Antimorphine antibodies as an indicator of chronic morphine intoxication and impaired immunological reactivity

Chronic intoxication of rats with morphine during 2- and 4-week periods resulted in the emergence of antimorphine antibodies in the blood of 50 and 80% of the animals, respectively, in hemagglutination titers 1∶20 and higher. Antibodies were not detected in the control animals (not treated with morphine) but were detected in 17% of rats given alcohol during a 3-month period. The animals with a high titer of antimorphine antibodies displayed a lower level of humoral reactivity in response to immunization with a thymus-dependent antigen (sheep erythrocytes) compared with the animals with a low titer of the antibodies. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 7, pp. 74–76, July, 1994     

The intricate association between gut microbiota and development of Type 1, Type 2 and Type 3 diabetes

It has been proposed that changes in the composition of gut microbiota contribute to the development of diabetes Types 1, 2 and 3 (the latter known as Alzheimer’s disease). The onset of these diseases is affected by complex interactions of genetic and several environmental factors. Alterations in gut microbiota in combination with specific diets can result in increased intestinal permeability leading via a continuous state of low-grade inflammation to the development of insulin resistance. Since a change in composition of gut microbiota is also suggested to be the underlying factor for the development of obesity, it is obvious to link gut microbiota with the pathogenesis of diabetes. In addition, insulin resistance in the brain has been recently associated with Alzheimer’s disease. These new paradigms in combination with data from studies with prebiotics and probiotics may lead to a novel way to control and even prevent diabetes in general.     

Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome

Microsatellite instability (MSI) is present in hereditary conditions due to mismatch repair (MMR) gene mutations. Following MSI analysis, tumor samples are classified into MSS (stable), MSI-L (low instability), and MSI-H (high instability) based on the fraction of unstable loci. Another MSI-based classification takes into account the size difference between mutant alleles in tumor DNA compared to wild-type alleles; two types of MSI, A and B, are recognized using this approach, type A being characterized by smaller, more subtle allelic shifts compared to type B. Biallelic mutations of MMR genes are associated with pediatric cancers, including glial tumors, in Turcot syndrome type 1 (TS1). However, most TS1-associated gliomas so far analyzed did not display MSI. We investigated the frequency of MSI in a series of 34 pediatric gliomas of different grade using a panel of five mononucleotide quasimonomorphic markers. Subtle qualitative changes were observed for the majority of markers in two glioblastomas (5.9% of the total series and 33.3% of glioblastomas). In both cases, family histories were compatible with TS1, and mutations of the PMS2 and MLH1 genes were identified. In one family, the MSI patterns were compared between the glioblastoma and a colon cancer from an affected relative, showing a clear qualitative difference, with the former displaying type A and the latter type B instability, respectively. These results were confirmed using additional microsatellite markers, indicating that knowledge of the association between TS1-related glial tumors and subtle type A MSI is important for full ascertainment of TS1 patients and appropriate counselling.     

Subjective sleepiness is a sensitive indicator of insufficient sleep and impaired waking function

The main consequence of insufficient sleep is sleepiness. While measures of sleep latency, continuous encephalographical/electro‐oculographical (EEG/EOG) recording and performance tests are useful indicators of sleepiness in the laboratory and clinic, they are not easily implemented in large, real‐life field studies. Subjective ratings of sleepiness, which are easily applied and unobtrusive, are an alternative, but whether they measure sleepiness sensitively, reliably and validly remains uncertain. This review brings together research relevant to these issues. It is focused on the Karolinska Sleepiness Scale (KSS), which is a nine‐point Likert‐type scale. The diurnal pattern of sleepiness is U‐shaped, with high KSS values in the morning and late evening, and with great stability across years. KSS values increase sensitively during acute total and repeated partial sleep deprivation and night work, including night driving. The effect sizes range between 1.5 and 3. The relation to driving performance or EEG/EOG indicators of sleepiness is highly significant, strongly curvilinear and consistent across individuals. High (>6) KSS values are associated particularly with impaired driving performance and sleep intrusions in the EEG. KSS values are also increased in many clinical conditions such as sleep apnea, depression and burnout. The context has a strong influence on KSS ratings. Thus, physical activity, social interaction and light exposure will reduce KSS values by 1–2 units. In contrast, time‐on‐task in a monotonous context will increase KSS values by 1–2 units. In summary, subjective ratings of sleepiness as described here is as sensitive and valid an indicator of sleepiness as objective measures, and particularly suitable for field studies.     

