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Biomedical subjects

M L Hayes

Publications and source records attributed to M L Hayes.

At least 19 recordsLinked to original sources
PubMed1999

Production of goats by somatic cell nuclear transfer.

In this study, we demonstrate the production of transgenic goats by nuclear transfer of fetal somatic cells. Donor karyoplasts were obtained from a primary fetal somatic cell line derived from a 40-day transgenic female fetus produced by artificial insemination of a nontransgenic adult female with semen from a transgenic male. Live offspring were produced with two nuclear transfer procedures. In one protocol, oocytes at the arrested metaphase II stage were enucleated, electrofused with donor somatic cells, and simultaneously activated. In the second protocol, activated in vivo oocytes were enucleated at the telophase II stage, electrofused with donor somatic cells, and simultaneously activated a second time to induce genome reactivation. Three healthy identical female offspring were born. Genotypic analyses confirmed that all cloned offspring were derived from the donor cell line. Analysis of the milk of one of the transgenic cloned animals showed high-level production of human antithrombin III, similar to the parental transgenic line.

Animals↗
PubMed1997

Characterization of anti-Toxoplasma activity of SDZ 215-918, a cyclosporin derivative lacking immunosuppressive and peptidyl-prolyl-isomerase-inhibiting activity: possible role of a P glycoprotein in Toxoplasma physiology.

The immunosuppressive agent cyclosporin A (CsA) also possesses broad-spectrum antimicrobial activity. Previous investigators have reported that the obligate intracellular protozoan Toxoplasma gondii is sensitive to CsA. We have measured the sensitivity of Toxoplasma to 26 CsA derivatives that maintain only a subset of the parent compound's activity. We identified one compound, SDZ 215-918, that is a particularly potent inhibitor of parasite invasion and replication, with a 50% inhibitory concentration of 0.45 microg/ml, which is 10-fold lower than that of CsA. Kinetic studies demonstrate that activity has a rapid onset (half-life, < or = 20 min) and is initially reversible, although long-term exposure (> 24 h) to 5 microg/ml is lethal; in contrast, this concentration had no effect on host cell protein synthesis or cell division. SDZ 215-918 acts directly on the parasite, as demonstrated by inhibition of macromolecular synthesis in host-free extracellular parasites. Inhibition of invasion is due to a reduction in parasite motility. SDZ 215-918 does not bind to cyclophilins, the ubiquitous cyclosporin-binding proteins, but is a potent inhibitor of the mammalian P glycoprotein, a member of the ATP binding cassette transporter superfamily and the pump responsible for multidrug resistance in cancer and parasite cell lines. SDZ 215-918 blocks the efflux of rhodamine 123 from extracellular parasites, consistent with inhibition of a P glycoprotein-like pump. We suggest that a P glycoprotein or a related transporter plays a crucial role in the biology of Toxoplasma and may be a novel target for antiparasitic compounds. Preliminary studies with animals indicate that SDZ 215-918 inhibits parasite growth in vivo; its relationship to CsA may make it suitable for clinical development.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Reduction in acid tolerance of Streptococcus downeii by fluoride and potassium laurate.

Streptococcus downeii MFe28 maintains a transmembrane pH gradient at low extracellular pH values using energy from glucose metabolism. The metabolic activity was measured in saturating glucose solutions using a pH-stat, and results were expressed as rates of titratable acid production at defined pH values. The tolerance to acid shock was studied in terms of the ability of cells to resume acid production at pH 8.0 following short-term exposure to low-pH environments. The results with control cells showed an optimum rate of acid production at pH 8.0. The activity extended to pH 4.5 with a half-maximal rate at pH 5.4. Addition of carbonyl cyanide-m-chlorophenylhydrazone, potassium laurate, or potassium fluoride inhibited acid production at lower but not at higher pH values. Inhibition by carbonyl cyanide-m-chlorophenylhydrazone and fluoride was found to be fully reversible at pH 8.0 when compared to control cells. In contrast, laurate inhibited irreversibly at pH values of 6.0 and below. The acid tolerance of S. downeii was severely compromised by laurate, and this action could be useful in dental caries control.

Acids↗
PubMed1993

Practical applications of Stark II to hospital operations.

