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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 469 records · Page 26Linked to original sources

Structural characterization of the isoenzymatic forms of human myeloperoxidase.

Myeloperoxidase from human neutrophils was isolated by ion-exchange and gel-filtration chromatography and shown by SDS-polyacrylamide gel electrophoresis to be comprised of alpha and beta subunits with apparent Mr values of 58,000 and 15,000, respectively. The apparent Mr of the native protein was 130,000-140,000, indicating that the holoenzyme has the quaternary structure alpha 2 beta 2. Automated Edman degradation of the separated alpha and beta subunits showed that the amino-terminal sequences were different from one another and demonstrated no sequence microheterogeneity. Comparison of these sequences with those in the National Biomedical Research Foundation data bank of protein sequences revealed that the subunits of human myeloperoxidase were not homologous to any known protein. Myeloperoxidase purified from HL-60 cells grown in culture demonstrated the same alpha 2 beta 2 subunit structure. Three isoenzymes of myeloperoxidase, prepared by gradient elution from a CM-Sepharose column, underwent quantitative analysis. No structural basis for the different elution pattern of the myeloperoxidase isoenzymes was discerned by amino-acid analysis, N-terminal sequence, polyacrylamide gel electrophoresis, or digestion with neuraminidase or enzymes known to cleave N-linked heterosaccharides. The structural basis for the myeloperoxidase isoenzymes of human neutrophils, each possessing equivalent activity, is not apparent from these studies.

Amino Acid Sequence↗

Blood glucose and plasma insulin responses to fat-free milk and low-lactose fat-free milk in young type 1 diabetics.

The blood glucose and plasma insulin responses to test milk samples were studied in eight insulin-dependent diabetics. After an overnight fast, the subjects (aged 20-45 years) were given a breakfast containing two Weetabix biscuits (20 g carbohydrate) with 500 ml of either regular (S) fat-free milk (25 g lactose) or 500 ml of a new low-lactose (D) fat-free milk (3.75 g lactose and 4.25 g fructose). The regular morning insulin dose was omitted. Mean basal plasma glucose level was slightly higher before S milk (11.4 vs. 10.1 mmol/l). The peak increment in plasma glucose was higher in S milk (9.4 vs. 6.6 mmol/l). The rise was 83% above basal (S) vs. 65% (D). Although the final mean plasma glucose concentration was not significantly higher 3 h after S milk compared with D milk (17.9 vs. 14.3 mmol/l) the incremental area under the plasma glucose curve was much greater (p less than 0.001) with S milk than with D milk (1266 +/- 295 units vs. 909 +/- 242 units). No galactose was detectable in any sample and there was no difference in plasma beta-hydroxybutyrate levels. The results suggest that the low-lactose fat-free milk (D) may be suitable for diabetic diets and weight reducing diets due to the lower contribution of energy. The results suggest that fat-free milk does not exert a fast action on blood glucose concentration and therefore fat-free milk and especially low-lactose fat-free milk may also prove to be suitable for diabetic diets.

Adult↗

Dermatomyositis and pulmonary fibrosis associated with anti-Jo-1 antibody.

Although fibrosing alveolitis is a rare complication of dermatomyositis, early detection and treatment are important in preventing pulmonary fibrosis. Anti-Jo-1 antibody, an antibody to the cellular enzyme histidyl-t-RNA synthetase, has been found to correlate closely with the subset of dermatomyositis/polymyositis associated with fibrosing alveolitis. This association is well known to rheumatologists but has received little attention in the dermatologic literature. We wish to alert dermatologists to the importance of the association of anti-Jo-1 antibody in patients with dermatomyositis and present a patient with anti-Jo-1 antibody who had Raynaud's phenomenon and mild arthritis in association with dermatomyositis and pulmonary fibrosis. We suggest screening patients with polymyositis/dermatomyositis for this antibody, to detect the population at high risk of developing pulmonary complications.

Antibodies, Antinuclear↗

Gamma-actin: unusual mRNA 3'-untranslated sequence conservation and amino acid substitutions that may be cancer related.

beta-Actin mutations in chemically transformed human cell lines have been associated with tumorigenicity, an association consistent with other evidence suggesting that altered cytoskeletal proteins may have an important role in cancer initiation or progression. From a human promyelocytic leukemia cell line, we have isolated a gamma-actin cDNA clone with amino acid substitutions in a region highly conserved in the many actins analyzed. To our knowledge, this is the first example of a variant gamma-actin in a human neoplasm. A separate finding from the analysis of this clone is that the gamma-actin 3'-untranslated region is among the most highly conserved of all 3'-untranslated sequences so far reported, but is entirely different from the beta-actin 3'-untranslated region. The high degree of evolutionary conservation suggests that the 3'-untranslated regions of these two mRNAs have important and distinct functional roles that were already fully differentiated more than 100 million years ago. Mutations affecting four major cytoskeletal components have now been identified in human neoplastic cells. These findings suggest that mutated cytoskeletal genes may be members of a class of oncogenes, fundamentally different from both the nuclear-acting (e.g., myc and simian virus 40 large tumor antigen) and growth factor/receptor/protein kinase-related (e.g., sis, erbB, and ras) types of oncogenes.

