Editöre Mektup
Inducible nitric oxide synthase expression in cerebellum of dogs naturally infected with canine distemper virus
Öz
The aim of this study is to investigate of inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) expression in the cerebellum of dogs naturally infected with canine distemper virus (CDV), a disease characterized by demyelination in the white matter of the cerebellum. Cerebellum samples collected from naturally infected twenty-three which were 14 acute and 9 chronically infected. with CDV and six non-infected dogs. The presence of CDV infection was confirmed using histopathology and immunohistochemical localization of CDV antigen in glial cells of the white matter of the cerebellum. The CDV infected cerebella were also categorized Luxol Fast Blue staining according to the severity of demyelination as mild (n=7), moderate (n=9), and severe (n=7). The streptavidin-biotin-peroxidase technique was used to detect immunolocalisation of the CDV antigen, iNOS, NT and glial fibrillary acidic protein (GFAP). CDV antigens, immunopositive astrocytes, oligodendrocytes and granular neurons were seen in the white matter of the infected dogs. In the control dogs, iNOS and NT immunopositivity were not seen in the white matter of the cerebellum. In CDV infected dogs, iNOS immunopositivity was observed especially in astrocytes in white matter of cerebellum. The number of iNOS immunopositive astrocytes were significantly higher in chronic cases compared to acute cases of CDV infected dogs (p < 0.05). iNOS immunopositive gemistocytic astrocytes were also immunopositive for NT. iNOS and NT immunopositivity was not detected outside the region of the demyelinated areas. The iNOS immunopositive total cell number was found to be significantly higher in severely affected demyelination areas (p < 0.05). These data indicated that there was a relationship between degrees of the CDV associated with demyelination and the level of iNOS immunopositivity in the glial cells
Anahtar Kelimeler
Kaynakça
- Adamson DC, Wildemann B, Sasaki M, Glass JD, McArthur JC, Christov VI, Dawson TM, Dawson VL (1996): Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 274, 1917-1921.
- Bignami A, Dahl DD (1994): Glial Cells in the Central Nervous System and their Response to Injury. In: Glial Cells in the Central Nervous System, Landes, Austin.
- Bo L, Dawson TM, Wesselingh S, Mork S, Choi S, Kong PA, Hanley D, Trapp BD (1994): Induction of nit- ric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol 36, 778-786.
- Buisson A, Plotkine M, Boulu RG (1992): The neuropro- tective effect of a nitric oxide inhibitor in a rat model of fo- cal cerebral ischaemia. Br J Pharmacol 106, 766-767.
- Cross AH, Manning PT, Stern MK, Misko TP (1997): Evidence for the production of peroxynitrite in inflammatory CNS demyelination. J Neuroimmunol 80, 121-130.
- Dal Canto MC, Rabinowitz SG (1982): Experimental models of virus-induced demyelination of the central ner- vous system. Ann Neurol 11, 109-127.
- Dawson VL, Dawson TM (1995): Physiological and toxicological actions of nitric oxide in the central nervous system. Adv Pharmacol 34, 323-342.
- De Groot CJ, Ruuls SR, Theeuwes JW, Dijkstra CD, Van der Valk P (1997): Immunocytochemical characteri- zation of the expression of inducible and constitutive iso- forms of nitric oxide synthase in demyelinating multiple sclerosis lesions. J Neuropathol Exp Neurol 56, 10-20.
- Defaux A, Zurich MG, Braissant O, Honegger P, Mon- net-Tschudi F (2009): Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination. J Neuroinflammation. 7, 15-28.
- Grisham MB, Jourd'Heuil D, Wink DA (1999): Nitric oxide. I. Physiological chemistry of nitric oxide and its me- tabolites: implications in inflammation. Am J Physiol 276, 315-321.
- Headley SA, Soares IC, Graca DL (2001): Glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in dogs infected with canine distemper virus. J Comp Pathol 125, 90-97.
- Higgins RJ, Krakowka SG, Metzler A, Koestner A (1982): Primary demyelination in experimental canine dis- temper virus induced encephalomyelitis in gnotobiotic dogs. Sequential immunologic and morphologic findings. Acta Neuropathol 58, 1-8.
