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Biomedical subjects

D J Weiss

Publications and source records attributed to D J Weiss.

At least 37 records · Page 2Linked to original sources

Role of platelet-activating factor in alveolar septal injury associated with experimentally induced pneumonic pasteurellosis in calves.

OBJECTIVE: To determine whether platelet-activating factor (PAF) is involved in acute lung microvascular injury associated with pneumonic pasteurellosis in calves. ANIMALS: 15 healthy 2- to 4-week-old male Holstein calves. PROCEDURE: Calves were anesthetized and inoculated intrabronchially with saline (0.9% NaCl) solution (n = 5) or 1x10(9) Pasteurella haemolytica organisms (n = 10). Of the 10 calves inoculated with P haemolytica, 5 also were treated with WEB 2086, a potent inhibitor of PAF, and 5 were treated with vehicle. Blood and bronchoalveolar lavage samples were collected before and 1, 2, 4, and 6 hours after inoculation of P. haemolytica. Blood samples were analyzed to evaluate total number and differential counts of leukocytes, dilute whole-blood leukocyte deformability, size of neutrophils, and neutrophil CD11b expression. Bronchoalveolar lavage samples were analyzed for total number and differential counts of nucleated cells, total protein concentration, and hemoglobin concentration. Size and gross and histologic appearance of lung lesions also was determined. RESULTS: Treatment of calves with WEB 2086 reduced size of lung lesions, attenuated the increase in microvascular permeability, and reduced neutrophil infiltration in the first 4 hours after inoculation. Treatment with WEB 2086 also attenuated a decrease in leukocyte deformability, increase in size of neutrophils, and CD11b expression by circulating neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: It appears that PAF is a major mediator for altered lung microvascular permeability and activation of circulating neutrophils in the first 4 hours after onset of pneumonic pasteurellosis in calves.

Animals↗

Association among filamentous actin content, CD11b expression, and membrane deformability in stimulated and unstimulated bovine neutrophils.

OBJECTIVE: To investigate rheologic properties of bovine neutrophils that may result in adhesion molecule-independent sequestration of neutrophils in inflamed lungs of cattle. ANIMALS: Healthy 2- to 4-week-old male Holstein calves. PROCEDURES: Neutrophil deformability, filamentous actin (F-actin) content, and CD11b expression was determined for unstimulated bovine neutrophils and bovine neutrophils incubated with the inflammatory mediators tumor necrosis factor-alpha (TNF), platelet-activating factor (PAF), interleukin-8 (IL-8), zymosan-activated plasma (ZAP), Pasteurella haemolytica-derived lipopolysaccharide (LPS), and P haemolytica leukotoxin. Neutrophils were separated into 3 subpopulations on the basis of size. The Factin content and CD11 b expression were evaluated by use of flow cytometry. Leukocyte deformability was evaluated by filtration of dilute whole blood. RESULTS: The subpopulation of the smallest-sized neutrophils (>90% of neutrophils) contained little F-actin. A subpopulation of slightly larger neutrophils had a profound increase in F-actin content and CD11 b expression. The subpopulation of the largest neutrophils had increased F-actin content and CD11b expression, compared with those for both subpopulations of smaller neutrophils. Incubation of neutrophils with PAF and ZAP but not TNF, IL-8, LPS, or leukotoxin, resulted in decreased neutrophil deformability and increased F-actin content. Incubation with PAF and TNF induced an increase in size of neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: Size can be used to identify subpopulations of large and rigid neutrophils in blood samples from healthy calves. Platelet-activating factor and activated complement fragments are potent inducers of F-actin formation and neutrophil rigidity. Physical changes in neutrophils may impede their transit through lung microvasculature and result in leukocyte trapping independent of adhesion molecule interactions with endothelial cells.

Actins↗

In vitro evaluation of intraluminal factors that may alter intestinal permeability in ponies with carbohydrate-induced laminitis.

