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Biomedical subjects

J M Slater

Publications and source records attributed to J M Slater.

87 records · Page 5Linked to original sources

Effect of acupuncture on allergic rhinitis: clinical and laboratory evaluations.

Of 22 subjects with allergic rhinitis who received a series of 6 acupuncture treatments, 11 (50%) were virtually symptom-free by the end of the series, 8 (36%) experienced a moderate reduction in symptoms, and 3 (14%) received no significant relief. Clinical assessment of symptoms was made on a 6-point scale before the first treatment and before each subsequent session. Laboratory tests included absolute blood eosinophils, percentage of nasal eosinophils, and radioimmunoassay of serum IgE, performed before the first treatment, at the end of the series, and 2 months later. A significant decrease in subjective clinical rating of symptoms correlated with a concurrent drop in absolute numbers of blood eosinophils and percentage of nasal eosinophils. IgE levels decreased in 64% of the subjects by completion of treatment and in 76% at 2-month follow-up.

Acupuncture Therapy↗

Modification of herpes 2-transformed cell-induced tumors in mice fed different sources of protein, fat and carbohydrate.

The effects of different sources of protein (milk, soy, wheat, fish and beef), fat (corn oil and butter), and carbohydrate (dextrin and sucrose) on tumor development and on spleen characteristics were investigated in BALB/c mice injected subcutaneously with 5 X 10(5) herpes simplex virus Type 2-transformed cells (H238 cells). Low or high levels of protein and fat were used. Several weeks post-injection results indicated that a high level of fat significantly enhanced tumor incidence. A high fat level was also associated with a lower spleen weight and a smaller proportion of mature granulocytes in the spleen. Butter, compared to corn oil, significantly restricted tumor volume. Among the most highly significant findings was the low tumor incidence in mice fed protein from either a milk or a fish source.

Animals↗

Different weekly changes in immune response in virus-transformed cell-injected mice fed two different diets.

Changes in tumor development and in certain immune responses were investigated at 7-weekly intervals after subcutaneous injection of 5 X 10(5) herpes simplex virus Type 2-transformed cells (H238 cells) into male BALB/c mice fed 2 different diets. One diet contained 11% casein and 5% fat while the other had 11% supplemented wheat gluten and 30% fat. Weanling mice (140/group) were fed one or the other of the diets for 12 weeks before injection and subsequent testing of 15 injected and 5 non-injected mice from each diet group each week. In mice fed the low-fat diet containing casein both tumor incidence and tumor volume were significantly lower (P less than or equal to 0.05) than in the group fed the 30% fat diet containing supplemented wheat protein. The casein-fed mice also had less splenomegaly and a higher proportion of mature lymphocytes in the spleen during tumor growth. The proliferative capability of the spleen cells after phytohemagglutinin stimulation was enhanced 2 weeks after H238 cell injection only in the casein-fed mice.

Animals↗

Direct data link between a CT scanner and a radiation treatment planning system.

A direct data link between a CT scanner and a radiation treatment planning system has been developed. The link transmits the data serially over a coaxial cable using the pseudo-paper-tape punch and reader (serial PIO) interfaces. The data transmission rate with error-check is approximately 25,000 8-bit bytes/s. This translates to about 7 s for transferring a CT scan with a 320-pixel diameter.

Computers↗

Applications of capillary electrophoresis in nephrology.

Capillary electrophoresis has recently emerged as a powerful technique for separating components in biological samples. A family of separation methods capable of handling a diverse range of samples has been developed, the sample volumes required are very small and a wide range of specialised detectors can be employed. This review examines some methods with particular application to the analysis of urine and tubular fluid samples and references relevant applications.

Amino Acids↗

A comparison of schedules combining fractionated hyperthermia and irradiation in mice.

A comparison was made of three study arms delivering localized fractionated hyperthermia followed by irradiation for two weeks. The treatment results demonstrated 18-week survival and NED survival to be 35 per cent (7/20) and 30 per cent (6/20) respectively for heat and irradiation 5 days per week, 57.9 per cent (11/19) and 52.6 per cent (10/19) for combined treatment 3 days per week and 27.8 per cent (5/18) for heat 3 days per week and irradiation 5 days per week. It is felt that thermotolerance will account for the lack of difference between 24 h and 48 h irradiation schedules when irradiation is given daily. Irradiation fraction size, however, is suggested as a moderating variable as well.

