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Biomedical subjects

R Turner

Publications and source records attributed to R Turner.

At least 253 records · Page 14Linked to original sources

Fast protein liquid chromatography scale-up procedures for the preparation of low-molecular-weight proteins from urine.

A system for the rapid isolation of low molecular weight proteins from urine has been devised, and illustrated by alpha 1-microglobulin, beta 2-microglobulin, retinol binding protein, lysozyme and monoclonal light chains. Urine proteins from patients with tubular dysfunction were concentrated, either by ultrafiltration or ammonium sulphate precipitation. This was followed by gel chromatography on Sephadex G-50. The appropriate fractions were then separated by chromatography on Pharmacia monobead columns. A Mono Q strong anion exchanger was used for beta 2-microglobulin, retinol binding protein, alpha 1-microglobulin and free monoclonal light chains. Lysozyme was separated on a Mono S cation exchanger. The chromatography was first optimized on HR 5/5 columns and then scaled up to HR 16/10 columns.

Alpha-Globulins↗

Outcome with desipramine therapy in subtypes of nonpsychotic major depression.

A consecutive series of 42 outpatients with major depression were classified as having endogenous or nonendogenous depression according to RDC, primary or secondary depression according to the criteria of Feighner et al. (1972) and suppression or nonsuppression according to a dexamethasone suppression test. These groups were then compared according to outcome after an initial placebo phase and after 6 weeks of treatment with desipramine. Patients with secondary depression were somewhat more likely to respond to placebo and were significantly less likely to complete the entire course of treatment. The primary/secondary distinction but not the endogenous/nonendogenous distinction predicted clinical status after desipramine therapy. In accord with earlier reports, nonsuppressors faired better than suppressors though this difference did not reach statistical significance. Moreover, nonsuppressors tended to have outcomes which were more discrete as reflected in a bimodal distribution for final scores, in contrast, final scores for suppressors assumed a more unimodal distribution.

Adolescent↗

Identification and measurement of paraprotein polymers by high performance gel filtration chromatography.

An evaluation of Superose 6, a new high performance gel filtration medium, has been made for the rapid separation and quantitation of paraprotein polymers. There is a significant correlation between relative serum viscosity and the concentration of polymeric IgA as demonstrated by FPLC using the Superose 6 columns. The retention times of the columns are highly reproducible and allow good resolution of polymers and provide a simple way of separating IgG3 from albumin. Scaling up to the preparative Superose 6B could be achieved with little loss of resolution.

Chromatography, Gel↗

Cluster analysis of chromatographic profiles of urine proteins.

A method to examine and classify the chromatograms of urinary proteins, separated on a fast protein liquid chromatography system, is presented. For the analyses a measure of similarity between chromatogram profiles is defined and this is used to implement a statistical cluster analysis technique for the identification of a system of classification. The resulting classification can be related to a clinical assessment of the proteinuria of the sample urines, which are from patients with various renal disorders.

Chromatography, High Pressure Liquid↗

Leukocyte regulation in depression and schizophrenia.

The distribution of leukocytes in the blood stream is affected by levels of circulatory glucocorticoids. Elevated concentrations of cortisol are usually associated with an increase in the number of neutrophils and a decrease in the number of lymphocytes. Since primary depressive illness is often associated with hypercortisolemia, we hypothesized that similar changes in the blood stream of depressive patients may occur. To test this hypothesis, we retrospectively compared leukocyte counts in 177 untreated depressive patients and 178 untreated schizophrenic controls. We found a significant increase in the absolute and relative numbers of neutrophils and a significant decrease in the absolute and relative numbers of lymphocytes in the depressive group. Furthermore, when compared to normative values from the general population, depressed patients showed higher frequencies of both neutrophilia and lymphopenia than the schizophrenic group. These results indicate differences in the regulation of leukocytes in depression and schizophrenia consistent with the effects of higher levels of plasma cortisol in the depressive group.

Adult↗

T cell subpopulations in alopecia areata.

Alopecia areata remains a disease of unknown cause and unsatisfactory treatment. Histologically it is characterized by a lymphocytic infiltrate that surrounds the lower half of the hair follicle. Our findings show that 64% to 92% of this infiltrate is composed of T lymphocytes bearing the Leu 3a (helper-inducer) phenotype. The remaining lymphocytes demonstrate the Leu 2a (cytotoxic-suppressor) phenotype. This helper T cell predominance is present in all patients, irrespective of clinical activity or duration of disease. The Leu 3a/Leu 2a ratio ranged from 2.6 to 19.8, the higher ratios being seen in patients with clinically active disease. The cutaneous infiltrate also is Ia-positive, indicating the activated nature of these lymphocytes.

