Do general practitioners miss dementia?
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Aged↗
Biomedical subjects
J Young
Publications and source records attributed to J Young.
Effects of cholesterol on (Na+,K+)-ATPase ATP hydrolyzing activity in bovine kidney.
The (Na+,K+)-ATPase ATP hydrolyzing activity from rabbit kidney medulla basolateral membrane vesicles was studied as a function of the cholesterol content of the basolateral membranes. The cholesterol content of the membranes was modified by incubation with phospholipid vesicles. When the cholesterol content was increased above that found in the native membrane, the (Na+,K+)-ATPase ATP hydrolyzing activity was inhibited. When the cholesterol content was decreased from that found in the native membranes, the (Na+,K+)-ATPase ATP hydrolyzing activity was inhibited. Analogous effects were found with the K+-activated phosphatase activity of the same membrane vesicles. Therefore, at low cholesterol contents, cholesterol was stimulatory, and at high cholesterol contents, cholesterol was inhibitory. The structural specificity of this effect was tested by introducing lanosterol and ergosterol as 50% of the membrane sterol. Ergosterol was the least effective at supporting (Na+,K+)-ATPase ATP hydrolyzing activity, while lanosterol was more effective, but still not as effective as cholesterol.
Adenosine Triphosphate↗
Characterisation of N-terminally extended met-enkephalin Arg6Gly7Leu8 variants in the porcine upper digestive tract.
Proenkephalin A-derived peptides are known to occur in the gut, but their precise identity is uncertain. We report here the isolation of N-terminally extended forms of Met-enkephalin Arg6Gly7Leu8 from porcine upper digestive tract monitored by radioimmunoassay. A single major form was identified in pyloric antral muscle and mucosa, but in the duodenum two major forms were detected. Microsequence analysis together with immunological data revealed that the antral mucosal peptide and the most acidic duodenal peptide had identical amino-acid sequences, corresponding to a 5.3 kDa peptide terminating in Met-enkephalin Arg6Gly7Leu8. The data indicate that high-molecular-weight peptides may constitute a major proportion of gut opioid peptide immunoactivity.
Amino Acid Sequence↗
N-linked glycosylation of a proenkephalin A-derived peptide. Evidence for the glycosylation of an NH2-terminally extended Met-enkephalin Arg6-Gly7-Leu8 variant.
To investigate the possibility that the opioid peptide precursor proenkephalin A was glycosylated, we utilized an antiserum raised against the COOH terminus of Met-enkephalin Arg6-Gly7-Leu8 (MERGL) to identify and characterize enkephalin-containing peptides from extracts of bovine adrenal medulla. Sephadex G-50 gel filtration separated two immunoreactive peaks which had apparent masses of 9 and 6 kDa. Anion-exchange chromatography and reverse-phase high pressure liquid chromatography (HPLC) revealed that the 9-kDa material was a heterogenous mixture of immunoreactive peptides, of which one (9K-MERGL Ia) was purified to homogeneity. The 6-kDa material separated into two major immunoreactive peaks (6K-MERGL I and 6K-MERGL II) on anion-exchange chromatography, and these were obtained in an homogenous form after reverse-phase HPLC. Amino acid sequencing, together with immunological characterization, indicated that the three peptides were identical in chain length, and corresponded to proenkephalin A 116-165. They contained the sequence Asn-Ser-Ser which is a potential N-glycosylation site. In 9K-MERGL Ia, but not the others, automated Edman amino acid sequencing was unable to detect the relevant asparagine residue, suggesting that this residue has been chemically modified. Further investigation of the 9K-MERGL material using lectin affinity chromatography provided direct evidence of glycosylation. Verification of this result was obtained using the specific enzyme glycopeptidase F (glycopeptide-N-glycosidase) which demonstrated that 9K-MERGL contained, in part, N-linked oligosaccharide chains. These results show that an NH2 terminally extended Met-enkephalin Arg6-Gly7-Leu8 variant was N-glycosylated, and hence indicate that the precursor polypeptide proenkephalin A can be glycosylated during translation in the rough endoplasmic reticulum.
Adrenal Medulla↗
Structure determination of a human lymphocyte derived neutrophil activating peptide (LYNAP).