A pre-reflective indicator of an impaired sense of agency in patients with Schizophrenia

In schizophrenia, passivity phenomenon are clinically related to an abnormal sense of agency, which has been experimentally studied through self-recognition tasks. However, Tsakiris et al. (Cognition 96(3):215–231, 2005) have recently shown in healthy controls that the sense of agency is distinct from self-recognition abilities. We propose a simple motor task to obtain an implicit indicator of the working status of the pre-reflective sense of agency in schizophrenia. Collision dynamics gave us the means to further dissociate agency from motor prediction. Twenty-four patients and a group of matched controls used a hand-held object to stop the fall of a pendulum that was released either by the Subject (task S) or by the Experimenter (task E). The objective indicator of the sense of agency was taken as the efficiency difference between tasks S and E, before the availability of afferent information from collision. Qualitative feedback was provided to assess the top-down effect of explicit information. Motor prediction was as accurate in patients as in controls in tasks E and S. Controls were more efficient in S than in E. Patients revealed similar efficiency levels in both tasks. Qualitative feedback helped but did not affect the efficiency difference between tasks. Our results suggest an impairment of a pure efferent-driven sense of agency in schizophrenia, which is (1) distinct from motor prediction and (2) not under voluntary control. The abnormal judgments previously reported in schizophrenia for self-recognition abilities might be the consequence of a low order deficit of a pre-reflective sense of agency. Study conducted in the Psychiatric Unit – University Regional Hospitals of Lille (France).     

Myoglobin as an indicator of stress-induced damage

Translated fromByulleten' Pksperimental'noi Biologii i Meditsiny, Vol. 115, No. 1, pp. 25–27, January, 1993.     

Headache as an indicator of systemic disease

Headaches can constitute a direct symptom and possibly the preliminary symptom of several autoimmune diseases and systemic vasculitis. In the majority of cases, the characteristics of the headache are not on their own sufficient to establish a certain diagnosis, which has to be based on the clinical context and on other migraine-associated signs. In practice, three main categories of headache can be indicative of systemic disease: craniofacial pain; migraine and pseudo-migraine; and headache caused by intracranial hypertension.     

MICA marks additional risk factors for Type 1 diabetes on extended HLA haplotypes: an association and meta-analysis

The association of the HLA complex on chromosome 6 does not explain total linkage of the HLA region to Type 1 Diabetes (T1D), leading to the hypothesis that there may be additional causal genes in the HLA region for immune-related disorders. Reports on the MHC Class I chain-related A (MICA) gene as candidate for association with T1D are contradicting. We investigated whether variation in MICA is associated to T1D in a cohort of 350 unrelated individuals with juvenile-onset T1D and 540 control subjects, followed by a meta-analysis of 14 studies. We also investigated an HLA-independent association for MICA with T1D. In our case-control study, we found that the MICA*A5 variant was significantly associated with an increased risk for T1D, while MICA*A6 was significantly associated with a decreased risk that was confirmed by our meta-analysis. However, the meta-analysis did not show an association of MICA*A5 T1D. Analysis of MICA alleles conditional on T1D-associated high-risk MHC class II haplotypes revealed that MICA*A6 was associated with an increased risk for T1D when this marker co-occurred with HLA DQ2DR17 T1D-risk-haplotypes. In contrast, MICA*A6 reduced the risk from the HLA DQ8DR4 T1D-risk haplotype. Moreover, MICA*A9 showed a significant association to increased risk for T1D on DQ8DR4 haplotypes. Co-inheritance of MICA*A6 with the HLA DQ2DR17 haplotype in T1D indicates this haplotype may carry the additional genetic factors for T1D, but our study does not support an independent association between MICA variants and T1D.     

Type 2 diabetes: The genetic conflict hypothesis

We propose that conflict between paternally and maternally derived genes in the fetus explains three apparently unrelated observations in epidemiological studies of type 2 diabetes mellitus (DM2): (i) low birth weight is a risk factor for the development of DM2, (ii) there is a high prevalence of low birth weight among babies of fathers who develop DM2, and (iii) an exceptionally high prevalence of DM2 exists in modern day Arabs. Genetic conflict is caused by a particular relationship between the parents, their genes and their offspring: (i) mothers are sometimes polyandrous i.e. have children with more than one man, (ii) mothers provide more biological resources to the fetus than fathers, and (iii) the genes that regulate fetal growth come from both parents and both sets of genes determine the use of resources which are only those of the mother. There is a tendency for maternally derived genes (that promote fetal growth) to be suppressed, in order to spare use of mother’s resources, while the same paternally derived genes tend to be expressed (to enhance use of the mother’s resources). These same genes are pleiotropic: they affect not only fetal growth (birth weight) but also insulin resistance and hence the development of DM2. Polyandry increases differences in the expression between two parental alleles in the fetus i.e. increases genetic conflict and results in the production of bigger babies whereas monandry has the opposite effect. Consequently, parent-of-origin-biased expression of pleiotropic developmental genes could explain why smaller babies are more common when the fathers have DM2. Similarly less genetic conflict in Arabs (resulting from the tradition of strict monandry, the practice of levirate, and preference for a paternal cousin as spouse) could explain, at least in part, their exceptionally high prevalence of DM2. This hypothesis links human mate selection with the risk of developing DM2.     

