Biomedical subjects
Publications and source records attributed to B M Smith.
Various materials have been used to repair orbital defects. This article advocates the use of autogenous conchal cartilage, especially in the repair of large posttraumatic defects, where contour, biocompatibility, and strength are most important. The technique for harvesting the cartilage is reviewed, and a case demonstrating its successful use is reported.
Previous studies examining the hypocholesterolemic effects of high-soluble-fiber diets have not been designed to control for dietary fat intake. Serum cholesterol reductions may therefore be accounted for by differences in consumption of fat. Moderately hypercholesterolemic, nonobese, Caucasian men and women, 30-50 y old were randomly assigned to low-fat, low-fat plus high-fiber, or usual-diet groups and followed for 12 mo. At 12 mo the high-fiber group consumed significantly more soluble fiber than both the low-fat and usual-diet groups (P = 0.0063 and P = 0.0001); the high-fiber group did not differ from the low-fat group in quantity of dietary fat consumed. The high-fiber group experienced a greater average reduction (13%) in serum cholesterol than did the low-fat (9%) and usual-diet (7%) groups. After adjustment for relevant covariates, the reduction in the high-fiber group was significantly greater than that in the low-fat group (P = 0.0482). Supplementation with soluble fiber reduces serum cholesterol beyond the reduction observed with low-fat diet alone.
Gene expression relevant to promotion of neoplastic transformation was investigated by measuring proteins differentially synthesized in two mouse epidermal JB6 cell lines sensitive (P+) or resistant (P-) to tumor promoter induced transformation. One dimensional polyacrylamide gel electrophoresis of proteins from cells that had been pulse labeled with 35S-methionine after various times of exposure to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) revealed two protein bands whose intensity increased after 20-24 hr exposure to TPA. Cell fractionation showed that these proteins of 15 and 16 kDa were localized in the nuclear, not the cytosolic, fraction. Parallel studies with 32P-labeled cells showed no evidence for phosphorylation of these proteins. Comparison of P- with P+ cells showed that the observed induction of p15/16 synthesis at 20 hr was specific for P+ cells, with little evidence for stimulated synthesis in P- cells during a 48 hr period. We thus conclude that the tumor promoter produces a late stimulation in the rate of synthesis of 15 and 16 kDa nuclear proteins preferentially in promotion sensitive cells.
We report a North American Indian family of five children in which dizygotic twin sisters and a third sibling had biliary atresia. This is in contrast to many reports of discordant biliary atresia in twins. Added to 29 previously documented cases of familial biliary atresia, these three cases support the theory that both genetic and acquired factors play a role in the pathogenesis of this disease.
Persons with diabetes are at increased risk for cardiovascular disease. Maintaining normal lipid levels is, therefore, a key goal in diabetes management. A high-carbohydrate, high-fiber diet provides effective, positive, and safe treatment for diabetes and lowers the associated risk for coronary artery disease.
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This study compared scores on the 40-item Narcissistic Personality Inventory for 14 Asian, 58 Caucasian, and 16 Hispanic American college women. Asian American women had significantly lower narcissism scores than Caucasian American women and also scored significantly lower on four of the seven component scales. Hispanic and Caucasian women had similar scores on narcissism. These results may be based on an ethnic response set and/or the influence of cultural values present in many traditional Asian cultures which are seemingly antithetical to narcissism and include modesty, respect for authority, and the valuing of relationship over individualism. The importance of including ethnic information in research is stressed.
Prophylactic closed suction drainage has been advocated in a variety of surgical wounds, but its use in wounds involving vascular anastomoses has not been studied. Fifty patients undergoing lower extremity revascularization that required bilateral groin incisions were randomly assigned to have either the right or left side of the groin drained with a closed suction catheter. The contralateral wound was closed without drainage. Statistically there was no difference between wound closed with drains and undrained wounds in the occurrence of hematomas, seromas, lymphoceles, superficial infections, subcutaneous infections, or graft infections; although serious complications were more frequent in the drained wounds. Prophylactic closed suction drainage appears to offer no advantage over closure without drainage in wounds of the groin resulting from elective vascular operations.
