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Biomedical subjects

G S Brown

Publications and source records attributed to G S Brown.

At least 19 recordsLinked to original sources
PubMed2001

Understanding patterns of genetic diversity in the oak gallwasp Biorhiza pallida: demographic history or a Wolbachia selective sweep?

The endosymbiont Wolbachia can be responsible for selective sweeps on mitochondrial DNA variability within species. Similar signals can also result from demographic processes, although crucially the latter affect nuclear as well as mitochondrial loci. Here we present data on Wolbachia infection status and phylogeographic patterning for a widely distributed insect host, the oak gallwasp Biorhiza pallida (Hymenoptera: Cynipidae). Two hundred and eighteen females from eight European countries were screened for Wolbachia. All individuals from Hungary, Italy, France, U.K., Ireland, Switzerland, Sweden, and northern and southern Spain were infected with a single group A strain of Wolbachia, while populations in central Spain were not infected. A mitochondrial marker (cytochrome b) shows low variation and departure from neutrality in infected populations, but greater variation and no deviation from neutrality in Wolbachia-free populations. This pattern is compatible with a Wolbachia-induced selective sweep. However, we also find parallel differences between infected and uninfected populations for nuclear markers (sequence data for ITS1 and ITS2). All markers support the existence of a deep split between populations in Spain (some free of Wolbachia), and those in the rest of Europe (all infected). Allelic variation for five allozyme loci is also consistent with the Spain-rest of Europe split. Concordant patterns for nuclear and mitochondrial markers suggest that differences in the nature and extent of genetic diversity between these two regions are best explained by differing demographic histories (perhaps associated with range expansion from Pleistocene glacial refugia), rather than a Wolbachia-associated selective sweep.

Animals↗
PubMed2001

Pushing the quality envelope: a new outcomes management system.

This article is based on the authors' experience in designing and implementing outcomes management systems for large managed care organizations. Topics addressed include design of instruments, use of cost-effective technology, development of computerized decision-support tools, and methods for case-mix adjustment. The case-mix-adjustment models are based on a data repository of several thousand treatment cases with multiple measurement points across the course of treatment. Data from controlled and field studies are described. These data suggest that the outcomes management methods outlined in this article can result in significantly improved clinical outcomes and a more rational allocation of behavioral health care resources.

Cost-Benefit Analysis↗
PubMed1999

Extraterrestrial handedness: a reply.

Recent investigations of stable isotope ratios of amino acids from the Murchison meteorite have shown them to be of unambiguous extraterrestrial origin, and examinations of their enantiomeric compositions, where terrestrial contamination can be excluded, have found a consistent excess of L-enantiomers. One explanation for this observation has been the asymmetric photolysis of racemic extraterrestrial amino acids by circularly polarized light (CPL) in the synchrotron radiation from orbiting electrons around the pulsar remnants of supernovae. Mason (1997) has attempted to discredit this mechanism on the grounds that circular dichroism (CD) bands for optically active molecules alternate in sign and sum to zero over the entire spectrum, and hence enantioselective photochemical reactions cannot be induced by broad band CPL. We submit arguments disputing this conclusion and present reasons for expecting that broad band CPL synchrotron radiation would be quite capable of inducing asymmetric photolysis, particularly in aliphatic amino acids.

Amino Acids↗
PubMed1997

Patterns of care for cancer of the larynx in the United States.

OBJECTIVE: To assess case-mix characteristics, treatment patterns, and outcomes for laryngeal cancer using the largest series of patients to date. DESIGN: Analyses performed on retrospectively collected survey data submitted by hospitals for diagnostic periods 1980 through 1985 and 1990 through 1992 (with a 9-year follow-up for the long-term group). SETTING: Broad spectrum of US hospitals (N = 769). PATIENTS: Consecutively accrued series of patients with laryngeal cancer (N = 16,936), with only squamous cell carcinomas (N = 16,213) analyzed. INTERVENTIONS: Surgery, radiation therapy, and chemotherapy. MAIN OUTCOME MEASURES: Descriptive analyses of case-mix, diagnostic, and treatment characteristics plus recurrence and 5-year, disease-specific survival outcomes. RESULTS: There was a slight increase across these years in stage IV disease and in radiation therapy (with or without surgery and/or chemotherapy). Overall diversity of management of this disease (by site and stage) was apparent. Five-year survival rates indicated a large difference between modified groupings of the T and N classifications, separating stages III and IV cases into localized disease (87.5% for T1-T2; 76.0% for T3-T4 cases) and regional metastasis (46.2%). CONCLUSIONS: Regardless of improvements in entering data in hospital records (most commendably, staging), more rigorous standards are needed. Also, the small increase in advanced-stage patients indicates that efforts toward early detection have not been successful. The rise in radiation therapy perhaps reflected an increased use of nonsurgical treatment for early-stage patients and organ-sparing radiochemotherapy protocols for advanced-stage patients. Regrouping stages III and IV cases into localized disease vs regional metastasis appears to predict survival better. Ongoing refinements of the American Joint Committee on Cancer staging scheme will hopefully improve this cancer's classification.