OBJECTIVES: To study the in vitro effects of cecal contents incubated with corn starch on colonic permeability in horses. ANIMALS: 4 healthy adult ponies. PROCEDURE: Mucosal specimens were obtained from the right ventral colon and mounted in Ussing chambers. Changes in short circuit current, conductance, and large-molecule permeability in response to addition of cecal contents and cecal contents incubated with corn starch were evaluated for 120 minutes. RESULTS: Incubation of cecal contents with corn starch for 8 hours resulted in a decrease in cecal content pH and an increase in lactic acid concentration. These changes were similar to those reported in vivo for ponies given corn starch. Exposure of colonic mucosa to cecal contents incubated with corn starch resulted in an increase in tissue conductance and permeability of technetium Tc 99m pentetate, compared with mucosa exposed to cecal contents alone. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro exposure of colonic mucosa to cecal contents incubated with starch resulted in increased paracellular permeability. Fermentation of excessive amounts of carbohydrate in the intestinal lumen of horses may directly induce increased intestinal permeability associated with carbohydrate-induced laminitis.

Animals↗

Development and standardization of a new telephonic cognitive screening test: the Minnesota Cognitive Acuity Screen (MCAS).

OBJECTIVE: The aim of this study was to determine the validity and reliability of a telephonically administered cognitive screening battery, consisting of nine brief tests (orientation, attention, delayed word recall, comprehension, repetition, naming, computation, judgment, and verbal fluency), to distinguish between patients with dementia and healthy control subjects. BACKGROUND: Existing telephonic screening instruments do not take full advantage of strategies that might increase precision. METHODS: A total of 228 elderly individuals received a telephone assessment of cognitive function (99 mildly to moderately demented nursing home residents with an established diagnosis of dementia residing in 1 of 12 nursing facilities, and 129 community-dwelling elderly individuals who were independently screened to verify normal cognitive function). RESULTS: Nurses and psychologists experienced in telephonic test administration typically completed the screening with each subject in less than 20 minutes. At the 100% sensitivity level, the test battery had a specificity of 87%. The post hoc optimal cut-score of the discriminant analysis yielded a sensitivity of 97.5% and a specificity of 98.5%. The split-half reliability of the test battery was 0.91. The more powerfully predictive subtests were orientation, delayed word recall, verbal fluency, computation, and judgment. CONCLUSIONS: This telephonic screening instrument appears to have promise to distinguish, with high precision, healthy elderly individuals from those individuals with cognitive impairment. The Minnesota Cognitive Acuity Screen (MCAS) should undergo further study in unselected elderly populations to better understand its value as a screening tool.

Age Distribution↗

Perflubron enhances adenovirus-mediated gene expression in lungs of transgenic mice with chronic alveolar filling.

Perfluorochemical (PFC) liquids have both low surface tension and a high capacity to dissolve O2 and CO2, and have been shown to improve gas exchange and lung compliance in animal models of lung injury. We have previously demonstrated that perflubron and other PFC liquids enhance transgene expression in lungs of spontaneously breathing normal rodents after intratracheal instillation of either adenoviral or liposomal vectors followed by a single instillation of PFC liquid. We reasoned that PFC liquids may also be useful for enhancing transgene expression in abnormal lungs. GM-CSF knockout mice develop chronic accumulation of surfactant lipids and proteinaceous material in alveolar spaces and serve as a useful model of chronic alveolar filling. Intratracheal instillation of the adenoviral vector Adlac-Z resulted in patchy in situ distribution of beta-Gal activity, predominantly in larger proximal airways. In contrast, in mice instilled with Adlac-Z followed by instillation of a single dose of perflubron (10 ml/kg body weight), increased expression was observed in distal airway and alveolar epithelial cells. In particular, expression was observed in epithelial cells of debris-filled alveoli. Spectrophotometric measure of quantitative beta-Gal activity in lung homogenates demonstrated increased activity in lungs of mice receiving Adlac-Z plus perflubron compared with lungs of animals receiving Adlac-Z alone. These studies demonstrate that use of perflubron enhances transgene expression in lungs of animals with a chronic alveolar filling process. This approach may be applicable for gene delivery in diseases marked by chronic airway or alveolar filling such as cystic fibrosis.

