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Biomedical subjects

L Summers

Publications and source records attributed to L Summers.

At least 19 recordsLinked to original sources
PubMed2000

Reduction of murine mammary tumor metastasis by conjugated linoleic acid.

Recent studies have shown that conjugated linoleic acid (CLA) can inhibit the initiation and thus, incidence of mammary tumors in rodents. The concentration of CLA required for these effects was as low as 0.1% of the diet, with no increased effects above 1%. To date, there is little evidence that CLA has any effect on growth or metastasis of mammary tumors. In this report, we demonstrate that CLA, at the concentrations used in previous studies, had a significant effect on the latency, metastasis, and pulmonary tumor burden of transplantable murine mammary tumors grown in mice fed 20% fat diets. The latency of tumors from mice fed CLA was significantly increased when compared with the 0% CLA control diet. The volume of pulmonary tumor burden, as a result of spontaneous metastasis, decreased proportionately with increasing concentrations of dietary CLA. With 0.5 and 1% CLA, pulmonary tumor burden was significantly decreased compared to mice treated with the eicosanoid inhibitor, indomethacin and fed diets containing no CLA. Tumors of mice fed as little as 0.1% CLA and as much as 1% had significantly decreased numbers of pulmonary nodules when compared with diets containing no CLA. The decrease in the number of pulmonary nodules by CLA was nearly as effective as indomethacin, a known suppressor of tumor growth and metastasis in this malignant model. These data suggest that effects of CLA on mammary tumorigenesis may go beyond the reported alterations in tumor incidence and effect later stages, especially metastasis.

Animals↗
PubMed1998

The distribution of CD1 molecules in inflammatory neuropathy.

The CD1 molecules have been shown to present non-protein antigens, such as complex lipids to Mycobacteria, and may be important in presenting glycolipids which are involved in inflammatory neuropathies. To study the expression of CD1 molecules in peripheral nerve, we examined nerve biopsies from two patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), five with acute axonal neuropathy, six with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), nine with chronic axonal neuropathy, six with vasculitic neuropathy and three with no histological abnormality. Immunocytochemical studies showed strong labelling of CD1b on endoneurial macrophages (CD68+) and on myelinated nerve fibres in both AIDP patients, but it was rarely observed in the other patients. Weaker staining was seen on endoneurial macrophages and/or other endoneurial cells in some of the patients with other peripheral neuropathies, but none of the control nerves. CD1a had a weaker, but similar pattern. There was endoneurial infiltration of CD4+ and CD8+ T cells in the AIDP and CIDP nerves and sometimes in the other peripheral neuropathy nerves, but not in the normal nerves. Most T cells had alpha beta+ T cell receptors (TCR), but gamma delta+ TCR T cells were found in the nerves of both AIDP patients and sometimes in the nerves of other patients with peripheral neuropathy. Staining for mannose receptor was almost universal, being more intense in AIDP, chronic axonal neuropathy and vasculitis patients. We conclude that CD1 molecule expression is upregulated in peripheral neuropathy, especially in association with inflammation.

Aged↗
PubMed1997

Characteristics of current hospital-sponsored and nonhospital birth centers.

OBJECTIVES: (1) To describe contemporary birth centers in terms of the population served, organizational and financial characteristics, services provided, mission and philosophy, and planning and marketing techniques. (2) To compare hospital-sponsored and nonhospital models with regard to the above characteristics. METHOD: Data from the National Survey of Women's Health Centers conducted in 1994 are analyzed using t-tests and chi-square tests. RESULTS: Contemporary birth centers serve a diverse population of women and provide a range of clinical and nonclinical services. Birth centers are both hospital-sponsored and nonhospital, with the former growing at a faster rate. Compared to hospital-sponsored centers, nonhospital centers serve a larger proportion of uninsured women, provide a broader range of clinical services, and are more committed to women-centered care. Centers utilize different marketing methods and are involved in a number of organizational changes to better position themselves in the changing health care environment. CONCLUSIONS: Birth centers offer an attractive option to consumers and are a viable model for delivering women-centered care. Given that all "birth center" facilities do not share the same philosophy and service mix, women need to have some assurance of what a "birth center" will, and will not, provide.

