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Biomedical subjects

M Dunn

Publications and source records attributed to M Dunn.

At least 19 recordsLinked to original sources

Antisense-mediated specific inhibition of P120 protein expression prevents G1- to S-phase transition.

A pentadecadeoxyribonucleotide (5'-AAAGCCCCCCACCAC), complementary to a splice junction site of mRNA for human proliferation-associated nucleolar protein P120, inhibited expression of the P120 gene and the mitogen-induced proliferation of human lymphocytes. The inhibition of P120 gene expression and proliferation was concentration dependent and reached 90% at 200 microM, as measured by [3H]thymidine uptake and by densitometric scanning of Northern (mRNA) and Western (protein) blots of P120. Inhibition was not observed in cells treated with the correspondent nonsense oligomer. P120 antisense oligomer treatment prevented S-phase entry of mitogen-stimulated lymphocytes, as determined by flow cytometric analysis, but did not block G0-G1 transition assessed by morphological blast transformation and induction of [3H]uridine incorporation. Results of this study suggest that P120 expression may be required for the upregulation of nucleolar function necessary for cell proliferation.

Base Sequence

Latex agglutination testing directly from throat swabs for rapid detection of beta-hemolytic streptococci from Lancefield serogroup C.

A latex agglutination method for the rapid detection of beta-hemolytic streptococci from Lancefield serogroup C in throat swabs from 403 university students with symptomatic pharyngitis was evaluated. Compared with culture, the rapid test was poorly sensitive (34.4%) but very specific (98.4%) in detecting group C beta-hemolytic streptococci. The sensitivity of the rapid test improved with an increasing quantity of growth on culture.

Adolescent

Pulmonary embolism in younger adults.

To test the hypothesis that the clinical presentation and outcomes are different when pulmonary embolism occurs in younger (age 18 to 40 years) as compared to older (age greater than 40 years) adults, 40 younger patients were compared with older patients. No risk factors could be identified in 28 percent of the younger group. Normal physical examinations were more common (58 vs 28 percent, p = 0.01) among younger as compared with older adults. Hypoxemia was absent in 29 percent of the younger and 3 percent of the older group (p = 0.004); P(A-a)O2 was significantly lower among younger patients even after controlling for age. Mortality was decreased sevenfold (2.5 vs 18 percent, p = 0.03) among younger patients. These data indicate that pulmonary embolism tends to have a subtle presentation in younger adults. When diagnosed and treated, the mortality rate is substantially less among younger as compared with older patients.

Adolescent

Anticoagulant treatment of atrial fibrillation in the elderly.

There is now adequate clinical evidence that the most appropriate treatment of elderly patients with non-valvular atrial fibrillation is with low dose warfarin. Patients may have contraindications to therapy with this agent, but should not be denied treatment based on age alone. Withholding treatment based on age places patients at unwarranted risk for severely disabling thromboembolic complications.

Aged

Clam enterocystoplasty in general urological practice.

A series of 45 patients (31 female) underwent clam enterocystoplasty for urgency and incontinence. The majority had detrusor instability. Prolonged conservative treatment had failed in all cases. Improvement occurred in 71% and those younger than 30 years had better overall results; 29% remained incontinent, with 9% requiring a urinary diversion. Many patients did not achieve maximum benefit until 9 months post-operatively. Surgery had no statistically significant effect on any urodynamic parameter and post-operative complications were common. The operation was performed in either the coronal (19) or the sagittal plane (26); this did not influence results. In general, surgery was found to be technically simpler in the sagittal group and it is recommended that this becomes the standard procedure. We feel that this operation involves major surgery and should only be offered with reluctance.

Adult

Characterization of murine polyclonal antisera and monoclonal antibodies generated against intact and denatured human papillomavirus type 1 virions.

Human papillomavirus type 1 (HPV1) virions, both as intact virion particles (IVP) and as detergent-denatured virions (DDV), were used to prepare polyclonal antisera and monoclonal antibodies (MAbs) in BALB/c mice. Anti-IVP antiserum contained type-specific HPV1 L2-reactive antibodies and no detectable HPV1 L1-reactive antibodies. Anti-IVP MAbs recognized a linear epitope between L2 amino acids 102 and 108 (PIDVVDP). Anti-DDV antiserum contained type-specific HPV1 L1-reactive and HPV1 L2-reactive antibodies. An anti-DDV MAb recognized a linear epitope between L1 amino acids 127 and 133 (AENPTNY). HPV1a L1- and L2-encoded polypeptides expressed in Saccharomyces cerevisiae and by in vitro translation were equivalent in size to the major and minor virion capsid proteins, respectively.

Amino Acid Sequence

Effects of endothelin on cultured human and rat glomerular mesangial cells.

Figure 5 summarizes our results and the data in the literature with regard to both short-term signalling and long-term signalling induced by endothelin. Short-term signalling, which induces vasoconstriction, is undoubtedly mediated by multiple signals including increments of cytosolic calcium, stimulation of protein kinase C and alkalinization of the cytosol. Endothelin also activates negative feedback pathways including arachidonate release with the synthesis of vasorelaxant prostaglandins and potentiation, in a prostaglandin-dependent manner, of beta-adrenergic-stimulated adenylate cyclase. Long-term signalling is less well understood and may depend not only on phospholipase activation with subsequent changes of calcium and protein kinase C but also stimulation of other protein kinases which phosphorylate key intermediates. Endothelin stimulates the transient appearance of protooncogenes that might play a role in the induction of cellular proliferation.

