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Biomedical subjects

S Shumiya

Publications and source records attributed to S Shumiya.

At least 37 records · Page 2Linked to original sources

High susceptibility of an analbuminemic congenic strain of rats with an F344 genetic background to induced bladder cancer and its possible mechanism.

The susceptibility of an analbuminemic congenic strain of rats (F344-alb) originating from the F344 strain to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. F344-alb rats were found to be highly susceptible to induction of urinary bladder cancers. The incidences of bladder cancers in F344-alb and F344 rats were 94% (15/16) and 31% (5/16) in males and 100% (16/16) and 19% (3/16) in females. The bladder weights of these rats, including tumors, were 307 +/- 294 mg, 123 +/- 26 mg, 183 +/- 80 mg and 93 +/- 11 mg, respectively. Administration of 0.05%, 0.1% and 0.3% BBN in the drinking water for 2 weeks resulted in greater increases in the bladder content of N-butyl-N-(3-carboxypropyl)nitrosamine in F344-alb rats than in F344 rats. This increase was prevented by the presence of rat albumin.

Animals↗

Establishment and characteristics of five analbuminemic inbred strains of rats.

Five analbuminemic inbred strains of rats (AD/1, AD/2, AD/3, AD/4, AD/5) were established from Nagase analbuminemic rats (NAR). They showed no genetic differences in coat color, biochemical marker gene loci and skin grafting test. Their serum levels of total cholesterol, phospholipids, triglycerides, and beta-lipoproteins were compared with normal inbred strains (L) derived from Sprague-Dawley rats. Their plasma apoproteins were also examined. All inbred strains of analbuminemic rats showed hyperlipidemia progressing with age although there were slight variations in their lipid and apoprotein levels. These analbuminemic inbred strains of rats may be multigenic models of lipid metabolism abnormality.

Animals↗

Prolongation of the life of a central nervous system-deficient mouse, the reeler.

Although the reeler, an autosomal recessive mutant mouse with the abnormality of lamination in the central nervous system, died about 3 weeks of age when fed ordinary laboratory chow, this mouse could grow up normally and prolong its destined, short lifespan to 50 weeks and more when given assistance in taking paste food and water from the weaning period. Histopathological examinations of the brain of this mutant mouse revealed no significant age-related difference, suggesting that this mutation does not fundamentally obstruct the spontaneous growth despite the abnormality of the central nervous systems. This mutant mouse is advantageous for investigations on influences of the central nervous system on the aging process and longevity.

Aging↗

Reproductive activity of analbuminemic rats.

Long-term feeding and breeding in a conventional environment have been investigated in analbuminemic rats, a mutant strain established from Sprague-Dawley rats. Analbuminemic rats kept alive for over two years and maintained normal reproductive performance for over one year. The rotational system of one male and four females was better reproductive efficiency than the continuous pairing system of one male and one female. The litter size and weaning rate in analbuminemic rats were similar to those in Sprague-Dawley rats. Although we tried to establish a caesarean delivered SPF colony of analbuminemic rats, no changes in reproductive performance were recognized.

Animals↗

Establishment and characteristics of three analbuminemic congenic strains of rats.

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.

Adrenal Glands↗

Urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)-nitrosamine in an analbuminemic congenic strain of rats with an ACI genetic background.

An analbuminemic congenic strain of rats originating from ACI (ACI-alb) rats was established. The rats were found to be highly susceptible to induction of urinary bladder cancer by N-butyl-N-(4-hydroxy-butyl)nitrosamine. Bladder cancers were observed in all male ACI-alb and normal ACI rats treated with the compound, but the average weight of the bladder including tumors was more in ACI-alb rats than in ACI rats (0.63 +/- 0.24 g and 0.18 +/- 0.05 g, respectively; ratio, 3.5:1).

Animals↗

Mammary tumor induction in analbuminemic rats by 7,12-dimethylbenz(a)anthracene.

Induction by 7,12-dimethylbenz(a)anthracene of mammary tumors was studied in analbuminemic rats, a mutant strain established from Sprague-Dawley rats which are characterized by the absence of serum albumin and hyperlipidemia. Twenty-three weeks after carcinogen administration, the incidence and average number of mammary tumors and the tumor weight per tumor-bearing rat were respectively 35.0%, 1.7 +/- 0.2 (S.E.) and 8.9 +/- 0.5 g in analbuminemic rats and 69.2%, 2.3 +/- 0.2 and 12.2 +/- 2.8 g in the controls. Associated with this lower mammary tumorigenic response, analbuminemic rats had significantly lower plasma prolactin levels than controls during proestrus at 7-8 weeks of age when carcinogen was given (176 +/- 62 vs 308 +/- 52 ng/ml).

