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Effect of a previous operative procedure on natural progression of splenic lymphoma in SJL mice
EXPERIMENTAL PATHOLOGY AN EXPI:RIIltN'I'AL MODEL OF IIYI'ERSENGITIVITY PNEUIIONITIS (EXTKINSIC ALLERGIC ALVEOLITIS) . RIIAGWAKDEEN*, G.T. ___ PANG# & R - L. CL!Wy# DEFT OF FAI'IIOLOGY, TllE MAlTLAND IIOSPITAI,, NSW PEPT OF PATHOI,OGY, UNIVERSITY OF NEWCASTLE, NSW G.R. +
R
We describe an animal modc?l in which IIypersensiLivity Fileurnonitis developed after exposure to a hacterial 50 u l o[ a 24 hour nutrient broth culture antigen. containing 10'0 cfu/ml of Pasturella aneurnotropica were inoculated intratracheal.ly into 8 - 12 week old pathogen free Brown Norway r a t s led a standard laboratory chow diet. Control rats were inoculated with nutrient broth only. Rats ( 3 test and 2 control) were killed at 0, 4 , 8 , 24 and 48 hours, 6 days and 1 0 days alter inoculation. Lung showed progression of interstitial pneumonia from early lesions ( 2 4 and 4 8 hours) of interstitial subacute inflammatory cellular infiltrate centred around bronchioles to later lesions (6 and 10 days) with bronchiolilis obliterans and typical granulomatous lesions. Vasculitis was not seen. The pattern of pathology is identical with human IIP. Our rat model, unlike several other models previously described. did not require pre-immunisation before challenge. Moreover we believe this is the first tiote that HP has been described following bacterial Our model might prove useful for the colonisation. study of immunopathogeuesis of HP.
KEY WORDS: Pathology.
Alveolitis,
Experimental,
Animal,
EBV GENOME RESCUED FROM NPC XENOCRAFTS. DP hang*, I.1 Lui#, LS Makll, KW Lo* 6 WH Lau# *Dept Morbid Anatomy, PWI. CUHK 6 # I R O , QEH, Hong Kong It is generally agreed that the Epstein-Barr virus (EBV)is intimately associated with undifferentiated nasopharyngeal carcinoma (NPC) ( 1 ) . The present investigation aims at study the biologic and antigenic behaviour of EBV from fresh NPC biopsy grown as turnour in athymic mice. EBV-carrying, undifferentiated NPC biopsies were grafted into subrenal capsule of athymic mice. Tumour lines (xenografts) were successfully estaplished(2). Histology showed strong morpliologic similarity of carcinoma cells between original biopsy and xenograft but the latter was found to be free of lymphoid infiltration. These xenografts represent a'source of homogenous population of EBV-positive NPC cells devoid of lymphoid elements. Characterization of the NFC xenografts found:(a)the human origin and EBV DNA content of the mouse-grown turnour remained consistently demonstrable by Southern blot hybridization(b)in vitro culture of xenograft tissue gave rise to monolayer outgrowth of epithelial cells with detectable expression o f latent EBV gene products(EBNA)(c)when these outgrowths were activated with TPA and IUDR, complete viral replication was observed(rnature and immature EBV particles under EM examination)(d)the activated culture outgrowth,when cocultivated with foetal cord blood lymphocytes, immortalized lymphoblas toid cell line (LCL)has formed and expressed EBNA. Virus capsid antigen/early antigen can be detected whenLCL is induced with IUDR indicating EBV particles can be rescued u s i n g this system b(e)analysia of DNA of the LCL gives a pattern similar to BL viral isolates when hybridized to EBV-W,H and K fragments. The EBV genome isolated from NPC xenografts should be a valuable source for f i n e r structure mapping of disease-specific subtypes of EBV. (1) Klein G. in: The Epstein-Barr Virus. Epstein MA 6 Achong BC(ed) 1979;340-350 ( 2 ) lluang DP et al. J Exp Clin Cancer R e s 1988;7:8
ABSTRACTS OF A PREVIOUS OPERATIVE PROCEDURE ON NATURAL PROGRESSION OF SPLENIC LYMPHOMA IN SJL MICE.
EFFECT
F.C.S. 110, E.Y.W. Chow* & A.N.Y. Cheung, Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong.