Phytohemagglutinin or Concanavalin A-stimulated human T-lymphocytes produce a factor (LYNAP) with potent chemotactic and enzyme degranulating activity in peripheral human neutrophils. Sequence analysis of LYNAP established an apparently novel 72 residue polypeptide structure. Examination of protein data bases showed that LYNAP had about 30% sequence homology with recently characterised connective tissue activating proteins produced by platelets. Furthermore, it was subsequently found that the amino acid sequence is largely the same as that predicted from a cDNA clone derived from mRNA elevated in peripheral human leukocytes stimulated by mitogens.
Amino Acid Sequence↗
Remote intramuscular injection of immobilising drugs into fish using a laser-aimed underwater dart gun.
Sixty coldwater and warmwater fish ranging in weight from 2 to 35 kg were injected intramuscularly with the hypnotics alphaxalone-alphadolone and metomidate hydrochloride and the non-depolarising muscle relaxant gallamine triethiodide using a laser-aimed underwater dart gun. Alphaxalone-alphadolone produced sufficient sedation for easy netting within five to 20 minutes at doses between 0.3 and 0.5 ml/kg, with induction being somewhat faster in warmwater species. The pattern of induction was similar with metomidate but required doses of 40 to 60 mg/kg. The muscle relaxant gallamine triethiodide showed promise as a practical agent for the capture and handling of large fish by virtue of its smooth induction of paralysis at doses between 1 and 3 mg/kg and its reversible supplementation with orally administered metomidate hydrochloride.
Anesthetics↗
Radiation therapy for transitional cell bladder carcinoma. A ten-year experience.
From 1969 to 1979, 185 patients with transitional cell bladder carcinoma were curatively irradiated; 147 were treated with radiation alone (RT) and 38 received a combined radiation + surgery (RT + S). At presentation, 40 percent of the patients had obstructive uropathy which yielded a much lower five-year survival (18%) than when it was absent (50%). The overall five-year disease-free survival was 30 percent and 53 percent for patients treated with radical RT and RT + S, respectively. Among patients subjected to preoperative irradiation, downstaging was seen in 40 percent of postsurgical specimens, with 27 percent of the specimens showing no evidence of tumor; these patients had excellent survival. Severe complications were seen in 3 percent, 10 percent, and 27 percent of patients in the radical RT, RT + S, and radical RT + salvage cystectomy groups. Survival results, pelvic controls, and patterns of failure are presented.
Adult↗
Delayed diagnosis of traumatic diaphragmatic hernia during pregnancy.
We present a case of delay in diagnosis of diaphragmatic rupture and herniation in a pregnant 25-year-old woman. The diaphragmatic rupture was secondary to trauma sustained five months prior to presentation. Subsequent to her accident, she was provided medical care on multiple occasions for symptoms of intractable nausea, vomiting, and weight loss that were probably related to an expanding uterus and diaphragmatic herniation of abdominal contents. At the time she presented to us the herniation had progressed and she was experiencing severe respiratory difficulty. A nasogastric tube was placed for diagnosis and decompression. A chest radiograph provided the diagnosis of herniation of gastrointestinal contents through the left hemidiaphragm. A healthy 5-lb boy was delivered vaginally and subsequently a left thoracotomy was performed for decompression and repair of the diaphragm. The patient's hospital course after hernia repair was uneventful.
Adult↗
Development of a questionnaire measure of adjustment to cancer: the MAC scale.
This paper describes the development of a self-rating scale to measure adjustment to cancer. The Mental Adjustment to Cancer (MAC) Scale has been completed by 235 patients with various types and stages of cancer. It is easily understood by, and acceptable to, patients. Data relating to reliability and internal consistency indicate that the MAC scale is a valuable research tool for clinical studies of patients' psychological adjustment to cancer.
Adaptation, Psychological↗
The dose in humans at which ICI 118,551 (a selective beta 2-adrenoceptor blocking agent) demonstrates blockade of beta 1-adrenoceptors.
The effects of four single oral doses of ICI 118,551 (a selective beta 2-adrenoceptor blocking agent: doses 10, 20, 50, and 100 mg) have been compared with placebo in five normal, healthy volunteers on some cardiovascular responses to intravenous infusions of dobutamine. Increasing infusions of dobutamine produced reproducible dose-dependent reductions in systolic time intervals and increases in systolic blood pressures, these responses representing positive inotropic effects of dobutamine. These effects of dobutamine were unaffected 2 hours after administration by 10 mg ICI 118,551 and minimally by 20 mg; the 50 mg dose attenuated the systolic time interval effect whereas the 100 mg dose attenuated further the systolic time interval reduction and also the increase in systolic blood pressure. These results allow a conclusion that at unit doses of 50 mg and above, ICI 118,551 will produce demonstrable effects on beta 1-adrenoceptors.
