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Biomedical subjects

J Scott

Publications and source records attributed to J Scott.

At least 397 records · Page 22Linked to original sources
PubMed1990

DNA sequencing of a mouse liver protein that binds selenium: implications for selenium's mechanism of action in cancer prevention.

Complementary DNA clones for liver protein 56K (SLP-56) were isolated by screening a lambda Zap mouse liver library. The cloned cDNAs represented the complete message. The correct reading frame was verified by alignment of the deduced amino acid sequence with that of peptides sequenced from the purified protein. The primary sequence has not been reported previously since homologous DNA sequences were not found in GenBank. Most importantly, the DNA sequence did not contain an in-frame TGA codon that would code for seleno-cysteine, as occurs in the prototypic selenoprotein, glutathione peroxidase. Hydropathy analysis suggested the protein was not a membrane-spanning protein. SLP-56 was previously localized as a cytosolic-soluble protein on the basis of cell fractionation experiments. The results suggest that SLP-56 is different from proteins whose synthesis and concentration are dependent upon selenium and require TGA to encode for selenocysteine. In this respect, SLP-56 appears to be similar to liver fatty acid binding protein (SLP-14) for which selenium is a ligand. Our working hypothesis is that selenium exerts its inhibitory effects on cell growth by modulating the properties of existing growth regulatory proteins. The two proteins that are readily labeled by selenium in many rodent tissues, SLP-56 and SLP-14, would fit into this category.

Amino Acid Sequence↗
PubMed1990

Hostility, hopelessness and deliberate self-harm: a prospective follow-up study.

Sixty-one consecutive patients who presented following an episode of deliberate self-harm (DSH) were assessed on a number of variables, including measures of hopelessness and hostility. Attempts were made to follow all of the patients. Those who were known to have had a further episode of DSH had significantly higher levels of hopelessness and intropunitive hostility after the index episode than those who did not repeat. The question of vulnerability to DSH is discussed as well as the possibility of using measures of hopelessness and intropunitive hostility to identify those at greater risk of repetition.

Adolescent↗
PubMed1990

Histologic assessment of the submandibular glands in autoimmune-disease-prone mice.

Submandibular glands were examined from three autoimmune-disease-prone strains of mice (NZB/W, MRL/l and MRL/n) and controls (C57BL/6J). Focal lymphocytic adenitis was more prevalent and more severe in autoimmune-disease-prone strains than controls and in females than males. Lymphocytic foci were more frequent in older age groups, but female MRL/1 mice exhibited high levels of focal lymphocytic adenitis irrespective of age. Salivary parenchyma was generally well preserved. In the strain-age groups with the highest focal lymphocytic scores proportional acinar volumes were significantly less than in controls. However, the proportion of acinar tissue showed no consistent relation to the severity of focal lymphocytic adenitis across all strains and age groups of either sex. Sexual dimorphism in granular duct prominence was weakened in NZB/W and MRL/l strains compared to controls.

Aging↗
PubMed1990

Lung function associated with histologically diagnosed acute lung rejection and pulmonary infection in heart-lung transplant patients.

A group of 34 heart-lung transplant patients were studied with serial pulmonary function measurements, chest radiographs, and transbronchial biopsies from the time of surgery. These investigations were carried out routinely at 3 and 6 months and then annually after transplantation as well as on clinical suspicion of acute lung rejection or infection. A total of 61 transbronchial biopsies and concurrent lung function and chest radiographs were obtained. Of the biopsies, 30 (49.2%) showed histologic evidence of lung rejection, 12 (19.7%) demonstrated various opportunistic infections, and 19 (31.1%) were normal. Compared to during episodes of normal biopsies, FEV1 decreased significantly with lung rejection (p less than 0.001) and with infection (p less than 0.01). Vital capacity (VC) and DLCO also fell with these acute lung complications. Using histologic diagnosis as a standard, lung function testing had a sensitivity of 86% in detecting lung rejection in the first 3 months postoperation and 75% in the subsequent period. Its sensitivity for detecting lung infection was 75%. Although not distinguishing between these two complications, lung function had a specificity of 84% for detecting occurrence of an acute lung complication. Chest radiographs, although of similar sensitivity in the first 3 months postsurgery, had a sensitivity of only 19% for rejection in subsequent months and 58% for infection. Its specificity was 100%. Lung function testing changes in a predictable fashion with lung rejection and infection, offers an improvement over chest radiographs, and provides a quantitative measurement to aid the decision of when to undertake transbronchial lung biopsy.