Adult↗
PubMed1997

The acylation-stimulating protein pathway and regulation of postprandial metabolism.

Much has recently been learned about the processes involved in postprandial triacylglycerol clearance. As discussed previously, important differences in the metabolism of chylomicrons and VLDL have become apparent. The ASP pathway has also been recognized and appears to play a critical role in chylomicron metabolism. The ASP pathway is activated in order to trap the fatty acids released from chylomicrons by the action of LPL and there is now unequivocal in vivo evidence in human subjects that ASP is generated by adipocytes in the postprandial period. These findings match the in vitro data showing that chylomicrons, but not the other plasma lipoproteins or fatty acids, activate the generation of ASP by cultured human adipocytes. An inverse relationship appears to exist between the proportion of fatty acids taken up by adipocytes and that released into the general circulation. Too great a release into the general circulation because of diminished trapping of fatty acids released from chylomicrons appears to be critical in the pathogenesis of the dyslipoproteinaemias associated with hyperapo B or FCHL and omental obesity. Evidence has been presented that dysfunction of the ASP pathway may be one of the causes of this disorder. Put differently, the ASP pathway is essential for the normal clearance and disposition of dietary fatty acids. Binding of chylomicrons to capillary endothelium followed by lipolysis by LPL results in the sudden liberation of fatty acids, and in the marked generation of ASP by adipocytes. The ASP that is generated is essential if LPL is to continue to form fatty acids at a normal rate. It is essential also if the fatty acids which are formed are to enter the adipocyte rather than exit into the general circulation. The transport vehicle, the chylomicron, therefore stimulates the formation of the peptide, ASP, which is responsible for its successful metabolism. Thus, the ASP pathway provides the metabolic coordination between the chylomicron and the adipocyte, which we describe as microenvironmental metabolic regulation and which we believe is essential for the normal clearance of dietary triacylglycerol from plasma.

Adipocytes↗
PubMed1994

Needleless i.v. therapy: comparing three systems for safety.

Three needleless systems were compared for general usability and cost. A closed, one-piece, nonmechanical unit was chosen as it proved safe in both peripheral and central lines, required minimal inservicing and yielded significant cost savings.

Equipment Design↗
PubMed1992

The relationship between onsets of depression and sudden drops in solar irradiation.

In a retrospective single-case study of a patient (L.S., the first author), who suffers from recurrent depression, we compared the onsets of his depression with meteorological data on light intensity, independently obtained, for the years 1975-1988. During those years there were 24 onsets or worsening of an existing depressive episode. Eleven of these occurred in the months September-December. Seven of these 11 autumn/winter onsets and 12 of the remaining 13 non-autumn/winter onsets coincided with a period of unusually low natural light intensity. Thus, 19 of 24 onsets (79%) were associated with falling light intensity, regardless of season. Some episodes that were not related to falling light intensity were associated with life events. For the years prior to the patient's use of light therapy, there was a statistically significant relationship between falling light and onset of depression. This supports the suggestion that depressive episodes (in certain individuals) may be triggered by unusually dull weather, regardless of season.

Aged↗
PubMed1991

Pharmacokinetics and toxicity of intraarterial adriamycin for hepatocellular carcinoma: effect of coadministration of lipiodol.