Adult↗

Massive amniotic fluid embolism.

A patient at 42 weeks of pregnancy called the emergency department complaining of painful uterine contractions for six hours. She was advised to come to the hospital immediately. An episode of vomiting caused a 60-minute delay in her arrival. Dyspnea, fatigue, and leg cramps developed. In the emergency department she was anxious, alert, and cyanotic. Fetal distress was diagnosed. Within 15 minutes the patient had bradycardic cardiopulmonary arrest. Resuscitation attempts and agonal caesarean section failed. Autopsy revealed massive pulmonary amniotic fluid emboli. Amniotic fluid embolus must be considered in the differential diagnosis of pregnant patients with complaints of shortness of breath and signs of shock with bradycardia.

Adult↗

Urinary protein isolation by high-performance ion-exchange chromatography.

Proteins excreted in urine, following renal failure, were analysed by high-performance anion-exchange chromatography and chromatofocusing. The analysis involved three steps: (1) removal of the low-molecular-weight fraction by rapid desalting, (2) anion exchange of the high-molecular-weight fraction by using combined salt and pH gradients and (3) further separation of the main peaks by chromatofocusing. The selection of the column and conditions were based on data obtained from electrophoretic titration curves. The purity of selected peaks was evaluated by sodium dodecyl sulphate polyacrylamide gel electrophoresis.

Chromatography, Ion Exchange↗

Separation of urine proteins on the anion-exchange resin mono Q.

Proteins excreted in urine due to renal failure were separated on Mono Q, a new strong anion exchange designed for fast high-resolution protein separations. The separation procedure was divided into two steps. The first step involved removal of low-molecular-weight substances by rapid desalting on a Sephadex G-25 Superfine column. In the second step, the total protein fraction (3--6 ml) was loaded onto the Mono Q column with the aid of a superloop. The proteins were adsorbed onto the top of the ion-exchanger column and gradually displaced by a combined pH and salt gradient in 40 min. The choice of ion exchanger and initial operating conditions were based on data obtained from electrophoretic titration curve experiments. Identification of separated proteins was achieved by fused rocket electrophoresis and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, respectively.

Chromatography, Ion Exchange↗

Multivariate analyses as aids to diagnosis and assessment of prognosis in gastrointestinal cancer.

The role of carcinoembryonic antigen (CEA), gamma glutamyl transpeptidase (gamma GT), phosphohexose isomerase (PHI), pseudouridine (psi) and acute phase reactant proteins (C-reactive protein (CRP) alpha 1-antichymotrypsin (ACT) and alpha 1-acid glycoprotein (AGP] in assessing the prognosis of gastrointestinal neoplasms and the discriminant function in distinguishing benign from malignant diseases of the GI tract was examined. In stomach cancer pre-operative levels of CRP can help in the identification of the patients with a resectable tumour; the pre-operative biochemical measurements do not give any further information on prognosis once stage and site are taken into account. In colorectal cancer pre-operative ACT levels give additional prognostic information once the clinical factors, Dukes stage, sex and age have been accounted for; PHI levels are on the border line of significance. A discriminant function has been devised using sex, CEA, psi, gamma GT, ACT and PHI that can identify 89% of Dukes "D" patients prior to surgery with a misclassification of 7% of other cases of colorectal cancer. A discriminant function using all the biochemical variates separated the cancer from non-cancer patients. The false positive rate for cancer was 16% and a false negative rate of 19%, when the cut-off level was set at 0.7.

Adult↗

Bleomycin-induced cutaneous toxicity in the rat: analysis of histopathology and ultrastructure compared with progressive systemic sclerosis (scleroderma).

Rats injected with bleomycin over a 58-week period developed weight loss, alopecia, hyperpigmentation, skin thickening and skin tautness when compared with saline-injected control animals. The only significant abnormality in laboratory blood tests was an increased sedimentation rate in the bleomycin-treated rats compared with controls. Histological examination of dorsal skin showed atrophied sebaceous glands and increased collagen fibres, with diameters ranging from 37.5 to 75 nm as compared with 72.5 to 100 nm in control animals. Chronic bleomycin exposure produces clinical, histological and ultrastructural skin changes similar to those found in human progressive systemic sclerosis (scleroderma).

Animals↗

Applications of fast protein liquid chromatography TM in the separation of plasma proteins in urine and cerebrospinal fluid.