Carcinoma, Squamous Cell↗
PubMed1997

Hypopharyngeal cancer patient care evaluation.

A survey was conducted to identify demographics and standards of care for treatment of hypopharyngeal squamous cell carcinoma in the United States. Data were accrued from voluntary submission of cancer registry and medical chart information from 769 hospitals representing 2939 cases diagnosed from 1980 to 1985 and 1990 to 1992. Clinical findings, diagnostic procedures employed, treatment practices, and outcome are presented. Overall, 5-year disease-specific survival was 33.4%, which segregated to 63.1% (stage I), 57.5% (stage II), 41.8% (stage III), and 22% (stage IV). Survival was best for patients treated with surgery only (50.4%), similar with combined surgery and irradiation (48%), and worse with irradiation only (25.8%). This analysis provides a standard to which current treatment practice and future clinical trials may be compared.

Aged↗
PubMed1996

Hematopoietic augmentation by a beta-(1,4)-linked mannan.

CARN 750 (injectable acemannan) is a polydispersed beta-(1,4)-linked acetylated mannan isolated from the Aloe barbadensis plant. It has multiple therapeutic properties including activity in wound repair and as a biological agent for the treatment of neoplasia in animals as well as the ability to activate macrophages. We report herein that CARN 750 directly or indirectly has significant hematoaugmenting properties. We observed that the subcutaneous administration of CARN 750 significantly increases splenic and peripheral blood cellularity, as well as hematopoietic progenitors in the spleen and bone marrow as determined by the interleukin-3-responsive colony-forming unit culture assay and the high-proliferative-potential colony-forming-cell (HPP-CFC) assay (a measure of primitive hematopoietic precursors) in myelosuppressed (7 Gy) C57BL/6 mice. The greatest hematopoietic effect was observed following sublethal irradiation in mice receiving 1 mg CARN 750/ animal, with less activity observed at higher or lower doses. Further, CARN 750, following daily injection, has activity equal to or greater than the injection of an optimal dose of granulocyte-colony-stimulating factor (G-CSF) in myelosuppressed mice. In this comparison, significantly greater activity was observed in the splenic and peripheral blood cellularity, and in the frequency and absolute number of splenic HPP-CFC as compared to the mice receiving G-CSF at 3 micrograms/animal. CARN 750, when administered to myelosuppressed animals, decreased the frequency of lymphocytes with a concomitant significant increase in the frequency of polymorphonuclear leukocytes (PMN). However, owing to the increased cellularity, a significant increase in the absolute number of PMN, lymphocytes, monocytes and platelets was observed, suggesting activity on multiple cell lineages. The latter is the primary difference in activity as compared to G-CSF which has activity predominantly on PMN.

Adjuvants, Immunologic↗
PubMed1996

Studies on optimal dose and administration schedule of a hematopoietic stimulatory beta-(1,4)-linked mannan.

Several complex carbohydrates have been found to significantly stimulate hematopoiesis. CARN 750, a polydispersed beta-(1,4)-linked acetylated mannan isolated from the Aloe vera plant, has been shown to have activity in wound repair, to function as a antineoplastic, and to activate macrophages. We report, herein, the hematoaugmenting properties of CARN 750 and its optimal dose and timing of administration in an animal model of irradiation-induced myelosuppression. We observed that subcutaneous injections of 1 mg/animal of CARN 750 had equal or greater stimulatory activity for white blood cell (WBC) counts and spleen cellularity as well as on the absolute numbers of neutrophils, lymphocytes, monocytes and platelets than did higher or lower doses of CARN 750 or an optimal dose of granulocyte-colony stimulating factor (G-CSF). Hematopoietic progenitors, measured as interleukin-3-supported colony forming units-culture (CFU-C) and high proliferative potential colony-forming cells (HPP-CFC) assays, were similarly increased by CARN 750 in the spleen but not in the bone marrow. The frequency of splenic HPP-CFCs and absolute number of splenic HPP-CFCs and CFU-Cs were optimally increased by 1 mg/animal of CARN 750. In contrast, bone marrow cellularity, frequency and absolute number of HPP-CFCs and CFU-Cs had as a dosage optimum 2 mg/animal of CARN 750. These parameters were similarly increased by G-CSF. In studies to determine the optimal protocol for the administration of CARN 750 we found that the hematopoietic activity of CARN 750 increased with the frequency of administration. The greatest activity in myelosuppressed mice was observed for all hematopoietic parameters except the platelet number in mice receiving daily administration of 1 mg/animal of CARN 750 with activity equal to or greater than G-CSF.

