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Biomedical subjects

K E Smith

Publications and source records attributed to K E Smith.

At least 73 records · Page 4Linked to original sources

Lower extremity residual limb slippage within the prosthesis.

OBJECTIVE: The ability to measure skin surface slippage relative to the internal wall of a lower extremity prosthesis under various loading conditions is important for evaluation of socket fit and function, and creation of finite element models. Skin surface three-dimensional (3D) shape measurements with tracking of fiducial displacements in situ under axial loading of the prosthesis have not previously been reported. Analysis of slippage within the prosthesis has been performed using a new experimental measurement method based on spiral x-ray computed tomography (SXCT) imaging. DESIGN: Small lead markers were placed on the residuum of an adult with a below-knee amputation, and SXCT scans were obtained with the prosthesis in situ under two static axial loading conditions (44.5N and 178N). The 3D scan data were used to assess slippage with three methods: gross displacement of the tibia and distal end of the residuum; relative displacement of markers; and distance measurements between markers. RESULTS: The markers affixed to the below-knee skin surface within the prosthesis were measured. The skin slipped from 2 to 6 mm relative to the internal prosthesis wall when an additional load of 133.5N was applied in the axial direction to the distal end of the prosthesis. The tibial remnant moved 10.0 mm distally relative to the prosthesis internal wall. CONCLUSION: This method provides a feasible means for measuring residuum skin slippage relative to the prosthesis and skin deformation relative to tibia within an in situ prosthesis under load.

Artificial Limbs↗

Finite element modeling and experimental verification of lower extremity shape change under load.

Prediction and measurement of residuum shape change inside the prosthesis under various loading conditions is important for prosthesis design and evaluation. Residual limb surface measurements with the prosthesis in situ were used for construction of a finite element model (FEM). These surface measurements were obtained from volumetric computed tomography. A new experimental method for modeling the shape of the in situ lower residual limb was developed based on spiral X-ray computed tomography (SXCT) imaging. The p-version of the finite element method was used for estimating the material properties from known load and displacement data. A homogeneous, isotropic, linear constitutive model with accommodation of the constitutive soft and hard tissues of the residuum was evaluated with static axial loading applied to the in situ prosthesis and compared with experimental results obtained in a human volunteer. Two FEMs were created for similar coronal cross sections of the below knee residuum under two loading conditions. Agreement between observed (from SXCT) and predicted (from FEA) residual limb shape changes inside the prosthesis were maximized with a single modulus of elasticity for the residuum soft tissue of 0.06 MPa, consistent with previously published results. This methodology provides a framework to predict and objectively evaluate FEMs and determine residuum material properties by inverse methods.

Anthropometry↗

Distribution of the neuropeptide Y Y2 receptor mRNA in rat central nervous system.

Our group has recently reported the expression cloning of the human neuropeptide Y Y2 receptor DNA and subsequently the cloning of the rat homologue. These studies have made it possible to localize the mRNA encoding this NPY receptor subtype in rat tissues. We have, thus, carried out in situ hybridization studies, using radiolabeled oligonucleotide probes to the rat Y2 receptor mRNA, to determine the distribution of Y2 mRNA in rat brain and limited peripheral ganglia. Probe specificity was confirmed by testing antisense and sense probes in transfected cells. In rat brain, hybridization signals obtained with the antisense probes were discrete and were restricted to neuronal profiles in specific subregions of the cortex, hippocampus, amygdala, thalamus, hypothalamus, mesencephalon and pons. Among the regions exhibiting the most intense labeling were the CA3 region of the hippocampus, the arcuate nucleus of the hypothalamus and layer 3 of the piriform cortex. Other regions containing labeled neurons included the medial amygdala, the centromedial thalamic nucleus, the dorsal raphe, the dorsal motor nucleus of the vagus and the trigeminal ganglion. The present results indicate that the mRNA encoding the Y2 receptor is discretely localized in the rat brain and that the distribution is generally consistent with previous radioligand-binding studies. This study should help clarify the relationship between the Y2 receptor distribution and functional studies of NPY receptor subtype classification and provides further evidence for the involvement of the Y2 receptor in multiple physiological processes.

