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Biomedical subjects

D J Weiss

Publications and source records attributed to D J Weiss.

At least 73 records · Page 4Linked to original sources
PubMed1995

Prothrombotic events in the prodromal stages of acute laminitis in horses.

Prothrombotic changes occurring in the prodromal stages of carbohydrate-induced laminitis were investigated. Hemostatic alterations were evaluated by determining platelet counts, platelet survival, activated partial thromboplastin time, one-stage prothrombin time, and monocyte procoagulant activity. Thrombosis of vessels in the hoof wall was evaluated by contrast arteriography and histologic examination. Of 5 horses, 4 became lame between 28 and 52 hours after carbohydrate administration. Mean platelet count in laminitis-affected horses was lower throughout the prodromal stages of laminitis, compared with that in control horses, but differences were not statistically significant. However, survival of indium-111-labeled platelets was less than the value in control horses by 6 hours after carbohydrate administration. Arteriography of disarticulated feet revealed marked reduction in blood supply to hooves in laminitis-affected horses. Histologic examination of the laminar dermis disclosed microthrombi in venules of the laminar dermis in 2 of 4 affected horses. Statistically significant changes in prothrombin time were not observed, and changes in activated partial thromboplastin time were slight and occurred only at the onset of lameness. Statistically significant changes in monocyte procoagulant activity were not observed. Plasma endotoxin-like activity was not detected in laminitis-affected horses. These data indicate that platelet survival was decreased within the first 6 hours after induction of carbohydrate-induced laminitis, but systemic activation of the coagulation system was not detected.

Angiography↗
PubMed1994

Regulation of interleukin-8 expression in porcine alveolar macrophages by bacterial lipopolysaccharide.

Interleukin (IL)-8 is a macrophage-derived neutrophil chemotactic factor that plays an important role in the recruitment of neutrophils to inflammatory loci. Hence, expression of IL-8 by alveolar macrophages may be a significant factor in host defense in the lung and in the pathogenesis of pneumonia in swine. To initiate molecular studies of IL-8 regulation in pigs, we cloned IL-8 cDNA and examined the regulation of its mRNA in alveolar macrophages. The porcine IL-8 cDNA consists of 1491 base pairs including a coding region of 309 base pairs. The deduced amino acid sequence was 75 and 81% similar to human and rabbit IL-8, respectively. Resting macrophages contained low levels of IL-8 mRNA, which increased markedly after exposure to bacterial lipopolysaccharide (LPS). LPS induction of IL-8 was direct, not mediated through elevation of tumor necrosis factor or interleukin-1. The effect of LPS on IL-8 expression was dose dependent, and induction was observed at a concentration of 10 pg/ml. IL-8 mRNA expression was detectable within 0.5 h after stimulation with LPS, peaked at 3-6 h at about 30-fold higher levels than in resting cells, and was maintained for 24 h. Secreted IL-8, measured by neutrophil chemotaxis, was induced within 4 h by LPS, and accumulated in the media throughout the 24-h period. The mechanism of induction of IL-8 mRNA appeared to involve transcription and RNA processing. Nuclear run-on analysis showed that the IL-8 gene was actively transcribed in noninduced cells; upon stimulation with LPS, the rate of IL-8 transcription was increased about 4-fold. A single mature mRNA species was detected by primer extension analysis. The half-life of IL-8 mRNA transcripts in aveolar macrophages was approximately 2 h and did not change after LPS stimulation. The ability of LPS to induce IL-8 expression was suppressed by recombinant human IL-4 and dexamethasone in a concentration-dependent manner. These observations indicate that the expression of IL-8 is an early event in the sequelae to bacterial infection in the lung.

Amino Acid Sequence↗
PubMed1994

Subchronic oral toxicity study of diisopropyl methylphosphonate in mink.

