Levels of histaminase and L-DOPA decarboxylase activity in the transition from C-cell hyperplasia to familial medullary thyroid carcinoma.

The distribution of calcitonin, L-dopa decarboxylase, and histaminase is studied in sectioned total thyroid glands from patients with different stages of familial medullary thyroid carcinoma. In 5 glands with gross carcinoma and in 3 with early microscopic carcinoma the distribution of all three parameters positively correlates (p less than .01 for each correlation). In contrast, in 6 glands with C-cell hyperplasia only the distribution of calcitonin and L-dopa decarboxylase correlates (r = 0.64, p less than .01) while those for histaminase vs. calcitonin (r = .17, p = N.S.) and histaminase vs. dopa decarboxylase (r = .03, p = N.S.) do not. In the glands with microscopic carcinoma the peak levels of histaminase occur in the areas of disease as defined by immunohistochemical staining of calcitonin; mean histaminase activity is the only one of the three parameters measured that distinguishes between C-cell hyperplasia and microscopic carcinoma (p less than .005). Immunohistochemical staining of histaminase shows positive cells in glands with gross and microscopic carcinoma, but in none of the glands with hyperplasia alone. Histaminase is thus found in high amounts in some malignant C-cells only and may be a useful marker to distinguish between hyperplasia and malignancy in thyroids with early C-cell proliferative disorders.

Cryptosporidiosis in an immunosuppressed renal-transplant recipient with IgA deficiency.

Cryptosporidia are sporozoan parasites that infect epithelial cells of the gastrointestinal tract. Infection with cryptosporidia has been found most commonly in a variety of animal species and only rarely in man. The authors report a case of an immunosuppressed renal-transplant recipient with IgA deficiency who experienced diarrhea and fever and was found to have cryptosporidia in a jejunal biopsy specimen and in air-dried smears of the specimen. By electron microscopy, trophozoite, schizont, and macrogamete forms were identified, and these forms ahd morphologic features similar to those of cryptosporidia previously found in guinea pigs. Treatment of the cryptosporidial infection in this case was with trisulfapyrimidines. The efficacy of this treatment could not be evaluated because of complications.

Variable content of histaminase, L-dopa decarboxylase and calcitonin in small-cell carcinoma of the lung. Biologic and clinical implications.

To ascertain whether the content of endocrine markers is constant in small-cell carcinoma of the lung, levels of three markers of medullary thyroid carcinoma were studied in this tumor. Histaminase was increased in six of six primary tumors (three to 14,000 times), L-dopa decarboxylase in four of six (six to 30 times), and calcitonin in one of one (eight times) over levels in adjacent lung. Marker levels in mediastinal metastases reflected those in primary tumors in four of five patients. However, in four of seven, multiple hepatic metastases contained low to absent levels despite simultaneously high values in chest lesions. Immunohistochemical studies of histaminase revealed that within each primary tumor different cells contained different amounts of the enzyme. Since marker content varied between tumor cells, between primary tumors and between metastases in individual patients we conclude that circulating levels of these three markers cannot be expected necessarily to mirror tumor burden in patients with small-cell lung tumors.

Calcitonin and histaminase in C-cell hyperplasia and medullary thyroid carcinoma. A light microscopic and immunohistochemical study.

The thyroid glands of 13 patients with gross medullary thyroid carcinoma (4 sporadic, 9 familial), 3 patients with clinically occult microscopic carcinoma, and 5 patients with C-cell hyperplasia have been studied using routine light microscopy and immunohistochemical techniques. The morphologic features of the spectrum of C-cell proliferative lesions are reviewed, and the distribution of calcitonin and histaminase in these lesions is compared. Calcitonin production is a property of normal, hyperplastic, and neoplastic C cells, and the hormone is present in the majority of tumor cells in medullary carcinoma. In contrast, histaminase is shown to be present only in some cells in medullary carcinoma and not in normal or hyperplastic C cells. We believe that the presence of histaminase in a C-cell proliferative lesion is an atypical phenomenon and indicative of malignancy.

Immunohistochemical localization of histaminase (diamine oxidase) in decidual cells of human placenta.

An immunohistochemical technique has been developed for the localization of histaminase (diamine oxidase) in human placenta. The procedure utilizes antibody to highly purified human placental enzyme prepared in rabbits. Histaminase is shown to be present in the cytoplasm of the decidual cells of the maternal placenta; the staining is specific and can be removed by preabsorption of the antisera with purified antigen. The present demonstration of histaminase in the maternal portion of placenta confirms previous biochemical data suggesting that the enzyme is not a fetal product in this tissue. This study also provides further evidence that the presence of histaminase in some human tumors and in normal tissues like kidney and intestine is the result of the expression of a mature and not a fetal genome.

Ectopic ACTH, prostatic oat cell carcinoma, and marked hypernatremia.

Locally recurrent, poorly differentiated carcinoma of the prostate was associated with hypokalemic alkalosis, marked hypernatremia, diabetes mellitus of recent onset, and hyperosmolar syndrome. These findings, with mild hypertension, in the absence of clinical features of Cushing's syndrome, suggested an ectopic ACTH syndrome. Plasma ACTH and cortisol levels were markedly elevated, and failed to suppress in response to either low or high-dose dexamethazone administration. The patient's condition deteriorated rapidly. Autopsy findings included carcinoma extensively infiltrating the prostate with extension to the urinary bladder, and metastases confined to the pelvic nodes and soft tissues. The adrenal glands weighed 23 g and showed diffuse hyperplasia. Extract of the prostatic tumor was analyzed for ACTH and showed approximately 40 times normal plasma levels (or about 4,010 pg/g of tissue); ultrastructural features showed secretory granules consistent with ACTH content of the tumor cells. Such cells were positive when stained for ACTH by peroxidase-tagged immunochemical methods. The case fulfills all established criteria for relating excess corticosteroid production and nonpituitary tumors.

Whipple's disease: demonstration by immunofluorescence of similar bacterial antigens in macrophages from three cases.

Although it is widely accepted that Whipple's disease is caused by microorganisms, there is little agreement as to the exact nature of those microbes. Several different types of bacteria have been reported from patients with Whipple's disease causing some workers to speculate that Whipple's disease may be due to a variety of microorganisms. Using an indirect immunofluorescence technique, we have demonstrated bacterial antigens in the granules of the foamy macrophages from three patients with Whipple's disease. The macrophages in each case stained with several types of antibacterial grouping sera. Jejunal biopsies from three normal subjects and one from a patient with celiac-like disease did not show significant reactions with any of the antisera. When these same antisera were reacted with homologous and heterologous bacteria, numerous cross-reactions were seen. However, each organism only reacted with certain antisera resulting in a distinctive pattern of reaction which could identify it. Therefore, if a different organism was present in each case of Whipple's disease, the antisera should give dissimilar reactions from case to case, but if the same type of microbe was present in each case, a similar pattern of reaction should be seen. In fact, the reactions were remarkably similar from case to case. These results suggest that a single, antigenically definable microorganism is present in the jejunal tissue of patients with Whipple's disease.