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S Milton

Publications and source records attributed to S Milton.

17 recordsLinked to original sources
PubMed2000

A conformation change in the carboxyl terminus of Alzheimer's Abeta (1-40) accompanies the transition from dimer to fibril as revealed by fluorescence quenching analysis.

Alzheimer's disease is characterized by the presence of insoluble, fibrous deposits composed principally of amyloid beta (Abeta) peptide. A number of studies have provided information on the fibril structure and on the factors affecting fiber formation, but the details of the fibril structure are not known. We used fluorescence quenching to investigate the solvent accessibility and surface charge of the soluble Abeta(1-40) dimer and amyloid fibrils. Analogs of Abeta(1-40) containing a single tryptophan were synthesized by substituting residues at positions 4, 10, 34, and 40 with tryptophan. Quenching measurements in the dimeric state indicate that the amino-terminal analogs (AbetaF4W and AbetaY10W) are accessible to polar quenchers, and the more carboxyl-terminal analog AbetaV34W is less accessible. AbetaV40W, on the other hand, exhibits a low degree of quenching, indicating that this residue is highly shielded from the solvent in the dimeric state. Correcting for the effect of reduced translational and rotational diffusion, fibril formation was associated with a selective increase in solvent exposure of residues 34 and 40, suggesting that a conformation change may take place in the carboxyl-terminal region coincident with the dimer to fibril transition.

Alzheimer Disease↗
PubMed1998

Nosocomial transmission of a drug-sensitive W-variant Mycobacterium tuberculosis strain among patients with acquired immunodeficiency syndrome in Tennessee.

OBJECTIVE: To use DNA fingerprinting to characterize nosocomial spread of Mycobacterium tuberculosis following hospitalization of a patient with acquired immunodeficiency syndrome and active pulmonary tuberculosis, for whom respiratory isolation was not initiated promptly. DESIGN: Epidemiological investigation. SETTING: A tertiary-care medical center in Tennessee. PARTICIPANTS: Patients and healthcare workers potentially exposed to the infectious patient in 1992. RESULTS: Of 172 healthcare workers exposed, 35 (20%) were judged to have acquired tuberculous infection. Risk of acquisition was greatest for nurses and medical receptionists. Active tuberculosis later developed in one healthcare worker and one hospitalized patient. Nosocomial transmission was supported by epidemiological evidence and DNA fingerprinting. The outbreak strain of Mycobacterium tuberculosis differed from other isolates at this hospital, but its DNA hybridization pattern was highly similar to that of the multidrug-resistant outbreak strain W that has been prevalent in New York City, suggesting a common strain ancestry. However, the Tennessee isolates were susceptible to all first-line antituberculous agents. CONCLUSIONS: This report suggests the possibility that a molecular characteristic(s) shared by these successful outbreak strains is associated with increased transmissibility or pathogenicity and emphasizes the need for continued vigilance for tuberculosis in the nosocomial setting.

AIDS-Related Opportunistic Infections↗
PubMed1997

Brain Na+/K+-ATPase activity in two anoxia tolerant vertebrates: crucian carp and freshwater turtle.

The crucian carp (Carassius carassius) and freshwater turtles (Trachemys scripta) are among the very few vertebrates that can survive extended periods of anoxia. The major problem for an anoxic brain is energy deficiency. In the brain, the Na+/K+-ATPase is the single most ATP consuming enzyme, being responsible for maintaining ion gradients. We here show that the Na+/K+-ATPase activity in the turtle brain is reduced by 31% in telencephalon and by 34% in cerebellum after 24 h of anoxia. Both changes were reversed upon reoxygenation. By contrast, the Na+/K+-ATPase activities were maintained in the anoxic crucian carp brain. These results support the notion that crucian carp and turtles use divergent strategies for anoxic survival. The fall in Na+/K+-ATPase activities displayed by the turtle is likely to be related to the strong depression of brain electric and metabolic activity utilized as an anoxic survival strategy by this species.

Animals↗
PubMed1997

Soluble amyloid Abeta-(1-40) exists as a stable dimer at low concentrations.

