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Biomedical subjects

D Kennedy

Publications and source records attributed to D Kennedy.

At least 19 recordsLinked to original sources
PubMed1992

Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris.

BACKGROUND AND METHOD: The role of thrombus formation in the pathogenesis of acute myocardial infarction (AMI) and unstable angina pectoris has been well established. However, comprehensive and systematic studies of the blood coagulation, fibrinolytic, and inhibitory proteins are not available in patients with these conditions. Fourteen patients with AMI, 10 patients with angina pectoris, and 32 normal volunteers were studied. Plasma antigen concentrations and/or activities of high-molecular-weight kininogen (HMWK), fibrinogen, fibronectin, plasminogen, D-dimer, tissue plasminogen activator (t-PA), alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, protein C, total and free protein S, antithrombin III (AT-III), von Willebrand factor (vWF), factors (F) XII, XI, IX, VIII, VII, X, V, II, and XIII, and plasma antiplasmin activity were measured using appropriate functional or immunologic assays. RESULTS: The AMI group showed a significant reduction in F XII activity, F XII activity-to-concentration ratio, and HMWK concentration. In addition, the AMI patients exhibited a significant elevation of plasma F XI activity, F IX concentration, and F IX activity, and vWF, fibrinogen, D-dimer, and t-PA concentrations. This was associated with significant reductions in F V, F II, and AT-III activity-to-concentration ratio. Many of the changes observed in AMI patients were also present in patients with angina pectoris. Furthermore, the latter group exhibited an elevation of F VIII activity, alpha 2-macroglobulin activity, and alpha 1-antitrypsin concentration and a significant reduction of antiplasmin activity despite a normal alpha 2-antiplasmin concentration. CONCLUSIONS: The observed reduction of the plasma F XII activity-to-antigen concentration ratio combined with a reduced HMWK concentration suggests intrinsic pathway activation, while the elevation of the D-dimer concentration indicates thrombin generation and fibrin formation and degradation in the AMI group. The latter changes were also present in patients with angina pectoris. Both AMI and angina groups showed several other abnormalities of the coagulation, fibrinolytic, and inhibitory systems. The results suggest the presence of a prothrombotic state associated with the activation of coagulation and fibrinolytic systems in patients with acute myocardial ischemia or infarction.

Adult↗
PubMed1992

Magnetic resonance imaging of body fat of athletes compared with controls, and the oxidative metabolism of estradiol.

The extent of 2-hydroxylation of estradiol (E2), which yields a non-estrogenic metabolite (2-OHE1), increased significantly with decreasing subcutaneous fat (ScF)/total volume percent (TV%) and total fat (TF)/TV% evaluated by magnetic resonance imaging (MRI) for five athletes during low- and high-intensity training, and four controls. The increase in 2-hydroxylation with decreasing adiposity was associated with anovulation and amenorrhea among the athletes.

Adipose Tissue↗
PubMed1992

Estimates of HIV infection among injecting drug users in Glasgow, 1985-1990.

OBJECTIVE: To use research and surveillance studies in Glasgow (Scotland, UK) to estimate the number of current injectors infected with HIV, the total number of injectors infected up to the end of 1990 and the recent incidence of infection. DESIGN: (A) Prevalence of injecting drug use was estimated using log-linear modelling. (B) Prevalence of HIV infection was determined from voluntary testing of a community-wide sample of injectors. (C) The number of infected current injectors was predicted by combining the distributions generated by (A) and (B). (D) Data on known HIV-positive injectors were used in conjunction with (C) to forecast the cumulative number of infected injectors. RESULTS: The number of current injectors was estimated to be 9400; the prevalence of HIV infection among 447 injectors recruited to the HIV prevalence study during 1990 was 1.1%. From these data, the number of HIV-positive current injectors in 1990 was estimated to be between 52 and 138. Between 1985 and 1990, 110 known HIV-positive injectors were registered or received treatment in Glasgow for HIV-related diseases; the total number of cases estimated to have occurred during this period was between 110 and 300. The incidence of infection in Glasgow during 1990 was likely to have been low in light of the finding that only one case in the prevalence study had not previously been diagnosed HIV-positive. CONCLUSIONS: Linkage of datasets from a variety of sources and studies has enabled the substantial refinement of estimates of the number of injectors and the proportion infected with HIV in Glasgow up to 1990.

Adolescent↗
PubMed1992

Transvaginal intra-abdominal impalement injury.

Impalement injuries due to sexual activity are highly unusual and variable. We have described a case of transvaginal impalement injury of the rectum, bladder, omentum, and mesentery manifested by vaginal bleeding. The patient could not recount how she had been injured. Management of such an injury requires extensive initial evaluation and a multidisciplinary approach to therapy.

Abdominal Injuries↗
PubMed1992

Diagnosis of Pneumocystis carinii pneumonia by multiple lobe, site-directed bronchoalveolar lavage with immunofluorescent monoclonal antibody staining in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis.

