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Biomedical subjects

K Fowler

Publications and source records attributed to K Fowler.

50 records · Page 3Linked to original sources
PubMed1988

Analysis of degradation of the basement membrane protein nidogen, using a specific monoclonal antibody.

A monoclonal antibody was produced against purified nidogen extracted from a mouse basement-membrane-producing tumor. This antibody reacted with a determinant on Nd-40, a rod which separates the globular domains of nidogen. Antigenicity depends on intrachain disulfide bonds within this rod. The monoclonal antibody was used to detect nidogen fragments after proteolytic cleavage of isolated nidogen, and nidogen complexed to laminin. The data indicate that thrombin and thermolysin generated very different patterns of degradation, but in both cases no differences were found between isolated and complexed nidogen. In contrast, nidogen in the laminin-nidogen complex was much less degraded by trypsin than isolated nidogen, indicating that an interaction between these basement membrane components reduces the susceptibility of nidogen to trypsin digestion. Immunofluorescent studies, using the monoclonal antibody on sections of the EHS tumor after proteolytic digestion, showed that the retention or disappearance of the Nd-40 determinant correlated with the in vitro digestion pattern of the laminin-nidogen complex.

Animals↗
PubMed1988

A human complement-fixing monoclonal anti-human lymphocyte antibody of rat origin.

MARCH 1E11 is an IgM monoclonal anti-human lymphocyte antibody of rat origin with the capacity to utilise both human and rabbit complement. The antibody reacts with all thymocytes and with all peripheral blood T and B lymphocytes. The treatment of human bone marrow or human peripheral blood mononuclear cells (PBMC) with MARCH 1E11 and either pooled human serum or autologous serum as a complement source resulted in cytolysis of greater than 99% of OKT3-positive lymphocytes. Under these conditions, progenitor cell recovery (colony-forming unit (CFU-c), burst forming unit--erythroid (BFU-e) and colony-forming unit--mixed (CFU-mix)) was greater than 90% of that of untreated cells. The response of treated marrow or PBMC to phytohaemagglutinin stimulation and in mixed leucocyte reactions demonstrated a reduction in thymidine incorporation to values similar to those obtained for unstimulated cells. The antibody does not cause modulation of the cell surface antigen and does not react significantly with non-lymphoid tissues. This monoclonal antibody may be useful for in vitro elimination of T lymphocytes from allogeneic bone marrow used for transplantation. The antibody may also be useful for treatment protocols requiring lymphoid depletion or immunosuppression as in organ transplantation.

Animals↗
PubMed1987

Computer-controlled, patient-interactive, multichannel, implanted neurological stimulators.

Programmable implantable neurological stimulation systems with multiple electrodes have many advantages in clinical use, but time-consuming postoperative adjustment of stimulation parameters is a distinct disadvantage. A personal computer interface to standard commercial radiofrequency-coupled devices has been developed, permitting direct patient interaction to expedite this process. In addition, the system permits simulated multichannel operation and implementation of various modulation schemes.

Electric Stimulation Therapy↗
PubMed1986

Vectors for expression and amplification of cDNA in mammalian cells: expression of rat phenylalanine hydroxylase.

We have constructed two recombinant plasmid vectors for direct expression and amplification of cDNA in mammalian cells. Each vector carries two dominant selectable markers (the bacterial neo gene and the mouse DHFR gene), a promoter sequence (viral LTR in pAV009/A+, and sheep metallothionein promoter in pMT010/A+), a polyadenylation signal sequence, and a Bam HI site to allow insertion of cDNA. We have used these vectors to prepare recombinant clones for the expression of rat phenylalanine hydroxylase (PH) in LTK- cells. Selection of transformants with neomycin followed by selection of the transformants in methotrexate led to a 30- to 60-fold amplification of the DHFR marker and co-amplification of the PH cDNA, with a corresponding increase in the level of PH mRNA and enzyme polypeptide. The expressed enzyme has a subunit molecular weight of 50,000 which corresponds to the W- allele of rat liver PH. PH activity was detected in the transfected cells by enzymatic measurement of the conversion of [14C]phenylalanine to [14C]tyrosine, and by growth of these cells in a tyrosine-free culture medium. Expression of rat PH in cell culture should facilitate the analysis of the biochemical properties of this enzyme.

