Thyrocalcitonin: evidence for release in a spontaneous hypocalcemic disorder.

Thyrocalcitonin content of thyroid gland extracts from normal postparturient cows was 3.9 times greater than in cows with postparturient paresis. The parafollicular cells in diseased cows were less numerous and appeared to have discharged their secretory products. An abrupt release of thyrocalcitonin near parturition may be related to the development of the hypocalcemia and hypophosphatemia in this disorder.

Adriamycin-induced cardiac damage in the mouse: a small-animal model of cardiotoxicity.

After one dose of adriamycin, a subacute cardiomyopathy was observed in the mouse by both light and electron microscopy. The microscopic alterations were characterized by single-cell necrosis and mitochondrial degeneration. These lesions were similar to those seen in man and shortly preceded fatal toxicity.

Histogenesis and Morphology of periosteal sarcomas induced by FBJ virus in NIH Swiss mice.

FBJ virus was injected i.p. into 145 neonatal NIH Swiss [N:NIH(s)] mice. Eighty mice developed a total of 110 neoplasms by 5 months of age. The mean latent period of the tumors was 71 days (26 to 145) postinjection. The frequency of occurrence of neoplasms at different sites was: diaphragm, 45%; ribs, 14%; vertebrae, 14%; femora, 9%; pelvic bones, 5%; tibiae, 4%; sternebrae, 3%; and inguinal area, 7%. The neoplasms were characterized histologically by elongated or rounded cells associated with an abundant connective tissue stroma. Occasional areas of bone formation and apparent osteoid metaplasia were seen. Bone tumors appeared to arise from periosteal cells, to grow by expansion, and to invade locally, but they failed to metastasize. Neoplasms of the diaphragm originated in the central aponeurosis and appeared histologically similar to bone neoplasms. Histochemical studies demonstrated abundant alkaline phosphatase in tumor cells, and ultrastructural observations revealed subcellular characteristics of osteoblasts and chondroblasts. Tumors were readily transplantable and had histopathological characteristics similar to those of the primary viral-induced tumors. The results of this study indicate that the FBJ virus induces in NIH Swiss mice a unique type of chondroosseous neoplasm derived from periosteal cells which has a resemblance to human juxtacortical (parosteal) osteosarcoma.

Prevention of renal failure in rats receiving cis-diamminedichloroplatinum(II) by administration of furosemide.

The clinicopathological signs of renal failure induced in rats by weekly i.v. administration of cis-diamminedichloroplatinum(II) were prevented by pretreatment with furosemide. Weight loss, anemia, and generalized toxic effects of the drug were not effected by furosemide.

Quantification of bleomycin pulmonary toxicity in mice by changes in lung hydroxyproline content and morphometric histopathology.

Bleomycin treatment produced dose-dependent changes in lung collagen content and in several measurable histopathological parameters. NIH/Swiss mice were treated twice weekly for 6 weeks with bleomycin, 0, 1, 20, or 40 mg/kg s.c. The two highest doses produced mortalities of 35 and 100%, respectively, as well as loss of body weight and increase in lung wet weight. Lung hydroxyproline content, an index of collagen, increased to 40 to 50% above control levels at 6 and 8 weeks after initiation of treatment with bleomycin 20 mg/kg. Morphometric analysis was applied to the following parameters at light microscopy: number of intraalveolar macrophages and leukocytes, total pulmonary cell count, alveolar wall thickness, and percentage of consolidation of lung parenchyma. The two highest doses produced increases in all of these parameters as compared to controls. The most marked changes occurred in the number of intraalveolar cells, which in the group given 20 mg/kg rose to 150, 190, and 210% of controls at 4, 6, and 8 weeks. The lowest dose of bleomycin, 1 mg/kg twice weekly for 6 weeks, evoked no pulmonary or other toxicity by the parameters examined. This model of chronic pulmonary toxicity may be useful in analog development, in testing potential antidotes, and in examining the effects of other factors that might modify the pulmonary toxicity of bleomycin.

Composition of cartilage from lysozyme-deficient rabbits.

Costal and auricular cartilage obtained from mutant rabbits exhibiting lysozyme deficiency has been found to be identical to similar tissue from control animals in a variety of biochemical parameters. These data seriously question the putative role of lysozyme as a structural component of cartilage.