The yields of both induced sputum examination and bronchoalveolar lavage (BAL) have been reported to be decreased for breakthrough episodes of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis. This study assessed whether the yield of a single middle or lower lobe BAL could be increased by the utilization of two techniques: (1) indirect immunofluorescent staining with a combination of two murine monoclonal anti-Pneumocystis antibodies in addition to routine toluidine blue O and cytopathologic staining, and (2) the performance of multiple lobe, site-directed BAL (i.e., both upper lobe and middle or lower lobe lavage, including the lobe with the greatest radiographic abnormality). Results of 252 fiberoptic bronchoscopies performed at the National Institutes of Health and the Los Angeles County-University of Southern California Medical Center were analyzed. P. carinii pneumonia was documented in 21 episodes in patients who did not receive prior anti-Pneumocystis chemoprophylaxis and in 41 episodes in patients who received aerosolized pentamidine. Monoclonal antibody staining and multiple lobe, site-directed BAL resulted in similar diagnostic yields for P. carinii in the nonprophylaxis (100%) and aerosolized pentamidine (98%) groups. If BAL had been performed without monoclonal antibody staining and multiple lobe, site-directed lavage, then the yield would have decreased to 95% in the nonprophylaxis group and to 80% in the aerosolized pentamidine group.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1991

cAMP-inducible chloride conductance in mouse fibroblast lines stably expressing the human cystic fibrosis transmembrane conductance regulator.

A cAMP-inducible chloride permeability has been detected in mouse fibroblast (L cell) lines upon stable integration of a full-length cDNA encoding the human cystic fibrosis transmembrane conductance regulator (CFTR). As indicated by a Cl(-)-indicator dye, the Cl- permeability of the plasma membrane increases by 10- to 30-fold within 2 min after treatment of the cells with forskolin, an activator of adenylyl cyclase. The properties of the conductance are similar to those described in secretory epithelial cells; the whole-cell current-voltage relationship is linear and there is no evidence of voltage-dependent inactivation or activation. In contrast, this cAMP-dependent Cl- flux is undetectable in the untransfected cells or cells harboring defective cDNA constructs, including one with a phenylalanine deletion at amino acid position 508 (delta F508), the most common mutation causing cystic fibrosis. These observations are consistent with the hypothesis that the CFTR is a cAMP-dependent Cl- channel. The availability of a heterologous (nonepithelial) cell type expressing the CFTR offers an excellent system to understand the basic mechanisms underlying this CFTR-associated ion permeability and to study the structure and function of the CFTR.

Animals↗
PubMed1991

Crystallization and preliminary X-ray studies of annexin IV (endonexin), a calcium-dependent phospholipid-binding protein.

Annexin IV (endonexin) has been purified from chicken liver and crystallized by the vapour diffusion method. Crystals which diffract to at least 2.2 A have been obtained. They belong to space group R3 and have unit cell dimensions of a = b = 99.4 A, c = 96.2 A, alpha = 90 degrees, beta = 90 degrees, gamma = 120 degrees. There is one molecule of 32,500 Da per asymmetric unit.

Animals↗
PubMed1991

Susceptibility contrast imaging of cerebral blood volume: human experience.

Magnetic resonance (MR) can offer a unique window on the structure/function relationships in the brain, by utilizing the established link between tissue function, metabolism, and hemodynamics. This report focuses on recent applications of MR-based cerebral blood volume (CBV) imaging in humans. Our methodology uses high-speed "single-shot" or echo planar imaging techniques, which provide the necessary temporal resolution for mapping the rapid cerebral transit of contrast agents. These MR CBV mapping techniques have been used to study normal human brain task activation and in the clinical study of patients with brain tumors. In the latter, positron emission tomography imaging was used for functional metabolic and CBV correlation. Susceptibility contrast CBV imaging should allow us to improve our understanding of the relationship between the detailed physiology and morphology of the microvascular bed and functional attributes of the brain. These techniques can be applied to understanding fundamental questions of cognitive neuroscience and can aid in improving diagnostic sensitivity and specificity in various neuropathologies.

Brain↗
PubMed1991

A second neutralizing epitope of B19 parvovirus implicates the spike region in the immune response.

We used 18 monoclonal antibodies against B19 parvovirus to identify neutralizing epitopes on the viral capsid. Of the 18 antibodies, 9 had in vitro neutralizing activity in a bone marrow colony culture assay. The overlapping polypeptide fragments spanning the B19 structural proteins were produced in a pMAL-c Escherichia coli expression system and used to investigate the binding sites of the neutralizing antibodies. One of the nine neutralizing antibodies reacted with both VP1 and VP2 capsid proteins and a single polypeptide fragment on an immunoblot, identifying a linear neutralizing epitope between amino acids 57 and 77 of the VP2 capsid protein. Eight of nine neutralizing antibodies failed to react with either of the capsid proteins or any polypeptide fragments, despite reactivities with intact virions in a radioimmunoassay, suggesting that additional conformationally dependent neutralizing epitopes exist.

