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Biomedical subjects

R Hawkins

Publications and source records attributed to R Hawkins.

At least 55 records · Page 3Linked to original sources

Integrin-mediated epithelial-T cell interaction enhances nitric oxide production and increased intracellular inhibition of Chlamydia.

T cell-mediated immunity against Chlamydia in mice is mediated at least in part by T cell-derived interferon-gamma (IFN-gamma) induction of the nitric oxide synthase (iNOS) system in infected epithelial cells. Although IFN-gamma alone could stimulate nitric oxide (NO) production from epithelial cells and inhibit the intracellular growth of Chlamydia, the effectiveness was less than when infected epithelial cells were co-cultured with IFN-gamma-producing T cell clones. In co-cultures containing T cells and infected epithelial cells, additional NO produced by activated T cells could augment chlamydial killing; however, T cell-derived NO was insufficient to account for the total NO present in the co-culture and therefore could not explain the dramatic increase in chlamydial inhibition under those conditions. To determine whether direct cell-to-cell interaction involving adhesion molecules was involved in increased NO induction, the ability of neutralizing monoclonal antibodies directed against intercellular adhesion molecule type 1 (ICAM-1) and leukocyte function antigen-1 (LFA-1) to suppress NO production and lower intracellular chlamydial inhibition was investigated. It was found that monoclonal antibodies against ICAM-1/LFA-1 could significantly reduce the capacity of a protective CD4+ type 1 (Thl) clone (clone 2.14-0) to inhibit the intracellular growth of the C. trachomatis agent of mouse pneumonitis (MoPn). The suppression of the anti-chlamydial action of the clone by antibodies correlated with approximately 50% decrease in NO production. Also, paraformaldehyde-fixed clone 2.14-0 could enhance NO induction and chlamydial inhibition mediated by IFN-gamma, and this effect could be reversed by anti-ICAM-1/LFA-1 antibodies. The results indicated that epithelial-T cell interaction via adhesion molecules enhances NO production and increased chlamydial inhibition by IFN-gamma-secreting T cells.

Animals↗

Rehabilitation of the shoulder.

Rehabilitation of the shoulder has undergone significant changes during the past few years due to many clinical and basic science projects that have taught us about biomechanics of the shoulder. The athlete's shoulder is a particularly good model to allow us an understanding related to rehabilitation for treatment of injuries, injury prevention and performance enhancement. A comprehensive rehabilitation program for athletes can be based on these clinical and basic science principles to aid in our understanding of rehabilitation for shoulders in general.

Athletic Injuries↗

A high efficiency method for purification and assay of bee venom phospholipase A2.

Phospholipase A2 (PLA2) is the main allergen of hymenopteran venoms. We describe a highly efficient reverse phase high performance liquid chromatographic method (HPLC) for isolating PLA2 from crude bee venom. This method removes all detectable contaminants such as melittin from PLA2 while preserving the hemolytic action of PLA2. In addition we describe a simple functional assay of PLA2 based on its propensity to cause hemolysis of guinea pig red blood cells. These techniques are particularly well suited to the isolation and assessment of PLA2 of venoms which are available in limited quantities.

Animals↗

A quantitative physiologic model of blood oxygenation for functional magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Variations in venous deoxyhemoglobin levels in response to neuronal activation represent a complex interplay between focal changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and regional metabolism. The authors present a mathematic model that characterizes the response of venous oxygenation to changes in these variables. METHODS: Using a mass balance approach, the equations for a simple input-output model are derived and solved using Matlab. Changes in blood oxygenation are related to available results from functional magnetic resonance imaging experiments. RESULTS: Increases in CBF produce declines in oxygen extraction fraction and venous deoxyhemoglobin according to Fick's law, and are quantitatively in agreement with available magnetic resonance and positron-emission tomography data. A flow-volume envelope defines the changes in CBF relative to CBV. CONCLUSIONS: It is possible to obtain a quantitative understanding of changes in blood oxygenation and to relate these changes to the observed dynamics of magnetic resonance signal change in the setting of functional stimulation.

