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Biomedical subjects

W Bell

Publications and source records attributed to W Bell.

At least 55 records · Page 3Linked to original sources

Effect of extracorporeal membrane oxygenation on platelets in newborns.

OBJECTIVES: To examine the effect of extracorporeal membrane oxygenation (ECMO) therapy on platelet function and number and to determine the in vivo survival of transfused platelets during ECMO. DESIGN: Prospective study of all neonates treated with ECMO during a 6-month period. SETTING: Neonatal intensive care unit in a tertiary referral center. PATIENTS: Ten infants, < 1 wk of age, with respiratory failure requiring ECMO. INTERVENTIONS: None. MEASUREMENTS: Platelet counts were measured at timed intervals to determine the effect of ECMO on platelet counts. The change in platelet counts after transfusion was also measured. Whole blood platelet aggregation studies were performed to determine the effect of ECMO on platelet function. MAIN RESULTS: A mean decrease of 26% from the baseline platelet count was found 15 mins after the initiation of ECMO, with an additional mean decrease of 16% by the end of 1 hr (p < .05). Fifteen minutes after platelet transfusions, a 17% mean increase in platelet counts was measured (p < .05). One hour after platelet transfusion, the platelet count had decreased to pretransfusion values. Platelet aggregation studies 15 mins after starting ECMO showed a 46% mean decrease in the response to collagen from baseline (p > .05), and a significantly (p < .05) reduced response to ristocetin and to adenosine 5'-diphosphate. Platelet adenosine triphosphate release was also significantly reduced. Single-unit platelet transfusions failed to correct platelet aggregation abnormalities. Resolution of platelet aggregation abnormalities and normalization of platelet counts occurred 8 hrs off ECMO. CONCLUSIONS: The results of these studies show that qualitative and quantitative platelet changes occur while a neonate is receiving ECMO. The survival rate of transfused platelets is reduced, and the acquired platelet dysfunction is not reversed by the transfusion of platelets with normal function while the patient is receiving ECMO.

Adenosine Triphosphate↗

Behavioural problems associated with the chronic fatigue syndrome.

Disturbances of memory, concentration and motor function are often reported by patients with the chronic fatigue syndrome (CFS). The present study objectively evaluated these behavioural problems using a computerized test battery measuring memory, attention and motor skills. Fifty-seven CFS patients were compared with 19 matched controls and all subjects completed the performance test battery and filled in questionnaires measuring psychopathology and mood. The patients reported significantly higher levels of depression, anxiety, physical symptoms and cognitive failures than the controls. Similarly, they reported more negative affect at the time of testing. The patients were slower on psychomotor tasks, showed increased visual sensitivity and impaired attention. Digit span and free recall were not impaired but retrieval from semantic memory and logical reasoning were slower. None of the performance differences between patients and controls could be attributed to differences in psychopathology. These results agree with recent findings from other laboratories, and it is now time to consider the nature of the neurological dysfunction underlying these effects.

Adult↗

The 70-kilodalton heat-shock proteins of the SSA subfamily negatively modulate heat-shock-induced accumulation of trehalose and promote recovery from heat stress in the yeast, Saccharomyces cerevisiae.

In the yeast, Saccharomyces cerevisiae, the disaccharide trehalose is a stress-related metabolite that accumulates upon exposure of cells to heat shock or a variety of non-heat inducers of the stress response. Here, we describe the influence of mutations in individual heat-shock-protein genes on trehalose metabolism. A strain mutated in three proteins of the SSA subfamily of 70-kDa heat-shock proteins (hsp70) overproduced trehalose during heat shock at 37 degrees C or 40 degrees C and showed abnormally slow degradation of trehalose upon temperature decrease from 40 degrees C to 27 degrees C. The mutant cells were unimpaired in the induction of thermotolerance; however, the decay of thermotolerance during recovery at 27 degrees C was abnormally slow. Since both a high content of trehalose and induced thermotolerance are associated with the heat-stressed state of cells, the abnormally slow decline of trehalose levels and thermotolerance in the mutant cells indicated a defect in recovery from the heat-stressed state. A similar albeit minor defect, as judged from measurements of trehalose degradation during recovery, was detected in a delta hsp104 mutant, but not in a strain deleted in the polyubiquitin gene, UB14. In all our experiments, trehalose levels were closely correlated with thermotolerance, suggesting a thermoprotective function of trehalose. In contrast, heat-shock proteins, in particular hsp70, appear to be involved in recovery from the heat-stressed state rather than in the acquisition of thermotolerance. Cells partially depleted of hsp70 displayed an abnormally low activity of neutral trehalase when shifted to 27 degrees C after heat shock at 40 degrees C. Trehalase activity is known to be under positive control by cAMP-dependent protein kinases, suggesting that hsp70 directly or indirectly stimulate these protein-kinase activities. Alternatively, hsp70 may physically interact with neutral trehalase, thereby protecting the enzyme from thermal denaturation.

