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J Chapman

Publications and source records attributed to J Chapman.

At least 253 records · Page 14Linked to original sources
PubMed1994

[Low density lipoprotein receptor and hypercholesterolemia].

Familial hypercholesterolaemia is the most frequent of the monogenic genetic disorders. The studies of Brown, Goldstein and collaborators have facilitated decisive progress in our understanding of the pathophysiology of this hypercholesterolaemia, and more specifically in our knowledge of the metabolism of the low-density lipoproteins (LDL) and of cholesterol at the cellular level. Indeed, they have documented the existence of a ubiquitous receptor which facilitates cellular uptake of LDL-cholesterol; such cholesterol is subsequently available to satisfy the metabolic requirements of the cell. The description of numerous mutations of the LDL receptor protein have allowed an exemplary approach to the study of the relationship between its structure and function. Familial hypercholesterolaemia represents a classical illustration of the atherogenic role of LDL-cholesterol in a clinical context in man. This disorder has already featured three minor therapeutic revolutions: LDL apheresis, inhibitors of HMG-CoA reductase (statins) and most recently, gene therapy.

Chromosomes, Human, Pair 19↗
PubMed1994

Structural domains of apolipoprotein(a) and its interaction with apolipoprotein B-100 in the lipoprotein(a) particle.

The structural domains of human apolipoprotein(a) [apo(a)] and its interaction with apolipoprotein B-100 (apo B-100) in the lipoprotein(a) [Lp(a)] particle were investigated by limited proteolysis with thermolysin and cathepsin D. We characterized the proteolytic products by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis, followed by immunoblotting using different antibodies. For apo B-100 in Lp(a), the digestion patterns were found to be identical to those previously described [Chen et al. (1989) J. Biol. Chem. 264, 14369-14375; Chen et al. (1991) J. Biol. Chem. 266, 12581-12587] for apo B-100 in LDL. Thus, we compared the digestion patterns of apo B-100 in Lp(a) resolved under reducing and nonreducing migrating conditions. Using an antibody specific for a synthetic peptide of apo B-100 (residues 4004-4021), we confirmed that apo B-100 was linked to apo(a) by its C-terminal end. Various Lp(a)s isolated from several donors, and containing different isoforms, were used to study the structural domains of apo(a). Using the same procedure as for apo B-100, several common features were found for the different isoforms. (1) Apo(a) can be cleaved into two structural domains: one was of constant size (170 kDa) and was linked to apo B-100. Using an antibody specifically directed against kringle V, we demonstrated that this fragment corresponded to the C-terminal part of apo(a). (2) The other domain, whose size varied according to the digested apo(a) isoform, was not linked to apo B-100.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein B-100↗
PubMed1994

Program for procurement of drugs for indigent patients.

A program for procuring free medications for indigent patients from pharmaceutical manufacturers is described. A medical center that provides $36 million in free care annually to indigent patients sought a way to offset drug costs for these patients while maintaining the same level of care. The pharmaceuticals with the greatest impact on the pharmacy budget were identified; manufacturers of these pharmaceuticals were surveyed to determine if they offered free drugs to qualified patients. The net potential cost avoidance resulting from procuring these free drugs was estimated at $150,000 for the first year. A full-time pharmacist was hired to identify patients likely to qualify for such assistance, help patients apply for assistance, and coordinate the receipt and distribution of the resulting medication supplies. The program served 200 patients the first year (fiscal year 1992) and more than 300 patients the next year. Medications obtained for these patients included i.v. immune globulin, cancer chemotherapy agents, growth factors, antimicrobials, antiemetics, and interferons. The acquisition cost of the medications received was $448,851 in 1992 and $504,211 in 1993. A pharmacy-based program to procure free medications for indigent patients has helped to defray a medical center's expense of providing care.

California↗
PubMed1994

Association of elevated lipoprotein(a) levels and coronary heart disease in NIDDM patients. Relationship with apolipoprotein(a) phenotypes.