Algorithms↗

Variable-dose patient-controlled analgesia. A preliminary report.

One size of patient-controlled analgesia demand dose does not suit all patients after surgery. We have constructed a new patient-controlled analgesia (variable-dose patient-controlled analgesia) in which patients have a choice of demand dose sizes. In an initial trial, patients could choose between 0.5, 1.0 or 1.5 mg morphine. Patients readily understood the system and were all 'satisfied' (n = 1) or 'very satisfied' (n = 9) with the system. Only two patients sought 'complete relief' from pain, most reported seeking 'moderate relief'. All patients obtained a 'lot of relief' or 'complete relief' with this patient-controlled analgesia system. This preliminary experience suggests that variable dose patient-controlled analgesia warrants further investigation and comparison with conventional patient-controlled analgesia.

Analgesia, Patient-Controlled↗

Serum antibody to lipopolysaccharide antigens of Shigella species among U.S. military personnel deployed to Saudi Arabia and Kuwait during Operations Desert Shield and Desert Storm.

During Operations Desert Shield and Desert Storm, U.S. troops were at high risk of diarrheal disease due to Shigella spp., particularly Shigella sonnei. In order to better understand the serologic response to Shigella infection, 830 male U.S. combat troops were evaluated before and after the deployment to Saudi Arabia and Kuwait for immunoglobulin A (IgA) and IgG anti-Shigella lipopolysaccharide (LPS) (antibody to S. sonnei form I and Shigella flexneri serotypes 1a, 2a, and 3a) in serum. Just before deployment, 10.3% of the subjects were seropositive for IgA and 18.3% were positive for IgG anti-Shigella LPS. IgA and IgG anti-LPS antibody levels in serum prior to deployment were significantly associated with nonwhite race and ethnicity, birth outside the United States, and antibody to hepatitis A virus and Helicobacter pylori. During the deployment, which lasted for a mean of 131 days, 60% of the subjects reported at least one episode of diarrhea and 15% reported an episode of diarrhea with feverishness; also, 5.5% of the subjects exhibited IgA seroconversion to Shigella LPS and 14.0% exhibited IgG seroconversion. A significant association between the development of diarrheal symptoms and either positive predeployment anti-LPS antibody or seroconversion was not found. These data indicate that in this population of U.S. Desert Storm troops who were at high risk of Shigella infection, there was no apparent relation between IgA or IgG anti-Shigella LPS in serum and diarrheal disease.

Adolescent↗

The risk of Helicobacter pylori infection among U.S. military personnel deployed outside the United States.

To determine whether military personnel deployed outside the United States are at increased risk of Helicobacter pylori infection, 1,000 male U.S. Navy and Marine Corps personnel (mean age 22 years) were evaluated. Study subjects included 200 recruits, 500 shipboard personnel deployed for six months to South America, West Africa, and the Mediterranean, and 300 ground troops deployed for five months to Saudi Arabia. Among all 1,000 subjects, 247 (25%) were seropositive for H. pylori IgG antibody by an enzyme-linked immunosorbent assay; 24% of new recruits and 25% of troops who had been on active duty for a mean of four years. The prevalence of H. pylori antibody was higher among subjects who were older, nonwhite, foreign-born, and seropositive for antibody to hepatitis A virus. Among the 601 initially seronegative subjects evaluated before and after a 5-6 month deployment outside the United States, five seroconverted, for a rate of infection of 1.9% per person-year of exposure. As found in other populations in developed countries, these data indicate that among U.S. military personnel a large proportion of H. pylori infections occur before adulthood and infection is related to demographic factors. These preliminary findings also suggest that deployed U.S. military personnel may be at increased risk of H. pylori infection compared with adult populations in developed countries either from exposure in developing countries or from crowding.

Adolescent↗

Myocardial viability in asynergic regions subtended by occluded coronary arteries: relation to the status of collateral flow in patients with chronic coronary artery disease.