- Hilla EK, Zollinger LV, Watta HE, Carlsona NG, Rose JW (2004): Inducible nitric oxide synthase in chronic acti- ve multiple sclerosis plaques: distribution, cellular expres- sion and association with myelin damage. J Neuroimmunol 151, 171-179.
- Iadecola C, Zhang F, Xu S, Casey R, Ross ME (1995): Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. J Cereb Blood Flow Metab 15, 378-384.
- Iadecola C, Zhang F, Casey R, Nagayama M, Ross ME (1997): Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the inducible nitric oxide synthase gene. J Neurosci 17, 9157-9164.
- Ju WK, Park KJ, Choi EK, Kim J, Carp RI, Wisniewski HM, Kim YS (1998): Expression of inducible nitric oxide synthase in the brains of scrapie-infected mice. J Neurovirol 4, 445-450.
- Jungi TW, Pfister H, Sager H, Fatzer R, Vandevelde M, Zurbriggen A (1997): Comparison of inducible nitric oxide synthase expression in the brains of Listeria monocy- togenes-infected cattle, sheep, and goats and in macrop- hages stimulated in vitro. Infect Immun 65, 5279-5288.
- Kabakci N, Yarim M, Karahan S, Guvenc T, Yagci BB, Gurcan IS (2004): Immunohistochemical investigation of cerebellum in dogs infected with canine distemper virus. Acta Vet Hung 52, 327-337.
- Kim S, Moon C, Wie MB, Kim H, Tanuma N, Mat- sumoto Y, Shin T (2000): Enhanced expression of consti- tutive and inducible forms of nitric oxide synthase in auto- immune encephalomyelitis. J Vet Sci 1, 11-17.
- Lee SC, Dickson DW, Liu W, Brosnan CF (1993): In- duction of nitric oxide synthase activity in human astrocy- tes by interleukin-1 beta and interferon-gamma. J Neuro- immunol 46, 19-24.
- Leon-Chavez BA, Aguilar-Alonso P, Gonzalez-Barrios JA, Eguibar JR, Ugarte A, Brambila E, Ruiz-Arguelles A, Martinez-Fong D (2006): Increased nitric oxide levels and nitric oxide synthase isoform expression in the cere- bellum of the taiep rat during its severe demyelination sta- ge. Brain Res 1121, 221-230.
- Marques CP, Cheeran MC, Palmquist JM, Hu S, Lo- kensgard JR (2008): Microglia are the major cellular so- urce of inducible nitric oxide synthase during experimental herpes encephalitis. J Neurovirol 14, 229-238.
- Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE (1993): Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol, 151, 2132-2141.
- Merrill JE, Murphy SP (1997): Inflammatory events at the blood brain barrier: regulation of adhesion molecules, cytokines, and chemokines by reactive nitrogen and oxygen species. Brain Behav Immun 11, 245-263.
- Moncada S, Palmer RM, Higgs EA (1991): Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43, 109-142.
- Montgomery DL (1994): Astrocytes: form, functions, and roles in diseases. Vet Pathol 31, 45-167.
- Murphy S, Simmons ML, Agullo L, Garcia A, Feinstein DL, Galea E, Reis DJ, Minc-Golomb D, Schwartz JP (1993): Synthesis of nitric oxide in CNS glial cells. Trends Neurosci 16, 323-328.
- Mutinelli F, Vandevelde M, Griot C, Richard A (1989): Astrocytic infection in canine distemper virus-induced demyelination. Acta Neuropathol 77, 333-335.
- Rao CR. Linear statistical inference and its appli-cations. John&Sons. New York, 1973.
- Raposo C, Nunes AK, Luna RL, Araşjo SM, da Cruz- Höfling MA, Peixoto CA (2013): Sildenafil (Viagra) pro- tective effects on neuroinflammation: the role of iNOS/NO system in an inflammatory demyelination model. Mediators Inflamm, 2013,321460-321471.
- Rose JW, Hill KE, Wadab Y, Kurtz CIB, Tsunoda I, Fujinami RS, Cross AH (1998): Nitric oxide synthase in- hibitor, aminoguanidine, reduces inflammation and dem- yelination produced by Theiler's virus infection. J Neuro- immunol 81, 82-89.