Animals↗

Effects of proton and gamma radiation on lymphocyte populations and acute response to antigen.

BACKGROUND: The clinical use of proton radiation in the management of cancer, as well as benign disorders, is rapidly increasing. The major goal of this study was to compare the effects of proton and gamma (60Co) radiation on cell-mediated and humoral immunological parameters. MATERIALS AND METHODS: C57BL/6 mice were exposed to a single dose of 3 Gray (Gy) protons or gamma-rays and intraperitoneally injected 1 day later with sheep red blood cells (sRBC). On 4, 10, 15, and 29 days after exposure, subsets from each group were euthanised; nonirradiated controls (with and without sRBC injection) were included. Body and relative spleen weights, leukocyte counts, spontaneous blastogenesis, lymphocyte populations, and anti-sRBC titers were evaluated. RESULTS: The data showed significant depression (p < 0.05) in nearly all assays on days 4 and 10 after irradiation. B lymphocytes (CD19+) were the most radiosensitive, although reconstitution back to normal levels was observed by day 15. T cell (CD3+) and T helper cell (CD4+) recovery was evident by day 29, whereas the T cytotoxic cell (CD8+) count remained significantly below normal. Natural killer cells (NK1.1+) were relatively radioresistant. Anti-sRBC antibody production was slow and low titers were obtained after irradiation. No significant differences were noted between the two types of radiation. CONCLUSIONS: Taken together, the data show that whole-body irradiation with protons or gamma-rays, at the dose employed, results in marked, but transient, immunosuppression. However, at the time points of testing and with the assays used, little or no differences were found between the two forms of radiation.

Animals↗

Combination of pGL1-TNF-alpha gene and radiation (proton and gamma-ray) therapy against brain tumor.

The major goal of this study was to determine if treatment with the newly constructed plasmid vector for tumor necrosis factor-alpha (pGL1-TNF-alpha) could enhance the radiation-induced growth reduction of C6 rat glioma. In addition, two different forms of ionizing radiation (gamma-rays and protons) were utilized. Body and spleen mass, leukocyte blastogenesis, and flow cytometry analysis of cell populations in blood and spleen were performed to detect toxicity, if any, and to identify mechanisms that may correlate with the anti-tumor action of combination therapy. C6 tumor cells were implanted subcutaneously into athymic mice and allowed to become established before treatment initiation. pGL1-TNF-alpha was injected into the implanted tumors, which were then irradiated 16-18 hr later; each modality was administered three times over 8-9 days. The addition of pGL1-TNF-alpha significantly enhanced the anti-tumor effect of radiation (p < 0.05). The effect was more than additive, since pGL1-TNF-alpha alone did not slow tumor progression and radiation alone had only a modest effect. Administration of pGL1-TNF-alpha together with proton radiation resulted in tumor volumes that were 23% smaller than those following pGL1-TNF-alpha + gamma-ray treatment; a similar differential in tumor size was observed in the groups receiving only radiation. Body weights and blood and spleen cell analyses did not reveal treatment-related toxicity. High basal proliferation of blood leukocytes and increased B cell levels in the spleen were associated with pGL1-TNF-alpha + 60Co (gamma-radiation) or proton treatment. Overall, the results suggest that the pGL1-TNF-alpha/radiation combination is effective and safe under the conditions employed. This is the first study to combine gene and proton radiation therapy and to show, under controlled experimental conditions, that proton radiation may have a greater effect against malignant tumors compared to the same physical dose of gamma-radiation.

Animals↗

Effect of pyridoxine and pyridoxal on the in vitro growth of human malignant melanoma.

The in vitro effect of vitamin B-6 supplementation on the growth of a human malignant melanoma cell line (M21-HPB) was investigated. Varying concentrations of pyridoxine (PN) or pyridoxal (PL) were added to cell cultures and incubated for 12 days. Pharmacologic levels of PL (0.25-0.5 mM) resulted in significant reductions in cell proliferation. Physiologic levels (0.005 mM) did not retard growth. Cells incubated with PN showed growth stimulation. Intracellular levels of PL and pyridoxal 5'-phosphate (PLP) were increased in cells exposed to pharmacologic PL (0.05-0.5 mM) concentrations, but not PN. These data suggest that PL or PLP may be involved in regulating the growth of melanoma cells and that vitamin B-6 may have potential use as an antineoplastic agent.

