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Biomedical subjects

J Post

Publications and source records attributed to J Post.

At least 19 recordsLinked to original sources
PubMed2006

Immune responses in Eimeria acervulina infected one-day-old broilers compared to amount of Eimeria in the duodenum, measured by real-time PCR.

T-cell responses are supposed to be the major immune reactions in broilers infected with Eimeria. The nature of such T-cell responses is influenced by the species of Eimeria involved, age of the host, amount of parasites and the preceding infection history. In young chicks the intestine is still developing in length while the lymphocyte populations in the gut develop and differentiate. In chicks infected at young age the immune response may be different in quality as compared to responses in adults. We investigated the (T-cell) immune responses of young broilers to a primary Eimeria acervulina infection in relation to the number of parasites used for infection. In our experiment we infected one-day-old broilers with a low (5 x 10(2) oocysts) and a high (5 x 10(4) oocysts) dose of E. acervulina. We used a newly developed species specific real-time PCR to quantify total amount of parasites in the duodenum as the number of oocysts in faeces may not be representative for the exposure of the gut immune system. We characterized T-cell subsets in the duodenum by means of FACS-analyses, lymphocyte proliferation assays with spleen lymphocytes and the mRNA profiles of different cytokines (TGF-beta2, -4, IFN-gamma, IL-2, -6, -8 and -18) in the duodenum by means of real-time PCR. From day 5 p.i. broilers with a high dose of E. acervulina had a significantly lower body weight than the control group. No increase in CD4(+) cells, but a strong increase in CD8(+) cells was observed at days 7 and 9 p.i. in the duodenum of broilers infected with a high dose E. acervulina. IL-8 mRNA responses were observed after infection with low and with high infection doses, but no IFN-gamma and TGF-beta mRNA responses were found in the duodenum. The specific proliferative T-cell responses to a low infectious dose were not significantly different as compared to the control group. In conclusion, based on the kinetics of observed responses a primary infection with a high dose of E. acervulina in one-day-old broilers seems to generate an immune response that shows a peak at the time of oocyst excretion, whereas the immune response to a low dose is less explicit.

Animals↗
PubMed2004

Vitamin and trace mineral content in feed of breeders and their progeny: effects of growth, feed conversion and severity of malabsorption syndrome of broilers.

1. A study was conducted to investigate the effects of several vitamins and trace elements chickens and in chickens experimentally infected with malabsorption syndrome (MAS). 2. Vitamins and trace minerals in feed were varied. Breeders received either a basal amount of vitamins and trace minerals (low mix) or an increased amount (high mix). Their progeny also received either a low mix or a high mix. Effects of different breeder and broiler mix combinations on broiler performance, heamatology, spleen weight and humoral response were examined in control chickens. The effects of the different feeds and breeder, broiler combinations at the severity and recovery of MAS infection were also studied. 3. In general, the immune system can be stimulated by addition of vitamins and trace minerals, without affecting the growth potential of the controls. The number of leukocytes increased on d 1 in the broilers descended from breeders receiving high mix. The response to Newcastle disease virus boost was affected by the different amount of vitamins. 4. When breeders received a high mix the number of infiltrating polymorphonuclear leukocytes in the intestine was higher compared with breeders receiving basal amounts of minerals and vitamins. Also the recovery rate of intestinal lesions, cystic crypts of Lieberkühn and villus atrophy, as observed by histopathology, was faster in the groups where the breeders received high mix.

Aging↗
PubMed2003

Automated blood cell count: a sensitive and reliable method to study corticosterone-related stress in broilers.

In chickens the heterophil/lymphocyte ratio (H/L) has proved to be a valuable tool in stress related research. In general, H/L is determined with the microscopic differential count on a blood film. We evaluated automated analysis for measuring blood cell parameters in relation to corticosterone in a recently introduced corticosterone model. Discrepancies between microscopic and automated counts were found for the percentage of monocytes and basophils. The relative H/L ratio appeared to be sensitive for increased plasma corticosterone levels. However, the increase in heterophil frequencies measured with the hematology analyzer proved to be the most sensitive method for the measurement of changes in plasma corticosterone concentrations. We therefore propose automated hematological analysis as a simple and sensitive tool to study the effects of physiological corticosterone concentrations on blood cell parameters in relation to stress in broiler chickens.

Animals↗
PubMed2003

Physiological effects of elevated plasma corticosterone concentrations in broiler chickens. An alternative means by which to assess the physiological effects of stress.