With the passage of the Omnibus Reconciliation Act of 1993, the Social Security Act was amended to substantially expand the Medicare self-referral prohibitions. The amended statute, commonly referred to as "Stark II," now covers Medicare and Medicaid referrals and substantially expands the list of services covered, effective January 1, 1995. This article illustrates how Stark II may apply to some of the most common financial relationships between hospitals and referring physicians.

Financial Management, Hospital↗
PubMed1990

The effects of medium chain fatty acids and fluoride on fissure caries in Wistar rats.

This work was to compare the degree of caries protection provided by fatty acids with chain lengths of 9-12 carbons and to assess the anti-caries potential of a fluoride-fatty acid mixture. Male Wistar rats were weaned at 21 days, maintained on a standard laboratory diet for 7 days and then provided with a cariogenic, 45% sucrose diet for 34 days. This regimen produced a very reproducible degree of fissure caries and the inclusion of 1% powdered potassium nonanoate or decanoate in the diet gave large and significant reductions in total and advanced lesions. Decanoate was significantly more inhibitory towards advanced lesions than was nonanoate. In contrast, 1% potassium laurate was considerably less effective under these conditions. Caries protection with a mixture of 0.25% decanoate and 76 parts/10(6) fluoride was found to be cumulative rather than synergistic. It is suggested that the optimal effect obtained with decanoate was due to a favourable combination of the surfactant and wetting properties of this molecule at the low pH values found in fissure dental plaque. It is also suggested that fluoride and decanoate acted in an independent manner to enhance remineralization of early lesions and to inhibit the acidogenic flora, respectively.

Animals↗
PubMed1989

[Chemical composition (carbohydrates) of dental plaque in different areas of the mouth. 1. Preliminary results].

In general differences in plaque composition between anterior and posterior teeth have been reported. Dental plaque from the upper lower anterior teeth shows differences in bacterial composition and pH. Results showed that plaque from lower anterior teeth contained less alkali soluble polysaccharide per unit weight than did plaque from upper anterior teeth. However no differences in the concentration of water soluble and insoluble polysaccharide were observed. Plaque from posterior teeth did not show differences.

Adult↗
PubMed1987

Critical region hypothesis: primary amenorrhea in an 18-year-old woman with a complex translocation (X;2;8).

An 18-year-old woman presented with primary amenorrhea. She was prepubertal and had a few minor anomalies. Nonreciprocal chromosome translocations involving the X, a 2, and an 8 included a break in the region of the Xq13-q26, considered critical for normal ovarian development. Breakpoints within this region are thought to interfere with normal gonadal development. Our patient had no evidence of normal ovarian tissue or evident manifestations of the Ullrich-Turner syndrome.

Adolescent↗
PubMed1986

Paramolybdate anion-exchange resin, an improved catalyst for the C-1-C-2 rearrangement and 2-epimerization of aldoses.

Aqueous solutions of molybdate at 90 degrees bring about the inversion of the C-1-C-2 fragment of aldoses having four or more carbon atoms, generating thermodynamically equilibrated mixtures of the starting aldose and its 2-epimer. In some cases, notably with the aldopentoses, substantial proportions of the 3-epimers are produced, as well as 2-epimers that have not undergone inversion of the C-1-C-2 fragment. These side-reactions can be controlled by using the paramolybdate form of an anion-exchange resin (AG MP-1) together with the formate form of the same resin. The latter acts to scavenge unbound molybdate and paramolybdate anions that appear to be responsible for the side reactions.

Anion Exchange Resins↗
PubMed1984

The conditioning role of saliva in streptococcal attachment to hydroxyapatite surfaces.

The solution properties of saliva and its role in conditioning both the substrate and the bacterial surface have been investigated with regard to the attachment of oral streptococci to hydroxyapatite surfaces. Saliva from eight subjects was used and the attachment of three organisms, Streptococcus mutans strains FA-1 (serotype b) and KPSK2 (serotype c) and S. sanguis T175-1, was studied. An adsorbed salivary layer on a hydroxyapatite surface substantially reduced the affinity of the organisms for the surface. Adsorbed saliva on the bacterial surfaces, however, tended to increase the organisms' affinity for saliva-coated apatite. The source of saliva was important in determining the extent of inhibition of attachment. The data indicated that the negatively charged and hydrophilic nature of salivary conditioning films was important in controlling bacterial adsorption to hydroxyapatite. The results also suggested that hydrophobic salivas could promote binding of the more hydrophobic bacteria known to be early colonizers of the teeth.

