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Biomedical subjects

N Hunter

Publications and source records attributed to N Hunter.

At least 145 records · Page 8Linked to original sources
PubMed1993

The association of carious dentin microflora with tissue changes in human pulpitis.

Correlations were sought between the number and type of microorganisms recovered from sampled carious dentin and the cellular responses observed in dental pulpal tissues from a sample of 65 vital, carious teeth extracted from adult humans who had declined the option of tooth restoration. Standardized homogenates of carious dentin were plated using selective and nonselective media under anaerobic and microaerophilic conditions. Pulpal responses were characterized histopathologically on the basis of the nature of the cellular infiltrate and the extent of degenerative changes. A significant association between the number of Prevotella intermedia and Prevotella melaninogenica in carious dentin and extensive, principally mononuclear, inflammatory infiltration was evident despite a high degree of complexity and intersubject variability in the microbial flora. There was no apparent association between other microorganisms or total microbial load and the histopathological category.

Actinomyces↗
PubMed1993

Production of an early release, M(r) 36,000 monokine by stimulated rat macrophages.

Supernatants from rat peritoneal macrophage cultures stimulated with bacterial products contain a M(r) 36,000 factor that protects immature cortical thymocytes from loss of viability over a 4-hr incubation period in vitro. This effect could not be produced with purified transforming growth factor-beta or recombinant interleukin-6 (IL-6). Further, the partially purified M(r) 36,000 fraction was inactive in bioassays for IL-1 and tumour necrosis factor. Maximal production of the factor occurred 2 hr after the addition of 20 micrograms/ml of lipopolysaccharide, as assessed by the titre resulting in 100% protection of thymocytes in a viability assay. The detection of protective activity within 5 min after addition of the stimulant could be attributed to the release of intracellular stores but protein synthesis was required to account for the increasing titre up to peak levels. The titre fell rapidly after 2 hr so that activity could not be detected at 4 hr. This profile of release was refractory to repeated stimulation with lipopolysaccharide. Conjoint addition of lipopolysaccharide and indomethacin, did, however, allow release in response to subsequent challenge. Related to this finding, prostaglandin E2 completely inhibited the release of protective activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Natural scrapie in British sheep: breeds, ages and PrP gene polymorphisms.

One hundred and sixty-seven sheep of 32 breeds and crossbreeds affected by natural scrapie throughout Britain were tested for the presence of restriction fragment length polymorphisms of the PrP gene observed when their DNA was digested with EcoRI or HindIII. These polymorphisms have already been associated with different susceptibilities to experimental scrapie (controlled by alleles of the Sip gene) in a flock of Cheviot sheep. In two studies 86 to 92 per cent of the sheep were found to carry the PrP gene EcoRI fragment e1 which is associated with high susceptibility (or the sA allele of Sip) to experimental scrapie. The PrP gene HindIII genotypes of the natural scrapie sheep were not apparently associated with differences in susceptibility to scrapie. There was no link between the polymorphisms and the age or breed of the affected sheep.

Age Factors↗
PubMed1992

Studies on maternal transmission of scrapie in sheep by embryo transfer.

The technique of embryo transfer was used to investigate the maternal transmission of scrapie in sheep. Embryo donor ewes were experimentally infected with scrapie (all eventually developing the disease) and artificially inseminated six months later with semen from an uninfected scrapie-susceptible ram. Embryos were harvested five and six days after insemination and transferred by laparoscopy, unwashed, into recipient ewes which had been genetically selected for very low susceptibility to scrapie. Six of the 26 lambs born to these recipients developed scrapie.

Animals↗
PubMed1992

Combination of interleukin-2 and irradiation in therapy of murine tumors.

Experiments were designed to investigate the therapeutic efficacy of interleukin-2 (IL-2) combined with radiotherapy. The effect of IL-2 and local thoracic irradiation (LTI) was determined on 4-day-old lung micrometastases, generated by i.v. injection of tumor cells into mice. IL-2 alone reduced the number of lung nodules more effectively when given from 1 to 4 than 4 to 7 days after tumor cell injection. The combination of IL-2 and LTI reduced the number of lung nodules more than did the individual treatments alone. When IL-2 therapy was combined with local irradiation of 8-mm leg tumors, there was no change in the TCD50 (radiation dose yielding 50% local tumor control). However, the combination of IL-2 treatment on days 1-4 with irradiation of tumor-bearing legs on day 1 after inoculation of tumor cells reduced the TCD50 by a factor of 1.3. These results show that IL-2 improves tumor radiotherapy, but that the improvement depends on anatomic localization and tumor size at the time of treatment.

