The role of psychiatry in the public mental health delivery system: An introduction

The papers which follow are revised and expanded versions of presentations made at the Conference on Improving Florida's Services for the Mentally Ill: The Role of Psychiatry, held in Tallahassee, Florida on October 7–8, 1986, and organized by the Florida Mental Health Institute, University of South Florida. The conference was sponsored by the Florida Department of Health and Rehabilitative Services through the Committee on Public Psychiatry. The authors and their organizational affiliations are listed below     

Effects of the soluble low-molecular-mass proteins on spleen activity and cellular composition of infiltrates in rat mammary gland tumors

We showed previously that soluble low-molecular-mass tumor-associated antigens (TAA) could suppress chemically-induced tumorigenesis. In this study, we analyzed the mechanism of those findings. Studies were performed on the spleen and mammary gland tumors obtained from the following groups of rats: i) control rats treated with dimethyl-benz(alpha)antracene (DMBA), ii) vaccinated and carcinogen-treated rats with non regressed tumors, iii) vaccinated and carcinogen-treated rats with regressed tumors. Different zones of the spleen and tumors and their cellular content (Ki67+ and CD8+ cells, and macrophages) were analyzed morphometrically and immunohistochemically. Reaction of the spleen to vaccination was manifested in a significant increase in all areas of the white pulp and in a decrease in the size of the red pulp. The total number of cells in the white pulp (germinal center and PALS) and in the marginal zone was significantly higher in the spleen of rats with regressed tumors. The number of Ki67+ cells decreased significantly in both groups of vaccinated rats, but most prominently in the marginal zone and the red pulp in rats with regressed tumors. An increased number of CD8+ lymphocytes and macrophages was also seen in the red pulp. Different areas of the tumors (peripheral vs. inside at depth) showed different responses to vaccination and this difference was related to conditions of carcinogenesis, i.e. non-regressed vs. regressed tumors. In regressed tumors, all parameters studied were easily distinguishable in both areas of the tumors, while in non-regressed tumors, a marked distinction was seen only at their periphery. In regressed tumors, a negative correlation was seen at depth tumors between the number of Ki67+ cells and the number of CD8+ lymphocytes (r=-0.48). The findings indicated a strict antitumor effect of vaccination with the soluble low-molecular-mass TAA, which prevents the development of insufficiency of the immune system when an intensive immune reaction takes place.     

The role of p53 tumor-associated protein in colon cancer detection and prevention (Review)

The role of the cytoplasmic fraction of p53 protein in the detection and prevention of colon cancer was analyzed by comparing results of the author's studies with data published in the literature. In cancer detection, although immunochemical methods are widely used for diagnostic purposes positive results are not always obtained. Using a new modification of affinity chromatography columns, we isolated the cytoplasmic, soluble form of tumor-associated antigens (TAA) from the serum of colon cancer patients. p53 protein was found to be one of the main components of such TAA. The serum level of p53 antigen was related to tumorigenicity: the correlation and regression coefficients between the serum level of p53 protein and the progress in colon cancer were 0.48 and 0.88, respectively, p<0.01. Thus HPLC-determination of the serum concentration of this protein could serve as a screening tool for cancer detection. The sensitivity and specificity of the method reached 92% and its accuracy was 88%. The method can be used to detect cancer development either as a primary disease or as a recurrent disorder. In cancer prevention, a few attempts have been made to utilize p53 protein as a tumor suppressor. IgG generated against the cytoplasmic p53 antigen from tumor-bearing rats prevents the carcinogenic effect of 1,2-dimethylhydrazine decreasing significantly the number of tumor-bearing rats in vaccinated group compared with non-vaccinated controls. Anti-p53 IgG not only had an antitumor effect but also prevents benign tumors from becoming malignant: the number of malignant tumors in vaccinated rats was half that in controls (29% and 58%, respectively). The antitumor effect of vaccination is accompanied with a significant increase in the serum-level of p53 antigen in vaccinated rats compared with non-vaccinated controls. p53 protein plays an important role in colon cancer: the unique mechanism involved in both cancer development and in cancer prevention appears to include high production of this protein.     