Adrenergic beta-Antagonists↗
Automation of routine coagulation testing using a random access centrifugal analyzer.
The results are reported of a clinical and laboratory evaluation of the use of a random-access centrifugal analyzer linked to a personal computer in the management of the routine workload of a hemostasis laboratory. Over a three-month period, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin clotting time (TCT), and derived fibrinogen (Fib) were performed on a total of 929 samples. Included in the study were 448 samples from patients receiving anticoagulants (oral anticoagulants, 228; heparin, 166; heparin and warfarin, 130) and 351 samples from patients requiring coagulation screens (PT, APTT, TCT, Fib). Tests were done in parallel with tilt-tube manual techniques and the results correlated. The correlation coefficients were PT, 0.99; TCT, 0.72; APTT, 0.96; Fib, 0.97. Discrepancies were analyzed and were due to hypofibrinogenemia and hyperlipidemia. The poorer correlation coefficient of TCT was attributable both to lower reproducibility of the manual test and the effect of dysfibrinogenemia or FDPs in liver disease. In no case was an abnormality or diagnosis missed using the centrifugal analyzer. In several cases the increased sensitivity of the analyzer improved the detection of the lupus anticoagulant. The use of automation was accompanied by a major reduction in workload and reagent costs. The machine has been used to assay a wide range of coagulation tests by clot based and chromogenic substrate methods. In conclusion, a programmed centrifugal analyzer is a safe, efficient, and flexible way of automating routine coagulation tests. It widens the reportoire of tests performed in the Hemostasis laboratory by using a machine capable of being used in other areas of pathology.
Blood Coagulation Tests↗
Health-related aspects of the devitrification of aluminosilicate refractory fibres during use as a high-temperature furnace insulant.
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Aluminum Silicates↗
Effects of the beta 2-adrenoceptor antagonist ICI 118,551 on blood pressure in hypertensive patients known to respond to beta 1-adrenoceptor antagonists.
1. The selective beta 2-adrenoceptor antagonist ICI 118,551, 50 mg orally given thrice daily, did not lower blood pressure in hypertensive patients known to respond to therapy with atenolol or propranolol. 2. This dosage regimen resulted in a small decrease in supine heart rate which might represent partial beta 1-adrenoceptor antagonism by ICI 118,551. 3. The results suggest that beta 2-selective antagonism does not play a role in the hypotensive action of beta-adrenoceptor antagonists.
Adrenergic beta-Antagonists↗
Proenkephalin A processing in the upper digestive tract: isolation and characterisation of phosphorylated N-terminally extended Met-enkephalin Arg6Phe7 variants.
Previous studies suggest the processing of proenkephalin A in the porcine upper digestive tract might differ from that in the brain. To characterise more precisely some of the products, we have used antibodies to Met-enkephalin Arg6Phe7 (MERF) in radioimmunoassay to monitor the isolation of immunoreactive peptides from extracts of porcine pyloric antral muscle, antral mucosa, and duodenum. Sephadex G50 gel filtration of each extract produced a single broad peak of high-molecular-weight MERF-immunoreactivity. On anion-exchange chromatography the antral muscle MERF-immunoreactivity fractionated into two major peaks, and that from the antral mucosa and duodenum each into four major peaks, suggesting tissue specific processing of proenkephalin A within the porcine gut. Reverse-phase HPLC and Edman degradation analysis revealed that the least acidic antral muscle peptide was a 31-residue N-terminally extended form of MERF that is equivalent to proenkephalin A 209-239. Alkaline phosphatase digestion of the N-terminally extended MERF variants indicated that some of these peptides were modified by phosphorylation. We conclude that there are complex patterns of proenkephalin A processing in the porcine gut, which in part are due to phosphorylation.
Alkaline Phosphatase↗
The sensitization phase of T-cell-mediated immunity.