Glucose↗

Characterization of the 56-kDa subunit of yeast trehalose-6-phosphate synthase and cloning of its gene reveal its identity with the product of CIF1, a regulator of carbon catabolite inactivation.

Trehalose-6-phosphate synthase is the key enzyme for biosynthesis of trehalose, the major soluble carbohydrate in resting cells of yeast. This enzyme was purified from a strain of Saccharomyces cerevisiae lacking vacuolar proteases. It was found to be a multimeric protein of 630 kDa. Monoclonal antibodies were raised against its smallest subunit (56 kDa) and used for screening a yeast cDNA library. This yielded an immunopositive cDNA clone of 1.7 kb, containing an open reading frame of 1485 base pairs. Its sequence, called TPS1 (for trehalose-6-phosphate synthase), was represented by a single gene in the yeast genome and was found to be almost identical with the recently sequenced CIF1, a gene important for carbon catabolite inactivation, believed to be allelic with FDP1. A mutant obtained by disruption of TPS1 had a very low activity of trehalose-6-phosphate synthase, indicating that TPS1 is an important component of the enzyme. The mutant also showed a growth defect when transferred from glycerol to glucose, a phenotype similar to that of the cif1 and fdp1 mutants deficient in carbon catabolite inactivation. Thus, the smallest subunit of the biosynthetic enzyme trehalose-6-phosphate synthase appears to have, in addition, a central regulatory role in the carbohydrate metabolism of yeast.

Amino Acid Sequence↗

Synthesis and structure-activity relationships of cephalosporins with C-3' catechol-containing residues.

Cephalosporins with new catechol substituents at C-3' have been synthesized, including novel compounds with C-3' carbon-carbon bonds. Many of these compounds have high potency against Gram-negative bacteria, in particular against resistant strains like Pseudomonas aeruginosa. Structure-activity relationships are discussed in terms of their dependence on the pKa of the C-3' catechol and also in terms of steric and conformational factors of the C-3' substituent. The best overall properties were found in compounds with a bulky and/or conformationally restricted acidic C-3' catechol.

Animals↗

Factor XI deficiency acquired by liver transplantation.

Factor XI deficiency (the Rosenthal syndrome), an autosomal recessive genetic defect, was transmitted to a patient after orthotopic liver transplantation. The deficiency was manifested by an isolated prolonged activated partial thromboplastin time (aPTT) after surgery. Hematologic evaluation using specific factor analysis revealed an absolute deficiency of factor XI. Stored serum obtained from the organ recipient before transplantation showed normal factor XI levels. When the liver donor's family was questioned, it was discovered that he was of Ashkenazi Jewish descent and that he had a history of bleeding after dental procedures. Before his death from intracerebral bleeding, he was documented to have an isolated prolonged aPTT value. This case shows that potentially morbid genetic defects can be transmitted by organ transplantation. It also provides evidence confirming that the liver is the only site of factor XI production.

Factor XI Deficiency↗

Platelet aggregation in hyperapobetalipoproteinemia.

Hyperapobetalipoproteinemia (HyperapoB) is a lipid disorder characterized by premature coronary disease, although the mechanisms have not been elucidated. Because abnormalities in platelet function may represent an enhanced susceptibility to coronary thrombosis, the aggregability of platelets was examined in hyperapoB subjects. Compared to controls, there were no significant differences in either platelet lipid composition or in aggregation to epinephrine, ADP, or collagen. In contrast to other dyslipidemias, platelet function does not appear to be abnormal in this well defined lipid disorder.

Adult↗

Stroke in the young. (Part I).

We have discussed some of the more common etiologic categories found in young patients with stroke. Though many of the causes are rare, in the aggregate they account for many of the conditions leading to stroke. In Part II of this series (July 1991), we will explore some of the less common causes of stroke in the young and outline an approach to the patient.

