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N Hunter

Publications and source records attributed to N Hunter.

At least 163 records · Page 9Linked to original sources
PubMed1991

Restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and their association with susceptibility to natural scrapie in British sheep.

We have investigated the correlation between restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and the incidence of natural scrapie in British sheep during the period from July 1988 to November 1990. Sixty percent of the scrapie-positive animals studied were homozygous for a 6.8 kb EcoRI fragment (e1) and a further 26% carried e1 as heterozygotes. This fragment is linked to susceptibility to experimental scrapie in a closed flock of Cheviot sheep. Twelve percent of cases were found to be homozygous for a 4.4 kb EcoRI fragment (e3) which in the Cheviot flock had been linked to relative resistance to scrapie. A third EcoRI fragment of 5.2 kb (e2) has also been found but is relatively rare and has not yet been associated with scrapie susceptibility. Four sets of flocks affected by natural outbreaks of scrapie divided into two groups. In three of these flocks, all scrapie cases carried e1 with high frequencies of e1e1 homozygotes. In the fourth, there were no e1e1 scrapie cases; all scrapie sheep carried e3 in approximately equal numbers of heterozygotes and homozygotes.

Animals↗
PubMed1991

Vascular expansion in chronic periodontitis.

Animal studies have demonstrated expansion and remodelling of gingival blood vessels in inflamed gingival tissues. However, there is a paucity of information, regarding the vascular response in human gingivitis and periodontitis. In this study, gingival biopsies were obtained from 51 separate patients. Fifteen minimally inflamed, 16 gingivitis and 20 periodontitis specimens were studied. Gingival biopsies were divided into five fields, and a quantitative survey of vascular changes was performed. In fields adjacent to the bacterial plaque irritant, vessel profiles were increased in number with the development of the advanced periodontal lesion. The diameter of blood vessels throughout the entire thickness of gingival biopsies was found to increase with advancing periodontal disease. It is concluded that considerable remodelling of the gingival vasculature occurs in chronic periodontitis, and that this may contribute to the tissue destruction seen in this disease.

Adult↗
PubMed1991

The role of oral bacteria in the pathogenesis of infective endocarditis.

Various micro-organisms have been implicated as causative agents for bacterial endocarditis, including lactobacilli and in particular the viridans streptococci which are more commonly associated with dental caries. Of these, the most frequently isolated one has the descriptive name Streptococcus sanguis. The disease is characterized by growth of micro-organisms within a platelet-fibrin thrombus protruding from a valve leaflet. An understanding of the pathogenesis involves knowledge of the mechanisms of conversion of the normal vascular surface to a thrombogenic one and the adhesion of micro-organisms to such surfaces. Model systems to study this interaction include experimental animals, mammalian epithelial cells and platelets, and proteins such as fibronectin and fibrinogen. Microbial protein surface components (adhesins) and lipoteichoic acid have also been implicated. Capsular polysaccharides may be involved, but the role of dextrans formed from sucrose has been over-emphasized as the polymers are not formed in situ. Antibiotic prophylaxis for patients at risk is based on bacteriostatic or bactericidal action. However, bacterial cell surface components involved in adhesion may also be affected, and knowledge of such reactions could provide a more rational basis for antibiotic prophylaxis.

Bacterial Physiological Phenomena↗
PubMed1991

An intradermal assay for quantification and kinetics studies of tumor angiogenesis in mice.

A method is reported for the study of early phases of neovascularization in syngeneic murine tumors and human tumor xenografts in nude mice. Using this method, the effect of irradiation of tumor cells or tumor bed on tumor angiogenesis was studied. Tumor cells were injected intradermally in the abdominal skin flap, which was reopened at 2-day intervals to quantify newly formed blood vessels at the site of tumor cell injection. Both tumor cell injection and blood vessel counting were performed under a dissecting microscope. Using three syngeneic murine tumors and two clones of a human colonic adenocarcinoma, it was observed that new blood vessels started appearing within a few days after tumor cell injection and that this event preceded measurable tumor growth. The number of blood vessels increased exponentially for several days but then their further growth slowed. The extent of angiogenesis depended on the tumor type and the number of tumor cells injected. The exposure of the skin flap to ionizing radiation prior to tumor cell injection reduced neovascularization. We further observed that heavily irradiated tumor cells retained their ability to induce angiogenic response and that lymphoid cells (peritoneal exudate and spleen cells) could also elicit an angiogenic response, although it is weaker than the response elicited by tumor cells. Thus this method is suitable for quantification and kinetics of early phases of tumor angiogenesis in individual mice bearing transplants of syngeneic tumors or human tumor xenografts, and it can be useful for investigating various regulators of tumor angiogenesis.

Animals↗
PubMed1991

Suppression of experimental allergic encephalomyelitis by alpha 2-macroglobulin.