Biopsy↗
PubMed1990

The use of home spirometry in detecting acute lung rejection and infection following heart-lung transplantation.

The value of home spirometry in detecting acute lung rejection and opportunistic infections was studied in 15 heart-lung transplant recipients over a six-month period. The patients measured their FEV1 and FVC twice daily at home using a portable turbine spirometer. The records were then reviewed in relation to the results of transbronchial lung biopsy carried out during occurrences of respiratory symptoms and during routine posttransplant assessment. FEV1 and FVC fell by a mean (+/- SD) of 10.4 +/- 6.9 percent and 9.3 +/- 7.9 percent, respectively, during 20 episodes of lung rejection. The corresponding figures during opportunistic infections were 12.8 +/- 10.1 percent and 12.5 +/- 14.3 percent. No such change was observed during routine normal biopsies. Regular home spirometry offered early detection of these complications allowing early transbronchial lung biopsy as well as assessing efficacy of their therapy. Above all, measurements can be made daily, which is unique in the assessment of solid organ transplants.

Acute Disease↗
PubMed1990

Functional and structural adaptation of the parotid gland to medium-term chronic ethanol exposure in the rat.

Male rats were maintained on a regimen of twice daily intragastric administration of ethanol or a calorifically equivalent sucrose solution for thirty days. A second control group received no intragastric solution and all groups received chow and water ad libitum. Parotid saliva elicited by pilocarpine was collected by unilateral duct cannulation. The parotid flow rate over the initial post-stimulatory five minute period was raised by 44% in ethanol-dosed rats and the salivary sodium concentration was also raised, in line with higher flow rate. There were no histopathological changes related to ethanol or sucrose dosing, but stereological analysis showed a 64% increase in the proportional volume of intralobular vascular tissue in ethanol-dosed rats. These quantified histological findings suggest that parotid intralobular haemodynamics may be altered after chronic ethanol-dosing and this may contribute to the hypersecretory response exhibited by the ethanol-dosed rats.

Alcoholism↗
PubMed1990

Finite element analysis of fixed prostheses attached to osseointegrated implants.

The effect of defined stresses on cantilevered prostheses attached to osseointegrated implants was assessed by finite element analysis. The effect of stress on a cantilever, consisting of a ductile alloy in contact with a brittle polymer, was demonstrated to be complex. The distribution of applied stresses also influenced the results. Possible fracture and distortion of both materials were demonstrated. Finite element analysis is a particularly useful system for predicting stress behavior and can be employed to produce an optimal prosthetic design that reduces the potential for clinical failure.

Acrylic Resins↗
PubMed1990

Cephalometric analysis and data display simplified for clinical use.

A review of the literature on cephalometrics was undertaken with the aim of clarifying the multiplicity of definitions of planes in common use and establishing a simple analysis for clinical purposes which uses the minimum number of planes and angles and yet utilises points of maximum accuracy of identification and good reproducibility. It is hoped that the outcome of this review may be of practical value to orthodontic clinicians.

Cephalometry↗
PubMed1990

A cross-species comparison of the apolipoprotein B domain that binds to the LDL receptor.

