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Biomedical subjects

K L Anderson

Publications and source records attributed to K L Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Conversion of cephapirin to deacetylcephapirin in milk and tissues of treated animals.

Cephapirin is one of six beta-lactam antibiotics approved for use in the treatment of food-producing animals in the United States. When used for treatment of mastitis by intramammary infusion, it is partially converted to a microbiologically active metabolite identified as deacetylcephapirin (DACEP). The degradation was followed in four cows with naturally acquired mastitis which were treated with cephapirin. DACEP persisted longer than the parent compound in the milk. When a calf was treated with cephapirin by intramuscular injection, the compound was almost completely converted to DACEP in tissues. The deacetyl form must be considered in the determination of residues in treated animals.

Animals↗
PubMed1999

PU.1 and the granulocyte- and macrophage colony-stimulating factor receptors play distinct roles in late-stage myeloid cell differentiation.

PU.1 is a hematopoietic cell-specific ets family transcription factor. Gene disruption of PU.1 results in a cell autonomous defect in hematopoietic progenitor cells that manifests as abnormal myeloid and B-lymphoid development. Of the myeloid lineages, no mature macrophages develop, and the neutrophils that develop are aberrantly and incompletely matured. One of the documented abnormalities of PU. 1 null (deficient) hematopoietic cells is a failure to express receptors for granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, and M-CSF. To elucidate the roles of the myeloid growth factor receptors in myeloid cell differentiation, and to distinguish their role from that of PU.1, we have restored expression of the G- and M-CSF receptors in PU.1-deficient cells using retroviral vectors. We have similarly expressed PU.1 in these cells. Whereas expression of growth factor receptors merely allows a PU.1-deficient cell line to survive and grow in the relevant growth factor, expression of PU.1 enables the development of F4/80(+), Mac-1(+)/CD11b(+) macrophages, expression of gp91(phox) and generation of superoxide, and expression of secondary granule genes for neutrophil collagenase and gelatinase. These studies reinforce the idea that availability of PU.1 is crucial for normal myeloid development and clarify some of the molecular events in developing neutrophils and macrophages that are critically dependent on PU.1.

Animals↗
PubMed1999

Roles of IFN consensus sequence binding protein and PU.1 in regulating IL-18 gene expression.

IL-18 is expressed from a variety of cell types. Two promoters located upstream of exon 1 (5'-flanking region) and upstream of exon 2 (intron 1) regulate its expression. Both promoter regions were cloned into pCAT-Basic plasmid to yield p1-2686 for the 5'-flanking promoter and p2-2.3 for the intron 1 promoter. Both promoters showed basal constitutive activity and LPS inducibility when transfected into RAW 264.7 macrophages. To learn the regulatory elements of both promoters, 5'-serial deletion and site-directed mutants were prepared. For the activity of the p1-2686 promoter, the IFN consensus sequence binding protein (ICSBP) binding site between -39 and -22 was critical. EMSA using an oligonucleotide probe encompassing the ICSBP binding site showed that LPS treatment increased the formation of DNA binding complex. In addition, when supershift assays were performed, retardation of the protein-DNA complex was seen after the addition of anti-ICSBP Ab. For the activity of the p2-2.3 promoter, the PU.1 binding site between -31 and -13 was important. EMSA using a PU.1-specific oligonucleotide demonstrated that LPS treatment increased PU.1 binding activity. The addition of PU.1-specific Ab to LPS-treated nuclear extracts resulted in the formation of a supershifted complex. Furthermore, cotransfection of ICSBP or PU.1 expression vector increased p1 promoter activity or IL-18 expression, respectively. Taken together, these results indicate that ICSBP and PU.1 are critical elements for IL-18 gene expression.

5' Untranslated Regions↗
PubMed1999

Conceptualization and measurement of quality of life as an outcome variable for health care intervention and research.

