Experimentally induced hypertensive G-minipigs were used for assessing the antihypertensive effects of acebutolol, a cardioselective βadrenergic blocking agent. In the acute experiment, six females were used. Acebutolol (3 mg/kg, iv.) alone or in combination with furosemide (1 mg/kg, iv.) or hydralazine (1 mg/kg, i.v.) was administered through an implanted catheter. In the chronic experiments, five females received oral acebutolol (100-200 mg/day) . The blood pressure, heart rate, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were used as parameters. In the acute experiment, there were no marked changes in the blood pressure or heart rate during the nondosing period. Acebutolol alone caused a marked decrease in the blood pressure and heart rate. In the two combination tests, combined administration with acebutolol and furosemide had a greater effect on the blood pressure and heart rate than did acebutolol alone. A combined acebutolol and hydralazine regimen caused a slight reduction not only in the blood pressure, but also in the heart rate compared with acebutolol alone. PRA and PAC remained essentially constant, with minor fluctuations, throughout the nondosing period. Following the injection of acebutolol alone, PRA showed an elevation with a significant rise after three hours and PAC showed a tendency to increase. PRA and PAC generally tended to increase in the case of combined administration with furosemide or hydralazine, but these tendencies were less conspicuous than with acebutolol alone. On the other hand, chronic treatment with acebutololproduced a significant decrease in the heart rate from two weeks after the administrationand in the blood pressure from four weeks. When subsequent doses were changed, no dose-related changes in systolic or diastolic pressure occurred two weeks after medication and only systolic pressure decreased significantly four weeks after treatment. The heart rate showed no further response to an increase in acebutolol dose. As mentioned above, hypertensive G-minipigs receiving acebutolol alone or in combination with furosemide or hydralazine showed antihypertensive effects.

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Alkaline phosphatase (Alp), esterase-I (Es-I), esterase-II (Es-II), carbonic anhydrase (CA), cell esterase (cEs), esterase-D (Es-D), isocitrate dehydrogenase (ICD), malate dehydrogenase (MDH), 6-phosphogluconate dehydrogenase (PGD), tetrazolium oxidase (To), ceruloplasmin (Cp), Haptoglobin (Hp) and hemoglobin (Hb) in 58-75 samples of three species of tamarins (Saguinus mystax, S. labiatus and S. oedipus) were detected by means of horizontal starch gel electrophoresis. Two types (Es-I 1 and Es-I 2) for Es-I, four types (Es-II 1, Es-II 2, Es-II 3 and Es-II 2-3) for Es-II, three types (cEs 1, cEs 2 and cEs 1-2) for cEs, three types (PGD 1, PGD 2 and PGD 1-2) for PGD, two types (To 1 and To 2) for To, and three types (Hp 3, Hp 1-3 and Hp 2-3) for Hp were observed. However, Alp, CA, Es-D, ICD, MDH, Cp and Hb were monomorphic. In the S. mystax, no Es-II or PGD variants were observed. No Es-II variant was seen in the S. oedipus. Gene frequencies of cEs, PGD and Hb were biased in the three species. It is concluded that six polymorphic loci are useful as genetic markers for a species or individual.

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In order to investigate coprophagy from the viewpoint of nutrition, fecal constituents were analyzed in freeze-dried samples. Feces were collected from 7: 00 to 11: 00 and from 19: 00 to 23: 00. Inorganic elements and crude fibers per unit weight were 3-4 times more concentrated in feces than in basal diet, whereas, crude proteins, crude fats and nitrogen-free extract showed various degrees of reduction. There were no differences in these tendencies with sampling time. As for some B vitamins, feces collected from 7 : 00 to 11: 00 contained 22-92 % more vitamins than feces collected from 19: 00 to 23: 00. In comparison with the dietary concentration, vitamin B₁₂ was increased by 124-197 times (520-730μg/100 g) in feces collected between 7: 00 and 11: 00. Folic acid in feces collected between 7: 00 and 11: 00 was 10 times greater than that in the diet. On the basis of the findings on vitamins, the effect of a vitamin B₁₂ fortified diet (1, 350 μg/100 g) on coprophagy was examined. Mean frequency of coprophagy per animal per day was 9.6 when animals were fed on the basal diet, whereas the frequency was immediately and significantly (p<0.05-p<0.01) reduced to 4.7 after the diet had been replaced by the fortified one. However, coprophagy was not completely inhibited by vitamin B₁₂ fortification. This indicates that some nutrient (s) in feces other than vitamin B₁₂ might be of use to the host, and that otherwise, coprophagy might be a basically habitual form of behavior. Furthermore, under the fortified diet, the frequency of coprophagy increased gradually. The cause of this was suspected to be alteration of the intestinal flora due to daily exposure to excessive vitamin B₁₂, affecting the nutritional status of the host.

