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Biomedical subjects

R L Price

Publications and source records attributed to R L Price.

At least 37 records · Page 2Linked to original sources
PubMed1994

Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix.

Cellular phenotype is the result of a dynamic interaction between a cell's intrinsic genetic program and the morphogenetic signals that serve to modulate the extent to which that program is expressed. In the present study we have examined how morphogenetic information might be stored in the extracellular matrix (ECM) and communicated to the neonatal heart cell (NHC) by the cardiac alpha 1 beta 1 integrin molecule. A thin film of type I collagen (T1C) was prepared with a defined orientation. This was achieved by applying T1C to the peripheral edge of a 100 mm culture dish. The T1C was then drawn across the surface of the dish in a continuous stroke with a sterile cell scraper and allowed to polymerize. When NHCs were cultured on this substrate, they spread, as a population, along a common axis in parallel with the gel lattice and expressed an in vivo-like phenotype. Individual NHCs displayed an elongated, rod-like shape and disclosed parallel arrays of myofibrils. These phenotypic characteristics were maintained for at least 4 weeks in primary culture. The evolution of this tissue-like organizational pattern was dependent upon specific interactions between the NHCs and the collagen-based matrix that were mediated by the cardiac alpha 1 beta 1 integrin complex. This conclusion was supported by a variety of experimental results. Altering the tertiary structure of the matrix or blocking the extracellular domains of either the cardiac alpha 1 or beta 1 integrin chain inhibited the expression of the tissue-like pattern of organization. Neither cell-to-cell contact or contractile function were necessary to induce the formation of the rod-like cell shape. However, beating activity was necessary for the assembly of a well-differentiated myofibrillar apparatus. These data suggest that the cardiac alpha 1 beta 1 integrin complex serves to detect and transduce phenotypic information stored within the tertiary structure of the surrounding matrix.

Animals↗
PubMed1994

Effect of ammoniation of aflatoxin B1-contaminated cottonseed feedstock on the aflatoxin M1 content of cows' milk and hepatocarcinogenicity in the trout bioassay.

The effectiveness of ammonia in inactivating aflatoxins in contaminated cottonseed was investigated. Two aflatoxin-contaminated cottonseed lots were treated separately using an atmospheric pressure, ambient temperature ammoniation procedure (APAT) or a high pressure, high temperature ammoniation procedure (HPHT), and incorporated into dairy cow rations. Isocalorific diets containing 25% defatted, dried milk from cows fed aflatoxin-contaminated cottonseed without or with APAT or HPHT treatment, or an aflatoxin-free human grade commercial milk powder, were then fed for 12 months to rainbow trout (Oncorhynchus mykiss). Aflatoxin M1 (AFM1) concentrations in milk powders without and with seed treatment were: APAT, 85 and < 0.05 microgram/kg; HPHT, 32 and < 0.05 microgram/kg. In the APAT experiment, trout consuming the diet containing milk from cows fed the aflatoxin-contaminated cottonseed had a 42% incidence of hepatic tumours; APAT cottonseed treatment reduced this to 2.5%. Positive controls were included to demonstrate trout responsiveness. AFB1 fed continuously for 12 months at 4 micrograms/kg resulted in a 34% tumour incidence, whereas positive controls fed 20 micrograms AFB1/kg, 80 micrograms AFM1/kg, or 800 micrograms AFM1/kg for 2 wk and killed 9 months later had a 37, 5.7 and 50% incidence of tumours, respectively. These data demonstrate that APAT ammonia treatment of aflatoxin-contaminated dairy cattle cottonseed feedstock abolished the detectable transfer of AFM1 or AFB1 into milk powder, and greatly reduced the carcinogenic risk posed by any carry-over of aflatoxins or their derivatives into milk. In addition, the results confirm AFM1 to be a lower level hepatocarcinogen in comparison with AFB1 in the trout carcinogenicity assay. In the separate HPHT experiment, no tumours were observed in the livers of trout fed diets containing milk from either the ammonia-treated or untreated source, or the control diet containing 8 micrograms AFM1/kg. Positive controls fed 64 micrograms AFB1/kg for 2 wk exhibited a 29% tumour incidence 12 months later. Thus in this experiment, neither AFM1 at 8 micrograms/kg nor any HPHT-derived aflatoxin derivatives that might have been carried over into milk, represented a detectably carcinogenic hazard to trout.

