Virus-provoked rhinitis in patients who have allergies.

The most common illnesses in humans are the respiratory tract infections caused by viruses. When limited to the upper respiratory region, these infections often are designated as "a common cold." Viruses commonly associated with these upper respiratory infections (URI) include rhinoviruses (RVs), respiratory syncytial virus, influenza virus, parainfluenza virus, corona virus, and adenoviruses. Clinical observations have suggested that patients with allergic rhinitis and asthma experience more pronounced symptoms during a viral URI than patients who do not have allergies and who are infected with the same virus under similar circumstances. Using an experimental virus infection model in human volunteers with and without allergic rhinitis, several groups of clinical investigators have studied the effects of experimental RV infections. These observations indicate that the experimental virus infection may induce host responses that provoke enhanced immunoglobulin E (IgE) synthesis. Whether this translates into enhanced symptoms has been suggested in one study but not in another. This article will review these studies, which suggest that it is the host response to the virus and not the virus itself that plays the major role in symptom pathogenesis.     

Why cancer patients have anorexia.

The theory has been advanced that the anorexia of cancer is the result of anorexigenic peptides and of other intermediary metabolites produced by the cancer and the tumor-bearing host. These metabolites are the signals to peripheral receptors and to the brain centers and are responsible for the state of satiety and aversion to food. Although the only effective way to stimulate the appetite of the cancer patient is to control the cancer, efforts should be made to increase the calorie intake even in the presence of anorexia and to maintain a calorie equilibrium. However, controlled studies have not shown that forced feeding can reverse for long periods the progressive tissue wasting process or prolong the cancer patient's survival.     

Brain-specific genes have identifier sequences in their introns.

The 82-nucleotide identifier (ID) sequence is present in the rat genome in 1-1.5 X 10(5) copies and in cDNA clones of precursors of brain-specific mRNAs. One brain-specific gene contains more than one ID sequence in its introns. There is an excess of ID sequences to brain genes, and some ID sequences appear to have been inserted as mobile elements into other genetic locations. Therefore, brain genes contain ID sequences in their introns, but not all ID sequences are located in brain gene introns. A brain ID consensus sequence has been obtained by comparing 8 ID nucleotide sequences.     

Smokers have severely disturbed peripheral micro-circulation.

AIM: The aim of this study was to determine the effect of smoking a single cigarette on the blood flow rates in capillaries and arteriovenous anastomoses (AVAs) in light and heavy smokers in: a) the skin fold between the first and second fingers, and b) the pulp of the thumb. METHODS: Five light (10-12 cigarettes/day) and 5 heavy (>20 cigarettes/day) chronic smokers participated (4 men and 6 women, median age 40.5 years). The blood flow rates were measured by the (133)Xenon local washout method (capillaries, skin fold) and the heat washout method (AVAs, thumb pulp), respectively, before, during, and after smoking of a single Prince cigarette (0.9 mg nicotine). RESULTS: The blood flow rate (f) in mL(100 g(min)(-1) [standard error, SE] in skin capillaries of light smokers was 24.4 [9], 8.9 [1.8], and 10.4 [3.3] before, during, and after smoking of one cigarette; in heavy smokers, f was 23.6 [10.9], 16.1 [5.3], and 7.1 [2.9]; f in pulp AVAs of light smokers was 130.6 [14.9], 49.2 [24.8], and 119.7 [20.9] before, during, and after smoking; in heavy smokers, the corresponding results were 134.4 [19.1], 136.2 [13.5], and 143 [15.3]. Thus, the blood flow rate in capillaries of both light and heavy smokers was higher before smoking the test cigarette than previously observed in non-smokers. In light smokers blood flow rate in AVAs decreased during smoking with a factor of 2.6, and it returned to the pre-smoking level immediately after the end of smoking the cigarette. In heavy smokers, f remained unchanged before, during, and after smoking. CONCLUSIONS: Smokers have severely disturbed peripheral microcirculation.     

Free fatty acids have nucleating effects in model biles.