Adenoviridae↗

Clinical features of inflammatory liver disease in cats: 41 cases (1983-1993).

OBJECTIVE: To compare the clinical and clinicopathologic findings in and prognosis for cats with lymphocytic portal hepatitis (LPH) versus cats with acute or chronic cholangiohepatitis (CH). DESIGN: Retrospective study. ANIMALS: 25 cats with LPH; 16 cats with CH (7 acute, 9 chronic). PROCEDURE: Cats with LPH and CH were selected by evaluating records from liver biopsy specimens submitted to the University of Minnesota Veterinary Teaching Hospital during a 10-year period. Clinical and clinicopathologic data were retrieved. RESULTS: Cats with CH had higher segmented and band neutrophil counts, alanine aminotransferase activities, and total bilirubin concentrations than did cats with LPH. Cats with acute CH had higher segmented and band neutrophil counts and lower serum alkaline phosphatase activities and total bilirubin concentrations than did cats with chronic CH. Twelve of 14 cats with LPH or CH had coarse or nodular texture to the liver on ultrasonography, with loss of portal vein wall clarity noticed in 4 of 8 cats with LPH. Sixteen of 23 cats with LPH and 8 of 15 cats with CH survived > 1 year. Of those cats living < 1 year, all cats with LPH and 5 of 7 cats with CH had a serious concurrent illness that may have been responsible for their deaths. CLINICAL IMPLICATIONS: LPH and CH can be detected and tentatively differentiated through evaluation of clinical laboratory test results, but histologic evaluation of liver specimens is necessary for definitive differentiation. Survival time was good regardless of the type of inflammatory liver disease.

Acute Disease↗

Histochemical discrimination of endogenous mammalian beta-galactosidase activity from that resulting from lac-Z gene expression.

Minces of several organs from the transgenic mouse ROSAbeta-gal 26 (ROSA-26), which robustly expresses bacterial lac-Z in most tissues, were exposed to 4-bromo-5-chloro-3-indoyl-beta-D-galactopyrosanide (X-gal) at pH ranging from 7.5 to 9.5 to determine the optimal pH for in situ demonstration of bacterial beta-galactosidase activity (neutral pH optimum) while minimizing detection of potentially confounding endogenous mammalian beta-galactosidase (acidic pH optimum). Similar studies were performed with organ minces from C57BL/6 mice, Sprague-Dawley rats, New Zealand white rabbits, and macaques to confirm the effect of pH on minimizing detection of endogenous mammalian beta-galactosidase. In all organs evaluated; heart, liver, spleen, kidney, brain, and skeletal muscle, endogenous beta-galactosidase activity was rarely detected following incubation at pH greater than 7.5. In contrast, bacterial beta-galactosidase activity in the ROSA-26 mice was strongly detected in organ minces following incubation at pH 8.0-9.0. These findings are similar to previous observations we have made in lung minces and confirm that a simple alteration of a commonly used histochemical technique for detecting in situ beta-galactosidase activity, raising the reaction buffer pH to weakly alkaline range, can reliably distinguish between endogenous activity and that resulting from exogenous bacterial gene expression.

Animals↗

Perfluorochemical liquid-enhanced adenoviral vector distribution and expression in lungs of spontaneously breathing rodents.