- Santiago E, Pérez-Mediavilla LA, López-Moratalla N (1998): The role of nitric oxide in the pathogenesis of mul- tiple sclerosis. J Physiol Biochem 54, 229-237.
- Shin T, Tanuma N, Kim S, Jin J, Moon C, Kim K, Kohyama K, Matsumoto Y, Hyun B (1998): An inhibitor of inducible nitric oxide synthase ameliorates experimental autoimmune myocarditis in Lewis rats. J Neuroimmunol 92, 133-138.
- Shin T, Weinstock D, Castro MD, Acland H, Walter M, Kim H, Ahn M, Purchase HG (2001): Neuronal constitu- tive and inducible nitric oxide synthase expression in the brain of Listeria monocytogenes-infected cattle. Acta Vet Brno 70, 43-47.
- Shin T, Weinstock D, Castro MD, Acland H, Walter M, Kim HY, Purchase HG (2000): Immunohistochemical study of constitutive neuronal and inducible nitric oxide synthase in the central nervous system of goat with natural listeriosis. J Vet Sci 1, 77-80.
- Smith KJ, Lassmann H (2002): The role of nitric oxide in multiple sclerosis. Lancet Neurol 1, 232-241.
- Summers BA, Appel MJG (1987): Demyelination in canine distemper encephalomyelitis: an ultrastructural analysis. J Neurocytol 16, 871-881.
- Tipold A, Moore P, Zurbriggen A, Burgener I, Barben G, Vandevelde M (1999): Early T cell response in the central nervous system in canine distemper virus infection. Acta Neuropathol 97, 45-56.
- Tipold A, Vandevelde M, Wittek R, Moore P, Summer- field A, Zurbriggen A (2001): Partial protection and int- rathecal invasion of CD8(+) T cells in acute canine dis- temper virus infection. Vet Microbiol 83, 189-203.
- Vandevelde M, Zurbriggen A (2005): Demyelination in canine distemper virus infection: a review. Acta Neuropathol 109, 56-68.
- Vandevelde M, Frankhauser R, Kristensen F, Kristen- sen B (1981): Immunoglobulins in demyelinating lesions in canine distemper encephalitis an immunohistological study. Acta Neuropathol 54, 31-41.
- Wei XQ, Charles IG, Smith A, Ure J, Feng GJ, Huang FP, Xu D, Muller W, Moncada S, Liew FY (1995): Alte- red immune responses in mice lacking inducible nitric oxi- de synthase. Nature 375, 408-411.
- Wong JM, Billiar TR (1995): Regulation and function of inducible nitric oxide synthase during sepsis and acute inf- lammation. Adv Pharmacol 34, 155-170.
- Wünschmann A, Alldinger S, Kremmer E, Baumgart- ner W (1999): Identification of CD4+ and CD8+ T cell subsets and B cells in the brain of dogs with spontaneous acute, subacute-,and chronic-demyelinating distemper en- cephalitis. Vet Immunol Immunopathol 67, 101-116.
- Wünschmann A, Kremmer E, Baumgartner W (2000): Phenotypical characterization of T and B cell areas in lymphoid tissues of dogs with spontaneous distemper. Vet Immunol Immunopathol 73, 83-98.
- Yarım M, Kabakcı N (2002): Distribution of 3beta- hydroxysteroid dehydrogenase in the cerebellum in canine distemper virus infection. J Comp Path 127, 290-296.
- Yarim M, Gulbahar MY, Guvenc T, Karahan S, Hara- da N, Kabak YB, Karayigit MO (2010): Aromatase Expression in the Cerebellum of the Dog Infected with Ca- nine Distemper Virus. BMTW 123, 301-306.