The role of dietary factors in prevention of chemically-induced cancers (review)

The role of dietary factors in prevention of chemically-induced cancer was reviewed on two models: i) the role of high fiber diets in prevention of colon cancer and ii) the role of high fat diets in prevention of mammary gland cancer, i) Experiments in colon cancer showed that 20% cellulose content decreased tumor incidence caused by 1,2-dimethylhydrazine (DMH) to 33% compared with 92% of tumors developed in animals fed a fiber-free diet. The tumor-preventive effect of a cellulose diet was accompanied by increased enzyme concentrations, such as ornithine decarboxylase, thymidine kinase and beta-glucuronidase. Corncob fiber (15%), treated with the fungus Pleurotus os., had a significant protective effect against DMH-induced rat colon cancer. This effect was accompanied by activation of some cellular mechanisms, i.e. apoptosis, proliferating cell nuclear antigen (PCNA) and p53 protein synthesis. A high positive correlation was found between tumor grade and p53 protein in the serum (r=0.97) or in the cell cytoplasm (r=0.77), and between tumor grade and PCNA (r=0.81). An inverse relationship was found between tumor grade and apoptosis (r=-0.63). ii) Experiments in mammary gland cancer showed that a 15% olive-oil diet reduced tumor incidence caused by 9,10-dimethyl-1,2-benzanthracene to 30%, compared with 55% in the control group. The antitumor effect of the olive oil diet was connected to its content of monounsaturated fatty acids, such as oleic and palmitic acids. The promotive tumorigenic effects of other high-fat diets (avocado, soybeans) were associated with high content of some polyunsaturated fatty acids (linoleic and alpha-linolenic). We concluded that different diets have different targets. The effect of the same diet depends on its content of anti-tumor substances.     

The tumorigenic phenotype of a mutated form of Fc gamma RIIB1, lacking the ability to generate soluble receptor and allowing a low-level of ligand binding

Non immunohematopoietic murine tumor cells ectopically expressing Fc gamma RIIB1 (B1) were recently shown to express a higher tumorigenicity phenotype than cells not expressing this receptor. Utilizing a genetic approach we studied the possible contribution of a soluble form of B1 to tumor enhancement. A mutated form of the B1, lacking the cleavage site responsible for the generation of soluble B1 was produced using gene splicing by overlap extension PCR. A deletion confirmed by sequence analysis from 172 to 178 residues was generated. Stable transfectants expressed the B1 deleted form (B1 Delta) both as specific RNA and as a membrane protein receptor allowing a low level of ligand binding. The soluble form of B1 was undetectable in tissue culture supernatants of Bib transfected cells while it was present in supernatants of wild type B1-transfectants. Stable B1 Delta transfectants were significantly more tumorigenic than negative control transfectants. Tumor incidence was almost as high as that of intact B1 and lagged in the latency period before the appearance of palpable tumors. It is suggested that the soluble B1 has a minimal contribution to tumor enhancement.     

Gel fiberglass as a new matrix of affinity chromatography columns for isolation of colon cancer-associated antigens

The serum levels of type IV collagen 7s domain (7s collagen) were determined in 80 patients with hepatocellular carcinoma (HCC) and in 105 with chronic liver disease without HCC. Among 86 patients with HCV infection, serum levels of the 7s collagen were significantly higher in those with HCC than-in those without HCC (p<0.05). In contrast, no significant differences were recognized between these two groups in 84 patients with HBV infection. Patients with HCV infection having high serum levels of the 7s collagen exceeding 7.0 ng/ml, were diagnosed as HCC with a sensitivity of 71.8%, a specificity of 74.5%, and a reliability of 77.9%. It was concluded that the progression of hepatic fibrosis plays an important role in the hepatocarcinogenesis of HCV, and that serum levels of the 7s collagen appeared to be useful as a risk factor of the development of HCV-related HCC.     

Occult papillary microcarcinoma of the thyroid--a potential pitfall of fine needle aspiration cytology?

The use of fine needle aspiration cytology detected papillary carcinoma in two patients with multinodular goitre measuring 0.7 cm and 0.9 cm in diameter, respectively. Like most of the cases from previous large series, the tumours progressed slowly as shown by absence of enlarged glands on surgical exploration and no clinical signs of metastasis after two and five years of follow up. This study shows that aspiration cytology can detect a virtually harmless occult papillary carcinoma that will oblige patients to have surgery. This very occasional "pitfall" of fine needle aspiration should not preclude this well known beneficial method from being used in the management of thyroid disease.     

Effects of nabumetone,celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors

Nonsteroidal anti-inflammatory drugs interfere with certain antihypertensive therapies. In a double-blind study, 385 hypertensive patients stabilized on an angiotensin converting enzyme inhibitor were treated with nabumetone, celecoxib, ibuprofen, or placebo for 4 weeks. Ibuprofen caused significantly greater increases in systolic (P < .001) and diastolic (P < .01) blood pressures (BPs) compared to placebo, but not nabumetone or celecoxib. The proportion of patients with systolic BP increases of clinical concern at end point was significantly higher (P < .001) for the ibuprofen group (16.7%; 15 of 90), but not for the nabumetone group (5.5%; 5 of 91) or the celecoxib group (4.6%; 4 of 87) compared to the placebo group (1.1%; 1 of 91).