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Showing papers in "Experimental Biology and Medicine in 1969"


Journal ArticleDOI
TL;DR: Conjugation of TNP directly to the erythrocyte surface by use of TNBS resulted in a stable reagent that permitted a study of the antihapten response to TNP-KLH and indicated the higher binding affinity of secondary antibody.
Abstract: SummaryA technique was developed for the detection of individual cells producing anti-TNP antibody by the hemolytic plaque technique. Conjugation of TNP directly to the erythrocyte surface by use of TNBS resulted in a stable reagent that permitted a study of the antihapten response to TNP-KLH. It was possible to induce a primary anti-TNP response with soluble TNP-KLH but the response was greater when the immunogen was made particulate by coating it onto bentonite. Both primary and secondary responding cells (those brought out by antiglobulin serum) were inhibited by TNP-BSA added to the plating medium but at an equivalent concentration of hapten only the secondary cells were completely inhibited. This was interpreted to indicate the higher binding affinity of secondary antibody.Author's note. As we were in process of submitting this manuscript, we became aware of an abstract which indicated that responses of similar magnitude to those reported here with TNP could be obtained in Balb/c mice to DNP using a ...

724 citations


Journal ArticleDOI
TL;DR: A simplified procedure for recognizing and quantitating fibrinolytic split products has been described, and would appear to be more useful with fibrin lysis than withfibrinogen lysis and to be especially applicable in the diagnosis of defibrination syndrome.
Abstract: Summary and ConclusionsA simplified procedure for recognizing and quantitating fibrinolytic split products has been described. It utilizes human group O cells which can be sensitized and stored at 4° for 3 weeks and at ‐20° for many months prior to use. It is very sensitive, detecting 1.0 μg/ml of fibrinogen or split products. Application of the test to the Microtiter and Autotiter systems permits assay of many samples at once. Only 1 hr is required to complete the test and read the results. The interpretation of the quantitative assay result should be carefully made since, while fibrin split products are not absorbed from the sera during the preparation of the sample and are relatively accurately measured, fibrinogen split products tend to be absorbed during sample preparation and are thus less accurately measured. The test would appear to be more useful with fibrin lysis than with fibrinogen lysis and to be especially applicable in the diagnosis of defibrination syndrome.

408 citations


Journal ArticleDOI
TL;DR: The development of a double antibody radioimmunoassay for rat prolactin capable of measuring the amount of Prolactin in 100 μl of serum from immature female rats or in 25 μl from normal females during diestrus is described.
Abstract: The most commonly used method for measuring prolactin in biological samples has been the pigeon crop bioassay of Lyons (1). It is possible with this method to estimate the prolactin content of pituitary preparations and of other tissues containing relatively high concentrations of this hormone (a minimum of about 0.03 IU or 2 μg of NIH-P-B1, 13 IU/mg); however, it was not possible to assay the prolactin present in serum from normal animals. Recently, double antibody radioimmunoassay techniques have been developed for ovine (2) and bovine prolactin (3) and a radioimmunoassay for rat prolactin (4) which uses a chromatoelectrophoresis step to separate free prolactin-125 I from that bound to the antibody has also been reported. These techniques are sufficiently sensitive to quantitate serum levels of prolactin. This communication describes the development of a double antibody radioimmunoassay for rat prolactin capable of measuring the amount of prolactin in 100 μl of serum from immature female rats or in 25 μ...

354 citations


Journal ArticleDOI
TL;DR: It is concluded that a fibrinogen layer must first be adsorbed to glass for the platelets to adhere, and according to other evidence, the protein film Adsorbed from plasma onto a surface no longer reacts with antiserum to fibr inogen after 3 min.
Abstract: SummaryPlatelets suspended in serum or afibrinogenemia plasma (heated or congenital) adhered to glass slides previously exposed to normal plasma or to fibrinogen but not to slides exposed to serum or afibrinogenemic plasma. Platelets in platelet-rich plasma from a patient with congenital afibrinogenemia adhered to glass coated with plasma from a normal subject or von Willebrand patient but not to areas coated with afibrinogenemic plasma or serum. Platelets in platelet-rich plasma from two thrombasthenia patients failed to adhere even when the slide was coated with fibrinogen or plasma. At times, a much higher percentage of platelets adhered to areas exposed to plasma for 5 sec than to areas exposed for 3 min. According to other evidence, the protein film adsorbed from plasma onto a surface no longer reacts with antiserum to fibrinogen after 3 min. We conclude that a fibrinogen layer must first be adsorbed to glass for the platelets to adhere.

