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PubMed1976

Immunological enhancement of rat renal allografts using rabbit antisera with specificity for rat transplantation antigens.

Rabbits immunized with particulate and soluble preparations of rat lymphoid tissue of the HO strain produced antisera which reacted without strain specificity on rat lymphocytes. Absorption of the sera with tissue from the AS strain of rat removed the antibodies reacting with AS tissue leaving activity against HO cells only. Studies with backcross rats showed that the antigens detected by these sera were products of the AgB genes or genes segragating with them. The immunosuppressive activity of rabbit antisera specific for Ag-B5 rat transplantation antigens was tested in a rat renal allograft assay. Some of the antisera markedly prolonged the survival of (AS X HO)F1 kidneys transplanted to AS rats. The prolongation of graft survival was not due to ALS activity since the sera were active in the absence of antibody directed against recipient antigens. There was no correlation between in vivo enhancement and anti-donor lymphocytotoxic titres of the xenoantisera.

Absorption↗

PubMed1979

Segregation of rat chromosomes in somatic cell hybrids between rat cells and HT 1080 human fibrosarcoma cells.

We produced somatic cell hybrids between HT 1080-6TG human fibrosarcoma cells and either rat white blood cells (WBC) or cells directly derived from rat spleen. Karyologic and isozyme analyses of hybrid cells indicated that they preferentially lose rat chromosomes. Hypoxanthine-aminopterine thymidine-selected hybrid clones expressing rat hypoxanthine phosphoribosyltransferase (HPRT), glucose-6-phosphate dehydrogenase (G6PD), and phosphoglycerate kinase (PGK) and containing the rat X chromosome were counterselected in a medium containing 30 micrograms/ml of 6-thioguanine. Concordant loss of the rat X chromosome and of the expression of rat HPRT and G6PD was observed in the hybrid clones.

Animals↗

PubMed1978

The catabolism of human and rat very low density lipoproteins by perfused rat hearts.

The catabolism of human and rat 125I-labelled very low density lipoproteins (VLDL) was compared by perfusing the lipoproteins through beating rat hearts. Triacylglycerol was removed from the VLDL to a greater extent than the protein moiety, leaving remnants containing relatively more apo-B and less apo-C. The change in apo-C content of the remnants correlated with the loss of triacylglycerol. The extent of removal of triacylglycerol from the rat and human VLDL was similar and in most cases appeared to saturate the heart lipoprotein lipase. The remnants were slightly smaller in size than the VLDL, and included particles which appeared to be partially emptied. In addition to remnants of d less than 1.019 g/ml, iodinated lipoproteins derived from rat and human VLDL were recovered at d 1.019-1.063 and 1.063-1.21 g/ml. The former contained largely cholesterol and cholesteryl esters, while phospholipids were the dominant lipid in the latter. An average of 40% of the 125I-labelled apoprotein lost from the VLDL was associated with the perfused hearts. Very little d 1.019-1.063 g/ml lipoprotein was produced from low (physiological) concentrations of rat VLDL, most of the lipoprotein being removed by the heart. However, lipoproteins of density 1.019-1.063 g/ml were formed from human VLDL at all concentrations in the perfusate, as well as from higher concentrations of the rat VLDL. Agarose gel filtration of lipoproteins following heart perfusion with human VLDL revealed large aggregates containing particles which resemble low density lipoproteins (LDL) in electron microscopic appearance and apoprotein composition, since they contain largely apo-B. These data suggest that at normal concentrations rat VLDL are almost completely catabolised and taken up by the heart without the formation of LDL, while LDL is produced from human VLDL at all concentrations.

Animals↗

PubMed1979

alpha-Fetoprotein and albumin genes of rats: no evidence for amplification-deletion or rearrangement in rat liver carcinogenesis.

Full-length radiolabeled albumin and alpha-fetoprotein (AFP) cDNAs were synthesized from pure albumin and AMP mRNA preparations by using avian myeloblastosis virus reverse transcriptase (RNA-dependent DNA polymerase). The cDNAs have been used to quantitate the number of albumin and AFP genes in different rat tissues by two independent methods, both of which yielded similar results. First, the kinetics of the association of these cDNAs with nuclear DNA from rat liver, rat kidney, and Morris hepatoma 7777 under conditions of vast DNA excess indicated that the albumin and AFP mRNA's are transcribed from "nonrepetitive DNA." Second, saturation hybridization experiments in which a constant amount of rat liver DNA or Morris hepatoma 7777 was hybridized with increasing amounts of cDNA to albumin mRNA have shown the presence of 1--2 albumin genes per rat haploid genome. The number of AFP genes obtained in similar titration experiments was approximately 2--3. This was true whether rat liver DNA or hepatoma 7777 DNA was used in the reassociation experiments. When high molecular weight DNA preparations from both these tissues were digested with the restriction endonuclease EcoRI and the fragments were transferred to a nitrocellulose filter, the albumin and AFP [32P]cDNA probes hybridized to different sets of DNA fragments. However, each probe gave the same hybridization pattern whether Buffalo rat liver DNA or hepatoma 7777 DNA was utilized.

