Neuron-specific enolase reactivity in hyperplasias and neoplasms of the thyroid.
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Biomedical subjects
Publications and source records attributed to C Kittas.
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The available staging systems for B-chronic lymphocytic leukemia (B-CLL) do not always predict the clinical course and the prognosis of the disease. In these systems, the pattern of bone marrow histology is not incorporated. In the current report we investigate the prognostic value of the diffuse or nondiffuse pattern of bone marrow involvement in 120 B-CLL patients in relation to their actuarial survival, and we compare these results with the actuarial survival based on the International Workshop system. In addition, we analyze the influence of the diffuse or nondiffuse pattern on the actuarial survival, in relation to the individual clinical stages (A, B, C). All patients were diagnosed and followed-up in the same Unit. Our patients were divided into Stage A (64), Stage B (22), and Stage C (34). They were also subdivided into those with a diffuse (46) and those with a nondiffuse (74) pattern of bone marrow histology. The difference in the actuarial survival in relation to their clinical stage (A, B, C) was statistically significant (P less than 0.025). A greater statistical difference (P less than 0.005) was found when the actuarial survival was analyzed in relation to the diffuse or nondiffuse pattern of bone marrow histology. No statistically significant differences could be found (P greater than 0.1), when the actuarial survival was calculated in every stage (A, B, C), on the basis of the diffuse or nondiffuse pattern of bone marrow histology. When our Stage A and B patients were analyzed for disease progression, in relation to the diffuse or nondiffuse bone marrow histology, it was found that 66.6% of the diffuse Stage A patients and 88% of the diffuse Stage B patients had disease progression as compared to only 8.6% for the nondiffuse Stage A patients and 33% for the nondiffuse Stage B patients. Our findings indicate that: the pattern of bone marrow histology in B-CLL patients is the single most important prognostic parameter in this disease; a clinicopathologic staging system for B-CLL may be justified; and the diffuse pattern of bone marrow histology could be considered as the best criterion for initiation of therapy in these patients.
Prednisolone administration in guinea pigs for 20 days induces significant hypergastrinemia and duodenal G-cell hyperplasia. Hypergastrinemia and duodenal G-cell hyperplasia are less prominent following 40 days of prednisolone administration and this could be partly attributed to the duodenal D-cell increased activity, which represents an adaptive response to the alterations of gastric secretory functions induced by corticosteroids.
Twelve dogs underwent an extensive proximal small bowel resection. Basal and postprandial serum gastrin levels increased significantly one and two months after the resection compared to the respective preoperative levels. The increase in serum gastrin levels two months after the resection was less prominent than the respective increase one month postoperatively. Antral G- and D-cell populations increased significantly two months after the resection compared to the respective populations before the resection. It is concluded that hypergastrinaemia following small bowel resection is due to the quantitative elimination of the inhibiting hormonal factors of gastric secretion and gastrin release. The adaptive increase of antral D-cell population could explain the temporary character of hypergastrinaemia.
Fourteen guinea pigs were given prednisolone daily for 20 days and 11 for 40 days. Another 20 formed the two control groups. Short-term prednisolone treatment significantly increased serum gastrin levels and antral G-cell population as compared to the control group. The same parameters significantly decreased following 40 days of prednisolone treatment as compared to the group of short-term prednisolone treatment. Forty days of prednisolone treatment significantly increased antral D-cell population as compared to the control and short-term prednisolone treatment groups. It is concluded that hypergastrinaemia and antral G-cell hyperplasia following corticosteroid administration is temporary and is accompanied by antral D-cell hyperplasia.
Eleven occult carcinomas (1.8%) were found in 611 specimens from partial and radical thyroidectomies performed in Metaxa's Memorial Hospital of Piraeus and 3 (1.5%) in 200 autopsies from Athens City Forensic Department. Both surgical and autopsy specimens were thoroughly examined. Autopsies were selected to match for age and sex to the surgical material, from non hospitalized relatively healthy individuals. The prevalence found by us was lower than that reported from other European countries. The prevalence found in autopsies and surgicals was almost identical and it appears that thyroid lesions due to which the patients were operated are not related to the presence of the tumors.
Thirty hairy cell leukemia patients were evaluated repeatedly for their bone marrow (BM) histology. At the time of diagnosis, 18 (60%) had diffuse, 9 (30%) had interstitial, and 2 (10%) had a mixed (diffuse and interstitial) pattern of BM disease. The follow-up BM specimens were obtained at intervals of 3-24 months, and the follow-up observation period was 12-94 months. In patients who were nontreated or only splenectomized, no significant changes were observed except of a persistent megaloblastoid picture of the red cell series and an increase of BM fibrosis. In the alpha-interferon treated patients a complete disappearance of hairy cells was observed in one and a dramatic reduction in five. The hairy cell index was reduced from a mean of 0.8 before to 0.1 after alpha-interferon therapy; most patients displayed megaloblastoid erythropoiesis. In the complete responder features of myelodysplasia were present.