Animals↗

A structure-activity analysis of the cloned rat and human Y4 receptors for pancreatic polypeptide.

We cloned and expressed the rat Y4 receptor for pancreatic polypeptide (PP). Structure-activity profiles derived from 125I-PP binding assays and [cAMP] radioimmunoassays reveal a selective receptor interaction with rat PP vs. neuropeptide Y (NPY) or peptide YY (PYY). Rat and human Y4 receptor clones share 75% amino acid identity. Based on [cAMP] radioimmunoassay, the human Y4 receptor exhibits a less selective interaction with rat PP vs. NPY or PYY and a greater dependence on N-terminal PP residues, relative to rat Y4. Differences in sequence and structure-activity profiles suggest the rat be used with caution to model human Y4 receptor function.

Animals↗

Predicting cognitive-language and social growth curves from early maternal behaviors in children at varying degrees of biological risk.

Growth modeling was used to examine the relation of early parenting behaviors (averaged across 6 and 12 months) with rates of change in children's cognitive-language and social response and initiating skills assessed at 6, 12, 24, and 40 months. Groups of full-term (n = 112) and very low birth weight children, divided into medically low (n = 114) and high risk (HR; n = 73), were included to evaluate whether children who vary in their rate of development are influenced in different ways by early parenting styles. Parenting behaviors that were sensitive to children's focus of interest and did not highly control or restrict their behaviors predicted greater increases and faster rates of cognitive-language and social development, with relations stronger for the HR versus the other two groups. These maternal behaviors may provide the support all infants need to establish an optimal early foundation for later development and the specific support HR children need to learn in spite of early attentional and organizational problems.

Adult↗

The use of carrion as breeding sites by the blowfly Lucilia sericata and other Calliphoridae.

To examine the species composition of flies breeding in carrion in the field, the carcasses of mice and quail were exposed on sheep farms in the South West of England. Calliphora vicina was the dominant species of Diptera; 19,294 individuals emerged from 175 of the 241 infested carcasses recovered. Lucilia sericata emerged from only 39 of the infested carcasses, at a median of 10 adults per infested carcass. Other species of Lucilia present were L.ampullacea, L.caesar and L.illustris. The highest number of L.sericata emerged from carcasses placed in open pasture, the highest numbers of C.vicina emerged from carcasses in hedgerow, whereas the highest numbers of L.caesar, L.ampullacea and L.illustris emerged from carcasses in woodland. The duration of exposure of carcasses in the field was negatively related to the size of the adult L.sericata which emerged and, in woodland and hedgerow habitats, to the number of L.sericata which emerged. These data indicate that the larvae of L.sericata in carcasses experience significant levels of competition and that the intensity of this competition may be sufficient to reduce the numbers of L.sericata able to emerge successfully. The size distributions of female L.sericata which emerged from carcasses or which were caught as adults in the field showed only a small degree of overlap, suggesting that only a relatively small proportion of the wild L.sericata population emerge from carcass breeding sites. The results are discussed in relation to the development of new approaches to the control of blowfly strike of sheep.

Animals↗

The potential for control of the blowfly Lucilia sericata using odour-baited targets.

