Sammanfattning Bakgrund Svårigheter i någon eller några av sväljningens faser definieras som dysfagi. Flexibel videoendoskopisk undersökning av sväljning (FUS) är en instrumentell undersökningsmetod av sväljning. Vid brist på tillgång till instrumentella undersökningsmetoder används screeningtest som kan identifiera individer med risk för dysfagi. The Timed Water Swallowing Test (TWST) är ett screeningtest som används vid bedömning av sväljförmåga av flytande konsistens. The Test of Masticating and Swallowing Solids (TOMASS) bedömer tugg- och sväljförmåga vid fast konsistens. Syfte Syftet med studien var att undersöka vilka utfallsmått bland screeningtesterna TWST och TOMASS som bäst korrelerade med resultatet vid en FUS. Studien avsåg även att undersöka huruvida samtliga enskilda utfallsmått bidrar till att identifiera personer med risk för dysfagi. Metod Studien omfattade 98 deltagare i åldrarna 20-80+ år. Deltagarna intog 150 ml vatten där utfallsmåtten tid, antal sväljningar, sväljkapacitet och kliniska tecken till felsväljning observerades i screeningtestet TWST. I screeningtestet TOMASS intog deltagarna ett Göteborgs Kex Guld Marie där utfallsmåtten tid, antal tuggor, tuggcykler och antal sväljningar observerades. FUS gjordes och resultatet skattades med DOSS-värden. Spearmans rangkorrelation användes för att beräkna korrelationen mellan screeningtesternas enskilda utfallsmått och FUS utfallsmått. Resultat Resultatet visade att utfallsmåtten som korrelerade bäst med FUS utfallsmått var TWST utfallsmått sväljkapacitet och harkling. Utfallsmåttet sväljkapacitet hade en måttlig negativ korrelation och utfallsmåttet harkling hade en måttlig korrelation. TOMASS samtliga utfallsmått hade svag korrelation med FUS utfallsmått. Slutsatser Sväljkapacitet och harkling var de utfallsmått som bäst kunde förutse fynden som gjordes vid FUS. Samtliga utfallsmått för TOMASS korrelerade svagt med FUS utfallsmått. Framtida studier rekommenderas att undersöka om gränsvärden för alla TOMASS utfallsmått behövs och om de ger relevant information. Studiens resultat indikerar att alla utfallsmått, för respektive screeningtest, inte bidrar till att förutse fynden vid en FUS. Vidare forskning kring de enskilda utfallsmåtten föreslås där utfallsmåtten även ställs mot videofluoroskopi.

No description available.

Aesthetic finger prosthetics provide functional and cosmetic benefits. Good suspension of the prosthesis plays a role in the functional and aesthetic effects, and a loose fit can lead to rejection of the prosthetic.  In this thesis, we will compare two different suspension techniques (the addition of ridges and the addition of a central tunnel) and their effect on prosthetic retention along with the effect of differing socket lengths. Method: Six finger prosthetics were fabricated with different techniques and lengths. The strength of suspension was evaluated using a novel approach. Results: Shorter sockets with more aggressive volume reduction resisted a mean maximum force of 9.25N, and the longer sockets resisted a mean force up till 32.66N. The prosthetic with a central tunnel and shorter socket resisted a mean force up till 46.04N. Ridges between short and long sockets had inconsistent readings. Conclusion: Whether ridges or central tunnel influenced suspension strength was inconclusive. How volume reductions were done had a notable effect on suspension. Prosthetics with a shorter socket provided a tighter fit and had better suspension. When adequate prosthetic fit was achieved, the central tunnel had an improved effect on suspension strength.

No description available.