Lewis rats sensitized with guinea-pig spinal cord in Freund's complete adjuvant developed an acute-phase protein response. This was characterized by a marked increase in plasma alpha 2-macroglobulin (alpha 2 M) levels which, however, declined towards normal values before the onset of clinical signs of experimental allergic encephalomyelitis (EAE). In contrast, levels of two other acute-phase proteins, fibrinogen and caeruloplasmin, remained variably elevated over the entire study period. Recovery from EAE coincided with an increase in alpha 2 M levels. Infusion of purified alpha 2 M effectively protected the rats against clinical EAE and this was associated with a restimulation of the acute-phase response. The protected rats were shown to be sensitized to myelin basic protein and to have comparable mononuclear infiltration of the central nervous system with the diseased animals. It is postulated that the infusion of alpha 2 M leads to the inhibition of the effector pathways of the delayed type hypersensitivity response.

Acute-Phase Proteins↗
PubMed1990

Dependence of indomethacin-induced potentiation of murine tumor radioresponse on tumor host immunocompetence.

In a previous study (Furuta, Y., Hunter, N., Barkley, H. T., Jr., Hall, E., and Milas, L., Cancer Res., 48:3008-3013, 1988), we demonstrated that inhibition of prostaglandins in murine tumors by indomethacin results in the augmentation of tumor response to single doses of ionizing radiation. The results of the present study show that indomethacin augmented tumor response to fractionated irradiation as well, the enhancement factor being more than 2. The effect of indomethacin on tumor growth and on tumor radioresponse was assayed in normal mice, mice deficient in T-cells (nude mice), and mice whose general immunocompetence was suppressed by whole-body irradiation. The antitumor activity of indomethacin was not significantly influenced by the immunocompetence of the tumor host. Since indomethacin inhibited tumor neoangiogenesis, we postulated that this inhibition is a major mechanism responsible for the antitumor activity of indomethacin. In contrast, potentiation of tumor radioresponse by indomethacin was greatly dependent on immunocompetence of tumor host: it was significantly reduced, or even abolished, when tumor grew in nude and whole-body irradiation mice. Thus, while immunocompetence of the tumor host has no significant effect on antitumor action by indomethacin, it plays a decisive role in the potentiation of tumor radioresponse by indomethacin.

Animals↗
PubMed1990

Bone growth retardation induced by single and multifractionated irradiation.

The right hind legs of 12- to 14-week-old mice were exposed to single and multifractionated courses of gamma-ray irradiation. The recovery curves, time-dose relationships, and fraction number-dose relationships were analyzed using femoral growth retardation as an endpoint. The bones grew 2 mm, about a 10% increase over their original lengths, in 12 months; and 63% and 85% in volume in 6 and 12 months, respectively. The ratio of the volume increase of the irradiated right leg per unit time, the actual growth, to the volume increase of the non-irradiated left leg, the potential growth, was calculated for each mouse. The doses necessary to produce a given degree of bone growth retardation in 50% of the tested animals were calculated for each treatment schedule. The isoeffect doses for a given degree of bone growth retardation after 2 and 4 equal fractionation exposure increased (peak at one day-interval) and decreased (trough at 2-day interval), and later increased additionally with increasing time intervals between doses.

Animals↗
PubMed1990

An automated method of quantifying retinal vascular responses during exposure to novel environmental conditions.

The width of retinal arteries and veins was measured by digital image analysis using an automated vessel-tracking software program. Mean coefficients of variations in vessel width of less than 3% were easily achieved from digitized 35-mm retinal photographs taken with a table-top or hand-held fundus camera. Retinal images were analyzed from seven subjects exposed to sea level or altitudes equivalent to 10,000 (3048 m), 17,500 (5334 m), and 25,000 (7620 m) ft and nine subjects exposed to sea level and 14,110 ft (4300 m). At each altitude, retinal veins dilated more than did arteries (5 +/- 1 versus 0 +/- 1% at 10,000 ft and 28 +/- 9% versus 9 +/- 2% at 25,000 ft; veins versus arteries, respectively). However, widths of retinal arteries and veins were reduced in nine subjects tested after 15 minutes, 24 hours, and 48 hours of 10 degrees head-down tilt; and values varied inversely with intraocular pressures (IOP). Hand-held retinal fundus photography and digital image analysis were found to provide a sensitive and objective method for detecting and quantifying retinal vascular responses in humans exposed to novel environments.

Adolescent↗
PubMed1990

Two alleles of a neural protein gene linked to scrapie in sheep.