A deterministic simulation model is used to explore the potential for control of the sheep blowfly, Lucilia sericata, using odour-baited targets. The simulations show that the ambient temperatures of 15 degrees C or 20 degrees C, 13% and 24% of the females present in a population would need to be killed per day, respectively, to prevent the population growing from its initial spring density during the summer blowfly season. In contrast, if both sexes could be sterilized, so that sterilized males were also able to disrupt the fertility of unsterilized females, only 6.5-13% of both sexes would need to be attracted and sterilized at 15 degrees C or 20 degrees C respectively. To examine whether these numbers of individuals could be attracted by targets baited with liver and sodium sulphide, mark-release-recapture studies in sheep pastures were used to quantify sticky target efficiencies. The percentage of the L.sericata population caught on any one day was shown to be positively related to average ambient temperature. At 15 degrees C each sticky target caught approximately 13% and at 20 degrees C, 41% of the females within a 20 m radius. The results indicate that, at ambient temperatures between 15 and 20 degrees C, if distributed at a density of approximately 5/ha, targets baited with liver and sodium sulphide could effectively suppress a population of L.sericata. Lower densities of targets would be required if they were able to sterilize both sexes rather than kill or if more attractive synthetic semiochemical baits could be developed.

Animals↗

Decreased levels of CD44 protein and mRNA in prostate carcinoma. Correlation with tumor grade and ploidy.

BACKGROUND: CD44, a transmembrane protein, is associated with cell-cell and cell-matrix interaction and with tumor growth and metastasis. Expression of both standard form and variant isoforms of CD44 protein has been associated with aggressive behavior and metastasis in various tumors, but has not been characterized in prostate adenocarcinoma (PAC). METHODS: The expression of CD44 standard (CD44s) and splice variant v3, v4/5, v6, v7/8, and v10 proteins were studied in 109 PACs and correlated with tumor grade, DNA ploidy, and mRNA levels. Monoclonal antibodies against the various CD44 proteins were applied to microwave irradiated, formalin fixed, paraffin embedded sections. The DNA content of the tumors was evaluated by the Feulgen method with the CAS200 Image Analyzer. Total RNA exhibiting 18s and 28s bands was derived from two benign prostatic tissues and 5 PACs exhibiting decreased levels of CD44 protein by immunohistochemistry. The RNA was analyzed with reverse transcriptase polymerase chain reaction using CD44 specific primers. RESULTS: The basal cells of the benign prostatic acini revealed uniform membranous staining for CD44s, v3, and v6 in 95-97% of cases. Similar staining was observed for v4/5, v7/8, and v10 in 40%, 30%, and 2% of cases, respectively. Secretory epithelial cells of the benign prostatic acini showed predominant expression of CD44s (97% of cases). Staining for CD44 variant proteins (v3, v4/5, v6, v7/8, and v10) in this location ranged from 9-22% of cases. Approximately 70% of the PACs showed significant loss of CD44s expression, which correlated with high tumor grade (Gleason > or = 7) (P = 0.01) and aneuploid status (P = 0.002). In 93-98% of the PACS, there was a complete lack of membranous expression for all CD44 variant isoforms. The metastatic PACS did not show preferential expression of either the standard form or any variant isoform. The cDNA from the normal prostates yielded a prominent CD44 standard form polymerase chain reaction product at 482 base pair (bp) and variant isoforms at approximately 650 and 850 bp. No CD44 products could be amplified from the subset of five PAC cDNAs, even when present at four-fold excess. CONCLUSIONS: PACS exhibit down-regulation of CD44 protein expression, which correlates with high tumor grade and aneuploidy. v6 and v3 isoforms were preferentially expressed in the basal cells of benign prostatic acini. Based on a subset of cases, loss of CD44 protein expression is associated with decreased abundance of CD44 mRNA.

Adenocarcinoma↗

A receptor subtype involved in neuropeptide-Y-induced food intake.

Neuropeptide Y (NPY) is a powerful stimulant of food intake and is proposed to activate a hypothalamic 'feeding' receptor distinct from previously cloned Y-type receptors. This receptor was first suggested to explain a feeding response to NPY and related peptides, including NPY2-36, that differed from their activities at the Y1 receptor. Here we report the expression cloning of a novel Y-type receptor from rat hypothalamus, which we name Y5. The complementary DNA encodes a 456-amino-acid protein with less than 35% overall identity to known Y-type receptors. The messenger RNA is found primarily in the central nervous system, including the paraventricular nucleus of the hypothalamus. The extent to which selected peptides can inhibit adenylate cyclase through the Y5 receptor and stimulate food intake in rats correspond well. Our data support the idea that the Y5 receptor is the postulated 'feeding' receptor, and may provide a new method for the study and treatment of obesity and eating disorders.