Animals↗
PubMed1996

In vivo haemoprotective activity of tetrapeptide AcSDKP combined with granulocyte-colony stimulating factor following sublethal irradiation.

We report that acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), which removes progenitor cells from cell cycle, in combination with granulocyte-colony stimulating factor (G-CSF) can significantly improve myelorestoration following irradiation (7 Gy). Peripheral blood, spleen and bone marrow (BM) cell recovery and progenitor cell reconstitution [IL-3-responsive colony-forming cells (CFC) and high proliferative potential colony-forming cells (HPP-CFC)] were studied. Studies on the optimal schedule of AcSDKP administration revealed maximal effects on progenitor cells when AcSDKP was administered as a continuous infusion for 3 d starting 24 h prior to irradiation and used in combination with G-CSF. The numbers of CFC and HPP-CFC in the BM were significantly increased following irradiation in mice receiving AcSDKP and G-CSF as compared to either drug alone. The numbers of CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on days 10 and 14 as compared to AcSDKP alone, but not G-CSF. Similarly, CFC and HPP-CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on day 18 as compared to mice receiving PBS and G-CSF. These studies suggest that AcSDKP in combination with G-CSF may have potential for the protection of progenitor cells in patients undergoing intensive chemo- and/or radiotherapy.

Animals↗
PubMed1996

Expert systems restructure managed care practice: implementation and ethics.

The development of computerized decision support technologies is having a profound impact on the management of patient care. This article describes different types of clinical decision support software, examines appropriate usage and current examples of implementation, and reviews a range of ethical considerations. The authors are in the midst of implementing a computerized decision support system for care management in their managed care organization.

Case Management↗
PubMed1996

In vivo protective effects of tetrapeptide AcSDKP, with or without granulocyte colony-stimulation factor, on murine progenitor cells after sublethal irradiation.

Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) demonstrated hemato-protective activity in mice after sublethal irradiation (7 GY). Bone marrow interleukin-3 (IL-3)-responsive colony-forming cells (CFC and high proliferative potential colony-forming cells (HPP-CFC) were significantly (p < 0.05) increased by day 10 after irradiation in mice receiving a continuous infusion of 1000 ng/day of AcSDKP compared to irradiated control mice. The maximum protective effect for bone marrow progenitors was achieved when AcSDKP was administered for 3 days beginning 24 hours before irradiation. Other dosages and schedules in relationship to irradiation were less active. Further, when granulocyte colony-stimulating factor (G-CSF) was administered for 10 days beginning 24 hours before irradiation. Other dosages and schedules in relationship to irradiation were less active. Further, when granulocyte colony-stimulating factor (G-CSF) was administered for 10 days after AcSDKP infusion in irradiated mice, significantly increased numbers of IL-3 responsive CSF-only control mice. In addition, platelets were significantly (p < 0.05) increased in mice receiving AcSDKP and G-CSF on days 18 and 21 after irradiation compared with mice receiving G-CSF alone. We conclude that ACSDKP has a radioprotective effect in vivo for progenitor cells, and that time of initiation and duration of AcSDKP administration relative to irradiation are crucial for these effects. Further, AcSDKP has a significant additive protective effect not only for progenitor cells but also for platelets when given in combination with G-CSF. We suggest that these in vivo observations provide a basis on which to design optimal clinical hypothesis and protocols.

Amino Acid Sequence↗
PubMed1994

Spatial association learning by rufous hummingbirds (Selasphorus rufus): effects of relative spacing among stimuli.

Gestalt theory predicts that when cues are spatially separated from response locations, associative learning is faster when distance between cue-response location pairs is increased. This prediction was tested with 20 rufous hummingbirds (Selasphorus rufus), which learned to select rewarding feeders signaled by a spatially separated light cue in 4 treatments in which distance between cues and feeders and between cue-feeder pairs was varied. As has been shown for other animals, the hummingbirds learned more slowly when the distance between cues and feeders was increased, and as predicted by Gestalt theory, they learned faster at a given distance when distance between cue-feeder pairs was increased. This result suggests that spatial association is influenced by the proximity of other stimuli in the visual field.