228 citations


Journal ArticleDOI
B. B. Pharriss1, L. J. Wyngarden1
TL;DR: Vaginal smear records of pseudopregnant rats receiving PGF2α subcutaneously showed a shortening of pseudipregnancy to 7 days from a normal of 14 days, which supports an indirect mechanism for local luteal control by uterine tissue.
Abstract: Psuedopregnant Spraque-Dawley rats were infused with prostaglandin F2 alpha (PGF2A) for 2 days at doses of 1 mg/kg/day. Infusion was begun on Day 5 and continued through Day 6 of pseudopregnancy. The study was designed to test an hypothesis of indirect action of PGs on Corpus luteum in some species. Infusion tubing was placed in the uterine lumen or the right heart. Progestogen content of the ovaries of the animals receiving PGF2A vs. controls receiving saline was compared. After treatment progesterone levels were decreased and 20 alpha-dihydroxyprogesterone levels were increased. Vaginal smears were prepared of rats also psuedopregnant who received subcutaneous injections of PGF2A and they showed a shortening of pseudopregnancy to 7 days from the normal 14 days. These results suggest the involvement of venous drainage. Whether PGF2A works by actions on the venous drainage from the ovary or via other mechanisms of venous involvement is unknown but an indirect mechanism of action for PGF2A is proposed.

221 citations


Journal ArticleDOI
TL;DR: A system appears capable of detecting microbial mutagenic activity in compounds which remain or become physiologically active after administration and which were induced by dimethylnitrosamine, N-methyl-N′-nitro-N-nitrosoguanidine, and streptozotocin.
Abstract: SummaryA procedure was established whereby a microbial indicator was incorporated in an animal system to identify and characterize mutagenic agents. The organisms, histidine auxotrophs of Salmonella typhimurium, were injected into mice intraperitoneally, and the test compound was administered intramuscularly. Mutagenesis, indicated by an increase in the incidence of prototrophs in the population, was induced by dimethylnitrosamine, N-methyl-N′-nitro-N-nitrosoguanidine, and streptozotocin. Such a system appears capable of detecting microbial mutagenic activity in compounds which remain or become physiologically active after administration.

198 citations


Journal ArticleDOI
TL;DR: This suspension was utilized to study the in vitro effects of agents that have previously been shown to affect renin production in vivo, and it is suggested that the reninstimulating effect of catecholamines in the intact animal might be due, at least in part, to a direct chemical action on the renal cells.
Abstract: SummaryThe preparation of a dog renal cell suspension suitable for the study of renin production is described. This suspension was utilized to study the in vitro effects of agents that have previously been shown to affect renin production in vivo. Since production and destruction of renin could not be separately quantified, data were limited to “net production” of renin. Incubated controls had only slightly higher renin content than did the nonincubated controls, but the addition of epinephrine, norepinephrine or cyclic AMP caused striking increases in “net production” of renin. The effects of these agents on “net renin production” were abolished by cycloheximide, an inhibitor of protein synthesis. It is suggested that the reninstimulating effect of catecholamines in the intact animal might be due, at least in part, to a direct chemical action on the renal cells. Cyclic AMP may play a role as an intracellular mediator of the action of catecholamines.

158 citations


Journal ArticleDOI
TL;DR: Whether this molecular structure was consistently present in all preparations, including those freed from the pentagonal unit, was determined to be consistently present.
Abstract: The major component of amyloid is a fibrous protein (1) with a unique organization as seen by high resolution electron microscopy (2). A second component, a pentagonal rod, has been isolated from amyloid deposits and demonstrated to be identical with a circulating a globulia (P-component) (3). This component is distinct from the fibril in its ultrastructure, chemistry, and immunological interactions and constitutes only a minute part of amyloid deposits.In 1960 we obtained an X-ray diffraction powder pattern of an amyloid-rich tissue. In subsequent years improved methods of isolation of amyloid were devised and X-ray diffraction patterns of these more purified preparations were obtained. Results were presented1 that indicated the presence of a cross-β pattern. The present study was carried out on amyloid fibrils isolated by various techniques to determine whether this molecular structure was consistently present in all preparations, including those freed from the pentagonal unit.Meterials and Methods Amyl...