Many cell-mediated immune responses appear to develop in two phases: A sensitization phase in which unprimed or memory T cells interact with dendritic cells to become active lymphoblasts, and an effector phase in which the T lymphoblasts and other presenting cells interact to eliminate the antigen. Antigen presentation is essential to both phases. Here we review several features that are pertinent to the special sensitization role of dendritic cells. First, dendritic cells from lymphoid tissues, blood, and lymph (lymphoid dendritic cells) express very high levels of class I and II MHC products, and these levels cannot be increased by exposure to cytokines such as immune interferon. Second, dendritic cells efficiently cluster antigen-specific T cells during primary responses. Other presenting cells, like macrophages and B lymphocytes, do not form clusters but do bind to sensitized T lymphoblasts. Dendritic-T-cell binding is not inhibited by mAb to CD4 and LFA-1 antigens. It is suggested that a dendritic-cell-specific molecule is required. Third, it is not yet clear if dendritic cells make a "lymphocyte activating factor." However, IL-1 is not produced, even when dendritic cells are in contact with responding T cells. Fourth, dendritic cells have the capacity to migrate from the tissues and move to T-dependent areas. Epidermal Langerhans cells represent a reservoir of tissue dendritic cells but seem to be immunologically immature. The viability and accessory function of the Langerhans cell greatly depend on a single cytokine, granulocyte-macrophage colony stimulating factor (GM-CSF), leading to the proposal that GM-CSF is critical in mobilizing active dendritic cells at the onset of a cell-mediated immune response.
Animals↗
Effect of carrier selection on immunogenicity of protein conjugate vaccines against Plasmodium falciparum circumsporozoites.
Conjugate vaccines against the sporozoite stage of Plasmodium falciparum were synthesized by covalently coupling the recombinant protein R32 [with the one-letter amino acid code of MDP-[(NANP)15NVDP]2LR] to tetanus toxoid, cholera toxin, choleragenoid, and Pseudomonas aeruginosa toxin A. Conjugates were produced by using adipic acid dihydrazide as a spacer molecule and carbodiimide as a coupling agent. The molar ratio of R32 to carrier protein ranged from 2.5:1 to 8.4:1. These conjugates were found to be stable, nontoxic, and nonpyrogenic. When adsorbed onto Al(OH)3, all conjugates were capable of inducing anti-R32 antibody. Conjugates made with either cholera toxin or Pseudomonas aeruginosa toxin A were significantly more immunogenic than those constructed with tetanus toxoid or choleragenoid. However, the magnitude of the immune response to the R32 moiety was not governed by the antibody response to the carrier protein.
Amino Acid Sequence↗
Does cyclosporin A adversely affect Pneumocystis carinii infection?
Fourteen immunosuppressed patients with Pneumocystis carinii infection presented in two clusters that were separated by 2 years. The diagnosis in all cases was made early by alveolar lavage with cytology. The first group of seven patients was immunosuppressed with cyclophosphamide or azathioprine and prednisolone. All recovered with high dose co-trimoxazole. The second group of seven patients was on prednisolone and cyclosporin A. Despite identical treatment three patients died and a further two who survived lost their grafts from rejection. Our data suggest that cyclosporin A adversely affects the prognosis from Pneumocystis carinii infection and raises the question of prophylactic co-trimoxazole in these patients. The clustering of Pneumocystis carinii infection suggests the possibility of nosocomial transmission although in this study we were unable to implicate person-to-person spread of infection.
Adult↗
C1q enhancement of antibody-dependent granulocyte-mediated killing of nonphagocytosable targets in vitro.
A possible role for C1q in antibody-dependent granulocyte-mediated killing of nonphagocytosable targets was investigated utilizing IgG-dependent granulocyte cytotoxicity directed against microfilariae of Dirofilaria immitis. Granulocyte-mediated killing of microfilariae is enhanced by addition of fresh serum. Lack of C4 did not significantly reduce the observed increase in cytotoxicity. The addition of highly purified monomeric human Clq (0.2 microgram/ml) in the presence of immune IgG resulted in a two- to fivefold enhancement of killing (P less than 0.025). C1q enhancement of killing occurred in the absence of fluid-phase IgG, but killing was significantly less than when both fluid-phase IgG and C1q were present. The effect of C1q was inhibited by the addition of solubilized type I collagen (44-92% inhibition of killing, P less than 0.05). Significant 125I-Clq binding to microfilariae occurred only in the presence of immune IgG. In addition, C1q in concentrations ranging from 0.5 to 2.0 micrograms/ml resulted in a dose-dependent increase in binding of 125I-immune IgG to microfilariae. Finally, when purified C1q was added to preopsonized, washed microfilariae, granulocyte production of superoxide was increased from 0.25 +/- 0.07 to 0.68 +/- 0.07 nm/10(6) cells.10 min (P less than 0.01). These results describe a novel functional role for C1q in enhancement of antibody-dependent cellular cytotoxicity towards nonphagocytosable targets.
Animals↗