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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 343 records · Page 19Linked to original sources

Polyunsaturated fatty acids of the n-6 and n-3 series: effects on postprandial lipid and apolipoprotein levels in healthy men.

OBJECTIVE: The present study was carried out to determine effects of test meals of different fatty acid compositions on postprandial lipoprotein and apolipoprotein metabolism. DESIGN: The study was a randomized, single blind design. SETTING: The study was carried out in the Clinical Investigation Unit of the Royal Surrey County Hospital. SUBJECTS: Twelve male normal subjects with an average age of 22.4 +/- 1.4 years (mean +/- SD) were selected from the student population of the University of Surrey; one subject dropped out of the study because he found the test meal unpalatable. INTERVENTIONS: The subjects were given three evening test meals on three separate occasions, in which the oils used were either a mixed oil (rich in saturated fatty acids and approximated the fatty acid intake of the current UK diet), corn oil (rich in n-6 fatty acids), or fish oil (rich in n-3 fatty acids) 40 g of the oil under investigation were incorporated into a rice-based test meal. Triacylglycerol-rich lipoproteins-triacylglycerol (TRL-TAG), TRL-cholesterol (TRL-cholesterol), plasma-TAG, plasma cholesterol (T-C), and serum apolipoprotein A-I and B (apo A-I and B) responses were measured. Postprandial responses were followed for 11 h. RESULTS: Postprandial plasma-TAG responses, calculated as incremental areas under the response curves (IAUC) were significantly reduced following the fish oil meal [365.5 +/- 145.4 mmol/l x min (mean +/- SD)[ compared with the mixed oil meal (552.0 +/- 141.7 mmol/l x min) (P < 0.05) and there was a strong trend towards the same direction in the TRL-TAG responses. In all instances, plasma-and TRL-TAG showed a biphasic response with increased concentrations occurring at 1h and between 3 and 7h postprandially. TRL-cholesterol, T-C, and serum apo A-I and B responses to the three meals were similar. CONCLUSIONS: The findings support the view that fish oils decrease postprandial lipaemia and this may be an important aspect of their beneficial effects in reducing risk of coronary heart disease (CHD). Further work is required to determine the mechanisms responsible for this effect.

Adult↗

Segmental colonic gangrene: a previously unreported complication of adult hemolytic uremic syndrome.

Gastrointestinal manifestations, however slight, must be carefully observed in patients with HUS regardless of age. Both clinical and diagnostic evaluations must be weighed expeditiously to rule out any surgically correctable disease. Although most patients with HUS can be treated nonoperatively, a considerable mortality still exists, especially in adults. Once surgical intervention is required, overall mortality is still favorable, especially with early diagnosis and proper treatment.

Colectomy↗

Pregnancy complicated by primary antiphospholipid antibody syndrome.

BACKGROUND: Primary antiphospholipid antibody syndrome is a clinical entity that may threaten the health of both fetus and mother. CASE: We report a fatal case of primary antiphospholipid antibody syndrome in a woman who developed catastrophic disease due to multisystem thrombosis in the postpartum period following a fetal death. Three years before her admission, primary antiphospholipid antibody syndrome was diagnosed on the basis of high titers of immunoglobulin G anticardiolipin antibody, a positive lupus anticoagulant, a false-positive VDRL, and fibrin deposits in the biopsy of a palmar lesion. CONCLUSION: The physician must recognize the potentially catastrophic complications of pregnancy and the postpartum period in patients with antiphospholipid antibodies, and appropriate patient counseling should be provided.

Adult↗

Matrix-degrading metalloproteinases in tumor progression.

The matrix-degrading metalloproteinases (MMPs) have been implicated in tumor invasion and metastasis. Recently it has become clear that the expression of MMPs in tumors is frequently localized to stromal cells surrounding malignant tumor cells. In the mouse skin model of multi-stage carcinogenesis, the MMP stromelysin is expressed in stromal fibroblast-like cells surrounding benign and malignant squamous cell carcinomas. Conversion of these tumors to highly invasive and metastatic spindle-cell tumors is however, associated with the expression of stromelysin-1 mRNA in the tumor cells themselves. The analysis of MMPs in human colon adenocarcinomas at different stages of tumor progression revealed that matrilysin was the only MMP expressed in the tumor cells, while stromelysin-1 and stromelysin-3 mRNA was detected in stromal cells surrounding malignant tumor cells. Matrilysin mRNA is detected in benign tumors as well as malignant tumor cells, and the relative level and percent of tumors expressing matrilysin correlates with the stage of tumor progression. These results suggest that both stromal and tumor cell metalloproteinases may contribute to tumor invasion and metastasis, and also suggests that MMPs may play a role in earlier events in the tumor progression pathway. A potential role for MMPs in tumor growth is illustrated by results which suggest that the expression of matrilysin in human colon cancer-derived cells increases tumorigenicity following injection into the cecum, and that transgenic mice expressing matrilysin mRNA show a marked proliferative response. MMPs may therefore play multiple roles in tumor progression.