9,10-Dimethyl-1,2-benzanthracene↗

Penetration of bilirubin into the brain in albumin-deficient and jaundiced rats (AJR) and Nagase analbuminemic rats (NAR).

An albumin-deficient and jaundiced strain of rats (AJR) was established by crossing Nagase analbuminemic rats (NAR) with jaundiced Gunn rats. AJR have no serum albumin and die with kernicterus within 3 weeks after birth. Their serum bilirubin level was 25 per cent (20 micrograms/ml) of that of Gunn rats at 1-2 weeks of age, while their brain bilirubin content was 1.2-2.7 times (4-5 micrograms/g brain) that of Gunn rats. Binding of bilirubin to NAR plasma proteins was examined. The bilirubin binding protein in NAR plasma was found to be lipoprotein, showing an association constant of 6.7 X 10(6) M-1. Bilirubin-transport into the brain of postnatal NAR was investigated by intravenous infusion of bilirubin with taurocholate. The brain bilirubin level of NAR infused with free bilirubin was 1.6 times that of normal rats. In NAR, the brain level on infusion of lipoprotein-bound bilirubin was similar to that on infusion of free bilirubin, but albumin-bound bilirubin scarcely entered the brain. These findings suggest that lipoprotein-bound bilirubin can diffuse across the blood-brain barrier into the brain.

Aging↗

Establishment of an albumin-deficient and fatty strain of rats.

An albumin-deficient and fatty strain of rats (AFR) was established from crosses between albumin-deficient rats (NAR) and fatty Zucker rats. AFRs have double homozygous mutant genes (alb/alb, fa/fa). The AFRs are heavier than the fatty Zucker rats and they have enlarged livers and adrenal glands. In addition, AFRs show more severe hyperlipidemia than fatty Zucker rats. This strain of rats may serve as a model of human obesity and hyperlipidemia.

Animal Husbandry↗

Anemia and potassium permeability of red blood cells in analbuminemic rats.

A mutant strain, Nagase analbuminemia rats (NAR), was established from Sprague-Dawley rats. Hematological evaluations were made on NAR of 4 to 52 weeks of age. NAR had an abnormally low number of red blood cells (RBC), a low hematocrit, a reduced hemoglobin concentration and an increased number of reticulocytes. Their plasma electrolyte level was normal. Osmotic fragility of RBC was slightly increased in the rats. Thus NAR shows a slight anemia. The in vitro experiments on RBC were performed. The incubation of blood showed a hemolytic tendency and elevated potassium efflux in the blood of NAR. In addition, an increased efflux of potassium was found in the RBC of NAR, when the RBC was washed with phosphate buffered saline and then was incubated with the saline containing CaCl2. This potassium efflux was prevented in the presence of rat albumin. These findings suggest that the deficiency of serum albumin may increase the permeability of potassium in erythrocyte membrane in NAR.

Anemia, Hemolytic↗

Plasma lipid concentrations and enzyme activities in Nagase analbuminemia rats (NAR).

Plasma lipid concentrations in NAR (Nagase Analbuminemia Rats) of 4 to 52 weeks old were examined. Plasma enzymes of NAR were also measured in relation to liver function. The concentrations of total lipid, total cholesterol, phospholipid and triglyceride tended to be increased in NAR, while that of non-esterified fatty acid (NEFA) was decreased. The lipid levels (except NEFA) were especially high in female adult NAR, and they were increased with aging. The effect of 17 beta-estradiol or testosterone administration on serum lipid concentrations was studied in gonadectomized NAR. Administration of 17 beta-estradiol to gonadectomized NAR increased lipid concentrations, while testosterone administration did not affect lipid levels. The effect of albumin injection on lipid concentrations in female NAR was also investigated. Albumin treatment to female NAR lowered serum lipid concentrations. Plasma glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase and leucine aminopeptidase activities were higher in NAR than in normal rats. Plasma alkaline phosphatase and cholinesterase activities of NAR were similar to those of normal rats.

Age Factors↗

Treatment and improvement of the breeding system of the albumin-deficient and jaundiced strain of rats.

The AJR (alb/alb, j/j) strain is semi-lethal and the rats die at about two weeks of age. Cross breeding with a pari of ACJ (alb/alb, j/+) is required for maintenance and production. We studied the treatment of AJRs for improvement of the breeding system. AJRs with jaundice on the skin at about 7 days of age were intraperitoneally administered 1 ml/rat of normal rat serum every few days and irradiated with visible light for 14 hours a day in an irradiation box. This treatment allowed us to obtain mature AJRs. The treatment was effective when applied for short periods of 1-4 weeks of age. The frequency of maturation of the treated AJRs was about 27% and the best mating combination was a female ACJ and male AJR. The treatment of AJRs, made the progeny test for the selection of ACJs for breeding pairs of ACJ X ACR unnecessary and increased the frequency of appearance of AJRs to 50%.

