Browsing by Author "Matondo, R. B."

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Clinico-pathological findings of the 2011 outbreak of peste des petits ruminants (PPR) in Tandahimba district, southern Tanzania
(Research Opinions in Animal and Veterinary Sciences, 2012) Matondo, R. B.; Muse, E. A.; Karimuribo, E. D.; Misinzo, G.; Albano, M. O.; Gitao, G. C.
Although PPR outbreaks were reported in Northern Tanzania since 2008, there has been no description of the clinical or pathological manifestation of the disease, an important criterion in guiding veterinarians and farmers on proper recognition and diagnosis of the disease. A study was therefore conducted to investigate and describe clinical signs and pathological lesions associated with 2011 Peste des petits ruminants (PPR) outbreak in goats and sheep in Tandahimba district located in Southern Tanzania. The investigation involved taking history and conducting clinical examination of PPR suspected cases (25 goats and 3 sheep) in the study district which had neither a history of vaccination against PPR nor previous illness due to PPR. This work was complemented by collection of pathological samples and specimens for laboratory examination. A detailed post-mortem was performed on three sacrificed animals followed by collection of specimens including lungs, liver, spleen and lymph nodes for histopathological examination. Clinical samples from 30 animals which included swabs from ocular, nasal and mouth lesions were also collected for confirmation of PPR through detection of PPR ribonucleic acid using reverse transcription polymerase chain reaction (RT-PCR). Clinical examinations of the cases showed signs suggestive of PPR including severe depression, high fever (41oC), anorexia, muco-pulurent nasal discharge, erosive and necrotic stomatitis, mild diarrhoea and skin nodules. Post mortem examination showed evidence of pneumonia including lung congestion and consolidation, increased thickness of inter-alveolar walls, moderate infiltration of inflammatory cells in bronchiolar subepithelial and perivascular layers. Overall 56.7% of the samples (n=30) tested were positive for PPR by RTPCR. This study has confirmed and described the presence of PPR in southern Tanzania. A more detailed study including other districts is recommended to provide more information regarding the magnitude and factors associated with PPR in Southern Tanzania.
E2f8 mediates tumor suppression in postnatal liver development
(The American Society for Clinical Investigation, 2016-08-01) Machiraju, Raghu; Kent, L. N.; Rakijas, J. B.; Pandit, S. K.; Westendorp, B.; Chen, H.; Huntington, J. T.; Tang, X.; Bae, S.; Srivastava, A.; Senapati, S.; Koivisto, C.; Martin, C. K.; Cuitino, M. C.; Perez, M.; Matondo, R. B.
E2F-mediated transcriptional repression of cell cycle–dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hepatocellular carcinoma (HCC). Here, we evaluated the function of the atypical repressor genes E2f7 and E2f8 in adult liver physiology. Using several loss-of-function alleles in mice, we determined that combined deletion of E2f7 and E2f8 in hepatocytes leads to HCC. Temporal-specific ablation strategies revealed that E2f8’s tumor suppressor role is critical during the first 2 weeks of life, which correspond to a highly proliferative stage of postnatal liver development. Disruption of E2F8’s DNA binding activity phenocopied the effects of an E2f8 null allele and led to HCC. Finally, a profile of chromatin occupancy and gene expression in young and tumor-bearing mice identified a set of shared targets for E2F7 and E2F8 whose increased expression during early postnatal liver development is associated with HCC progression in mice. Increased expression of E2F8-specific target genes was also observed in human liver biopsies from HCC patients compared to healthy patients. In summary, these studies suggest that E2F8-mediated transcriptional repression is a critical tumor suppressor mechanism during postnatal liver development
Large induction of type III deiodinase expression after partial hepatectomy in the regenerating mouse and rat liver
(Oxford University Press, 2008-09-11) Kester, M. H. A.; Matondo, R. B.; Toussaint, M. J. M.; Punt, C. A.; Aarnio, A. M.; Darras, V. M.; Everts, M. E.; Bruin, A.; Visser, T. J.
The deiodinase types 1 (D1) and 2 (D2) catalyze the activation of T4 to T3, whereas type 3 deiodinase (D3) catalyzes the inactivation of T3 and T4. D3 plays a key role in ontrolling thyroid hormone bioavailability. It is highly expressed during fetal evelopment, but also in other processes with increased cell proliferation, e.g. in vascular tumors. Because tissue regeneration is dependent on cellular proliferation and is associated with activation of fetal genes, we evaluated deiodinase activities and mRNA expression in rat and mouse liver, as well as the local and systemic thyroid hormone status after partial hepatectomy (PH).Weobserved that in rats, D3 activity was increased 10-fold at 20 h and 3-fold at 48 h after PH; D3 mRNA expression was increased 3-fold at 20 h. The increase in D3 expression was associated with maximum 2- to 3-fold decreases of serum and liver T3 and T4 levels at 20 to 24 h after PH. In mice, D3 activity was increased 5-fold at 12 h, 8-fold at 24 h, 40-fold at 36 h, 15-fold at 48 h, and 7-fold at 72 h after PH. In correlation with this, D3 mRNA was highest (6-fold increase), and serum T3 and T4 were lowest at 36 h. Furthermore, as a measure for cell proliferation, 5-bromo-2_-deoxyuridine incorporation peaked at 20–24 h after PH in rats and at 36 h in mice. No significant effect on D1 activity or mRNA expression was found after PH. D2 activity was always undetectable. In conclusion, we found a large induction of hepatic D3 expression after PH that was correlated with an increased cellular proliferation and decreased serum and liver T3 and T4 levels. Our data suggest that D3 is important in the modulation of thyroid hormone levels in the regenerating liver, in which a decrease in cellular T3 permits an increase in proliferation
Lymphoid leukosis in commercial layers in Morogoro
(Tanzania Veterinary Association, 2010) Mathew, C.; Matondo, R. B.; Malago, J. J.; Maselle, R. M.; Mwamengele, G. L.
