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Biomedical subjects

J M Slater

Publications and source records attributed to J M Slater.

At least 73 records · Page 4Linked to original sources

RADPLANET--a functional radiology digital image network.

RADPLANET is a functioning LAN (Local Area Network) designed to integrate the many and varied facilities of a university medical center radiology department (Department of Radiation Sciences) into an efficient unified resource providing state-of-the-art diagnostic capabilities and delivering precision radiotherapy. RADPLANET links diagnostic work stations, radiation-therapy planning work stations, and therapy machine stations into an integrated whole. The RADPLANET project exploits technology currently evolving in the PACS (Picture Archiving and Communicating Systems) community but also addresses digital image networking requirements peculiar to radiation therapy. RADPLANET is designed as a modular, expandable, piecemeal updatable system in order to incorporate new, more cost-effective technology as it becomes available and to provide new resources to meet the needs of a growing department and an increasingly sophisticated medical profession. The paper discusses design criteria and rationale, current status of the network, and plans for continuing expansion and enhancement.

Hospital Departments↗

Denitrification in aquifer soil and nearshore marine sediments influenced by groundwater nitrate.

We estimated rates of denitrification at various depths in sediments known to be affected by submarine discharge of groundwater, and also in the parent aquifer. Surface denitrification was only measured in the autumn; at 40-cm depth, where groundwater-imported nitrate has been measured, denitrification occurred consistently throughout the year, at rates from 0.14 to 2.8 ng-atom of N g day. Denitrification consistently occurred below the zone of sulfate reduction and was sometimes comparable to it in magnitude. Denitrification occurred deep (14 to 40 cm) in the sediments along 30 km of shoreline, with highest rates occurring where groundwater input was greatest. Denitrification rates decreased with distance offshore, as does groundwater influx. Added glucose greatly stimulated denitrification at depth, but added nitrate did not. High rates of denitrification were measured in the aquifer (17 ng-atom of N g day), and added nitrate did stimulate denitrification there. The denitrification measured was enough to remove 46% of the nitrate decrease observed between 40- and 14-cm depth in the sediment.

Journal Article↗

Suppression of tumor growth and enhancement of immune status with high levels of dietary vitamin B6 in BALB/c mice.

Effects of dietary vitamin B6 at levels ranging from deficiency to megadoses on the development of herpes simplex virus type 2-transformed (H238) cell-induced tumors and on in vitro responses relating to cell-mediated immunity were examined. Male BALB/cByJ mice (n = 260), 5 weeks of age, were fed 20% casein diets containing pyridoxine (PN) at 0.2, 1.2 for the control diet, 7.7, or 74.3 mg/kg diet for 4-11 weeks. After 4 weeks of dietary treatment, 120 of the mice received an injection of H238 cells; mice without H238 injection served as controls. At 4, 8, and 11 weeks, animals from each group were euthanized and blood and spleen samples obtained. Mice fed 0.2 mg PN developed mild deficiency symptoms and gained significantly less weight than those fed 1.2-, 7.7-, and 74.3-mg PN diets. Thirteen to 16 days after tumor cell injection, primary tumor incidence was lowest in mice fed 74.3 mg PN; later, incidence among groups was similar. Mice fed 1.2 mg PN had the largest primary tumor volume, the highest incidence of lung metastases, and the greatest number of metastatic nodules per animal at 7 weeks post injection. Overall, lower tumor volumes were found in animals fed 7.7 and 74.3 mg PN (14 and 32% less than the tumor volume for those fed 1.2 mg PN, respectively); mice fed 0.2 mg PN had the lowest tumor volume. Blood and spleen lymphoproliferative response to stimulation by phytohemagglutinin or concanavalin A generally tended to be higher in mice fed 7.7 and 74.3 mg PN as compared to that in animals fed either 0.2 or 1.2 mg PN. However, decreased mitogen-stimulated responsiveness was observed in all animals with progressive tumor growth. Tumor growth also resulted in splenomegaly and increased thymic atrophy. Significant negative relationships between tumor volume and tumor pyridoxal 5-phosphate (PLP) concentrations were observed for 1.2-, 7.7-, and 74.3-mg PN diet groups. These data suggest that high dietary intake of vitamin B6 may have suppressed tumor development by either immune enhancement or PLP growth regulation of this tumor.