Köpek gençlik hastalığı virusu ile doğal olarak enfekte köpeklerin serebellumunda indüklenebilir nitrik oksit sentaz ekspresyonu
Öz
Bu çalışmanın amacı, köpek gençlik hastalığı virusu (KGHV) ile doğal olarak enfekte köpek serebellumlarının beyaz maddesinde demyelinasyonla karakterize alanlarda indüklenebilir nitrik oksit sentaz (iNOS) ve nitrotirozin (NT) ekspresyonunun immunohistokimyasal olarak incelenmesidir. Çalışmada, KGHV ile 14 adedi akut ve 9 adedi kronik olmak üzere toplam 23 adet doğal enfekte ve 6 adet enfekte olmayan kontrol köpek serebellumu kullanıldı. KGHV enfeksiyonu histopatolojik ve immunohistokimyasal olarak serebellumun beyaz maddesindeki glial hücrelerde viral antijen varlığına dayanılarak doğrulandı. KGHV ile enfekte serebellumlar Luxol Fast Blue boyama ile demyelinasyonun şiddetine göre hafif (n=7), orta (n=9) ve şiddetli (n=7) olarak sınıflandırıldı. KGHV, iNOS, NT ve glial fibriler asidik proteinin (GFAP) immunpozitifliği ve immunolokalizasyonunu belirlemek için streptavidin-biotin-peroksidaz tekniği kullanıldı. KGHV immunopozitifliği enfekte köpek serebellumlarının beyaz maddesindeki astrositlerde, oligodendrositlerde ve granüler nöronlarda görüldü. Kontrol serebellumlarda iNOS ve NT immun pozitifliğinin bulunmadığı, enfekte köpek serebellumlarında ise glial hücrelerde özellikle astrositlerde immunopozitiflik olduğu belirlendi. iNOS immunopozitif astrosit sayısının kronik olgularda akut olgulara göre önemli derecede yüksek olduğu saptandı (p<0.05). Hem iNOS ve hem de NT immunopozitifliği gemistositik astrositlerde görüldü. Demyelinasyon alanlarının dışındaki bölgelerde iNOS ve NT immunopozitifliğine rastlanılmadı. Demyelinasyon alanlarında iNOS immunopozitif hücre sayısı önemli derecede yüksekti (p<0.05). Bu bulgular, KGH’daki demyelinasyonun derecesi ile iNOS immunopozitifliğinin düzeyi arasında bir ilişkinin olduğunu göstermektedir
Anahtar Kelimeler
Demyelinasyon iNOS köpek gençlik hastalığı virusu serebellum
Kaynakça
- Adamson DC, Wildemann B, Sasaki M, Glass JD, McArthur JC, Christov VI, Dawson TM, Dawson VL (1996): Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 274, 1917-1921.
- Bignami A, Dahl DD (1994): Glial Cells in the Central Nervous System and their Response to Injury. In: Glial Cells in the Central Nervous System, Landes, Austin.
- Bo L, Dawson TM, Wesselingh S, Mork S, Choi S, Kong PA, Hanley D, Trapp BD (1994): Induction of nit- ric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol 36, 778-786.
- Buisson A, Plotkine M, Boulu RG (1992): The neuropro- tective effect of a nitric oxide inhibitor in a rat model of fo- cal cerebral ischaemia. Br J Pharmacol 106, 766-767.
- Cross AH, Manning PT, Stern MK, Misko TP (1997): Evidence for the production of peroxynitrite in inflammatory CNS demyelination. J Neuroimmunol 80, 121-130.
- Dal Canto MC, Rabinowitz SG (1982): Experimental models of virus-induced demyelination of the central ner- vous system. Ann Neurol 11, 109-127.
- Dawson VL, Dawson TM (1995): Physiological and toxicological actions of nitric oxide in the central nervous system. Adv Pharmacol 34, 323-342.
- De Groot CJ, Ruuls SR, Theeuwes JW, Dijkstra CD, Van der Valk P (1997): Immunocytochemical characteri- zation of the expression of inducible and constitutive iso- forms of nitric oxide synthase in demyelinating multiple sclerosis lesions. J Neuropathol Exp Neurol 56, 10-20.
- Defaux A, Zurich MG, Braissant O, Honegger P, Mon- net-Tschudi F (2009): Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination. J Neuroinflammation. 7, 15-28.
- Grisham MB, Jourd'Heuil D, Wink DA (1999): Nitric oxide. I. Physiological chemistry of nitric oxide and its me- tabolites: implications in inflammation. Am J Physiol 276, 315-321.
- Headley SA, Soares IC, Graca DL (2001): Glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in dogs infected with canine distemper virus. J Comp Pathol 125, 90-97.