Perfluorochemical (PFC) liquids have been shown to improve gas exchange and lung compliance in models of lung injury. We reasoned they may also be useful as a vehicle for gene transfer by improving transgene distribution throughout the lung as well as increasing total transgene expression. We have developed a model for PFC liquid use in spontaneously breathing rodents that obviates the need for intubation and ventilation. Intratracheal instillation of the adenoviral vector Adlac-Z resulted in patchy distribution of beta-galactosidase (beta-gal) activity as demonstrated using X-gal histochemistry. In contrast, in rats instilled with Adlac-Z followed by instillation of PFC liquid, more uniformly distributed and increased beta-gal activity was observed. Activity in distal airway and alveolar epithelium was particularly increased. Quantitative measure of beta-gal activity in lung homogenates demonstrated a 3- to 6-fold increase in total activity in lungs of rats receiving Adlac-Z and PFC liquid compared to animals receiving Adlac-Z alone. These studies show that PFC liquids can enhance both the distribution and the total amount of transgene expressed following adenoviral-mediated vector transfer to lungs during spontaneous breathing. Use of PFC liquids may increase the efficacy of gene transfer strategies for treatment of cystic fibrosis and other lung diseases.

Adenoviridae↗

Collagen accumulation is decreased in SPARC-null mice with bleomycin-induced pulmonary fibrosis.

Secreted protein acidic and rich in cysteine (SPARC) has been shown to be coexpressed with type I collagen in tissues undergoing remodeling and wound repair. We speculated that SPARC is required for the accumulation of collagen in lung injury and that its absence would attenuate collagen accumulation. Accordingly, we have assessed levels of collagen in SPARC-null mice in an intratracheal bleomycin-injury model of pulmonary fibrosis. Eight- to ten-week-old SPARC-null and wild-type (WT) mice received bleomycin (0.0035 U/g) or saline intratracheally and were subsequently killed after 14 days. Relative levels of SPARC mRNA were increased 2.7-fold (P < 0.001) in bleomycin-treated WT lungs in comparison with saline-treated lungs. Protein from bleomycin-treated WT lung contained significantly more hydroxyproline (191.9 microg/lung) than protein from either bleomycin-treated SPARC-null lungs or saline-treated WT and SPARC-null lungs (147.4 microg/lung, 125.4 microg/lung, and 113. 0 microg/lung, respectively; P < 0.03). These results indicate that SPARC is increased in response to lung injury and that accumulation of collagen, as indicated by hydroxyproline content, is attenuated in the absence of SPARC. The properties of SPARC as a matricellular protein associated with cell proliferation and matrix turnover are consistent with its participation in the development of pulmonary fibrosis.

Animals↗

Attitudes of military personnel toward homosexuals.

The purpose of this study was to assess attitudes of enlisted military personnel with regard to homosexuality. Seventy-two male members of the Marine Corps Reserve responded to a questionnaire exploring attitudes toward lesbians and gay men and attitudes toward homosexuals in the military. Results showed that attitudes with respect to these topics were mildly unfavorable. In addition, several predictor variables employed in similar studies with civilians were examined. Correlational evidence showed that participants expressing more negative attitudes tended to have more conservative political ideology, reported more religious attendance, and were more likely to have had no contact with a gay or lesbian person than those expressing less negative attitudes. These findings suggest that the attitudes held by enlisted personnel are similar to those of their civilian counterparts.

Adult↗

Evaluation of structural and functional alterations of circulating neutrophils in calves with experimentally induced pneumonic pasteurellosis.