155 citations


Journal ArticleDOI
Charles Shipman1
TL;DR: HEPES had a minimal effect on the oxidation-reduction potential of well-poised media and had no effect on rubella virus titrations or on hemagglutination assays of polyoma or Sendai virus.
Abstract: SummaryThe amino acid 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) has been evaluated as a tissue culture buffer. HEPES has a molecular weight of 238.3, a pKa2 of 7.31 at 37°, a δpK/° of —0.014, exhibits no metal binding and is soluble to the extent of 2.25 M at 0°. HEPES (0.01 M) produced adequate buffering in all cell systems tested. HEPES was not toxic to primary monkey kidney, chick embryo fibro-blasts or puppy salivary gland cells, human embryonic lung, BHK-21/4, BS-C-1, Detroit 6-YT, GPS. HEp-2 KB, LM, MA-134, or RK-13 cells. The GPS cells were grown in suspension in HEPES and NaHCO3 buffered media. Although the population doubling times were not significantly different, a higher maximum cell density and viability were seen in the HEPES buffered system. HEPES had a minimal effect on the oxidation-reduction potential of well-poised media. HEPES had no effect on rubella virus titrations or on hemagglutination assays of polyoma or Sendai virus. The formulation of a HEPES buffered salt sol...

154 citations


Journal ArticleDOI
TL;DR: Comparative reactivity of mature albino rabbits and of healthy man to the pyrogenic activity of purified S. typhosa, E. coli, and Pseudomonas endotoxins is presented to provide a more definitive base line for interpreting studies with bacterial endotoxin that involve extrapolation of rabbit febrile responses to man.
Abstract: SummaryComparative reactivity of mature albino rabbits (1.8–2.2 kg) and of healthy man to the pyrogenic activity of purified S. typhosa, E. coli, and Pseudomonas endotoxins is presented. On a per kilogram basis, rabbit and man are approximately equally reactive to threshold pyrogenic quantities of endotoxin. When larger doses of endotoxin are employed, the dose-response relationships become considerably steeper for man. On a total dose basis, rabbits require smaller quantities of endotoxin to elicit threshold febrile responses, but as total toxin dose is increased, febrile responses of man rapidly exceed those of the rabbit. Subjective toxic responses of man parallel the pyrogenic responses. These data provide a more definitive base line for interpreting studies with bacterial endotoxin that involve extrapolation of rabbit febrile responses to man.

144 citations


Journal ArticleDOI
Jordi Casals1
TL;DR: A viral strain isolated in the USSR from apatient suffering from Crimean hemorrhagic fever, has been shown to be antigenically indistinguishable from Congo virus.
Abstract: SummaryA viral strain isolated in the USSR from apatient suffering from Crimean hemorrhagic fever and reported to be etiologically related to the illness, has been shown to be antigenically indistinguishable from Congo virus.

Journal ArticleDOI
TL;DR: Measles virus was isolated from brain cell tissue cultures derived from two SSPE patients that proved to contain intracellular measles antigen which was not released in the fluid phase.
Abstract: SummaryMeasles virus was isolated from brain cell tissue cultures derived from two SSPE patients. These cultures proved to contain intracellular measles antigen which was not released in the fluid phase. Infectious, complete virus was obtained when mixed cultures containing the brain cells and HeLa cells were prepared. It appears that SSPE is due to suppressed measles virus infection. Once “rescued” through the mixed culture technique, the virus recovered from SSPE patients proved indistinguishable from measles virus.Note added in proof: At the time of galley review of this paper, confirmation of our previous isolation of complete infectious measles virus was reported by Payne, F. E., Baublis, J. V. and Itabashi, H. H. (Isolation of Measles Virus from Cell Cultures of Brain from a Patient with Subacute Sclerosing Panencephalitis, New England Journal of Medicine 281, 585, 1969). These authors used the mixed culture technique which we reported for this purpose (Horta-Barbosa, L., Fuccillo, D. A., Sever, J. ...