I n a previous study of spontaneous lymphomas in SJL mice, we observed a difference in morphology as well as inimunophenotype in the tumours of younger mice ( < 4 2 wks) compared with older mice (>42 wks). One explanation for this was evolution o f the tumour with age, from a more differentiated to a less differentiated phenotype. I n order to test this hypothesis, we studied 2 sequential samples of spleen in 12 mice. A partial splenectomy was performed under anaesthesia in mice aged 36 or 40 wks, followed by autopsy after an interval of 8 or 12 wks. 10/12 mice had developed early microscopical foci of tumours at the time of splenectomy. I n only 3 was a change observed in morphology of the splenic tumour at autopsy which indicated dedifferentiation, although 4 other mice showed progression as assessed by extent o f tunour involvement. I n 2 mice, increasing tumour size was accompanied by increase in maturation. Two showed no change in either size or differentiation. In one mouse, tumour was no longer detectable at autopsy. I n a control g r o u p of the same age (without operation), established splenic tumours were found at autopsy in 10/11 mice, compared to 6/12 in the post-operative spleens. Although the numbers were too small to reach statistical significance, we believe that the operation itself may have modified the local environment so that the natural progression of the tumour could have been affected. This may have implications for studying the effects of incomplete excision on residual tumours.
THE LOCALISATION OF EOSINOPHIL MAJOR BASIC PROTEIN I N THE LUNGS OF 64 CASES OF FATAL ASTHMA.
L. Holloway*, P. Culbert, A. Cluroe, R . Beasley. The Wellington School of Medicine, University o f Otaao and Wellinqton Hospital, P.O. Box 7343, Weljington South, New Zealand Eosinophil major basic protein (MBP) 'which forms the core of the eosinophil granule is toxic to respiratory epithelium in vitro. An immunoperoxidase method has been used to demonstrate MBP in formalin Fixed paraffin sections of lung from a rstrospective series of 64 cases of fatal asthma. The method we describe offers advantages over the imtnunofluorescence technique used previously to detect MBP. Permanent preparations are produced allowing detailed histological examination by standard microscopy. Specific staining for MBP was found within eosinophils and this clearly demonstrated considerable variability i n the eosinophilia o f bronchial walls eYen between airways in the same histological section. Extra cellular MBP was detected within mucus plugs and deposited in a linear fashion along denuded basement membrane. I n many airways however epithelial shedding was present without significant tissue eosinophilia or linear MBP deposition.
R
We describe an animal modc?l in which IIypersensiLivity Fileurnonitis developed after exposure to a hacterial 50 u l o[ a 24 hour nutrient broth culture antigen. containing 10'0 cfu/ml of Pasturella aneurnotropica were inoculated intratracheal.ly into 8 - 12 week old pathogen free Brown Norway r a t s led a standard laboratory chow diet. Control rats were inoculated with nutrient broth only. Rats ( 3 test and 2 control) were killed at 0, 4 , 8 , 24 and 48 hours, 6 days and 1 0 days alter inoculation. Lung showed progression of interstitial pneumonia from early lesions ( 2 4 and 4 8 hours) of interstitial subacute inflammatory cellular infiltrate centred around bronchioles to later lesions (6 and 10 days) with bronchiolilis obliterans and typical granulomatous lesions. Vasculitis was not seen. The pattern of pathology is identical with human IIP. Our rat model, unlike several other models previously described. did not require pre-immunisation before challenge. Moreover we believe this is the first tiote that HP has been described following bacterial Our model might prove useful for the colonisation. study of immunopathogeuesis of HP.
KEY WORDS: Pathology.
