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Biomedical subjects

D M Scott

Publications and source records attributed to D M Scott.

At least 55 records · Page 3Linked to original sources
PubMed1988

Use of vancomycin and tobramycin polymethylmethacrylate impregnated beads in the management of chronic osteomyelitis.

Over the past several years there has been a growing interest in the use of locally implanted beads containing antibiotics for the treatment of chronic osteomyelitis. This method has been popularized in Europe and, with few exceptions, gentamicin has been the only antibiotic used. There have been only a few reports from the U.S. and there is little information regarding the pharmacokinetics of antibiotics used in this fashion. To our knowledge this is the first report using vancomycin. Three patients with chronic osteomyelitis were treated with vancomycin and/or tobramycin polymethylmethacrylate beads. These beads were extemporaneously compounded and implanted for up to six weeks. From the site of bead implantation local fluid aliquots were collected for the measurement of antibiotic concentrations. In two patients, initial tobramycin concentrations exceeded 400 mg/L. In one patient receiving vancomycin, initial localized concentrations were approximately 100 mg/L. In all three patients therapeutic concentrations of localized antibiotic were maintained with immeasurable systemic concentrations throughout the period of bead placement. Localized antibiotic therapy for the management of chronic osteomyelitis represents a potential therapeutic alternative to long-term parenteral therapy. Data presented here suggest that other antibiotics, such as vancomycin and tobramycin, can be used successfully in polymethylmethacrylate beads and provide preliminary facts for future investigations of such applications.

Adult↗
PubMed1987

Differentiation in vitro of primary cultures and transfected cell lines of epithelial cells derived from the thick ascending limb of Henle's loop.

The use of primary cell cultures derived from defined locations of the kidney has enabled the study of certain kidney cell type-specific characteristics under defined environmental conditions. The use of primary cell cultures, however, has a number of inherent disadvantages, many of which may be overcome by the use of differentiated cell lines of defined origin. In this paper I describe in detail an approach to: (a) the isolation and culture of primary cultures derived from the thick ascending limb of Henle's loop (TALH), and (b) the production of differentiated cell lines by the transfection of these primary cell cultures with early region SV40 virus genes. The characteristics of these cultures and other TALH-derived cell lines are described.

Animals↗
PubMed1987

Localization of Tamm-Horsfall protein in chloride transporting epithelia: lack of correlation with the Na, K, Cl cotransporter.

In order to test the hypothesis that Tamm-Horsfall protein (THP) and the Na, K, Cl cotransporter in chloride transporting epithelia are functionally related, the presence of THP in various rat epithelia was investigated by indirect immunocytochemical procedures. Positive staining was found in the apical cytoplasmic portion of the renal thick ascending limb, in apical large secretory granules of the pancreatic acinar cells, in the cytoplasm of the serous acinar cells of the salivary gland, and in the apical cytoplasm of mucosal cells in the jejunum. No staining was observed in the tracheal epithelial cells. These studies show that THP, or antigenically related substances, can be found in a variety of extrarenal organs. Only in the renal thick ascending limb the intracellular distribution of THP coincides partly with the distribution of the Na, K, Cl cotransporter. In all other epithelia investigated no correlation between THP staining and presence of the cotransporter was found. Thus, it seems very unlikely that Tamm-Horsfall protein and the Na, K, Cl cotransporter are functionally related.

Animals↗
PubMed1986

Development of differentiated characteristics in cultured kidney (thick ascending loop of Henle) cells.

This study describes the characterization of epithelial cells in culture following their isolation from the thick ascending limb of Henle's loop of rabbit kidney, by enzymatic digestion and subsequent purification using density gradient centrifugation. In culture, these cells expressed a variety of morphological, enzymatic and functional parameters expected of such cells in vivo. These cells were polarised, formed tight junctions and exhibited considerable lateral interdigitation between adjacent cells. They also developed characteristically high levels of activity of Na,K-ATPase, comparable to those seen in freshly isolated cells, and also expressed the functionally important Na,K,Cl-co transport system. The development of these systems in culture, however, was not coincident and their activities were reduced upon extended culture. The ability of these cells to develop and express differentiated characteristics in culture indicates that cells derived from defined kidney cell populations should provide valuable models for the study of the factors involved in the development and regulation of kidney cell type-specific characteristics.

Alkaline Phosphatase↗
PubMed1986

Maintenance of expression of differentiated function of kidney cells following transformation by SV40 early region DNA.