Research on physical or psychological stress, in order to monitor objective parameters for animal welfare, is usually performed during experimental stress induction. To avoid treatment of animals with physical or physiological stress, addition of the stress-related hormone corticosterone to the drinking water, may serve as a practical alternative to reproducibly investigate hormone-related stress in broiler chickens. Rapid uptake of the hormone and distribution in the bloodstream were affirmed by elevated plasma corticosterone concentrations immediately after start of the treatment. The effect of hormone administration was evaluated by examination of corticosterone-sensitive organs. Comparable to the observations during physiological stress, we found in our model that uptake of endogenous corticosterone reduced body and spleen growth, increased heterophil counts, and decreased formation of antibodies against sheep red blood cells. Furthermore, corticosterone decreased adrenal gland responsiveness, measured by corticosterone production, after a challenge with adrenocorticotropic hormone. The simple performance, and the close relation between circulating corticosterone levels and heterophil counts, makes this an easy and quick method that is sensitive to increased levels of circulating corticosterone from base levels. The changed responsiveness of the adrenal glands to adrenocorticotropic hormone after increased circulating corticosterone levels may be an indication of the coping strategies during stress. Therefore, this test may be a promising tool in the research of adaptation to stress by broiler chickens.

Adrenal Glands↗
PubMed2002

Effect of an in ovo infection with a Dutch avian leukosis virus subgroup J isolate on the growth and immunological performance of SPF broiler chickens.

The effect of an in ovo infection with a Dutch isolate of avian leukosis virus subgroup J (ALV-J) on the growth of specific pathogen free (SPF) broiler chickens was analysed. During this study, possible immune suppressive effects of ALV-J were assessed by measuring delayed-type hypersensitivity with keyhole limpet haemocyanin (KLH), natural killer (NK) cell activity, the production of radicals of nitric oxide (NO) by macrophages, humoral immune response against Newcastle and infectious bursal disease vaccine viruses, and automated total and differential leukocyte counts. In an attempt to elucidate the underlying causal mechanisms of the induced growth retardation, 3,3',5-triiodothyronine (T3) concentrations in serum were measured. Four experiments were conducted. In experiment 1, ALV-J-injected birds were compared with ALV subgroup A (ALV-A)-injected and negative control chickens. In experiment 2, ALV-J-injected birds were only compared with negative controls. Finally, in experiments 3a and 3b, ALV-J-injected chickens were compared with negative controls and a group of chickens in which only 10% of birds had been injected with ALV-J. Birds were injected in ovo at day 7 of incubation with 10(4) median tissue culture infectious dose (TCID(50)) ALV-J or ALV-A, except in experiment 3a where 10(2) TCID(50) ALV-J was injected. Significant growth suppression was found in all 100% of ALV-J-infected groups. The average growth retardation of ALV-J-infected birds compared with negative controls at 6 weeks of age was approximately 8, 11, 2.5 and 6% for the four successive experiments performed. The delayed-type hypersensitivity test against KLH of ALV-J-infected birds showed a tendency towards lower wattle thickness; however, the difference with controls was not significant (P > 0.05). The same was true for NK cell activity and NO production by macrophages, although the difference was not significant. The total and differential leukocyte counts performed on blood samples from birds at 3, 4 and 6 weeks of age as well as the humoral immune response against Newcastle and infectious bursal disease vaccine viruses did not show significant differences between treatment groups either. Only the number of basophils were significantly higher (P = 0.02) in ALV-J-infected birds at 3 weeks of age. No significant lower T(3) levels were found in ALV-J-infected birds in weeks 2 and 3 (experiment 2) and weeks 3 and 5 (experiment 3b); however, at 4 weeks (experiment 2) and 6 weeks (experiment 3b) of age, T(3) levels were significantly lower suggesting mild hypothyroidism in these broilers. In conclusion, the present experiments show the occurrence of significant growth retardation in SPF broilers after an ALV-J in ovo infection. The various studies performed to assess the immune competence of ALV-J-infected chickens did not show significant differences in immune responsiveness. The assays on cellular immunity showed a tendency to a lower response in ALV-J-infected birds, but these differences were not statistically significant.

Animals↗
PubMed2002

Development of organs and intestinal mucosa leukocytes in four broiler lines that differ in susceptibility to malabsorption syndrome.