OBJECTIVES: This study aimed to determine whether angiographically visualized collateral vessels in patients with chronic coronary artery disease imply the presence of viable myocardium in asynergic regions subtended by completely occluded coronary arteries. BACKGROUND: Patients with chronic coronary artery disease who are being considered for revascularization frequently exhibit angiographically visualized collateral vessels to completely occluded coronary arteries supplying severely asynergic myocardial regions. However, little is known about the relation between angiographic collateral flow and myocardial viability in these patients. METHODS: We studied 42 patients with 78 completely occluded coronary arteries supplying asynergic territories. Angiographic collateral vessels were interpreted as absent (grade 1) in 14 patients, minimal (grade 2) in 27 and well developed (grade 3) in 37. Myocardial viability was determined with positron emission tomography using nitrogen-13 (N-13) ammonia and fluorine-18 (F-18) deoxyglucose for assessment of regional perfusion and glucose uptake, respectively. Positron emission tomographic patterns were interpreted as mismatch (perfusion defect with enhanced F-18 deoxyglucose uptake); transmural match (severe concordant reduction or absence of both perfusion and F-18 deoxyglucose uptake) or nontransmural match (mild to moderate concordant reduction of both perfusion and F-18 deoxyglucose uptake). RESULTS: There was no significant correlation (p = 0.14) between the severity of perfusion deficit assessed by positron emission tomography and the collateral grade. The extent of mismatch was unrelated to either the presence or the magnitude of collateral vessels. Conversely, with increasing collateral vessels from grade 1 to 3, the total extent of positron emission tomographic match remained similar, whereas the ratio of transmural to nontransmural match decreased. Myocardial viability was usually present in severely hypokinetic regions (82%). It was lower in akinetic-dyskinetic regions (49%). Of the 64 regions with angiographic collateral vessels, 37 (58%) (95% confidence interval [CI] 46% to 70%) showed positron emission tomographic mismatch. In contrast, 7 (50%) of 14 (95% CI 24% to 76%) regions without collateral vessels on angiography exhibited positron emission tomographic mismatch. The presence of angiographically visualized collateral vessels was a sensitive (84%) but not specific (21%) marker of viability. CONCLUSIONS: In patients with chronic coronary artery disease, angiographically visualized collateral vessels to asynergic myocardial regions subtended by occluded coronary arteries do not always imply the presence of viable myocardium, suggesting that revascularization may not always provide a functional benefit.

Adult↗

Modulation of thrombospondin expression during differentiation of embryonal carcinoma cells.

The thrombospondins (TSPs) are a family of extracellular glycoproteins that display distinct patterns of temporal and spatial expression during development. In this study, we investigated the expression of two of the TSPs--TPS1 and TSP2--during the course of differentiation of embryonal carcinoma cells in vitro. We report that both TSP1 and TSP2 mRNA and protein synthesis are induced during the differentiation of P19EC cells into neurons, glial cells, and fibroblasts. Immunofluorescence studies indicate that TSP1 displays a fibrillar pattern of staining, characteristic of an extracellular matrix protein, in differentiated P19EC cells. In contrast, TSP2 is cell-associated and is present on differentiated P19EC cells and on primary neurons and glial cells obtained from a 17-day embryonic mouse cerebral cortex. Interestingly, although both TSP1 and TSP2 are more prevalent in areas of differentiated cells, they display distinct patterns of deposition. These observations suggest that TSP1 and TSP2 may function differently during neurogenesis. The response of TSP1 and TSP2 to differentiation of P19EC cells indicates that this cell system will serve as a valuable model for the study of TSP expression and function during neurogenesis.

Amino Acid Sequence↗

Positron emission tomography diagnosis of pulmonary metastases in osteogenic sarcoma.