The purpose of this study is 1) to examine the presence of the antigen in serum by employing a newly developed ELISA immunoassay that quantifies the total antigen and bound antigen (antigen-antibody complex) using polyclonal chicken antibodies directed against an IgM-binding epitope of the new antigen, and 2) to determine the location of the antigen in carcinoma and normal cells. Sera from healthy volunteers (n = 147) and cancer patients (n = 26) were compared for both bound and total antigen concentrations using the new ELISA. Healthy volunteers were subdivided into three groups: those with a personal history of cancer (n = 13), those with no personal or family history of cancer (n = 36) and those with a family history of cancer (n = 97). Ovarian, breast, colon carcinoma tissues and their normal counterparts and cultured ovarian and prostatic carcinoma cells were subjected to immunofluorescence using IgY antibodies and goat anti-chicken fluorescent secondary antibodies. Basic imaging was performed on tissue sections while confocal microscopy was performed on cultured cells. Furthermore, immunohisto-chemical staining using an anti-chicken HRP-conjugated secondary antibody was performed on 16 normal ovarian tissues, 53 ovarian adenocarcinomas, and 3 borderline ovarian tumors. Statistical analysis revealed significant differences in cancer patients' bound and total antigen levels compared to that of healthy volunteers (p < 0.005). Bound and total antigen levels of cancer patients were also significantly higher than those of the healthy volunteers with no personal or family history of cancer and those with a family history of cancer (p < 0.01). However, no significant difference existed between the bound (p > 0.120) and total antigen levels (p > 0.076) of cancer patients and patients with a personal cancer history. Immunohistochemical staining of ovarian tissues revealed a significant difference in the lumenal staining of the carcinomas compared to that of the normal ovarian tissues. Furthermore, fluorescence imaging revealed that the antigen is localized to the cell membranes of the carcinoma cells but is absent from the normal tissues. Confocal microscopy further emphasized the antigen's association with the membrane and also revealed some filamentous cortical staining.

The human colonic cell line T84, a model for studying epithelial chloride secretion and cystic fibrosis chloride channel (CFTR) function, was used to investigate the regulatory role of estrogens in transepithelial ion transport. Estrogens and other steroid hormones do not stimulate chloride secretion by themselves. However, 17 β-estradiol (17β-E2) rapidly (within seconds to minutes) potentiates carbachol- and thapsigargin-stimulated chloride secretion measured as short circuit current in voltage-clamped T84 monolayer cultures. The cholinergic agonist carbachol and the SR Ca2+ ATPase inhibitor thapsigargin stimulate chloride secretion by elevating intracellular calcium. 17α-estradiol, a stereoisomer that does not activate nuclear estrogen receptors, is equipotent with 17β-E2. Other non-estrogen steroids produce much less, if any, potentiation of calcium-stimulated chloride secretion. The estrogen receptor antagonist tamoxifen does not block 17β-E2 potentiation of calcium-stimulated chloride secretion, indicating that the classical estrogen receptors are not involved. Potentiation is greater when 17β-E2 is applied to the apical membrane than to the basolateral membrane. 17β-E2 effects on chloride secretion coincide with an increase in monolayer electrical conductance, which is consistent with activation of one or more ion channel species. Potentiation is not blocked by the chloride channel blockers DIDS and NPPB but is abolished by the PKA inhibitor H89, suggesting that 17β-E2 potentiation depends on the activity of CFTR but not other types of apical membrane chloride channels. 17β-E2 does not increase the activity of calcium-activated potassium channels in the basolateral membrane as measured in nystatin-permeabilized monolayers. 17β-E2 effects are not blocked by the MAP kinase kinase inhibitor PD 98059, or by the PKC inhibitor bisindoylmaleamide, suggesting that these signal transduction pathways are not involved. 17β-E2 potentiation requires extracellular Ca2+. Paradoxically, 17β-E2 reduces the rise in intracellular free Ca2+ levels in thapsigargin-stimulated T84 cells, as measured by fura-2 fluorescence. From my studies I conclude that 17β-E2 causes an increase in the sensitivity of T84 cells to calcium-elevating secretagogues. This effect may be due to nongenomic actions of 17β-E2 on CFTR function and/or the activity of store-operated calcium channels, which leads to a change in CFTR functional regulation.