Animals↗
PubMed1992

Radiation protection against early and late effects of ionizing irradiation by the prostaglandin inhibitor indomethacin.

Protective effects of indomethacin, a prototype prostaglandin-inhibiting agent, against early and late sequelae of radiation injury (after X-rays or gamma rays) in mice were investigated. The following tissues or organs were examined: hematopoietic tissue, esophagus, jejunum, colon, lung, hair follicles, and tissues involved in the development of radiation-induced leg contractures. In addition, the effect of indomethacin was tested against radiation-induced carcinogenesis. In all experiments, the radiation was delivered as a single dose. Indomethacin led to significant protection of hematopoietic tissue, by a factor of 1.3. There was also some protection against radiation-induced pneumonitis and against radiation-induced carcinogenesis (protection factor of 1.2). The other tissues tested showed no change in their radioresponse after being treated with indomethacin. Thus, indomethacin can act as a radioprotective agent against both early and late sequelae of radiation, but its effect is dependent on the tissue tested. This protection is smaller than that observed with WR-2721. However, indomethacin combined with WR-2721 produced a radioprotective effect greater than the radioprotection achieved by individual treatments.

Amifostine↗
PubMed1992

Are Sinc and the PrP gene congruent? Evidence from PrP gene analysis in Sinc congenic mice.

Congenic mouse strains VM/Dk and VM-Sincs7/Dk differ at the Sinc gene, which controls the incubation period of scrapie in mice; VM/Dk mice are Sincp7p7 and VM-Sincs7/Dk mice are Sincs7s7. Restriction fragment length polymorphism and DNA sequencing analysis demonstrated that the PrP genes also differ in these strains, confirming the close genetic linkage of Sinc and PrP. Using the restriction enzyme HhaI, we have shown that at least 100 kb of DNA flanking the PrP gene differs between the two strains, and therefore the congruence of the Sinc and PrP genes is still not certain.

Animals↗
PubMed1992

Polymorphisms of a scrapie-associated fibril protein (PrP) gene and their association with susceptibility to experimentally induced scrapie in Cheviot sheep in the United States.

The duration of the incubation period for scrapie, a fatal transmissible neurodegenerative disorder of sheep and goats, is mainly determined by the Sip gene, which has 2 alleles (sA--susceptible and pA--resistant). A diagnostic test is not available to detect scrapie in live animals. We analyzed genomic DNA extracted from frozen sheep brains collected from Cheviot sheep of the United States that had been inoculated with the SSBP/1 scrapie inoculum. Digestion of the DNA with EcoRI or HindIII followed by the addition of a scrapie-associated fibril protein (PrP)-specific marker probe, yielded fragments of 6.8 (e1) and 4.0 (e3) kb, or 5.0 (h1) and 3.4 (h2) kb, respectively. Fragments e1 and h2 were associated with the histopathologic diagnosis of scrapie, and fragments e3 and h1 were associated with survival. A valine/alanine polymorphism within the PrP coding region that resulted in a BspHI site was further used to determine the genotype of these Cheviot sheep. Digestion of polymerase chain reaction fragments with BspHI resulted in an undigested fragment b- (0.840 kb), digested fragments b+ (0.460 and 0.380 kb), or both types of fragments. Survival time of b+/b+ homozygous sheep was significantly (P < 0.01) shorter (218 +/- 26.0 days) than survival time for b-/b- sheep (> 700 days after inoculation). Results indicated that b+ and b- are markers for the Sip sA and pA alleles, respectively. The intermediate duration of the incubation period for heterozygous sheep (b+/b-; 342.9 +/- 25.3 days) indicated that the Sip sA allele is expressed codominantly to the Sip pA allele.