Diisopropyl methylphosphonate (DIMP), produced during manufacture of the chemical agent GB (Sarin), is a groundwater contaminant at Rocky Mountain Arsenal, Colorado. DIMP was fed for 90 days to dark brown "Ranch Wild" mink housed under controlled indoor conditions. One-year-old mink, 10 of each sex, were fed 0, 50, 450, 2700, 5400, or 8000 ppm in standard ranch diet. Actual DIMP consumption was 0, 8, 73, 400, 827, and 1136 mg/kg body wt/day, respectively. Two additional groups of 10 served as "pair-fed" controls. Body weight and food intake were recorded weekly. Complete blood count and 15 chemical analytes were measured at Weeks 0, 3, 7, and 13. Necropsy and microscopic examination were performed on all mink. No clinical morbidity or deaths occurred. Both sexes fed 8000 ppm ate approximately 20% less and weighed approximately 20% less than the controls; 5400 ppm females had a 10% weight decrement. Plasma cholinesterase (ChE) decreased in the top three dose groups starting at Week 3. At 13 weeks, decrements were approximately 50% but returned to normal after 1 week without DIMP. Erythrocyte ChE was not reduced. Heinz bodies occurred in 10-15% of RBCs in 50% of 8000 ppm mink at 13 weeks, and 0.1-2.0% of RBCs in 25% at 2700 ppm. There were mild decreases in RBC count, hematocrit, and hemoglobin, and increases in reticulocyte count, at the 5400 and 8000 ppm doses. All recovered within 3 weeks after DIMP was withdrawn. The 8000 ppm group had marginal splenic hematopoiesis, histologically. No other treatment-related changes were noted. The 450 ppm dose was a clear no-effect level (approximately 73 mg DIMP/kg body wt/day). Compared to reports of similar studies of DIMP in rats and dogs, these mink displayed no unique species susceptibility.

Animal Feed↗
PubMed1994

The comparative metabolism of diisopropyl methylphosphonate in mink and rats.

This study reports the metabolism of carbon-14labeled diisopropyl methylphosphonate (DIMP) in mink and rats, undertaken to better understand the dose-related mortality reported for mink in a previous study. In both male and female mink and rats, DIMP was rapidly absorbed after oral administration; it was metabolized by a saturable pathway to a single metabolite, isopropyl methylphosphonate (IMPA), which was rapidly excreted, primarily in the urine (90%). Fecal radioactivity, also identified as IMPA, was 1.7-3.1% of the administered dose. Female rats had a slower rate of conversion of DIMP to IMPA and less total excretion of IMPA than male rats. Metabolism of DIMP administered intravenously was not very different from that given orally in both species. These data indicate that mink absorb, metabolize, and excrete DIMP (as IMPA) in a manner very similar to mice, rats, and dogs.

Administration, Oral↗
PubMed1994

The effects of furosemide and pentoxifylline on the flow properties of equine erythrocytes: in vitro studies.

The effects of various concentrations of furosemide and pentoxifylline on equine RBC in vitro were evaluated to facilitate better understanding of the potential effects of these drugs on blood flow properties. Furosemide induced increased mean cell volume (MCV), increased RBC potassium concentration, increased whole blood viscosity, and decreased the RBC filtrability. These data indicate that furosemide may block the RBC membrane transport pathways resulting in potassium and water retention. The increase in size and the resultant decrease in the surface-area-to-volume ratio may have caused the impaired RBC filtrability and increased blood viscosity. Pentoxifylline improved RBC filtrability without changing the RBC size or the potassium or chloride concentrations, suggesting that pentoxifylline may increase the deformability of the RBC membrane. The study indicated that pentoxifylline has potential therapeutic applications for improving microvascular blood flow but that furosemide may have adverse effects on blood flow.

Animals↗
PubMed1994

Hyperinsulinemia is associated with menstrual irregularity and altered serum androgens in Pima Indian women.

To determine whether hyperinsulinemia is associated with menstrual irregularity or hyperandrogenemia among Pima Indians, a population with a high prevalence of hyperinsulinemia, we retrospectively studied 20 hyperinsulinemic (higher insulin [HI ) and 20 relatively nonhyperinsulinemic (lower insulin [LI]) nondiabetic Pima women 18 to 45 years of age. Reproductive histories were obtained by review of medical records. Stored serum samples were used for measurement of total testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS) levels. Fifty percent (nine of 18) of HI women had irregular menses, as compared with none of the LI women (0 of 19, P = .0004). HI women were significantly more obese than LI women. Serum testosterone and androstenedione levels were similar in HI and LI women (median testosterone, 1.13 v 1.13 nmol/L, P = .55; median androstenedione, 3.79 v 3.26 nmol/L, P = .90). Serum DHEAS was lower in HI than in LI women (median, 2.85 v 4.55 mumol/L, P < .01). HI women with irregular menses had significantly higher testosterone levels than HI women with regular menses (median, 1.62 v 0.76, nmol/L, P = .04). Androstenedione and DHEAS levels were not different between these women. In conclusion, the association of obesity, hyperinsulinemia, irregular menstruation, and high testosterone concentration described in the polycystic ovarian syndrome (PCO) also occurs in Pima Indian women. Moreover, low concentrations of DHEAS are associated with hyperinsulinemia in these women.

