Genetics of the hydrophilic surfactant proteins A and D

The use of candidate genes has increased the ability to identify genetic factors involved in diseases with complex and multifactorial etiology. The surfactant proteins (SP) A and D are involved in host defense and inflammatory processes of the lung, which are often components of pulmonary disease. Therefore, the SP-A and SP-D genes make particularly good candidates to study factors contributing to pulmonary disease etiopathogenesis. Moreover, SP-A also plays a role in the surface tension lowering abilities of pulmonary surfactant, which is essential for normal lung function. Although genetic variability at the SP-D locus may exist among humans, allelic variants have not yet been characterized. On the other hand, the human SP-A genes (SP-A1 and SP-A2) are characterized by genetically dependent splice variants at the 5' untranslated region and allelic variants. The polymorphisms that give rise to SP-A1 and SP-A2 alleles are contained within coding regions, potentially having an effect on protein function. There appears to be a correlation between SP-A genotype and SP-A mRNA content. Furthermore, one SP-A2 allele (1A0) shown to associate with low SP-A mRNA levels is found with higher frequency in a subgroup with respiratory distress syndrome. The evidence gathered thus far indicates that SP-A, possibly by interacting with other surfactant components, may play a role (e.g. be a susceptibility factor) in the development of respiratory disease.     

Biological markers of Alzheimer''s disease

A 49-year-old woman presented with splenic lymphoma with villous lymphocytes (SLVL) that showed a clonal abnormality of del(7)(q22q32) in addition to inv(10)(p13q23), the latter being a previously undescribed abnormality in chronic lymphoproliferative disorders. A review of the literature on cytogenetic abnormalities of SLVL indicates that del(7q) is strongly associated with SLVL and may be important in the pathogenesis of this disorder.     

Prognostic markers of disease activity in Hodgkin''s disease

The prognostic significance of specific cytogenetic abnormalities in follicular lymphoma (FL) is an area of ongoing research. A small percentage of FL are characterized by a polyploid karyotype. Several studies have analyzed ploidy level to determine its role as an independent prognostic factor in non-Hodgkins lymphoma, with equivocal results, mostly using DNA flow cytometry to ascertain ploidy status. We have performed cytogenetic analyses on 180 cases of FL with a t(14;18) diagnosed between 1980 and 1995. Cases were divided into a polyploid group (20 cases) and a non-polyploid group (160 cases), polyploidy defined as a modal chromosome number of 58 or greater. Each group included examples of the 3 subtypes of FL, [Working Formulation]: 1) follicular small cleaved cell (FSC), 2) follicular mixed, small and large cell (FM), and 3) follicular large cell (FLC). The median follow-up time was 38.5 months. The histological subclassification of the polyploid group revealed much less FSC (30% vs 66%, p < 0.004) and much more FLC (25% vs 4%, p < 0.003) than the non-polyploid group, implying histological progression may occur in parallel with the development of polyploidy. Recognized clinical prognostic factors were evenly distributed between the two groups and no survival difference was detected. We show that polyploidy as determined by classical cytogenetics is present in different frequencies across the subtypes of FL with a t(14;18), but is not an independent prognostic factor for survival in FL.     

Huntington's disease and dentatorubral-pallidoluysian atrophy: proteins, pathogenesis and pathology

Each of the glutamine repeat neurodegenerative diseases has a particular pattern of pathology largely restricted to the CNS. However, there is considerable overlap among the regions affected, suggesting that the diseases share pathogenic mechanisms, presumably involving the glutamine repeats. We focus on Huntington's disease (HD) and Dentatorubral-pallidoluysian atrophy (DRPLA) as models for this family of diseases, since they have striking similarities and also notable differences in their clinical features and pathology. We review the pattern of pathology in adult and juvenile onset cases. Despite selective pathology, the disease genes and their protein products (huntingtin and atrophin-1) are widely expressed. This presents a central problem for all the glutamine repeat diseases-how do widely expressed gene products give rise to restricted pathology? The pathogenic effects are believed to occur via a "gain of function" mechanism at the protein level. Mechanisms of cell death may include excitotoxicity, metabolic toxicity, apoptosis, and free radical stress. Emerging data indicate that huntingtin and atrophin-1 may have distinct protein interactions. The specific interaction partners may help explain the selective pathology of these diseases.     