Aflatoxin B1↗
PubMed1994

Distribution of beta-1 integrin in the developing rat heart.

Cell-cell and cell-matrix interactions play critical roles in various developmental processes including differentiation, proliferation, and migration. Members of the integrin family of cell surface components are important mediators of these cell-extracellular matrix (ECM) contacts or interactions. The ECM provides signals to individual cells essential for development and differentiation and plays essential roles in establishing and maintaining the complex structure of the vertebrate heart. Integrins provide a fundamental link for transduction of developmental signals to cells. Integrin expression by cardiac myocytes is altered during neonatal heart development and disease; however, little is known regarding the spatial and temporal patterns of integrin expression during embryonic and fetal heart development. Essential to understanding the role of integrins in the organization of the heart, the present studies have localized beta-1 integrin protein and mRNA in fetal and neonatal rat hearts. Beta-1 integrin is predominantly found in regions of remodeling (trabeculae) in the early heart (10-13 days of gestation). Later in development (15 days of gestation onward), beta-1 integrin is abundant in regions containing an elaborate ECM, such as the valves. These studies further support the hypothesis that the expressions of integrins and ECM are coordinately regulated in the developing heart.

Animals↗
PubMed1993

Neurofilaments assume a less random architecture at nodes and in other regions of axonal compression.

Neurofilament distributions were mathematically characterized in four chicken somatic motor axons at each of four histologically distinct regions: compact myelinated regions, compact myelinated regions associated with Schwann cell nuclei, Schmidt-Lanterman clefts, and nodes of Ranvier. Compact myelinated regions had the largest cross-sectional areas, the lowest neurofilament densities, and the most random neurofilament organizations--nodes of Ranvier had the smallest cross-sectional areas, the highest neurofilament densities, and the most ordered architectures. In these myelinated axons, the closest natural neurofilament spacing was 25 nm. Mathematical analyses of serial sections suggested that neurofilament interactions are sufficiently weak and transient to permit a full range of variation from random to ordered cytoskeletal architectures as the neurofilaments move longitudinally through the few micron span of the paranodal-nodal region of a single axon.

Animals↗
PubMed1993

Double-blind evaluation of patient-controlled epidural analgesia during labor.

A double-blind randomized study was designed to compare the efficacy of patient-controlled epidural analgesia (PCEA) with continuous epidural analgesia (CEA) with regards to patient satisfaction with analgesia, analgesic efficacy, and local anesthetic usage. After establishing effective epidural analgesia with 8 ml of 0.25% bupivacaine, 39 parturients were randomized to 1 of 2 groups. The CEA group received a continuous infusion of 12 ml/h of 0.125% bupivacaine. The PCEA group received a background infusion of 4 ml/h of 0.125% bupivacaine and were able to self-administer additional boluses of 3 ml of 0.25% bupivacaine every 10 min up to 15 ml/h. In both groups, when patients complained of inadequate analgesia, supplemental doses of 5 ml of 0.25% bupivacaine were administered by a physician. The 2 groups were similar in age, height, weight, gravidity, labor duration, motor block, sensory block, and infant Apgar scores. The 2 groups also did not differ significantly in terms of patient satisfaction, pain assessment, or total drug usage. However, the PCEA group required significantly fewer supplemental doses (15%) compared with the CEA group (40%). The decreased need for supplemental doses in the PCEA group may suggest a potential advantage in consistency of analgesia and possibly decreased man-power needs.

Journal Article↗
PubMed1993

Spontaneous direct carotid-cavernous fistula in childhood.

We report the occurrence, surgical treatment and long-term follow-up of a spontaneous, direct carotid-cavernous fistula in a child. It is the third angiographically documented, spontaneously occurring fistula to be reported in this age group and the first to arise directly from the internal carotid artery based on our review of the literature. Although our patient required fistula closure, other reported fistulae were nonprogressive and did not require treatment. The communication between the internal carotid artery and the cavernous sinus was left sided while the contralateral eye was proptotic. The clinical features, selected hemodynamic characteristics, and treatment of carotid-cavernous fistulas are reviewed.