Albumins↗

PubMed1975

Analysis of regulatory factors for urea synthesis by isolated perfused rat liver. II. Comparison of urea synthesis in livers of rats subjected to different dietary conditions.

Capacities for urea synthesis and amino acid patterns in the perfused livers isolated from rats fed low and high-protein diets were compared. Urea formation with amjonium chlorode as the nitrogen source in perfused livers isolated from rats fed on a 70% casein diet was rapid and the efficiency of conversion of ammonia to urea was 97.9%. However, that in livers isolated from rats fed on a 5% casein diet was much slower and the efficiency of conversion of ammonia to urea was only 36.1%. The ratios of the rate of urea formation from ammonium chloride to activity of ornithine transcarbamylase [EC 2.1.3.3.] in the perfused livers of rats fed on 5 and 70% casein diets were calculated. The ratio of the former condition was much lower than that of the latter. The ratios reached nearly the same level by the addition of ornithine and N-acetylglutamate, the addition of which to the perfusate caused marked elevation of the ratios in both cases. In the perfused livers from rats fed on a 5% casein diet a considerable portion of the ammonia added to the perfusate was fixed into an amino ro an amide group of amino acids such as alamin, aspartate, and glutamine. On the other hand, in the perfused livers from rats fed on a 70% casein diet most of the ammonia added was converted to urea. The regulation of urea synthesis and the relation between anabolism and catabolism of amino acids in rat livers subjected to different dietary conditions were compared.

Amino Acids↗

PubMed1978

Rat adrenal androgen receptor: a possible mediator of androgen-induced decreased in rat adrenal weight.

Many previous studies have demonstrated effects of gonadal steroids on adrenal weight in the rat. Most of these effects are indirect, depending upon alterations in the pituitary-adrenal axis for their expression. In this study we have attempted to examine the direct effects of gonadal steroids on adrenal weight in the rat. This was done using hypophysectomized, castrated male rats receiving ACTH replacement, a model which excludes pituitary-adrenal feedback effects. Estradiol-treated rats did not differ from controls, whereas testosterone-treated rats exhibited a small but statistically significant decrease in adrenal weight. As a first step in exploring the mechanism of this androgen effect, we have identified a specific dihydrotestosterone-binding protein in the rat adrenal gland. A single class of high affinity (Kd = 0.6-2.0 x 10(-8) M), saturable (28 fmol/mg cytosol protein), cytoplasmic binding sites was found using both protamine sulfate precipitation and dextran-coated charcoal assays. The specificity, sedimentation coefficient on sucrose gradient, and sensitivity to sulfhydryl reagents and heat of this dihydrotestosterone-binding protein are typical of the cytoplasmic androgen receptor from other androgen target tissues such as prostrate. We conclude that testosterone can decrease rat adrenal weight directly, and that the mechanism may involve a high affinity binding protein, as has been shown in other androgen-responsive systems.

Adrenal Glands↗

PubMed1979

Kidney distension during IV urography in normal rats and in rats with artificial unilateral renal artery stenosis.

Acute changes in kidney size during IV urography were studied in normal rats and in rats with artificial unilateral renal artery stenosis. In normal rats, IV bolus injection of sodium iothalamate (400 mg I/ml), 1.5 ml/kg body weight, produced an increase in area of the renal silhouette by an average maximum of 12.7% after 60 seconds. In nine out of ten rats which developed hypertension after left sided renal artery clamping, renal distension was either small or absent on the stenosed side, while the contralateral right kidney showed normal distension during IV urography. Two out of three rats, which remained normotensive after renal arterial clamping, showed normal distension of both kidneys. These results confirm earlier observations in man that the acute changes in size of the kidney during IV urography can be used as an aid in the urographic screening of hypertensive patients for significant renal arterial stenosis. In all rats with arterial clamp and hypertension, the stenosed kidney was smaller than its contralateral mate. An index between the size of the non-stenosed and the stenosed kidneys greater than 1.15 was only seen in these particular rats.

Animals↗

PubMed1976

Catabolism of homologous and heterologous hemopexin in the rat and uptake of hemopexin by isolated perfused rat liver.