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A collaborative study was conducted to investigate the teratological susceptibility of the Pika (Ochotona rufescens rufescens) to selected teratogenic chemicals: cyclophosphamide, 6-mercaptopurine, 5-fluorouracil, 6-aminonicotinamide, actinomycin D, ethylurethan, ampicillin, tetracycline, thalidomide, diphenylhydantoin, hypervitaminosis A, aspirin, dexamethasone, betamethasone and bredinin. Some of the chemicals were shown to be teratogenic in the Pika, but this animal was generally more resistant to their teratogenicity than the rabbit and rodents. In the Pika, thalidomide did not induce any typical limb defects, which have been produced in the rabbit. Pikas reproduce well and appear to have no substantial disadvantages as an animal species for teratological studies. Thus, the Pika may be useful as a new non-rodent species for teratological testings.

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We have established three analbuminemic congenic strains of rats (ACI-alb, F344-alb, and SHR-alb) by repeated backcrossing with a progeny test or intercrossing. Some coat color and biochemical marker genes of each congenic strain agreed with those of the background inbred strain of rats, except for the alb gene locus. These established congenic strains were maintained by cross-intercrossing. Body weights, organ weights and serum lipid concentrations of each strain were measured up to 30 weeks of age. Body weights of ACI-alb congenic strains (alb/alb and alb/+) were similar to those of the original ACI (+/+) strain, but those of F344-alb and SHR-alb were heavier in the order of +/+, alb/+ and alb/alb. The liver and adrenal weights of all strains were higher in the order of alb/alb, alb/+ and +/+. Serum lipid concentrations were also higher in the same order. These three analbuminemic congenic strains originating from different inbred strains should be useful in studies of carcinogenesis and genetically modified mechanisms of albumin functions.

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The tibia of 117 aged ICR mice was examined histologically to provide further information on degenerative osteoarthrosis. Incidence of the lesion became higher in the male older than 480 days of age and in the female older than 450 days. Main gross changes were roughening of the articular surface, narrowing or focal thickening of the articular cartilage, and osteophytes at the margins of the joint. Histology revealed loosening of the matrix, erosion, and marginal osteophytes in the articular cartilage, and sclerotic changes of the subchondral bone.

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Amputated hindlimbs of Xenopus laevis, develop various types of regenerates in relation with amputation level as well as stage development. The present experiments is an attempt to study the histological characteristics of Xenopus regenerations, i.e., rational changes of tissue components along the length of the regenerated part with special emphasis on the degree of muscle regeneration. Four types of regenerates were studied viz; (A), a 4th toe obtained from a completely restored regenerated limb at 126 days after amputation of limb at base level in stage 51. (B), an amputated limb with no external sign of regeneration of limb at thigh level in stage 60. (C), a spikeshaped regenerate at 96 days after amputation of limb at shank level in stage 63. (D), a spike-shaped regenerate at about 2 years after amputation of limb at shank level in stage 60. Cross sectional areas of muscle, skin gland, epidermis and cartilage in each of the four types of regenerates were measured with Image Analyzing Apparatus (VIP 121 CH, Olympus Co.) . The relative area of each tissue was expressed as a percentage of the cross sectional area of the limb. The obtained values were plotted along the length of the regenerate. Digitif orm regenerates were found to be more or less similar to the control limbs, i.e., provided joints and muscle, while the heteromorphic spike or rod shaped regenerates were simply provided with cartilaginous axial core without joint formation. Muscle area were reduced rapidly near the amputation area of these heteromorphic regenerates with no more continuation in the regenerated tissue. It is interesting to mention that percentage cartilage area of about 2 years old spike regenerate was higher than that of similar 96 days regenerate. In addition muscle regeneration was completely absent even in such an aged regenerate. The area showed fairly similar ratio irrespective of the external appearance of the regenerate. In 32 regenerates of which limbs were amputated at various developmental stages ranging between stage 51 and adult stage, the histological condition of muscle at the amputation site, were well observed. In all digitated types of regenerates even in those with reduced number of toes, muscles were found grown well in the regenerates. In heteromorphic regenerates without toe formation muscle did not usually regenerate. In few cases, however, a small mass of myoblastic like cells or small aggregation of differentiated muscle cells without any structural continuation with the stump muscles, were seen to develop in the midst of the regenerate. It may be said, therefore, that heteromorphic limb re-generates are devoid of muscle regeneration. However, in rare case weak sign of muscle regeneration was recognized by careful histological observation.