Animals↗
PubMed1994

Technology transfer in digital mammography. Report of the Joint National Cancer Institute-National Aeronautics and Space Administration workshop of May 19-20, 1993.

Digital mammography is one of the most promising novel technologies for further improvement of early detection of breast cancer, offering important potential advantages: 1) improved image quality; 2) digital image processing for improved lesion contrast; 3) computer-aided diagnosis for enhanced radiologic interpretation; and 4) teleradiology for facilitated radiologic consultation. The Diagnostic Imaging Research Branch of the National Cancer Institute (NCI) recently funded an international, multidisciplinary, multi-institutional Digital Mammography Development Group for collaborations between NCI, the academic community, and industry to facilitate the integrated development and implementation of digital mammographic systems. Currently, however, digital mammography faces a number of fundamental technological roadblocks: 1) cost-effective digital detectors and displays for imaging systems; 2) the need for novel algorithms for image processing and computer-aided diagnosis; and 3) high performance, low cost digital networks to provide an "information superhighway" for teleradiology. To solve some of these technological problems, the Diagnostic Imaging Research Branch of NCI joined efforts with the Technology Transfer Division of the National Aeronautics and Space Administration to pursue a federal technology transfer program in digital mammography. The authors discuss the findings and recommendations of the workshop entitled "Technology Transfer in Digital Mammography," which was organized and held jointly by the NCI and the National Aeronautics and Space Administration in May, 1993. Numerous innovative technologies of varying degree of promise for digital mammography were presented at the conference. In this article, specific technologies presented at the workshop by the federal and federally-supported laboratories are described, and critiques of these technologies by the leaders of the medical imaging community are presented.

Breast Neoplasms↗
PubMed1993

Accumulation of PDGF B and cell-binding forms of PDGF A in the extracellular matrix.

PDGF is a powerful mitogen initially identified within platelets, but also shown to be produced by a wide variety of cell types. PDGF is encoded on two separate genes. These give rise to three polypeptides, PDGF B and two forms of PDGF A (SA and LA), resulting from alternative splicing of the PDGF A gene primary transcript. We report that in CHO cells transfected with PDGF gene constructs and producing moderate levels of PDGF homodimers, much of the PDGF LA and B produced, but little if any SA, is found in the matrix laid down beneath the cells. Immunoreactive PDGF in cells, and in matrix below expressing cells, was visualized by laser confocal microscopy. Western blotting of protein in matrix extracts, cell extracts, and secreted into the growth medium was used to demonstrate that the range of PDGF A polypeptides seen in the matrix was overlapping with those reported previously to be cell associated in cell types such as NIH3T3 and COS 7. This suggests that attachment to matrix or cell surface may be alternative fates for these polypeptides, with fate dependent on the characteristics of the producing cells. Immunoreactive PDGF A and B could be partially released by incubation of matrix material with heparin but not with other glycosaminoglycans. Digestion of matrix with chondroitin ABC lyase but not heparitinase or collagenase displaced some PDGF from its attachment sites. The results indicate attachment of PDGF to matrix proteoglycans, at least partly through the glycosaminoglycan moieties, and perhaps to additional components. The significance of matrix deposition for PDGF action is discussed.

Animals↗
PubMed1993

Behaviour of white blood cells and the complement system.

Seven different types of dialysers were investigated in five dialysis centres in four countries with respect to behaviour of white blood cells and the complement system. The results of this controlled crossover study demonstrated significant differences in the dialysers. Those containing cuprammonium cellulose (G10-3N and G120 M) showed the greatest changes in white blood cell count, including monocytes and neutrophils, as well as the greatest complement activation. With regard to lymphocytes the subpopulation of low-mobility cells, which were predominantly the B-cells, showed the greatest mobility with dialysers containing cuprammonium cellulose. The PAN copolymer- and PMMA-containing dialysers Filtral and T 150 clearly caused the least changes in white blood cells and complement factors. Dialysers containing cellulose acetate and polysulphone membranes (Duo-Flux Artificial Kidney, CD 4000, and F 60) produced only a moderate decrease of WBC, monocyte, neutrophil, and lymphocyte counts, and this result corresponded to a relatively small change in complement factors.

Acrylic Resins↗