Positron emission tomography (PET) is an imaging technique that can produce high-quality tomographic images reflective of the metabolic characteristics of imaged tissue. Among the many positron-emitting tracers utilized in conjunction with PET is [18F]fluoride ion; it is actively taken up in bone in proportion to bone metabolic activity, analogous to standard nuclear medicine bone scanning agents such as technetium methylenediphosphonate ([99mTc]MDP). Whole-body imaging with PET and [18F]fluoride ion generates tomographic images that are useful in mapping patterns of bone metabolism, as well as identifying extraosseous site of bone formation or calcification. We report the case of a patient with polyostotic fibrous dysplasia, metastatic osteogenic sarcoma, and a breast mass, who presented with pulmonary nodules, in whom [18F] fluoride ion/PET imaging was useful in confirming the nature of the pulmonary nodules.

Adult↗

A comparative study of intravenous versus intralymphatic interleukin-2, with assessment of effects of interleukin-2 on both peripheral blood and thoracic-duct lymph.

Recombinant human interleukin-2 (IL-2) was administered by the intravenous (i.v.) or intralymphatic (i.l.) route to 14 patients with advanced malignancy. IL-2 was given in doses of 600,000 IU/kg or 1,050,000 IU/kg daily x 5. Thoracic duct (TD) catheters were placed, and both TD lymphocytes (TDL) and peripheral blood lymphocytes (PBL) were studied. Five of eight patients at the 600,000 IU/kg dose experienced grade III toxicity as did five of six patients at the 1,050,000 IU/kg dose. Two episodes of grade IV toxicity were seen at the higher dose. The i.l. and i.v. routes had a similar toxicity profile excepting lymphangitis/pedal infection, seen only with i.l. administration. One partial response was seen in a patient with renal cell carcinoma. Lymphopenia was seen early in therapy, with lymphocytosis by day 6. Lymphoid yield of the TD catheter fell early in therapy, then increased over baseline by the end of treatment. Intralymphatic administration resulted in a prolonged serum t1/2 and lower serum levels than did i.v. administration, but resulted in higher TD levels. Antibodies against IL-2 were ubiquitous but had no clear effects. Lymphocyte trafficking studies suggested that IL-2 affected lymphocyte redistribution to liver, spleen, bone marrow, and lymph nodes. NK activity and phenotype and LAK activity increased in response to IL-2, with no advantage for TDL. Tumor necrosis factor-alpha and gamma-interferon levels increased sporadically with treatment. The i.l. route offered no advantage over the i.v. route, and TDL offered no advantage over PBL.

Adult↗

Social and functional impact of reduced posterior dental units in older adults.

The number of teeth needed to maintain adequate dental function in older adults is unknown. The purpose of this study was to examine the relationship between oral function and the number of opposing pairs of posterior teeth. We identified 338 subjects with complete anterior dentitions from an interview and examination survey of Ontario adults aged 50 and over; 261 had no partial denture and 77 had removable partial dentures (RPD). Oral function was measured using questions assessing chewing ability, mandibular function and socio-psychological impact. Subjects with no partial dentures were further allocated to five groups, based on their dental status: complete dental arch (n = 69); 5-7 functional units-pairs of opposing posterior teeth (n = 109); 3 or 4 functional units (n = 48) and 0-2 functional units (n = 35). Oral function problems increased with decreasing functional units being markedly more prevalent among the groups with 0-2 functional units. 34% of subjects in the 0-2 group reported one or more problems with chewing ability compared to 6-17% in the other groups (chi 2 P = 0.001 d.f. = 3). The 77 subjects who wore removable partial dentures, reported social and dental function at levels comparable to those with no dentures. From these results, there appears to be little socio-functional need to replace lost posterior teeth with a partial denture unit the person has fewer than, 3 posterior functional units. The low number of partial denture wearers limited our ability to detect a lasting benefit from RPD treatment.

Aged↗

The comprehensive health enhancement support system.

This article describes the process of using needs assessment data to develop an interactive information technology specifically designed to support patients in a health-related crisis. The Comprehensive Health Enhancement Support System (CHESS) is an interactive information, social support, and problem-solving system that was developed by a team at the University of Wisconsin. This article looks at the program developed for breast cancer patients and their families.

Breast Neoplasms↗