Studies on in-vivo erythrocyte sensitization and anaemia in acute Salmonella gallinarum infection of chickens

Factors sensitizing the erythrocytes in-vivo during acute Salmonella gallinarum infection in chickens, the probable mechanism of the associated haemolytic anaemia,and the respective roles played by the phenomena of in-vivo erythrocyte sensitization and the haemolytic episode in the overall pathogenesis of this disease syndrome, were investigated.Detailed pathological study of the blood during the acute disease showed that, at the time of death, the infected chicken had developed a very severe anaemia and leucocytosis. By relating the reticulocyte response and the absolute haematologic values to the gross and histopathological changes in the bone-marrow, spleen and the liver, it was shown that the anaemia observed was not of the dyshaemopoeitic type; it was, however, macrocytic and normochromic.It was observed that the erythrocytes regularly became sensitized in-vivo during infection and this was subsequently shown to be a common occurring phenomenon in this disease. By examining the biologic, serologic, immunologic, immunochemical and electrophoretic properties of these in-vivo sensitizing factor(s) it was conclusively established that these factors were specific bacterial 1ipo-polysaccharide and its homologous antibody.Examination of the patterns of sensitization revealed 4 types of in-vivo erythrocyte sensitization, which were found to be intimately related to the severity and mortality of the haemolytic and the disease syndromes respectively. It was also shown that, chickens in which erythrocyte sensitization was detected, a characteristic binodal erythrocyte fragility curve could be demonstrated.Techniques were developed for obtaining from infected animals.. [Page missing]... destruction. It was demonstrated that the sensitized cells recovered from infected animals may consist of a mixed, heterogeneous cell population of a small minority of •maximally' sensitized erythrocytes and a larger number of non-sensitized reticulocytes .Normal chicken serum was found to contain a high con¬ centration of heat-stable, non-gamrna globulin components which inhibit erythrocyte sensitization by bacterial polysaccharide. These inhibitors, determined to act by either neutralising or altering the polysaccharide in such a way as to prevent its sub¬ sequent adsorption by the erythrocyte, were also shown to be signi ficantly decreased in concentration at the peak of the haemolytic episode during acute fowl typhoid.A moderately severe imrnuno-haemolytic anaemia could be induced in chickens by single or multiple injections of endotoxin; evidence for the unequivocal participation of specific antibody in the production of this .anaemia was obtained by challenging endotoxin-injected chickens with homologous anti-endotoxin antibody.The significance of the anaemia in the overall pathogenesis of this infection was investigated and it was shown that the anaemia per se did not increase the susceptibility of the chicken to endotoxin. However, prior intravenous administration of invivo sensitized, homologous or normal, heterologous erythrocytes markedly decreased the of the subsequently injected endotoxin. This latter increase in susceptibility to endotoxin . was suggested to be due to a blockaded reticulo-endothelial system, resulting from increased phagocytosis of the foreign and altered homologous erythrocytes.These results were discussed in relation to the immunological basis of the mechanism of the anaemia and the significance of this anaemia in the overall pathogenesis of this disease syndrome. It was submitted that they were consistent with the hypothesis that the anaemia is the consequence of an immune reaction, involving the specific bacterial polysaccharide and homologous antibody. Furthermore, the anaemia plays an extremely important role in the pathogenesis of the fowl typhoid syndrome.The possibility that similar phenomena and iinnunologic mechanisms may be occurring in other acute gram-negative bacterial infections was also stressed

The impact of regulation on the performance of universal banks in Ghana

Undergraduate thesis submitted to the Department of Business Administration, Ashesi University, in partial fulfillment of Bachelor of Science degree in Business Administration, April 2019This research paper studies the impact of banking regulations on the performance of universal banks in Ghana. The study uses OLS regression for panel data to analyze the impact of the banking regulations on profitability and efficiency metrics of six universal banks listed on the Ghana Stock Exchange. The research uses data collected from 2005 to 2017. The first aim of the study is to identify previous regulatory changes and their impact on the performance of the universal banks. The second aim is to forecast the impact of future regulations on universal banks after the recent Ghana banking crisis. The use of capital adequacy ratio as the sole regulation is because of the recent banking crisis that mainly affected universal and commercial banks. The results of the study show that banking regulation has a positive relationship with return on assets, but a negative relationship with operating expense ratio.Ashesi Universit

Mechanisms controlling anaemia in Trypanosoma congolense infected mice.

Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia. The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng. The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from haemolysis induced anaemia after infection

Screen for IDH1, IDH2, IDH3, D2HGDH and L2HGDH Mutations in Glioblastoma

Isocitrate dehydrogenases (IDHs) catalyse oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). IDH1 functions in the cytosol and peroxisomes, whereas IDH2 and IDH3 are both localized in the mitochondria. Heterozygous somatic mutations in IDH1 occur at codon 132 in 70% of grade II–III gliomas and secondary glioblastomas (GBMs), and in 5% of primary GBMs. Mutations in IDH2 at codon 172 are present in grade II–III gliomas at a low frequency. IDH1 and IDH2 mutations cause both loss of normal enzyme function and gain-of-function, causing reduction of α-KG to D-2-hydroxyglutarate (D-2HG) which accumulates. Excess hydroxyglutarate (2HG) can also be caused by germline mutations in D- and L-2-hydroxyglutarate dehydrogenases (D2HGDH and L2HGDH). If loss of IDH function is critical for tumourigenesis, we might expect some tumours to acquire somatic IDH3 mutations. Alternatively, if 2HG accumulation is critical, some tumours might acquire somatic D2HGDH or L2HGDH mutations. We therefore screened 47 glioblastoma samples looking for changes in these genes. Although IDH1 R132H was identified in 12% of samples, no mutations were identified in any of the other genes. This suggests that mutations in IDH3, D2HGDH and L2HGDH do not occur at an appreciable frequency in GBM. One explanation is simply that mono-allelic IDH1 and IDH2 mutations occur more frequently by chance than the bi-allelic mutations expected at IDH3, D2HGDH and L2HGDH. Alternatively, both loss of IDH function and 2HG accumulation might be required for tumourigenesis, and only IDH1 and IDH2 mutations have these dual effects

Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. I. Parasitological, Hematological and Pathological Parameters

African trypanosomiasis is a severe parasitic disease that affects both humans and livestock. Several different species may cause animal trypanosomosis and although Trypanosoma vivax (sub-genus Duttonella) is currently responsible for the vast majority of debilitating cases causing great economic hardship in West Africa and South America, little is known about its biology and interaction with its hosts. Relatively speaking, T. vivax has been more than neglected despite an urgent need to develop efficient control strategies. Some pioneering rodent models were developed to circumvent the difficulties of working with livestock, but disappointedly were for the most part discontinued decades ago. To gain more insight into the biology of T. vivax, its interactions with the host and consequently its pathogenesis, we have developed a number of reproducible murine models using a parasite isolate that is infectious for rodents. Firstly, we analyzed the parasitical characteristics of the infection using inbred and outbred mouse strains to compare the impact of host genetic background on the infection and on survival rates. Hematological studies showed that the infection gave rise to severe anemia, and histopathological investigations in various organs showed multifocal inflammatory infiltrates associated with extramedullary hematopoiesis in the liver, and cerebral edema. The models developed are consistent with field observations and pave the way for subsequent in-depth studies into the pathogenesis of T. vivax - trypanosomosis

The unique resistance and resilience of the Nigerian West African Dwarf goat to gastrointestinal nematode infections

<p>Abstract</p> <p>Background</p> <p>West African Dwarf (WAD) goats serve an important role in the rural village economy of West Africa, especially among small-holder livestock owners. They have been shown to be trypanotolerant and to resist infections with <it>Haemonchus contortus </it>more effectively than any other known breed of goat.</p> <p>Methods</p> <p>In this paper we review what is known about the origins of this goat breed, explain its economic importance in rural West Africa and review the current status of our knowledge about its ability to resist parasitic infections.</p> <p>Conclusions</p> <p>We suggest that its unique capacity to show both trypanotolerance and resistance to gastrointestinal (GI) nematode infections is immunologically based and genetically endowed, and that knowledge of the underlying genes could be exploited to improve the capacity of more productive wool and milk producing, but GI nematode susceptible, breeds of goats to resist infection, without recourse to anthelmintics. Either conventional breeding allowing introgression of resistance alleles into susceptible breeds, or transgenesis could be exploited for this purpose. Appropriate legal protection of the resistance alleles of WAD goats might provide a much needed source of revenue for the countries in West Africa where the WAD goats exist and where currently living standards among rural populations are among the lowest in the world.</p

Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. II. Immunobiological Dysfunctions

Trypanosoma vivax is the main species involved in trypanosomosis, but very little is known about the immunobiology of the infective process caused by this parasite. Recently we undertook to further characterize the main parasitological, haematological and pathological characteristics of mouse models of T. vivax infection and noted severe anemia and thrombocytopenia coincident with rising parasitemia. To gain more insight into the organism's immunobiology, we studied lymphocyte populations in central (bone marrow) and peripherical (spleen and blood) tissues following mouse infection with T. vivax and showed that the immune system apparatus is affected both quantitatively and qualitatively. More precisely, after an initial increase that primarily involves CD4+ T cells and macrophages, the number of splenic B cells decreases in a step-wise manner. Our results show that while infection triggers the activation and proliferation of Hematopoietic Stem Cells, Granulocyte-Monocyte, Common Myeloid and Megacaryocyte Erythrocyte progenitors decrease in number in the course of the infection. An in-depth analysis of B-cell progenitors also indicated that maturation of pro-B into pre-B precursors seems to be compromised. This interferes with the mature B cell dynamics and renewal in the periphery. Altogether, our results show that T. vivax induces profound immunological alterations in myeloid and lymphoid progenitors which may prevent adequate control of T. vivax trypanosomosis