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Biomedical subjects

N Hunter

Publications and source records attributed to N Hunter.

At least 217 records · Page 12Linked to original sources
PubMed1984

Protection by S-2-(3-aminopropylamino)ethylphosphorothioic acid against radiation- and cyclophosphamide-induced attenuation in antitumor resistance.

Studies were performed to investigate whether S-2-(3-amino-propylamino)ethylphosphorothioic acid (WR-2721) can protect antitumor immune rejection responses against the damaging effects of whole-body irradiation ( WBI ) and cyclophosphamide (CY). Among these damaging effects were radiation-induced enhancement of s.c. tumor take and radiation- and CY-induced enhancement of lung colonization by tumor cells injected i.v. The ability of WR-2721 to protect against WBI -induced decreased radioresponse of solitary tumors was also investigated. All experiments were performed with an immunogenic fibrosarcoma syngeneic to C3Hf/ Kam mice. WR-2721 was given i.p. at a dose of 400 mg/kg 30 min before WBI with gamma-rays or CY injection. WBI with 650 rads reduced the number of tumor cells needed for tumor take in 50% of animals from 5.1 X 10(4) cells in normal mice to 2.0 X 10(2). WR-2721 given before WBI almost entirely abolished the effect of WBI : the number of tumor cells needed for tumor take in 50% of animals was 1.4 X 10(4). Treatment of mice with WBI or CY increased the number of tumor nodules in the lung generated by fibrosarcoma cells injected i.v. 5 days later, in a linear dose response. WR-2721 greatly reduced this metastasis enhancement effect of WBI and CY with protection factors of 2.5 for WBI and 1.8 for CY. Fibrosarcomas of 8 mm in diameter exhibited a decreased radiocurability when growing in WBI mice: the dose of irradiation yielding local tumor control in 50% of animals in these mice was 5950 compared to a dose of irradiation yielding local tumor control in 50% of animals of 4160 rads in normal mice. WR-2721 given before WBI inhibited this effect of WBI : the dose of irradiation yielding local tumor control in 50% of animals was 5210 rads. The proportion of macrophages in tumors growing in WBI mice was significantly reduced, but not when WR-2721 was first given. WR-2721 greatly reduced the damaging effects of WBI and CY on natural killer cell activity. Therefore, WR-2721 was capable of protecting the immune mechanisms involved in antitumor resistance against WBI and CY. This might be of therapeutic benefit when WR-2721 is combined with radio- or chemotherapy.

Amifostine↗
PubMed1983

Survey of radiographic requirements and techniques in United States dental assisting programs, 1982.

A survey of dental assisting programs revealed little standardization of student requirements for dental radiography in the United States. Areas for concern were (1) the high proportion of programs in which classmates exposed one another to ionizing radiation for training purposes and (2) the continued use of closed cones in some cases. Preclinical laboratories in radiography were, on average, of considerably longer duration than those previously reported for dental students. Conversely, clinical requirements in intraoral techniques were less for dental assisting students than is the case for dental students. Available methods of reducing patient exposure to ionizing radiation are not being fully implemented.

Clinical Competence↗
PubMed1983

Inhibition of artificial and spontaneous lung metastases by preirradiation of abdomen--II. Target organ and mechanism.

We have previously reported that irradiation of the abdomen of mice before i.v. injection of both immunogenic and nonimmunogenic tumour cells is capable of suppressing their ability to form metastatic lung nodules in a time and dose-dependent fashion. Experiments with segmental exposure indicated the target organ to be located in the ventral half of the abdomen. The effect has now been shown positively to depend upon irradiation of the caecum, and can be abolished either by shielding the caecum from irradiation or by surgically removing it prior to irradiation. Further experiments have shown that the effect cannot be elicited in germ-free mice and that its magnitude is markedly reduced in animals given gut-sterilizing antibiotics. Split-dose irradiation only slightly reduced the magnitude of suppression, provided both doses were given within the time window of effectiveness of single doses. Tumour-growth retardation was observed and spontaneous lung metastases were also suppressed when tumour-bearing mice received abdominal irradiation 7 days after tumour cell transplantation into the leg. However, abdominal irradiation did not significantly reduce subsequent tumour transplantability by the s.c. or i.p. routes. The experimental data are consistent with a mechanism by which transmigration of enteric bacteria across the radiation-damaged mucous membrane of the caecum effectively results in an endogenous infusion of endotoxin.

Abdomen↗
PubMed1983

Characteristics of a high molecular weight extracellular protein of Streptococcus mutans.

