Will genetics revolutionize psychiatry?

After a declining period by the mid-1980s and its stabilization in 1985-1995, the morbidity rates of tuberculosis in Uzbekistan increased in 1996 by 20.7% as compared to 1995, by 24% among children in the past decade, and 2 times among adolescents and young individuals aged under 30 years within 5 years. The rise of mortality rates is accompanied by aggravation of the clinical forms of the tuberculosis cases detected. The goal-oriented examinations of populations at risk of the disease in 14 districts of the Republic indicated a 1.5-fold increase in total mortality rates, followed by an upward tendency.     

A retrospective study of the learning history origins of anxiety sensitivity

Under non-epidemic conditions, Neisseria meningitidis causes disease primarily in children under the age of 5 and the cases are sporadic without any evident relationship between them. Occasionally, localized outbreaks of meningococcal disease occur, and sometimes epidemic waves of disease may spread to several countries or even continents and constitute a pandemic. In the past 10 years or so, population genetic analyses have provided insights into the biology of the bacterium and the epidemiology of meningococcal disease, improving our understanding of the cause of epidemics. Through the application of molecular methods, and especially multilocus enzyme electrophoresis, to N. meningitidis strains of worldwide origin, it has been possible to identify virulent clones and provide a surveillance system to warn of meningococcal epidemics. The characteristics of the predominant clones which are nowadays causing meningococcal disease in the world are summarized here and the importance of population genetics in interpreting the epidemiological data is illustrated.     

Effects of increased solar ultraviolet radiation on materials

Synthetic polymers such as plastics, as well as naturally occurring polymer materials such as wood, are extensively used in building construction and other outdoor applications where they are routinely exposed to sunlight. The UV-B content in sunlight is well known to affect adversely the mechanical properties of these materials, limiting their useful life. Presently their outdoor lifetimes depend on the use of photostabilizers in the case of plastics and on protective surface coatings in the case of wood. Any increase in the solar UV-B content due to a partial ozone depletion would therefore tend to decrease the outdoor service life of these materials. It is the synergistic effect of increased UV radiation with other factors such as the temperature that would determine the extent of such reduction in service life. The increased cost associated with such a change would be felt unevenly across the globe. Those developing countries that depend on plastics as a prime material of construction and experience high ambient temperatures are likely to be particularly affected in spite of the relatively small fractional decrease in ozone at those locations. Assessment of the damage to materials, associated with ozone depletion, requires a knowledge of the wavelength dependence as well as the dose-response characteristics of the polymer degradation processes of interest. While the recent literature includes some reliable spectral sensitivity data, little dose-response information has been reported, so it is difficult to make such assessments reliably at the present time. This is particularly true for the naturally occurring materials popularly used in construction applications. To maintain polymers at the same useful lifetime in spite of increased solar UV-B content, the amount of photostabilizers used in the formulations might be increased. This strategy assumes that conventional stabilizers will continue to be effective with the spectrally altered UV-B-enhanced solar radiation. While the present understanding of the degradation chemistry suggests the strategy to have merit, its effectiveness, in an altered solar radiation environment, has not been demonstrated for common polymers. The availability of these data is crucial for reliably estimating the cost of mitigating the increased damage to materials as a result of a possible partial depletion of the ozone layer using this approach.     

Participation of AT1 and AT2 receptor subtypes in the tonic inhibitory modulation of baroreceptor reflex response by endogenous angiotensins at the nucleus tractus solitarii in the rat