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In the present study antral G-cells which secrete gastrin and antral and fundic D-cells which secret somatostatin, an inhibitor of gastric acid secretion were revealed immunocytochemically and the population size estimated along with serum gastrin levels in ten male and eight female guinea pigs. Serum gastrin, antral G-cells, antral D-cells and fundic D-cells were 41.90 +/- 6.10 SD pg/ml, 210 +/- 18.03 SD cells/cm, 128.20 +/- 17.64 SD cells/cm and 121 +/- 17.91 SD cells/cm respectively in males and 35 +/- 4.62 SD pg/ml, 176 +/- 13.80 SD cells/cm, 108.40 +/- 6.90 SD cells/cm and 106.8 +/- 6.50 SD cells/cm respectively in females. The differences in serum gastrin levels, antral G-cell population and antral D-cell population between the two sexes were statistically significant (P less than 0.05, P less than 0.001, P less than 0.01). It is possible that endogenous androgens induce a relative hyperplasia and endogenous oestrogens a relative hypoplasia of G-cells. Antral D-cell differences may reflect an adaptive hormonal mechanism to the possible different states of gastric secretory functions.
Thirty-nine primary gastric and 22 intestinal malignant lymphomas collected from 1969 to 1980 have been studied morphologically and immunohistochemically. Eighteen of the 61 gastrointestinal lymphomas were of low-grade malignancy (9 lymphoplasmacytoid/cytic, 3 centrocytic, 6 centroblastic/centrocytic) and 43 were of high-grade malignancy (14 centroblastic, 7 lymphoblastic, 22 immunoblastic malignant lymphomas) according to the Kiel classification. The peroxidase-antiperoxidase (PAP) method was used in 53 of the 61 cases. Twenty-seven of them revealed a monoclonal positivity for intracytoplasmic IgS: kappa light chains in 18 and lambda light chains in 7 cases. Two cases represented alpha chain disease, revealing only a heavy chain positivity. The most frequent staining pattern of the lymphoma cells was that of kappa/mu. Cells with a mixed centrocytic and plasma cell configuration (centrocytoid plasma cells) proved to be positive for intracytoplasmic IgS. Lymphoma cells of all tested cases proved to be negative for all histiocytic markers. Histologically and immunohistochemically, the Greek cases of primary gastrointestinal malignant lymphomas seem to resemble "western" type lymphomas.
The microvasculature of lymph nodes of 55 cases of T-cell lymphoma was studied by light microscopy, immunohistochemistry and electron microscopy. A modified peroxidase-antiperoxidase (PAP) method was used for staining paraffin sections with lectin I of Ulex europaeus (UEA-I), which is a specific marker for vascular endothelial cells. The T-cell nature of each case was proven by immunohistochemistry, including immunoperoxidase staining of frozen sections with monoclonal T-cell antibodies. The cases were subclassified according to previously established criteria, but with the addition of a separate group showing a high content of clear cells. For the purpose of the present study, the small blood vessels were separated into two main variants, viz.: high endothelial venules (HEV) and all other types of vessels with flat endothelium (SVFE). The development of each of these variants and the extent of lymphocyte migration through the vascular wall were assessed semiquantitatively. The findings suggest that the blood microvasculature, as a whole, is similar in all types of T-cell lymphoma. There were distinct differences, however, in the development of the two main categories of small vessels between the various types. Chronic lymphocytic leukaemia of T-type (T-CLL) and Sézary's syndrome were poor in SVFE and rich in HEV, and there was considerable lymphocyte traffic through the latter. In contrast, T-immunoblastic and especially T-lymphoblastic lymphocyte traffic. The appearance of the microvasculature varied markedly in the various subtypes of "pleomorphic T-cell lymphoma". In the small cell subtype HEV predominated and SVFE represented only a small or moderate fraction of the microvasculature. As the size of the neoplastic lymphoid cells increased towards the medium-sized and large cell subtype, there was a decrease in the number of HEV and an increase in the number of SVFE accompanied by a decrease in lymphocyte migration. In T-cell lymphoma of the clear cell type the microvasculature showed features between those of T-CLL and the small cell subtype of pleomorphic T-cell lymphoma. Electron microscopy confirmed the light microscopic findings and revealed many similarities in vascular changes between "pleomorphic T-cell lymphomas" and lymphogranulomatosis X.