A high molecular weight protein antigen, designated P1, has been isolated from the culture fluid of chemostat-grown Streptococcus mutans strain Ingbritt and shown to be free of other antigens including glucosyltransferase. Antiserum against the protein was used in rocket immunoelectrophoresis to confirm and extend the previous observation that there were major differences in the amount of the protein produced under different growth conditions. Physico-chemical and serological studies indicated that protein P1 was indistinguishable from antigens B, I/II and IF isolated in other laboratories. Mammalian tissue cross-reactivity of protein P1 was demonstrated by binding of antiserum to P1 to sections of normal rabbit tissues, particularly heart. There was also a statistically significant increase in the number of mononuclear leucocytes in heart tissue of rabbits which had been injected with protein P1, when compared with the levels in control uninjected rabbits; injection with whole cells of S. mutans Ingbritt did not produce this effect.

Amino Acids↗
PubMed1983

Effect of tumor size on S-2-(3-aminopropylamino)ethylphosphorothioic acid and misonidazole alteration of tumor response to cyclophosphamide.

The influence of tumor size on the ability of S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) or misonidazole (MISO) to alter cyclophosphamide (CY) antitumor activity was investigated, using a chemically induced fibrosarcoma (FSA) and a spontaneous fibrosarcoma (NFSA) in C3Hf/Kam mice. Tumors were of two sizes at the time of treatment, 8-mm leg tumors and 4-day-old micrometastases in the lung. The antitumor activity of CY and its modification were assessed by growth delay of leg tumors and the reduction in the number of lung metastases. Both measures of tumor response were more pronounced as the dose of CY increased, and FSA was more sensitive to CY than was NFSA. WR-2721 (400 mg/kg), given 30 min before treatment with CY, reduced the effectiveness of CY on both FSA and NFSA. This reduction in effectiveness of CY was only minimal for leg tumors (dose-modifying factors were 1.1 for FSA and 1.03 for NFSA) but remarkable for lung micrometastases (dose-modifying factors were 1.81 for FSA and 1.55 for NFSA). Protection increased with the increase in the dose of WR-2721 and was also dependent on the time of injection relative to CY. The greatest protection occurred when WR-2721 was given within 30 min before to 15 min after CY. Tumor size had the opposite effect on MISO from that on WR-2721. MISO (1 mg/g) enhanced the effect of CY more effectively for leg tumors than for lung micrometastases: dose-modifying factors were 1.74 for FSA and 2.21 for NFSA growing in the leg and 1.27 for FSA and 1.11 for NFSA lung micrometastases. Therefore, tumor size appears to be a very important factor in determining the extent of WR-2721- and MISO-induced modification of CY antitumor effect.

Amifostine↗
PubMed1983

Protection by S-2-(3-aminopropylamino)ethylphosphorothioic acid against radiation-induced leg contractures in mice.

S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR-2721) was shown to provide marked protection against development of radiation-induced leg contractures in C3Hf/Kam mice whose legs were exposed to single doses of gamma-radiation. The radiation doses ranged from 3300 to 6200 rads delivered to the right hind thighs from two parallelly opposed 137Cs sources. WR-2721 was given i.p. 30 min before irradiation. The severity of radiation-induced leg contractures in untreated and WR-2721-treated mice was followed for 342 days after irradiation. The degree of leg contractures in both control and WR-2721-treated mice increased up to 100 days after radiation, when the change stabilized, remaining more or less at the same level to the end of the observation period. During this entire period, the severity of contractures was less in WR-2721-treated mice. The dose-modifying factor for the level of 5 mm reduction in leg extension was 1.5 at 182 days after irradiation. Since WR-2721 did not prevent the radiocurability of 8-mm fibrosarcomas growing in the same legs, these data imply that WR-2721 has a high potential for increasing therapeutic gain when combined with irradiation in the treatment of tumors of an appreciable size.

Animals↗
PubMed1982

Studies on the antitumor activities of pyrimidinone-interferon inducers. I. Effect against artificial and spontaneous lung metastases of murine tumors.

Since pyrimidinone compounds induce interferon production in several animal species and have potent antivirus activities, it appeared important to determine whether these compounds could also induce antitumor activities in their recipients. Pyrimidinone compounds 2-amino-5-bromo-6-methyl-4-pyrimidinone (ABMP), 2-amino-5-brome-6-phenyl-4-pyrimidinone (ABPP), and 2-amino-5-iodo-6-phenyl-4-pyrimidinone (AIPP) were studied for their activities against artificial lung metastases of the weakly immunogenic spontaneous fibrosarcoma NFSa, the moderately immunogenic spontaneous mammary carcinoma MCa-K, and the strongly immunogenic 3-methylcholanthrene-induced fibrosarcoma FSa syngeneic to inbred C3Hf/Kam mice. In addition, the therapeutic efficacy of ABPP and AIPP was also determined against spontaneous lung metastases of NFSa. ABPP and AIPP given ip at 250 mg/kg for 2 or 3 consecutive days before or after iv inoculatin of NFSa, FSa, or MCa-K cells greatly reduced the number of tumor nodules developed in the lungs. ABMP, however, was considerably less effective. ABPP and AIPP were also effective in therapy of spontaneous lung metastases of NFSa, especially when these compounds were given before surgical removal of the primary tumor. Neither ABPP nor AIPP was effective against tumor nodules growing in whole-body irradiated (WBI) mice, but both protected mice against enhancement of lung metastasis formation induced by exposure to whole-body irradiation. ABPP was more effective than AIPP in inducing production of interferon in normal mice. When treated with ABPP, WBI mice, however, were unable to produce interferon. These results show that 6-phenyl-pyrimidinone compounds induce strong antitumor activities in mice, which correlated with neither tumor immunogenicity nor the ability of these agents to induce interferon, but which depended on the immune status of the tumor host.