Adolescent↗

Stroke in the young. Part II.

Evaluation of the young stroke patient often requires an interdisciplinary approach because of the complexity of the problems encountered. We discuss some of the less common causes of stroke and present an approach to the patient.

Adolescent↗

Effects of 1 alpha, 25-dihydroxyvitamin D3 on the human chronic myelogenous leukemia cell line RWLeu-4.

The effects of 1 alpha, 25-dihydroxyvitamin D3 (VD3) on proliferation, differentiation, and macromolecular synthesis in the new Philadelphia chromosome-positive chronic myelogenous leukemia cell line, RWLeu-4, were investigated. Binding of [3H]VD3 was saturable, with approximately 2000-3000 sites/cell, and half-maximal binding occurring at 0.21-0.33 nM. Treatment of RWLeu-4 cells with VD3 induced 24R-hydroxylase activity, a marker of vitamin D3 responsiveness in many tissues. Exposure of RWLeu-4 cells to VD3 also inhibited proliferation and DNA synthesis with a 50% effective dose of 3.5-10 nM within 72 h; in addition, protein and RNA synthesis were inhibited by VD3 treatment. Exposure of RWLeu-4 cells to 5 nM VD3 for 72 h caused 50% of the cells to differentiate into macrophage/monocyte type cells as judged by nitroblue tetrazolium staining and adherence to plastic. Progressive expression of cell surface maturation-specific antigens of the monocyte/macrophage lineage was induced by treatment of RWLeu-4 cells with VD3 for 24 to 72 h at doses that inhibited cellular proliferation. c-myc RNA, which is constitutively expressed in RWLeu-4 cells, increased after 0.5 h of treatment with 50 nM VD3 and then rapidly decreased to barely detectable levels after 4 h of treatment. Finally, the in vitro tyrosine kinase activity associated with the p210bcr-abl oncogene product was decreased approximately 50% by VD3 treatment. Because of the presence of a functional receptor-effector system for VD3 and multiple biological responses to the hormone, these cells provide a unique model system with which to probe the specific effects of VD3 on cell growth and differentiation in chronic myelogenous leukemia.

Calcitriol↗

Specific identification of fibrin(ogen) degradation products in plasma and serum using blotting and peroxidase labeled antiserum.

We describe a method for identifying fibrinogen and fibrin split products using electrophoresis on agarose gel with sodium dodecyl sulfate (SDS) followed by blotting in nitrocellulose paper. Detection of these derivatives after blotting is accomplished with peroxidase-conjugated rather than by isotopically labeled antibodies. This technique can detect diverse fibrinogen derivatives produced in vivo or in vitro by the combined action of thrombin, plasmin, and factor XIII. This methodology is applicable to plasma, serum, and other body fluids including urine and ascitic fluid. This sensitive and specific assay, distinguishing the products of cross-linked fibrin from those of fibrinogen and detecting fibrin polymers in plasma, can be achieved without the use of radioactivity.

Blood↗

Effectiveness of a method used in bonding resins to metal.

Currently, several methods are available for bonding resin veneers to dental casting alloys. Recently a new system (Silicoater) has been developed that involves the chemical bonding of polymers to dental substrates. This study determined bond strengths of several proprietary composite resin luting agents to three different types of casting alloys. The results were compared with those obtained using electrolytic etching techniques. The pyrogenically silica-treated specimens generated the highest bond strengths.

Acid Etching, Dental↗

The effect of back closure on detrusor function in neonates with myelomeningocele.