Recent studies have implicated the amyloid Abeta peptide and its ability to self-assemble as key factors in the pathogenesis of Alzheimer's disease. Relatively little is known about the structure of soluble Abeta or its oligomeric state, and the existing data are often contradictory. In this study, we used intrinsic fluorescence of wild type Abeta-(1-40), fluorescence resonance energy transfer (FRET), and gel filtration chromatography to examine the structure of Abeta-(1-40) in solution. We synthesized a series of mono-substituted fluorescent Abeta-(1-40) derivatives to use as donors and acceptors in FRET experiments. We selected fluorescent peptides that exhibit aggregation properties comparable to wild type Abeta for analysis in donor-acceptor pairs; two labeled with 5-(2-((iodoacetyl)amino)ethyl)aminonaphthylene-1-sulfonic acid at Cys-25 or Cys-34 and fluorescein maleimide at Cys-4 or Cys-7. Another peptide containing a Trp substitution at position 10 was used as an acceptor for the intrinsic Tyr fluorescence of wild type Abeta-(1-40). Equilibrium studies of the denaturation of Abeta-(1-40) by increasing concentrations of dimethyl sulfoxide (Me2SO) were conducted by monitoring fluorescence, with a midpoint value for the unfolding transition of both the substituted and wild type peptides at among 40 and 50% Me2SO. Abeta-(1-40) is well solvated and largely monomeric in Me2SO as evidenced by a lack of FRET. When donor and acceptor Abeta derivatives are mixed together in Me2SO and then diluted 10-fold into aqueous Tris-HCl buffer at pH 7.4, efficient FRET is observed immediately for all pairs of fluorescent peptides, indicating that donor-acceptor dimers exist in solution. FRET is abolished by the addition of an excess of unlabeled Abeta-(1-40), demonstrating that the fluorescent peptides interact with wild type Abeta-(1-40) to form heterodimers that do not exhibit FRET. The Abeta-(1-40) dimers appear to be very stable, because no subunit exchange is observed after 24 h between fluorescent homodimers. Gel filtration confirms that nanomolar concentrations of 14C-labeled Abeta-(1-40) and fluorescein-labeled Abeta-(1-40) elute at the same dimeric position as wild type Abeta-(1-40), suggesting that soluble Abeta-(1-40) is also dimeric at more physiologically plausible concentrations.

Amyloid beta-Peptides↗
PubMed1996

Increased plasma corticosterone levels in bovine growth hormone (bGH) transgenic mice: effects of ACTH, GH and IGF-I on in vitro adrenal corticosterone production.

Previous work from our laboratory provided evidence for increased plasma corticosterone levels in mice transgenic for human and bovine growth hormone (GH). Corticosterone was elevated in both sexes, under both basal and ether-induced stress conditions. The objectives of the present study were to investigate the in vitro adrenal sensitivity to ACTH, GH and/or IGF-I in normal and bGH transgenic mice, to examine plasma corticosterone levels at different times of the day, and to determine plasma levels of ACTH in these animals. For the measurement of plasma corticosterone and ACTH levels, transgenic and normal siblings were housed 2 per cage and decapitated simultaneously within 20 seconds of the first disturbance of the cage. The corticosterone production by in vitro adrenal incubations did not differ between adrenals from normal and transgenic mice at the basal level or in the presence of different doses of ACTH. Growth hormone or IGF-I did not have any effect on corticosterone production in vitro when given alone, and did not modify the effects of ACTH on the accumulation of corticosterone production in vitro when alone, and did not modify the effects of ACTH on the accumulation of corticosterone in the media. Plasma corticosterone concentrations were higher in transgenic than in normal animals in both morning and evening. Plasma concentrations of ACTH in animals killed in the morning were sharply increased in transgenic males as compared with their normal siblings. The results indicate that increased circulating levels of corticosterone in transgenic mice are not due to a potentiation of ACTH actions by GH or IGF-I, but rather to a chronic increase in plasma ACTH levels. The increase in ACTH is presumably a reflection of GH actions in the hypothalamic-pituitary system.

Adrenal Cortex↗
PubMed1992

Transgenic female mice with high human growth hormone levels are fertile and capable of normal lactation without having been pregnant.