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The mandibular glands of the Japanese field vole were examined by light microscopy, and transmission and scanning electron microscopies. The acinar cells contained light and coarse secretory granules, and reacted with PAS and stained slightly with AB; they were considered to be seromucous in nature. The acinar epithelium was composed of light and dark cells containing many secretory granules. The intercalated duct cells consisted of light cells possessing a few dense granules. A few cytoplasmic crystalbides of moderate density were observed in occasional light cells. The striated ducts were comprized of two distinct portions, a secretory portion and a typical striated portion without secretory granules. The epithelium secretory portion consisted of light and dark cells containing acidophilic granules and exhibited a sexual dimorphism in these granules: The male epithelia contained the granules of low to high densities, while the female epithelia had only dense granules being smaller than those in the males. The epithelium of typical striated portion was composed of light and dark cells containing fine vacuoles and vesicles.

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Normal hematological values including erythrocyte count (RBC), hematocrit value (Ht), hemoglobin concentration (Hb), total leucocyte count (WBC), and differential leucocyte count were determined with 206 healthy cynomolgus monkeys (Macaca fascicularis) aged in 1 to 18 years. These animals were born and reared at Tsukuba Primate Center for Medical Science, NIH, Japan. Additionally, 32 cynomolgus monkeys of wild origin estimated to be 5 or more years old were examined for their hematology. The presence or absence of sex- and age-related differences in the values was statistically analysed. As regards infant and juvenile monkeys, there were no significant differences in RBC, Ht and Hb between males and females. However, these values became significantly larger in males than in females after sexual maturation. Lymphocyte count was larger than neutrophil count until 3 to 4 years of age after birth, but this relation was inverted in adult monkeys aged more than 5 years. Segmentation of the nucleus was a prominent finding in neutrophils. Neither sex- nor age-related difference in the number of nuclear segmentation was noted.

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Changes in hematological values were studied with 131 healthy cynomolgus monkeys aged less than 11 months. The parameters measured were erythrocyte count (RBC), hematocrit value (Ht), mean corpuscular volume (MCV), hemoglobin concentration (Hb), total leucocyte count (WBC), and differential leucocyte count. No remarkable change was found with RBC during the whole period of this study. Relatively high values were obtained with Ht, MCV, and Hb in the newborns aged 0 to 7 days. These values continued to decrease unil 3 months of age, after which the values increased again attaining approximately adult levels at 11 months of age. WBC was very high at birth and then decreased to the minimum level at 3 days of age. It was followed by gradual increase until about 4 months of age at which a nearly adult level was attained. Lymphocyte counts were smaller than neutrophil counts on the day of birth. However, this numerical relation was inverted 2 days after birth and the lymphocyte counts became markedly larger than the neutrophil counts about 1 week after birth. Additio-nally, the values obtained from the cord blood of 6 Cesarean-delivered newborns were compared with those from the blood taken 5 hours after cesarean delivery.

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The effects of ketamine anesthesia (15 mg/kg body weight) on hematological and serum biochemical values were examined in six female Cynomolgus monkeys (Macaca fascicularis) who were born in the wild. As control, another six female Cynomolgus monkeys of the same origin were injected with physiological saline. The white blood cell count, total protein concentration, albumin concentration and calcium concentration decreased after the injection of ketamine, whereas the red blood cell count, hematocrit value, hemoglobin concentration, total cholesterol concentration, free cholesterol concentration, triglyceride concentration, transaminase activities (GOT, GPT) and alkaline phosphatase activity were not affected. A transient increase of the serum glucose level was observed within 10 minutes after ketamine injection. The relationship between these effects of ketamine anesthesia and serum cortisol levels measured by radioimmunoassay was discussed.

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Bacteriological and serological examinations were made on Pasteurella multocida infection in two rabbit-breeding colonies. The organism was localized in the paranasal sinuses of 53 of 54 infected rabbits, excreting to the external nares of 49 rabbits. It was also isolated from the trachea and middle and inner ear of half of the infected animals and occasionally from the conjunctiva, lung and heart. The infection rate of the organism was very low (4.30) in sucklings younger than a month old, but increased with advancing age, reaching nearly 100% in adults more than five months of age. A rapid increase of the infection rate was observed at two to three months of age. Serum antibody against somatic antigen of P. multocida was demonstrated in infected rabbits by use of the tube agglutination test, showing a close correlation with isolation of the organism in adults. Sucklings younger than one month of age from infected dams were significantly resistant to experimental nasal infection of P. multocida.