Animals↗
PubMed1984

Clearance of 9-micron spheres and rubidium in the intestinal circulation.

Rubidium clearance and 9-micron-sphere entrapment were studied and compared in isolated intestinal preparations under various physiological conditions in 10 dogs anesthetized with intravenous pentobarbital sodium. The chosen intestinal segment was pumped with aortic blood at a constant rate and pressure of about 90-100 mmHg. The temperature of the isolated loop was maintained at 37-38 degrees C with an electrical pad. A mixture of 86Rb and 9-micron-spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop while mesenteric venous blood was collected for activity counting. Three to four intestinal segments were used from each dog. The following three experimental conditions were randomly used for each intestinal segment preparation: 1) a mesenteric venous pressure (MVP) equaling 0 cmH2O and warmed normal saline infused into the lumen of segment; 2) an MVP equaling 0 cmH2O and 5% glucose in saline infused into the intestinal lumen; and 3) the reservoir with venous blood elevated to provide an MVP equaling 17 cmH2O and warmed normal saline infused into the intestinal lumen. A very strong and significant correlation was found between rubidium and microsphere clearances (r = 0.99, P less than 0.0001). Rubidium extraction was inversely associated with blood flow through the intestinal segment (r = 0.49, P = 0.02), while microsphere entrapment (extraction) was independent from intestinal blood flow (r = 0.16). The data suggest that the shunting of 9-micron spheres through tissue reflects the arteriovenous shunting of blood and, therefore, can be used as a tool to study the nutritive and nonnutritive blood flows in tissues.

Animals↗
PubMed1983

Regional blood flow during cross-clamping of the thoracic aorta and infusion of sodium nitroprusside.

Labeled microspheres, 15 microns in diameter, were used to determine cardiac output and regional blood flow response to cross-clamping of the midthoracic aorta and subsequent sodium nitroprusside (SNP) infusion in 11 dogs. During aortic cross-clamping, mean arterial pressure above the occlusion (MAPa) increased 30% to 35%, mean arterial pressure below the occlusion (MAPb) decreased 87%, cardiac index decreased 12% to 14%, left atrial pressure (LAP) doubled, and renal and spinal cord (lower part) blood flows decreased substantially (85% to 94%). SNP infusion returned MAPa to baseline values, decreased MAPb by half, and substantially and further decreased renal blood flow (to 3% to 5% of baseline values). Myocardial and cerebral blood flows increased substantially (up to 250% to 400%). An increase in preload (fluid load) was accompanied by an increase in LAP, cardiac index, and myocardial blood flow only but not in renal or spinal cord flow. There was a strong association between cortical renal blood flow and MAPb (r2 = 0.92; p less than 0.0001), which suggests that blood flow through organs and tissues below the occlusion is pressure dependent. The data show that SNP infusion during thoracic aortic cross-clamping improves systemic and regional circulation above the occlusion but decreases MAPb and therefore blood flow below the occlusion. SNP infusion should be used with caution during aortic cross-clamping, since arterial hypotension of any degree may be deleterious to organs below the cross-clamp.

Animals↗
PubMed1982

beta-hydroxyisobutyryl coenzyme A deacylase deficiency: a defect in valine metabolism associated with physical malformations.

An infant, born to parents who were first cousins had multiple physical malformations. An associated biochemical abnormality was suggested by the urinary excretion of cysteine and cysteamine conjugates of methacrylic acid. The coenzyme A (CoA) ester of this compound is an intermediate in the pathway of valine oxidation. Subsequent investigation revealed a deficiency of beta-hydroxyisobutyryl-CoA deacylase, an enzyme unique to valine metabolism. The enzyme defect results in accumulation of methacrylyl-CoA, a highly reactive compound, which readily undergoes addition reactions with free sulfhydryl groups. Tissue damage due to reactions between methacrylyl-CoA and important sulfhydryl-containing enzymes and cofactors may account for the teratogenic effects seen in this patient.

Abnormalities, Multiple↗
PubMed1980

Isolation and characterization of a myeloma--spleen-cell hybrid producing antibody to phenylalanine hydroxylase.