- Higgins RJ, Krakowka SG, Metzler A, Koestner A (1982): Primary demyelination in experimental canine dis- temper virus induced encephalomyelitis in gnotobiotic dogs. Sequential immunologic and morphologic findings. Acta Neuropathol 58, 1-8.
- Hilla EK, Zollinger LV, Watta HE, Carlsona NG, Rose JW (2004): Inducible nitric oxide synthase in chronic acti- ve multiple sclerosis plaques: distribution, cellular expres- sion and association with myelin damage. J Neuroimmunol 151, 171-179.
- Iadecola C, Zhang F, Xu S, Casey R, Ross ME (1995): Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. J Cereb Blood Flow Metab 15, 378-384.
- Iadecola C, Zhang F, Casey R, Nagayama M, Ross ME (1997): Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the inducible nitric oxide synthase gene. J Neurosci 17, 9157-9164.
- Ju WK, Park KJ, Choi EK, Kim J, Carp RI, Wisniewski HM, Kim YS (1998): Expression of inducible nitric oxide synthase in the brains of scrapie-infected mice. J Neurovirol 4, 445-450.
- Jungi TW, Pfister H, Sager H, Fatzer R, Vandevelde M, Zurbriggen A (1997): Comparison of inducible nitric oxide synthase expression in the brains of Listeria monocy- togenes-infected cattle, sheep, and goats and in macrop- hages stimulated in vitro. Infect Immun 65, 5279-5288.
- Kabakci N, Yarim M, Karahan S, Guvenc T, Yagci BB, Gurcan IS (2004): Immunohistochemical investigation of cerebellum in dogs infected with canine distemper virus. Acta Vet Hung 52, 327-337.
- Kim S, Moon C, Wie MB, Kim H, Tanuma N, Mat- sumoto Y, Shin T (2000): Enhanced expression of consti- tutive and inducible forms of nitric oxide synthase in auto- immune encephalomyelitis. J Vet Sci 1, 11-17.
- Lee SC, Dickson DW, Liu W, Brosnan CF (1993): In- duction of nitric oxide synthase activity in human astrocy- tes by interleukin-1 beta and interferon-gamma. J Neuro- immunol 46, 19-24.
- Leon-Chavez BA, Aguilar-Alonso P, Gonzalez-Barrios JA, Eguibar JR, Ugarte A, Brambila E, Ruiz-Arguelles A, Martinez-Fong D (2006): Increased nitric oxide levels and nitric oxide synthase isoform expression in the cere- bellum of the taiep rat during its severe demyelination sta- ge. Brain Res 1121, 221-230.
- Marques CP, Cheeran MC, Palmquist JM, Hu S, Lo- kensgard JR (2008): Microglia are the major cellular so- urce of inducible nitric oxide synthase during experimental herpes encephalitis. J Neurovirol 14, 229-238.
- Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE (1993): Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol, 151, 2132-2141.
- Merrill JE, Murphy SP (1997): Inflammatory events at the blood brain barrier: regulation of adhesion molecules, cytokines, and chemokines by reactive nitrogen and oxygen species. Brain Behav Immun 11, 245-263.
- Moncada S, Palmer RM, Higgs EA (1991): Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43, 109-142.
- Montgomery DL (1994): Astrocytes: form, functions, and roles in diseases. Vet Pathol 31, 45-167.
- Murphy S, Simmons ML, Agullo L, Garcia A, Feinstein DL, Galea E, Reis DJ, Minc-Golomb D, Schwartz JP (1993): Synthesis of nitric oxide in CNS glial cells. Trends Neurosci 16, 323-328.
- Mutinelli F, Vandevelde M, Griot C, Richard A (1989): Astrocytic infection in canine distemper virus-induced demyelination. Acta Neuropathol 77, 333-335.
- Rao CR. Linear statistical inference and its appli-cations. John&Sons. New York, 1973.
- Raposo C, Nunes AK, Luna RL, Araşjo SM, da Cruz- Höfling MA, Peixoto CA (2013): Sildenafil (Viagra) pro- tective effects on neuroinflammation: the role of iNOS/NO system in an inflammatory demyelination model. Mediators Inflamm, 2013,321460-321471.