Journal ArticleDOI
TL;DR: The activities of acetyl CoA carboxylase and fatty acid synthetase were significantly higher in adipose tissue but not liver of meal-eating as compared to nibbling animals, in accord with the concept that adiposes tissue is the primary site of fatty acid biosynthesis and the major site of the lipogenic adaptive changes induced by meal-feeding.
Abstract: SummaryThe activities of acetyl CoA carboxylase and fatty acid synthetase in liver and adipose tissue of meal-eating (limited to a single, daily, 2-hr meal) and nibbling (adlibitum-fed) rats were determined. The activities of both enzymes were significantly higher in adipose tissue but not liver of meal-eating as compared to nibbling animals. This observation is in accord with the concept that adipose tissue is the primary site of fatty acid biosynthesis and the major site of the lipogenic adaptive changes induced by meal-feeding.

Journal ArticleDOI
TL;DR: The observation that virulent M. pneumoniae produced tissue damage more effectively than did an attenuated strain suggest that this experimental model may be useful for the analysis of factors contributing to organism pathogenicity.
Abstract: SummaryThe applicability of organ culture systems to the study of mycoplasma infections is illustrated by the experiments described. Tracheal organ culture provided a controllable environment for analysis of the interaction between M. pneumoniae and the natural target cell of this pathogen, the ciliated respiratory epithelium. Mycoplasma pneumoniae produced distinct cytopathology in this system that was not seen with other human mycoplasmas tested. In addition, virulent M. pneumoniae produced tissue damage more effectively than did an attenuated strain. The observations suggest that this experimental model may be useful for the analysis of factors contributing to organism pathogenicity.

Journal ArticleDOI
TL;DR: Methylazoxymethanol, the aglycone of cycasin, reacted with nucleic acids and proteins in the fetus of rats injected with the compound on Day 14 of pregnancy, and Guanine methylated in the seven position was found in both DNA and RNA.
Abstract: SummaryMethylazoxymethanol, the aglycone of cycasin, reacted with nucleic acids and proteins in the fetus of rats injected with the compound on Day 14 of pregnancy. Guanine methylated in the seven position was found in both DNA and RNA. The protein reaction products were not identified. The distribution of the injected compound in the tissues and fluids of the mother rat was determined.This communication is published as Hawaii Agricultural Experiment Station Journal Series No. 1111. This investigation was supported in part by Public Health Service Research Grant NB-3909 from the National Institute of Neurological Diseases and Blindness, U. S. Public Health Service.

Journal ArticleDOI
TL;DR: Injections of reserpine, thyroxine or cyproterone acetate, and cervical stimulation, failed to induce ovulation, whereas ovariectomy resulted in anestrus, suggesting changes in hypothalamic function account for constant estrus in old female rats.
Abstract: SummaryOld female rats in constant estrus were given different treatments in an attempt to induce ovulation. Subcutaneous injections of progesterone for 3 days or epinephrine for 10 days, induced ovulation in 6 out of 10 and 11 out of 22 rats respectively, with normal appearing estrous cycles observed in many epinephrine-treated rats. Electrical stimulation of the preoptic area of the hypothalamus produced ovulation in 3 out of 5 old rats. Injections of reserpine, thyroxine or cyproterone acetate, and cervical stimulation, failed to induce ovulation, whereas ovariectomy resulted in anestrus. These observations suggest that changes in hypothalamic function account for constant estrus in old female rats.

Journal ArticleDOI
TL;DR: The foregoing data, together with previous data on such other tests as the chick embryo and pertussis-treated mouse, indicate that the Limulus gel test is the most sensitive test available for the detection of endotoxin in its toxic or undegraded state.
Abstract: SummaryThe foregoing data, together with previous data on such other tests as the chick embryo and pertussis-treated mouse (7), indicate that the Limulus gel test is the most sensitive test available for the detection of endotoxin in its toxic or undegraded state. The test appears to be specific for endotoxin, since the amebocyte lysate is not clotted by normal blood or plasma or the individual vasoactive constituents known to be present in plasma of rabbits, dogs, or man. Because of its advantages in cost, simplicity, and sensitivity over all other available tests, it is to be preferred for monitoring a known endotoxemia, and for the detection of spontaneous endotoxemia.