Infectious proteins or prions. A new mechanism of disease

Culturing egg contents to detect Salmonella enteritidis (SE) has become an important tool for identifying infected laying flocks and thereby reducing the transmission of SE to humans by contaminated eggs. The present study evaluated the efficacy of supplementing incubating egg pools with selective and nonselective enrichment broth media (prepared at higher than usual concentrations) for rapidly isolating SE by a direct plating culture method. When 100-ml pools of liquid whole egg from a mixture of 60 egg contents were contaminated with approximately 10 SE cells each, supplementation with ferrous sulfate or with concentrates of either tryptone soya broth or Rappaport-Vassiliadis broth significantly improved SE recovery. When 100-ml egg-contents pools were contaminated with approximately 2 SE cells each, the addition of concentrated tryptone soya broth to incubating egg pools resulted in significantly better SE recovery than did iron supplementation. Efficient presumptive detection of very low incidences and levels of SE contamination by direct plating was thus accomplished in a total of 48 h by adding concentrated tryptone soya broth to incubating egg pools.     

Association between serum amyloid A proteins and coronary artery disease: evidence from two distinct arteriosclerotic processes

BACKGROUND: Serum amyloid A (SAA) proteins are a family of inflammatory apolipoproteins that may modify high-density lipoprotein structure and function. Elevations of SAA have been reported in unstable coronary syndromes, but the levels and types of SAA protein in humans with spontaneous or transplant-associated coronary artery disease are not known. METHODS AND RESULTS: SAA levels were analyzed using an ELISA in 76 sera from 36 patients after cardiac transplantation and in 346 other individuals, 85 patients with atherosclerotic coronary disease plus 261 of their relatives. The mean SAA level was 5-fold higher in transplant patients (203+/-181 microg/mL [23 to 934 microg/mL]) compared with normal subjects without coronary disease (36+/-16 microg/mL [2.8 to 193 microg/mL], P<.005). The mean SAA level was significantly elevated in patients with transplant coronary disease (206+/-160 microg/mL, n=23) compared with those without (140+/-104 microg/mL, n=12, P=.02). Elevated SAA levels were associated with increased mortality after transplantation. On multiple regression analysis, SAA levels were predicted by corticosteroid dose, pretransplant diagnosis of atherosclerotic coronary artery disease, and the presence of transplant coronary disease. SAA levels were elevated in patients with spontaneous atherosclerotic coronary disease (49+/-31 microg/mL) compared with unaffected relatives (39+/-36 microg/mL, mean+/-SD, P=.02). There was no evidence for a genetic contribution to SAA levels. All inducible human SAA protein types were documented by immunoblotting in both spontaneous and transplant coronary disease. CONCLUSIONS: Environmentally determined elevations in SAA levels in patients with both spontaneous and transplant coronary artery disease provide further evidence for a potential pathophysiological link between inflammation, lipoprotein metabolism, and the development of atherosclerosis.     

Circulating endothelial cell markers in peripheral vascular disease: relationship to the location and extent of atherosclerotic disease

We examined the relationship between specific endothelial cell markers soluble E-selectin, von Willebrand factor and soluble thrombomodulin and the location or extent of atherosclerosis by analysing plasma samples from 200 patients with symptomatic peripheral vascular disease and 213 age- and sex-matched asymptomatic control subjects. Using ELISAS, we found increased von Willebrand factor and thrombomodulin (both P < 0.0001) in the patients relative to the control subjects, but no significant change in soluble E-selectin. Soluble thrombomodulin was increased in patients with disease at one locus (i.e. of the carotid or iliac/femoral arteries), with an additional significant increase in patients with disease at multiple loci (i.e. any combination of carotid, coronary or iliac/femoral artery disease). No marker differentiated carotid artery disease from iliac/femoral artery disease. We conclude that von Willebrand factor is a marker of generalized atherosclerosis, but that soluble thrombomodulin is related to the extent of disease. Further research into these endothelial cell products are warranted to explore their diagnostic and/or prognostic potential.     

Exploring linkage of chromosome 18 markers and bipolar disease

Effect of oral administration of fenvalerate, a pyrethroid insecticide was studied in different behavioral paradigms in mice. Fenvalerate at 15, 30 and 45 mg/kg dose increased start latency, decreased ambulation and rearing in open-field, increased immobility in tail-suspension test and attenuated haloperidol-induced catalepsy in a dose-dependent manner. The time-course of data shows that these effects of fenvalerate may sustain up to several hours of its oral administration. The study indicates that pyrethroids can cause adverse behavioral effects even after a very low-level exposure. Although, it is difficult to extrapolate these findings directly to behavioral changes in man, they indicate that subtle behavioral dysfunction also occur in humans at exposures which do not cause acute toxicity.     