Cell Division↗

Evaluation of pre-irradiation on monoclonal antibody localization in colon tumor xenografts expressing a cell-associated antigen.

We have previously demonstrated that external beam irradiation can increase radiolabeled monoclonal antibody (MAb) targeting of tumors expressing carcinoembryonic antigen (CEA), a secreted glycoprotein. Increased tumor uptake was seen with both protons and gamma radiation (60Co). However, although pre-irradiation with protons resulted in greater activity within tumors than conventional radiation, normal tissues also exhibited increased uptake. This suggested that proton beam irradiation allowed more CEA to escape and bind to radiolabeled MAb in sites other than tumor. The purpose of the present study was to determine if a similar effect could be achieved, but without an increase in normal tissue activity, with a MAb directed against a cell-bound antigen. T380 and LS174T human colon tumors were implanted s.c. into athymic nude mice and irradiated with 10 Gy 60Co or proton beam. 111In-CYT-103 MAb (anti-TAG-72) was injected i.p. 2 hr later and the biodistribution of activity was determined 2 days thereafter. Tumor size at the time of external beam irradiation and biodistribution studies was similar among the groups within each tumor type. Increased targeting of radiolabeled MAb within tumors was not observed in either model after external beam irradiation compared to their respective nonirradiated controls, although some differences were observed in normal tissue uptake. These findings demonstrate that preirradiation for the purpose of enhancing MAb delivery to the tumor site is not a universal phenomenon and may be successful only with certain antibody/tumor antigen systems.

Adenocarcinoma↗

Effect of pre-irradiation on radiopharmaceutical localization in human colon tumor xenografts using mono- and bispecific monoclonal antibodies.

In previous investigations we found that pre-irradiation of a tumor can significantly increase site-specific accumulation of radiolabeled monoclonal antibodies (MAb). The aims of the present study were to compare the effects of radiation on the localization of conventional MAb and a bifunctional delivery system and to evaluate a new time-dose schedule. T380 human colon tumors in athymic nude mice were irradiated (60Co, 10 Gy single dose) and the antibodies were injected 2 hours later. For mice given 111In-ZCE025, an anti-carcinoembryonic antigen (CEA) MAb, the biodistribution of activity was determined 7 days later. The animals receiving ECA001, a bispecific antibody binding to CEA and to a hapten on 111In-DBX, were injected with the radiolabeled hapten 5 days after cold annbody and sacrificed 2 days later. The mean percentage of injected dose (%ID/g) within tumors was significantly increased (p < 0.05) for both anti-CEA antibodies after pre-irradiation compared to their respective nonirradiated controls (%ID/g = 22.8 versus 47.8 for conventional MAb; %ID/g = 12.5 versus 25.9 for bifunctional system). Tumor-to-normal tissue ranos were also higher in the pre-irradiated groups. The data show that pre-irradiation can increase the delivery of conventional MAb within solid tumors by over 200%. In addition, the efficacy of the approach can be enhanced by manipulation of the time-dose schedule. The results with the bispecific antibody system were unexpectedly confounded by significant differences in tumor growth rate after treatment a phenomenon not seen in the groups receiving the conventional MAb.

Animals↗

Enhancement of prostate cancer xenograft growth with whole-body radiation and vascular endothelial growth factor.

Prostate cancer research has been limited by the slow growth of human prostate tumors In athymic rodent models. This study sought to determine if low-dose radiation and vascular endothelial growth factor (VEGF) could enhance the development of PC-3 human prostate adenocarcinoma xenotransplanted into nude mice. Whole body radiation (2 Gy) was delivered only once, whereas VEGF (39 ng total/mouse) was injected subcutaneously over a 17-day period. The combination of the two agents, compared to nontreated controls, resulted in significantly higher tumor incidence (100% versus 50%) and more-rapid tumor progression (1288 mm3 versus 190 mm3 by day 60). Treatment-associated changes were observed in body weights and assays of blood and spleen cells. In addition, 3H-thymidine uptake by PC-3 cells cultured in the presence of VEGF and transforming growth factor-beta 1 was compared. These results show that low-dose, whole-body radiation and VEGF can be used in concert safely and effectively to facilitate growth of PC-3 prostate tumor and that the mechanisms of interaction may involve leukocyte modulation.

Animals↗