Nucleating factors are thought to be responsible for the more rapid nucleation of gallbladder bile from patients with gallstones as compared to controls. Biliary proteins and, in particular, mucus and non-mucus glycoproteins are the focus of current research. Non-protein nucleating factors were not extensively investigated. In this study we studied the role of free fatty acids (FFA) as possible nucleating factors. Palmitic, oleic and linoleic acid were added to model biles in increasing concentrations from 0 to 20 mu mol/ml. The nucleation time of model biles decreased to 45%-60% of the initial following the addition of 0.5 to 1 mu mol/ml of each of the three fatty acids. Only a small further decrease in the nucleation time was noted with higher concentrations of up to 20 mu mol/ml. The pronucleating effect of FFA added to whole model bile was also examined in the isolated vesicular and non-vesicular fractions. The decrease in the nucleation time at each concentration of the three fatty acids was in the following order of magnitude: whole bile greater than vesicular phase greater than non-vesicular phase. The addition of each of the three fatty acids resulted in a partial solubilization of vesicles, with transfer of their lipid contents to the non-vesicular fraction. The effect was more marked with oleic acid and least marked with linoleic acid. The vesicular cholesterol to phospholipid ratio did not change following the addition of exogenous free fatty acids. Studies with labeled FFA showed that they migrated with the non-vesicular fraction on gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mouse genetics have uncovered new paradigms in bone biology.

In the past decade, mouse models have improved our understanding of bone biology. Given the fact that osteoporosis is among the most common diseases, this review will focus on the regulation of differentiation and function of the bone-resorbing osteoclasts and the bone-forming osteoblasts. Mouse genetic studies have revealed a cascade controlling osteoclastogenesis that includes the recently discovered molecules osteoprotegerin, RANK and RANK ligand. In terms of osteoblast differentiation, CBFA1 and Indian hedgehog have been identified as activators. Moreover, recent evidence demonstrates that osteoblast function is, at least in part, controlled by the hypothalamus.     

How the first biopolymers could have evolved.

In this work, we discuss a possible origin of the first biopolymers with stable unique structures. We suggest that at the prebiotic stage of evolution, long organic polymers had to be compact to avoid hydrolysis and had to be soluble and thus must not be exceedingly hydrophobic. We present an algorithm that generates such sequences for model proteins. The evolved sequences turn out to have a stable unique structure, into which they quickly fold. This result illustrates the idea that the unique three-dimensional native structures of first biopolymers could have evolved as a side effect of nonspecific physicochemical factors acting at the prebiotic stage of evolution.     

Growing Xenopus oocytes have spare translational capacity.

Previous studies have shown that exogenous mRNAs injected into full-grown (stage 6) Xenopus oocytes are translated only at the expense of endogenous messages; translational capacity is limited. In this report, we demonstrate that injection of globin mRNA into small, stage 4 oocytes results in an increase in total protein synthesis without a concomitant decrease in the translation of endogenous mRNAs. The absence of competition with endogenous messages in stage 4 oocytes, injected with globin mRNA, compared with stage 6 oocytes, was not due to differential turnover of the injected mRNA. Hybridization of RNA from mRNA-injected oocytes at both stages revealed that similar amounts of globin mRNA were present. These results are interpreted to mean that protein synthesis in growing oocytes is limited by the availability of mRNA and not components of the translational machinery. This conclusion, however, does not apply to all mRNA classes. The capacity of stage 4 oocytes to translate a mRNA (zein) on membrane-bound polysomes is as restricted as reported previously for stage 6 oocytes. This result suggests that putative membrane binding sites or rough endoplasmic reticulum content are limited in oocytes at both stages. The possible role of association of injected mRNA with endogenous proteins that prevent translation is discussed.     

Norepinephrine transporters have channel modes of conduction.

