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G Chejfec

Publications and source records attributed to G Chejfec.

71 records · Page 4Linked to original sources

Effects of radiation on parafollicular C cells of the thyroid gland.

While radiation has well-recognized effects on follicular cells of the thyroid gland, those on parafollicular C cells are not yet established. Low-dose radiation that has been proved to be nonablative and carcinogenic to follicular cells was administered to 8-week-old Long-Evans rats to study the changes in C cell number and function. Circulating calcitonin levels were significantly reduced in animals that had undergone radiation at age 24 months. Mean calcitonin values were 0.66 (+/- 0.20) ng/ml and 1.64 (+/- 0.59) ng/ml for control males and females compared with 0.14 (+/- 0.06) ng/ml and 0.11 (+/- 0.01) ng/ml for males (P less than 0.05) and females (P less than 0.001) that had undergone radiation, respectively. These levels correlated well with C cell population density in thyroid glands in the control group and in the group that had undergone radiation as evidenced by light microscopy. Routine hematoxylin and eosin staining showed C cell hyperplasia in 77% of control animals of both sexes compared with 4% in animals that had undergone radiation (P less than 0.005). Immunoperoxidase staining with an anticalcitonin antibody showed virtual absence of C cells in most animals that had undergone radiation compared with diffusely scattered cells in animals in the control group. Medullary carcinomas occurred in 14% of animals in the control group compared with 3% of animals that had undergone radiation (P less than 0.05). These data indicate that the radiation dosage that is carcinogenic to the follicular epithelium causes lethal injury to C cells and thus suggest that C cells are more sensitive to radiation than are follicular cells. This increased sensitivity could explain the virtual absence of C cells, decrease in calcitonin levels, and reduced numbers of medullary carcinomas in the animals that had undergone radiation.

Animals

Neuroendocrinoma of the jejunum: electron microscopic and biochemical analysis.

A 56-year-old woman presented with a sudden, severe hemorrhage per rectum. Angiography localized a jejunal tumor, which was excised. Light microscopy suggested a neuroendocrine tumor, but neither a smooth muscle tumor nor a lymphoma could be excluded. Electron microscopy showed dense cored, single membrane bound secretory granules 150--220 nm in diameter; myofilaments were not observed. Biochemical analysis of tumor tissue yielded considerable amounts of catecholamines. VMA, 5-HIAA, and metanephrines. These combined ultrastructural and biochemical observations establish the diagnosis of neuroendocrine tumor; however, in this case neither type of information is sufficiently specific to define the tumor as either a paraganglioma or a carcinoid. Although paraganglia and mucosal endocrine cells in the GI are currently thought to constitute distinct cell types, they share numerous structural and functional properties, and they are both thought to be part of the APUD cell system. These parallels and similarities are shared by the neoplasms derived from them which often display features of both. In the absence of specific granule types or specific substances isolated from tumor tissue, only the application of specific immunocytochemistry techniques may allow the precise "functional" classification of such tumors.

APUD Cells

Ultrastructural and biochemical analysis of "undifferentiated" pulmonary carcinomas.

Seven cases of "undifferentiated" pulmonary carcinoma were studied ultrastructurally; five were of the typical oat cell variety and the remaining two consisted of larger cells. In three of the former and both of the latter cases neurosecretory-like granules were demonstrated. Biochemical analysis of tumor tissue extracts revealed 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in all instances. No hormonal syndrome or metabolic abnormality was detected in any of the patients. The concomitant morphologic demonstration of neurosecretory-like granules and the presence of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamines in neoplastic tissue would provide further evidence that these tumors may indeed arise from bronchial endocrine cells and could therefore be classified within the group of neuroendocrine carcinomas. Also it seems apparent that these neuroendocrine bronchial carcinomas may include tumors consisting of cells somewhat larger than the typical oat cell. The observation of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in two oat cell carcinomas in which neurosecretory granules could not be demonstrated poses an interesting problem whose solution may only derive from further studies.