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Spontaneous thyroid micro-follicular adenoma was found in an 18-month-old nursing Swiss albino mouse. The lesion was first noted as a tiny bulge at the base of the neck. The tumor was solid, and within two months, had grown such an enormous size that movement, feeding and suckling of the litter were greatly hampered. The litter of seven mice later died due to improper nursing while their mother remained generally unaffected by the mass.

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Detection rates of complement fixation antibodies in mice and rats were compared between two antigen strains of each of mouse hepatitis virus (MHV) and mouse adenovirus (MAV) . Among 66 and 47 naturally infected MHV-positive sera of mice (18 facilities) and rats (16 facilities) respectively, 17 mouse and 21 rat sera reacted with both Nu-67 and MHV-2 strains, but 49 mouse and 25 rat sera were positive to Nu-67 strain alone. Only one rat serum reacted with MHV-2 strain alone. In comparison with K87 and FL strains of MAV, all 8 positive mouse sera (3 facilities) reacted with K87 strain alone whereas out of 53 positive rat sera (20 facilities), 43, 6 and 4 sera reacted with K87 strain alone, with FL strain alone and with both the two strains, respectively.

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Thymus and spleen weights and lymphocytes in the blood were examined in mice transferred from 22°C to 12°C or 32°C environments. After the exposure to either environment, organ weights tended to decrease. In mice exposed to 12°C, the number of WBCs and mononuclear cells and the ratio and the number of T cells decreased on day 1 and/or 3 after the exposure. The number of B cells also declined on day 3, but the ratio of B cells increased on days 3 and 7. In mice exposed to 32°C, the number of WBCs and mononuclear cells and the number of T cells decreased on day 1 and increased on day 7 and/or 14. The ratio of T cells declined on days 1, 3 and 7, while that of B cells increased on day 3, and the number of B cells increased on day 7. These results show that wide variations in environmental temperature affect the weights of organs and the number of cells which act on immune responses in mice.

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Serological surveys of mice and rats naturally infected with Corynebacterium kutscheri were performed by examining serum samples collected from breeder and laboratory colonies between 1981 and 1983. Among 756 mice from 73 conventional colonies, only 4 animals (0.5%) from 3 colonies (4.1%) developed C. kutscheri antibody of 1: 40 to 1: 2, 560 titers. Three of them suffered from abscess caused by the organism. Regarding a titer of 1: 40 or higher as reliably positive, 87 (13.0%) of 669 conventional rats or 20 (32.8%) of 61 colonies were found to be infected with the organism. The antibodies were detected in both types of animals older than 6 months of age. No lesions caused by C. kutscheri were found in almost all the rats examined. Germ-free and SPF mice and rats were all negative for antibody at 1: 5 serum dilution.

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One handred and sixty rabbit sera from 10 breeding colonies and 13 laboratory colonies were tested for antibodies to Sendai virus and rotavirus by enzyme-linked immunosorbent assay (ELISA) . Antibodies were detected to Sendai virus in 53% and to rotavirus in 81%, indicating the prevalence of these viral infections in laboratory rabbit colonies.

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NOD mice spontaneously develop diabetic syndrome similar to that of insulin-dependent diabetes mellitus in man. Insulitis, i. e., lymphocytic infiltration into the pancreatic islets is the etiologic pathological lesion in the development of diabetes mellitus in NOD mice. In the present study, we examined the role of the T cell in the development of insulitis and overt diabetes in NOD mice using NOD athymic and euthymic congenic mice. None of the NOD athymic mice developed insulitis at 9 weeks of age or overt diabetes up to 30 weeks of age. In contrast, NOD euthymic littermates showed almost the same incidences of insulitis and overt diabetes as those of NOD mice. These observations suggest that T cells are essential for the development of insulitis and overt diabetes in NOD mice.

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Aspiration pneumonia observed in eight of 60 Sprague-Dawley rats which were orally treated with 0.5% carboxymethyl cellulose solution was investigated. Grossly, the lung showed white nodular foci in the parenchyma. Histologically, changes were characterized by fibrous material accompanied by inflammatory cells in the alveoli and bronchioles and formation of granulomas. It appeared that the inhaled fibrous material had originated from the carboxymethyl cellulose solution.