Neurotransmitter transporters couple to existing ion gradients to achieve reuptake of transmitter into presynaptic terminals. For coupled cotransport, substrates and ions cross the membrane in fixed stoichiometry. This is in contrast to ion channels, which carry an arbitrary number of ions depending on the channel open time. Members of the gamma-aminobutyric acid transporter gene family presumably function with fixed stoichiometry in which a set number of ions cotransport with one transmitter molecule. Here we report channel-like events from a presumably fixed stoichiometry [norepinephrine (NE)+, Na+, and Cl-], human NE (hNET) in the gamma-aminobutyric acid transporter gene family. These events are stimulated by NE and by guanethidine, an hNET substrate, and they are blocked by cocaine and the antidepressant desipramine. Voltage-clamp data combined with NE uptake data from these same cells indicate that hNETs have two functional modes of conduction: a classical transporter mode (T-mode) and a novel channel mode (C-mode). Both T-mode and C-mode are gated by the same substrates and antagonized by the same blockers. T-mode is putatively electrogenic because the transmitter and cotransported ions sum to one net charge. However, C-mode carries virtually all of the transmitter-induced current, even though it occurs with low probability. This is because each C-mode opening transports hundreds of charges per event. The existence of a channel mode of conduction in a previously established fixed-stoichiometry transporter suggests the appearance of an aqueous pore through the transporter protein during the transport cycle and may have significance for transporter regulation.     

Recombinant E-peptides of pro-IGF-I have mitogenic activity.

In mammals, the post-translational proteolytic modification of many pro-hormones generates multiple peptides with similar or distinct biological activities. The production of mature insulin-like growth factor I (IGF-I) involves the cleavage of an E-peptide from pro-IGF-I. Although the IGF-I E-peptides are conserved among vertebrate species, their fate and biological roles have not been identified. To test whether the E-peptides possess any biological activity, three recombinant E-peptides of pro-IGF-I, namely Ea-2-, Ea-3- and Ea-4-peptides of rainbow trout, Oncorhynchus mykiss, were produced in vitro with a His-tag expression system and partially purified with an affinity Ni++ column. The mitogenic activity of each E-peptide was determined by (1) the stimulation of total DNA content increase as measured by a fluorometric method and/or (2) stimulation of [3H]-thymidine incorporation into DNA. Recombinant Ea-4-peptide elicited a dose-related increase in both mitogenic assays in NIH3T3 cells. To further test the specificity of the mitogenic activity of Ea-4-peptide, three other cell lines were used: retroviral transformed human embryonic kidney cells (293GP), human mammary gland tumor cells (MCF-7) and caprine mammary epithelial cells (CMEC). Similar levels of mitogenic activity were observed in all cell lines tested for Ea-4-peptide. Mitogenic activity was also observed with recombinant Ea-2- and Ea-3-peptides when assayed in NIH3T3 cells. These results suggest that E-peptides of rainbow trout pro-IGF-I possess mitogenic activity in heterologous systems.     

Prevalence of pollen sensitization in younger children who have asthma.

It is commonly believed that young children are incapable of pollen sensitization; therefore, skin testing usually is not performed to these allergens. The purpose of this study was to identify the frequency of positive skin tests to outdoor allergens among younger children who have asthma. Patients who have asthma, aged 6 months to 10 years, were evaluated for pollen sensitization over a 10-year period. Skin-prick testing was performed to relevant individual aeroallergens including trees, grasses, and weeds. Testing for perennial indoor allergens such as dust mites, cats, dogs, cockroaches, and molds was performed also. A total of 687 children with asthma were evaluated. No child <12 months old was sensitized to pollens. Children between 12 and 24 months of age had a 29% incidence of pollen sensitization. Three-year-old children were as likely to be skin test positive to pollen as an indoor allergen. Notably, 49% of 3- and 4-year olds were sensitized to outdoor allergens. Primary sensitizing pollens in this age group were short ragweed, box elder, and June grass. In this population, pollen sensitization was not related to tobacco or wood smoke exposure. Although it is widely believed that young children with asthma are most commonly allergic to indoor allergens, almost 40% of our 1- to 3-year old children with asthma showed IgE-mediated sensitivity to outdoor allergens. Pediatric allergists should consider performing skin-prick testing to their local common aeroallergens in young children with asthma and seasonal symptoms.