Adolescent↗
PubMed1994

Hematologic and serum chemistry reference values for adult brown mink.

Hematologic and serum chemistry reference values were determined for 160 12-month-old brown untamed captive mink (Mustela vision). Blood was obtained by jugular venipuncture after administration of ketamine and xylazine. There were no statistically significant differences between male and female mink. The packed cell volume, hemoglobin, and red blood cell count were 10 to 20% lower than previously reported for non-anesthesized mink. Serum glucose, alanine aminotransferase and aspartate aminotransferase values also were lower than previously reported values.

Anesthesia↗
PubMed1994

Hemorheologic alterations induced by incremental treadmill exercise in thoroughbreds.

Hemorheologic alterations induced by incremental treadmill exercise were examined in 5 Thoroughbreds. Blood viscosity; PCV; RBC filterability, density gradient profile, and shape; serum and RBC electrolyte concentrations; and plasma total solids and lactate concentrations were measured before exercise, at treadmill speeds of 9 and 13 m/s, and 10 minutes after exercise. Exercise was associated with significant (P < 0.05) increases in PCV, blood viscosity, and plasma total solids concentration. After adjustment of PCV to 40% by adding or removing each horse's own plasma, blood viscosity remained significantly greater in the sample obtained at 13 m/s, compared with that in samples taken at rest. Filterability of RBC was significantly decreased at 13 m/s, compared with values from other sampling times. During exercise, a significantly greater proportion of the RBC were less dense and were found in the upper layers of the RBC density gradient profile, compared with resting values. This change was associated with a significant increase in RBC mean cell volume. Rapid increases in serum sodium and potassium concentrations during exercise were accompanied by significant increases in RBC potassium and chloride concentrations. This study revealed a consistent pattern of hemorheologic alterations associated with exercise in Thoroughbreds, suggesting that multiple hemorheologic tests are needed to adequately define these complex alterations during exercise in horses.

Animals↗
PubMed1994

Comparison of microscopic and flow cytometric detection of platelet antibody in dogs suspected of having immune-mediated thrombocytopenia.

A flow cytometric platelet immunofluorescence assay (FC-PIFA) was compared with a previously developed microscopic platelet immunofluorescence assay (MI-PIFA) for detection of circulating platelet antibody. Both assays were performed on serum from 10 healthy dogs with normal platelet count, and on serum from 27 thrombocytopenic dogs--18 had primary immune-mediated thrombocytopenia (IMT), and 9 had IMT in addition to other immune-mediated disease (secondary IMT). Both assays yielded negative results for all control dogs. The MI-PIFA and FC-PIFA results were in agreement in 23 dogs with IMT (14 positive and 9 negative). There was linear correlation between MI-PIFA scores and FC-PIFA results (r = 0.873). Positive results were obtained for 55.5% of the dogs with suspected IMT, using the MI-PIFA, compared with 67%, using the FC-PIFA; however, the difference was not statistically significant. Use of fresh or frozen fixed donor platelets as the antigen source yielded similar results in the FC-PIFA.

Animals↗
PubMed1994

Microvascular thrombosis associated with onset of acute laminitis in ponies.