Although myelin basic protein (MBP)-recognizing T cells are not readily obtained after immunization of BALB/c mice with MBP (reflecting the BALB/c resistance to actively induced experimental autoimmune encephalomyelitis (EAE)), they can be expanded and cloned after several rounds of in vitro culture. The majority of BALB/c-derived clones recognize an epitope defined by MBP peptide 59-76. When transferred to naive BALB/c recipients, these clones cause classical EAE, with characteristic inflammation and demyelination of the central nervous system (CNS). We previously showed that two related clones recognizing a minor epitope, defined by MBP peptide 151-168, cause inflammation and demyelination preferentially of the peripheral nervous system (PNS). Because MBP has alternatively spliced isoforms, residues 151-168 are not present contiguously in all MBP isoforms. In order to determine whether induction of PNS disease is idiosyncratic to these sister clones, or related to their properties of epitope recognition, an independent T-cell line with similar recognition properties was studied. Clone 116F, derived from a BALB/c shiverer mouse, expresses a different T-cell receptor (TCR), with distinct TCR contact residues, but like the previously described T cells, this clone requires residues from both exons 6 and 7 for optimal stimulation. When adoptively transferred to BALB/c recipients, this clone preferentially induces disease of the PNS. A control BALB/c shiverer-derived MBP 59-76-recognizing clone, in contrast, induces CNS disease. These data strongly suggest that the site of disease initiation may correlate with epitope recognition, particularly when alternative isoforms are involved.     

Incidence and prevalence of symptomatic celiac disease among adults in Denmark

The purpose was: 1) to determine annual incidence rates of adult coeliac disease, 2) to calculate the risk of having developed coeliac disease in adult life, and 3) to calculate the life time prevalence by five-year birth cohorts. All patients fulfilling defined criteria for adult coeliac disease living in the county of Copenhagen and diagnosed during the years 1976-1991 were included. The reference population consisted of 503,283 subjects. The overall incidence had been stable during the period, and was 1.27/10(5). The figures for females and males were 1.55/10(5) and 0.96/10(5), respectively (p = 0.04). The median (range) age at the time of diagnosis was 40.1 (16-81). Age specific incidence rates varied considerably, with the peak rate located in the middle-aged population. The incidence rates were influenced by age at diagnosis (p = 0.01) and sex (p = 0.04), but not by the year when diagnosed. For a subject aged 89 years, the risk was 0.88/1000. The overall prevalence was 45.9/10(5). In conclusion, this incidence/prevalence is one of the lowest reported, and is definitely lower than prevalences reported from our neighbouring Scandinavian countries. Nothing points to higher incidence rates being present in Danish adults to compensate for the previously demonstrated very low rates in Danish children.     

Development of CD8 alpha/beta + TCR alpha beta intestinal intraepithelial lymphocytes in athymic nu/nu mice and participation in regional immune responses

On the basis of the CD8 coreceptor expression, T-cell receptor (TCR)alpha beta-bearing intestinal intraepithelial lymphocytes (i-IEL) segregate into two populations. The CD8 alpha alpha + TCR alpha beta i-IEL develop thymus independently, whereas the CD8 alpha beta + TCR alpha beta i-IEL are generally considered to be thymus dependent. Flow cytometry analysis revealed a distinct population of CD8 alpha beta + TCR alpha beta i-IEL in individual athymic nu/nu mice. The i-IEL encompassing CD8 alpha beta + TCR alpha beta cells expressed potent cytolytic and interferon-gamma-producing activities. These findings demonstrate that CD8 alpha beta + TCR alpha beta i-IEL can develop in nu/nu mice independently from a functional thymus and suggest that these cells, directly or indirectly, perform biological functions in the gut.     

Effect of adding the topoisomerase I poison 7-ethyl-10-hydroxycamptothecin (SN-38) to 5-fluorouracil and folinic acid in HCT-8 cells: elevated dTTP pools and enhanced cytotoxicity

Checkpoints maintain the interdependency of cell cycle events by permitting the onset of an event only after the completion of the preceding event. The DNA replication checkpoint induces a cell cycle arrest until the completion of the DNA replication. Similarly, the DNA damage checkpoint arrests cell cycle progression if DNA repair is incomplete. A number of genes that play a role in the two checkpoints have been identified through genetic studies in yeasts, and their homologues have been found in fly, mouse, and human. They form signaling cascades activated by a DNA replication block or DNA damage and subsequently generate the negative constraints on cell cycle regulators. The failure of these signaling cascades results in producing offspring that carry mutations or that lack a portion of the genome. In humans, defects in the checkpoints are often associated with cancer-prone diseases. Focusing mainly on the studies in budding and fission yeasts, we summarize the recent progress.