categories of dendrites, generally being more conspicuous in motor than visual cortex, and more in basal than apical dendrites. Under the conditions of chronic caloric restriction, the phenomenon of exuberance was retarded and pruning was not observed. On the contrary, there was a progressive increase in the spine densities on both basal and apical dendrites, in motor and visual cortex. By 150 days of age, the spine densities were not only greater than the final counts for respective segments in the normal animal, but even greater than the exuberant counts. Postweaning caloric rehabilitation had only a modest impact against this deviation. Preliminary data (intersections) of dendritic branching also indicated a similar pattern of changes (lag followed by increase), but of a lesser degree. These alterations in neuronal development are interpreted as biological adaptations evoked in shaping the homeostasis of the organism's brain and behaviour by factors of nurture.

Aging↗
PubMed1986

Polychlorinated biphenyls in the electrical machinery industry: an ethnological study of community action and corporate responsibility.

Environmental and occupational health problems cannot be understood through purely medical and epidemiological analyses, the social forces affecting biologically adaptive behavior must also be analyzed. Research on the political economy of health needs to generate an ethnology of community action relevant to the analyses of corporate structures for which it is best known. In studying the community of Pittsfield, Mass., where a General Electric plant is located, we encountered environmental and occupational health problems in just this context. This essay is, therefore, an effort to extend the political economy of health into the ethnological domain of community research.

Community Participation↗
PubMed1988

Photoimmunology: the mechanisms involved in immune modulation by UV radiation.

Ultraviolet radiation (UVR) may be the most prevalent agent that man encounters in his environment. As a result, certain biological adaptations take advantage of the beneficial effects of UVR exposure, e.g. the photoactivation steps involved in vitamin D metabolism. In this regard, UVR plays an important role in maintaining our good health; however, it must be noted that UVR is potentially the most harmful naturally occurring agent in our environment. Thus, it appears that several mechanisms have evolved to protect us against the detrimental effects of UVR overexposure. Although epidermal melaninization or "tanning" may be the most obvious example of these processes, we would argue that adoptive mechanisms within the immune system also provide protection against UVR-induced skin damage. It is now known that UVR affects the distribution and functional activities of various immunocompetent cells within the skin, as well as modifying the production of inflammatory and hematopoietically active cytokines. This review will focus on the known mechanisms involved in the immune modulatory effects of UVR and how adoptive immune responses to UVR-induced skin damage contribute to specific pathological processes.

Immune System↗
PubMed2004

[Monitoring of heparin therapy during extracorporeal bypass: what are the remaining questions?].

Cardiac surgery with extracorporeal circulation induces major alterations of haemostasis and requires high level of anticoagulation, usually achieved by unfractionated heparin infusion. Optimization of anticoagulant regimen, through adapted biological monitoring, can probably improve postoperative course, at least for postoperative haemostatic status. Despite increasing knowledge on extracorporeal circulation-induced haemostatic abnormalities and the development of new biological devices for heparin monitoring, the optimal level of anticoagulation remains matter of debate, as well as the monitoring procedures. This critical review presents the current available data on heparin anticoagulation and monitoring in this specific context, and underlines the pending issues about anticoagulation management during extracorporeal bypass.

Anticoagulants↗
PubMed2005

Criteria for consciousness in humans and other mammals.

The standard behavioral index for human consciousness is the ability to report events with accuracy. While this method is routinely used for scientific and medical applications in humans, it is not easy to generalize to other species. Brain evidence may lend itself more easily to comparative testing. Human consciousness involves widespread, relatively fast low-amplitude interactions in the thalamocortical core of the brain, driven by current tasks and conditions. These features have also been found in other mammals, which suggests that consciousness is a major biological adaptation in mammals. We suggest more than a dozen additional properties of human consciousness that may be used to test comparative predictions. Such homologies are necessarily more remote in non-mammals, which do not share the thalamocortical complex. However, as we learn more we may be able to make "deeper" predictions that apply to some birds, reptiles, large-brained invertebrates, and perhaps other species.

Adaptation, Physiological↗
PubMed2006

On modeling and simulating transitions between microbial growth and inactivation or vice versa.

Resumed growth of the survivors of a heat or chemical treatment after cooling or a disinfectant dissipation is not an uncommon phenomenon. Similarly, the inverse, the onset of mortality in a growing microbial population as a result of exposure to increasing temperature or concentration of an antimicrobial agent, is also a familiar scenario. Provided that in either regime, the organism has no time to adapt biologically, the continuous transition from growth to inactivation or vice versa can be simulated with conventional growth and inactivation models, whose rate constant is allowed to change sign. Where both the growth and inactivation follow first-order kinetics, the sign change has no effect on the model equation's solutions. The same applies when the growth and inactivation patterns are described by a rate model, like the differential logistic equation or its various variants. However, determination of such models' coefficients from experimental isothermal growth and inactivation data can be difficult for technical reasons, unless the model can be integrated analytically. If not, or when the model itself is unknown a priori, then the rate equation would have to be derived from the fit of empirical models like the Weibull, modified versions of the logistic function and the like. But this may create a new kind of problem as a result of that the log and certain power operations cannot be used for negative numbers. For certain models at least, the problem can be solved through modification of the procedure by which the rate equation is solved numerically. This is demonstrated in simulated transitions between growth and inactivation and between inactivation and growth based on the log linear and Weibullian-power law models and three logistic patterns based on a shifted logistic function, the Baranyi-Roberts model and a shifted arctan model.