Alveolitis,
Experimental,
Animal,
EBV GENOME RESCUED FROM NPC XENOCRAFTS. DP hang*, I.1 Lui#, LS Makll, KW Lo* 6 WH Lau# *Dept Morbid Anatomy, PWI. CUHK 6 # I R O , QEH, Hong Kong It is generally agreed that the Epstein-Barr virus (EBV)is intimately associated with undifferentiated nasopharyngeal carcinoma (NPC) ( 1 ) . The present investigation aims at study the biologic and antigenic behaviour of EBV from fresh NPC biopsy grown as turnour in athymic mice. EBV-carrying, undifferentiated NPC biopsies were grafted into subrenal capsule of athymic mice. Tumour lines (xenografts) were successfully estaplished(2). Histology showed strong morpliologic similarity of carcinoma cells between original biopsy and xenograft but the latter was found to be free of lymphoid infiltration. These xenografts represent a'source of homogenous population of EBV-positive NPC cells devoid of lymphoid elements. Characterization of the NFC xenografts found:(a)the human origin and EBV DNA content of the mouse-grown turnour remained consistently demonstrable by Southern blot hybridization(b)in vitro culture of xenograft tissue gave rise to monolayer outgrowth of epithelial cells with detectable expression o f latent EBV gene products(EBNA)(c)when these outgrowths were activated with TPA and IUDR, complete viral replication was observed(rnature and immature EBV particles under EM examination)(d)the activated culture outgrowth,when cocultivated with foetal cord blood lymphocytes, immortalized lymphoblas toid cell line (LCL)has formed and expressed EBNA. Virus capsid antigen/early antigen can be detected whenLCL is induced with IUDR indicating EBV particles can be rescued u s i n g this system b(e)analysia of DNA of the LCL gives a pattern similar to BL viral isolates when hybridized to EBV-W,H and K fragments. The EBV genome isolated from NPC xenografts should be a valuable source for f i n e r structure mapping of disease-specific subtypes of EBV. (1) Klein G. in: The Epstein-Barr Virus. Epstein MA 6 Achong BC(ed) 1979;340-350 ( 2 ) lluang DP et al. J Exp Clin Cancer R e s 1988;7:8
ABSTRACTS OF A PREVIOUS OPERATIVE PROCEDURE ON NATURAL PROGRESSION OF SPLENIC LYMPHOMA IN SJL MICE.
EFFECT
F.C.S. 110, E.Y.W. Chow* & A.N.Y. Cheung, Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong.
I n a previous study of spontaneous lymphomas in SJL mice, we observed a difference in morphology as well as inimunophenotype in the tumours of younger mice ( < 4 2 wks) compared with older mice (>42 wks). One explanation for this was evolution o f the tumour with age, from a more differentiated to a less differentiated phenotype. I n order to test this hypothesis, we studied 2 sequential samples of spleen in 12 mice. A partial splenectomy was performed under anaesthesia in mice aged 36 or 40 wks, followed by autopsy after an interval of 8 or 12 wks. 10/12 mice had developed early microscopical foci of tumours at the time of splenectomy. I n only 3 was a change observed in morphology of the splenic tumour at autopsy which indicated dedifferentiation, although 4 other mice showed progression as assessed by extent o f tunour involvement. I n 2 mice, increasing tumour size was accompanied by increase in maturation. Two showed no change in either size or differentiation. In one mouse, tumour was no longer detectable at autopsy. I n a control g r o u p of the same age (without operation), established splenic tumours were found at autopsy in 10/11 mice, compared to 6/12 in the post-operative spleens. Although the numbers were too small to reach statistical significance, we believe that the operation itself may have modified the local environment so that the natural progression of the tumour could have been affected. This may have implications for studying the effects of incomplete excision on residual tumours.
THE LOCALISATION OF EOSINOPHIL MAJOR BASIC PROTEIN I N THE LUNGS OF 64 CASES OF FATAL ASTHMA.
L. Holloway*, P. Culbert, A. Cluroe, R . Beasley. The Wellington School of Medicine, University o f Otaao and Wellinqton Hospital, P.O. Box 7343, Weljington South, New Zealand Eosinophil major basic protein (MBP) 'which forms the core of the eosinophil granule is toxic to respiratory epithelium in vitro. An immunoperoxidase method has been used to demonstrate MBP in formalin Fixed paraffin sections of lung from a rstrospective series of 64 cases of fatal asthma. The method we describe offers advantages over the imtnunofluorescence technique used previously to detect MBP. Permanent preparations are produced allowing detailed histological examination by standard microscopy. Specific staining for MBP was found within eosinophils and this clearly demonstrated considerable variability i n the eosinophilia o f bronchial walls eYen between airways in the same histological section. Extra cellular MBP was detected within mucus plugs and deposited in a linear fashion along denuded basement membrane. I n many airways however epithelial shedding was present without significant tissue eosinophilia or linear MBP deposition.