The estimated number of employees in the United Stated screened annually for illicit drugs is approximately 20 million, with marijuana being the most frequently abused drug. Urine adulterants provide an opportunity for illicit drug users to obtain a false negative result on commonly used primary drug screening methods such as the Fluorescence Polarized Immunoassay (FPIA) technique. Typical chemical adulterants such as nitrites are easily detected or render the urine specimen invalid as defined in the proposed federal guidelines for specimen validity testing based on creatinine, specific gravity and pH. Papain is a cysteine protease with intrinsic ester hydrolysis capability. The primary metabolite of the psychoactive chemical in marijuana, 11-norcarboxy-delta-9-tetrahydrocannibinol (THC-COOH), was assayed by FPIA in concentrations ranging from 25 to 500 ng/mL, at pH values ranging from 4.5 to 8, over the course of 3 days with papain concentrations ranging from 0 to 10 mg/mL. FPIA analysis of other frequently abused drugs: amphetamines, barbiturates, benzodiazepines, cocaine, opiates, and phencyclidine, along with gas chromatography/mass spectrometry (GC/MS) of THC-COOH and high pressure liquid chromatography/ultraviolet detection (HPLC/UV) of nordiazepam was performed in order to determine if the mechanism of urine adulteration by papain was analyte specific. Control and adulterated urine specimens (n=30) were assayed for creatinine, specific gravity and pH to determine if papain rendered the specimens invalid based on the proposed federal guidelines. There was a direct pH, temperature, and time dependent correlate between the increase in papain concentration and the decrease in THC-COOH concentration from the untreated control groups (p<0.01). The average 72 hour THC-COOH concentration decrease at pH 6.2 with a papain concentration of 10 mg/mL was 50%. Papain did not significantly decrease the concentration of the other drugs analyzed with the exception of nordiazepam. GC/MS of THC-COOH and HPLC/UV of nordiazepam revealed a 66% and 24% decrease in concentration of the respective analyte with 10 mg/mL papain after 24 hours at room temperature (~23 °C). No adulterated specimens were rendered invalid based on the SAMHSA guidelines. Immediate FPIA analysis is suggested to minimize the interfering effects of papain with regards to primary drug screening.

The nuclear lamins form a karyoskeleton providing structural rigidity to the nucleus. One member of the lamin family, lamin A, is first synthesized as a 74 kDa precursor, prelamin A. Following the endopeptidase and methylation reactions which occur after farnesylation of the CAAX-box cysteine, there is a second endoproteolysis that occurs 15 amino acids upstream from the C-terminal farnesylated cysteine residue. Studies with knockout mice have implicated the enzyme Zmpste24 as a candidate to carry out one or both of these proteolytic reactions. In this body of work, the CAAX endopeptidase activity of recombinant, membrane reconstituted, Zmpste24 is demonstrated using a prelamin A farnesylated tetrapeptide as substrate. To monitor the second upstream endoproteolytic cleavage a 33 kDa prelamin A carboxyl terminal tail of prelamin A was expressed in insect cells. This purified substrate possesses a fully processed CAAX box, and, therefore, constitutes a valid substrate for assaying the second endoproteolytic step in lamin A maturation. In vitro reactions with this substrate and insect cell membranes bearing recombinant Zmpste24 demonstrate that Zmpste24 may possess the ability to directly catalyze the second endoproteolytic cleavage. Previous studies on nuclear envelope fractions have ascribed this second activity to a chymotrypsin like protease. However, Zmpste24 contains the canonical HEXXH domain, a common characteristic of zinc metalloproteinases. Experiments on Zmpste24 in this work demonstrate that inactivating the HEXXH domain by site directed mutagenesis results in a loss of the first endoproteolysis reaction, while the second endoproteolytic activity is retained. Supporting these data is the observation that a truncated mutant of Zmpste24 (residues: Met1 - Pro230) that does not contain the HEXXH motif, loses the first endoproteolytic activity while retaining the second. Furthermore, this second activity is not sensitive to the metalloproteinase inhibitors EDTA and 1,10-orthophenanthroline, but is sensitive to the chymotrypsin inhibitor TPCK and its fluorescent analogue, FFCK. The fact that Zmpste24 can be affinity labeled with FFCK suggests that this second activity is directly caused by a second, yet unidentified, active site with a chymotrypsin-like catalytic mechanism.

