Evolution of the major histocompatibility complex: molecular cloning of major histocompatibility complex class I from the amphibian Xenopus.

Class I major histocompatibility complex (MHC) cDNA clones have been isolated from an expression library derived from mRNA of an MHC homozygous Xenopus laevis. The nucleotide and predicted amino acid sequences show definite similarity to MHC class I molecules of higher vertebrates. The immunoglobulin-like alpha-3 domain is more similar to the immunoglobulin-like domains of mammalian class II beta chains than to those of mammalian class I molecules, and a tree based on nucleotide sequences of representative MHC genes is presented.     

Does previous infection protect against atopic eczema and recurrent wheeze ininfancy?

BACKGROUND: Frequent infection in infancy and early childhood has been hypothesized to explain the low prevalence of asthma and other atopic disease among children in developing countries (the so-called 'hygiene hypothesis'), but the low prevalence in Eastern Europe remains unexplained. OBJECTIVE: To test the hygiene hypothesis in the Republic of Belarus by examining the relationship between gastrointestinal (GI) and respiratory infection and two potentially atopic outcomes in the first 12 months of life: atopic eczema and recurrent wheeze. METHODS; We carried out two case-control studies nested within a large (n=17 046) randomized trial in Belarus, with cases defined as (1) first occurrence of atopic eczema (n=819) and (2) second episode of wheezing (n=112). Incidence density sampling was used to select four matched controls born within 1 month at the same hospital as the case. Exposure was defined as one or more episodes of GI or respiratory infection (examined separately) with onset >7 days before onset of the case's atopic outcome. Analyses controlled for family atopic history, duration of exclusive breastfeeding, sex, birth weight, maternal education, and (for recurrent wheeze) maternal smoking. RESULTS: For atopic eczema, prior GI infection occurred in 7.4% of cases vs. 6.0% of controls [adjusted OR=1.27 (0.94-1.72)] and prior respiratory infection in 35.2% vs. 32.6% [adjusted OR=1.14 (95% CI=0.94-1.37)]. For recurrent wheeze, prior GI infection occurred in 9.8% of cases vs. 7.4% of controls [adjusted OR=1.30 (0.60-2.82)]. CONCLUSION: Our results do not support the hypothesis that infection protects against atopic eczema or recurrent wheezing in the first 12 months of life.     

Trophic effects of unsulfated cholecystokinin on mouse pancreas and human pancreatic cancer.

The effect of unsulfated cholecystokinin on pancreatic growth was evaluated in two experimental models in vivo and in vitro. Mice were injected with sulfated cholecystokinin (CCKs) or unsulfated cholecystokinin (CCKu) (10 or 20 micrograms/kg) or vehicle twice daily for 15 days. Animals were then killed and pancreatic weights, protein, amylase, and DNA content were evaluated. In vitro, growth was evaluated by DNA synthesis and viable cell counts. MIA PaCa-2 and BxPC-3 human pancreatic cancer cells were treated with CCKs or CCKu (10(-12) to 10(-9) M) for 48 or 72 h in the presence of [3H]thymidine to evaluate DNA synthesis. Viable cell counts were performed on both cell lines grown in the presence or absence of unsulfated CCK (10(-12) to 10(-9) M) for 96 h. Pancreatic weight, protein, amylase, and DNA were significantly increased in animals treated with either CCKs or CCKu. However, pancreatic weight, protein, and amylase were significantly higher in mice treated with CCKs compared to CCKu (p less than 0.005). DNA content and index of hyperplasia were the same whether mice were treated with CCKs or CCKu. CCKu was as potent a stimulus for DNA synthesis as CCKs in MIA PaCa-2 and BxPC-3 cells. Finally, CCKu increased cell counts in both pancreatic cancer cell lines. These data suggest that the mechanisms responsible for CCK-induced growth of normal pancreas and pancreatic cancer may differ from those that regulate secretion.     

Prenatal cocaine exposure disrupts the development of the serotonergic system.

Prenatal cocaine exposure has been found to result in a number of neurobehavioral abnormalities in both clinical and laboratory studies. We have previously shown that cocaine inhibits the growth of developing serotonin neurons in culture. This study examines the effects of cocaine on the developing serotonin system in vivo. Pregnant rats were injected with cocaine (40 mg/kg s.c.) from gestational day 13 to parturition. One group of rats was additionally injected on postnatal days 1-5 with cocaine (10 mg/kg s.c.). [3H]Paroxetine, a selective ligand for the serotonin uptake carrier, was used to quantify serotonin terminal fiber density at one day, one week, and four weeks postnatal. Cocaine exposure was found to significantly decrease [3H]paroxetine-labelled sites and thus the density of serotonin fibers in the cortex and hippocampus at one day and one week postnatal. By four weeks postnatal, no significant effect was observed, indicating that a recovery had occurred. Serotonin immunocytochemistry performed at one month revealed normal fiber distribution in the cortex but a loss of fibers in the CA1 and CA2 hippocampal fields. Postnatal treatment alleviated the effects of prenatal cocaine exposure, resulting in [3H]paroxetine binding levels at one week which were comparable to and, in the cortex, even higher than those of saline controls. We conclude that cocaine delays the maturation of the serotonin system when administered prenatally but may accelerate maturation when administered both pre- and postnatally.     