Arteriovenous Fistula↗
PubMed1993

Comparison of digestibility, nutritive value, and storage characteristics of different forms of cottonseed in diets fed to lactating dairy cows.

Thirty-two Holstein cows averaging 70 d postpartum were used to compare digestibility of whole short staple cottonseed (SS) to whole Pima (WP), coarsely cracked Pima (CrP), and ground Pima (GP) cottonseeds and their effects on lactational performance. Cottonseed was fed at 15% of diet DM. Milk and solids-corrected milk (SCM) yields were higher for cows fed GP than for cows fed CrP or WP but were not different from yields of cows fed SS. Feed efficiency (SCM/DMI) was higher for cows fed GP and SS than for those fed WP. Milk of cows fed GP was lower in stearic acid but higher in linoleic and linolenic acids than milk of cows fed SS. Whole seeds passing into the feces (percentage of consumed) were higher for WP (12.3%) than for SS (6.2%). Total tract digestibility of ether extract was lower for WP than for other diets. Digestibilities of other nutrients were not different. To test storage characteristics, samples of cottonseed were incubated at 32 degrees C and 30% relative humidity for 0, 10, 20, and 30 d, or stored at ambient temperatures in covered buckets for 9 mo. No differences in amount of free fatty acids between incubated samples were noted, and only CrP stored in buckets for 9 mo was significantly higher in free fatty acids than initial or frozen seed. No differences in aflatoxin were detected, and levels were very low. Milk yield of cows fed GP diets was similar to that of cows fed SS diets and slightly higher than those of cows fed CrP or WP diets. Processing the Pima seed increased feed efficiency.

Animal Feed↗
PubMed1992

Ultrastructural localization of laminin on in vivo embryonic, neonatal, and adult rat cardiac myocytes and in early rat embryos raised in whole-embryo culture.

The temporal and spatial distribution of the basement membrane component laminin was examined in vivo in developing rat hearts at 11.5 and 15 days of embryonic development (ED), and in neonates and adults, by pre-embedding ultrastructural immunocytochemistry. In addition, the patterns observed at 11.5 days ED were compared to the distribution of laminin in embryos maintained in whole-embryo culture. At 11.5 days ED laminin was localized in punctate patches on the surface of the plasma membrane, with large gaps between areas of staining. The development of myocytes and localization of laminin in the whole embryo-cultured embryos was similar to that found in the in vivo embryos. At 15 days ED, laminin localization was limited to distinct patches of developing extracellular matrix material associated with the sarcolemma. Gaps between areas of localization were shorter than in the 11.5-day hearts. In neonates, distribution of laminin localization was more extensive with fewer gaps and was associated with the developing basement membrane. In adult hearts, laminin was localized along the entire length of the basement membrane and was heaviest in areas of morphological specialization, such as Z-bands, where collagen bundles contacted the sarcolemma.

Animals↗
PubMed1991

Microtubules have special physical associations with smooth endoplasmic reticula and mitochondria in axons.

Ultrastructural morphometry was used to document the non-random spatial distributions of organelles within the compact myelinated region of avian oculomotor axons. These regions contain large numbers of loosely packed neurofilaments (NFs) (241/microns 2) and only a relatively small number of microtubules (MTs) (4/microns 2), mitochondria (0.6/microns 2), and smooth endoplasmic reticulum (SER) (1.6/microns 2). Random co-occurrences between the relatively sparsely distributed MTs, mitochondria, and SER are probably infrequent in these axons. The actual co-occurrences of MTs, mitochondria, and SER with MTs were counted and compared to the co-occurrences expected in a random Poisson distribution. At long distances (200 nm), the co-occurrences were random. At shorter distances (40 nm and less), MTs were still randomly associated with other MTs. However, at these shorter distances, the spatial associations of mitochondria with MTs and of SER with MTs were not random; such preferential stable associations may be produced by specific MT associated cross-bridging proteins. In axons, MTs tend to be clustered together, giving the appearance of MT bundles. We propose that the MT-MT bundling is an indirect result of MT concentration along the continuous intra-axonal SER network, to which the MTs are apparently tied directly by dynamic molecular cross-bridges.