Growth retardation in young broiler chicks due to poor nutrient metabolism, commonly known as malabsorption syndrome (MAS), is a widespread problem caused by enteric infections with a combination of pathogens mainly viruses. Genetic lines of broiler chickens differ in susceptibility to the syndrome. A difference in growth retardation was observed among four broiler lines (BL) after oral inoculation at 1 d of age with intestinal homogenates obtained from MAS-affected birds. Two of the lines that are more susceptible to MAS had severe weight gain depression. To uncover the factors that play a role in the susceptibility to MAS, we analyzed the growth rate of the body and vital organs and the quantity of leukocytes in the peripheral blood and intestinal mucosa. The development of the intestine, liver, bursa of Fabricius, and spleen was similar among the BL. The resistant BL had higher numbers of peripheral blood leukocytes, especially lymphocytes, at 1 d of age. A significant difference was noted in the numbers of CD4+ T cells and CD8+ T cells in the intestinal villi. At the ages of 3 and 8 d, the susceptible BL had more CD8+ T cells in the villi, whereas the ratios of CD4+:CD8+ T cells were higher in the resistant BL. This difference in the number of T-cell subpopulations in the intestinal mucosa might be an important factor in the difference in susceptibility to the enteric infections associated with MAS.

Animals↗
PubMed2001

Teledermatology as a tool for communication between general practitioners and dermatologists.

A feasibility study of teledermatology was undertaken in Groningen. Six general practitioners (GPs) sent digital images by email, along with relevant patient information, to dermatologists at the Martini Ziekenhuis Groningen, a general non-academic hospital. The dermatologists returned their responses by email. A total of 89 cases were dealt with in this way. On average, the GPs took three photographs per patient. The time taken by the GP to produce and transmit the images, and to implement the telemedicine advice received from the dermatologist, was 9 min and 3 min, respectively. The time spent on diagnosis, provision of advice and response by email amounted to 10 min for the dermatologist. It was concluded that teleconsultations by email are feasible in the daily practice of GPs and dermatologists in a general non-academic hospital. Generally, GPs, dermatologists and patients were satisfied with teleconsultations. Furthermore, GPs reported that 63% of the teleconsultations were of educational value.

Attitude of Health Personnel↗
PubMed2000

Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors.

Inhibitors based on the benzimidazole scaffold showed subnanomolar potency against Factor Xa with 500-1000-fold selectivity against thrombin and 50-100-fold selectivity against trypsin. The 2-substituent on the benzimidazole ring had a strong impact on the FXa inhibitory activity. Crystallography studies suggest that the 2-substituent may have a conformational effect favoring the extended binding conformation.

Anticoagulants↗
PubMed2000

Chronic salicylism resulting in noncardiogenic pulmonary edema requiring hemodialysis.

Salicylate intoxication is frequently overlooked as a cause of noncardiogenic pulmonary edema and altered mental status in adult patients. We describe a 42-year-old woman who presented with two episodes of recurrent noncardiogenic pulmonary edema requiring intubation. The first admission to hospital triggered an extensive initial workup that did not indicate a cause for the pulmonary edema. At the second presentation, recognition of the clinical syndrome in the emergency department led to the correct diagnosis of salicylate intoxication. The patient was successfully treated with hemodialysis and urinary alkalinization, leading to rapid resolution of pulmonary edema and extubation. Several aspects of the clinical presentation suggest that the patient suffers from chronic salicylism, probably complicated by episodic superimposed acute intoxication, a condition often misdiagnosed or diagnosed late in the course of disease, contributing to substantial morbidity and mortality in these patients. Maintenance of a high index of suspicion and rapid institution of appropriate therapy including hemodialysis once the diagnosis is established is an important determinant of outcome in this serious but underdiagnosed disorder.

Acetaminophen↗
PubMed2000

The urine/plasma electrolyte ratio: a predictive guide to water restriction.

Patients with hypotonic hyponatremia are encountered commonly in the general practice of medicine. Nearly all strategies for the management of subacute or chronic hyponatremia call for some amount of water restriction. The considerations for such a prescription have not been addressed in the literature. We describe therefore a simple approach grounded in the physiology of electrolyte-free water clearance that can be used at the bedside.

Electrolytes↗
PubMed2000

Effects of ZK-807834, a novel inhibitor of factor Xa, on arterial and venous thrombosis in rabbits.