Comparison of global and mode of action-based models for aquatic toxicity.

The ability to estimate aquatic toxicity is a critical need for ecological risk assessment and chemical regulation. The consensus in the literature is that mode of action (MOA) based toxicity models yield the most toxicologically meaningful and, theoretically, the most accurate results. In this study, a two-step prediction methodology was developed to estimate acute aquatic toxicity from molecular structure. In the first step, one-against-the-rest linear discriminant analysis (LDA) models were used to predict the MOA. The LDA models were able to predict the MOA with 85.8-88.8% accuracy for broad and specific MOAs, respectively. In the second step, a multiple linear regression (MLR) model corresponding to the predicted MOA was used to predict the acute aquatic toxicity value. The MOA-based approach was found to yield similar external prediction accuracy (r(2) = 0.529-0.632) to a single global MLR model (r(2) = 0.551-0.562) fit to the entire training set. Overall, the global hierarchical clustering approach yielded a higher combination of accuracy and prediction coverage (r(2) = 0.572, coverage = 99.3%) than the other approaches. Utilizing multiple two-dimensional chemical descriptors in MLR models yielded comparable results to using only the octanol-water partition coefficient (log K(ow)).

Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid.

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, therefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metastatic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hürthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2), and in human thyroid tissues (papillary, follicular, medullary, and Hürthle cell cancers, follicular adenomas, and Graves' thyroid tissue) by Northern blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilobase VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and higher in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic thyroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell lines stained more intensely than normal thyroid cells and follicular tumor cells more intensely than parafollicular tumor cells. Again, no difference was noted in VEGF staining between primary and metastatic thyroid tumors. Deparafinized sections of papillary, follicular, and Hürthle cell cancers also stained much stronger than those of medullary thyroid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also secreted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastatic thyroid tumors were similar. VEGF mRNA is therefore expressed, and VEGF protein is secreted by normal, hyperplastic, and neoplastic thyroid tissues. The higher levels of VEGF expression in differentiated thyroid cancers of follicular cell origin suggests a role in oncogenesis.

Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo.

BACKGROUND: Without angiogenesis, tumor growth is limited to a few millimeters, the limit of diffusion. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen and a major regulator of angiogenesis. METHODS: To investigate the relationship between VEGF and thyroid tumor angiogenesis, we xenografted human dermal matrix inoculated with FTC-133 cells into nude mice or directly injected FTC-133 cells subcutaneously. To block the function of VEGF, the neutralizing anti-VEGF monoclonal antibody A.4.6.1 (mAb A.4.6.1) was injected intraperitoneally twice weekly. As control, an antibody of the same isotype (Ab 5B6) or phosphate buffer saline solution (PBS) was used. To evaluate the dermal matrix as a model for angiogenesis studies, recombinant human VEGF was inoculated into the dermal matrix pocket and xenografted into mice. RESULTS: In the dermal matrix angiogenesis model, the number of blood vessels paralleled the concentration of recombinant human VEGF and was highest at 100 ng/mL. Mice that were treated with the mAb A4.6.1 developed fewer blood vessels (mean, 6.6 per HPF) than control mice (18 per HPF in Ab 5B6 and 22 per HPF in PBS; P <.01). Tumors from mice that were treated with mAb A.4.6.1 were much smaller (mean +/- SD, 0.09 +/- 0.02 gm) at 5 weeks, compared with the tumors treated with Ab 5B6 (5.38 +/- 1.15 gm) or PBS (4.0 +/- 0.72 gm; P <.001). CONCLUSIONS: VEGF is produced by the follicular thyroid cancer cell line and stimulates angiogenesis and growth of thyroid cancer. This stimulation can be blocked by mAb A.4.6.1.

Isolation of Campylobacter jejuni in Hunan, the People's Republic of China: epidemiology and comparison of Chinese and American methodology.

The incidence of infection with Campylobacter jejuni was determined in individuals with and without diarrheal disease seen at a hospital in Changsha, China. Stool specimens were cultured by two methods: one developed by the Chinese and a second control method used commonly in the United States. Among people with diarrhea, 18.7% of the 48 children and 8.7% of 104 adults were infected with Campylobacter jejuni. In the group without diarrhea, 8.6% of 105 children but none of 76 adults tested had the organism in their stool. Of the 27 total positive cultures, the Chinese method was positive in 26, compared with 21 for the control method. The Chinese culture method was at least as sensitive and specific as the American method. The biochemical characteristics and antibiotic sensitivities of Chinese isolates were similar to organisms isolated in other parts of the world. This study shows that Campylobacter jejuni is a common enteric pathogen in China and that the asymptomatic carrier state of this organism is significant in children.