ATP-Binding Cassette Transporters↗
PubMed1991

An interactive perspective on the health beliefs & practices of rural elders.

1. In this study, major themes involving health were closely tied to an affective response of "feeling good" and cognitive appraisal of health status as "being able to function." 2. Rural elderly who participated in the study reported engaging in at least one activity to maintain their health and tended to rely on their own appraisal and resources to manage health problems. 3. Half of the participants indicated a need for services such as blood pressure and diabetic screening, health education classes on diet, cholesterol reduction, hypertension and diabetes management, new therapies in health care, and life management counseling.

Aged↗
PubMed1990

Direct angioplasty of the basilar artery in baboons.

The lower portion of the basilar artery is a site of significant disease, both aneurysmal and stenotic, but has been considered inaccessible via traditional surgical approaches. A baboon model was used to evaluate the feasibility of a direct surgical reconstruction via a transoral-transclival approach, utilizing temporary occlusion of the basilar artery. An arteriotomy was performed and either repaired primarily or a venous patch graft was sutured in place. All animals survived the surgery; one suffered fatal postoperative upper airway obstruction, but the other four were neurologically intact at the time of death. Patency at the site of repair was confirmed both angiographically and histologically. We conclude that temporary clamping in conjunction with direct reconstruction of the basilar artery is feasible in this primate model. Future studies will focus on further applications of this technique.

Animals↗
PubMed1990

Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene.

Additional mutations in the cystic fibrosis (CF) gene were identified in the regions corresponding to the two putative nucleotide (ATP)-binding folds (NBFs) of the predicted polypeptide. The patient cohort included 46 Canadian CF families with well-characterized DNA marker haplotypes spanning the disease locus and several other families from Israel. Eleven mutations were found in the first NBF, 2 were found in the second NBF, but none was found in the R-domain. Seven of the mutations were of the missense type affecting some of the highly conserved amino acid residues in the first NBF; 3 were nonsense mutations; 2 would probably affect mRNA splicing; 2 corresponded to small deletions, including another 3-base-pair deletion different from the major mutation (delta F508), which could account for 70% of the CF chromosomes in the population. Nine of these mutations accounted for 12 of the 31 non-delta F508 CF chromosomes in the Canadian families. The highly heterogeneous nature of the remaining CF mutations provides important insights into the structure and function of the protein, but it also suggests that DNA-based genetic screening for CF carrier status will not be straightforward.

Adenosine Triphosphate↗
PubMed1990

Calcitonin inhibits thyrotropin-releasing hormone-induced increases in cytosolic Ca2+ in isolated rat anterior pituitary cells.

Calcitonin (CT) and related peptides, such as CT gene-related peptide and salmon CT (sCT)-like peptide, are present in the rat nervous system and the pituitary gland, and sCT markedly inhibits basal and TRH-stimulated PRL release from anterior pituitary (AP) cells. Because TRH-induced PRL release is known to involve increases in cytosolic free Ca2+ derived from both extracellular and intracellular sources, the objective of the present study was to test whether sCT interferes with this effect. Secretogogue-induced elevations of cytosolic free Ca2+ ([Ca2+]i) in acutely dispersed AP cells were monitored using the fluorescent Ca2+ indicator Indo-1 AM and flow cytometry. AP cells were enzymatically dispersed to single cell suspensions and loaded with 20 microM Indo-1 AM for 30 min. Indo-1-loaded AP cells were scanned at a rate of approximately 500 cells/sec for 200-300 sec in a flow cytometer, and the ratio of fluorescence due to Ca2+ bound to Indo-1 to free Indo-1 (Indo-1 ratio), which is an index of [Ca2+]i, was determined for each cell. Under basal conditions, AP cells showed stable Indo-1 ratios during the scans, and 100% of the cells responded to the Ca2+ ionophore ionomycin with increases in the Indo-1 ratio. Approximately 25-30% of the AP cells responded to a 1 microM pulse of TRH with marked increases in the Indo-1 ratio, indicative of increases in [Ca2+]i, with the response consisting of two phases, an initial rapid rise that was unaffected by the presence of EGTA in the extracellular environment, followed by a decrease to a sustained secondary phase that was completely eliminated by EGTA. In a normal extracellular Ca2+ environment, pretreatment with 100 nM sCT almost totally inhibited the response to 1 microM TRH. In EGTA-pretreated AP cells, the initial EGTA-insensitive phase of the TRH-induced [Ca2+]i increase was also abolished by prior exposure to sCT. These results suggest that sCT inhibits TRH-stimulated PRL release in AP cells by attenuating the TRH-induced increase in [Ca2+]i, an effect that probably occurs as a consequence of inhibition of the stimulatory effect of TRH on the Ca2+/phospholipid messenger system.

Animals↗