Animals↗

Enhancement of monoclonal antibody binding to melanoma with single dose radiation or hyperthermia.

We undertook this study to determine whether radiation (10 Gray, single dose) or water bath hyperthermia (41 degrees C, 45 min) could enhance binding of 111In-labeled anti-p97a monoclonal antibody (MAb) to human melanoma tumors transplanted subcutaneously into nude mice. Sixty animals were given injections of 1-2 X 10(7) Brown C5513 melanoma cells. At 1-2 weeks postinjection, two-thirds of the mice were treated (one-third served as controls). Within 3 hours after treatment, each animal was given iv 2 muCi 111In-anti-p97a MAb. At 24 and 48 hours thereafter, whole-body scans were done with the use of a MaxiCamera 300 A/M unit, and the ratio of activity at the tumor and liver was determined. Some animals were kept for 7 days posttreatment, whereas others were taken after the 48-hour scan for determination of biodistribution of the radiolabeled complex. Enhancement of MAb binding was demonstrated by either modality, although enhancement was more consistent with radiation. The therapeutic efficacy of MAb may be enhanced with increased binding of radioactive MAb complexes through single dose radiation or hyperthermia.

Animals↗

Hyperthermia and radiation in vivo: effect of 2-deoxy-D-glucose.

Since hypoxic cells rely heavily on glucose metabolism for energy, 2-deoxy-D-glucose (2-DG), an inhibitor of anaerobic glycolysis, would be expected to increase tumor cell killing by heat and thus enhance the effect of concurrent radiation. In order to test this hypothesis two types of BALB/c mouse tumors, one induced by subcutaneous injection of 10(6) herpes virus Type 2-transformed (H238) cells and the other by injection of 1.6 X 10(5) 1,2-dimethylhydrazine-transformed (#51) cells in the right thigh, were subjected to radiation, 2-DG, and heat used singly and in various combinations. Control mice were injected with saline. Three to four weeks after inoculation the mice were assigned to one of eight treatment groups (28 mice/group) so that average tumor volume/group before treatment would be equivalent. A single 2000 rad dose of radiation 3 hr prior to heat and 2-DG injected intraperitoneally at 1 g/kg 30 min before heating were given to some of the groups. Localized heat at 43.5 +/- 0.1 degrees C for 30 min, when used, was administered by means of a water bath. Rectal temperatures were kept below 39 degrees C, whereas intratumor temperatures reached a maximum of 42 degrees C. After treatment, tumor volume, mouse weight, and mortality were noted twice a week for four weeks. In both tumor models, mice receiving radiation plus heat, and radiation plus heat plus 2-DG, had significantly smaller tumors over the entire 4 to 28 day range after treatment than saline-injected control mice. In addition, in the H238 tumor model, addition of 2-DG to treatment with radiation and heat resulted in significantly smaller tumors at 25 days. 2-DG alone or in combination with heat (without radiation) resulted in significantly smaller H238 cell-induced tumors at day 28 post-treatment when compared to the saline controls. The H238 tumor-bearing mice experienced a significant (4.7%) loss in total body weight after heating. It could be that heating trauma produced dehydration and possibly also decreased caloric intake to an extent which could be measured in weight loss. This observation, however, was not made in the heated mice in the #51 tumor model.

Animals↗

Mouse neoplasia and immunity: effects of radiation, hyperthermia, 2-deoxy-D-glucose, and Corynebacterium parvum.