Actins↗

Ventricular septal rupture complicating myocardial infarction: is earlier surgery justified?

Fifty-five consecutive cases of ventricular septal rupture following myocardial infarction were reviewed in order to ascertain clinical and haemodynamic determinants of in-hospital mortality. Factors associated with a poor prognosis included clinical evidence of a poor haemodynamic state or biochemical evidence of impaired renal function. Twenty-six patients managed before 1982 (group 1) were then compared with 29 managed subsequently (group 2) when a policy of earlier surgical intervention had been adopted. Patients in group 2 were more haemodynamically compromised and had greater impairment of renal function. The surgical mortality in group 1 was 3 of 18 patients (17%) which was not significantly different from that in group 2 (7 of 22 patients, 32%). Earlier surgical intervention in ventricular septal rupture is frequently undertaken in critically ill patients whose prognosis is poor. However their surgical risk is not significantly increased and such an approach can therefore be justified as it may salvage some patients who otherwise would not survive.

Adult↗

Dreams and contemporary stress: a disruption-avoidance-adaptation model.

A disruption-avoidance-adaptation model is proposed to provide a framework for understanding the seemingly disparate findings from studies of dream function. The model is based on the notion that there is an oscillation between disruption of sleep caused by dreaming about a stressful stimulus followed by an avoidance of the stimulus in order to achieve homeostasis. The oscillation is postulated to continue until there is adaptation to the disruptive stimulus. Continuity is assumed to exist between waking and sleeping experience.

Adaptation, Psychological↗

An analysis of the liability insurance crisis.

The problem of the growing liability insurance crisis is examined from historical, economic, policy, and legislative perspectives. Specifics of arguments presented by physicians, nurses, lawyers, and insurers are provided to illustrate the conflict inherent in the situation. Reports of policy actions accomplished by these groups are presented with a discussion of related bills proposed in past years. Specific nurse populations directly affected by the insurance crisis are presented and actions to be taken by nurses and legislators to deal with the problem are suggested.

Delivery of Health Care↗

The contribution of immunohistochemical staining in tumour diagnosis.

With the increasing use of immunohistochemical stains in the diagnostic laboratory, it becomes relevant to review the contributions of this new technology in the area of tumour diagnosis. During 1986, our laboratory received 21,479 biopsy specimens of which 2013 were tumours. Nine hundred and fifty-eight tumours (47.5%) were subjected to immunohistochemical analysis. The biopsy and immunohistochemistry reports of 200 consecutive tumours, including 41 consultation cases, were retrospectively reviewed and assigned to one of the five categories. Immunohistochemical stains confirmed the preferred H & E diagnosis in 106 cases (53%); made the definitive diagnosis from a list of differential diagnosis in 29 cases (14.5%); provided contributory information in 36 cases (18%); were non-contributory in 27 cases (13.5%); and rendered an unsuspected diagnosis in two cases (1%). Immunohistochemical stains were particularly useful in distinguishing between malignant lymphoma and anaplastic carcinoma and in the identification of amelanotic melanoma. The application of a panel of antibodies chosen in accordance with the differential diagnoses considered was very useful in the typing of anaplastic round cell and spindle cell tumours. In 27 cases (13.5%), immunohistochemical stains were non-contributory. About half of these were referred cases and the failure to demonstrate the relevant antigens in normal tissues which served as in-built controls suggested that part of the problem may be due to differences in methods of fixation which led to sub-optimal preservation of tissue antigens. We conclude that immunohistochemical stains provide important and sometimes essential information for definitive typing of anaplastic tumours. Often the information derived was of therapeutic and prognostic relevance. We argue that this is a cost-effective test although we would caution that in all circumstances the interpretation of immunostaining must be made in the context of the histological as well as the clinical and laboratory data.

Diagnosis, Differential↗

Magnetic resonance imaging of the pulmonary arteries and their systemic connections in pulmonary atresia: comparison with angiographic and surgical findings.