Iodinated hemopexin (Hx) from three different species, rabbit, human and rat, was injected into rats and its clearance from the plasma measured. Rabbit, human and rat apo-Hx were cleared from the plasma with a T 1/2 of 20--31 h, 31--32 h, and 48--60 h respectively. Heme injection (10 mg/kg) after equilibration of the protein immediately accelerates elimination of the hemopexins of all three species (T 1/2 of 4.5 to 10 h). This indicates that the two heterologous hemopexins maintain their function in heme transport. The T 1/2 of rabbit and human Hx return to pre-heme injection values 16 to 20 hours after the injection of heme. For rat Hx, however, the T 1/2, which was 54 +/- 3.5 h before heme injection, was reduced to 25 +/- 1.3 h 20 hours after heme injection. Administration of 1.2--1.3 mg of protoporphyrin IX or uroporphyrin III, after equilibration of iodinated rat Hx, did not change the T 1/2 of the protein, whereas the same amount of coproporphyrin III significantly reduced its T 1/2 from 54 +/- 3.5 to 37 +/- 0.4 h. In addition, the uptake of rat apo-Hx, heme-Hx and albumin by rat liver tissue was measured in an isolated liver perfusion system using radioiodinated proteins screened in vivo. The uptake of apo-Hx by the liver after 2 h (46.8 ml/100 g) was less than that of heme-Hx (67.3 ml/100 g). The amount of apo-Hx and heme-Hx associated with the liver, relative to that circulating in the perfusate, was greater than that of albumin (12.1 ml/100 g). These results are considered to represent selective uptake of Hx by the liver induced by its interaction with heme.

Animals↗

PubMed1976

[Effect of diet and of the microbial flora of the digestive tract on the intestinal pool and fecal excretion of bile acids in the rat: a comparative study in axenic, ghotoxenic and holoxenic rats].

When axenic rats are given a microflora which causes the caecum distension present to disappear but does not metabolize bile acids, the intestinal pools and fecal excretion of bile acids are intermediary between those of axenic and those of holoxenic rats. This flora acts non-specifically on bile acids metabolism by changing the physiological characters related to caecal distension in axenic rats. The intestinal pools and fecal excretion of bile acids are higher in rats given a commercial chow than in those receiving a semi-synthetic feed containing the same amount of cholesterol; the difference between axenic and holoxenic rat fecal excretions is greater than in rats given the semi-synthetic feed. This wider difference is especially due to greater fecal excretion of bile acids in holoxenic rats given the commercial diet; it is thus related to modification of the gut microbial flora due to diet.

Animal Feed↗

PubMed1975

Thiamine absorption in the rat. ii. intestinal alkaline phosphatase activity and thiamine absorption from rat small intestine in-vitro and in-vivo.

The correlations between intestinal alkaline phosphatase (IAP) activity and thiamine absorption and glucose absorption were studied in the rat. An everted sac in-vitro technique was used in adult rats whereas in-vitro experiments were performed in young rats 10 days old. All incubation experiments were done with 14-C-labeled thiamine. The patterns of IAP activity along the small intestines differed greatly between young and adult rats but were closely paralleled by the distribution of active thiamine transport in adult rats and thiamine absorption in young rats, respectively. When IAP was specifically inhibited in adult rats by L-phenylalanine active thiamine transport in-vitro was abolished. No correlation was found between IAP activity and active transport or glucose in-vitro, nor did inhibition of the enzyme in any way affect glucose transport capacity. It is suggested that the enzyme intestinal alkalinephosphatase is involved in the process of active thiamine absorption.

Age Factors↗

PubMed1979

A comparison of the anti-anaphylactic activities of salbutamol and disodium cromoglycate in the rat, the rat mast cell and in human lung tissue.

1 Salbutamol and disodium cromoglycate were compared for anti-anaphylactic activity against passive anaphylaxis in rat skin and peritoneum in vivo and in rat mast cells and human lung fragments in vitro.2 Salbutamol administered intravenously to rats inhibited cutaneous anaphylaxis, but also inhibited cutaneous responses to histamine and 5-hydroxytryptamine. Salbutamol administered intraperitoneally inhibited the release of slow reacting substance of anaphylaxis (SRS-A) but not the release of histamine in the peritoneum. It was a very weak inhibitor of histamine release from rat mast cells in vitro.3 Disodium cromoglycate administered intravenously to rats inhibited cutaneous anaphylaxis. Disodium cromoglycate administered intraperitoneally to rats inhibited the release of histamine and, to a lesser extent, SRS-A in the peritoneum. It was an effective but short-acting inhibitor of histamine release from rat mast cells in vitro.4 Salbutamol was a potent inhibitor of the anaphylactic release of histamine and SRS-A from fragments of human lung.5 Disodium cromoglycate was a weak inhibitor of the anaphylactic release of histamine and SRS-A from fragments of human lung. The inhibition was variable and not dose-related.6 The concentration of salbutamol required to inhibit anaphylaxis in human lung is of the same order as that required to relax human bronchial muscle. It is suggested that salbutamol may be more effective in allergic asthma if given in a prophylactic regimen.