Animals↗
PubMed1982

Protective effects of S-2-(3-aminopropylamino)ethylphosphorothioic acid against radiation damage of normal tissues and a fibrosarcoma in mice.

S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR-2721) was investigated for its protective effect against radiation-produced damage of jejunum, testis, lung, hair follicles, and a fibrosarcoma of C3Hf/Kam mice. Most of these tissues were radioprotected, and the degree of radioprotection depended on the dose of WR-2721 and the time interval between administration of WR-2721 and radiation treatment. WR-2721 increased resistance of jejunal epithelial cells and spermatogenic cells to single doses of gamma-rays by factors of 1.64 and 1.54, respectively. Protection against hair loss was less pronounced; the dose-modifying factor here was 1.24. The radiation-induced acute damage of the lung expressed by the increased formation of tumor nodules in the lung was not decreased by treatment of animals with WR-2721 before radiation. In contrast, WR-2721 augmented the radiation-induced enhancement of metastasis formation in the lung. WR-2721 protected fibrosarcoma micrometastases in the lung against therapeutic effect of radiation by a factor of 1.238. In contrast, this compound had no effect on the therapy of an 8-mm fibrosarcoma growing in the legs of mice.

Amifostine↗
PubMed1981

Long-term effects of pulmonary damage in mice on lung weight, compliance, hydroxyproline content and formation of metastases.

The development of "metastatic" colonies of fibrosarcoma in the lungs of mice after IV injection of a single-cell suspension of tumour cells varied with time after irradiation or administration of bleomycin. Most notably, there was a late radiation-induced enhancement of colony-forming efficiency that coincided with an increase in lung weight and hydroxyproline content and a decrease in compliance. There was no radiation-induced enhancement of "spontaneous" metastases from a mammary carcinoma implanted in the thighs of the animal. The sequence of events after administration of bleomycin was similar to that after irradiation, but the duration of the treatment was different and the temporal relationship between enhanced colony-forming efficiency and changes in lung weight and hydroxyproline content was not as clear cut.

Animals↗
PubMed1981

Therapy of artificial and spontaneous metastases of murine tumors with maleic anhydride-divinyl ether-2.

A 15,500 molecular-weight fraction of a pyran copolymer, (MVE-2) was investigated for its therapeutic efficacy against artificial lung metastases of a weakly immunogenic spontaneous fibrosarcoma (NFSa), a relatively strongly immunogenic fibrosarcoma (FSa), a moderately immunogenic spontaneous mammary carcinoma (MCa-K-, and a weakly immunogenic spontaneous mammary carcinoma (MDAH-MCa-4) syngeneic to C3Hf/Kam mice. In addition, the therapeutic efficacy of this polyanionic compound against spontaneous lung metastases of NFSa was also determined. Systemic i.v. or i.p. application of MVE-2 in doses ranging from 10 to 50 mg/kg body weight greatly reduced the number of artificial NFSa lung metastases and prolonged the survival of the mice. Multiple injections of MVE-2 given at weekly intervals were more effective than were single treatments. Although various treatment schedules with MVE-2 were capable of reducing the number of metastases and prolonging survival of tumor-bearing mice, no cures were observed. A therapeutic effect was also evident against spontaneous lung metastases of NFSa. The effect, however, was more profound when MVE-2 was given before rather than after surgical removal of the primary tumor. MVE-2 was not effective in mice exposed previously to whole-body or local thoracic irradiation. In contrast, MVE-2 protected mice against enhancement of lung metastases induced by exposure of the mice to these irradiations. NFSa growing i.m. promoted the formation of lung metastases from tumor cells given i.v. This concomitant enhancement of metastases was abolished by treatment of the mice with MVE-2. MVE-2 was also effective against tumor deposits in the other three tumors. The extent of its therapeutic efficacy was independent of tumor immunogenicity. These results suggest several approaches to the clinical application of MVE-2 and provide additional data on the therapeutic activity of the pyran copolymer derivatives in different animal models.