We have examined the effect of chronic administration of phenytoin on Purkinje cells of cerebellum in adult mice. After daily intramuscular administration of phenytoin for a period of six months no difference in the number of Purkinje cells could be found between the treated and control animals.
Forty-eight patients with chronic lymphocytic leukemia (CLL), and 12 patients with small (well differentiated) lymphocytic lymphoma (WDL) were histologically evaluated for their pattern of bone marrow (BM) involvement. Four different types of BM infiltration were recognized: nodular (N), interstitial (I), nodular and interstitial (mixed) and diffuse (D). The pattern of BM involvement was compared with the clinical, laboratory, and survival status in all patients. The extent of the disease in CLL patients, was determined by the Rai and the International Workshop on CLL Staging Systems, while in WDL patients the Ann Arbor staging system was used. In the CLL group the N pattern was found in 8%, the I in 33%, the mixed in 31%, and the D in 27% of the patients. Based on the International Workshop on CLL Staging System, the I pattern of BM involvement was more frequently found in Stage A (56%), the mixed in Stage B (68%), and the D in Stage C disease (90%). All CLL patients with D pattern required treatment from the beginning, contrary to CLL patients with the other patterns, in whom therapy was required in less than 50%. Similarly, deaths were more common in the D pattern in whom therapy pattern than in the other patterns. In the WDL patients BM involvement was found in 4 of 12, (33%) and its pattern of positivity was always nodular, although most patients (10 of 12) had advanced disease. It is concluded that the frequency of BM involvement may contribute in the differential diagnosis of WDL from CLL. In addition, the pattern of BM infiltration correlates very well with the International Staging System for CLL, and the pattern of BM positivity in CLL patients also has prognostic significance.
We have studied the distribution of lysozyme (Ly), a1-antitrypsin (a1AT) and a1-antichymotrypsin ( a1AChy ) in the normal, chronically inflamed and neoplastic gall bladder mucosa using the peroxidase-anti-peroxidase (PAP) method. Ly was absent from the normal mucosa but it was found only in areas of glandular metaplasia of true antral type and in crypts of possible early metaplastic nature in cases of chronic cholecystitis. a1AT and a1AChy were also found in such metaplastic areas, but their presence was also observed immunohistochemically in areas of essentially normal and in non-metaplastic, chronically inflamed gall bladder mucosa. The possible local production of these substances by gall bladder epithelial cells is discussed. Ly, a1AT and a1AChy were also found in various histological types of adenocarcinoma of the gall bladder in varying degrees of frequency and intensity, unrelated to the histological type and invasiveness of the tumour.
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The topography and the severity of the brain lesions induced in male and female white mice 1-6 weeks following inoculation with Toxoplasma gondii were studied by conventional histological and peroxidase-antiperoxidase (PAP) immunohistochemical techniques. The medulla oblongata and fourth ventricle were the most severely damaged areas of the brain, while the cerebellum was only minimally involved in this only in the later stages of the disease. Toxoplasma cysts were revealed by the PAP method as early as 2 weeks after infection. The number of cysts and the severity of the lesions increased gradually each week following inoculation. The lymphoplasmacytic element in the lesions was less intense in male than in female mice. The significance of these findings in respect to the possible immunological pathogenesis of CNS toxoplasmic changes is discussed. A correlation of the experimental findings with the known neurologic manifestations of the disease is also attempted. The advantage of the PAP method in the study of toxoplasmic infection is stressed.
The subcellular effects of bilateral adrenalectomy on the rat myocardium were examined on 50 male rats. The animals, divided into groups of ten, were killed 3, 17, 18, 19 and 21 after adrenalectomy. The early changes consisted of moderate intracellular edema of many cardiac muscle cells and disarrangement of their myofibrils. The late changes consisted of prominent intracellular edema of many cardiac muscle cells, destruction of numerous myofibrils, dilatation of the sarcoplasmic reticulum and accumulation of numerous irregular mitochondria in subsarcolemma areas of the sarcoplasm. The lipofuscin granules seemed to be increased in number. Many endothelial cells were edematous and platelet aggregations filled the lumen of some small vessels.
Lysozyme, alpha 1-Antichymotrypsin and alpha 1-Antitrypsin were demonstrated by an immunoperoxidase technique (PAP) in malignant cells of adenocarcinomas of the stomach but not of the large intestine. Lymph-node metastases showed identical immunoreactivity to that of the primary tumour. Neoplasms arising from the cardia, the body and the pyloric antrum of the stomach showed different immunostaining reactions. It seems that these differences partly reflect the distribution of lysozyme, alpha 1-Antichymotrypsin and alpha 1-Antitrypsin in the normal gastric mucosa. The usefulness of our findings in the identification of the primary tumour in cases of lymph node metastases of unknown origin, is also discussed.