To determine the effect of back closure on the detrusor-external sphincter coordination, we reviewed the medical records of 40 neonates with myelodysplasia studied prospectively with urodynamic assessment and renal ultrasonography before closure of the spinal defect, within 7 days of closure and at 3-month intervals thereafter. Only 31 of the 40 neonates met all criteria for inclusion. All renal sonograms were normal before and after closure. Urodynamic evaluation demonstrated coordinated detrusor-sphincter activity in 18 neonates before and after closure. During prolonged followup 1 patient had detrusor areflexia and 4 had detrusor-sphincter dyssynergia. Of 11 neonates who demonstrated detrusor areflexia and no external sphincter activity before closure 10 were unchanged on initial post-closure evaluation (4 had detrusor-sphincter dyssynergia during followup), while 1 demonstrated detrusor areflexia with external sphincter overactivity and vesicoureteral reflux after closure. The latter patient subsequently had detrusor hyperreflexia, more severe reflux and upper tract deterioration. She was temporized with a cutaneous vesicostomy. One patient demonstrated detrusor-sphincter dyssynergia before closure and detrusor areflexia with no external sphincter activity after closure, the consequence of surgical division of the neural placode during back closure. The remaining patient demonstrated detrusor-sphincter dyssynergia before and after closure. This patient had coordinated detrusor-sphincter activity during followup. Those neonates who presented with or later had detrusor-sphincter dyssynergia were managed initially with neuropharmacological agents and clean intermittent catheterization. An unsuccessful outcome was managed by cutaneous vesicostomy. Our study demonstrates that neonatal closure of the spinal cord defect does not appear to affect detrusor-sphincter coordination adversely, and re-emphasizes the need for careful and regular followup in children with myelodysplasia to detect deterioration of the urinary tract.

Back↗

Co-morbidity: lessons learned about post-traumatic stress disorder (PTSD) from developing PTSD scales for the MMPI.

Results from efforts to develop and validate PTSD measures are promising, but a "gold standard" has not been achieved. Keane, Malloy, and Fairbank (1984) have developed an MMPI PTSD subscale that has been cross-validated with clinicians' classification of PTSD at acceptable levels of agreement, specificity, and sensitivity. There is, however, room for improvement. Empirical evidence is presented that indicates that the next round of efforts to increase reliability and validity of PTSD measures must account for the presence/absence of co-morbidity (i.e., the simultaneous occurrence of other psychiatric disorders). For example, differences are noted in MMPI group profiles and PTSD scales between psychiatric patients and substance abusers. Second, different MMPI items emerge as indicative of PTSD; these vary as a function of the presence of other Axis I disorders among groups of Vietnam combat veterans who seek treatment for substance abuse. Results substantiate that different MMPI items for classifying PTSD occur with groups that differ in co-morbidity. Improvements in PTSD scale development are more likely when the contributions of pre-existing or subsequently co-occurring psychiatric disorders are taken in account, as well as variations in level of personality maturity. The evidence suggests that a "family" of PTSD scales need to be developed that take into account co-morbidity differences.

Adaptation, Psychological↗

Ethnicity: post-traumatic stress disorder (PTSD) differences among black, white, and Hispanic veterans who differ in degrees of exposure to combat in Vietnam.

Clinical observations and empirical evidence suggest that, among Vietnam combat veterans, Blacks are more maladjusted than Whites (e.g., Parsons, 1985; Penk et al., 1985). The prediction that minority group status is associated with poorer post-war adjustment and higher rates of PTSD was examined among Vietnam combat veterans who were seeking treatment for addiction disorders. Adjustment scores among groups comparable in combat exposure were found to be similar for both Whites and Hispanics; Blacks, however, score significantly higher on both PTSD symptoms on MMPI scales. These findings indicate that ethnicity contributes importantly to PTSD in selected instances, but that minority group status alone does not account for observed differences. Additional research is indicated in which careful attention is given to the complicating and interacting role of addiction disorders in sampling.

Adaptation, Psychological↗

Depletion of white cells from platelet concentrates with a new adsorption filter.

Removal of white cells (WBCs) from platelets may reduce alloimmunization to WBC antigens, prevent febrile reactions, and improve platelet increments in multiply transfused patients receiving HLA-matched platelets. A new surface-modified fibrous polyester filter was evaluated; it requires no special processing of pooled platelet concentrates and can be used at the patient's bedside. The studies were designed to measure WBC removal, platelet function, in vitro platelet recovery, and in vivo platelet survival. WBC mean removal was 99.8 percent +/- 0.56 (n = 37) when a pool similar in volume to 6 platelet concentrates was tested. The mean number of residual WBCs after filtration was 5.6 x 10(5). In vitro mean platelet recovery was 86.9 percent for a pool size of 6 units (n = 37). Clot retraction and platelet aggregation were unaffected by filtration. Survival studies of 111Indium-labeled platelets done with filtered autologous platelets showed no reduction in the normally expected survival. These studies indicated that the filter efficiently removes WBCs without substantially decreasing platelet number, survival, or function. This device offers the potential of considerably improving platelet transfusion therapy.

Adsorption↗