The cellularity and composition of the spleen lymph node thymus and peripheral blood and tempo of regeneration were studied at various time points after syngeneic bone marrow transplantation(BMT) in C3H/Hen mice. Significant depression of absolute lymphocyte count was noted on week 1 after lethal whole-body irradiation and BMT. In comparison to the lymph node thymus and spleen had an rapid regeneration of cellularity. The distinct cell populations($CD4^+,\;CD8^+,\;CD28^+,\;B220^+) have determined in the lymphoid tissue of mice subjected to irradiation. The relative representation of these subpopulations was significantly different from that in nonirradiated control. $CD4^+\;and\;CD8^+$ cells were present in very low numbers whereas the $B220^+$ cells reached more than normal range at 2 weeks after BMT. The number of $CD4^+$ cells returned to normal relatively soon than $CD8^+$ cell. At week 4 after BMT, the cellularity and composition of spleen lymph node and peripheral blood lymphocyte reached about 50% of the normal range therefore we can choose this time point for the other tests of immune function after BMT.

Lethally irradited C3H/HeN mice were transplanted with syngeneic bone marrow. The B cell regeneration levels of spontaneous serum Ig, fecal igA and specific ig to diphtheria toxoid were determined at various time points. The number of B220+ cells reached normal range at 4 weeks after bone marrow transplantation(BMT) in spleen and lymph node. The B cell number of spleen returned to normal relatively soon than in the lymph node. Within 5 to 7 weeks after BMT, the transplanted mice contained nearly normal levels of spontaneous serum IgA, IgG2b and fecal IgA, but 2 fold lower levels of serum IgG2a, IgM and IgG3. Especially IgG3 levels were within low-normal range throughout the study. One to two weeks after immunization the predominant anti-diphtheria toxoid subtype was IgM. The levels of specific serum Ig were very low and after booster immunization at week 6, the short-lasting increase of Ig production was notd.

The anticarcinogenic effects of dimethyl disulfide(DMDS, methyl disulfide)and diallyl disulfide(DADA, allyl disulfide) were studied in a 28 weeks rat multi-organ carcinogenesis model. neoplastic and preneoplastic lesions were observed in the liver kidney thyroid gland esophagus duodenum colon, rectum and adrenal gland. Tesults showed that neoplastic lesions in the kidney liver and thyroid gland were inhibited by DADS but those in the liver and colon were enhanced by DMDS when compared to positive control group. incidence of neoplastic lesions in the other organs were not changed by DMDS or DADS exposure. While GST-p positive foci in the liver were increased by DMDS, DADS had no effect. There was no significant histopathological lesion in DMDS or DADS treated group without pretreatment with carcinogens.

Protein kinase C an enzyme of signal transduction has been known to regulate cell proliferation activation as well as apoptosis in some cancer cell lines. To explore the role of PKC in the course of cell mediated autoimmune disease such as experimental autoimmune encephalomyelitis (EAE) EAE was induced in Lewis rats(6-8 weeks old) with immunization of myelin basic protein supplemented with complete Freund's adjuvants and affected spinal cords were sampled at days 13 postimmunization(PI) as peak stage of EAE and at days 21 PI as recovery stage. The spinal cords with EAE were subjected to Northern blot analysis and insitu hybridization of PKC delta which is one of prominant isotypes of PKC in the haematopoietic cells. Northern blot analysis showed that levels of PKS delta mRNA in the spinal cords of rats withEAE was significantly increased at days 13 PI in which inflammatory cells including T cells and macrophages in the EAE lesions appeared. however the stage. By in situ hybridization signals of PKC delta in EAE lesions was intensely expressed on the delta is also expressed on some brain cells in normal rat central nervous system This finding suggests that PKC plays an important role on either activation of inflammatory cells including encephalitogenic T cells and macrophages or apoptotic elimination of some inflammatory cells depending on the stge of EAE.

We investigated metabolism and carcinogenesis in livers of Sprague-Dawley rats fed juices and pelleted diets containing Korean native plants petasites japonicus Maxim by evaluating cell localization and expression of cytochrome P450s and GST-P. Anti-cytochrome P450s application in liver sections revealed three to four times increased expression of cytochrome P450E1 immunoreactivity in degenerative hepatocytes when compared to histologically normal hepatocytes. Anti-GST-P in showed positive pren plastic foci as well as in individual hepatocytes randomly scattered throughout all liver sections examined. Additionally GST-P was evident in proliferative endothelial cells and biliary epithelial cells in exposed rat livers. These results suggested that the increased level of cytochrome P4502E1 in affected hepatocytes was a direct consequence of Petasites japonicus toxicity. Further immunoreactivity to anti-GST-P in hepatocytes endothelial cells and biliary epithelial cells indicated a possible preneoplastic effects of Petasites japonicus in Sprague-Dawley rat.

The phototoxic potentials of LB20304a a new quinolone compound being developed by LG Chemical Ltd, and reference compounds (Ciprofloxacin; CPFX, Enoxacin; ENX and Lomefloxacin; LFLX) were compared in a murine model. in addition photostability of these compunds was studied after irradiation with long-wave UV light(UVA, 0, 0.3 1 or 3 Joule/$Cm^2$) When hairless mice(9 to 11 weeks old 19-26g) were orally administered with different dose levels of test compunds and exposed to UVA(40J/$cm^2$) inflammatory reactions were observed in a dose dependent manner. Among the compounds tested, LB20304a demonstrated the least phototoxic effects and showed no inflammatroy lesions at a dose level of 100mg.kg (Low dose). ENX and LFLX demonstrated much greater phototoxic reactions while CPFX showed similar or slightly greater phototoxic reactions compared to LB20304a. Similar to the in-vivo results the solutions of LB20304a and CPFX irradiated with UVA demonstrated reduced spectral changes compared to those of ENX and LFLX. In conclusion these data suggest that phototoxic potencies of the quinolones tested were; LFLX > ENX > CPFX $\geq$ LB20304a. No phototoxic dose of LB20304a in mice was 100 mg/kg.