The hypothesis that equine laminitis is caused by thrombosis of vessels in the laminar corium (dermis) was investigated. Hemostatic alterations were evaluated by determining platelet count, platelet survival, platelet adhesiveness to vascular subendothelium, activated clotting time, and whole blood recalcification time. Thrombosis of vessels in the hoof wall was evaluated by scintigraphic studies of the hoof wall after administration of indium-111 (111In)-labeled platelets, contrast arteriography, and histologic examination. Platelet count remained constant before and at the onset of lameness; however, survival of 111In-labeled platelets was shortened. Scintigraphy of affected feet revealed accumulation of 111In-labeled platelets distal to the coronary band. Arteriography of disarticulated saline-perfused feet revealed marked reduction in blood supply to affected hooves. Histologic examination of the laminar dermis disclosed variable numbers of microthrombi in dermal veins of affected feet from 3 of 4 ponies with laminitis. Whole blood recalcification time was shortened at 8 hours after administration of carbohydrate and was prolonged at the onset of laminitis. Activated clotting time was prolonged at 32 hours after carbohydrate administration and at the onset of lameness. Plasma endotoxin-like activity was detected in 1 of 4 affected ponies. These data confirm that microvascular thrombosis existed at the onset of lameness in ponies with carbohydrate-induced laminitis and indicate that systemic coagulopathy may have preceded development of thrombosis.

Acute Disease↗
PubMed1994

Effects of echinocytosis on hemorrheologic values and exercise performance in horses.

Effects of echinocytosis on blood rheology and exercise performance were evaluated for 5 Thoroughbreds. Echinocytosis was induced by administration of furosemide (1 mg/kg of body weight, IM, q 12 h) for 4 days. Furosemide treatment resulted in decreases in serum sodium and serum chloride concentrations and in RBC chloride and potassium concentrations. Echinocytosis was associated with increased RBC density as determined by RBC density gradient centrifugation. However, samples containing echinocytes were more filterable than control samples, indicating that echinocytes were not rigid cells. Erythrocyte sedimentation rate was decreased in blood samples containing echinocytes, indicating that cell-to-cell interaction was reduced. Whole blood viscosity was not altered by presence of echinocytes. Echinocytes did not impair the capacity of horses to complete treadmill exercise tests, nor did they alter heart rate or blood gas variables. However, plasma lactate concentration was higher in samples obtained during exercise at a treadmill speed of 9 m/s. Echinocytosis was associated with higher postrace creatine kinase activity. These data indicate that echinocytes may be dense, but not rigid cells, which have decreased tendency to aggregate and do not increase whole blood viscosity. Therefore, echinocytes are unlikely to inhibit or obstruct microvascular blood flow.

Animals↗
PubMed1994

Hematologic response of adult brown mink to oxidative stress.

We evaluated the response of mink to oral administration of the oxidant compound propylene glycol (PG) to better understand the relative susceptibility of mink red blood cells (RBC) to oxidant injury. Feeding a diet containing 12% PG to 6 mink for 1 w resulted in a 17% decrease in hematocrit, a 21% decrease in RBC count and a 4.8-fold increase in reticulocyte count. A marked increase in Heinz body and eccentrocyte numbers was consistent with oxidative injury to RBC. Because of high food intake, mink ingested approximately twice the quantity of PG/kg body weight compared to domestic cats fed diets containing 12% PG. Therefore, the severity of the hematologic dyscrasia in mink may be the result of greater intake of PG rather than unique sensitivity of mink RBC of oxidative injury. However, the high food intake and the mink's position at the top of the food chain may increase its exposure to environmental contaminants.

Animals↗
PubMed1993

Echinocytosis in horses: 54 cases (1990).

Retrospective review of CBC and serum chemical data from 124 horses admitted to the veterinary teaching hospital over a 9-month period (Feb 1, 1990 to Oct 31, 1990) indicated that 54 horses had echinocytosis (prevalence = 44%). In horses with echinocytosis, the most frequent diagnosis was colitis (23 horses; 43%). Odds ratios (measure of association) were calculated to determine the association of echinocytosis with specific hematologic and biochemical abnormalities. When evaluated in a multivariate model, low serum sodium concentration (< 136 mEq/L) was the only variable significantly associated with the incidence of echinocytosis. Within the group of 54 horses with echinocytosis, hyponatremia (35 horses; 65%), hypochloremia (35 horses; 65%), low total carbon dioxide concentration (35 horses; 65%), hypoosmolality (30 horses; 55%), and hypocalcemia (22 horses; 41%) were the most common biochemical abnormalities. It was concluded that hyponatremia was associated with increased incidence of echinocytosis. It was suggested that systemic electrolyte depletion might be involved in the induction of echinocyte formation.

Analysis of Variance↗
PubMed1993

Drugs affecting the hematologic system of the performance horse.