Radiation (XRT), hyperthermia, 2-deoxy-D-glucose (2DG), and Corynebacterium parvum were given in various combinations to BALB/c mice injected with herpes virus type 2-transformed (H238) cells. Addition of heat significantly increased the antitumor effects of XRT, and the combination of XRT + 2DG + heat resulted in the highest incidence of complete tumor regression. Enhanced activity of phytohemagglutinin-responsive T lymphocytes and natural killer cells capable of killing YAC-1 tumor cells was noted in some of the treatment groups while tumor volume was similar for all of the groups. This enhancement was most likely to be achieved when heat was included as part of the treatment protocol.

Animals↗

Factors influencing the success of in vitro fertilization for alleviating human infertility.

The program for in vitro fertilization at Bourn Hall began in October 1980. Various types of infertility have been treated during this time using the natural menstrual cycle or stimulation of follicular growth with antiestrogens and gonadotrophins. Follicular growth and maturation are assayed by urinary estrogens and LH, monitored regularly during the later follicular stage. Many patients had an endogenous LH surge; others needed an injection of HCG to induce ovulation. All oocytes were recovered by laparoscopy. Wide variations occurred in the time interval between the start of the LH surge and oocyte recovery and between oocyte recovery and insemination. Embryos taken between the one- and the eight-cell stage were replaced into their mother, no standard procedure being adopted for all patients. The results of all treatments including patient's responses during the follicular and luteal phases, oocyte recovery, fertilization, cleavage, replacement, implantation, abortion, and birth and the effect of factors such as replacing two or more embryos, maternal age, and previous obstetric history are described in detail. The incidence of implantation after embryo replacement improved from 16.5% initially to 30% currently. More than 118 babies have been born, and many pregnancies are continuing.

Abortion, Spontaneous↗

Modification of a transplantable colon tumor and immune responses in mice fed different sources of protein, fat and carbohydrate.

The effects of different sources of dietary protein, fat and carbohydrate on tumor development and on tests relating to cell-mediated immunity were investigated in male BALB/c mice after subcutaneous injection of 8 X 10(4) 1,2-dimethylhydrazine (DMH)-induced colon tumor (no. 51) cells. Results indicated that mice fed the milk protein source (especially at the low protein level) had smaller tumors, a higher spleen cell proliferative response to stimulation by phytohemagglutinin (PHA), and greater cytotoxic T-cell activity against the tumor cells than those fed the comparable diets containing protein from the other sources. Peripheral blood lymphocytes only from the milk-fed mice, regardless of tumor presence, exhibited a relatively low response to PHA stimulation, thereby suggesting a dietary effect on the migration pattern of PHA-responsive lymphocytes. The level of protein significantly affected both T-cell and natural killer cell cytotoxicity. The tumor-bearing mice fed the diet containing sucrose (table sugar) had a significantly lower spleen cell response to PHA stimulation than those fed the comparable diet containing dextrin. The level or source of fat did not significantly affect any of the parameters tested in this system.

Adenocarcinoma↗

Modification of spontaneous mammary tumors in mice fed different sources of protein, fat and carbohydrate.

The effects of different sources of dietary protein (milk, soy, wheat, fish and beef), fat (corn oil and butter), and carbohydrate (dextrin and sucrose) on the development of spontaneous mammary tumors in virgin female C3H/HeJ mice were investigated. Weanling mice were randomly divided (28 mice/group) and fed ad libitum one of 14 equicaloric diets containing either 11% or 33% protein and 5% or 30% fat or a standard mouse feed for approximately 2 years. Beginning at 6 months of age, tumor incidence, non-specific deaths, individual weights and amount of food consumed were monitored. Variations in tumor incidence were most pronounced when the mice fed different sources of protein (at a high level) were compared. The mice fed the low fat diets containing either low milk protein (high carbohydrate) or high fish protein generally exhibited the lowest tumor incidence and highest percent survival. High weight gain was correlated with early tumor appearance, but not with tumor incidence later in the experiment. The mice fed a low fat diet containing low milk protein were tumor-free significantly longer than mice fed the diets containing fish or beef. The only groups with 100% tumor incidence by 120 weeks of age were those fed diets containing sucrose (table sugar) or a high fat level.