Albuterol↗

PubMed1976

Differences between pyrimidine nucleoside monophosphate kinase from rat Novikoff ascites hepatoma and rat liver.

Pyrimidine nucleoside monophosphate kinase [deoxycytidine monophosphate:adenosine triphosphate (dCMP:ATP) phosphotransferase. EC 2.7.4.14] has been purified from rat Novikoff ascites hepatoma and rat liver, each to a single major band appearing on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Differences exist in regard to efficiency and regulation of enzymatic activities. The Km values of the tumor kinase for cytidine monophosphate (CMP) (0.0053 +/- 0.0008 MM) and dCMP (0.715 +/- 0.068 MM) are approximately one-fourth the Km values of the rat liver kinase, for CMP (0.030 +/- 0.007 MM) and dCMP (2.77 +/- 0.39 MM). The tumor dCMP kinase exhibits a lower Km for ATP (0.134 +/- 0.008 MM) than the rat liver kinase (0.68 +/- 0.09 mM). Moreover, the dCMP:CMP kinase activity ratio for the tumor enzyme is 1.12, while that for the rat liver enzyme is 0.45. The uridine monophosphate:CMP kinase activity ratio for the tumor enzyme is 1.93, while that for the rat liver enzyme is 2.68. Lower concentrations of dithiothreitol are required for 50% reactivation of the tumor dCMP kinase (1.00 mM) and CMP kinase (0.10 mM) than rat liver dCMP kinase (2.20 mM) and CMP kinase (0.57 mM). Thus, the kinase from Novikoff hepatoma exhibits properties of increased efficiency and relaxed regulation of activity which render it more suitable for a tumor, in which active DNA synthesis is ongoing.

Animals↗

PubMed1977

Altered cobalamin distribution in rat hepatomas and in the livers of rats treated with diethylnitrosamine.

The distribution of cobalamin cofactors was investigated in the livers and tumors of rats bearing transplanted Morris 7777 or 7800 hepatomas, in the livers of rats treated with the hepatocarcinogen diethylnitrosamine, and in normal rats. There was a significant increase in the proportion of methylcobalamin both in livers and tumors from rat bearing the hepatomas 7777 and 7800 compared to the proportion of methylcobalamin in the livers of normal rats. The total cobalamin content of the hepatomas was significantly lower than that of host or control livers. Similarly, the total cobalamin content of the livers from the tumor-bearing rats was less than that in control animals. The administration to rats of an acute dose of diethylnitrosamine led to an 84% increase in the hepatic concentration of methylcobalamin. Chronic administration of diethylnitrosamine slightly increased the hepatic methylcobalamin concentration, but this was not statistically significant. Liver weight was reduced, and the hepatic content of total cobalamin fell to 55% of that in control animals.

Animals↗

PubMed1977

Catabolism of rat beta2-microglobulin in the rat.

Highly purified rat beta2-microglobulin (beta2m) as well as cytochrome c and lysozyme were radiolabeled and their catabolism studied in the rat. More than 90 percent of these low molecular weight proteins were removed from the serum within an hour and excreted into the urine by 24 hours. Except for the kidney in which the concentration of these protein is ten- to twentyfold greater than in the serum, there is little evidence that rat tissues are concentrating these proteins. The stomach was found to concentrate radioiodine. The catabolism of rat beta2m differed from that of cytochrome c and lysozyme in that the kidney contained twice as much labeled rat beta2m. In addition, the rat excretes 10 to 15 percent of the injected rat beta2m but only 1 to 5 percent of the cytochrome c or lysozyme. These studies established a basis for turnover studies of beta2m complexed with other cell membrane proteins, for example, HL-A or H-2 peptides.

Animals↗

PubMedDate not supplied

Sympathetic nerve activity and blood pressure in normotensive backcross rats genetically related to the spontaneously hypertensive rat.