Animals↗
PubMed1980

Inhibition of artificial lung metastases in mice by pre-irradiation of abdomen.

A phenomenon by which pre-irradiation of the abdomen of mice reduced the lung-colony-forming efficiency of i.v.-injected tumour cells is described. The extent of lung-colony inhibition was shown to depend on both the dose and timing of abdominal irradiation. The maximum inhibitory effect was obtained when mice received 1200 rad gamma-irradiation to the abdomen 5--7 days before tumour-cell challenge, but there was no effect when abdominal irradiation was given 1 or greater than or equal to 14 days before challenge, or when radiation doses were less than 600 rad. In mice less than 3 weeks old, the effect was much less marked than in adults. The target tissue which, when irradiated, exerted the inhibitory influence on lung-colony formation was located in the ventral half of the abdomen in all 4 quadrants, and was probably gut. Radioactively labelled tumour cells were arrested normally in the lungs of irradiated mice, but were cleared more rapidly without evidence of sequestration in the irradiated gut. The most plausible mechanism seems to be that irradiation of the gut induces the production of natrual killer cells with anti-tumour activity, though this has not been conclusively established.

Abdomen↗
PubMed1980

Lipopolysaccharide Composition of the Wilt Pathogen, Pseudomonas solanacearum: CORRELATION WITH THE HYPERSENSITIVE RESPONSE IN TOBACCO.

In the induction of the hypersensitive response (HR) in tobacco by Pseudomonas solanacearum, the recognition between host and pathogen is thought to involve an interaction between plant lectins and bacterial lipopolysaccharide (LPS). The LPS of a series of strains of P. solanacearum were examined to determine if there are structural differences that might account for the ability or inability of these strains to induce the hypersensitive response. Analysis of the components of LPS by gas chromatography indicates a clear difference in sugar composition between the HR-inducing and non-HR-inducing strains, especially in terms of the percentage of glucose, xylose and rhamnose. Sodium dodecyl sulfate polyacrylamide gel electrophoresis shows there are two distinct kinds of LPS, differing greatly in size, which correspond to rough and smooth LPS in other systems. In addition, a phage, CH154, was isolated which lyses non-HR-inducing bacteria and which is inactivated by LPS from these bacterial strains. Therefore, differences in LPS structure correlate strongly with host recognition of Pseudomonas solanacearum.

Journal Article↗
PubMed1980

Cell-mediated immune response during experimental arthritis induced in rats with streptococcal cell walls.

Chronic, remittent, erosive arthritis was produced in rats by a single intraperitoneal injection of an aqueous suspension of cell wall fragments isolated from group A streptococci. Arthritis could be induced in rats which had been immunologically compromised by neonatal thymectomy. Delayed hypersensitivity to cell wall peptidoglycan could not be elicited in these rats, although progressive joint disease was obvious by clinical and radiological measurements. A delayed skin test was elicited with peptidoglycan in non-thymectomized rats at 6 to 14 days after injection of low doses of cell wall fragments. Between 2 to 4 weeks after cell wall injection the skin test could not be elicited and these rats could not be sensitized again with peptidoglycan. After a high dose of cell wall the skin test could not be elicited at any time. These non-thymectomized rats which had been injected with cell walls remained hyporesponsive to peptidoglycan for at least 3 months. Lymphocytes from non-thymectomized cell wall-injected rats also showed a non-specific depression of lymphocyte response to phytohaemagglutinin in vitro, but this function was recovered between 2 to 4 weeks after cell wall injection. We conclude that cell-mediated immunity against bacterial cell wall antigens is not a pathogenetic factor in this experimental model of arthritis.

Animals↗
PubMed1980

Antibody response to streptococcal cell wall antigens associated with experimental arthritis in rats.

The antibody response to group A streptococcal cell wall components was measured in rats during the development of chronic, remittent experimental arthritis. The arthritis was induced by a single intraperitoneal injection of an aqueous suspension of group A streptococcal cell wall fragments and antibodies were measured by a radioactive antigen-binding assay. Antibodies in serum against both peptidoglycan and A polysaccharide reached maximum levels at 1 or 2 weeks and declined to preimmunization levels by day 63. The kinetics and magnitude of the antibody responses were similar in neonatally thymectomized and non-thymectomized rats. A relationship between chronic joint lesions and anti-peptidoglycan concentration in serum was indicated, since all rats which produced high levels of antibody developed severe chronic arthritis. However, 46% of the rats which produced very low levels of antibody also developed moderate to severe arthritis. There was no correlation between anti-A polysaccharide antibodies and joint disease, although the concentration of this antibody was 10- to 100-fold greater than the anti-peptidoglycan. We conclude that antibody can be a component in the pathogenesis of this experimental model of arthritis, but its role requires further elucidation.

Animals↗