If health care providers are to be able to document effective outcomes resulting from their interventions, they must first develop clear conceptual definitions for the outcomes, and then select measures that represent these concepts. No consensus exists in the health care disciplines about what quality of life is or how it should be measured. This paper presents historical and conceptual arguments in favour of a particular definition of quality of life, and distinguishes between quality of life and concepts often confused with it in the literature: symptoms, mood, functional status, and general health status. Whether quality of life is actually amenable to change as a result of health care interventions, and whether we ought to be trying to influence clients' quality of life is also discussed. We conclude that quality of life is an important outcome of health care intervention. However, traditional approaches to influencing quality of life may be misdirected, and the relative importance of our interventions to clients--whose opinions matter the most--ought to be put into perspective.

Humans↗
PubMed1999

Alterations in pulmonary function following exercise are not caused by the work of breathing alone.

Both pulmonary function and respiratory muscle strength decrease following exercise in healthy humans. The alterations in respiratory muscle are not the same following exercise and voluntary isocapnic hyperpnea that simulates that exercise. Therefore, in this study we measured pulmonary and respiratory muscle function following maximal exercise or hyperpnea that simulated the ventilation seen during exercise. Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1.0), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and handgrip strength were measured before and following voluntary hyperpnea in which minute ventilation and breathing frequency were controlled to levels identical to those obtained during the exercise test, and before and following a period of rest of equal duration to the exercise and hyperpnea tests. FVC decreased by 400 ml (7%, p<0.05) immediately post-exercise. MIP decreased by 12 mmHg (15%, p < 0.005) following exercise and remained depressed for 15 minutes. Neither MEP nor FEV1.0 decreased following exercise, and none of the variables were altered following the control or hyperpnea bouts. These data indicate that pulmonary function and respiratory muscle strength are altered following exercise but not by similar bouts of hyperpnea without accompanying exercise. Therefore, exercise affects pulmonary function independent of the respiratory muscle work done.

Adult↗
PubMed1999

Perceiving the sweet spot.

Many sports involve aligning a hitting implement with a ball trajectory such that contact is made at the implement's center of percussion or 'sweet spot'. This spot is not visibly distinct; its perception must be haptic. Although it is functionally defined with respect to contact--it is the point of impact that produces the least vibration in the hand holding the implement--hitting success requires appreciating the location of the sweet spot prior to contact. Two experiments verified that perceivers (novices as well as expert tennis players) distinguished perception of length from perception of the position of the sweet spot simply on the basis of wielding, both for tennis rackets and for bats contrived from wooden rods with attached masses. Results conformed to previous research on dynamic touch in showing that perceiving the lengths of wielded objects, including selectively perceiving partial lengths, is constrained by inertial properties of the object.

Adult↗
PubMed1999

Regulation of cellulose-inducible structures of Clostridium cellulovorans.

Scanning electron microscopy was used to detect ultrastructural protuberances on the cellulolytic anaerobe Clostridium cellulovorans. Numerous ultrastructural protuberances were observed on cellulose-grown cells, but few were detected on glucose-, fructose-, cellobiose-, or carboxymethylcellulose (CMC)-grown cells. Formation of these protuberances was detected within 2 h of incubation in cellulose medium, but 4 h incubation was required before numerous structures were observed on the cells. When a soluble carbohydrate or CMC was mixed with cellulose-grown cells, the ultrastructural protuberances could no longer be detected. In fact, no protuberances were observed within 5 min following the addition of glucose, cellobiose, or methylglucose to cellulose-grown cells. The presence of these protuberances corresponded with the binding of the Bandeiraea simplicifolia BSI-B4 isolectin to the cell. Cellulose-grown cells had a greater level of observable lectin binding than cellobiose-grown cells, and lectin binding was not detected on glucose- or fructose-grown cells. In addition, lectin binding ability was lost by cellulose-grown cells following the addition of glucose, fructose, or methylglucose to the cellulose medium. A cellulose-affinity protein fraction expressing cellulase activity was also detected in cell extracts of cellobiose- or cellulose-grown cultures. However, this protein fraction was not detected in extracts of glucose-grown cultures, and was rapidly lost (within 5 min) following the addition of glucose to cellulose-grown cultures. The ability of C. cellulovorans to adhere to cellulose was also affected by the energy substrate, but not in the same manner as the protuberance formation or the cellulase-containing protein fraction. Rather, cellobiose-, cellulose-, and CMC-grown cultures adhered to cellulose, but this adherence was not affected by addition of glucose to the medium. This is the first report that soluble carbohydrates caused the rapid loss of some cellulose-inducible systems of C. cellulovorans.