Fast Protein Liquid Chromatography TM (FPLC), in which an anion-exchange column is used, provides rapid separation and reproducible profiling of the plasma proteins in urine and cerebrospinal fluid (CSF). Chromatographic separation of the proteins takes 1 h for urine specimens and 45 min for CSF. The elution sequence from the anion-exchange column is similar to the electrophoretic mobility. Individual proteins have the same retention times independently of which type of specimen is used. The elution characteristics of 21 plasma proteins have been identified. We illustrated some applications of this system, including the profiling of tubular protein-uria, the isolation of Bence Jones proteins from urine, and the investigation of hemoglobin-derived products in the CSF.

Adult↗

Factors protective against retinopathy in insulin-dependent diabetics free of retinopathy for 30 years.

To investigate which factors might protect against the development of retinopathy 40 insulin-dependent diabetics who had remained free from retinopathy despite diabetes of long duration (mean+/-1 SD 30+/-10 years) were compared with 40 patients who had background and 47 who had proliferative retinopathy (mean durations of disease 16+/-5 and 19+/-5 years respectively). The three groups had had similar mean ages at onset of diabetes. The mean of all postprandial blood glucose measurements at hospital clinics from diagnosis of diabetes to detection of retinopathy, or to the most recent negative eye examination, was 9.9+/-2.1 mmol/l (178+/-38 mg/100 ml) in the group with no retinopathy, 11.8+/-2.1 mmol/l (213+/-38 mg/100 ml) in those with background retinopathy, and 12.4+/-2.1 mmol/l (223+/-38 mg/100 ml) in those with proliferative retinopathy (p <0.0001). This difference was not reflected in present concentrations of haemoglobin A(1C), probably because glycaemic control had been improved after the development of retinopathy. In the groups with background and proliferative retinopathy there were significant negative correlations between mean blood glucose concentrations and the number of years that had elapsed from diagnosis of diabetes to detection of retinopathy, suggesting that the development of both grades of retinopathy depends on the degree and duration of glycaemic exposure.The patients with no retinopathy had attended clinic more frequently (p <0.025), more of them had required emergency hospital treatment for hypoglycaemia (p <0.0025), and they tended to have had a lower prevalence of hyperglycaemic coma than the other groups. Although mean percentage ideal body weight and diastolic blood pressure were lower in the patients with no retinopathy at the time of study, mean body weight, blood pressure, and the prevalence of smoking in the years before the development of retinopathy had been similar in all groups, suggesting that these did not influence the development of retinopathy.

Blood Glucose↗

Genetic predictors of patient response and side effects in the treatment of rheumatoid arthritis with a high dose nonsteroidal antiinflammatory drug regimen.

Clinical, laboratory, genetic, and radiologic studies were evaluated for 18 patients with rheumatoid arthritis who were treated for a mean of 16.6 months with a regimen involving supplementary aspirin and piroxicam, an investigational, nonsteroidal antiinflammatory agent. Although improvement in disease activity was seen, progression was evident on successive radiographs. Disease activity was not associated with the presence of any of the genetic markers. Peptic ulcers developed in 33% of patients, all of whom had type O blood. ABO blood typing may therefore be useful in patients with rheumatoid arthritis before consideration of therapy with potentially ulcerogenic drugs.

Adult↗

Serological diagnosis of influenza B virus infection: comparison of an enzyme-linked immunosorbent assay and the hemagglutination inhibition test.

The sensitivity of an enzyme-linked immunosorbent assay (ELISA) for the detection of antibody to influenza B virus was compared with that of the hemagglutination inhibition test on acute- and convalescence-phase sera obtained from adults and children infected with influenza B virus. Two whole virus, tissue culture-grown antigen preparations were used in the ELISA, influenza B/West Virginia/81 and influenza B/Hong Kong/72. Four antigens were used in the hemagglutination inhibition test. These included the tissue culture-grown whole virus antigens that were used in the ELISA. In addition the standard egg-grown antigens, influenza B/Singapore/79 and influenza B/Hong Kong/72, were included for comparison. The ELISA antibody titer was significantly correlated to the hemagglutination inhibition antibody titer, and 10 of 10 adults and 17 of 21 children infected with influenza B had fourfold antibody increases as detected by ELISA with either antigenic type of tissue culture-grown whole virus. Increases in geometric mean antibody titers of 16- to 71-fold were detected by ELISA. Increases in geometric mean antibody titers of 3- to 10-fold were detected by hemagglutination inhibition depending on the type of antigen utilized. We found that ELISA with whole virus antigens was a sensitive and specific test for the detection of antibody to influenza B virus.

Adult↗