Application of the technique of myeloma--spleen-cell fusion [Kohler & Milstein (1975) Nature (London) 256, 495--497] has allowed the isolation of a cell colony that produced a monoclonal antibody against monkey liver phenylalanine hydroxylase. The antibody exhibited cross-reactivity against hepatic phenylalanine hydroxylase from other mammalian species, including human, rat and mouse. Cross-reactivity was established by (a) enzyme-inhibition assay, (b) double-immunodiffusion reaction, and (c) two-dimensional polyacrylamide-gel-electrophoretic analysis of immunoprecipitate. The various properties of the monoclonal antibody and its use in the study of mammalian phenylalanine hydroxylase are presented.

Animals↗
PubMed1980

Genetics of mammalian phenylalanine hydroxylase system. IV. Evidence of phenylalanine hydroxylase in a cultured human hepatoma cell line.

We report here te identification of a cultured human hepatoma cell line which possesses an active phenylalanine hydroxylase system. Phenylalanine hydroxylation was established by growth of cells in a tyrosine-free medium and by the ability of a cell-free extract to convert [14C]phenylalanine to [14C]tyrosine in an enzyme assay system. This enzyme activity was abolished by the presence in the assay system of p-chlorophenylalanine but no significant effect on the activity was observed with 3-iodotyrosine and 6-fluorotryptophan. Use of antisera against pure monkey or human liver phenylalanine hydroxylase has detected a cross-reacting material in this cell line which is antigenically identical to the human liver enzyme. Phenylalanine hydroxylase purified from this cell line by affinity chromatography revealed a multimeric molecular weight (estimated 275,000) and subunit molecular weights (estimated 50,000 and 49,000) which are similar to those of phenylalanine hydroxylase purified from a normal human liver. This cell line should be a useful tool for the study of the human phenylalanine hydroxylase system.

Animals↗
PubMedDate not supplied

Conservation of the expression of Dll, en, and wg in the eye-antennal imaginal disc of stalk-eyed flies.

We studied the developmental basis of exaggerated eye span in two species of stalk-eyed flies (Cyrtodiopsis dalmanni and Sphyracephala beccarn). These flies have eyes laterally displaced at the end of eyestalks, and males have greatly exaggerated eye span, which they use as a sexual display. To investigate eye span development we have compared eye-antennal disc morphology and the expression of three key regulator genes of Drosophila head development, Distal-less (Dll), engrailed (en), and wingless (wg), in the stalk-eyed flies and Drosophila. We found great similarity in the basic division of the disc into anterior-antennal and posterior-eye portions and in the general patterning of Dll, en, and wg. Unexpectedly, our results showed that although the eye and antenna are adjacent in adult stalk-eyed flies, their primordia are physically separated by the presence of an intervening region between the anterior and posterior portions of the disc. This region is absent from Drosophila eye-antennal discs. We chose two stalk-eyed fly species that differed in the degree of eye-stalk exaggeration but surprisingly we found no corresponding difference in the size of the en-wg expression domains that mark the boundaries of the dorsal head capsule primordia. In summary, our expression data establish the regional identity of the eye-antennal disc and provide a framework from which to address the developmental genetics of hypercephaly.

Animals↗
PubMedDate not supplied

An assessment of the health communication job market across multiple types of organizations.

This study seeks to answer three questions: (1) What is the employment outlook for health communication practitioners? (2) What specialized knowledge and skills should a competent health communication practitioner possess? and (3) How much academic training or professional experience is necessary to become a competent health communication practitioner? To this end, 104 employers of health communication practitioners, representing different types of large, medium, and small companies and organizations from various regions of the United States, were interviewed by telephone. The interview protocol was based on nine core health communication responsibilities identified by a working group of health communication academicians and practitioners. The study suggests a positive employment outlook, where those seeking jobs in health communication before the year 2000 could enjoy varied job opportunities in the wake of an anticipated moderate expansion in the field. Those with 1 to 10 years of experience are most in demand. While an undergraduate degree provides an academic background to perform most responsibilities, for six of the nine core responsibilities an advanced degree was preferred by at least one-third of respondents.

Employment↗