Aged

Neuroendocrine carcinomas of the colon. Ultrastructural and biochemical evidence of their secretory function.

Four cases of malignant colonic tumors diagnosed by light microscopy as "small cell undifferentiated carcinomas" were shown by electron microscopy to have neurosecretory-type granules. Biochemical analysis of tumor tissue extracts disclosed the presence of considerable levels of VMA and catecholamines in all tumors; 5-HIAA was present in one tumor. Clinically, there had been no signs or symptoms attributable to those or related substances. Similar observations have been reported in a variety of neuroendocrine neoplasms; for example, the demonstration of neurosecretory-type granules and determination of amine or peptide materials in tumor tissue or body fluids may not be necessarily reflected in clinical hormonal syndromes or obvious metabolic abnormalities. Our structural and biochemical observations indicate that, regardless of clinically evident hormonal activity or lack thereof, some small cell "undifferentiated" colonic cancers derive from APUD elements, and therefore they should be classified within the group of neuroendocrine carcinomas. The evident secretory capabilities of these carcinomas suggest obvious diagnostic possibilities and could conceivably lead to a reappraisal of current therapy.

APUD Cells

Allopurinol-induced granulomatous hepatitis with cholangitis and a sarcoid-like reaction.

A 36-year-old man had pain in both knees and an elevated uric acid concentration; his liver function was normal. Allopurinol therapy was started, 100 mg twice daily. After one month fever, lethargy, and severe polyarthralgia developed. On admission to our hospital liver function was abnormal, and a liver biopsy specimen showed granulomas with cholangitis and pericholangitis. He also had lymphopenia with a reduced number of T cells and granulomas in the bone marrow. One month after discontinuation of allopurinol therapy the patient was clinically well with normal liver function and a normal lymphocyte count. A repeated liver biopsy specimen showed normal liver tissue with no granulomas. The onset of the symptoms and findings shortly after the initiation of allopurinol therapy, and their disappearance after the discontinuation of therapy suggest a drug-induced hypersensitivity.

Allopurinol

Malignant gastric neuroendogrinomas. Ultrastructural and biochemical characterization of their secretory activity.

In two cases of malignant gastric tumors originally diagnosed as undifferentiated carcinomas electron microscopy revealed a neurosecretory type of granule. Subsequently tumor extracts were tested by biochemical methods and shown to have vanillylmandelic acid and 5-hydroxy-3-indoleacetic acid activity. Neither patient had signs or symptoms referable to the presence of these or related substances. These observations parallel those made in a variety of neuroendocrine tumors in which demonstration of neurosecretory granules or isolation of amine or peptide materials or their metabolites has not necessarily been reflected in clinical hormonal syndromes. Our findings indicate that regardless of clinically apparent hormonal activity or lack thereof, some undifferentiated gastric carcinomas may in fact derive from neuroendocrine APUD elements.

Aged

Neuroendocrine carcinomas of the esophagus.

Of a total of 928 primary esophageal cancers, 16 cases of "undifferentiated" esophageal carcinoma were isolated. The topographic and age distributions as well as the clinical presentation and evolution of these tumors were basically similar to those of the usual esophageal squamous carcinoma. By light microscopy, the tumors were comprised exclusively or predominantly of small, round-to-fusiform cells. The cytoplasm appeared scanty and the nuclei were comparatively large and hyperchromatic. Mitotic activity was prominent. Four of the sixteen neoplasms showed occasional foci of squamous differentiation. Argyrophilic cells were seen in all cases, although their number and distribution were variable. Occasional mucosubstance droplets were present in 2 cases. Argentaffin and amyloid stains were negative in all tumors. Ultrastructural studies revealed variable numbers of granules consisting of a dense core, a pale halo, and a single, delimiting membrane; these measured between 80 and 220 nm in diameter. Four of the sixteen cases displayed conspicuous tonofilament bundles and rare keratohyalin granules. The predominant ultrastructural common denominator of these tumors was the presence of characteristic neurosecretory-type granules; thus, their classification as neuroendocrine carcinomas would appear justified. Nevertheless, the abundant tonofilaments and the rare keratohyalin granules and mucosubstance droplets seen in several cases indicate that some of these epithelial cancers possess and express variable capabilities toward multidirectional differentiation.