Bacteria↗
PubMed2005

Treatment of mandibular condylar process fractures: biological considerations.

The topic of condylar injury in adults has generated more discussion and controversy than any other in the field of maxillofacial trauma. It is an important subject because such injuries are common and complications of trauma to the temporomandibular joint (TMJ) are far-reaching in their effects. Why are there so many different methods to treat this injury? How can seemingly disparate treatment options all produce satisfactory outcomes in the majority of patients? The reason lies with the biological adaptations that occur within the masticatory system that are poorly understood, not readily quantifiable, and variable from one person to the next. This discussion presents our current understanding of the adaptations that must occur to provide the patient with a satisfactory outcome. The adaptations for patients treated open are different than for those treated closed. However, it is when these adaptations fail to occur that unsatisfactory outcomes occur, regardless of how they were treated.

Adaptation, Physiological↗
PubMed2005

Metabolic depression in hibernation and major depression: an explanatory theory and an animal model of depression.

Metabolic depression, an adaptive biological process for energy preservation, is responsible for torpor, hibernation and estivation. We propose that a form of metabolic depression, and not mitochondrial dysfunction, is the process underlying the observed hypometabolism, state-dependent neurobiological changes and vegetative symptoms of major depression in humans. The process of metabolic depression is reactivated via differential gene expression in response to perceived adverse stimuli in predisposed persons. Behavior inhibition by temperament, anxiety disorders, genetic vulnerabilities, and early traumatic experiences predispose persons to depression. The proposed theory is supported by similarities in the presentation and neurobiology of hibernation in bears and major depression and explains the yet unexplained neurobiological changes of depression. Although, gene expression is suppressed in other hibernators by deep hypothermia, bears were chosen because they hibernate with mild hypothermia. Pre-hibernation in bears and major depression with atypical features are both characterized by fat storage through overeating, oversleeping, and decreased mobility. Hibernation in bears and major depression with melancholic features are characterized by withdrawal from the environment, lack of energy, loss of weight from not eating and burning stored fat, changes in sleep pattern, and the following similar neurobiological findings: reversible subclinical hypothyroidism; increased concentration of serum cortisol; acute phase protein response; low respiratory quotient; oxidative stress response; decreased neurotransmitter levels; and changes in cyclic-adenosine monophosphate-binding activity. Signaling systems associated with protein phosphorylation, transcription factors, and gene expression are responsible for the metabolic depression process during pre-hibernation and hibernation. Antidepressants and mood stabilizers interfere with the hibernation process and produce their therapeutic effects by normalizing the fluctuation of activities in the different signaling systems, which are down-regulated during hibernation and depression and up-regulated during exodus from hibernation and the hypomanic or manic phase of mood disorders. The ways individuals cognitively perceive, understand, communicate, and react to the vegetative symptoms of depression, from downregulation in energy production, and in the absence of known medical causes, produce the other characteristics of depression including guilt, helplessness, hopelessness, suicidal phenomena, agitation, panic attacks, psychotic symptoms, and sudden switch to hypomanic or manic episodes. The presence of one or more of these characteristics depends on the person's neuropsychological function, its social status between the others, and the other's response to the person. Neurobiological changes associated with metabolic depression during entrance, maintenance, and exodus from hibernation in bears is suggested as a natural animal model of human depression and mood disorders.

Animals↗
PubMed2004

The hypoxic tumor microenvironment and gene expression.

Solid tumors are not static entities but are constantly responding to environmental signals as they grow and develop. One mechanism by which they respond to the adverse conditions of the tumor microenvironment is through coordinated changes in gene expression. The synchronized turning of genes on and off leads to biologic adaption to the adverse oxygen-poor environment. Because tumor hypoxia can be found in almost every solid tumor, it represents one of the most pervasive microenvironmental stresses that can impact malignant progression and therapeutic response. Interestingly, tumors that exhibit robust induction of hypoxia-responsive gene expression networks show a clinically more aggressive natural history. The contribution of hypoxia-responsive gene networks to malignant response is currently under investigation. An understanding of the coordinated functions of hypoxia induced and repressed genes can lead to a better understanding of the clinical significance of the hypoxic tumor phenotype.

Apoptosis↗
PubMed1986

Porosity of the basement membrane overlying Peyer's patches in rats and monkeys.

The porosity of the epithelial basement membrane (basal lamina) overlying lymphoid follicles within Peyer's patches was studied in rats and monkeys by scanning electron microscopy. Basement membranes of lymphoid follicles are markedly porous, more conspicuously so than those of adjacent villus cores. The porosity increases centrifugally from the apex of the follicle to its periphery, where the basement membrane continues into the cul-de-sacs of the crypts. Such porosity may facilitate bidirectional passage of lymphocytes during an immune response. The unique structure of the basement membrane overlying lymphoid follicles suggests a biologic adaptation of this tissue boundary to a specific physiologic activity of the organism.

Animals↗