The hematology and clinical chemistry data based on the well defined normal data are essential in the safety assessment. It is important that normal values of cliniclal pathology parameters would be optimized to be accurate. So the purpose of this experiment was to compare the ranges of normal data in hematology value and serum chemistry between both sexes of F344 and Wistar rats at 5, 10, 20, 40 and 90 weeks. of age. The neutrophils eosinophils and monocytes increased with age in male Wistar rats. And serum total bilirubin and potassium were highest and alkaline phosphatase was lowest at 90 weeks in Wistar rats. As compared with Wistar rat the serum aspartate aminotransferase of F344 rats increased with age in both sexes but inorganic phosphorus decreased with age. The serum alkaline phosphatase decreased with age and potassium was highest at 90weeks. These normal data would be useful in improving the accuracy of clinical pathology value in the safety assessment.

Enterotoxemia caused by Clostridium perfringens(Cl. perfringens)has occurred sporadically with devastating effect in Korean cattle. The disease is confirmed by detecting bacterial toxin the interstinal contents. however diagnosis has been challenging since the toxin is short lived and it must be demonstrated within one hour following death. The purpose of this paper is to provide additional clinicall and pathological information derived from observation of cattle administered with Cl. perfringens type A and/or its toxins isolated from natural case. Clinically cattle died suddenly in lateral recumbency with dyspnea tachycardia and muscle tremor without increased rectal temperature. hematology showed leukopenia with absolute decrease of all leukocytes. Blood glucose AST and ALT were increased. Grossly lungs were hyperemic haemorrhagic and edematous. Small intestine especially ileum was hyperemic and hemorrhagic with diffuse areas of necrosis. This study demonstrated that death without increased rectal temperature combined with leukopenia increased serum glucose pulmonary haemorrhage and edema plus necrotizing ileitis are important features associated with enterotoxemia due to Cl. perfringens type. A.

Epizootic streptococal infction is one of the common disease in guinea pig. We have confirmed 54 case of epizootic streptococal infection in guinea pig by histopathology and epidemiology. Grossly infection is characterized by the presense one to several enlarged lymph nodes particularly of the mandible cervical lymph nodes and accompanied by pleuropneumonia. Histologically there were lymphadenitis with abscesses surrounded by loose connective tissue fibrinopurulent pneumonia pleuritis myocarditis pericarditis and peritonitis. Epidemiological survey revealed that mortality was high in young adult female(15.1%) and changeable weather season such as spring and fall. From findings it was suggested that epizootic streptococal infection of guinea pig begin to infect in breeding colony around weaning period and died from that infection at animal facility during the quarantine period.

Eighteen NZW rabbits used for local skin irritation study were examined grossly and microscopically for natural infection with Encephalitozoon cuniculi. For microscopic tissue evaluation histochemical techniques such as PAS Gram iron hematoxylin and HE stain were used. Although rabbits in the study had no abnormal clinical signs 7/18(38.9%) animals were microscopically infected with E. cuniculi. The affected rabbits had gray-whitish and depressed approximately 0.1∼0.6 cm diameter lesions in the kidneys. All other organs examined were grossly unremarkable. Histopathologically however in addition to segmental interstitial nephritis focal lymphocytic myocarditis and granulomatous inflammatory reaction in portal areas of the liver multifocal granulomatous foci with vasculitis were present in the brain kidney and lungs. Aggregates of minute oval organisms were observed in brain and kidney sections frequently within the granulomatous foci and sometimes without any inflammatory reaction particularly in the renal tubules. in histochemical stains the organisms were gram positive stained with iron hematoxylin and had PAS positive granule at one pole. They measured approximately 1.5×2.5μm consistent with E. cuniculi. Histochemical characterization is important to differentiate E. cuniculi from other common protozoal infection such as Toxoplasma gondii. This study demonstrate the importance of subclinical. E. cunuculi infection and the associated histological alterations may interfere with tissue evaluation in toxicologic studies.

Histological investigation of the number of follicles following gonadotropin treatments for superovulation was carried out in mature Sprague-Dwaley(SD) rats. Routinely serial sections of paraffin-embedded ovaries were stained with hematoxylin-eosin and evaluated with light microscope. During the study unusual cases of microscopic alterations were observed in the medulla of ovaries in two rats. Case one: An ovum and its follicular fluid outflowed in medulla of ovary. The follicular fluid was densly proteinuous. Corona raiata consisted of 2-6 layers thick cells in the periphery of the ovum. While the cortical side of the follicular wall was intact with normal granulosa cell layer the meullary side of it was ruptured. Case two: A large cyst was present in medulla of ovary hilus. The cyst occupied the entire medulla displacing the ovarian archetecture and enclosed by connective tissue and smooth muscle wall.

Capillaria hepatica a primary trichuroid nematode parasite in rodents, has been reported in wide range of secondary hosts including humans. We report a rare case of Capillariasis in a 4-year old raccoon dog(Nyctereutes procyonoides) submitted to the Veterinary Diagnostic Laboratory Chonbuk National University for necropsy on July 5, 1996. Grossly the thoracic cavity contained approximately 200 mls of blood-tinged exudate. Edematous lesion was present around aorta and vena cava. liver was slightly swollen and mottled and contained multifocal yellowish-white lesions ranging from 1 to 3 mm in diameter. Histologically liver lesions were localized around central veins and were characterized by cell swelling and necrosis with mixed inflammatory cells surrounding parasite eggs. These eggs were barrel-shaped with polar caps consistent with Capillaria hepatica.