To determine the effect of coadministration of lipiodol on the pharmacokinetics and systemic toxicity of intraarterial Adriamycin in patients with hepatocellular carcinoma, nine patients were studied in detail. Each received two courses of a bolus injection of Adriamycin (60 mg/m2), in one of which the Adriamycin was mixed with 10 ml of lipiodol. Analysis of the paired data, and additional 'non-paired' data from a further seven patients, showed that there was no significant difference in the area under the concentration-time curve for Adriamycin or adriamycinol or, in the case of Adriamycin, the terminal half-life. Likewise the fall in haemoglobin concentration, white cell count and platelet count following treatment, and the degree of nausea and vomiting were not significantly different. Comparison with a series of 12 patients receiving intravenous Adriamycin, in the same dose schedule, revealed no difference in terms of pharmacokinetic parameters or toxicity with intraarterial administration of Adriamycin, with or without lipiodol.

Adult↗
PubMed1990

Crystals of the NC1 domain of human type IV collagen.

Crystals of the non-collagenous C-terminal region (NC1) of type IV collagen have been obtained from human placenta. These crystals diffract to 2.0 A, and belong to space group P22(1)2(1), with cell dimensions a = 81 A, b = 158 A, c = 138 A, alpha = beta = gamma = 90 degrees. The crystals contain one hexamer in the asymmetric unit; they are very stable with respect to X-rays.

Animals↗
PubMed1990

Ascariasis.

Ascaris lumbricoides is the most common helminth to infect humans. Infection occurs when contaminated soil containing mature eggs is swallowed. Clinically, infection ranges from the asymptomatic carrier state to life-threatening pulmonary disease or intestinal obstruction. Diagnosis is most frequently established by identification of the eggs in stool specimens. Treatment with antiparasitic drugs is effective in preventing serious complications and eradicating the parasite from all members of the household.

Anthelmintics↗
PubMed1990

Prognostic factors determining survival in breast cancer patients presenting with metastatic disease.

Although patients with advanced breast cancer usually die of their disease, the clinical course is highly variable. Numerous investigators have examined potential prognostic factors predicting time to recurrence for primary (localized) breast cancer. Less attention has been paid to evaluating prognostic factors in patients presenting with metastatic disease. A group of 86 women with metastatic breast cancer diagnosed between 1974 and 1984 was studied to determine the effect of certain prognostic factors on survival. Univariate analysis of these factors indicates that specific sites of recurrence, estrogen receptor (ER) status, size of the primary tumor at original diagnosis, and tumor histology; i.e., tumor differentiation, were significantly associated with predicting survival in patients presenting with metastatic disease. Poor survival, i.e., less than, or equal to, 22 months from initial presentation, is associated with a primary tumor greater than five cm., ER level less than 10 fmol/mg. of protein, lung and bone marrow recurrence, and poorly differentiated histology. Menstrual status, age, bone or lymph node site of metastases, and elapsed time between patient knowledge of symptoms and subsequent initial medical evaluation were not significant predictors of survival in patients presenting with metastatic disease.

Adult↗
PubMed1987

Quantitative flow cytometric and clonogenic evaluation of glass bead affinity fractionation of antibody-labeled murine bone marrow.

Monoclonal antibodies and a glass bead affinity fractionation technique were used to selectively deplete subpopulations of murine bone marrow cells. Flow cytometric analyses permitted quantitative measurement of subpopulation depletion and characterization (light scatter and fluorescence intensity) of both the eluted and bound cell subpopulations. Mouse bone marrow cells were labeled with selected monoclonal rat anti-mouse antibodies directed against cell surface antigens and were eluted through a glass bead column coated with goat anti-rat immunoglobulin. Unlabeled cells passed through the column, whereas cells labeled with the antibody were selectively retained. Column operating conditions for optimal depletion of labeled cells were determined. With specific column conditions, 97% of the antibody positive cells were retained on the column. In addition, clonogenic assays on cells sorted from unfractionated and column fractionated preparations provided estimates of the fraction of granulocyte macrophage progenitors (CFU-GM) in the different cell subpopulations. The enrichment of CFU-GM achieved in the eluted cell populations was dependent upon the antibody used for cell labeling and ranged from four- to six-fold. Since large numbers of cells can be processed rapidly, this technique, in combination with antibodies specific for non-clonogenic cells, is particularly suitable when preparations enriched in colony-forming progenitors are required.