This study describes the isolation and characterization of epithelial cell lines that maintain their differentiated phenotype following the stable integration of SV40 genes. Epithelial cells were derived from a defined location of rabbit kidney, the thick ascending limb of Henle's loop, and were co-transfected with genes from the early region of SV40 together with pSV2-neo DNA (which confers resistance to the antibiotic G418). These cells were shown to be resistant to G418, express SV40 large T-antigen and continued to express differentiated characteristics typical of cells of their origin. Such characteristics include the expression of high levels of activity of both Na,K-ATPase and the functionally important Na,K,Cl-co-transport system, the synthesis of Tamm-Horsfall glycoprotein and the presence of a barium-sensitive K+ channel on the apical membrane surface.

Animals↗
PubMed1985

The use of membrane vesicles to study the NaCl/KCl cotransporter involved in active transepithelial chloride transport.

Properties of the NaCl/KCl cotransport system were investigated in isolated membranes by flux measurements and binding studies. Chloride competes with "furosemide-like loop diuretics" for its two binding sites at the cotransporter as evidenced by the decrease in piretanide sensitivity of sodium flux and inhibition of high affinity N-methylfurosemide binding by chloride in rectal gland plasma membranes. In the rectal gland lithium inhibits sodium flux but is not translocated whereas in the renal thick ascending limb (TALH) it is also transported. Ammonium is a substrate for the sodium and potassium site in the rectal gland but only for the potassium site in the TALH. The latter finding raises the possibility that part of the ammonium reabsorption in the TALH is mediated by the cotransport system as NaCl/NH4Cl cotransport.

Animals↗
PubMed1985

Monocyte-derived inhibitor of interleukin 1 induced by human cytomegalovirus.

It has previously been shown that human cytomegalovirus (HCMV) can exert immunosuppressive effects, and it has been suggested that these may be mediated by monocytes, although the mechanism is unclear. We showed that infection of human monocytes with the AD169 strain of HCMV abrogates their production of interleukin 1 (IL-1) activity. This was associated with the release from infected monocytes of an inhibitor of IL-1 activity which was also released after HCMV infection of the U937 macrophage-like cell line. The inhibitor of IL-1 activity is a protein with an apparent molecular weight of ca. 95,000. This action of HCMV strain AD169 was virus specific and required infectious virus but occurred without virus replication or detectable expression of viral proteins. This effect may account, at least in part, for the previously observed immunosuppressive properties of HCMV.

Cell Line↗
PubMed1983

Stimulation of fatty acid utilization by sodium clofibrate in rat and monkey hepatocytes.

The acute effects of sodium clofibrate (NaCPIB) on the metabolism of [1-14C]palmitate, [1-14C]octanoate, [1-14C]butyrate, and [2-3H]glycerol by freshly isolated hepatocytes were tested to explore its mechanism of action. Labeled long-, medium-, and short-chain fatty acids were incorporated into all the major lipid classes and were oxidized to 14CO2 by the liver cells. The partitioning of labeled fatty acids from lipogenic towards oxidative pathways was inversely related to fatty acid chain length. [1-14C]Palmitate was incorporated mainly into cellular triglycerides and phospholipids; [1-14C]octanoate, mainly into triglycerides and free cholesterol; and [1-14C]butyrate, mainly into free cholesterol and phospholipids of the cells. NaCPIB (1-3 mM) rapidly stimulated the esterification of labeled palmitate or glycerol to triglycerides, but drug levels greater than 5 mM were inhibitory to esterification. NaCPIB (1 mM) increased the oxidation of [1-14C]palmitate to 14CO2 by either rat or monkey hepatocytes and enhanced the release of labeled lipids from [2-3H]glycerol-prelabeled cells into the extracellular medium. Accelerated [1-14C]octanoate incorporation into glycerolipids and sterols and increased [1-14C]octanoate conversion to 14CO2 were observed in rat liver cells incubated with 1 mM NaCPIB. In contrast, the same drug level stimulated the oxidation of [1-14C]butyrate to 14CO2 but greatly diminished its incorporation into hepatocellular sterols or glycerolipids. These results indicate that (a) NaCPIB acutely alters hepatic ultilization of fatty acids by actions at diverse loci; (b) these metabolic alterations vary with fatty acid chain length; and (c) these effects are probably due to rapid changes in biochemical regulatory mechanism and/or in substrate channelling within the cells. These data further suggest that the early hypolipidemic effect of the drug in rats and primates may be related to an enhanced hepatic oxidation of long-chain fatty acids, but cannot be attributed simply to a reduction in their esterification to complex lipids.

Animals↗
PubMed1983

Investigation of the attachment of bovine corneal endothelial cells to collagens and other components of the subendothelium. Role of fibronectin.