Animals↗
PubMed1991

Human keratinocytes cultured on collagen gels form an epidermis which synthesizes bullous pemphigoid antigens and alpha 2 beta 1 integrins and secretes laminin, type IV collagen, and heparan sulfate proteoglycan at the basal cell surface.

Single cell suspensions of human keratinocytes when seeded onto floating three-dimensional gels constructed with type I collagen form a tissue resembling epidermis. These morphogenetic events occur in a serum-free environment in the absence of fibroblasts. Light and transmission electron microscopy show that cells form a basal layer plus suprabasilar cell layers corresponding to the stratum spinosum, stratum granulosum, and stratum corneum. The suprabasilar keratinocyte layers show morphologies which resemble intact skin in which cells are connected by desmosomes and contain intermediate filaments and keratohyalin-fillagrin granules. The basal cell layer differs from skin in vivo in that there is no connection to a basement membrane via hemidesmosomes. Cells in the basal layers are polarized as evidenced by the secretion of type IV collagen, heparan sulfate proteoglycans, and laminin at the cell membrane interface with the collagen gel. These proteins are not organized into a cytological basement membrane. Bullous pemphigoid antigen, a protein component of hemidesmosomes, is synthesized by basal keratinocytes, but like the basement membrane proteins it is not incorporated into a definable cytological structure. Keratinocytes in the basal and suprabasilar layers also synthesize alpha 2 beta 1 integrins. The mechanisms of keratinocyte adhesion to the gel may be through the interactions of this cell surface receptor with laminin and type IV collagen synthesized by the cell and/or direct interactions between the receptor and type I collagen within the gel. This in vitro experimental system is a useful model for defining the molecular events which control the formation and turnover of basement membranes and the mechanisms by which keratinocytes adhere to type I collagen when sheets of keratinocytes are used clinically for wound coverage.

Adolescent↗
PubMed1990

Internal axonal cytoarchitecture is shaped locally by external compressive forces.

The cross-sectional architecture of the axon and the area of its surrounding Schwann cell were quantified at selected histological regions along the length of avian myelinated axons. The number of neurofilaments (NFs), the density of NFs, axoplasmic area, and Schwann cell cross-sectional area were measured. These parameters were examined at Schmidt-Lanterman (S-L) clefts, at paranodal-nodal regions, and at regions of compact myelin Schwann cell nuclei. The results were then compared with the same parameters in adjacent compact myelinated regions of the same axons. At S-L clefts, paranodal-nodal regions, and Schwann cell nuclei, the axonal areas were smaller and the NF densities were higher than at compact myelinated regions. From other studies, it has been suggested that NF organization is responsive to local compressive forces--NF packing density tends to increase with increasing compression of the axon. We found that the NF packing densities were relatively small and the axon diameters were relatively large in the compact myelinated regions; this result suggests that in these axonal regions external constraints on axonal architecture are minimal. The higher NF packing densities and smaller axon diameters in the other histological regions suggest that external compressive effects on the axon increase in the following order: simple compact myelin less than Schwann cell nucleus less than S-L cleft less than paranodal-nodal region. Ultrastructural comparisons of these 4 histological regions show that the Schwann cell cross-sectional areas differ reproducibly, and this is consistent with the idea that variations in the organization of extra-axonal elements that envelop the axon produce different amounts of physical constraint on the axon and that this can affect the amount of external pressure on the internal architecture of the axon.

Animals↗
PubMed1990

Is there central respiratory depression after intravenous administration of propranolol?