A previous report demonstrated that mouse JB6 cells transformed to promotion sensitive (P+) phenotype by transfection with an activated promotion sensitivity (pro) gene showed both evidence for the presence of the transfected gene and sensitivity to phorbol ester induced transformation similar to that observed in parental P+ cells. In addition, pro-1 and pro-2 transfectants were similar to each other in phorbol ester response. The current report extends these findings to ask whether pro-1 or pro-2 transfectants are also sensitive to promotion of transformation by other classes of tumor promoters such as epidermal growth factor (EGF), lanthanides, and phthalate esters and to inhibition of phorbol ester promoted transformation by several classes of antipromoters. The results showed that both pro-1 and pro-2 transfectants resembled parental P+ cells in sensitivity to promotion of anchorage independent transformation by lanthanides and by diethylhexylphthalate. In addition both pro-1 and pro-2 transfectants showed inhibition of phorbol ester induced transformation by antipromoters ganglioside GT1b, ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and forskolin. Thus the pathways implicated by these inducers and inhibitors of transformation appear similar to those implicated for parental P+ cells and similar when controlled by pro-1 or pro-2. The single differential response was that of EGF-induced transformation. pro-2 transfectants but not pro-1 transfectants were sensitive to EGF-induced neoplastic transformation. The nonresponsiveness could not be attributed to lack of EGF receptors since 125I-EGF binding to pro-1 transfectants was similar to that for pro-2 transfectants and parental P+ cells. Thus pro genes transfer responsiveness to a C-kinase mediated promotion of transformation pathway and to putatively non-C kinase pathways triggered by lanthanides or phthalate esters, but not necessarily to an EGF receptor kinase mediated pathway.
Calcium- and phospholipid-dependent protein kinase C activity and substrates were characterized in cell lysates of preneoplastic JB6 cells, a model system of genetic variants for sensitivity to tumor promoter-induced neoplastic transformation. Protein kinase C activity was similar for sensitive and resistant variants, as measured by calcium- and phospholipid-dependent phosphorylation of an exogenous substrate (histone HIII). Of 13 endogenous protein kinase C substrates, identified by labeling proteins with [gamma-32P] ATP, at least two (80 and 23 kDa) are potential candidates for mediating events on the pathway for promotion of transformation. 32P incorporation into the 80-kDa protein kinase C substrate was stimulated by tetradecanoylphorbol acetate and correlated with phenotype: the highest incorporation was found in promotion-insensitive cells, an intermediate level in promotion-sensitive cells and the lowest in the transformed cells. The phosphorylation of an 80-kDa protein, found by labeling intact cells in monolayer growth with [32P]orthophosphate, was also stimulated by tetradecanoylphorbol acetate and correlated inversely with phenotype. The 80 kDa protein kinase C substrate from cell lysates and the 80-kDa phosphoprotein from intact cells appear to be identical, as indicated by peptide mapping with protease V8 from Staphylococcus aureus. This finding suggests that the 80-kDa substrate is relevant to promoter-induced signal transduction in the intact cell. The 23-kDa protein kinase C substrate exhibited a band shift in sodium dodecyl sulfate gels in response to another transformation promoter in JB6 cells, the calcium analog, lanthanum (Smith, B. M., Gindhart, T. D., and Colburn, N. H. (1986) Carcinogenesis 7, 1949-1956). In summary, there are no unique substrates that distinguish the variants. Quantitative differences in certain substrates or their phosphorylation may, however, account for the difference in promotion sensitivity among the variants.
Transfection of activated promotion sensitivity genes (pro genes) confers on insensitive (P-) cells susceptibility to induction of anchorage-independent growth by tumor-promoting phorbol esters. Promotion-sensitive (P+) JB6 cell variants, from which activated pro-1 and pro-2 were cloned, respond to 12-O-tetradecanoylphorbol-13-acetate (TPA) and various nonphorbol tumor promoters with anchorage-independent transformation that is irreversible 60-80% of the time. Anchorage-independent (Tx) clonal lines derived from these TPA-induced agar colonies were also tumorigenic in nude mice. This report has addressed the question of whether the phenotypes associated with parental P+ cells are transferred by transfection of activated pro-1 and pro-2. Clonal lines were established after transfection of JB6 P- cells with activated pro-1 or pro-2, induction of anchorage-independent colony formation by TPA, and growth of individual agar colonies to yield clonal transfectant lines. The lines so derived from transfected populations included Tx, P+, and P- lines, reflecting irreversible neoplastic transformation and greater and lesser degrees of preneoplastic progression, respectively. The anchorage-independent transfectants were found to be tumorigenic. Since untransfected P- cells subjected to the same single-cycle TPA treatment and cloning in agar yielded no anchorage-independent and few P+ transfectants, the appearance of P+ and Tx transfectants after pro-1 and pro-2 transfection is therefore likely to be due to the transfected pro genes. Indirect assay of pro gene uptake by quick-blot hybridization of transfectant cell DNA with the vectors into which pro genes had been cloned confirmed the association of transferred P+ and Tx phenotypes with the presence of the transfected DNA. Finally, assay of the sensitivity of P+ pro-1 and pro-2 transfectants to transformation by TPA at various concentrations showed that transfection with pro-1 or pro-2 conferred about equal responses that were somewhat lower than those observed with parental P+ controls. Taken together these data indicate that promotion-insensitive JB6 cells need only an activated pro gene and TPA exposure to become neoplastically transformed.