Bacterial Adhesion↗
PubMed1999

A preliminary survey of antibiotic residues and viable bacteria in milk from three Caribbean Basin countries.

There is widespread concern about the presence of antimicrobial drugs in milk. The presence of drug residues in milk may have public health implications. Milk samples (n = 25 to 65/country) were collected from bulk tanks and commercial vendors in Barbados, Costa Rica, and Jamaica between February 1996 and August 1997. Bulk tank samples were collected from high milk-producing regions of Jamaica and Costa Rica and from 26 dairy farms in Barbados. Milk pH, bacterial growth (total CFU/ml and the presence of Streptococcus agalactiae and Staphylococcus aureus), and the presence of antimicrobials were determined. Milk samples were tested by a microbial inhibition test (Delvotest-P, Gist-Brocades Food Ingredients, Inc.) to screen for antimicrobial drugs. All positives were retested for the presence of beta-lactam antibiotics after incubating with penicillinase and some positives were identified by high-pressure liquid chromatography-UV. Mean pH values ranged from 6.5 to 6.7. S. aureus was identified in bulk tank samples from Costa Rica (52%), Barbados (44%), and Jamaica (46%). S. agalactiae was identified in bulk tank samples from Costa Rica (28%), Barbados (8 and 16%), and Jamaica (18%). Antimicrobial residues were detected in some bulk tank samples from Barbados (8%) and Jamaica (10%) but not in samples from Costa Rica. All positives in milk from Jamaica and Barbados were determined to be beta-lactams. No residues were detected in pasteurized milk samples from Barbados or ultrahigh-temperature milk from Jamaica. The presence of beta-lactam residues in some of these samples suggests the appropriateness of testing milk prior to processing for consumption.

Animals↗
PubMed1999

Change in quality of life after lung volume reduction surgery.

BACKGROUND: Lung volume reduction surgery has been reintroduced for treatment of severe emphysema. Goals of this surgery are to decrease dyspnea, increase exercise tolerance, and improve quality of life. OBJECTIVES: To describe the effect of lung volume reduction surgery on overall quality of life, disease severity, dyspnea, and functional status during the first 12 months after surgery. METHODS: Data were collected for 20 patients (mean age, 63 years; 15 men) before and 3, 6, and 12 months after lung volume reduction surgery. Disease severity was determined by percentage of forced expiratory volume in 1 second (compared with established norms); functional status, by a 6-minute walk test; dyspnea, by scores on a visual analog scale; and overall quality of life, by scores on the Quality of Life Scale. RESULTS: Scores on the Quality of Life Scale and distance walked increased significantly after surgery, and these increases were maintained at 6 and 12 months, respectively. Percentage of forced expiratory volume in 1 second increased significantly 3 months after surgery, but changes at 6 and 12 months were not significant. Changes in dyspnea ratings were not significant. No pattern of correlations among study variables was significant. CONCLUSIONS: Quality of life and functional status are improved after lung volume reduction surgery. Because none of the physiological variables were related to changes in quality of life, alternative explanations for these improvements must be explored in future studies.

Analysis of Variance↗
PubMed1998

Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1.

Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)-linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1 were found to have no effect on mutant-mediated disease, which demonstrates that the use of SOD mimetics is unlikely to be an effective therapy and raises the question of whether toxicity arises from superoxide-mediated oxidative stress. Aggregates containing SOD1 were common to disease caused by different mutants, implying that coaggregation of an unidentified essential component or components or aberrant catalysis by misfolded mutants underlies a portion of mutant-mediated toxicity.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Neutrophils deficient in PU.1 do not terminally differentiate or become functionally competent.