Animals

Contribution of the bronchial circulation to lung preservation.

Short preservation time still severely limits lung transplantation. To determine the effect of bronchial arterial flush preservation, we studied 54 dogs using the isolated perfused working lung model. After baseline measurements, lungs were flushed with lactated Ringer's solution (60 ml/kg at 8 degrees C) by one of three methods: pulmonary artery perfusion, bronchial artery perfusion through a 15 cm closed aortic segment, or simultaneous pulmonary-bronchial artery perfusion. These groups were further subdivided and tested after 0, 4, and 17 hours of storage at 4 degrees C (n = 6 each). Lungs were ventilated (flow rate 140 ml/kg/min; inspired oxygen fraction 0.21) and continuously reperfused with normothermic deoxygenated autologous blood in a closed loop. Measured variables were hemodynamics, aerodynamics, and leukocytes in bronchoalveolar lavage. Survival time was determined from initial reperfusion to failure of the lung to oxygenate. After 0 and 4 hours of storage, there was no significant difference in survival times. After 17 hours, lungs subjected to pulmonary-bronchial artery perfusion survived longer than those perfused via either the pulmonary or bronchial arteries alone (120 +/- 24 versus 38 +/- 14 or 52 +/- 16 minutes; p less than 0.01). Pulmonary artery pressure and resistance in all groups except at failure were never different from baseline values in the intact animal. Shunts in the pulmonary-bronchial artery perfusion groups were closest to baseline at onset (8% +/- 4%) and remained lower throughout reperfusion than in the groups subjected to pulmonary or bronchial artery perfusion alone. After 17 hours, static compliance of pulmonary artery-perfused lungs was worse than baseline (1.1 +/- 0.2 x 10(-2) versus 3.2 +/- 0.7 x 10(-2) L/cm H2O/sec; p less than 0.05), whereas compliance in the pulmonary-bronchial artery perfusion groups remained constant (3.6 +/- 1.5 x 10(-2) L/cm H2O/sec). Elastic work performed by lungs subjected to pulmonary-bronchial artery flushing at onset was significantly lower when these lungs were reperfused immediately (201 +/- 14 versus 295 +/- 35 gm-m/min for pulmonary artery-flushed lungs) or after 4 hours of storage (229 +/- 30 versus 290 +/- 24 gm-m/min for pulmonary artery-flushed lungs). Bronchoalveolar lavage after 17 hours in the group subjected to pulmonary bronchial artery flushing demonstrated leukocyte counts similar to those of intact lungs (45 +/- 5 versus 29 +/- 8/mm3) and significantly less than in lungs subjected to pulmonary or bronchial artery flushing (137 +/- 18 or 82 +/- 10/mm3, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

[A comparison of three different techniques for measuring glomerular filtration rate].

The clearance of inulin, creatinine and radioactive tracers from the blood may be used to measure glomerular filtration rate (GFR). These techniques, however, are usually invasive and time-consuming. Although the clearance of a radioactive tracer is usually applied in nuclear medicine for the determination of GFR, it is also possible to convert the concentration of the tracer in the kidneys to absolute GFR by means of a regression equation. As this new technique is much faster, we have compared it with the conventional technique. A good correlation was found with the standard radionuclide techniques (r = 0.91), but the reference method was under-estimated on the average by 14 ml/min. The new regression equation derived in our clinic will ensure future accurate GFR measurements within 6 minutes.

Chromium Radioisotopes

Cystocerebral syndrome. Acute urinary retention presenting as confusion in elderly patients.

The diagnosis of acute mental status changes in the elderly patient is often very difficult. Many causes are possible, and there is often little history obtainable. The physical examination occasionally provides the essential clues needed to discover the source of the sudden deterioration. We have recently evaluated four episodes of acute delirium in three elderly patients who presented with no readily apparent cause for these changes. On further evaluation, the patients were found to have marked bladder distention associated with acute urinary retention. None of these patients complained of discomfort, and none had any awareness or recollection of their deterioration. Each patient had rapid resolution of symptoms on bladder decompression. To our knowledge, this "cystocerebral syndrome" has not been previously described, and we suggest that it be considered in the evaluation of acute confusional states in elderly men.

Aged

The TAPS Project. 4: An observational study of the social life of long-stay patients.

Observations of long-stay patients in a club in a psychiatric hospital were carried out unobtrusively over several months. Much of the social activity that went on was stimulated by an economy based around the purchase and exchange of tea and cigarettes, and the borrowing and lending of small change. Most patients could be fitted into one of four social categories: helpers, friends, nuisances, and the asocial. The inter-rater reliability of the observations was found to be 0.95. A close correspondence emerged between the observations of patients' social behaviour and material reported by patients when interviewed with the Social Network Schedule.

Humans