Degranulation of basophils as an indicator of stress

Regular appearance of degranulation of basophilic blood leukocytes was shown to occur not only during the development of allergic inflammation in a joint and in the skin, but also during experimental acute and chronic blood loss, burn trauma, and acute radiation sickness. The degranulation reaction reflects stress developing in response to stress situations.Red Army Kuban Medical Institute, Krasnodar. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 599–601, November, 1979.     

The effect of parity on the later development of non-insulin-dependent diabetes mellitus or impaired glucose tolerance

To determine the effect of parity on the later development of non-insulin-dependent diabetes mellitus or impaired glucose tolerance, we studied a population-based sample of 1186 women at least 40 years of age; those who had been given a diagnosis of diabetes mellitus before the age of 40 or who had insulin-dependent diabetes mellitus were excluded from the study. On the basis of the World Health Organization's criteria, 714 had normal glucose tolerance, 326 had impaired glucose tolerance, and 146 had non-insulin-dependent diabetes mellitus (NIDDM). After adjustment for age, obesity, and family history of diabetes, increased parity was associated with a significantly increased risk of both NIDDM (odds ratio, 1.16 [95 percent confidence interval, 1.04 to 1.29] per pregnancy) and impaired glucose tolerance (odds ratio 1.10 [95 percent confidence interval, 1.01 to 1.19] per pregnancy). Obesity, whether estimated by means of the body-mass index or the waist-hip ratio, was significantly associated with an increased risk of both NIDDM and impaired glucose tolerance, but this factor did not explain the association between parity and diabetes or impaired glucose tolerance; neither the maximal lifetime body-mass index nor the waist-hip ratio was significantly associated with parity in this cohort. We conclude that there is a slight increase in the risk of NIDDM or impaired glucose tolerance with increasing parity many years after childbearing and that this association is not explained by obesity.     

Stress as an indicator of individual-typologic differences]

Typological peculiarities of the behaviour of adult white male rats were determined using the "emotional resonance" test, i. e. reaction of avoidance of the signals of the defensive state of the other animal of the same species (vocalization, release of pheromones, motor excitation). The rats developed a conditional motor food reflex, and then they were subject to a stress of inescapable pain reaction. Judging by the preserved conditional food reflexes, the rats which avoided the partner's pain screams proved to be the most stable. The rats unable to determine the dominating motivation and incessantly running from one section of the chamber to the other are the least stable. The highest level of catecholamines was found in the blood of the latter group. The sensitivity to the partner's signals of defensive excitation correlates with the degree of such shifts, occurring under the stress influence as the content of noradrenaline, dopamine and 5-oxyndolacetic acid in the tissues of the brain, the state of the lipid component of the cerebral membranes. According to the obtained results the stress reveals the individual peculiarities of the physiological functions which are not obvious without the stress influences. The animals, highly sensitive to the signals of the partner's emotional state, possess high resistance to the action of the most various stresses. It can be assumed that thanks to such stability natural selection preserved the capacity for zoosocial "empathy"--phylogenetic predecessor of human altruism.     

Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress

Elevated plasma homocysteine levels are associated with an increased risk of atherosclerosis and thrombosis, as well as a variety of other pathologies such as birth defects, Alzheimer’s disease and other dementias, osteoporosis, diabetes and renal disease. Homocysteine metabolism is catalyzed by a number of enzymes that require B-vitamins as cofactors, and homocysteine levels are particularly responsive to folate status. The predictive power of plasma homocysteine level as a risk factor for atherothrombotic orders raised the appealing hypothesis that reduction of homocysteine levels by vitamin supplementation might result in a commensurate reduction is the risk of atherothrombotic events. Unfortunately, most clinical trials failed to show a significant benefit of vitamin supplementation on cardiovascular events, in spite of significant lowering of plasma homocysteine levels. Thus, it is not clear whether homocysteine actually plays a causal role in many pathologies with which it is associated, or whether it is instead a marker for some other underlying mechanism. A large body of data links hyperhomocysteinemia and folate status with oxidant stress. In this article I review data that suggests that homocysteine not only promotes cellular and protein injury via oxidant mechanisms, but is also a marker for the presence of pathological oxidant stress. Thus, it is possible that hyperhomocysteinemia is not a common primary cause of atherothrombotic disorders in the general population, but rather a marker of systemic or endothelial oxidant stress that is a major mediator of these disorders.