- Rose JW, Hill KE, Wadab Y, Kurtz CIB, Tsunoda I, Fujinami RS, Cross AH (1998): Nitric oxide synthase in- hibitor, aminoguanidine, reduces inflammation and dem- yelination produced by Theiler's virus infection. J Neuro- immunol 81, 82-89.
- Santiago E, Pérez-Mediavilla LA, López-Moratalla N (1998): The role of nitric oxide in the pathogenesis of mul- tiple sclerosis. J Physiol Biochem 54, 229-237.
- Shin T, Tanuma N, Kim S, Jin J, Moon C, Kim K, Kohyama K, Matsumoto Y, Hyun B (1998): An inhibitor of inducible nitric oxide synthase ameliorates experimental autoimmune myocarditis in Lewis rats. J Neuroimmunol 92, 133-138.
- Shin T, Weinstock D, Castro MD, Acland H, Walter M, Kim H, Ahn M, Purchase HG (2001): Neuronal constitu- tive and inducible nitric oxide synthase expression in the brain of Listeria monocytogenes-infected cattle. Acta Vet Brno 70, 43-47.
- Shin T, Weinstock D, Castro MD, Acland H, Walter M, Kim HY, Purchase HG (2000): Immunohistochemical study of constitutive neuronal and inducible nitric oxide synthase in the central nervous system of goat with natural listeriosis. J Vet Sci 1, 77-80.
- Smith KJ, Lassmann H (2002): The role of nitric oxide in multiple sclerosis. Lancet Neurol 1, 232-241.
- Summers BA, Appel MJG (1987): Demyelination in canine distemper encephalomyelitis: an ultrastructural analysis. J Neurocytol 16, 871-881.
- Tipold A, Moore P, Zurbriggen A, Burgener I, Barben G, Vandevelde M (1999): Early T cell response in the central nervous system in canine distemper virus infection. Acta Neuropathol 97, 45-56.
- Tipold A, Vandevelde M, Wittek R, Moore P, Summer- field A, Zurbriggen A (2001): Partial protection and int- rathecal invasion of CD8(+) T cells in acute canine dis- temper virus infection. Vet Microbiol 83, 189-203.
- Vandevelde M, Zurbriggen A (2005): Demyelination in canine distemper virus infection: a review. Acta Neuropathol 109, 56-68.
- Vandevelde M, Frankhauser R, Kristensen F, Kristen- sen B (1981): Immunoglobulins in demyelinating lesions in canine distemper encephalitis an immunohistological study. Acta Neuropathol 54, 31-41.
- Wei XQ, Charles IG, Smith A, Ure J, Feng GJ, Huang FP, Xu D, Muller W, Moncada S, Liew FY (1995): Alte- red immune responses in mice lacking inducible nitric oxi- de synthase. Nature 375, 408-411.
- Wong JM, Billiar TR (1995): Regulation and function of inducible nitric oxide synthase during sepsis and acute inf- lammation. Adv Pharmacol 34, 155-170.
- Wünschmann A, Alldinger S, Kremmer E, Baumgart- ner W (1999): Identification of CD4+ and CD8+ T cell subsets and B cells in the brain of dogs with spontaneous acute, subacute-,and chronic-demyelinating distemper en- cephalitis. Vet Immunol Immunopathol 67, 101-116.
- Wünschmann A, Kremmer E, Baumgartner W (2000): Phenotypical characterization of T and B cell areas in lymphoid tissues of dogs with spontaneous distemper. Vet Immunol Immunopathol 73, 83-98.
- Yarım M, Kabakcı N (2002): Distribution of 3beta- hydroxysteroid dehydrogenase in the cerebellum in canine distemper virus infection. J Comp Path 127, 290-296.
- Yarim M, Gulbahar MY, Guvenc T, Karahan S, Hara- da N, Kabak YB, Karayigit MO (2010): Aromatase Expression in the Cerebellum of the Dog Infected with Ca- nine Distemper Virus. BMTW 123, 301-306.
Toplam 47 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Veteriner Cerrahi |
| Diğer ID | JA94FZ75BT |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Eylül 2015 |
| Yayımlandığı Sayı | Yıl 2015 |