LIPIDAT: a database of lipid phase transition temperatures and enthalpy changes. DMPC data subset analysis.

The systematic study of the mesomorphic phase properties of synthetic and biologically derived lipids began some 30 years ago. In the past decade, interest in this area has grown enormously. As a result, there exists a wealth of information on lipid phase behavior, but unfortunately these data have until now been scattered throughout the literature in a variety of books, proceedings and journals. The data have recently been compiled in a centralized database, LIPIDAT, with a view to providing ready access to the data and to the appropriate literature. LIPIDAT consists of a tabulation of all known mesomorphic and polymorphic phase transition temperatures and enthalpy changes for synthetic and biologically-derived lipids in the dry and in the partially and fully hydrated states. Also included is the effect of pH, and of salt and metal ion concentration and other additives such as proteins, drugs, etc., on the thermodynamic values. The methods used in making the measurements and the experimental conditions are reported. Bibliographic information includes comprehensive literature referencing and list of authors, but does not at the present time include article titles. As of this writing, the database is current through June, 1990 and is approaching 10,000 records in length. Each record contains 28 fields. In this paper we report the contents and present an analysis of LIPIDAT as it refers to fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). This database subset represents about 7% of all LIPIDAT records. It includes data collected over a 23-year period from 1967 to 1989 and consists of 702 records obtained from 336 articles in 55 different journals. The number of records per year rises steadily beginning in 1971, reaches a maximum of 89 records/year in 1977 and remains relatively constant at 60-70 records/year in the succeeding period. Journals making the greatest contribution to the DMPC subset include Biochimica et Biophysica Acta, Biochemistry, Chemistry and Physics of Lipids and the Biophysical Journal. These four journals account for 71% of the total records in the database subset. The analysis shows that differential scanning calorimetry, electron spin resonance, fluorescence, nuclear magnetic resonance and Raman spectroscopy are the methods most commonly used for DMPC transition temperature determination. An interesting pattern emerges as to the place in time the different methods assume or loose popularity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prevalence and intensity of Thelazia spp. (Nematoda: Thelazioidea) in a Musca autumnalis (Diptera: Muscidae) population from Central Alberta

A face fly (Musca autumnalis) population near Wetaskiwin, central Alberta, Canada, was sampled 9 times from 26 July to 29 September 1988 for the early larval stages of Thelazia spp. Of 426 female flies examined, 159 (37%) contained Thelazia spp. (almost exclusively T. skrjabini), with an average worm burden of 4.2 larvae per infected fly. Prevalence ranged from 17 to 56% over 9 collections. This is the first report of Thelazia skrjabini in flies from western North America and the highest Thelazia prevalence in face flies yet reported in North America. The face fly population was also parasitized by Heterotylenchus autumnalis, with a prevalence of 5.5%.     

Binding of pigment epithelium-derived factor (PEDF) to retinoblastoma cells and cerebellar granule neurons. Evidence for a PEDF receptor.

Pigment epithelium-derived factor (PEDF) has neuronal differentiation and survival activity on retinoblastoma and cerebellar granule (CG) cells. Here, we investigated the presence of PEDF receptors on retinoblastoma Y-79 and CG cells. PEDF radiolabeled with (l25)I remained biologically active and was used for radioligand binding analysis. The binding was saturable and specific to a single class of receptors on both cells and with similar affinities (K(d) = 1.7-3.6 nM, B(max) = 0.5-2.7 x 10(5) sites/Y-79 cell; and K(d) = 3.2 nM, B(max) = 1.1 x 10(3) sites/CG cell). A polyclonal antiserum to PEDF, previously shown to block the PEDF neurotrophic activity, prevented the (125)I-PEDF binding. We designed two peptides from a region previously shown to confer the neurotrophic property to human PEDF, synthetic peptides 34-mer (positions 44-77) and 44-mer (positions 78-121). Only peptide 44-mer competed for the binding to Y-79 cell receptors (EC(50) = 5 nM) and exhibited neuronal differentiating activity. PEDF affinity column chromatography of membrane proteins from both cell types revealed a PEDF-binding protein of approximately 80 kDa. These results are the first demonstration of a PEDF-binding protein with characteristics of a PEDF receptor and suggest that the region comprising amino acid positions 78-121 of PEDF might be involved in ligand-receptor interactions.     

Epitope analysis and molecular modeling reveal the topography of the C-terminal peptide of the beta-subunit of human chorionic gonadotropin.

Human chorionic gonadotropin (hCG) belongs to a family of heterodimeric glycoprotein hormones that share a common alpha-subunit and a hormone-specific beta-subunit. Among the gonadotropin beta-subunits, greater than 85% homology exists between lutropin (hLH)beta and hCGbeta in their first 114 amino acid residues. However, unlike hLHbeta, hCGbeta contains a 31-amino acid hydrophilic stretch at its carboxyl end (CTPbeta: C-terminal peptide). Although the crystal structure of deglycosylated hCG has been solved, the topography of CTPbeta remains unknown. In this study, we have attempted to define the topology of CTPbeta using mAb probes. We investigated three epitopes on hCGalpha, which are hidden in the hCGalphabeta dimer. However, these epitopes are not hidden in hLH, which has a similar subunit interface to that of hCG, but lacks CTPbeta. This suggested that these epitopes are not masked at the subunit interface of hLH or hCG. Hence, we hypothesized that, in the case of hCG, these epitopes are masked by the CTPbeta. Consistent with this view, several treatments of hCG that removed CTPbeta unmasked these epitopes and enhanced their reactivity with the corresponding mAbs. In order to localise the position of CTPbeta on the alpha-subunit, we used an epitope-mapping strategy [N. Venkatesh & G. S. Murthy (1997) J. Immunol. Methods 202, 173-182] based on differential susceptibility of epitopes to covalent modifications. This enabled us to predict the possible topography of CTPbeta. Further, we were also able to build a model of CTPbeta, completely independently of the epitope-mapping studies, using a homology-based modeling approach [S. Krishnaswamy, I. Lakshminarayanan & S. Bhattacharya (1995) Protein Sci. 4 (Suppl. 2), 86-97]. Results obtained from these two different approaches (epitope analysis and homology modeling) agree with each other and indicate that portions of CTPbeta are in contact with hCGalpha in the native hCG dimer.     

Chronic viral hepatitis C: management update

The management of chronic viral hepatitis C is evolving rapidly. Monotherapy with interferon, the accepted standard of treatment until recently, achieves only a modest sustained virological response rate of 15%. Combination treatment with alpha-2b interferon and ribavirin has been shown to increase sustained response rates to 40% in patients who have never been treated with interferon and to 50% in those who have relapsed following monotherapy with interferon. However, side effects, which have led to the discontinuation of combination treatment in a significant proportion of patients, must be carefully monitored. Treatment with interferon alpha-2b and ribavirin has now been approved in Canada, but the selection and monitoring of patients suitable for combination treatment requires special expertise. Although improvements in current therapeutic options may be possible with more frequent, higher doses or long-acting forms of interferon together with ribavirin, low sustained response rates (i.e., below 30%) for patients with hepatitis C virus genotype 1 emphasize the need for novel antiviral medications that will target the functional sites of the HCV genome.