PU.1 is an ets family transcription factor that is expressed specifically in hematopoietic lineages. Through gene disruption studies in mice we have previously shown that the expression of PU.1 is not essential for early myeloid lineage or neutrophil commitment, but is essential for monocyte/macrophage development. We have also shown that PU.1-null (deficient) neutrophils have neutrophil morphology and express neutrophil-specific markers such as Gr-1 and chloroacetate esterase both in vivo and in vitro. We now demonstrate that although PU.1-null mice develop neutrophils, these cells fail to terminally differentiate as shown by the absence of messages for neutrophil secondary granule components and the absence or deficiency of cellular responses to stimuli that normally invoke neutrophil function. Specifically, PU.1-deficient neutrophils fail to respond to selected chemokines, do not generate superoxide ions, and are ineffective at bacterial uptake and killing. The failure to produce superoxide could, in part, be explained by the absence of the gp91 subunit of nicotinamide adenine dinucleotide phosphate oxidase, as shown by our inability to detect messages for the gp91(phox) gene. Incomplete maturation of PU.1-deficient neutrophils is cell autonomous and persists in cultured PU.1-deficient cells. Our results indicate that PU.1 is not necessary for neutrophil lineage commitment but is essential for normal development, maturation, and function of neutrophils.

Animals↗
PubMed1998

Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant.

Mutations in superoxide dismutase 1 (SOD1), the only proven cause of amyotrophic lateral sclerosis (ALS), provoke disease through an unidentified toxic property. Neurofilament aggregates are pathologic hallmarks of both sporadic and SOD1-mediated familial ALS. By deleting NF-L, the major neurofilament subunit required for filament assembly, onset and progression of disease caused by familial ALS-linked SOD1 mutant G85R are significantly slowed, while selectivity of mutant-mediated toxicity for motor neurons is reduced. In NF-L-deleted animals, levels of the two remaining neurofilament subunits, NF-M and NF-H, are markedly reduced in axons but are elevated in motor neuron cell bodies. Thus, while neither perikaryal nor axonal neurofilaments are essential for SOD1-mediated disease, the absence of assembled neurofilaments both diminishes selective vulnerability and slows SOD1(G85R) mutant-mediated toxicity to motor neurons.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Myeloid development is selectively disrupted in PU.1 null mice.

The ets family transcription factor PU.1 is expressed in monocytes/macrophages, neutrophils, mast cells, B cells, and early erythroblasts, but not in T cells. We have recently shown that PU.1 gene disruption results in mice with no detectable monocytes/macrophages and B cells but T-cell development is retained. Although neutrophil development occurred in these mice, it was delayed and markedly reduced. We now proceed to demonstrate that PU. 1 null hematopoietic cells fail to proliferate or form colonies in response to macrophage colony-stimulating factor (M-CSF), granulocyte CSF (G-CSF), and granulocyte/macrophage CSF (GM-CSF). In contrast, PU.1 null cells did proliferate and form colonies in response to interleukin-3 (IL-3), although the response was reduced as compared with control littermates. Compared with control cells, PU.1 null cells had minimal expression of G- and GM-CSF receptors and no detectable M-CSF receptors. The size of individual myeloid colonies produced from PU.1 null primitive and committed myeloid progenitors in the presence of IL-3, IL-6, and stem cell factor (SCF) were reduced compared with controls. Under these conditions, PU.1 null progenitors produced neutrophils but not monocytes/macrophages. These observations suggest that PU.1 gene disruption induces additional cell-autonomous effects that are independent of the alterations in myeloid growth factor receptor expression. Our results demonstrate that PU.1 gene disruption affects a number of developmentally regulated hematopoietic processes that can, at least in part, explain the changes in myeloid development and reduction in myeloid and neutrophil expansion observed in PU.1 null mice.

Animals↗
PubMed1998

Cellular interactions in the thymus regulate the protein kinase C signaling pathway.

