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Biomedical subjects

E King

Publications and source records attributed to E King.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

Binding of nascent collagen by amyloidogenic light chains and amyloid fibrillogenesis in monolayers of human fibrocytes.

Light (L) chain dimers expressed by multiple myeloma cells and collected as Bence-Jones proteins from the urine of human subjects were tested for their ability to form deposits in fibroblast monolayer cell cultures. Bence-Jones proteins from subjects with primary amyloidosis associated with L chains were shown to form fibrillar deposits by the in vitro assay introduced in this report. Filaments interspersed with nascent collagen could be detected after only 48 h. Deposition of L chains continued over a period of 72 h culminating in the appearance of dense fibrils with widths of 80-100 A and a variety of lengths. Formation of amyloid-like fibrils was accompanied by interference with the maturation of the collagen produced by the fibroblast cells. Fibrils composed of the Mcg lambda-type L chain were deposited between collagen fibers, thus expanding them laterally and leading to their partial disintegration. Mature collagen was completely missing from fibroblast monolayers exposed to the Sea lambda chain and the Jen kappa chain. Collagen with the characteristic striped pattern matured normally in control samples, such as those not dosed with amyloid precursors or those treated with a non-amyloidogenic Bence-Jones protein (e.g., the Hud lambda chain dimer). By immunochemical techniques using fluorescein- and gold-labeled anti-L chain antibodies, amyloidogenic L chains were shown to decorate the strands of nascent collagen. This observation suggests that amyloidogenic L chains are concentrated in the extracellular matrix by monovalent antigen-antibody type reactions. The capacity of the Mcg L chain dimer to bind collagen-derived sequences was tested by soaking crystals with a collagenase substrate, PZ-Pro-Leu-Gly-Pro-D-Arg. Difference Fourier analysis at 2.7 A resolution indicated that the PZ-peptide is a site-filling ligand. It could not be removed from the active site by perfusion of the crystal with ammonium sulfate crystallizing media. Similar experiments with the collagen-derived peptide (Pro-Pro-Gly)(5) showed substantial hysteresis effects extending from one end of the Mcg dimer to the other. After the ligand was withdrawn, the active site of the Mcg dimer could no longer bind the PZ-peptide. However, if the active site was first blocked by the PZ-peptide and subsequently exposed to the (Pro-Pro-Gly)(5) peptide, the difference Fourier map was indistinguishable from that obtained with the PZ-peptide alone. We concluded that amyloidogenic L chains such as the Mcg dimer could be concentrated in the perivascular space by binding to normal tissue constituents. These components include nascent collagen, which can be deterred from maturing as a result of this binding. Participation in such pathological activity is also self-destructive to the amyloidogenic L chains, which lose their binding capabilities for collagen-derived peptides and also become susceptible to irreversible conversion to amyloid fibrils. All of these events may be prevented by prior treatment of the amyloidogenic L chains with site-filling ligands. (c) 2000 John Wiley & Sons, Ltd.

Amyloid↗
PubMedDate not supplied

Constructional apraxia in Alzheimer's disease: association with occipital lobe pathology and accelerated cognitive decline.

The functional impact and progression of occipital lobe pathology in sporadic late onset Alzheimer's disease (AD) is barely explored. It is accepted that the primary and association visual areas are affected relatively late, in the neocortical stages of AD. We analysed 60 prospectively assessed AD patients in whom global cognitive deterioration and constructional apraxia were evaluated longitudinally using the CAMDEX. Radioactive immunohistochemistry was used to assess the amount of AD-related pathology in Brodmann areas 18 and 17. Braak staging of each case was also carried out. This study showed that in AD patients constructional apraxia is associated with higher expression of hyperphosphorylated tau. Additionally our findings indicate that early constructional apraxia is a predictor of accelerated cognitive decline in AD.

Age Factors↗
PubMedDate not supplied

Spending on mental health and substance abuse treatment, 1987-1997.

This paper is the result of an ongoing effort to track spending on mental health and substance abuse (MH/SA) treatment nationwide. Spending for MH/SA treatment was $85.3 billion in 1997: $73.4 billion for mental illness and $11.9 billion for substance abuse. MH/SA spending growth averaged 6.8 percent a year between 1987 and 1997, while national health expenditures grew by 8.2 percent.

Adult↗
PubMedDate not supplied

Multistrategy health education program to increase mammography use among women ages 65 and older.

Mammography use decreases with age although the risk of breast cancer increases with age. Medicare now provides biennial coverage for screening mammography. This study was designed to simulate the Medicare condition by subsidizing mammography among women in eight retirement communities in the metropolitan Philadelphia area. The study also measured the impact of health education interventions and the presence of a mobile mammography van on increased use of mammography. Retirement communities were assigned randomly to the control (cost subsidy alone) or experimental group (cost subsidy, mammography van, and tailored health education interventions). A total of 412 women ages 65 and older who had not had mammograms in the previous year were surveyed at baseline and 3 months later. Analytic techniques reflected the cluster nature of the randomization. Women in the experimental group were significantly more likely than the control group women to have obtained mammograms. Forty-five percent of the experimental group women compared with 12 percent of the control group women subsequently had mammograms in the 3 months after the baseline interview (P less than .001). Logistic regression analysis for mammography use indicated an odds ratio of 6.1 associated with being in the experimental group. For women in the experimental group, a separate logistic regression for mammography use showed an odds ratio of 7.8 associated with attendance at the educational presentation. The results suggest that Medicare coverage alone will not increase mammography use sufficiently to achieve year 2000 objectives. However, the addition of access enhancing and health education interventions boosts utilization dramatically.

Aged↗
PubMedDate not supplied

Why do some women get regular mammograms?

One in nine American women will be diagnosed with breast cancer at some time in their lives. Although mammography is a proven technology for diagnosing early, curable breast cancer, most women do not obtain regular mammograms. The purpose of this study was to identify the characteristics of women who received more than one mammogram. Such information is needed to develop health education programs aimed at fostering adherence to routine mammographic screening. The data were obtained from a 1989 random telephone survey of 910 women 50-74 years of age. The survey is part of the evaluation strategy for a five-year breast screening study. Two-thirds of the respondents reported having had mammograms. Most of these women had one or two mammograms. We report two logistic regression models which describe women who had mammograms in the past year and those who had one versus two or more mammograms. The most important variable in the models was physician support. Other consistently significant variables included being willing to pay $75-$100 (although most women did not pay this amount), visiting the doctor at least annually when healthy, being a nonsmoker, and recognizing that women older than 50 are at greater risk for breast cancer. The results indicate that two-pronged educational strategies aimed at both women and their physicians are needed to increase the percentage of women who obtain regular mammograms.

Aged↗