Peptide mapping of 125I-labelled influenza virus proteins. Matrix proteins as markers in recombination

We have examined the matrix proteins of A/Okuda/57, A/Finland/4/74 and A/New Jersey/8/76 viruses and several recombinant strains by radioiodination of the purified polypeptides followed by tryptic peptide mapping. The method is rapid and requires only small amounts of material. Reproducible differences were detected between the matrix proteins of the above parents and allowed origin of the matrix proteins of the recombinant viruses to be determined. The possible use of matrix protein identity as a marker in recombination work is discussed.     

A comparative analysis of Ungulata species by different molecular genetic markers (proteins, RAPD-PCR)]

The investigation of genetic interrelation between a number of Artiodactyla and Perissodactyla species with the use of different types of molecular-genetic markers (proteins, RAPD-PCR) were carried out. The marker-specific features of interspecific relations and their similarities on the groups of markers of both types were revealed. The distinctions between interspecies genetic relations and ones estimated from the phylogeny on the determined group of different types of markers were observed. It was supposed that these discrepancies may be related with common selection factors and involving this marker group in selection in some species.     

Type D retrovirus markers in healthy Africans from Guinea

Sixteen matching sera and DNA samples from healthy African blood donors living in rural areas of Guinea were analysed for the presence of type D retrovirus markers. Screening for the antibodies against structural proteins of Mason-Pfizer monkey virus (M-PMV) was carried out by Western blot with a purified M-PMV as an antigen. Eight out of 16 sera samples were found to contain antibodies against at least two gag gene-coded proteins, and three of these were weakly positive against env gene-coded protein. Using PCR amplification and Southern hybridization, we detected M-PMV-like gag sequences in 11 out of 16 samples and env-related sequences in 8 out of 16 samples. Six DNAs were found to contain both M-PMV gag- and env-related sequences. Restriction endonuclease analysis of the PCR-amplified gag sequences from two individuals and direct DNA sequencing analysis of the amplimers confirmed their M-PMV-like origin. Detection of antibodies and M-PMV-related sequences in blood donors from Guinea, but not in French or Algerian blood donors, indicated exogenous SRV infection in humans from certain geographic areas of Western Africa.     

Psychophysiologic markers of psychopathology: A review.

Presents research criteria for the identification and evaluation of a characteristic as a genetic marker of the functional psychoses. Each of 5 psychophysiologic variables (smooth-pursuit eye tracking, nailfold capillary visibility, electrodermal nonresponding, reducing/augmenting of the visual EP, and resting EEG) is reviewed for its marker potential. With the possible exception of nailfold capillary visibility, each of these variables provides an assessment of sensory input regulation and attentional functioning, both of which have been considered to be part of the core deficit of schizophrenic and major affective disorders. It is suggested that the possibility that these variables may tap information-processing deficiencies that lie at the core of the functional psychoses adds further validity to the claim that they have potential as markers. The need to investigate the intercorrelations of these traits is emphasized. (French abstract) (115 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vitamin D metabolite-binding proteins in human tissue

Serum and post-microsomal supernatants of human lymphocyte, erythrocyte, skeletal muscle and parathyroid adenoma homogenates were examined for specific binding of 25-hydroxycholecalciferol (25-OHD3) and 1, 25-dihydroxycholecalciferol (1,25-(OH)2D3). Muscle, lymphocytes and parathyroid adenomata extracts contained a 6-S 25-OHD3-binding protein which was not found in erythrocyte extracts, and which was distinct from the smaller serum transport alpha-globulin. A cathodal, 1, 25-(OH)2D3-binding protein, which sedimented at 3-4 S was also detected in parathyroid tissue. These observations suggest the possibility of direct physiologic interaction between vitamin D metabolites and nucleated human tissues other than intestine and bone.     

