The changes in the nasal cavity volume of rats with age and the area exposed to nasal drops administered into the nasal cavity were investigated. Results indicated that the nasal cavity volume lineally increased as rats grew older. In 7-week-old rats, the exposed area in the case of an administration volume of 25 μl, based on practice, was naso-, maxillo-, and ethmoid turbinate and this volume was enough to expose the whole area of the nasal cavity including the ethmoid turbinate. On the other hand, in 27-week-old rats, administration volumes of 10 and 25 μl were not enough to expose the ethmoid turbinate. This indicated that the exposed area tended to become narrower in 27-week-old rats than in 7-week-old rats, but the exposed area in the case of an administration volume of 50 μl was naso-, maxillo-, and ethmoid turbinate in 27-week-old rats. In this case, the volume was enough to spread to the ethmoid turbinate. Differences in the exposed area might be caused by differences in the volume of the nasal cavity. It was also indicated that the main exposed area was the inferior meatus in the 30 min immediately after administration. At all administration volumes, however, notice should be taken of the outflow of nasal drops into the oral cavity through the nasopalatine.

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Recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 1 to 300 μg/kg/day was administered intravenously to rats daily for 13 weeks. Serum alkaline phosphatase (ALP) activity increased dose-dependently with leukocytosis. Most of the increased leukocytes were segmented neutrophils, and neutrophil alkaline phosphatase (NAP) scores were elevated markedly. Serum ALP activity correlated very well with the segmented neutrophil counts, and the coefficient of correlation was more than 0.97 in both sexes. Pathological examinations revealed splenomegaly and a marked increase in neutrophils in the red pulp of the spleen. In the spleen, phagocytosis of neutrophils by macrophages was observed. These data indicate that the increased ALP was of neutrophil origin. Serum ALP activity may be increased by the direct release of ALP from the high number of neutrophils into the blood, or by the leakage of ALP into the blood mainly from the spleen where many neutrophils are pooled and destroyed by the macrophage system.

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In vitro fertilization and embryo transfer were performed for rederivation of four strains of mice harbouring mouse hepatitis virus (MHV) and/or Pasteurella pneumotropica (P. pneumotropica). Superovulated oocytes were fertilized by preincubated cauda epididymis sperm in vitro. Fertilized eggs at 2-cell stage were transferred into the oviducts of specific pathogen free (SPF) recipients. Microbial examination of sperm and/or oocyte donors verified the presence of P. pneumotropica and/or of antibodies to MHV in all strains, but neither in the recipients nor in the offspring antibodies to MHV could they be detected. The results indicate that an in vitro fertilization-embryo transfer (IVF-ET) system is an effective and simple alternative to cesarean operation in infected mice.

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The hematological and serum biochemical values of a total of 18 pregnant female squirrel monkeys were determined during the pre-and postpartum period. Pregnancy was determined by abdominal palpation in adult females cohabiting with robust males. The mean body weight of the pregnant females gradually increased toward parturition and dramatically decreased at parturition due to delivery of the infant monkey. The red blood cell count, hematocrit and hemoglobin levels diminished toward parturition and then increased to their normal levels by week 6 after delivery. The Wintrobe constant, MCHC, did not fluctuate, but MCH and MCV values increased in late pregnancy and the early nursing periods. The mean white blood cell count varied between 65.8 and 87.3 (× 10²/mm ³) during the experimental periods. The mean serum total cholesterol concentration and glutamic-oxaloacetic transaminase activity were lower in the pregnant group during the mid- and late gestation stage than in nonpregnant and nursing females. The mean serum total protein and albumin values were lower in pregnant females than in the controls. Alkaline phosphatase activity increased in late pregnancy and the nursing periods. Since the pregnant females examined gave birth to healthy newborn monkeys and nursed them normally, the hematological and serum biochemical measurements should represent the physiological values for squirrel monkeys during pregnancy and the postpartum period.