Transgenic mice carrying the phosphoenolpyruvate carboxykinase promoter region-human growth hormone (PEPCK-hGH) fusion gene are characterized by accelerated growth and plasma hGH levels ranging from 100 to 700 ng/ml. Both sexes are fertile, in contrast to previous findings in metallothionein-I/hGH transgenic mice in which females are sterile, apparently due to luteal failure. Virgin transgenic PEPCK/hGH females from this line produce milk and can successfully raise foster litters to weaning. We conclude that the life-long presence of very large amounts of hGH in the circulation is compatible with ovulation, can override the effects of hGH-induced suppression of endogenous PRL release, and can support full lactation in animals that have not been primed by hormonal changes associated with pregnancy.

Animals↗
PubMed1987

New antitumor agents containing the anthracene nucleus.

A series of 21 new compounds related to bisantrene was synthesized and tested in vitro by using clonogenic assays against a variety of human tumor cell lines, fresh human tumors, and P-388 leukemia. Those most closely related to bisantrene were less active than it was, but a subset of compounds with saturated side chains containing two basic nitrogens showed good activity. Two compounds of this subset, N,N'-bis[2-(dimethylamino)ethyl]-9,10-anthracenebis(methylamine)(6 ), and N,N'-bis(1-ethyl-3-piperidinyl)-9,10-anthracenebis(methylamine)(19 ), were very active in vitro against human tumor cell lines, but not active against fresh human tumors or P-388 leukemia cells. They had only marginal activity in mouse tumor models. Thus, the fresh human tumors and P-388 leukemia cells in vitro were better predictors than the established cell lines for the activity of these anthracene compounds in vivo against mouse tumors. These compounds appear to be distinct from bisantrene in aspects of mode of action. For example, 6 did not cause inhibition of macromolecular synthesis and promotion of DNA single strand breakage at cytotoxic drug concentrations. Toxicological studies showed that its rapid administration caused acute neurotoxicity resulting in apnea. It also produced skin ulcers on id administration, but they were less severe than those caused by bisantrene.

Animals↗
PubMed1979

Rural-urban differences in the structure of services for the elderly in upstate New York counties.

This research examines the impact of federal intervention and local community effort on the development of programs for the elderly. The study was designed, first, to gather longitudinal data on the structure of services for the elderly in 53 upstate New York counties for comparison with a study conducted in 1967 and, second, to measure the effectiveness of 43 counties with a County Office for the Aging (COFA) in mobilizing resources to increase services for the elderly. The findings reveal: (1) federal intervention has had the effect of an overall increase in services while at the same time decreasing rural-urban differences; (2) urban COFAs score consistently higher on the measures of community effectiveness; (3) the educational attainment of COFA directors is not a good predictor of success in mobilizing outside resources in both urban and rural counties; (4) in urban but not in rural counties, directors with administrator/planner experience have greater success in mobilizing outside resources.

Aged↗
PubMedDate not supplied

The DIAL-log study 1: Profiling the experience of people with dementia.

Between July 1996 and December 1997 telephone helpline staff from the Alzheimer's Disease Society (ADS) in London, and six participating ADS regions in England and one in Northern Ireland, documented calls from people with dementia who contacted the service. Each call was recorded as soon as practicable after its completion on a Dementia Information and Advice Line (DIAL) log form (DIAL-log). Sixty-four calls were recorded in this way and 62 completed DIAL-logs were included in the study findings. Analysis of the data was undertaken via SPSS 6.1 for Windows. This article, the first of two, introduces the background to the study and notes that callers reported memory loss and forgetfulness as the most frequently noticed first signs of dementia. The study aims and limitations are also outlined in this first article. The second article will detail the main findings and the challenges that the DIAL-log study may provide for future dementia care practice and research.

Adaptation, Psychological↗
PubMedDate not supplied

The DIAL-log study. 2: Support in the early stages of dementia.

In the previous article (Vol 8(6): 387-93) the background information and study aims/limitations of the Dementia Information and Advice Lines (DIAL-log) project were outlined. This article introduces the main findings of the project and suggests that the transition into dementia is experienced through rising degrees of uncertainty and anxiety. People with the early experience of dementia also requested strategies for coping with memory loss and uncertainty over the meaning and purpose of memory testing. Building on the main findings of the project, the article concludes with a five-stage framework to help shape future research and service support.

Adaptation, Psychological↗