Pharmacologic alterations in the hematologic and rheologic properties of blood may have an important effect on transport and delivery of oxygen to working muscle during exercise. This article briefly reviews erythropoiesis, hematologic and rheologic responses to training and exercise, and the influence of these alterations on exercise performance. The hemorrheologic and performance effects of hematinics, hematopoietic stimulants, and alterations in blood rheology are discussed. The effects of exercise on blood coagulation, fibrinolysis and platelet function, and the effects of drugs that alter platelet function are briefly described.

Animals↗
PubMed1993

Enhancement of neutrophil-mediated injury to bovine pulmonary endothelial cells by Pasteurella haemolytica leukotoxin.

In this study, we used an in vitro coculture system to determine which virulence factor from Pasteurella haemolytica A1 was responsible for augmenting bovine polymorphonuclear neutrophil (PMN)-mediated killing of bovine pulmonary artery endothelial cells (BPAEC). A 51Cr release cytotoxicity assay was used as a measure of BPAEC killing. The mechanisms associated with this BPAEC killing were also studied. Our results demonstrated that the leukotoxin and not the lipopolysaccharide from P. haemolytica was responsible for augmenting the PMN-mediated killing of BPAEC. Furthermore, this augmented killing was related to the stimulation of PMNs by the leukotoxin. Killing of BPAEC by leukotoxin-stimulated PMNs was diminished in the presence of the H2O2 inactivator, catalase. The membrane-permeant H2O2, hydroxyl radical (HO.) scavenger 1,3-dimethyl-2 thiourea, and the HO. scavenger dimethyl sulfoxide but not the myeloperoxidase inhibitor sodium azide attenuated this BPAEC killing. Pretreatment of BPAEC with a 21-aminosteroid (U74500A), a potent iron chelator-antioxidant, provided the most effective protection against BPAEC killing induced by leukotoxin-stimulated PMNs. These data were compatible with the concept that the H2O2 generated by leukotoxin-stimulated PMNs interacts with intracellular iron in the endothelial cell to form highly reactive HO.. We suggest that HO. may be a key factor in BPAEC killing. Furthermore, since the elastase-specific inhibitor N-methoxy-succinyl-Ala-Ala-Pro-Val-chloromethyl ketone (CMK) also attenuated BPAEC killing and both CMK and 1,3-dimethyl-2 thiourea functioned additively in protecting against BPAEC killing, we conclude that both HO. and elastase may jointly contribute to BPAEC killing induced by leukotoxin-stimulated PMNs. This study broadens our understanding of how leukotoxin-stimulated PMNs injure lung endothelial cells and provides new insight into the pathogenesis of bovine pneumonic pasteurellosis.

Amino Acid Sequence↗
PubMed1993

Leukocyte response to toxic injury.

Exposure to a variety of drugs and toxins can induce hematopoietic damage. These agents exert their effects through several distinct mechanisms including destruction or suppression of hematopoietic stem cells, cytotoxic destruction of rapidly proliferating precursor cells, immune-mediated hematotoxicity, altered hematopoietic microenvironment, genetic mutation, and microvascular injury. Some toxins consistently produce suppression of granulopoiesis in a dose-dependent manner, whereas others produce idiosyncratic reactions. Although all types of injury tend to result in granulocytopenia, the time course of the changes varies with the type of injury. With acute destruction of the proliferative pool of granulocytes, neutropenia develops within 7 days and recovery occurs within days after discontinuing treatment. With stem cell injury, the onset of hematotoxicity is variable and damage is often permanent. Immune-mediated reactions may occur acutely or after months or years of treatment with a drug. Drugs or toxins that act as mutagens can induce a variety of hematopoietic disorders including aplastic anemia, myelodysplasia, and leukemia. Therefore, the time course of onset of leukopenia after drug or chemical exposure and the rapidity of hematopoietic recovery give clues to the mechanism by which granulopoiesis is suppressed.

Animals↗
PubMed1993

Systemic cytomegalovirus infection mimicking an exacerbation of Wegener's granulomatosis.

A patient with Wegener's granulomatosis developed a systemic cytomegalovirus infection that mimicked an exacerbation of her vasculitis including pulmonary infiltrates, renal insufficiency, and cutaneous necrotizing ulcers. All of her symptoms resolved with ganciclovir. Physicians should maintain a high index of suspicion for similar presentations in other patients with vasculitis with or without immunosuppressive therapy.

Aged↗