Bovine corneal endothelial cells adhered equally well to a variety of collagens (types I, III, IV and V) consistent with a role for fibronectin in this process. They did not exhibit a preferential binding to collagen type IV--as might be anticipated if laminin were to play a significant role in their adhesion. Inhibition studies with anti-fibronectin antibodies demonstrated the importance of endogenous fibronectin in the mediation of attachment. Consistent with this, binding did not appear to require the presence of exogenous protein, since cells bound to collagens equally well in the presence or absence of added fibronectin and binding was not stimulated by pretreatment of collagens with this protein.

Animals↗
PubMed1983

The development and evaluation of an interdisciplinary health training program: a pharmacy perspective.

This program integrates training with the clinical interdisciplinary aspects of health care by directly involving pharmacy and other health professional students in an on-going team model of health care delivery. The training program model allows pharmacy students to learn the conceptual basis of team care and to experience directly how this concept is applied in an ambulatory health care setting. Learning strategies include specialty and team delivery of health care, participation in weekly interdisciplinary team training seminars, involvement in problem-solving and other skill building activities, and development of an interdisciplinary team project. Program evaluation results have indicated that students perceive that the interdisciplinary training increased their knowledge and positive attitudes towards interdisciplinary teams. The training also increased their sensitivity to patients, and enhanced the understanding of the problems of delivering health care to an urban community. The results have also shown that through this structured interdisciplinary experience, students reported having a better understanding of the roles of other health professionals and a greater awareness of how these different roles are integrated into a health care team.

Analysis of Variance↗
PubMed1982

Formation of bone by isolated, cultured osteoblasts in millipore diffusion chambers.

Osteoblast-like and osteoclast-like cells freed from neonatal calvaria by sequential enzymatic digestion after 6-7 days in culture were placed in diffusion chambers and implanted in the peritoneal cavities of CD-1 mice. About half of the chambers also contained a dead calvarium to test for the need of an "inducer." After 20 days, 11 of 18 chambers containing to osteoblast-like cells formed large foci of mineralized bone that corresponded to alkaline phosphatase activity throughout the chambers. Moreover, only type I (i.e., bone) collagen was formed. Occasional deposits of bone were found in only 3 of 22 chambers containing the osteoclast-like cells. The presence of dead bone did not affect any of the results. These data confirm the osteoblast-like nature of the isolated cell populations and demonstrate that these cells retain their differentiated function in culture.

Animals↗
PubMed1982

Microcomputer as patient educator.

A computer-assisted lesson on general drug knowledge as a patient education tool is described. A drug I.Q. quiz is one of seven microcomputer lessons available to patients in the waiting room of an ambulatory-care clinic. The drug quiz consists of 19 multiple-choice and six true or false questions. After each question, the computer responds with a brief paragraph keyed to the answer selected by the user. If the answer for a multiple-choice question is incorrect, the user can reanswer the question before proceeding. At the end of the lesson, a score is graphically displayed and the user is asked to evaluate the lesson. The computer stores the total number of lessons completed, total scores, number of times each question was answered incorrectly on first and second attempts, number of times each question was answered a second time, and each user's responses to the quiz and evaluation questions. Based on 313 completions of the drug quiz from September 1981 through May 1982, 86% of the users stated that they learned at least something useful, and 72% liked the quiz. The mean (+/- S.D.) number of correct answers on the first attempt was 16 +/- 5; scores improved by an average of 2.5 +/- 2 by reanswering questions. Of 2421 multiple-choice questions answered incorrectly, 62% were reanswered. Of these second attempts, 52% were correct. Item validity scores indicated that the drug quiz serves as a realistic appraisal of drug knowledge. The microcomputer can be an effective medium for patient education.

Computers↗
PubMed1981

The role of carbohydrate in the structure and function of nephritic factor.

Six nephritic factors (NeFs) were purified from the IgG fraction of sera of patients with PLD and/or MPGN by elution from EA C43bBb. All had at least one abnormal H chain component when examined by PAGE-SDS and two additionally had a large L chain. Four different H chains were found. Their apparent molecular weights and the frequency with which they occurred were: 65,000 (one NeF), 61,500 (four NeFs), 57,000 (two NeFs) and 55,000 (one NeF) compared with 53,500 daltons for normal H chain. The molecular weight of the large L chains was 26,500 daltons (cf. 23,500 for normal L chain). Both the NeF activity and the large components were located in the F(ab')2 fragment of the molecule and after reduction the large component was found in the Fd fragment of the H chain. Neuraminidase treatment of purified NeF caused a 1-2% decrease in apparent molecular weight of the large H chain on PAGE-SDS. Mild periodate oxidation, sufficient to cause primarily loss of carbohydrate, caused a marked loss of activity. Reduction and alkylation of NeF under neutral conditions caused only a small loss of activity but after acid dissociation the H and L chains were completely inactive.

Autoantibodies↗