In vivo toxicity to lymphoid tissue by 2'-deoxycoformycin.

The enzyme adenosine deaminase has an essential role in lymphocyte metabolism. To examine the in vivo effects of inhibition of this enzyme healthy BDF1 mice were injected intraperitoneally with 2'-deoxycoformycin, a stoichiometric tight-binding inhibitor of adenosine deaminase. Of the treated animals, 20% died of overwhelming infection, and histopathological examination of these, and surviving animals sacrificed 10 days following treatment indicated a selective toxicity to lymphoid cells. No toxicity to tissues other than the lymphoid system was observed, which is consistent with the hypothesis that 2'-deoxycoformycin offers a new and selective approach to the treatment of lymphoid malignancies.

Invasion of human follicular thyroid carcinoma cells in an in vivo invasion model.

Models that demonstrate histological invasion of extracellular matrix barriers by tumor cell lines are useful for assessing new methods to treat or prevent tumor metastasis. An in vivo invasion model using acellular human dermal matrix has been described in a murine squamous cell carcinoma line. The present study examined the application of this tumor invasion model to another epithelial cell line derived from a different species. A human follicular thyroid carcinoma cell line, known to be invasive by other assays, was grown on the dermal-epidermal basement membrane surface of human acellular dermal matrix in culture and then grafted in athymic mice. Immunohistochemical staining of type IV collagen was used to identify the basement membrane and invasion was determined as penetration of the basement membrane by tumor cells. Identification of the human tumor cells in the in vivo grafts was done by in situ hybridization with species specific probes. FTC-133 tumor cells did not invade the matrix after 4 weeks of growth in in vitro culture, but there was extensive loss of the basement membrane and infiltration of the tumor cells into the dermis after 2 weeks growth in vivo. This study suggests that the in vivo dermal matrix model of invasion is applicable to a broad range of epithelial carcinoma cell lines to study their capability to penetrate basement membrane. A model such as this may be useful for studying the local effects of genetic manipulations of implanted tumor cell populations, leading to the development of therapeutic agents that block invasion.

Evaluation of a rapid specific ward based assay for creatinine in blood.

We have evaluated a dry reagent stick test for the quantitation of creatinine in plasma employing a whole blood sample. The assay was found to be specific for creatinine and correlated well (r = 0.993) with an established laboratory procedure. The precision found indicated that the method was suitable for use in the diagnosis and monitoring of renal disease.

The initial coverage and impact of the pneumococcal and influenza vaccination program for at-risk indigenous adults in Far North Queensland.

OBJECTIVES: To describe the initial coverage and impact of a pneumococcal and influenza vaccination program for at-risk Indigenous adults in Far North Queensland that formally commenced in 1996. DESIGN: Ascertainment of vaccine coverages, and prospective laboratory surveillance of invasive pneumococcal disease occurring in Indigenous adults in the region. MAIN OUTCOME MEASURES: Coverages of the first doses of both vaccines administered since 1995, and the incidence of invasive pneumococcal disease in Indigenous adults in the region between 1993-2000. RESULTS: Most (96% and 73%) of the Indigenous adults > or = 50 years of age received influenza and pneumococcal vaccines, respectively, for the first time between 1995-2000. Assuming that either 33% or 50% of Indigenous adults 15-49 years of age in Far North Queensland were eligible for vaccination, then either 109% or 72% of this population received influenza vaccine, and either 75% or 50% received pneumococcal vaccine, respectively, for the first time between 1995-2000. The incidence of vaccine-preventable invasive pneumococcal disease fell from 111 (95% confidence interval [CI] 77-154) cases per 100,000 per year in 1993/94 to 28 (95% CI 13-53) cases per 100,000 per year in 1999-2000 (p<0.05). CONCLUSION: Although there was a significant decline in the incidence of invasive pneumococcal disease, the vaccine coverages after five years of the program were suboptimal. Because of the difficulties in targeting the 15-49 years age group and because of unrecognised risk factors, we suggest that a universal Indigenous adult pneumococcal and influenza vaccination program should be considered.