Sheep are the natural hosts of the pathogens that cause scrapie, an infectious degenerative disease of the central nervous system. Scrapie-associated fibrils [and their major protein, prion protein (PrP)] accumulate in the brains of all species affected by scrapie and related diseases. PrP is encoded by a single gene that is linked to (and may be) the major gene controlling the incubation period of the various strains of scrapie pathogens. To investigate the role of PrP in natural scrapie, we have determined its gene structure and expression in the natural host. We have isolated two sheep genomic DNA clones that encode proteins of 256 amino acids with high homology to the PrPs of other species. Sheep PrPs have an arginine/glutamine polymorphism at position 171 that may be related to the alleles of the scrapie incubation-control gene in this species.

Alleles↗
PubMed1990

Congenital rubella after previous maternal immunity.

Two mothers who had asymptomatic rubella infection in pregnancy gave birth to severely affected infants. In both, the presence of preexisting antibody was well documented, although it could not be established whether it was the result of vaccine or natural infection.

Adult↗
PubMed1990

Radioprotection of hematopoietic tissues in mice by indomethacin.

We recently reported that indomethacin, an inhibitor of prostaglandin (PG) synthesis, increased the radioresponse of PG-producing murine tumors, but it protected the hematopoietic system from radiation damage [Furuta et al., Cancer Res. 48, 3008-3013 (1988)]. Here we have investigated possible mechanisms responsible for the radioprotective effect of indomethacin. In the exogenous spleen colony assay, bone marrow cells from indomethacin-treated mice showed a similar radioresponse to those from mice not treated with indomethacin, thus excluding true radioprotection as a mechanism. Also, neither the total number of bone marrow cells nor the number of stem cells in bone marrow were affected by the treatment with indomethacin. However, indomethacin induced significant splenomegaly, which was associated with an increased number of both nucleated cells and hematopoietic stem cells in the spleen. The latter was determined by the exogenous spleen colony assay. Thus indomethacin protected hematopoietic tissue indirectly through stimulation of hematopoietic cells in the spleen. When indomethacin was combined with WR-2721, which is a true radioprotector, we obtained a greater radioprotective effect than with either used alone according to the endogenous spleen colony assay.

Amifostine↗
PubMed1990

Intraocular pressure, retinal vascular, and visual acuity changes during 48 hours of 10 degrees head-down tilt.

Intraocular pressures, retinal vascular diameters, and visual acuities of nine men (ages 19-29), were repeatedly measured while the subjects were tilted 10 degrees head-down for 48 h and while they were seated before (baseline), and after the tilt. An immediate increase in intraocular pressure, measured by pneumatonometer (4.7 +/- 0.6 mm Hg, p less than 0.001) was recorded when subjects assumed the head-down position, and diurnal variations in intraocular pressures were observed for the 48 h. The initial and final head-down intraocular pressures were not significantly different (18.9 +/- 1.2 mm Hg vs. 17.9 +/- 1.4 mm Hg, respectively). However, when subjects resumed the sitting position, intraocular pressures fell below the initial sitting values (14.2 +/- 0.9 pre vs. 11.2 +/- 0.5 post, p less than 0.04). Computer image analysis of the retinal vasculature detected a 6% and 2% reduction in the caliber of arteries and veins, respectively, as compared with sitting baseline values. No changes in visual acuity were documented during the 48 h of head-down tilt. Our data suggest that the choroidal blood reservoir increases in volume over 48 h at continuous head-down position with a compensatory decrease in aqueous volume. These findings may explain intraocular pressure changes noted in astronauts during previous space missions and in studies associated with change in body position.

Adult↗
PubMed1989

Adoptive immunotherapy as an adjunctive treatment to thoracic irradiation for pulmonary tumor deposits in mice.

The study was performed to determine whether local thoracic irradiation (LTI) causes accumulation of adoptively transferred peritoneal exudate (PE) cells in the lung and whether such treatment improves the response of tumor deposits in the lung to LTI. Tumors in the lung were generated by sarcoma SA-NH cells injected i.v. into syngeneic (C3Hf/Kam mice. Exposure of mice to a single dose of gamma-rays ranging from 2 to 10 Gy caused a dose-dependent decrease in the number of alveolar exudate cells. Also, LTI caused a dose-dependent reduction in the number of lung tumor nodules in mice that were treated with tumor cells 4 days before irradiation. Adoptive i.v. transfer of syngeneic PE cells several hours or 2 days after LTI not only restored the radiation-depleted alveolar exudate cells to their normal levels but also led to an accumulation of transferred cells in the irradiated lung to a several-fold excess of the normal value. Maleic anhydride-divinyl ether-2-activated PE cells accumulated in the irradiated lung much more than normal PE cells and exerted antitumor activity in normal mice and in mice exposed to LTI. Their antitumor action, however, was much more pronounced in the latter, resulting in the augmentation of radioresponse of tumor nodules by a factor of 1.23. The better antitumor action of activated PE cells in mice given LTI can be ascribed to accumulation of these cells in the irradiated lung. Thus, these results show that the irradiation of the lung predisposes this tissue to accumulation of lymphoid cells, which can be beneficial in the therapy of malignant tumors by combinations of radiotherapy and adoptive immunotherapy.