Adsorption↗
PubMed1984

The effects of fatty acids and their monoesters on the metabolic activity of dental plaque.

We examined the effects of the saturated series of fatty acids and their esters on plaque bacterial metabolism. Fatty acids with a chain length of 8-15 carbons inhibited Streptococcus mutans and dental plaque in vitro. The glycerol monoesters with a fatty acid chain of 10-14 carbons were inhibitory to a similar extent. The glycolipid (sucrose monolaurate) reduced plaque bacterial glycolysis and sucrose oxidation in a non-competitive manner but stimulated sucrose incorporation at low sucrose concentrations. The relationship between surface activity and inhibition is discussed, since this may help to explain the anti-caries effects of these compounds.

Adult↗
PubMed1983

The acidogenic microbial composition of dental plaque from caries-free and caries-prone people.

Plaque samples collected from caries-free and caries-prone subjects were analysed for total bacteria, the ratio of acidogenic to total organisms and the proportions of streptococci, Streptococcus mutans and Actinomyces. The acidogenic composition of plaque reflected the dietary habits and caries status of an individual. A high acidogenic ratio was found in individuals with active lesions or recent restorations; individuals who were caries-free or had no recent lesions had a lower ratio although total organisms were similar. The ratio remained constant in sequential samples from caries-prone subjects but was increased by frequent exposure to sugar. Streptococci, Actinomyces and Strep. mutans were isolated from all samples but no consistent relationship was found between either their isolation frequency or proportions and caries status.

Actinomyces↗
PubMed1980

Effects of 2-deoxy D-glucose and other sugar analogues on acid production from sugars by human dental plaque bacteria.

Solutions (10-25 microM) of D-glucose, N-acetyl-D-glucosamine, D-fructose, sucrose, maltose, lactose and maltotriose were readily metabolised to acid (140-250 mumol H+ wet g-1h-1) by anaerobic suspensions of fresh plaque at pH 7.5. D-Mannose, D-galactose, D-glucosamine and trehalose were broken down more slowly (35-115 mumol H+ wet g-1h-1). Inhibition of this acid production occurred on adding excess amounts of 2-deoxy-D-glucose or 5-thio-D-glucose. Similarly, excess amounts of cellobiose specifically inhibited acid liberation from lactose. No acid production was detected from a number of other sugars and sugar derivatives, some of which may be useful sucrose substitutes.

Adult↗
PubMed1979

Carbohydrate of the human plasminogen variants. III. Structure of the O-glycosidically linked oligosaccharide unit.

The preceding two manuscripts in this issue (Hayes, M. L., and Castellino, F. J. (1979) J. Biol. Chem. 254, 8768-8771, 8772-8776) describe the isolation and characterization of glycopeptides from human plasminogen affinity chromatography variants 1 and 2. Plasminogen variant 1 contains an asparagine288-based branched carbohydrate structure, which has been established in the immediately preceding manuscript. This structure is absent in variant 2. Plasminogen variants 1 and 2 contain a threonine-based glycoconjugate. This latter structure has been established by combination of methylation data, glycosidase digestions, periodate oxidations, and Smith degradations of the beta-eliminated reduced oligosaccharides. One glycopeptide unit, isolated from both plasminogen variants 1 (1D) and 2 (2D) possessed the following structure: Sia alpha 2 yields 3Gal beta 1 yields 3GalNAc-Thr. The threonine was found to be residue 345 in the Glu-plasminogen sequence. Another glycopeptide unit was also found to be present, in lower yields in both variants 1 (1E) and 2 (2E). The structure of this unit was: Sia alpha 2 yields 3Gal beta1 yields 3GalNAc-Thr. : formula: (see text), alpha 2,6 Sia. Again Thr 345 was the glycosylated amino acid. The amino acid sequence around the glycosylated threonine was found to be NH2-Ala.Pro.Thr(CHO).Ala.Pro.Pro.Glu.

Amino Acid Sequence↗