Aging↗

BALB/c mice fed milk or beef protein: differences in response to 1,2-dimethylhydrazine carcinogenesis.

The development of 1,2-dimethylhydrazine (DMH)-induced colon tumors and immune responses were investigated in male BALB/c mice fed six different equicaloric diets. Milk or beef at a low (11%) or high (33%) level supplied the dietary protein, and corn oil (primarily) at a low (5%) or high (30%) level supplied the fat. Eleven weekly injections of DMH (at 20 mg/kg mouse) or saline were administered. At 59 weeks of age, the milk-fed mice had a significantly higher (P less than or equal to .05) colon tumor incidence than the beef-fed mice, 67 and 16%, respectively. Tumor volume and colon weight in the milk-fed mice were also significantly greater. Low natural killer cell activity against [125I]5-iodo-2'-deoxyuridine-labeled colon tumor cells and high serum blocking of antitumor cell activity were observed in the milk-fed-mice. These mice also exhibited higher T-lymphocyte cytotoxicity against colon tumor cells. These results differ from those of our previous studies and those of numerous epidemiologic investigations.

1,2-Dimethylhydrazine↗

DNA polymerases alpha and gamma during pre-emergence and early larval development of Artemia.

DNA polymerases alpha and gamma have been studied in cryptobiotic cysts and developing embryos and larvae of the brine shrimp Artemia. The two enzymes readily separate on Cibacron blue 3-GA Matrex gel. Assay requirements with activated DNA as primer-template are pH 8.0, 1 mM Mg2+, 50 mM K+ for DNA polymerase alpha and pH 8.4, 10 mM Mg2+, 80 mM K+ for DNA polymerase gamma. DNA polymerase alpha is inhibited by N-ethylmaleimide (94% and 100% at 1 mM and 10 mM respectively) and aphidicolin (96% at 60 microM). DNA polymerase gamma is also sensitive to N-ethylmaleimide (83% and 100% inhibition at 1 mM and 10 mM respectively) but is resistant to aphidicolin. 2',3'-Dideoxythymidine 5'-triphosphate (ddTTP) inhibits the gamma polymerase by 88% when in fivefold excess over dTTP whereas the alpha polymerase is unaffected by this compound. DNA polymerase alpha has a sedimentation coefficient of 7.6 S which is reduced to 6.2 S by a phenylmethylsulphonyl fluoride-sensitive proteinase. The gamma polymerase sediments at 8.3 S. No DNA polymerase beta activity could be detected. After the reinitiation of development both activities increased twofold up to 8 h (gamma polymerase) and 16 h (alpha polymerase), then declined before the onset of nuclear DNA replication after hatching. Thymidine kinase activity increased over 200-fold up to the time of replication. Analysis on Percoll density gradients of the intracellular distribution of both polymerases during development suggests that the changes in their activities may be due to migration from storage sites to replication complexes in the nuclei and mitochondria. The content of the mitochondrial DNA polymerase gamma in different batches of cysts may reflect the relative viabilities of the cysts.

Animals↗

Responses of mouse spleen morphology to the growth of subcutaneously injected virally transformed cells.

The changes in the fractional volume of six structural components in the spleens of Balb/C mice injected with Herpes simplex virus Type 2-transformed cells (H238 tumor cells) were quantitated during progressive tumor growth. Spleen stereology was performed at three time intervals during the early stages of tumor development. The results revealed that the volume of the compact myeloid tissue and reaction center of lymphoid nodules increased about four- to five-fold from 10 to 33 days after H238 tumor cell injection. A progressive increase was also seen in the red pulp volume. Although an increase in volume of the marginal zones around the lymphoid nodules was evident early during the test period, by day 33 the mean value was similar to the control value. These results indicate that the spleen undergoes significant morphological changes in three splenic components during progressive growth of a tumor produced by subcutaneous injection of a virally-transformed cell line.