Animals↗
PubMed1991

Improvement in therapeutic ratio of radiotherapy for a murine sarcoma by indomethacin plus misonidazole.

In this study we asked whether the improvement in the therapeutic ratio of radiotherapy by indomethacin (INDO), which potentiates tumor radioresponse through stimulation of the immune system, could be further improved by combining it with the hypoxic cell radiosensitizer misonidazole (MISO). Mice bearing the syngeneic sarcoma fibrosarcoma (8 mm) in the leg were treated with single graded doses of gamma-rays to the tumor or with irradiation combined with INDO, MISO, or both drugs. Local tumor control was the end point of tumor radioresponse. In addition, the effect of these drugs on radiation-caused hair loss and leg contractures was assessed. INDO increased tumor radioresponse by a factor of 1.31, but it did not affect either hair loss or leg contractures. MISO increased tumor radioresponse by a factor of 1.86, hair loss by a factor of 1.69, and leg contractures by a factor of 1.54, thus providing only a small therapeutic gain. The combined INDO plus MISO treatment increased tumor radioresponse by a factor of 2.72, which was more than the additive effect of the individual drugs. On the other hand, the combined treatment caused no additional hair loss compared to that caused by MISO only. Overall, our results show that INDO plus MISO treatment increased tumor radioresponse more than INDO or MISO alone and provided a significant therapeutic gain. Furthermore, they illustrate that combinations of two radiopotentiating agents with different mechanisms of action may improve the radiotherapeutic effect.

Animals↗
PubMed1991

The epidemiology of tuberculosis among North Carolina migrant farm workers.

Although tuberculosis (TB) has been recognized as a significant health problem of migrant farm workers, the nature and extent of the problem have been poorly defined. We report the first population-based study of TB in a random sample of farm workers (n = 543) and the first use of recall antigens in an epidemiologic study of TB. Purified protein derivative positivity ranged from 33% in Hispanics to 54% in US-born blacks and 76% in Haitians. Active tubercular disease occurred in 3.6% of US-born blacks and 0.47% of Hispanics. Among US-born blacks, risk factors associated with farm work were most significant. Blacks born in the United States also had the highest prevalence of anergy. The use of recall antigens made possible a better description of the epidemiology of TB by excluding false negatives and clarifying associations between infection and risk factors. We conclude that TB among farm workers represents a serious public health problem with previously unrecognized risk factors. Additional resources for migrant health care, improvements in health care access, and fundamental changes in the system of migrant labor are all necessary to reduce the transmission of TB.

Agriculture↗
PubMed1991

Concurrent lipopolysaccharide enhances chemotactic response of human polymorphonuclear leukocytes to bacterial chemotaxin.

Polymorphonuclear neutrophil (PMN) function is thought to be critical in resistance to infectious agents and this implies that the PMN must be able to migrate into, and to function in, environments that may have high levels of bacterial lipopolysaccharide (LPS). Therefore, we have evaluated the effect of LPS on the in vitro migration of PMNs. Our data reveal that the human PMN is resistant to the deleterious effects of high levels of LPS, that in high concentrations LPS is, itself, a direct chemoattractant for PMNs, and that PMN migration toward a bacterial chemotaxin is enhanced if LPS is also present. Such capabilities suggest that the PMN may be uniquely qualified to migrate into microenvironments that are rich in LPS.

Cell Migration Inhibition↗
PubMed1991

Chronic adult periodontitis and burst progression may reflect local neutrophil defects due to perivascular hyaline deposits.

Chronic adult periodontitis (CAP) is a common disease of the supporting tissues of teeth, and is a major cause of tooth loss. This disease is distinguished from more rare rapidly progressing forms of periodontitis, in which a variety of neutrophilic polymorphonuclear leukocyte (PMN) defects have been identified. PMN dysfunctions have, however, not been observed in CAP. In CAP, destructive episodes of the disease occur sporadically and independently in different parts of the mouth. In this paper, it is proposed that CAP is due to highly localized defects in PMN function. Impaired PMN function is suggested as resulting in the formation of a virulent bacterial plaque, which is capable of initiating periodontal pocket formation. A previously reported perivascular hyaline material may account for localized PMN defects, by reducing the number of PMNs entering affected sites. The proposed model may explain both the presence of CAP in otherwise normal patients, and the sporadic pattern of tissue destruction seen in this disease.