Adenocarcinoma↗

alpha-Crystallin chaperone activity is reduced by calpain II in vitro and in selenite cataract.

This study reports the first demonstration of a marked reduction in alpha-crystallin chaperone activity in an experimental model of cataract, and the study implicates activation of the cysteine protease calpain II (EC 3.4.22.17) as the in vivo protease responsible for decreased chaperone activity. Chaperone activity of normal alpha-crystallin from lenses of young rats was assayed by measuring attenuation of heat-induced aggregation and scattering of beta L-crystallin. alpha-Crystallin from the nucleus of lenses with selenite cataract showed specific selective proteolysis, and chaperone activity was diminished. Proteolysis of alpha-crystallin from selenite cataract lenses was mimicked by incubating normal alpha-crystallin with calpain II, and this also resulted in loss of chaperone activity. Two-dimensional gel electrophoresis and peptide mapping were used to identify four partially degraded alpha A- and alpha B-crystallin polypeptides following incubation of normal alpha-crystallin with calpain. Similar partially degraded alpha A and alpha B polypeptides were found in selenite cataract. Previous experiments indicated that alpha-crystallin chaperone activity decreases because of removal of the COOH terminus. Our experiments support this observation and suggest that calpain proteolysis of alpha-crystallin at the COOH terminus may result in a loss of chaperone activity in selenite cataract.

Amino Acid Sequence↗

Elastic properties of titin filaments demonstrated using a "freeze-break" technique.

A "freeze-break" technique (Trombitás, K.: Acta Biochim. Biophys. Hung. 6:419-427, 1971) and immunoelectron microscopy were used to study the elastic properties of titin filaments. Small bundles of freshly prepared rabbit psoas muscle fibers were quickly frozen and broken under liquid nitrogen to fracture sarcomeres in planes perpendicular to the filament axis, in each of various regions along the sarcomere. The still-frozen specimens were thawed during fixation to allow elastic filaments to retract. The broken specimens were then labelled with monoclonal anti-titin antibodies against an unique epitope in the I-band. The titin epitopes were normally positioned symmetrically about the Z-line. However, in sarcomeres broken at the A-I junction, the epitopes no longer remained symmetrical: the titin filaments in the broken half-sarcomere retracted, independently of the thin filaments, forming a dense band just near the Z-line. The retracted density apparently did not reach the Z-line; retraction stopped at the level of the so-called N1-line. In sarcomeres broken at the Z-line level, the titin filaments retracted in the opposite direction. In this case the titin epitope retracted all the way to the ends of the thick filaments. It appears then that titin molecules form elastic filaments that are independent of thin filaments in most of the I-band. Near the Z-line, however, the titin filaments either have an inelastic domain or associate firmly with the thin filaments at the N1-line level.

Actin Cytoskeleton↗

Nebulin is a full-length template of actin filaments in the skeletal muscle sarcomere: an immunoelectron microscopic study of its orientation and span with site-specific monoclonal antibodies.

Nebulin, a giant myofibrillar protein with size variants from 700 to 900 kDa in various skeletal muscles, has been proposed to constitute a set of inextensible filaments anchored at the Z-line and coextensive with actin filaments. To elucidate the architectural organization of this fourth set of myofilaments in the skeletal muscle sarcomere, we performed immunoelectron microscopic localization of epitope profiles of a number of site-specific monoclonal antibodies against cloned human nebulin fragments of known sequence loci. Monoclonal antibody N113, which is directed to fragment ND8 at approximately 300 residues away from the C-terminus, labelled the edges of Z-lines in both human quadriceps muscle and rabbit psoas muscle. Monoclonal antibody N101, which is directed to fragment NB5 near the N-terminal side, is localized to a single locus at 0.89 micron from the Z-line in human quadriceps muscle and 0.80 micron from the Z-line in rabbit psoas muscle. Additionally, monoclonal antibody N109, which is directed to fragment NA3 on the carboxy side of the adjacent fragment NB5, is localized at 0.76 micron away from the Z-line in rabbit psoas muscle. This one-to-one correspondence between epitope loci and sequence loci demonstrates that a single nebulin polypeptide spans the length of the thin filament with its C-terminus anchored at the Z-line. The epitope spacings of site-specific antibodies are consistent with the notion that the nebulin filament is uniform in mass density along its length.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Macroscopic marital interaction coding systems: are they interchangeable?

The present study sought to determine the convergent validity of two macroscopic marital interaction coding systems: the Marital Interaction Coding System-Global and the Global Couple Interaction Coding System. The sample consisted of 40 couples who completed the Dyadic Adjustment Scale, the Potential Problem Checklist and a 30-min problem solving interactional task. Filmed interactions were coded by separate teams of observers using the Marital Interaction Coding System-Global and the Global Couple Interaction Coding System. Results showed that interobserver agreement, as assessed through intraclass correlations, was satisfactory for both coding systems. Between-system comparisons revealed that convergent validity coefficients were moderate; thus, it seems premature to conclude that macroscopic coding systems are interchangeable. Finally, multiple regression analyses indicated that both systems contained significant non-redundant behavioral predictors of marital adjustment. Implications of these results are discussed.