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A tumor developed spontaneously in the subcutaneous tissue of the hind leg of a 7-month-old female ddY mouse. Light and electron microscopical examinations revealed that the original tumor was composed of an admixture of fibroblast-like and histiocyte-like cells arranged predominantly in a storiform or cartwheel pattern. The tumor cells gave positive reactions for acid phosphatase, N-acetyl-β-glucosaminidase, non-specific esterase, β-glucuronidase, alpha-1 antitrypsin and fibronectin. The original tumor was diagnosed as a malignant fibrous histiocytoma (MFH). The tumor was serially transplanted into syngeneic mice up to the 92nd generation. The tumor was also consistently transplanted into allogeneic mice of several inbred strains. The allogeneic mice used in the present study were strains having different H-2 haplotypes. During succeeding passages, transplanted tumors showed aberrant growth properties. The tumor transplanted into mice of inbred strains took well to back transplantation for mice of original strain and allotransplantation for other inbred strains. The pathological features of these transplantable tumors were basically similar to those of the original tumor. As mentioned above, a MFH developed spontaneously in the ddY mouse was consistently transplantable into both syngeneic and allogeneic mice.

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To compare the atherogenecity of different fats and oils, a total of forty, 40-day-old male Japanese quails were fed one of the following diets for three months: basal diet (control), a diet-containing 15% corn oil (CO) and 2% cholesterol (CH), a diet-containing 15% oleic acid (OL) and 2% CH, a diet-containing 15% perilla oil (PE) and 2% CH, a diet-containing 15% primrose oil (PR) and 2% CH. A higher plasma cholesterol concentration was found in the birds in the CO and OL groups, whereas the PE and PR groups showed a much lower level of plasma cholesterol than the CO and OL groups. In proportion to the increased plasma cholesterol, both CO and OL groups showed narrowing of the lumen of the ascending aorta and its large branches due to marked lipid-rich intimal thickening. Ultrastructural changes in the ascending aorta and its large branches were correlated with the degree of intimal thickening. The major foam cell types were macrophages and fibroblastic cells. The PE and PR groups showed the fewest lipid-rich intimal thickening lesions in their ascending aorta and its large branches. These findings suggest that the alpha-linolenic acid contained in perilla oil is less atherogenic than oleic and linoleic acid, and gamma-linolenic acid contained in primrose oil has a tendency to decrease the plasma lipid level.

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The effects of high protein feeding on food and water intake, and the retention and urinary excretion of macrominerals (magnesium (Mg), phosphorus (P), and calcium (Ca)) were examined in growing cats. Seven female cats aged 4 months were fed diets containing 55% crude protein (n=4) or 29% crude protein (n=3) for 12 months on an ad libitum basis. Mineral balances were determined at 0.5, 2, 6, 10, and 12 months of feeding. The higher protein intake stimulated daily water intake and urine excretion throughout the study, although daily food intake was not affected by dietary protein levels. The urinary Mg concentration was decreased by the high protein intake, resulting from both increased urine volume and reduced excretion of urinary Mg. In contrast, the concentration and daily excretion of urinary P were increased by the high protein intake. The protein-induced increase in urinary P would not necessarily imply the increased excretion of PO₄^3-, the anion responsible for struvite crystallization, because the dissociation of phosphate depends on urinary pH. Urinary Ca excretion was not affected by the dietary protein levels, but the high protein intake caused less retention of P and Ca as a result of enhanced urinary P excretion and lowered Ca absorption. The possibility of high protein feeding for the prevention of struvite crystallization in growing cats is discussed.

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The rat dilute-opisthotonus (dop) autosomal recessive gene, causing ataxia and coat color dilution, was mapped on chromosome 8 by PCR-amplified microsatellite markers. To facilitate the linkage analysis, an intersubspecific cross with a Japanese wild rat strain was used. The recombination frequencies were 12.8% between Apoc3 and dop, and 32.1% between dop and Mylc1v. The following order of three genes is proposed; Apoc3-dop-Mylc1v. This mutation appears to be homologous to dilute-lethal (d^l) of the mouse in terms of clinical symptoms, coat color effect and chromosomal location of the gene loci.