OBJECTIVES: To determine the structural and functional alterations in circulating neutrophils that may lead to sequestration in lung microvasculature and endothelial injury in calves with experimentally induced pneumonic pasteurellosis. ANIMALS: 10 healthy, 2- to 4-week-old male Holstein calves. PROCEDURES: Holstein calves were anesthetized and inoculated intrabronchially with Dulbecco phosphate buffered saline (0.9% NaCl) solution (DPBSS; 5 control calves) or 1 x 10(9) Pasteurella haemolytica organisms (5 infected calves). Blood samples were collected before and 1, 2, 4, and 6 hours after inoculation. Total and differential WBC count, dilute whole blood leukocyte deformability, neutrophil size distribution, and neutrophil surface CD11b expression were measured in blood samples. RESULTS: A progressive decrease in leukocyte deformability and increase in neutrophil size was detected 1, 2, 4, and 6 hours after inoculation of P haemolytica. Neutrophil surface CD11b expression was greater than baseline values at 6 hours after inoculation of P haemolytica. Two populations of neutrophils with an increase in size were detected in P haemolytica-infected calves. Both subpopulations had increased CD11b expression, compared with neutrophils that were typical in size. CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophils circulate in an activated and nondeformable state in calves with experimentally induced pneumonic pasteurellosis. A decrease in neutrophil deformability and neutrophil aggregation may contribute to neutrophil trapping in the lung microvasculature during pneumonic pasteurellosis in calves.

Animals↗

Low back pain caused by a duodenal ulcer.

The common diagnoses in low back pain are lumbar strain, lumbosacral radiculopathy, osteoarthritis, degenerative disc disease, spinal stenosis, and sacroiliac joint dysfunction. Unusual causes of low back pain that have been previously identified include abdominal aortic aneurysms, pelvic neoplasms, and retroperitoneal hemorrhages. This report describes a case of back pain that was apparently caused by a duodenal ulcer. A 54-year-old man with no significant medical history presented with a complaint of mid to low back pain (T10-L2), which was diagnosed as joint dysfunction. A comprehensive treatment program was prescribed and the patient was instructed to return to clinic in 4 weeks. Three weeks later, he experienced a syncopal episode followed by coffee ground emesis. He immediately sought medical attention at an emergency room, where he was admitted to the hospital with a diagnosis of upper gastrointestinal bleed. Esophagogastroduodenoscopy showed a large duodenal ulcer, and the patient underwent vagotomy and pyloroplasty. He returned to his physiatrist's office 3 weeks after hospital discharge with minimal back pain. The cause of the back pain proved to be referred visceral pain from his duodenal ulcer. This case is presented to reemphasize the need to include the uncommon phenomena in the differential diagnosis of low back pain.

Duodenal Ulcer↗

Dyspnea resulting from fibromyalgia.

Two patients with chronic, severe, episodic dyspnea underwent prolonged, extensive, and invasive evaluations without a diagnosis being made. Both were subsequently diagnosed with fibromyalgia, and therapy directed at this condition resulted in resolution of their symptoms. Fibromyalgia is rarely included in the differential diagnosis of dyspnea, and timely diagnosis and treatment may be delayed. However, this condition must be considered because it can only be established by seeking the appropriate history and physical findings.

Adrenergic Uptake Inhibitors↗

Evaluation of platelet activation and platelet-neutrophil aggregates in Thoroughbreds undergoing near-maximal treadmill exercise.

OBJECTIVES: To determine whether platelets become activated and form platelet-neutrophil aggregates during near-maximal treadmill exercise in horses. ANIMALS: 4 Thoroughbreds. PROCEDURE: Horses were subjected to 4 standardized exercise tests on a treadmill, and blood samples were collected before exercise, at treadmill speed of 12 m/s, and 5 minutes after exercise. Flow cytometric techniques were used to identify activated platelets, and flow cytometric and microscopic techniques were used to identify platelet-neutrophil aggregates. RESULTS: Platelet-neutrophil aggregates increased from 2.8 +/- 0.4% at rest to 17.2 +/- 1.1% and 14.7 +/- 1.6% during and after exercise, respectively. Platelet activation was not detected during or after exercise. CONCLUSIONS: Platelet-neutrophil aggregates consistently form during strenuous exercise in horses.

Animals↗

Effect of a competitive inhibitor of platelet aggregation on experimentally induced laminitis in ponies.