Adult↗

Viscoelasticity of the sarcomere matrix of skeletal muscles. The titin-myosin composite filament is a dual-stage molecular spring.

The mechanical roles of sarcomere-associated cytoskeletal lattices were investigated by studying the resting tension-sarcomere length curves of mechanically skinned rabbit psoas muscle fibers over a wide range of sarcomere strain. Correlative immunoelectron microscopy of the elastic titin filaments of the endosarcomeric lattice revealed biphasic extensibility behaviors and provided a structural interpretation of the multiphasic tension-length curves. We propose that the reversible change of contour length of the extensible segment of titin between the Z line and the end of thick filaments underlies the exponential rise of resting tension. At and beyond an elastic limit near 3.8 microns, a portion of the anchored titin segment that adheres to thick filaments is released from the distal ends of thick filament. This increase in extensible length of titin results in a net length increase in the unstrained extensible segment, thereby lowering the stiffness of the fiber, lengthening the slack sarcomere length, and shifting the yield point in postyield sarcomeres. Thus, the titin-myosin composite filament behaves as a dual-stage molecular spring, consisting of an elastic connector segment for normal response and a longer latent segment that is recruited at and beyond the elastic limit of the sarcomere. Exosarcomeric intermediate filaments contribute to resting tension only above 4.5 microns. We conclude that the interlinked endo- and exosarcomeric lattices are both viscoelastic force-bearing elements. These distinct cytoskeletal lattices appear to operate over two ranges of sarcomere strains and collectively enable myofibrils to respond viscoelastically over a broad range of sarcomere and fiber lengths.

Animals↗

The effect of non-starch polysaccharide supplementation on circulating bile acids, hormone and metabolite levels following a fat meal in human subjects.

The effects of guar gum, sugar-beet fibre (SBF) and wheat bran supplementation of a high-fat test meal were compared with an NSP-free control meal and a meal containing an equivalent amount of the ion-exchange resin cholestyramine in healthy non-obese human volunteers. Their effects on gastric emptying, postprandial circulating bile acids, triacylglycerols and gastrointestinal hormone levels were studied. The in vitro binding of NSP and cholestyramine to [1-14C]glycocholic acid was measured and compared with their in vivo effect. Guar gum and cholestyramine supplementation significantly lowered circulating postprandial bile acid, triacylglycerol and gastric inhibitory polypeptide concentrations, but sugar-beet fibre and wheat bran were without effect. Liquid gastric emptying, as assessed by circulating paracetamol levels, was slightly accelerated in the guar gum-supplemented meal. Glycocholic acid bound strongly to the insoluble fraction of cholestyramine and the soluble fraction of guar gum. The insoluble fractions of SBF and wheat bran bound only small quantities of glycocholate; no bile acid binding was detected in the soluble fractions of these NSP. The study demonstrates that measurement of postprandial bile acids enables an indirect measurement to be made of bile acid binding to NSP in vivo. The results support the hypothesis that the hypocholesterolaemic action of guar gum is largely mediated via interruption of the enterohepatic bile acid circulation, but indicate that the hypocholesterolaemic action of SBF is mediated by another mechanism.

Adult↗

Bereavement support: evaluation of a palliative care memorial service.

A memorial service providing bereavement support in a palliative care unit is evaluated. Results indicate that respondents found it to be a positive experience, particularly in relation to its formality and content. One-fifth of respondents experienced distress during the service, but this was evaluated as appropriate, being related to personal thoughts, feelings of loss and sadness, and remembrance.

Bereavement↗

Glucagon-like peptide-1 (7-36)amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns.

The acute effects of different macronutrients on the secretion of glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) and glucose-dependent insulinotropic polypeptide (GIP) were compared in healthy human subjects. Circulating levels of the two hormones were measured over a 24-h period during which subjects consumed a mixed diet. In the first study, eight subjects consumed three equicaloric (375 kcal) test meals of carbohydrate, fat and protein. Small increases in plasma GLP-1(7-36) amide were found after all meals. Levels reached a maximum 30 min after the carbohydrate and 150 min after the fat load. Ingestion of both carbohydrate and fat induced substantial rises in GIP secretion, but the protein meal had no effect. In a second study, eight subjects consumed 75 g glucose or the equivalent portion of complex carbohydrate as boiled brown rice or barley. Plasma GIP, insulin and glucose levels increased after all three meals, the largest increase being observed following glucose and the smallest following the barley meal. Plasma GLP-1(7-36)amide levels rose only following the glucose meal. In the 24-h study, plasma GLP-1(7-36)amide and GIP concentrations were increased following every meal and remained elevated throughout the day, only falling to fasting levels at night. The increases in circulating GLP-1(7-36)amide and GIP levels following carbohydrate or a mixed meal are consistent with their role as incretins. The more sustained rises observed in the daytime during the 24-h study are consistent with an anabolic role in lipid metabolism.

Adult↗