Patients with pulmonary atresia require several investigations and operations. The role of magnetic resonance imaging in assessing the anatomy of the central pulmonary arteries, the origin and course of systemic collateral arteries, and the patency of surgical shunts has been studied with the aim of reducing the need for invasive angiography. Transverse, coronal, and sagittal images were obtained in ten adult patients and assessed without knowledge of surgical and angiographic data. Central pulmonary artery anatomy varied from full development to complete absence. Transverse slices showed hypoplastic arteries particularly well and the findings accorded with surgical and angiographic data in all patients. The origin and proximal course of 15 large collaterals were identified on the magnetic resonance images and 18 were identified by surgical and angiographic data. Magnetic resonance imaging did not show their distal connections; if such information is required angiography will be needed. Five surgical shunts were shown to be patent and two occluded at surgery and angiography, and this was confirmed on the magnetic resonance images. The patency of a further four shunts was uncertain, but they were not seen by magnetic resonance and were presumed to be occluded.

Adult↗

Genetic variation between woodchuck populations with high and low prevalence rates of woodchuck hepatitis virus infection.

Woodchuck hepatitis virus (WHV) infection is known to be endemic in areas of the mid-Atlantic states but is apparently absent from populations in New York and much of New England. Blood samples of 40 woodchucks (Marmota monax) from New York and from Delaware were examined by starch gel electrophoresis, and 18 monomorphic and six polymorphic protein-coding genetic systems were identified. Mendelian inheritance of variants of the six polymorphic systems was confirmed in 52 laboratory offspring of the original samples. Average heterozygosity of 0.066 in New York woodchucks and 0.039 in Delaware woodchucks were high values for mammals, although similar to those of other sciurids. Significant heterogeneity between samples from New York and Delaware woodchucks was observed at two loci (peptidase with glycyl leucine-4 and phosphogluconate dehydrogenase), suggesting that these populations were genetically distinct. Whether there are genetically determined differences in response to WHV infection remains to be determined experimentally.

Alleles↗

Palliation in cyanotic congenital heart disease. Fifteen years' experience of various shunt procedures.

During the past 15 years, 143 systemic pulmonary shunt procedures have been performed in 117 patients. These have been evaluated for their clinical effectiveness, the need for a repeat operation and the mortality; particular attention was paid to the Teflon shunt. Variations were found in shunt performance, depending on the primary defect, the type of shunt that was employed and the year of operation. The overall shunt patency after three years was 77% (85% with the Teflon shunt). Although, in our total experience, mortality at 30 days was 12%, with 16% late deaths, "modified Blalock" (Teflon) shunts had only a 5% hospital mortality and a 5% late mortality within three years. Pulmonary atresia, without a ventricular septal defect, is often insufficiently palliated by a shunt alone. Ten of 82 patients with variations of the tetralogy complex died within 30 days of operation, and a further 11 died in the late follow-up period. Six of these 21 shunts were patent at autopsy. Less common defects, such as univentricular heart, transposition and double-outlet right ventricular connections, that are associated with pulmonary stenosis had no early mortality but led to four late deaths among 27 patients. Two of the four patients had patent shunts. Results in the early part of this experience were less than acceptable owing to inferior shunting techniques, postoperative management errors and, particularly, inadequate follow-up surveillance. With correction of these factors we find that the modified Blalock shunt provides very good early and late mortality results, with excellent clinical palliation and patency rates.

Adolescent↗

Changing patterns of transfusion practice in a tertiary care hospital from 1977 to 1984.

Patterns of blood transfusion practice over an eight-year-period (1977-1984) are described. Use of blood and blood products increased annually as did the number of patients crossmatched and transfused. Programs such as the "Blood Group & Antibody Screen" and the "Maximum Surgical Blood Order Schedule" were important in improving transfusion practices. There was improvement in blood use by all subspecialties; the overall C:T (crossmatched:transfused blood) ratio declined from 4.4 to 2.8. Approximately a quarter of both crossmatches performed and transfusions of red cells were associated with cardiac surgery. Incidence of outdated units of blood declined markedly (2.6 per cent in 1984), as did requests for and administration of single unit transfusions. Seven per cent of patients received one unit of blood during hospitalization; since 85 per cent of these were associated with surgery (57 per cent cardiac surgery), it is suggested that single unit transfusions may sometimes be more appropriate than inappropriate. Two per cent of patients had clinically significant alloantibodies. About two per cent of patients had positive direct antiglobulin tests; nine per cent of the sera of these patients contained both auto and alloantibodies. Such data are important for transfusion quality assurance as well as for optimal logistical use of facilities both at hospital Blood Bank and blood collection agency levels.

Antibodies↗

Orotracheal intubation in suspected laryngeal injuries.

Airway control in patients with suspected laryngotracheal injury following blunt trauma is a challenging problem. Tracheostomy remains the treatment of choice in most instances. This report describes a patient with a laryngotracheal injury in whom initial airway control was achieved using orotracheal intubation. The indications for this method are discussed, and an approach to initial airway management in these injuries is outlined.

Adult↗