Animals↗

Eosinophilic granuloma of bone.

Eosinophilic granuloma of bone is an uncommon granulomatous process for which therapy recommendations vary considerably. Consequently, a survey of the world literature from 1940 to 1974 was undertaken in an attempt to develop more concrete guidelines. This survey revealed that the disease manifests itself primarily in males under 20 years of age of all races. The most common symptom is pain, with or without swelling. Multiple sites in a single case are frequent. The clinical course is generally benign, unlike Letterer-Siwe disease or Hand-Schuller-Christian disease. A remission rate of 95% was noted, with relapses usually occurring as distant disease within the first year. Simple excision or curettage was the most common surgical procedure utilized, and radiotherapy doses varied widely. Excellent local control of the disease can be provided using conservative surgery, low-dose irradiation, or both. Morbidity secondary to pathologic fracture or to overly aggressive treatment are the major concerns, not failure to control the disease.

Adolescent↗

Effect of L1210 leukemia on the susceptibility of mice to Candida albicans infections.

This study was carried out to determine whether animals bearing L1210 leukemia were more susceptible to candida infection in the absence of immunosuppression and to determine also if the L1210 cells suppressed the inflammatory response of the animal host. Systemic infection was studied by intravenous injection of Candida albicans and checking for the number of candida organisms cultured from the blood and the kidneys. Localized infection was studied by intramuscular injection of C. albicans into the thighs and measuring the changes in the thigh size. Compared with tumor-free controls, the intravenous injection resulted in higher counts of C. albicans from the blood and the kidneys of tumor-bearing animals. No significant difference in the localized swelling was noted between tumor- and nontumor-bearing mice with respect to intramuscular injection of C. albicans. The results thus indicate that L1210 leukemia increases susceptibility of tumor-bearing animals to systemic candida infection. L1210 cells were shown to reduce the accumulation of neutrophils and to suppress the inflammatory reaction elicited by C. albicans.

Animals↗

Antiinflammatory reaction associated with murine L1210 leukemia.

Mice bearing L1210 leukemia did not show impaired humoral or cellular immune response to antigenic stimulation druing the early stage of the tumor, and a depressed response was noted only in the terminal stage. L1210 cells were shown to suppress inflammatory reaction in vivo.

Animals↗

Effect of therapeutic irradiation on the immune responses.

The immune responses of 60 patients undergoing therapeutic irradiation were evaluated according to four anatomical sites irradiated. In vitro lymphocyte transformation tests with PHA, Con-A, and PWM and quantitative assays of IgG, IgA, and IgM were performed on blood obtained from each patient before and during therapy, and two weeks, two months, and six months after therapy. At these same testing intervals, skin tests with PPD, mumps antigen, Candida antigen, and SD-SK were performed. During irradiation, the mean values of all lymphocyte transformation tests were depressed, varying from 48% to 64% of pretreatment baseline. This depression persisted until about two months after completion of treatment. By six months, response rose to pretreatment values. When response was evaluated according to sites irradiated with all mitogens, the pelvic and pelvic plus abdominal groups showed consistently greater depression than the chest or head and neck groups. Radiation effected no significant changes in the mean values of IgG, IgA or IgM. A decrease in skin sensitivity was noted during radiation; 73% of the subjects responded positively before therapy while only 53% had at least one positive test during therapy. By two months postirradiation, 73% of the group clinically free of disease had positive skin tests. A comparison of clinical condition with test results is significant when one considers the 17 patients who developed metastatic disease or died from disease. The depression for all three mitogens during radiation therapy was greater for this group. Of the 17, only four had IgG levels in the normal range, and consistently fewer positive skin tests were demonstrated.

Abdominal Neoplasms↗