A total of 25 commercial layer carcases from seven poultry farms in Morogoro municipality were examined for gross and histopathological changes. Grossly, splenomegally, renomegally and hepatomegally were striking features. Both the liver and spleen were almost twice the size of normal organs. The surfaces of the liver, spleen, kidneys, lungs and the heart had yellowish white to grey multifocal and focally extensive patches of variable sizes. The lungs were consolidated. Histologically, the liver, spleen, kidneys, lungs, and the heart had heavy infiltration of large lymphocytes with abundant cytoplasm and poorly stained eosinophilic cytoplasm. There were also small lymphocytes with scant cytoplasm and deeply stained eccentrically placed nuclei and numerous mitotic figures. The history, clinical signs, and pathologic features were suggestive of avian lymphoid leukosis
Peste des Petits Ruminants (PPR) outbreak in southern, Tanzania
(RUFORUM, 2012) Muse, E. A.; Matondo, R. B.; Karimuribo, E. D.; Misinzo, G.; Mellau, L. S. B.; Msoffe, P. L. M.; Albano, M. O.; Gitao, G. C.
Peste des petits ruminants (PPR) was first confirmed in Tanzania in 2008, however description of clinical or pathological signs was not carried out although this is important to assist quick identification and reporting of PPR cases by both livestock keepers and field-based animal health workers. A study was therefore conducted to investigate and describe clinical signs and pathological lesions associated with suspected PPR cases in southern Tanzania. It involved history taking and clinical examination of suspected cases of 25 goats and 3 sheep. Post- mortem examination of some cases was performed followed by collection of specimens for histopathological examination. Swabs were also collected for confirmation of PPR by detecting ribonucleic acid using reverse transcription polymerase chain reaction (RT-PCR). Serum samples were analysed using competitive enzyme linked immunosorbent assay (cELISA). Severe depression, high fever, anorexia, muco-pulurent nasal discharge, erosive and necrotic stomatitis, mild diarrhoea and skin nodules were major signs suggestive of PPR. Post mortem examination showed evidence of pneumonia including lung congestion and consolidation. RT-PCR confirmed presence of the PPR virus in samples and serum antibodies showed seroprevalence of 31%.
Surgical resection and radiofrequency ablation initiate cancer in cytokeratin-19+-liver cells deficient for p53 and Rb
(2016-08-23) Matondo, R. B.; Toussaint, M. J. M.; Govaert, K.M.; Vuuren, L. D.; Nantasanti, S.; Nijkamp, M. W.; Pandit, S. K.; Tooten, P. C. J.; Koster, M. H.; Holleman, K.; Schot, A.; Gu, G.; Spee, B.; Roskams, T.; Borel, R. I.; Schotanus, B.; Kranenburg, O.; de Bruin, A.
The long term prognosis of liver cancer patients remains unsatisfactory because of cancer recurrence after surgical interventions, particularly in patients with viral infections. Since hepatitis B and C viral proteins lead to inactivation of the tumor suppressors p53 and Retinoblastoma (Rb), we hypothesize that surgery in the context of p53/Rb inactivation initiate de novo tumorigenesis. We, therefore, generated transgenic mice with hepatocyte and cholangiocyte/ liver progenitor cell (LPC)-specific deletion of p53 and Rb, by interbreeding conditional p53/Rb knockout mice with either Albumin-cre or Cytokeratin-19-cre transgenic mice. We show that liver cancer develops at the necrotic injury site after surgical resection or radiofrequency ablation in p53/Rb deficient livers. Cancer initiation occurs as a result of specific migration, expansion and transformation of cytokeratin- 19+-liver (CK-19+) cells. At the injury site migrating CK-19+ cells formed small bile ducts and adjacent cells strongly expressed the transforming growth factor β (TGFβ). Isolated cytokeratin-19+ cells deficient for p53/Rb were resistant against hypoxia and TGFβ-mediated growth inhibition. CK-19+ specific deletion of p53/Rb verified that carcinomas at the injury site originates from cholangiocytes or liver progenitor cells. These findings suggest that human liver patients with hepatitis B and C viral infection or with mutations for p53 and Rb are at high risk to develop tumors at the surgical intervention site.