Amino Acid Sequence↗

Distribution of a rat galanin receptor mRNA in rat brain.

In situ hybridization histochemistry has been employed to determine the distribution of the mRNA encoding a recently cloned rat galanin receptor (rGalR1). The galanin receptor mRNA has been found to be discretely localized in rat brain. The most intense hybridization signals were found over neurons in the nucleus of the lateral olfactory tract, in the ventral posterior hippocampus, and in the lateral external subdivision of the parabrachial nucleus. A number of other brain regions also contain significant hybridization signals, including the hypothalamus, brain stem and spinal cord. The localization of rGalR1 mRNA indicates that this receptor may play a role in the varied functions ascribed to GAL, among them feeding, cognition and modulation of sensory information.

Animals↗

Microbial transformations of steroids--X. Cytochromes P-450 11 alpha-hydroxylase and C17-C20 lyase and a 1-ene dehydrogenase transform steroids in Nectria haematococca.

Nectria haematococca contains four enzymes that metabolise exogenous steroids. Two of these are microsomal cytochromes P-450 which act sequentially on progesterone producing firstly, by side-chain cleavage, the C19 steroid androstenedione (C17-C20 lyase), and then, in a subsequent set of transformations, 11 alpha-hydroxylated derivatives (11 alpha-hydroxylase). Two other conversions occur after side-chain cleavage. Unsaturation, in the form of a double bond at C1-C2, is introduced into the A ring by a catalytically self-sufficient microsomal 1-ene dehydrogenase. This enzyme is specific for C19 substrates. A C17-specific oxidoreductase is also involved in the production of androstenedione and testosterone from progesterone. The lyase, 11 alpha-hydroxylase and 1-ene dehydrogenase were purified to homogeneity.

Androstenedione↗

Precision of surface measurements for below-knee residua.

OBJECTIVE: To determine the absolute and relative precision of geometric measurements made of below knee (BK) residua and their BK plaster positive casts using calipers, electromagnetic digitizer, optical surface scanner (OSS), and spiral x-ray computed tomography (SXCT). DESIGN: The experimental measurement protocol for a single measurement session was as follows: Dot markers were placed on the residuum, and volume and distances were measured using water displacement and calipers; residuum was measured using electromagnetic digitizer; residuum was scanned using three-dimensional (3D) OSS; a negative plaster cast of subject's residuum was made; the residuum was scanned using SXCT scanner. These steps were repeated at a second measurement session. Plaster positive casts were constructed and subsequently measured using the same protocol. PARTICIPANTS: Thirteen adult below-knee amputee volunteers (subjects) participated in the study, and nine subjects returned for a second measurement session. The study group consisted of 9 men and 4 women; 10 Caucasians and 3 African Americans. RESULTS: Distance measurements for all measurement devices were repeatable within 1% in vivo and within 0.5% on plaster casts; and volumes were within 1% in vivo and within 0.1% on plaster casts. Distance measurements for each device were precise within 3% in vivo and within 1% on plaster casts; and volumes were within 5% in vivo and within 6% on plaster casts when compared with caliper and water displacement measures. CONCLUSION: These measurement systems were found to be substantially equivalent in terms of repeatability and precision for measurement of lower extremity residua.

Adult↗

The profound impact of patient age on pregnancy outcome after early detection of fetal cardiac activity.