Animals↗
PubMed1989

Linkage of the gene for the scrapie-associated fibril protein (PrP) to the Sip gene in Cheviot sheep.

The gene Sip with two alleles, sA and pA, is the major gene determining the incubation period of scrapie in its natural host, sheep. Two lines of Cheviot sheep have been bred which differ in their response to experimental infection with SSBP/1 scrapie. The negative line have a decreased incidence of disease caused by SSBP/1 and are SippApA. The positive line have an increased incidence of disease and the majority are either SipsAsA or SipsApA; it is not possible to distinguish between the two genotypes on the basis of scrapie incubation time because the sA allele is fully dominant with SSBP/1 scrapie. There are also rare SippApA segregants in the positive line. The major protein (PrP) of scrapie-associated fibrils is encoded by a cellular gene and a cDNA copy of the hamster PrP mRNA has been used to analyse the restriction fragment length polymorphism of the two lines of Cheviot sheep. Two polymorphisms of the sheep PrP gene were found, by using HindIII and EcoRI, which appear to act as markers for the alleles of Sip. Using these polymorphisms it is now possible to assign a Sip genotype to the sheep in the Cheviot flock. Preliminary results from Anglo-Nubian goats and a cow are also reported.

Alleles↗
PubMed1989

High endothelial-like venules in chronically inflamed periodontal tissues exchange polymorphs.

A survey of 58 gingival biopsies revealed the presence of periodontal high endothelial-like venules (PHELVs) in chronically inflamed gingival tissues. PHELVs were found to exchange polymorphonuclear cells (PMNs) almost exclusively in advanced periodontitis, with PMNs greatly exceeding the number of mononuclear cells found in PHELVs (P less than 0.001). Electron microscopy confirmed the emigration of PMNs from these vessels. The enzyme histochemical and ultrastructural features as well as the 35SO4 uptake properties of PHELVs were similar to those of the well-characterized high endothelial venules (HEVs) of rat lymph nodes. It is generally accepted that HEVs in lymphoid tissues and inflammatory sites are specially adapted to assist in the emigration of lymphocytes. However, the observation of preferential PMN emigration in the apparent absence of lymphocyte exchange from PHELVs compels further investigation of other possible functions for HEVs. In relation to this, endothelial cells are capable of producing potent cytokines and inflammatory mediators which may contribute to the development of lesions, and the possibility is discussed that high endothelial cells are functionally adapted to enhance the production of such factors.

Cell Movement↗
PubMed1989

Radiosensitivity of pre-irradiated mouse skin to second courses of single and multi-fractionated irradiation--skin shrinkage.

The hind legs of mice were re-irradiated with various gamma-ray doses in single or multi-fractionated exposures 6 or 12 months after conditioning irradiation was administered using a variety of treatment schedules. Dose-response relationships were evaluated to ascertain "residual injuries", permissible doses during the second treatments. Fifty to 60 days after the second treatments, the degrees of shrinkage of the skin on the dorsal aspects of the hind legs were measured and used as endpoints. The residual injuries were affected by the biologically effective doses, or by the treatment schedules of not only the first, but also the second exposure. The higher the biologically effective doses, the greater were the residual injuries. Compared to the previously untreated skin, the pre-irradiated skin was relatively radioresistant to the second course of treatments, regardless of the treatment schedule used. The response of the pre-treated skin to a given test dose (25 or 40 Gy) lessened with increasing dose for each treatment schedule used during the first treatment course.

Animals↗
PubMed1989

Tumor bed effect-induced reduction of tumor radiocurability through the increase in hypoxic cell fraction.

Two murine tumors, designated FSA and SA-NH, that exhibit strong tumor bed effect (TBE), were found to be less radiocurable if they grew in the preirradiated s.c. tissue. Tumors were transplanted into the right thighs irradiated with 30 Gy one day earlier, and were irradiated when they grew to 6 mm. The TBE-caused reduction in tumor radiocurability was manifested by the increase in TCD50 values. Tumor irradiation under hypoxic conditions increased TCD50 values less, and the hypoxic cell radiosensitizer misonidazole reduced TCD50 values more, when tumors grew in preirradiated than when they grew in unirradiated legs. This implies that TBE-induced increase in TCD50 was due to increase in hypoxic fraction of tumor cells. For 6 mm SA-NH tumor the estimated increase in hypoxic cell fraction was from the control value of 3% to 12%. Thus, TBE causes the reduction in tumor radiocurability through the increase in hypoxic fraction of tumor cells.

Aerobiosis↗