Depression, dementia, and reversible dementia.

This article reviews the syndromic concepts of depression and dementia and the concurrence of these common entities. In DAT, depression appears to be a reversible source of excess disability, amenable to pharmacologic as well as environmental interventions. In the vascular dementias, depression appears to be a specific complicating feature, in which localization of the lesion plays a significant role. The abulic state should not be mistaken for a depressive syndrome, although its presence should alert the clinician to evaluate for dementia and depression. Depression is especially prevalent in the subcortical dementias. Future studies using dynamic neuroimaging will help define the limits of this important concept. Reversible forms of dementia are much less common than previously suspected. The clinician's task is to identify causes of excess disability due to superimposed illnesses while avoiding diagnostic or therapeutic nihilism. The appropriate use of medication and the ongoing surveillance for adverse drug reactions are the foremost tasks of today's clinician treating the elderly patient.     

Method for the quantitative assessment of contrast agent uptake in dynamic contrast-enhanced MRI

In previous papers relative signal intensity increase was used as a quantitative assessment parameter for contrast uptake in contrastenhanced MRI. However, relative signal intensity increase does not only reflect contrast uptake but depends also on tissue parameters (native T₁ relaxation time) and sequence parameters (repetition time and flip angle); thus, the contrast uptake cannot be assessed accurately using relative signal intensity increase. Based on an analysis of the contrast behavior of spoiled gradient echo sequences, a method is described in this paper that overcomes the limitations of relative signal intensity increase measurement. A parameter, called “enhancement factor” (EF) is introduced that approximates differential T₁ relaxation rate. The enhancement factor scales linearly with contrast uptake and is independent of tissue and sequence parameters. The additional measurement time involved in determining the enhancement factor is less than 1 min and computation is straightforward. The practicality of the new method was confirmed by phantom measurements using T₁-weighted and proton density-weighted spoiled gradient echo sequences (FLASH-2D). Enhancing tissues were simulated by water phantoms doped with increasing concentrations of Gd-DTPA.     

Behandlung des hypoplastischen Linksherz-Syndroms

In contrast to other types of congenital heart defects, the treatment of hypoplastic left heart syndrome (HLHS) has become comparably successful only within the last decade. Postnatal management of circulatory disturbances of HLHS was previously often performed, similarly to other types of neonatal shock, without considering the peculiarities of postnatal hemodynamics. It is of overwhelming importance to limit pulmonary hyperperfusion by reducing systemic afterload and avoiding artificial respiration. The invention of selective hypothermic cerebral perfusion using the modified Blalock-Taussig shunt has decreased the need for long circulatory arrest times involving the brain, and promises a better neurological outcome. Postoperatively, sophisticated hemodynamic monitoring is mandatory to provide sufficient systemic oxygen delivery. α-blockers are usually given for strong afterload reduction. Hospital mortality is as low as 10–15% in centers experienced with the Norwood operation. The next surgical steps to create a serial systemic and pulmonary circulation involve superior cavopulmonary anastomosis performed as early as possible (4–6 months) and finally total cavopulmonary connection at an age of 3–4 years.     

Sudden death in young soldiers. High incidence of syncope prior to death

During the years 1974 to 1986, 44 young soldiers (mean age 21 +/- 3 years) died suddenly and unexpectedly in the Israel Defense Forces. Cardiac causes accounted for 54 percent of deaths; neurologic causes, 14 percent of deaths; other diseases, 9 percent; and in 23 percent, cause of death was unknown. Although most sudden deaths are considered unpredictable, preceding symptoms were reported in more than one half of the patients. We found that syncope had occurred in 23 percent of cases, chest pain in 11 percent, and febrile disease in 16 percent. Exercise-associated syncope occurred in 16 percent and exercise-associated death occurred in most (86 percent) of those cases. Diagnosis at the time of the preceding symptoms failed to predict the fatal diseases in most cases. Our report points out the high incidence of syncope prior death in young soldiers with sudden death. Although further prospective controlled studies are needed in order to confirm that impression, we suggest that the possibility of syncope followed by sudden death should be kept in mind while evaluating young patients presenting with exercise-associated syncope.