Beta-adrenergic blockers have been reported to depress central ventilatory drive. The authors investigated this possibility in a double-blind, randomized fashion in 12 healthy volunteers who received 0.1 mg.kg-1 of propranolol and normal saline intravenously at two separate study sessions. A modified Read rebreathing technique was used. Both ventilatory and occlusion pressure responses to CO2 were measured to help separate peripheral (airway) from central mechanisms. Significant beta blockade was demonstrated by statistically lower heart rate responses to CO2 rebreathing after propranolol, but not normal saline. Nevertheless, propranolol exerted no significant effect on resting end-tidal CO2 or the ventilatory and occlusion pressure responses to CO2. Although health subjects appear to have minimal alterations in their ventilatory response to CO2 after beta-adrenergic blockade, patients with airway disease may still experience significant changes in ventilation. In addition, drug interaction studies may give further insight into the presence or absence of any respiratory effects of propranolol.

Adult↗
PubMed1988

Neurofilaments are spaced randomly in the radial dimension of axons.

The organization of the cytoskeleton is compared in the large myelinated parasympathetic and somatic motor axons of the avian oculomotor system. Electron microscopic studies demonstrate that neurofilaments are the chief structural elements in these axons, and quantitative analyses of the distribution of neurofilaments in axonal cross-sections found that the average neurofilament packing density is 25% greater in the parasympathetic axons than in the somatic motor axons. In both types of axon the distributions of neurofilaments matched a randomly generated (Poisson) distribution. In axoplasm, a Poisson distribution could arise if the neurofilaments were distributed in the cross-sectional plane by stochastic forces operating randomly and without significant neurofilament-neurofilament interactions. Thus, in these axons, the neurofilaments behave as if they are inert 'molecules' in a dilute solution-subject to non-specific stochastic forces that tend to distribute them at random. We propose that neurofilaments normally are relatively free to move apart from each other and to fill the available space within the axon.

Animals↗
PubMed1988

Recession and anterior transposition of the inferior oblique for treatment of superior oblique palsy.

We evaluated the effectiveness of inferior oblique recession with anterior transposition in treating 12 patients with superior oblique palsy. Mean decreases of hypertropia measured 17 prism diopters in the primary position, 24 prism diopters in adduction, and 21 prism diopters on ipsilateral head tilt. Head tilt and diplopia were uniformly eliminated. No surgical complications were encountered. Postoperative deviations were mild and infrequent. Only one patient demonstrated postoperative underaction of the recessed inferior oblique.

Adolescent↗
PubMed1987

Evaluation of aflatoxin B1 mutagenesis: addition of glutathione and glutathione-S-transferase to the Salmonella mutagenicity assay.

The effects of glutathione (GSH) and the combination of GSH and glutathione-S-transferase (GST) on aflatoxin B1 (AFB1) mutagenesis in the Salmonella mutagenicity assay using Salmonella typhimurium strains TA98 and TA100 were tested. Ten concentrations of AFB1 (0-1.0 micrograms/plate) were added to a liver microsomal homogenate (S9 mix) or to S9 mix containing GSH or S9 mix containing the combination of GSH + GST. One-third of the samples were plated directly. Two-thirds were incubated for 30 min at 37 degrees C prior to plating, and of those, half included bacteria. All samples were plated according to Ames et al [1975]. The results show that the addition of GSH and GSH + GST affected AFB1 mutagenesis by forming the AFB1-GSH conjugate and decreasing the availability of AFB1-8,9-epoxide. The effect of GST on GSH activity varied with the strain because of the different amounts of S9 mix used. The formation of the AFB1-GSH conjugate was verified by using reverse-phase high-performance liquid chromatography for quantitation of AFB1 and detection of AFB1-GSH.

Aflatoxin B1↗
PubMed1985

Developmental anomalies of the optic disc and carotid circulation. A new association.

Three patients with developmental abnormalities of the optic disc (two morning glory anomalies and one retinochoroidal-optic disc coloboma) had angiographically documented aberrancies of the carotid circulation including large trunk occlusions, moya-moya-like collaterals, dolichoectasia, and absent ophthalmic artery. Although developmental optic disc abnormalities have been linked with other problems such as basal encephalocele, congenital heart defects, and eyelid hemangiomas, these three patients are the first to our knowledge to have related malformations of the intracranial circulation. We suggest, therefore, that the presence of a congenital optic disc anomaly may herald a similar defect in the cerebral circulation.

Abnormalities, Multiple↗