Journal ArticleDOI
TL;DR: Leukocytes cultured from patients with Hodgkin's disease and with chronic lymphocytic leukemia were also hyporesponsive to PHA stimulation, but again the inhibitory effect was not transmissible to normal leukocyte cultures.
Abstract: SummaryThe PHA-stimulated leukocyte cultures from healthy donors were inoculated with representatives from picornavirus, picodnavirus, arbovirus, myxovirus, paramyxovirus, rhabdovirus, reovirus, adenovirus and papovavirus groups. Cultures were harvested after 6 days of incubation and assayed for virus multiplication and for DNA synthesis of the leukocytes by uptake of thymidine-3H. Virus replication and inhibition of the PHA response of the lymphocytes by these viruses were limited primarily to viruses which replicated and assembled in the cytoplasm of the cell. Leukocytes from 15 patients with viral hepatitis were studied, and in 8 of them the cells were hyporesponsive to PHA stimulation after 3 days of incubation. This pattern was observed in all samples taken within the first week after onset of jaundice. Sera from patients with viral hepatitis when added to normal leukocyte cultures showed some inhibition of the PHA response, but the effect could not be serially passed to fresh cultures. The same patt...

Journal ArticleDOI
TL;DR: If the resistance to intracellular bacteria observed in mice chronically infected with Toxoplasma gondii or Besnoitia jellisoni extends also against viruses, mice infected with these protozoa were challenged with Mengo virus, and resistance to viral challenge persisted in some groups of mice for longer than 1 year.
Abstract: SummaryTo determine if the resistance to intracellular bacteria observed in mice chronically infected with Toxoplasma gondii or Besnoitia jellisoni extends also against viruses, mice infected with these protozoa were challenged with Mengo virus. Significantly greater survival and/or prolonged time to death were noted in the protozoal infected animals when compared with controls. This resistance to viral challenge persisted in some groups of mice for longer than 1 year. Resistance to viral challenge was also noted in mice infected with Listeria monocytogenes but less marked and persisted for a shorter period of time than in protozoal-infected animals. To define a possible role for interferon, serum, peritoneal fluid, and spleens of the protozoal-infected mice were assayed for interferon levels at various intervals following initial infection. Interferon was demonstrable only during the acute stage of the infections, whereas resistance to viral challenge in the same animals persisted in some instances for m...

Journal ArticleDOI
TL;DR: Comparison of cytadsorptive activity and peroxide formation by measurement of hemadsorption and hemolysis revealed variations between heterologous strains, but no differences consistently related to virulence.
Abstract: SummaryA study of the relationship between virulence, peroxide formation, and cytadsorption in M. pneumoniae was undertaken. Two pairs of homologous virulent and attenuated strains were derived by passage of parent strains in animals and artificial media. Comparison of their cytadsorptive activity and peroxide formation by measurement of hemadsorption and hemolysis revealed variations between heterologous strains, but no differences consistently related to virulence. The existence of additional mediators of virulence is suggested.

Journal ArticleDOI
TL;DR: It appears that zinc, but not manganese, is required for normal metabolism of calcium, and the skeletal abnormals are not the result of abnormal calcium metabolism.
Abstract: SummaryThe metabolism of calcium was studied in manganese-deficient and zinc-deficient rats by a method combining a kinetic study using 45Ca with a short-term classical balance study. There were no differences in managanese-deficient rats as compared with controls in any of the parameters of calcium metabolism, including pool size, endogenous fecal calcium, urinary clacium, or in the rates of calcium entering or leaving bone. The zinc-deficient animals, however, showed significant decreases, as compared with both ad libitum and restricted-intake controls, in a number of parameters of calcium metabolism. These included the rates of calcium entering and leaving bone, pool size, the rate of slow exhange, and the slowly exchangeable calcium in bone. The results suggest that the skeletal abnormals are not the result of abnormal calcium metabolism. In zinc deficiency, on the other hand, specific effects on calcium metabolism were noted. Thus it appears that zinc, but not manganese, is required for normal metabo...