We provide evidence that thymocytes receive signals from the thymic microenvironment which regulate the protein kinase C (PKC) signaling pathway. Thus, phorbol 12-myristate 13-acetate (PMA) causes a PKC-dependent down-regulation of CD4 expression and induces apoptosis in isolated thymocytes but has little effect on thymocytes maintained within intact thymic lobes or in reaggregate lobes containing purified thymocytes with either thymic or non-thymic stromal cells. Moreover, compact pellets of thymocytes alone are protected from the effects of PMA. This protection is maintained when the compacted thymocytes are rigorously depleted of MHC class II-expressing cells. We conclude that signals arising from thymocyte-thymocyte contact control the utilization of the PKC cascade. These observations have implications for thymocyte signaling in general as well as for the interpretation of studies carried out on thymocyte suspensions.

Animals↗
PubMed1998

A novel locus for Leber congenital amaurosis on chromosome 14q24.

Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous autosomal recessive retinal dystrophy and the most common genetic cause of congenital visual impairment. We used a DNA pooling strategy comparing the genotypes of affected to unaffected control pools in a genome-wide search for identity-by-descent on a consanguineous Saudi Arabian LCA family. A shift to homozygosity was observed in the affected DNA pool compared with the control pool at linked markers D14S606 and D14S610. Genotyping of individual DNA samples from the entire pedigree for marker D14S74, closely linked to these loci, and several flanking markers confirmed linkage with a ZMAX=13.29 at theta=0.0. These data assign a third locus (LCA3) for LCA to chromosome 14q24. This locus and the previously identified loci are excluded for other Saudi Arabian pedigrees, both confirming that this clinical disorder is genetically heterogeneous and that additional LCA genes remain to be identified.

Chromosomes, Human, Pair 14↗
PubMed1998

Changes in kinesin distribution and phosphorylation occur during regulated secretion in pancreatic acinar cells.

In secretory cells, microtubule- (Mt-) based motor enzymes are thought to support transport of secretory vesicles to the cell surface for subsequent release. At present, the role of Mts and kinesin in secretory vesicle transport in exocrine epithelial cells has not been defined. Furthermore, it is unclear whether an agonist-induced secretory event modifies kinesin function and distribution, thus altering vesicle transport. To this end, we utilized isolated rat pancreatic acini and cultured rat pancreatic acinar cells to examine the role of Mts and kinesin in regulated secretion. Exposure of cells to cytoskeletal antagonistic drugs demonstrated that the observed movements of apically clustered zymogen granules (ZGs) are supported by Mts, but not actin. Morphological studies of Mt organization in polarized acini show that Mt plus ends extend outward from the apical membrane toward the cell center. Immunofluorescence microscopy in both cell models revealed a clear association of kinesin with apical ZGs, while quantitative immunoblot analysis of pancreatic subcellular fractions confirmed kinesin enrichment on ZG membranes. In addition, microinjection of kinesin antibodies into cultured acinar cells inhibited ZG movements. Indirect immunofluorescence staining of isolated cells and quantitative Western blotting of isolated ZGs revealed that kinesin association with granule membranes increased up to 3-fold in response to a secretory stimulus. Autoradiographic studies of 32P-labeled acini showed up to a 6-fold increase in kinesin heavy chain (KHC) phosphorylation during stimulated secretion. These studies provide the first direct evidence that Mts and kinesin support ZG movements and that physiological agonists induce a marked phosphorylation of KHC while increasing the association of kinesin with ZG membranes. These changes during agonist stimulation suggest that the participation of kinesin in zymogen secretion is regulated.

Amino Acid Sequence↗
PubMed1998

Pharmacokinetic parameters and milk concentrations of ketoprofen after administration as a single intravenous bolus dose to lactating goats.

Six clinically normal lactating does were administered ketoprofen (2.2 mg/kg intravenously (i.v.)). Blood and milk samples were collected prior to and for 24 h after drug administration. Drug concentrations in serum and milk were determined by high performance liquid chromatography. Pharmacokinetic parameters from each goat were combined to obtain mean estimates (mean +/- SD) of half-life of elimination (t1/2beta) of 0.32 +/- 0.14 h, systemic clearance (Cl) of 0.74 +/- 0.12 L/kg x h, and volume of distribution at steady state (V(ss)) of 0.23 +/- 0.051 L/kg. In milk, ketoprofen was unmeasurable by the method employed (level of detection 25 ng/mL) for all samples.

Animals↗