During the past decade, the rice agroecosystem and its associated mosquitoes have been the subject of an extensive research effort directed toward the development and implementation of integrated pest management (IPM) strategies. The objective of this work was to synthesize the literature and unpublished data on the rice agroecosystem into a comprehensive simulation model of the key elements of the system known to influence the population dynamics of Psorophora columbiae. Subsequent companion papers will present a validation of these models, provide an in-depth analysis of the population dynamics of Ps. columbiae, and evaluate current and proposed IPM strategies for this mosquito. This paper describes the development of 2 models: WaterMod: Because spatial and temporal distributions of surface water and soil moisture play a decisive role in the dynamics of Ps. columbiae, an essentially hydrological simulator was developed. Its purpose is to provide environmental inputs for a second model (PcSim) which simulates the population dynamics of Ps. columbiae. WaterMod utilizes data on weather, agricultural practices, and soil characteristics for a particular region to generate a data set containing daily estimates of soil moisture and depth of water table for 12 representative areas comprising the rice agroecosystem. This model could be used to provide hydrologic inputs for additional simulation models of other riceland mosquito species. PcSim: This model simulates the population dynamics of Ps. columbiae by using the computer to maintain a daily accounting of the absolute number of mosquitoes within each daily age class for each life stage. The model creates estimates of the number of eggs, larvae, pupae, and adults for a representative l-ha area of a rice agroecosystem.
In an earlier paper, the development of 2 simulation models designed to describe the interaction between key elements of the rice agroecosystem and the population dynamics of Psorophora columbiae were presented (Focks et al. 1988a). The objective of the work reported herein was to validate these models with field data. The first model (WaterMod) predicts soil hydrology conditions as a function of weather, agricultural practices, and soil characteristics for a variety of habitats found within the rice agroecosystem which are utilized by Ps. columbiae. Using a continuous series of hydrologic data collected in southwestern Louisiana during 1984 and 1985, WaterMod was demonstrated capable of adequately predicting runoff rates and the temporal timing of soil moisture and surface water. The second model (PcSim) simulates the population dynamics of Ps. columbiae based upon a host of variables including the output from WaterMod. This model was validated by comparisons made with density estimates from the literature on the temporal and spatial distribution of various life stages and by correspondence with light trap data gathered during the same time and location as the hydrologic data. PcSim was seen to respond appropriately to host animal densities and unusual meterological events occurring during 1984 and 1985 in southern Louisiana. A discussion is presented of the interaction between agricultural practices and certain key factors of the life history strategy of Ps. columbiae which permit the unusually successful exploitation of the rice agroecosystem by this species. A subsequent paper will use these models to evaluate current and proposed IPM strategies for this mosquito (Focks et al. 1988b).
Percutaneous transluminal angioplasty (PTA) has received widespread publicity as a safe, simple, and successful alternative to operation for the management of renal artery stenoses and renovascular hypertension (RVH). Although, in our institution, the primary management of RVH remains operative revascularization, with more than 750 such procedures having been done, we have had the opportunity to manage a spectrum of PTA failures in nine patients during the last 5 years. These include (1) acute dissection of atherosclerotic lesions and occlusion of the distal renal artery requiring emergency operation; (2) unilateral perforation and bilateral thrombosis of fibrodysplastic branch renal artery lesions requiring staged ex vivo reconstruction; (3) cholesterol embolization and recurrence to total occlusion of orificial atherosclerotic lesions with loss of excretory renal function; (4) chronic dissection from repeated "temporarily successful" PTAs of medial fibrodysplastic lesions; and (5) rapid recurrence and acceleration of hypertension in a 17-year-old girl with congenital renal artery stenoses. In each instance operation was complicated by an intense perivascular inflammatory response from the previous PTA and required a more complex reconstruction than would have been needed originally. These sequelae argue for moderating enthusiasm for the use of PTA and for limiting its routine use to nonorificial atherosclerotic lesions and fibrodysplastic lesions restricted to the main renal artery. Orificial atherosclerotic lesions, branch fibrodysplastic lesions, and congenital stenoses have a high probability of failure, complications, or both when treated by PTA and should be considered for primary operative intervention.