Journal ArticleDOI
TL;DR: In this paper, the renin-angiotensin axis may be a potent factor in the development of acute renal failure in the rat given glycerol intramuscularly.
Abstract: SummarySubstitution of 1% saline for drinking water largely prevents the development of established acute renal failure in rats given glycerol intramuscularly. Control experiments indicate that this protection from acute renal failure is not due to the blood volume expansion, polyuria, polydypsia, lower urine osmolality, or other parameters studied. It is suggested that the depletion of renin, associated with chronic saline-loading, may have played a protective role, and that the renin-angiotensin axis may be a potent factor in the development of glycerol-induced acute renal failure in the rat.

Journal ArticleDOI
TL;DR: A direct immunofluorescent (FA) test was used to facilitate typing of Herpesvirus hominis (HVH) strains and there was total agreement between results using the FA technique and those obtained previously by a mieroneutralization test in the typing of 95 HVH isolates.
Abstract: SummaryA direct immunofluorescent (FA) test was used to facilitate typing of Herpesvirus hominis (HVH) strains. Using specific dilutions of fluorescein-conjugated rabbit anti-type 1 and anti-type 2 sera, HVH strains grown in HEp-2 cells could be typed as 1 if they reacted with both conjugated sera and as type 2 if they reacted only with anti-type 2 sera. In addition, a difference in staining between type 1 and type 2 infected cells was observed: type 1 infected cells showed perinuclear staining and fluorescent granules with either conjugated serum; type 2 infected cells showed no coarse granules and had both perinuclear and nuclear staining.There was total agreement between results using the FA technique and those obtained previously by a mieroneutralization (MN) test in the typing of 95 HVH isolates. When an additional 96 HVH isolates were tested by the FA technique only, the type found correlated well with site of isolation. Current experience with 322 HVH isolates typed by the MN test only, FA test onl...

Journal ArticleDOI
TL;DR: Poly I:C was therapeutic against PVM infection in mice when given as late as 3 days after infection and the duration of protective effect induced by poly I: C persisted for almost 7 days in the PVM system.
Abstract: SummaryStudies were conducted in mice and chicks to measure the prophylactic and therapeutic efficacy of poly I:C in a variety of infections by both DNA and RNA viruses. Drug and virus were given by a variety of routes in a number of different regimens including variable drug and virus dosage. Marked prophylactic protection was obtained against PVM, Columbia SK, vaccinia, and parainfluenza 1 virus infections in mice. Poly I:C was therapeutic against PVM infection in mice when given as late as 3 days after infection and the duration of protective effect induced by poly I:C persisted for almost 7 days in the PVM system. Weak responses were noted against rabies, influenza B, and Rous sarcoma viruses, while the responses to influenza A, yellow fever, and Marek's agent were negative. The highly complex relationships between virus and drug administration will necessitate further study before optimal prophylactic and therapeutic regimens can be developed.The authors are indebted to Carolyn Saydah, Carol Bonoma, ...

Journal ArticleDOI
TL;DR: The antibacterial activity produced by a mold commonly used in an oriental food fermentation is considered significant for those people whose diets are often nutritionally inadequate and potentially ingestion of this material may confer disease resistance.
Abstract: SummaryStrains of R. oligosporus produce an antibacterial compound especially active against some gram-positive microorganisms. The material can be extracted with water from soybeans fermented by R. oligosporus. It can also be recovered from culture broth by ammonium sulfate precipitation. The compound is fairly stable in its semi-purified state and may consist of four or five components. The antibacterial activity produced by a mold commonly used in an oriental food fermentation is considered significant for those people whose diets are often nutritionally inadequate. Conceivably ingestion of this material may confer disease resistance.

Journal ArticleDOI
TL;DR: It was confirmed in this study that tissue culture fluid harvested from rabies virus infected cell culture and inactivated by BPL or UV irradiation can be used for immunization against rabies.
Abstract: Summary and ConclusionsIt was confirmed in this study that tissue culture fluid harvested from rabies virus infected cell culture and inactivated by BPL or UV irradiation can be used for immunization against rabies. The protective activity of such preparation in mice was, however, generally not much higher than that of the NIH reference vaccine in a mouse potency test.