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Effects of anti-thymocyte serum (ATS) and anti-Thy 1, 2 monoclonal antibody on the spontaneously occurring diabetes in NOD mice were examined. Spontaneous diabetes in female mice was markedly suppressed by intravenous injection of rabbit antimouse thymocyte serum diluted to 1: 4 on three consecutive days during the time period from 70 to 100 days after birth; the cumulative incidence of overt diabetes upto 195 days of age was greatly reduced and the onset of diabetes was delayed. Similar effect was observed with anti-Thy 1, 2 antibody treatment. These findings suggest that T lymphocytes play a role in the production of spontaneous diabetes in this mouse strain.

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The open field test (OFT) was carried out on Wistar and Sprague-Dawley rats between the ages of 3 to 20 weeks. At that time, the behavior of each naive rat was observed for two 3-minute periods separated by an interval of 24 h (Day) . The OFT scores varied depending on the day and the age. Comparatively higher activity was observed in the extent of ambulation and rearing at 5 weeks old, rearing and preening at 7 weeks old, and preening and defecation at 11 weeks old in the Sprague-Dawley rats compared with the Wistar rats.

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Pathological examination was performed on a male 196-day-old Sprague-Dawley rat with hindrance of the motility. A tumor was found to locate in the right lateral ventricle. It was poorly demarcated, and was reddish gray in color. The tumor cells were pleomorphic, fusiform or polygonal in shape and varied in size, sometimes with formation of pseudorosettes. The tumor was diagnosed as ependymoma.

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In a [ (BN×TM) ×TM] Backcross progeny of rats, nine significant linkage associations were found among 105 pairwise combinations of 15 loci. After comparing this with other published data and data of personal communications, we considered that the d gene we tentatively designated may be identical to the gene for pink-eyed dilution (p), and that the associations of Gc-Hbb, RT 1-h, and Gc-Fh were due to chance rather than real linkage. The linkages obtained in this study, therefore, were Hbb-p (26.5±5.5) in LG I, Mup-1-Acon-1 (12.5±4.1) in LG II, Hao-1-Svp-1 (23.8±6.6) in LG IV, Es-1-Es-3 (17.2±4.7) in LG V, h-Gc (10.9±3.3) in LG VI, and Fh-Pep-3 (32.3±5.9) in LG X.

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S. pneumoniae, S. zooepidemicus, Salmonella spp., B, bronchiseptica and Sendai virus were examined in a total of 45 guinea pig colonies (17 institutional and 28 breeder's colonies) of Hartley strain, and found to be positive in 6, 3, 5, 20 and 14 colonies, respectively. Sendai virus was highly prevalent among guinea pigs, showing so high rates positive as 80 to 100% of animals obtained from 11 of the 14 contaminated colonies. B. bronchiseptica was also shown to be prevalent within contaminated colonies by indication of rates positive more than 40% of animals examined in 14 of the 20 colonies. Infection rates of other 3 pathogens, however, ranged from lower than 20% to higher than 80% according to colonies. All strains of Salmonella isolated in this survey were indentified as S. typhimuriuna and those of S. pneumoniae as serotype 19F.

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F344/Slc and F344/JCL rats 2 years of age were histologically examined for the incidence and distribution of calcification. In the male rats of both strains, calcification was observed in the testis, lung, brain, kidney, heart, aorta, cornea, prostate and seminal vesicle respectively. In the female F344/JCL rats, calcification appeared in the kidney, lung, cornea, brain, stomach, ovary and heart. Among these of both sexes, the lung was one of the most affected organs for calcification. On the other hand, calcification in the kidney was more severe and frequent in the females than in the males, suggesting that the sex may be one of enhancing factors for calcification.

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The vomeronasal organ (VNO) of the rat was removed completely using the following operation procedure. The mouth of the anesthetized rat was opened. A midline incision was made in the plate of the upper jaw, the tissue was retracted and a hole was drilled at both the anterior and posterior points of attachment of the VNO. The location of these holes allowed removal of the bone to which the VNO is attached together with the VNO itself.

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A serological survey for 15 murine pathogens was performed on 269 mouse sera collected from 21 conventional and 12 barrier colonies, and on 376 rat sera collected from 21 conventional and 23 barrier colonies. Animals having an antibody against at least one of the antigens were contained in 81.0% of conventional and 16.7% of barrier mouse colonies and also in 81.0% of conventional and 43.5% of barrier rat colonies. Main contaminants were mouse hepatitis virus and Sendai virus in mice, and Sendai virus and pneumonia virus of mice in rats. Results also indicated that antibodies to Toolan's H-1, minute virus of mice and PVM were positive in mice from a considerable number of colonies and those to Kilham rat virus, Mycoplasma pulmonis and Toolan's H-1 were sometimes detected in rats, suggesting prevalences of these pathogens in mice and rats in Japan.

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