Plasma proteins glycosylation and its alteration in disease

Most plasma proteins are glycoproteins, that is, they possess oligosaccharide chains attached to the polypeptide core. These oligosaccharides have important structural and functional roles; they serve as recognition markers (ligands), especially for lectin receptors, thus modulating the glycoprotein interactions. Protein glycosylation is a posttranslational event which depends on the proteic core and biosynthetic cell type and results in a set of microheterogeneous forms (glycoforms) of an individual glycoprotein. Under pathological conditions an alteration of the glycosylation pattern of plasma glycoproteins occurs. So, degalactosylated IgG and IgA1 detected in rheumatoid arthritis and IgA nephropathy, respectively, are implicated in the pathogenic mechanisms. Alteration of transferrin, alpha 1-acid glycoprotein and alpha-fetoprotein glycosylation (reduced sialylation and increased branching of oligosaccharide chains) occurs in liver diseases. In inflammations and infections the alteration is dependent on the disease studied, while increased sialylation and fucosylation of acute-phase proteins are detected in cancer sera. Lectin-based methods have been developed for clinical purposes, in order to improve the diagnosis, prognosis evaluation, or treatment monitoring.     

The relationship between argyrophilic proteins and some immunophenotypic markers in acute leukemia cells

Stroke is a leading cause of death and disability among Americans. The recent US Food and Drug Administration approval of recombinant tissue plasminogen activator (rt-PA, Activase) for the treatment of acute ischemic stroke offers the first proven therapy to reverse or ameliorate stroke symptoms. rt-PA is thought to restore circulation in the patient with acute ischemic stroke by dissolving an occluding thrombus or embolus. A basic understanding of cerebral circulation and the mechanism by which stroke compromises brain tissue is fundamental to appreciating this new therapy. The importance of prompt stroke diagnosis and treatment cannot be underestimated.     

Some remarks on biological markers of Alzheimer''s disease

Despite recent improvements in the management of Crohn's disease, steroids are still the most efficacious treatment in flare ups of the disease. However they have significant side effects and are only effective in the short term. There is no consensus regarding initial dose or duration of corticotherapy. With 1 mg/Kg a day of oral prednisolone given for 3 to 7 weeks, 92% of the patients achieve clinical remission. Topical acting oral corticosteroids such as budesonide seem to represent an important therapeutic advance due to their better tolerance. The promising results of budesonide in mild and moderate flare ups need to be confirmed and its indication in severe disease beside high dose prednisolone has to be clarified.     

Urinary markers of disease activity in multiple sclerosis

This article documents the prevalence of injection-related HIV risk behaviors among a sample of 758 Mexican-American, Puerto Rican, and African-American drug injectors derived from the National Institute on Drug Abuse Cooperative Agreement database. The results show that the two Hispanic subgroups had higher injection-related risks than the African-American group. Further, among Hispanics, Puerto Ricans had higher rates of drug injection than Mexican-Americans, but Mexican-Americans had higher rates of sharing injection paraphernalia than Puerto Ricans. The research suggests that more aggressive HIV/AIDS intervention efforts be targeted to minority injection drug users, especially those that are contextualized by the racial/ethnic group targeted.     

Bone metabolism markers in patients with Basedow-Graves disease

Collagen type I is the main collagen type found in bones. Carboxyterminal propeptide, deriving and cleaved from procollagen type I (PICP) during collagen synthesis, is delivered into the blood, where it might represent an useful marker of bone formation similarly to osteocalcin. PICP, osteocalcin, alkaline phosphatase, serum and urinary calcium excretion were measured in 58 premenopausal females affected by Graves' disease and also 28 of them after attainment of euthyroidism by methimazole treatment to study these biochemical indices of bone remodelling before and after treatment. Before therapy PICP (mean +/- S.D.: 244.2 +/- 112.3 vs. 136.8 +/- 32.4 micrograms/l), osteocalcin (mean +/- S.D.: 17.8 +/- 6.7 vs. 7.5 +/- 2.7 micrograms/l) and other markers were significantly (p < 0.05) higher than sex and age matched controls (n = 24). Treatment induced a significant decrease of PICP, alkaline phosphatase, calcaemia and calciuria compared to pretreatment values, while osteocalcin did not significantly differ (mean +/- S. D.: 17.8 +/- 6.7 vs. 14.7 +/- 8.7 micrograms/l). These data suggest that hyperthyroidism due to Graves' disease causes an increase of serum levels of these markers, but further studies are necessary to asses the differences between PICP and osteocalcin as markers of osteoblast activity in hyperthyroidism.