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OBJECTIVE: We examine whether the pervasive income gradient in health among senior citizens can be explained in part by multiple risk exposure. METHOD: A representative sample of 457 older persons (M = 74.29 years) living independently at home were assessed in a longitudinal study. Health was assessed with a standard self-report index. Risks included loss of a loved one, caregiver burden, low housing quality, and low social integration. RESULTS: The prospective link between income and subsequent health 2 years later is largely explained by exposure to a confluence of multiple risk factors during the 2-year period. These findings incorporate controls for negative affectivity. DISCUSSION: Low-income, older persons are significantly more likely to have lost a loved one or close friend, be burdened by extensive caregiving demands for someone else, be more socially isolated, and live in lower quality housing. These risk exposures, in turn, largely account for the prospective link between income and health. [ABSTRACT FROM AUTHOR]

Immune resistance experiments were carried out in guinea-pigs employing two tick species that as adults are ectoparasites of cattle (Ixodes holocyclus and Rhipicephalus appendiculatus). These studies showed that susceptibility of non-immune guinea-pigs to infestation with tick larvae varies according to the species of tick and the strain of guinea-pig. With both tick species, greater than 90% acquired resistance was achieved in several guinea-pig strains. Immune resistance was evident within a week following primary infestation and lasted up to 9 months following a single sensitizing exposure to tick feeding. The strength and duration of resistance was influenced strongly by the size of the initial sensitizing dose. Immune resistance was readily transferred to naive recipients by intravenous administration of either peritoneal exudate cells or immune serum from donors sensitized by a single prior infestation with ticks. Doses of serum as small as 0.5 ml transferred resistance. These studies demonstrate that both sensitized cells and immune serum factors contribute significantly to acquired host resistance to ticks that as adults are ectoparasites of cattle. [ABSTRACT FROM AUTHOR]

The antigenic cross-reactivity of the excretions-secretions (E-S) of Litomosoides carinii was investigated. Immunoprecipitation using pooled sera from a number of human filarial infections in combination with sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed variations in the cross-reactivity of individual molecules. Some were specific to L. carinii, the major examples in this category being two E-S components of 140 and 160 kDa released by day 40- to 42-dy-old female worms. Another, a high-molecular-weight product of 26- to 28-day E-S, was broadly cross-reactive. A third group appeared to exhibit reactivity to antibody to some but not all human filarial parasites. The most striking examples of this were two distinct 14-kDa products that bound solely to antibodies in an onchocerciasis serum pool. These results are discussed in relation to the use of cross-reacting molecules in investigating the immunisation potential, defining the function, and evaluating the diagnostic utility of human filarial E-S. [ABSTRACT FROM AUTHOR]

Transforming growth factor beta (TGF-beta) is a multifunctional peptide that controls proliferation, differentiation, and other functions in a variety of cell types. Transforming growth factor beta activities have been implicated in a variety of diseased states including arthritis, prostate cancer, and AIDS, and in the repair of tissue injury caused by trauma, burns, and surgery. We describe the development and characterization of novel murine monoclonal antibodies (MAbs) to the latency-associated peptide (LAP) of TGF-beta 1, and the subsequent development of an ELISA for the detection and quantitation of TGF-beta 1-LAP in buffer and serum matrices. Fusion of immune splenocytes with myeloma cells yielded 576 hybridomas, 110 of which were antibody secreting. Five were selected for extensive characterization. Clinically, the MAbs described here should be valuable for studying potentially abnormal production and/or function of the LAP, and its relationship to TGF-beta.

Recombinant human transforming growth factor beta (rhTGF-beta 1) enhances the healing process after topical application to various animal wound models. A detailed pharmacokinetic and tissue distribution study was performed to support the clinical development of rhTGF-beta 1 for wound healing indications. Rats received radioiodinated or unlabeled rhTGF-beta 1 as an intravenous (iv) bolus or as a topical formulation applied to a full thickness wound. Plasma concentrations of TGF-beta 1 were estimated from TCA-precipitable radioactivity or were measured by ELISA. Following iv administration, the initial half-life was rapid (< 11 min), regardless of whether radiolabeled or unlabeled rhTGF-beta 1 was used. The terminal half-life was long (163 min) when the test material was radioiodinated and administered as a trace dose and relatively short (< or = 61 min) when given at high doses and assayed by ELISA. Analysis of plasma radioactivity by SDS-PAGE revealed a time-dependent clearance of the 25-kDa parent molecule without a significant appearance of lower molecular weight radiolabeled metabolites. The majority of the radioactivity was associated with highly perfused organs, known iodide elimination pathways, and the thyroid at 1 and 8 hr after iv injection. After topical administration of a high dose (0.8 mg/kg), no immunoreactive TGF-beta 1 was detectable in plasma samples taken over a 48-hr period. However, trace amounts (< or = 0.05 ng/mL) of acid-precipitable radioactivity were detected in plasma after topical application of [125I]rhTGF-beta 1 (1 microgram/kg, 126 microCi/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