Non-insulin-dependent diabetes mellitus (NIDDM) is a strong and independent risk factor for coronary heart disease. We assessed the potential relationship between plasma Lp(a) levels, apo(a) phenotypes and coronary heart disease in a population of NIDDM patients. Seventy-one patients with coronary heart disease, who previously have had transmural myocardial infarction, or significant stenosis on coronary angiography, or positive myocardial thallium scintigraphy, or in combination, were compared with 67 patients without coronary heart disease, who tested negatively upon either coronary angiography, myocardial thallium scintigraphy or a maximal exercise test. The prevalence of plasma Lp(a) levels elevated above the threshold for increased cardiovascular risk (> 0.30 g/l) was significantly higher (p = 0.005) in patients with coronary heart disease (33.8%) compared to the control group (13.4%). The relative risk (odds ratio) of coronary heart disease among patients with high Lp(a) concentrations was 3.1 (95% confidence interval, 1.31-7.34; p = 0.01). The overall frequency distribution of apo(a) phenotypes differed significantly between the two groups (p = 0.043). However, the frequency of apo(a) isoforms of low apparent molecular mass (< or = 700 kDa) was of borderline significance (p = 0.067) between patients with or without coronary heart disease (29.6% and 16.4%, respectively). In this Caucasian population of NIDDM patients, elevated Lp(a) levels were associated with coronary heart disease, an association which was partially accounted for by the higher frequency of apo(a) isoforms of small size. In multivariate analyses, elevated levels of Lp(a) were independently associated with coronary heart disease (odds ratio 3.48, p = 0.0233).

Apolipoproteins A↗
PubMed1994

Sensitivity of the platelet immunofluorescence test (PIFT) and the MAIPA assay for the detection of platelet-reactive alloantibodies: a report on two U.K. National Platelet Workshop exercises.

This report presents the results of two National Workshop exercises which were designed to evaluate interlaboratory and interassay variation in sensitivity of techniques used for the detection of platelet-reactive alloantibodies. Most workshop participants used the platelet immunofluorescence test. Sensitivity of this assay was improved when fluorescence was measured by flow cytometer rather than by microscope. The MAIPA assay was found to be highly sensitive but required considerable technical expertise, and the choice of antiglycoprotein IIb/IIIa (CD61/41) monoclonal antibody was found to have a significant effect on its ability to detect anti-HPA-1a.

Antibodies, Monoclonal↗
PubMed1994

Comparison of serological and DNA HLA-DR typing results for transplantation in Western Europe, Eastern Europe, North America and South America.

In a previous study, DNA typing revealed that 25% of serological HLA-DR typings of kidney transplants were incorrect. In the current study, we analyzed whether this error rate had improved in recent years, and whether there were differences according to geographical region. From 1988 to 1991 the error rate of serological typing improved slightly in Western Europe from 19% to 16%, and in North America, from 21% to 16%. In Eastern Europe, the error rate decreased from 49% to 33% in 1991, whereas the rate remained high in South America at 60% in 1988 and 72% in 1991. The high error rates in South America and Eastern Europe reflected a lack of good quality serological typing reagents. The 16% typing errors in Western Europe and North America demonstrated the current limit of serological techniques for cadaver donor typing and underlined the need for prospective DNA typing.

DNA↗
PubMed1994

The risk of developing Creutzfeldt-Jakob disease in subjects with the PRNP gene codon 200 point mutation.

We determined the penetrance of the PRNP 200Lys mutation in the large cluster of Creutzfeldt-Jakob disease (CJD) cases among Jews of Libyan-Tunisian origin living in Israel, utilizing data from 52 carriers with definite or probable CJD and 34 unaffected mutation carriers. A life table analysis was carried out with development of CJD as the end point. The probability of developing CJD rose with age, fitting a second-order regression curve (R = 0.97, p < 0.001). The cumulative penetrance reached 50% at the age of 60 and 80% at 80 years. Including seven elderly possible CJD patients in the analysis made the penetrance approach 100% by age eighty. The penetrance of the mutation is high, and although age is a predominant influencing factor, other factors, such as gender, may also play a role.

Adult↗