Adult↗
PubMed1991

Changes in TCD50 as a measure of clonogen doubling time in irradiated and unirradiated tumors.

Dose-cure experiments have been carried out on a moderately well differentiated murine mammary carcinoma, designated MCA-4, at different stages of growth after tumor-cell inoculation or after 8 mm established tumors had been exposed to 60 Gy. TCD50 assays were performed at 1, 3, 7, 14, or 21 days after tumor cell inoculation, or when tumors reached a size of 6 or 8 mm. Likewise, TCD50 assays were performed at 0.25, 1, 3, 5, 8, 12, 16, or 21 days after 8 mm tumors had been exposed to a 60 Gy priming dose, or when the recurrent tumors reached 6 or 8 mm. All irradiations were performed under hypoxic conditions. The TCD50 (95% confidence limits) was 64.0 (61.7-68.3) Gy for the 6-mm and 71.9 (70.1-73.9) Gy for the 8 mm tumors, and these values were unaffected by preirradiation. Direct analysis was used for the simultaneous estimation of D0, clonogen number, and clonogen doubling time from the pooled data. There was no significant difference between D0 estimates for the preirradiated and control tumors, and the pooled estimate was 10.6 (9.6-11.8) Gy for tumors assayed at specified time points where the size was unknown. This is clearly higher than in tumors of known size [estimate for 6- and 8-mm tumors: D0 = 5.4 (4.5-6.6) Gy] owing to size and other heterogeneity. The clonogen doubling times (Tclon) were 3.4 (3.0-4.0) days in the preirradiated tumors and 5.8 (4.9-7.1) days in the unirradiated tumors. It is not unreasonable to assume that the systematic error due to heterogeneity was approximately the same for D0 and Tclon (since variable clonogen number is likely the predominant source of heterogeneity), and thus the ratio of D0 for tumors of unknown sizes (10.6 Gy) and D0 for tumors of known sizes (5.4 Gy) can be used to "correct" the Tclon estimates, with the result that Tclon (preirradiated) = 1.7 days and Tclon (unirradiated) = 3.0 days. We conclude that the clonogen doubling time was shorter in tumors exposed to a single high-dose irradiation than in unirradiated controls, which implies the existence of faster cell repopulation in irradiated tumors.

Animals↗
PubMed1991

Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon.

Current models of the virus-like agents of scrapie and bovine spongiform encephalopathy (BSE) have to take into account that structural changes in a host-encoded protein (PrP protein) exhibit an effect on the time course of these diseases and the survival time of any man or animal exposed to these pathogens. We report here the sequence of different forms of the bovine PrP gene which contain either five or six copies of a short, G-C-rich element which encodes the octapeptide Pro-His-Gly-Gly-Gly-Trp-Gly-Gln or its longer variants Pro-Gln/His-Gly-Gly-Gly-Gly-Trp-Gly-Gln. Out of 12 cattle, we found eight animals homozygous for genes with six copies of the Gly-rich peptide (6:6), while four were heterozygous (6:5). Two confirmed cases of BSE occurred in (6:6) homozygous animals.

Alleles↗
PubMed1991

Different scrapie-associated fibril proteins (PrP) are encoded by lines of sheep selected for different alleles of the Sip gene.

The incubation period of scrapie in sheep is controlled by the Sip gene which has two alleles (sA and pA). Following experimental challenge with SSBP/1 scrapie, a short incubation period is conferred by the partially dominant sA allele. Restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene are associated with the Sip alleles. By sequencing the protein coding region of the PrP gene in Cheviot sheep selected for differing Sip genotypes, we have found four PrP protein variants which differ at three positions: amino acid 112 (Ala/Val), amino acid 130 (Arg/His) and amino acid 147 (Arg/Gln). The Val 112 variant can be distinguished at the DNA level by an RspXI restriction site which is not present in the Ala 112 form. Val 112 appears to be linked to a short incubation period of experimentally induced scrapie in the Cheviot sheep and therefore with the Sip sA allele. These results provide new evidence that the PrP protein may be a product of the Sip locus.

Alleles↗