OBJECTIVES: To determining whether inhibition of platelet aggregation prevents development of carbohydrate overload-induced alimentary laminitis. ANIMALS: 22 healthy adult ponies. PROCEDURES: Acute laminitis was induced by oral administration of corn starch/wood flour to 16 ponies, 8 of which were treated with a synthetic analogue of the platelet fibrinogen receptor antagonist peptide (RPR) RGDS (arginine-glycine-aspartic acid-serine) 110885; 6 ponies served as negative controls. Blood was collected before and at 4, 8, 12, 24, 28, and 32 hours after administration of carbohydrate overload, and PCV, total plasma protein concentration, platelet count, activated clotting time, whole blood recalcification time, spontaneous platelet aggregation, ex vivo platelet aggregation responses, in vivo platelet activation, and platelet-neutrophil aggregates were evaluated. RESULTS: Of 16 ponies given carbohydrate, 6 of 8 untreated ponies developed laminitis and 0 of 8 ponies treated with RPR 110885 developed laminitis. The RPR 110885 treatment attenuated the increase in platelet-neutrophil aggregates observed in untreated ponies. CONCLUSIONS: Platelets are involved in the pathogenesis of equine alimentary laminitis. CLINICAL RELEVANCE: Platelet aggregation inhibitors may be useful for prevention or treatment of laminitis, or both.

Animals↗

Changes in plasma protein concentrations in ponies with experimentally induced alimentary laminitis.

OBJECTIVE: To determine whether plasma protein concentrations were altered in ponies with alimentary laminitis. ANIMALS: 12 adult ponies. PROCEDURE: Acute laminitis was induced in 6 ponies by oral administration of carbohydrate (85% corn starch, 15% wood flour); the other 6 ponies were used as controls. A physical examination was performed and blood samples were collected immediately before and 4, 8, 12, 24, and 28 hours after administration of carbohydrate. Plasma protein concentrations were determined by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis. RESULTS: 19 plasma proteins ranging from a molecular weight of 24,000 to a molecular weight of 350,000 were identified in all 12 ponies. Plasma concentrations of proteins with molecular weights of 350,000 (fibrinogen), 130,000 (ceruloplasmin), 118,000 (c-reactive protein), 67,000 (alpha1-antitrypsin I), 65,000 (alpha1-antitrypsin II), 50,000 (haptoglobulin), and 45,000 (acid glycoprotein) were significantly increased in ponies with laminitis, compared with concentrations in control ponies. CONCLUSION: Changes in plasma protein concentrations are detectable within 4 hours after the onset of alimentary laminitis in ponies. Clinical Relevance-Measurement of plasma protein concentrations may be useful in monitoring the progression of laminitis in ponies.

Animals↗

Shear-induced platelet activation and platelet-neutrophil aggregate formation by equine platelets.

OBJECTIVES: To determine whether platelets become activated and form platelet-platelet or platelet-neutrophil aggregates, or both, when subjected to shear. SAMPLE POPULATION: Blood obtained from 3 Thoroughbreds. PROCEDURES: Blood, with PCV adjusted to 32 (low hematocrit) or 60 (high hematocrit)%, was subjected to shear rates of 11.25, 22.5, 45, 90, 225, and 750/s for 3 minutes by use of a cone-plate viscometer. Flow cytometric techniques were used to identify activated platelets, platelet-platelet aggregates, and platelet-neutrophil aggregates. RESULTS: Shear resulted in decreased platelet count, increased mean platelet volume, platelet activation, and formation of platelet-platelet and platelet-neutrophil aggregates. These changes occurred at lower shear rates in blood with high hematocrit. Platelet-neutrophil aggregate formation was inhibited by blocking P-selectin, but not CD11/CD18 receptors. CONCLUSIONS: Shear-induced platelet activation and aggregate formation occur at physiologic shear rates. CLINICAL RELEVANCE: Shear-induced platelet activation may explain the exercise-associated platelet-neutrophil aggregates observed in Thoroughbreds undergoing treadmill exercise.

Animals↗