Modular group therapy in a community mental health center.

To use staff resources more efficiently, a community mental health center in South Carolina initiated an eight-session modular psychoeducational and group therapy program with a classroom format. Groups were composed of three to 12 patients with the same or similar diagnoses. Each session in the series constituted a complete module and included didactic presentations and group discussion about the material. At follow-up two years after the program started, the program was well accepted by staff and patients. The proportion of patient contacts for group therapy and revenue generated by group contacts had increased. Although an aim of the program was to reduce the frequency of contacts for individual therapy, these contacts did not decline over the follow-up period.

Mercury-reactive lymphocytes in peripheral blood are not a marker for dental amalgam associated disease.

OBJECTIVES: The popular press and publications associated with alternative medicine increasingly report that chronic ill health, particularly myalgic encephalitis like conditions, are associated with mercury amalgam fillings. There are no scientifically proven definitive tests to support these claims. One of the more scientific tests in vogue is to assess the level of blood-borne mercury-reactive lymphocytes and to conclude that patients with high levels have developed a hypersensitivity reaction to mercury. The objective of this study was to determine the diagnostic value of this test. METHODS: This study represents an open comparison of mercury-reactive lymphocyte levels in healthy control individuals with those in patients complaining of symptoms associated with adverse effects of dental metal amalgam fillings. The healthy control group consisted of 51 male and female individuals, aged between 12 and 82 years, with and without dental amalgam fillings. The patient group consisted of 70 male and female individuals, aged between 12 and 87 years, and with the exception of one patient, with three or more mercury amalgam fillings of more than 1 year's duration. In vitro lymphocyte responses to mercury, and to nickel, as an example of a metal commonly associated with hypersensitivity reactions, and to more conventional protein antigens were determined. RESULTS: In the blood of patients and controls, there were similar levels of specifically reactive lymphocytes to all of the in vitro stimulating agents, but there were significantly higher numbers of sub-normal and non-responders within the patient group. CONCLUSIONS: The incidence and quantity of mercury-reactive lymphocytes in the blood are not pathogenic markers of illness associated with dental metal amalgams, but may rather reflect exposure to mercury. The clinical relevance of the decreased in vitro lymphocyte responses in the patient group needs further investigation.

Species-specific in situ hybridization with fluorochrome-labeled DNA probes to study vascularization of human skin grafts on athymic mice.

The skin replacements presently used for wound coverage vascularize less well than do autologous split-thickness skin grafts. Understanding how autologous grafts vascularize can lead to methods to improve skin-replacement vascularization. Fresh human skin was grafted on athymic mice. Endothelial cells were stained by immunohistochemistry. Human and mouse cells were distinguished by in situ hybridization with fluorescent species-specific DNA probes. The number of mouse and human endothelial cells in the graft were counted. Initial vascularization of the graft is limited solely to anastamosis of severed ends of human vessels in the graft-to-mouse vessels in the recipient bed. Mouse endothelial cells gradually replace human endothelial cells in the graft. This demonstrates that initial vascularization of skin grafts is solely the result of inosculation rather than neovascularization. Skin replacements that contain vessels should vascularize like skin grafts, and methods to repopulate replacements with capillaries should be sought.

A court-mandated workshop for adolescent children of divorcing parents: a program evaluation.

This article provides a description and an empirical evaluation of a predivorce workshop established by the Family Court of Allen County, Indiana, for adolescent children (N = 48) of divorcing parents. Highlighted are the concerns of the adolescents, the approaches taken by the workshop staff, and the impact of the program on the participants. Viewpoints on the clinical, ethical, and legal issues involved in "required" predivorce counseling for adolescents are presented. The preventive nature of the program, its means of transforming initial resentment toward the workshop experience into positive feelings, and the implications for future practice and research are also discussed.

Shrinking the western Pacific: psychiatric training for medical students from Micronesia.

In 1989 the Hawaii State Hospital became the primary site for clinical teaching of psychiatry to students of the Pacific Basin Medical Officer Training Program, a program designed to train clinicians for the western Pacific. The psychiatry clerkship was developed to provide practical training in psychiatry to clinicians who will practice in Micronesia. Challenges encountered by the educators, including transcultural issues, are discussed. Interventions found to be effective in resolving these challenges are described.