The purpose of this study was to determine the effect of selected physical socio-environmental variables on total percent body fat. The sample population consisted of single, LDS, white women attending Brigham Young University (BYU) and California State University at Fullerton (CSUF). Significant data as well as trends that appeared were included in this paper.From the data collected, it was concluded that the sample populations at BYU and CSUF were the same. The incidence of obesity was determined only among individuals attending both universities. The entire sample population mean was 22.19 percent. This percentage did not meet the obesity criteria.Analysis of data indicated a high correlation at the 0.05 level of confidence between total percent body fat and the variables of age, height, and weight.

Apoptosis is essential for cellular homeostasis and is also a pathologic feature of various diseases. The balance between Bcl-2 family proteins determines whether a cell will live or die. Bax, a member of the BCL-2 family proteins, is a pro-apoptotic protein that exists in both a soluble, cytoplasmic form and a membrane-bound form. Upon apoptotic stimuli, Bax undergoes a conformational change and translocates to the mitochondria, initiating apoptotic events. However, little is known about whether Bax is involved in the regulation of mitochondrial function under non-apoptotic conditions, and how Bax binds to mitochondria to exert its activity. Here, we investigate the role of Bax in the regulation of mitochondrial function under non-apoptotic conditions and explore the molecular mechanisms for Bax binding mitochondria under apoptotic stimuli. Using Bax-containing and Bax-deficient (Bax⁻/⁻) HCT-116 cells, we examined Bax cellular localization and its effects on mitochondria bioenergetics, and also tested whether over-expression of full-length Bax in Bax⁻/⁻ cells would recover mitochondrial metabolic activity. To determine the effects of Bax localization upon mitochondrial function, we measured citrate synthase activity and ATP generation. We showed that Bax localized to the outer and inner mitochondrial membranes in non-apoptotic cells, enabling the activity of citrate synthase and the generation of ATP. Loss of Bax led to impairment of respiring mitochondria morphology and reduced oxidative capacity, all of which was restored by expression of full-length or C-terminal-deleted Bax. These findings indicate that under non-apoptotic conditions, the constitutive expression of Bax is necessary for mitochondrial bioenergetics. To determine the molecular mechanisms for Bax binding mitochondria under apoptotic stimuli, we previously performed in silico-mutagenesis and predicted that Lysines 189/190, in the C-terminal [alpha]9 helix, could regulate Bax binding to mitochondria. We demonstrated here that these lysines are the structural elements responsible for controlling how Bax interacts with the mitochondrial membrane. Expression of full-length Bax led to mitochondrial translocation and apoptosis, whereas deletion of the [alpha]9 helix resulted in cytosolic retention and dramatically reduced cell death. Mutation of the two lysine residues changed how Bax bound to mitochondrial membranes. We replicated the results achieved with full-length Bax by attaching the [alpha]9 helix of Bax to GFP or to a regulatory element, the degradation domain (DD), and induced apoptosis upon expression in cells. We demonstrated that the [alpha]9 helix alone promoted the mitochondrial translocation of Bax and increased apoptosis. These results indicate that the C-terminal [alpha]9 helix could be further studied for use in cancer therapies. Overall, we have demonstrated that the constitutive expression of the inactive form of Bax in non-apoptotic cells is necessary for mitochondrial bioenergetics, and have identified the C-terminal [alpha]9 helix of Bax as the effector domain of apoptotic function.