Animals↗
PubMed1987

Multivariate flow cytometric characterization and enrichment of murine megakaryocyte progenitors (CFU-Meg).

Multivariate flow cytometric analysis and sorting of mouse bone marrow cells viably stained with Hoechst 33342 (HO) was utilized to obtain a subpopulation enriched at least 30- to 60-fold for clonogenic megakaryocyte precursors (CFU-Meg). HO fluorescence intensity, forward light scatter, and perpendicular light scatter were measured on each HO-stained bone marrow cell as it passed through a dual beam flow cytometer. Cells were sorted on the basis of their light scattering and HO fluorescence intensity properties. The sorting region which included cells with high forward light scatter, low perpendicular light scatter, and low (0.1-0.65 times the modal channel) HO fluorescence intensity contained approximately 0.6% CFU-Meg. Of all CFU-Meg, 75% were contained in the light scatter gate, and 56% of all CFU-Meg were in the low HO-sorting region. This technique offers a simple, one-step procedure to obtain preparations enriched in murine clonogenic megakaryocyte precursors.

Animals↗
PubMed1984

The molecular structures and interactions of bovine and human gamma-crystallins.

Knowledge of the three-dimensional structure of bovine gamma II-crystallin has provided the basis for building molecular models using computer graphics of two human gamma-crystallins, the sequences of which have recently been determined. The tertiary structures of these gamma-crystallins are predicted to be highly conserved. They have extensive networks of interacting charges on their surfaces, which may contribute to their thermodynamic stability and partially define the degree of water retention in the lens. The human crystallins appear to be more hydrophobic than the bovine molecule. All have arrangements of cysteine thiols which may be important as electron sinks and reserve redox potential in the normal lens but which may contribute to protein aggregation in cataract.

Amino Acid Sequence↗
PubMed1983

X-ray analysis of the eye lens protein gamma-II crystallin at 1.9 A resolution.

We report the X-ray structure analysis and refinement at 1.9 A resolution of calf gamma-II crystallin, a lens-specific protein. The sequence of Croft (1972) has been modified to give a polypeptide chain of 174 residues (cf. 165). The protein has a symmetrical, hierarchical structure of two globular domains each comprising two similar "Greek key" motifs, consecutive along the polypeptide chain, and related by a pseudo 2-fold axis. The two domains pack together with a single connection and are related by a further pseudo 2-fold axis which bisects the angle between the intra-domain dyads. Forty-two pairs of C alpha positions for the two most similar motifs have root-mean-square separation at best fit of 0.69 A. The N and C-terminal domains gave root-mean-square separation of 0.89 A for 82 pairs of C alpha atoms at best fit. In each domain the two Greek key motifs form a pair of four-stranded antiparallel beta-pleated sheets, each sheet composed of three stands from one motif and one from the other. The sheets pack together in a wedge shape, closed at the top by the loops connecting the third and fourth strands of each motif. The first two strands of each motif form an extended beta-hairpin which is folded on to the beta-sheet. The packing of each motif into the globular domains involves a staggered bilayer of side-chains between each pair of beta-sheets which does not preserve the pseudo 2-fold axes observed in the C alpha position topology. In the core of each domain there are interactions between polarizable aromatic groups and sulphur-containing residues which may contribute to stability and may also serve to protect aromatic side-chains from ultraviolet light damage in the lens. At the surface of the molecule over half the ionic side-chains are closely paired, which probably stabilizes the tertiary fold and may reduce the water bound. Crystal lattice interactions are described which may be similar to those occurring in vivo in the lens between crystallins. Seven cysteine residues have been identified in the structure and these may have a role in the thermodynamic stability of the molecule, its intermolecular interactions under the normal reducing conditions of the lens, and also in the aggregation and cross-linking which occur in some forms of cataract. Three of these residues, Cys18, Cys23 and Cys74, form a cluster in the N-terminal domain.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