The genetic basis of hyperactivity of the sympathetic nervous system (SNA) in spontaneously hypertensive rats (SHR) was assessed by measuring SNA in animals derived from a backcross (BC) breeding program designed to isolate single gene differences causing changes in blood pressure. Selective breeding of the male hypertensive rats with inbred normotensive female Wistar/Lewis rats yielded progeny with a range of blood pressures, but whose group mean pressures were lower than the group mean pressures of the original SHR. Progressive generations had progressively lower group mean pressures. There was a positive correlation between SNA and mean arterial pressure in BC rats. These results indicate that the genetic defect in SHR may be abnormality in SNA, and the hypertension in these animals is a secondary result of this primary defect. Baroreceptor function was also assessed in SHR and in BC rats. In young (8 to 24 weeks old) SHR, baroreceptor function was similar to that in BC rats, whereas SNA was markedly increased. Only in older (24 to 40 weeks old) SHR was there an abnormality in the gain of baroreceptors. The development of hypertension in SHR therefore appears to be due to increased SNA resulting from a defect in the central nervous system. Changes in baroreceptor function are secondary to the hypertension and occur after the hypertension is established.

Aging↗

PubMed1977

Experimental infection of adult axenic rats with Parker's rat coronavirus.

The pathogenesis of Parker's Rat Coronavirus (PRCV) was studied in axenic CD rats. Three to four 9 to 10 week old rats were euthanized daily for eight days after intranasal inoculation. Rats remained free of clinical disease. Virus was recovered from the nasopharynx and trachea after twenty-four hours and from the lung by day three but was not detected in respiratory tract after seven days. Viral antigen was detected by indirect immunofluorescence in the mucosal epithelium of upper respiratory tract and in pulmonary alveolar septae from day two to six postinoculation. Acute rhinitis developed by day two and was associated with mild focal necrosis of respiratory mucosal epithelium. Mild nonsuppurative tracheitis and multifocal interstitial pneumonia appeared by day five and persisted through day eight. Dacryoadenitis did not occur, sialoadenitis was detected in only three rats and virus was recovered from only one submaxillary salivary gland. This experiment indicates that PRCV can be a primary pathogen for the respiratory system of adult rats. In contrast to sialodacryoadenitis (SDA) virus the tropism of PRCV for salivary and lacrimal glands is low.

Animals↗

PubMed1979

Effect of serum lipoproteins of bile obstructed rats on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in perfused rat liver.

Total lipoproteins as well as fractionated VLDL + LDL and HDL from fasted control rats and bile-ligated rats were tested in liver perfusion for their effect on 3-hydroxy-3-methylglutaryl CoA reductase activity in normal rat livers. The total lipoproteins of bile-obstructed rats had 3 times greater capacity to increase 3-hydroxy-3-methylglutaryl CoA reductase activity than that of the control total lipoproteins. When the fractionated lipoproteins were tested from fasted control rats, it was found that the major stimulating activity was in the HDL fraction with minor activity in the VLDL + LDL fraction. When these plasma components isolated from fasted bile-ligated rats were tested, it was found that the major activity had shifted to the VLDL + LDL fraction with the HDL having only a minor stimulatory role. The possible mechanism of action of the abnormal lipoproteins associated with bile obstruction in regulating 3-hydroxy-3-methylglutaryl CoA reductase activity is discussed.

Animals↗

PubMed1977

Effect of increased serum urate levels on virgin rats with no arteriosclerosis versus breeder rats with preexistent arteriosclerosis.

Healthy virgin and breeder rats (Sprague-Dawley) with naturally occurring hypertension and arteriosclerosis were fed 5% oxonic acid and 1% uric acid added to their regular diet for 30 days. Although rats are able to convert uric acid into excretable allantoin, abnormal urinary and serum urate levels appeared. Males and females, virgins and breeders, differed in the severity of their increased urate levels. Animals with elevated urate levels developed hypertension, hyperglycemia, and hypertriglyceridemia, with only slight changes in cholesterol and free fatty acids. The kidneys were greatly enlarged and manifested medullary streaking indicative of urate deposits but were free of significant damage; BUN levels in these animals were abnormally high. Adrenal glands were reduced in size and depleted of lipid, circulating corticosterone levels were subnormal, and thymi were involuted. Serum enzymes CPK and LDH were greatly increased, whereas SGOT and SGPT levels were not elevated. The abnormal urate levels did not induce de novo arterial disease in the formerly healthy virgin rats and did not cause exacerbation of the pre-existing, naturally occurring arteriosclerosis characteristic of repeatedly bred rats. It is suggested that Sprague-Dawley rats are endowed with an especially efficient hepatic and renal capacity to metabolize uric acid. Increased urate levels in rats may have some direct metabolic relationship to the production of hypertension, hyperglycemia, and hypertriglyceridemia.

Animals↗