A monoclonal antibody (2A5B9), previously shown to be reactive with a 14 kD surface associated antigen of Onchocerca microfilariae, was found to recognise a 92 kD molecule present in an adult worm extract. The antibody was used to select cDNA clones with a coding capacity larger than 14 kD, from a lambda gt11 library of O. volvulus. Nucleotide sequencing of the cDNA of one such clone revealed extensive homology to the myosin (unc-54) and paramyosin (unc-15) genes of Caenorhabditis elegans, similarly to myosin and paramyosin genes of Onchocerca volvulus, Brugia malayi, Dirofilaria immitis and Schistosoma mansoni. The immunological implications of antigenic cross-reactivity between a surface molecule and paramyosin, a known protective antigen, are discussed.

A 14-kDa antigen present on the surface of uterine microfilariae of Onchocerca spp. has been identified using monoclonal antibodies. The antigen was also found in skin microfilariae, but in a masked or cryptic form. A complementary DNA clone encoding the epitope recognised by one of the monoclonal antibodies was identified in a lambda gt11 library. Nucleotide sequencing revealed that the 233-bp cDNA fragment codes for the carboxy-terminus of the antigen. The deduced amino acid sequence consists of three hydrophobic domains with high potential for beta-sheet formation. The amino-terminal hydrophobic domain is followed by 4 positively charged residues (positions 22-25) which contribute to the rather basic character of the protein. Another interesting feature of the polypeptide is its richness in phenylalanine (12.7%). From the sequence information, a synthetic peptide was synthesised which was recognised by one of the monoclonal antibodies directed against the 14-kDa antigen and a small number of sera from patients with onchocerciasis. The relevance of this to vaccination is discussed.

A specific and high throughput 96-well format bioassay for recombinant human relaxin (rhRLX) has been developed using human endometrial cells (NHE cells). rhRLX caused a time- and dose-dependent stimulation of cyclic AMP (cAMP) with 1/2 maximal activity of 3.56 +/- 0.65 ng/ml (n = 30). The range of the standard curve was 0.39 to 25 ng/ml with interplate precision of 17 and 22% CV for high and low controls respectively. The cAMP response requires forskolin and 3-isobutyl-1-methylxanthine, and is enhanced by prostaglandin E2 and F2 alpha. The NHE cells do not respond to A or B chains of rhRLX, or a whole array of hormones. Preincubation of rhRLX with specific monoclonal antibody completely abolished the cAMP response. This bioassay has been used to determine the biological activity of several manufactured lots of recombinant human relaxin.

The biophysical properties of the surface lipid of a range of nematode species and their developmental stages were examined, using fluorescent lipid probes and fluorescence recovery after photobleaching (FRAP). These methods can be applied to living, intact parasites, and the analysis confined to lipid on the outermost surface. In all cases, surface lipid was unusual in its selectivity for the insertion of the lipid probes. In addition, a polar lipid probe was generally not free to diffuse in the plane of the surface, in contrast to a non-polar lipid probe which was free to diffuse. This is evidence that the surface lipid layer is heterogeneous, and possibly comprises lipid domains. The infective larvae of Acanthocheilonema viteae, Nippostrongylus brasiliensis, Trichinella spiralis and Ostertagia ostertagi were found to exhibit a rapid change in lipophilicity upon exposure to conditions simulating entry into a mammalian host environment. Parasitic nematodes, therefore, present their hosts not only with a highly unusual biological surface, but also one which can be rapidly re-organised upon a change of environment.

Antibody responses were measured in a volunteer infected four times with Necator americanus over a 27-month period. The main source of antigen was culture fluid in which living adult N. americanus had been maintained for several days. Antibodies to worm acetylcholinesterase and IgE antibodies were detected only with this material, but antibodies were identified by the enzyme-linked immunosorbent (ELISA) assay, with either adult worm secretions or extracts of third-stage infective larvae. The total serum IgE level fell after the first infection, but although it then increased during subsequent infections, it never rose above 600 U per ml. None of the antibody responses suppressed the rat of worm development to maturity, or reduced the fecundity of the parasites. However, it is suggested that the development of the immune response may be associated with the waning of the severe gastro-intestinal symptoms which were experienced in this infection, and which are frequently characteristic of hookworm infections.