Journal ArticleDOI
TL;DR: Wheeler and Alexander have shown that cytoxan-resistant and sensitive tumors implanted bilaterally in hamsters show the same extent of incorporation of the alkylating agents, cytxan, nitrogen mustard, and thioTEPA into their DNA fractions when these drugs are administered systemically, indicating that the DNA of resistant tumors is just as vulnerable as that of sensitive tumors.
Abstract: One of the frustrating aspects of tumor therapy has been the resistance developed by tumors to the agents used therapeutically. Alkylating agents and ionizing radiation, which are used frequently in tumor therapy at the present time, are designed to cause damage to the DNA of tumor cells such that they can no longer divide. However, it has been demonstrated that both bacterial (1–4) and mammalian cells (5–8) have the ability to repair such damage to their DNA by means of specific enzymic mechanisms.Mammalian cell lines have been isolated which show resistance to specific alkylating agents. After the development of this resistance, these cells show a cross resistance to other types of alkylating agents and X-rays with little or no change in their response to such antimetabolites as amethopterin, mercaptopurine, florodeoxyuridine, and azaserine (9). This suggests that a common mechanism may be responsible for the resistance shown by tumors toward alkylating agents and ionizing radiation. Wheeler and Alexand...

Journal ArticleDOI
TL;DR: The Vero cell line provides the virologist with another tool for diagnostic and research work, and perhaps offers advantages for large scale production of viral agents for vaccine.
Abstract: SummaryA continuous cell line derived from kidney tissue of the African green monkey (Cercopithecus aethiops), and designated as Vero, has been maintained and was studied at passage 107–165 levels for susceptibility to various viruses. Vero cells supported the growth of a number of viruses to high titers. Extensive cytopathic effects and plaque formation in Vero cell cultures make possible an efficient and reproducible direct technique for the demonstration of a number of viruses and of specific neutralizing antibodies. In addition, growth of a number of viruses (such as rubella, SV-5, and the Tacaribe group of viruses) to a high titer in a continuous simian cell line provides a convenient source of virus and antigen for other studies. Thus, the Vero cell line provides the virologist with another tool for diagnostic and research work, and perhaps offers advantages for large scale production of viral agents for vaccine.

Journal ArticleDOI
TL;DR: Oxonic acid and allantoxaidine were potent in vivo inhibitors of uricase and the oxonic acid-treated rat may serve as a useful animal model for the study of hyperuricemia andhyperuricosuria.
Abstract: SummaryOxonic acid and allantoxaidine were potent in vivo inhibitors of uricase. Oxonic acid, when fed to rats or injected intraperitoneally, produced a marked increase in blood plasma urate levels and urinary uric acid output with a concomitant decrease in urinary allantoin excretion. Addition of 5% oxonic acid plus 1% uric acid to the diet resulted in a 22-fold increase in urinary uric acid by day 23 of treatment with deposition of uric acid in the kidney tubules. The oxonic acid-treated rat may serve as a useful animal model for the study of hyperuricemia and hyperuricosuria.

Journal ArticleDOI
TL;DR: Evidence further supports the suggestion that gastrin may be a trophic hormone for parts of the digestive tract and is qualitatively identical to those reported previously from an in vitro system.
Abstract: SummaryRats were injected with 14C-leucine and either gastrin or saline and killed 2 hr later. Protein was precipitated from various tissues and the incorporation of the radioactive amino acid determined as an index of protein synthesis. Gastrin produced an 11–32% stimulation of protein synthesis in tissues from the duodenum and stomach but had no effect on liver, and decreased the incorporation in skeletal muscle. These effects are qualitatively identical to those reported previously from an in vitro system. We conclude that this evidence further supports the suggestion that gastrin may be a trophic hormone for parts of the digestive tract.This study was supported by Veterans Administration Research Funds and by NSF Grant GB 7285X and by U. S. Army Grant DA-HC19-67-G-0004. The authors are grateful to Mr. Lawrence Yuen for expert technical assistance and to Dr. Morton I. Grossman for advice and support. This work was done while Dr. Leonard Johnson held an NIH Postdoctoral Fellowship. Dr. Johnson's current...