Animals↗

Age-related changes in plasma proteins of analbuminemic rats.

A mutant strain, Nagase analbuminemia rats (NAR), was established from Sprague-Dawley rats. Age-related changes in plasma proteins of NAR were investigated to obtain information of their abnormalities of protein metabolism. The total protein concentration in the serum of NAR of various ages was almost the same as that of normal rats of the same age. The albumin level of NAR was less than 0.05 mg/ml at all ages examined. The concentrations of serum alpha 1-antitrypsin, alpha-X protein, alpha 2-macroglobulin, transferrin, ceruloplasmin, IgG, IgA and IgM were higher in NAR than in normal rats except for the perinatal stage, but alpha 1-acid glycoprotein level in NAR was normal. The serum transferrin and ceruloplasmin levels were especially high in female adult NAR. The plasma fibrinogen concentration was also increased in NAR. These findings indicate that the normal total serum protein level of NAR was maintained by increase in the globulin concentration.

Aging↗

High incidence of renal tumors induced by N-dimethylnitrosamine in analbuminemic rats.

Analbuminemic rats were found to be highly susceptible to induction of renal tumors. Thirty-nine weeks after N-dimethylnitrosamine administration, the incidence of renal tumors and average weight of kidneys (including tumors) were 76.0% and 10.8 +/- 4.1 g in male analbuminemic rats, respectively, whereas they were 37.1% and 3.5 +/- 0.1 g, respectively, in normal male SD rats.

Animals↗

Linkage of the analbuminemia locus (alb) and the hooded locus in the rat, Rattus norvegicus.

A linkage study of the analbuminemia (alb) with some coat color loci (a,b,c,h) has been carried out by crossing the analbuminemic random-bred mutant NAR strain with the abh tester strain of rats, the Agouti-Irish inbred ACI strain and the Agouti-Nonhooded inbred IS strain. The analbuminemia (alb) locus is not linked to a, b, and c loci but linked to hooded locus from F2 and backcross progeny of the F1 hybrids of abh X NAR, ACI X NAR and IS X NAR to NAR. Recombination value between alb and h was 16.4 +/- 2.3 per cent from the data of F2 and backcross progeny of (ACI X NAR) F1 and (IS X NAR) F1 to NAR. This is the third locus on the sixth linkage group of the rat.

Animals↗

Establishment of an albumin-deficient and jaundiced strain of rats.

An albumin deficient and jaundiced rat (AJR) strain was established from crosses between Albumin-Deficient rats (NAR) and jaundiced Gunn rats. AJRs have a double homozygous mutant trait (alb/alb, j/j), and systemic jaundice and various neurological signs are observed 5--7 days after birth, kernicterus occurs and they die within three weeks after birth. This strain of rats may serve as a model of human kernicterus and also be useful in elucidating the mechanism of bilirubin metabolism.

Animals↗

Albumin-deficient rat mutant: an animal model for analbuminemia.

An analbuminemic rat colony (NAR, Nagase Analbuminemia Rat) was established from Sprague-Dawley rats. The Analbuminemia was inherited as an autosomal recessive trait. The rate of growth or propagation of the mutant rats was not different from those of normal rats. Biochemically the mutant was characterized by an extraordinarily low serum albumin and hyperlipidemia. Total protein level of the serum in the mutant rat was similar to that of control Sprague-Dawley rats and globulin increased compensatorily. Serum cholesterol concentration was inversely correlated with a decrease in albumin, its correlation coefficient was -0.92. NAR may serve as a model of human familial analbuminemia. It should be also useful in elucidating the functional roles of albumin.

Animals↗

Albumin-deficient rat mutant.

An analbuminemic colony was established from Sprague-Dawley rats. Analbuminemia was inherited as an autosomal recessive trait. The rates of growth and reproduction of the mutant rats were no different from those of normal rats. Biochemically, the mutant was characterized by an extraordinarily low serum albumin content and a hyperlipidemia. Total serum protein in the mutant rat was similar to that of control Sprague-Dawley rats, with increased globulin. Serum cholesterol was inversely correlated with a decrease in albumin; the correlation coefficient for ablumin was --.92. These mutant rats may serve as a model of human familial analbuminemia and may also be useful in elucidating the functional roles of albumin.

Animals↗