Apolipoprotein (apo)-B-100 is the ligand that mediates the clearance of low density lipoprotein (LDL) from the circulation by the apoB,E (LDL) receptor pathway. Clearance is mediated by the interaction of a domain enriched in basic amino acid residues on apoB-100 with clusters of acidic residues on the apoB,E (LDL) receptor. A model has been proposed for the LDL receptor binding domain of apoB-100 based on the primary amino acid sequence (Knott, T. J., et al. 1986. Nature. 323: 734-738). Two clusters of basic residues (A: 3147-3157 and B: 3359-3367) are apposed on the surface of the LDL particle by a disulfide bridge between Cys 3167 and 3297. Support for this single domain model has been obtained from the mapping of epitopes for anti-apoB monoclonal antibodies that block the binding of apoB to the LDL receptor. Here we test this model by comparing the nucleotide (from 9623 to 10,442) and amino acid sequence (from 3139 to 3411) of apoB-100 in seven species (human, pig, rabbit, rat, Syrian hamster, mouse, and chicken). Overall, this region is highly conserved. Cluster B maintains a strong net positive charge and is homologous across species in both primary and secondary structure. However, the net positive charge of region A is not conserved across these species, but the region remains strongly hydrophilic. The secondary structure of the region between clusters A and B is preserved, but the disulfide bond is unique to the human sequence. This study suggests that the basic region B is primarily involved in the binding of apoB-100 to the apoB,E (LDL) receptor.

Amino Acid Sequence↗
PubMed1990

Cross-correlation of cyclosporine concentrations and biochemical measures of kidney and liver function in heart and heart-lung transplant recipients.

Cross-correlation of cyclosporine concentrations with results of biochemical tests of renal and liver function, measured during the first three months post-operatively, was carried out retrospectively in 24 heart and eight heart-lung transplant recipients to assess the temporal relationship between cyclosporine treatment and the development of possible toxic side-effects. We found a statistically significant negative correlation (95% confidence interval of the mean correlation coefficient did not overlap zero) between the five-day mean concentration of cyclosporine in whole blood (but not plasma) as measured with nonselective (NSRIA) and selective radioimmunoassays (SRIA) and the mean reciprocal creatinine concentration measured in the subsequent five days. In 15 of 32 (47%) patients the negative correlation coefficient exceeded 0.7 (high susceptibility), whereas in 11 of 32 (34%) it was between 0.5 and 0.7 (medium susceptibility), and in only six of 32 (19%) was it less than 0.3 (low susceptibility). We found no consistent correlations between cyclosporine measurements and results of other renal-function tests or liver-function tests. This suggests that therapeutic doses of the drug are not hepatotoxic in most patients. There was, however, a significantly correlated decrease in the NSRIA/SRIA ratio and in serum bilirubin concentration with time post-operatively, reflecting improvement in hepatic function and clearance of the cyclosporine metabolites that are detected by NSRIA. Assays of cyclosporine in whole blood, but not in plasma, are of value in anticipating changes in renal function after heart and heart-lung transplantation.

Biomarkers↗
PubMed1989

The use of monoclonal antibodies to localize the low density lipoprotein receptor-binding domain of apolipoprotein B.

Human apolipoprotein (apo) B-100 is composed of 4536 amino acids. It is thought that the binding of apoB to the low density lipoprotein (LDL) receptor involves an interaction between basic amino acids of the ligand and acidic residues of the receptor. Three alternative models have been proposed to describe this interaction: 1) a single region of apoB is involved in receptor binding; 2) groups of basic amino acids from throughout the apoB primary structure act in concert in apoB receptor binding; and 3) apoB contains multiple independent binding regions. We have found that monoclonal antibodies (Mabs) specific for a region that spans a thrombin cleavage site at apoB residue 3249 (T2/T3 junction) totally blocked LDL binding to the LDL receptor. Mabs specific for epitopes outside this region had either no or partial ability to block LDL binding. In order to define the region of apoB directly involved in the interaction with the LDL receptor we have tested 22 different Mabs for their ability to bind to LDL already fixed to the receptor. A Mab specific for an epitope situated between residues 2835 and 2922 could bind to its epitope on LDL fixed to its receptor whereas a second epitope between residues 2980 and 3084 is inaccessible on receptor-bound LDL. A series of epitopes near residue 3500 of apoB is totally inaccessible, and another situated between residues 4027 and 4081 is poorly accessible on receptor-bound LDL. In contrast, an epitope that is situated between residues 4154 and 4189 is fully exposed. Mabs specific for epitopes upstream and downstream of the region 3000-4000 can bind to receptor-bound LDL with a stoichiometry close to unity. Our results strongly suggest that the unique region of apoB directly involved in the LDL-receptor interaction is that of the T2/T3 junction.

Antibodies, Monoclonal↗