OBJECTIVE: To evaluate the influence of maternal age on pregnancy loss rates after early documentation of fetal cardiac activity by transvaginal ultrasound (US) in previously infertile women. DESIGN: Retrospective, observational study. SETTING: Tertiary fertility center. PATIENTS: One hundred eighty-six previously infertile women 20 to 43 years of age undergoing ovulation induction. MAIN OUTCOME MEASURE: We analyzed 201 clinical pregnancies in which cardiac activity had been documented by transvaginal US 35 to 42 days after ovulation in a previously infertile population treated at a tertiary fertility center. Patient age, infertility diagnosis, ovulation induction protocol, and mode of insemination were analyzed by chi 2, Fisher's exact test and logistic regression analyses. RESULTS: A profound increase in spontaneous abortion rates occurred as a function of maternal age in this population (chi 2 for trend = 15.1). A spontaneous abortion rate of 2.1% was observed for maternal ages < or = 35 years but this rate increased to 16.1% for patients > or = 36 years (odds ratio, 8.72; 95 percent confidence interval 2.3 to 32.9). A fivefold increase in spontaneous abortion rate was observed in women > or = 40 years compared with women 31 to 35 years (3.8% versus 20.0%. Infertility diagnosis, mode of insemination, and ovulation induction protocol were not associated with an increased risk of spontaneous abortion. CONCLUSIONS: The incidence of pregnancy loss after confirmation of early fetal cardiac activity by transvaginal US is substantially greater in infertile patients than previously reported, when considered as a function of maternal age. In particular, patients > or = 36 years should be counseled that their risk of spontaneous abortion is significant even after fetal heart motion is present on transvaginal US. Cautious optimism and greater surveillance may be required during the first trimester of pregnancy in these women.

Abortion, Spontaneous↗

Experimental infection of Culicoides lahillei (Diptera: Ceratopogonidae) with epizootic hemorrhagic disease virus serotype 2 (Orbivirus: Reoviridae).

To evaluate the vector competence of Culicoides lahillei Lutz for epizootic hemorrhagic disease (EHD) viruses, wild-caught females were allowed to feed on 4 viremic white-tailed deer, Odocoileus virginianus Zimmermann, experimentally infected with EHD virus serotype 2 (EHDV-2). Colonized C. variipennis sonorensis (Coquillett) were included as a positive control. Virus was not isolated from 13 C. lahillei tested 4-15 d after feeding on deer with viremias of 3.0 or <2.1 log10 tissue culture infectious dose50 (TCID50) virus per milliliter of blood. Virus was isolated from 6 of 69 (8.7%) C. lahillei tested 4-15 d after feeding on deer with viremias of 5.3 or 6.0 TCID50 virus per milliliter of blood. The average amount of EHDV-2 ingested in the blood meal ranged from <log10 1.5 to log10 1.9 TCID50 per C. lahillei. Titers of EHDV-2 in C. lahillei that tested positive 4-15 d after feeding peaked at log10 2.7 TCID50 EHDV per fly. Replication of EHDV-2 also occurred in control C. variipennis. This report of infection of C. lahillei with an EHD virus serotype indicates that C. lahillei may be a vector of EHD viruses.

Animals↗

Culicoides (Diptera:Ceratopogonidae) collected during epizootics of hemorrhagic disease among captive white-tailed deer.

To help determine specific vectors of epizootic hemorrhagic disease (EHD) and bluetongue (BT) viruses for white-tailed deer, Odocoileus virginianus Zimmermann, in the southeastern United States, Culicoides sp. midges were collected during epizootics of hemorrhagic disease among captive white-tailed deer in Georgia, Mississippi, and North Carolina. Culicoides variipennis (Coquillett), a confirmed vector of EHD and BT viruses, was present in low numbers in light-trap collections made at all sites. Collections from deer made in Georgia and North Carolina yielded only a single specimen of C. variipennis. Other Culicoides species present in far greater numbers during the epizootics included C. lahillei Lutz, C. paraensis (Goeldi), and C. stellifer (Coquillett) C. lahillei warrants particular attention as a potential vector because its readily feeds on white-tailed deer and was by far the predominant species collected from deer during the epizootics.

Animals↗