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The role of macrophages in the development of diabetes following infection with encephalomyocarditis (EMC) virus was examined in 3 strains of mice (DBA/2 and BALB/c: susceptible, C57BL/6: resistant). After infection with 100 plaque forming units (PFU) / head of EMC-D (highly diabetogenic variant), the incidence of diabetes at 3 days post infection (DPI) (DBA/2: 7/8, BALB/c: 3/8, C57BL/6: 0/8) was well correlated with the severity of macrophage infiltration with β cell damage in the pancreatic islets (DBA/2: sever, BALB/c: moderate, C57BL/6: slight). Silica-pretreatment depleted macrophage infiltration in the pancreatic islets and decreased the incidence of diabetes at 7 DPI from 100% to 40% in DBA/2 and from 80% to 0% in BALB/c mice, respectively. These results suggest that macrophages play a critical role in the process of pancreatic β cell damage in EMC virus infection in mice.

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Viral growth and histopathological changes in the liver after intraperitoneal infection with mouse hepatitis virus, strain JHM were compared among normal C57BL/6 mice, those depleted of CD4⁺ T cells, CD8⁺ T cells and both T cell subsets. Viral growth in mice depleted of CD4⁺ T cells increased slightly, but pathological changes resembled those in normal mice. In contrast, the hepatitis was exacerbated in mice depleted of CD8⁺ T cells and those depleted of both T cell subsets. These results suggest that CD8⁺ T cells play a key role although both T cell subsets are involved in protection against mouse hepatitis virus infection in mice.

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Biopsied canine liver tissues were investigated histochemically by electron microscopy to demonstrate copper localization. The samples were fixed and stained with the modified sulfide-silver method with a combination of iron and zinc removal. Using this method, the hepatic copper, even at a low concentration of 30 μg/g dry weight, was detectable. Copper was found in the hepatocyte lysosomes or in the cytoplasm as electron-dense granules.

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We examined histologically whether the severity of arterial stretch injury is related to the degree of subsequent intimal hyperplasia. In six male New Zealand White rabbits, the common carotid artery was hyperextended with a 3F Fogarty balloon catheter. Two weeks later, no proliferative change was evident in the intima in the most hyperextended portion. Paradoxically, however, intimal hyperplasia due to smooth muscle cell proliferation was observed in the moderately extended portions. The intimal hyperplasia appeared to be exacerbated where the arterial stretching was more severe. It is concluded that the severity of arterial stretch injury is closely related to the intimal proliferation of smooth muscle cells.

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Morphological characterization of the skeletal malformations caused by the Dh gene was carried out. Skeletal preparations from newborn mice of Dh/Dh, Dh/+ and +/+ genotypes, and adult Dh/+ mice were examined. The Dh gene induced skeletal deformities at the axial regions from the thorax to the tail. Attachment of the ribs to the sternum was sometimes irregular, and normal segmentation of the sternum was also disrupted. Abnormal fusion of the ventral part of the rib was observed in some cases. Lumbar vertebrae were fewer in number and abnormal in shape. Although it was rare, a curled tail was also observed due to distortion of the caudal vertebrae.

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The present study demonstrates the incidence of high lethality of F₁ (Dh/+) male mice, the offspring of DDD females and inbred DH (Dh/+) males. Among the newborn pups, the numbers of F₁ (Dh/+) males are comparable to those of mice having other genotypes (+/+ male, Dh/+ female and +/+ female), but many F₁ (Dh/+) males died before weaning. On the other hand, among the F₁ mice from the cross between DH (Dh/+) females and DDD males, there are no biased numbers of Dh genotype pups. These results suggest the existence of defects in the interaction between the male derived Dh gene and the genetic traits of the DDD female.

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