Inhibition of factor Xa (FXa) may interrupt thrombus progression. This study compared the antithrombotic activity of a novel FXa inhibitor, ZK-807834 [MW, 527 D; Ki (human FXa), 0.11 nM], with recombinant tick anticoagulant peptide [rTAP; MW, 6,685 D; Ki, (human FXa) = 0.28 nM], and DX-9065a [MW 445 D, Ki (human FXa), 40 nM] in rabbits with arterial thrombosis induced by electrical vascular injury. ZK-807834 also was compared with low molecular weight heparin (LMWH; MW, 5,500 D) during venous thrombosis induced by placing a copper wire and threads in the vena cava. Inhibitors were administered as an i.v. bolus and 2-h infusion. Total dosages of ZK-807834, > or =0.7 micromol/kg (n = 18); rTAP, > or =1 micromol/kg (n = 18); or DX-9065a, > or =11 micromol/kg (n = 18) decreased the incidence of arterial thrombotic occlusion compared with control animals (p < 0.05). However, five of six animals given the lowest effective dosage of rTAP and four of six animals given DX-9065a bled from a surgical incision >5 min, but only two of six animals given ZK-807834 bled >5 min. Venous clot weights were reduced compared with controls for dosages of ZK-807834 > or =0.007 micromol/kg (n = 36) or LMWH > or =0.2 micromol/kg (n = 18). Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were unchanged from baseline at the minimally effective dose of ZK-807834, whereas aPTT was increased twofold at the effective dose of LMWH. Thus ZK-807834 may be useful to attenuate thrombosis at lower dosages and with less perturbation of systemic hemostasis compared with available agents.

Amidines↗
PubMed1999

Efficacy of an anti-CD138 immunotoxin and doxorubicin on drug-resistant and drug-sensitive myeloma cells.

Multidrug resistance is an increasing problem in the treatment of cancer. We evaluated in vitro the effect of an anti-CD138 plasma-cell-specific immunotoxin (IT, B-B4-SO6) in combination with the chemotherapeutic drug doxorubicin on drug-sensitive and drug-resistant variants of the multiple-myeloma (MM)-derived cell line RPMI8226 and freshly isolated malignant-myeloma cells. Drug-resistant RPMI8226 cells were still sensitive to the IT, although to a lesser extent than drug-sensitive cells. In the clonogenic assay, using 10 nM B-B4-SO6, at least 5 logs kill was found for drug-sensitive RPMI8226 cells, vs. 2.5 logs kill for the drug-resistant RPMI8226 cells. When a sub-optimal dose of 1 nM IT was combined with 3 ng/ml doxorubicin, which was toxic for drug-sensitive but not for drug-resistant cells, an additive effect was found for drug-sensitive RPMI8226 cells. The IT did not influence the sensitivity of resistant cells for doxorubicin. We therefore speculate that this type of IT, may be of more value in combination with primary chemotherapy. The effect of B-B4-SO6 on malignant-myeloma cells of patients was investigated in a viability assay. Both drug-sensitive and drug-resistant cells from MM patients were sensitive to B-B4-SO6. After 2 days, a 50% kill of malignant cells was found when 10 nM IT were used. Doxorubicin was effective only on sensitive cells, and there was a tendency for an additive effect in the combination of these cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Unusual cluster of mild invasive serogroup C meningococcal infection in a university college.

The objective of this study was to describe the epidemiology and public health response to an apparent cluster of Neisseria meningitidis serogroup C infection in university students in a residential college. A conventional epidemiological approach was taken, supported by routine and novel diagnostic techniques. Over the two days of 21-22 August 1997, three cases of suspected meningococcal infection were notified from a residential college complex at a university campus in the Sydney metropolitan area. Neisseria meningitidis was grown from throat swabs of all three cases, and was isolated from the blood of one case only. All three isolates were typed as C:2a:P1.5,2. Seroconversion was demonstrated by a novel method in the three cases. Rifampicin was given to all identified contacts. Forty-seven days after the index case, a 19 year old female living in the same complex was diagnosed with bacterial meningitis, and identified contacts given rifampicin. When this isolate was found to be group C, it was decided to vaccinate residents of the college complex. Genotyping and serotyping (C:2a:P1.5) later revealed the fourth isolate to be distinct from isolates from Cases 1-3. In conclusion the authors note that Australia's increasing capacity to type meningococcal strains is essential to understanding the epidemiology of this disease. Furthermore, typing information is of critical importance when decisions are made regarding mass vaccination. As early antibiotic treatment may inhibit isolation of the organism, development of novel approaches to diagnosis and typing should be supported.

Adolescent↗
PubMed1999

FK506-induced leukoencephalopathy in children with organ transplants.

FK506-induced leukoencephalopathy is a well-known entity in adult organ transplant patients. The neurotoxicity of FK506 immunosuppression is frequently reversible, with either reduction or cessation of the drug. This neurologic syndrome is not well documented in children. We report the clinical and radiologic features in four pediatric cases of FK506 leukoencephalopathy. In two of the four patients this syndrome was reversible.

Brain↗
PubMed1998

Generation and characterization of mice deficient in hepsin, a hepatic transmembrane serine protease.