The rare earth elements lanthanum and terbium (0.1-1.0 mM), pharmacological analogs of calcium, induced neoplastic transformation of 12-O-tetradecanoylphorbol-13-acetate (TPA)-sensitive (P+) and to a lesser extent TPA-resistant (P-) preneoplastic mouse JB6 epidermal cells. A maximum of 2500 anchorage-independent colonies per 10(4) cells were induced in P+ lines, a response comparable to that induced by phorbol esters (1.6-16 nM). The maximum lanthanide-induced colony yield in P- lines was 20% of that in P+ lines (approximately 550 colonies), and was observed under conditions where TPA induced less than 30 colonies per 10(4) cells. Lanthanides and TPA produced a synergistic effect on colony size in P+ cells. Lanthanides are not promoting transformation merely by mimicking high calcium: adding exogenous extracellular calcium (up to 50.0 mM) or using calcium ionophore (up to toxic concentrations) to increase intracellular calcium does not promote transformation. Lanthanum will substitute for calcium in activating partially purified protein kinase C (PKC), the calcium-dependent phorbol ester receptor. However, lanthanides must be promoting transformation by a mechanism other than PKC activation because lanthanides failed to activate PKC in intact JB6 cells. Three independent experiments showed a lack of lanthanum effect on PKC-dependent events in intact cells. First, in contrast to TPA, lanthanum pretreatment of JB6 cells did not produce elevated phosphorylation of an 80-kd substrate. Second lanthanum pretreatment did not cause decreased PKC activity after prolonged exposure. Third, lanthanum and TPA affected epidermal growth factor binding with a different magnitude, time course and calcium dependency. We found, however, a PKC substrate in P+, P- and tumorigenic cell lines that is sensitive to lanthanum and increases its migration in sodium dodecylsulfate-polyacrylamide gels from 23 to 21 kd. The above data suggest that: (i) alterations in cation binding may be sufficient for inducing the transformed phenotype; and (ii) lanthanide promotion of neoplastic transformation may be linked to a lanthanide-sensitive PKC substrate, but is not due to a direct PKC activation.
In instances in which coexistent significant carotid artery disease and internal carotid redundancy coexist, we have found that use of the resected autogenous internal carotid artery to be a convenient and satisfactory way of patching the frequently small distal internal carotid artery following resection of the redundant portion. There has been no morbidity associated with additional suture lines, and in follow-up care extending through 24 months, there have been no recurrent symptoms.
Extracellular calcium is required in the induction of neoplastic transformation of preneoplastic mouse JB6 epidermal cells by 12-O-tetradecanoylphorbol-13-acetate (TPA). Depleting extra-cellular calcium by chelation or by use of commercial calcium-depleted medium inhibited TPA-promoted transformation of promotion-sensitive JB6 cells with a half-maximal inhibition at 1.2 mM calcium. Inhibition was reversible by the addition of calcium. The calcium channel blockers lanthanum and nifedipine inhibited promotion of anchorage-independent transformation by TPA maximally at 10.0 microM and 1.0 nM, respectively, suggesting that calcium entry occurs partially via cell channels. None of the above treatments altered expression of transformation in anchorage-independent tumorigenic JB6 cell lines, indicating that the extracellular calcium requirement was at the level of induction, not expression of transformation. The calcium requirement was not merely a requirement for proliferation; calcium concentrations from 0.2 to 1.8 mM had no effect on JB6 cell monolayer growth. Extracellular calcium was required for 7 days for maximal colony induction. The calcium ionophore A23187 was not a promoter and moderately inhibited TPA-promoted transformation, indicating that increases in free cytosolic calcium concentrations are not sufficient for promotion of transformation and may even activate calcium-dependent antipromoting events. The results suggest that a cellular calcium pool supplied by extracellular calcium, but not distinguishable by ionophoretic increases in free cytosolic calcium, is essential in TPA-promoted neoplastic transformation.
Phorbol 12-myristate 13-acetate (PMA)-treated macrophages exhibited a two-fold increase in the rate of 45Ca++ efflux and over a three-fold increase in the size of the exchangeable calcium pool, resulting in almost a seven-fold increase in the slow phase of calcium efflux. The calcium antagonist 8-(N,N-diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) by itself did not affect calcium efflux in macrophages; but abolished the PMA-induced increase in the rate of calcium efflux. The divalent cationphore A23187 increased the rate constant of the fast phase of calcium efflux two-fold when applied alone or when applied with PMA. These effects might be linked to ionophore enhancement and TMB-8 inhibition of PMA-induced macrophage chemotaxis and spreading (previously reported in Cell Calcium 3:503-514 and Cancer Research 43:3385-3391). No change in calcium efflux was observed if cells were exposed to PMA only during the efflux experiment suggesting that a prolonged exposure to PMA is required to elicit changes in calcium flux. Increased 45Ca++ remained in treated cells at each time point perhaps reflecting the PMA-induced increase in exchangeable calcium.