Hepsin is a type II transmembrane serine protease highly expressed on the surface of hepatocytes. The physiological function of hepsin is not known, although in vitro studies indicate that hepsin plays a role in the initiation of blood coagulation and in hepatocyte growth. To determine the functional importance of hepsin, we generated hepsin-deficient mice by homologous recombination. Homozygous hepsin-/- mice were viable and fertile, and grew normally. In functional assays including tail bleeding time, plasma clotting times, and tissue factor- or LPS-induced disseminated intravascular coagulation models, no significant difference was found between hepsin-/- and wild-type litter mates. Liver weight and serum concentrations of liver-derived proteins or enzymes were similar in hepsin-/- and wild-type mice. Interestingly, serum concentrations of bone-derived alkaline phosphatase were approximately twofold higher in hepsin-/- mice of both sexes when compared with wild-type litter mates. No obvious abnormalities were found in major organs in hepsin-/- mice in histological examinations. Our results indicate that hepsin is not essential for embryonic development and normal hemostasis. Hepsin-/- mice will help to evaluate the long-term effects of hepsin deficiency in these animals.

Alkaline Phosphatase↗
PubMed1996

Metastatic uveal melanoma. A morphologic and immunohistochemical analysis.

BACKGROUND: Uveal melanoma often metastasizes late and preferentially to the liver, in contrast to cutaneous melanoma. The objective of the current study was to evaluate the histopathologic and immunohistochemical changes in primary uveal melanomas and their corresponding metastases. METHODS: The morphology and immunohistochemical reactivity for the melanoma-associated antibodies HMB-45, S-100 protein, and NKI-C3 were assessed for 29 primary uveal melanomas and their corresponding metastatses. RESULTS: A significant difference in cell type of the primary and the metastatic uveal melanoma was found (P = 0.0001). The metastases derived from the 29 patient's revealed 82.5% epithelioid or nonclassifiable cells. Positive staining of the primary uvea melanomas and their metastases was found to be 93% and 91%, respectively, for HMB-45, 80% and 66%, respectively, for S-100, and 56% and 71%, respectively, for NKI-C3. CONCLUSIONS: Metastases of uveal melanomas are comprised of a higher grade of malignant cell types. Nonclassifiable cells can be observed in 40% of metastatic lesions. In the current study, HMB-45 proved to be the most sensitive immunohistochemical marker in the analysis of metastatic uveal melanoma and should be used as part of a panel of monoclonal antibodies in the analysis of any metastatic tumor of unknown origin.

Antigens, Neoplasm↗
PubMed1996

Efficacy and toxicity of plasma-cell-reactive monoclonal antibodies B-B2 and B-B4 and their immunotoxins.

Immunotherapy based on the delivery of toxic agents to the tumor site using monoclonal antibodies (mAb) may be a promising modality in the treatment of hematological malignancies. In the selection of mAb, both for ex vivo but even more for in vivo therapy, not only their reactivity to the neoplastic cells should be considered, but also reactivity to other body constituents. Here we describe the screening of two human plasma-cell-reactive mAb B-B2 and B-B4, which may be used for immunotherapy of multiple myeloma. Cross-reactivity of B-B2 and B-B4 was determined by immunohistochemistry on a series of tissues. This revealed for both B-B2 and B-B4 a strong staining of epithelial cells in various organs, e.g. lung, liver, skin, kidney and gut, while only a weak and diffuse staining was seen with endothelial cells. In bone marrow reactivity was only found with plasma cells and not with hemopoietic precursors (CD34+ cells). Immunotoxins from B-B2 and B-B4 were constructed by coupling them to the plant-derived ribosome-inactivating protein saporin. Both B-B2 and B-B4 immunotoxins appeared to be efficient in specific inhibition of protein synthesis in plasma cell lines (IC50 respectively 1 nM and 0.1 nm). The immunotoxins were also tested on epithelial cell line A431, on liver cell line HepG2 and on human umbilical vein endothelial cells. The epithelial cell line A431 was reactive with both B-B2 and B-B4, but was only inhibited by B-B4 immunotoxin. Cell line HepG2 was reactive with both mAb, but was not inhibited by either immunotoxin. The endothelial cells showed no reactivity with B-B2 and B-B4 and were not inhibited by either immunotoxin. Bone marrow treated with B-B2 and B-B4 immunotoxin did not show a decrease in colonies of hemopoietic precursor cells. Incubation of multiple-myeloma-derived bone marrow with these immunotoxin resulted in a clear decrease of the number of plasma cells. From these data we conclude that B-B2 and B-B4 immunotoxin can be used for ex vivo bone marrow purging. Discrepancies were found between immunohistochemistry, binding assays and cytotoxicity assays with the mAb and the immunotoxin, which underlines the necessity for these various assays as a preclinical screening.

Antibodies, Monoclonal↗