Adult

Immunohistochemical features of giant cell carcinoma of the lung: patterns of expression of cytokeratins, vimentin, and the mucinous glycoprotein recognized by monoclonal antibody A-80.

Giant cell carcinoma of the lung (GCCL) is an uncommon and extremely aggressive variant of lung cancer. Characteristic microscopic findings include marked pleomorphism, aggregates of mononucleated or multinucleated giant cells (or both), a general lack of architectural cohesiveness, extensive necrosis, and endocytosis by the giant cells. Although the epithelial character of GCCL has been confirmed by a number of studies, controversy persists as to whether it represents a variant of poorly differentiated adenocarcinoma or of squamous carcinoma. Histochemical studies for mucosubstances have yielded variable and conflicting results. This report describes conventionally fixed and processed samples from 10 cases of GCCL studied with a panel of monoclonal antibodies (Mabs) recognizing different cytokeratin polypeptides (AE1, AE3, AE1/AE3 cocktail, and CAM 5.2), vimentin, and Mab A-80, the last of which binds to a mucinous glycoprotein associated with exocrine differentiation. All 10 cases of GCCL reacted with all cytokeratin Mabs; the extent and intensity of the reaction varied notably. All cases stained strongly and diffusely with Mab AE1 and AE1/AE3, the reaction was less extensive and weaker with CAM 5.2. Significantly, 2 cases reacted focally with Mab AE3. Nine cases reacted extensively and intensely with the vimentin Mab, often showing prominent paranuclear globular profiles. All cases reacted with Mab A-80; the reaction was often strong, but the extent was variable. Findings indicate that all GCCL are indeed cytokeratin positive but that most express polypeptides toward the low-molecular weight end of the spectrum; a small subset also expresses heavier polypeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal

Neuroendocrine carcinoma of the stomach with extensive somatostatin immunoreactivity.

Upper gastrointestinal tract neuroendocrine tumors producing predominantly somatostatin have thus far been described only in the duodenum; their characteristic features include the frequent presence of psammoma bodies (psammomatous somatostinomas), and the association with von Recklinghausen's neurofibromatosis. Gastric neuroendocrine tumors, on the other hand, tend to display immunoreactivity to serotonin but may include small subpopulations producing gastrin, motilin, pancreatic polypeptide, and somatostatin. In this report we describe a neuroendocrine carcinoma of the stomach with rapidly fatal outcome, displaying neurosecretory granules by electron microscopy and immunoreactivity to pan-neuroendocrine markers, ie, chromogranin and neuron-specific enolase. The only neuroendocrine regulatory peptide detected in the tumor was somatostatin, identified by immunohistochemistry in the majority of neoplastic cells. In contrast with duodenal somatostinomas, there were no psammoma bodies and no demonstrable association with von Recklinghausen's neurofibromatosis. To our knowledge this appears to be the first report of a malignant neuroendocrine tumor with diffuse somatostatin immunoreactivity.

Aged

Barrett's esophagus. The cytology of dysplasia in comparison to benign and malignant lesions.

Barrett's esophagus (BE) is the replacement of esophageal squamous epithelium by columnar-lined mucosa and carries an increased risk of carcinoma. Endoscopic surveillance has been suggested, but esophageal brush cytology (BC) has not been widely utilized. Cytologic descriptions of BE, especially dysplasias, are sparse. We studied matched cytologic and histologic materials from 26 patients with BE and 4 patients with concurrent BE and adenocarcinoma. In six patients without dysplasia on biopsy, BE was recognized on BC by the presence of goblet cells within clusters of uniform columnar cells with vesicular nuclei. Dysplasia in 18 BC samples revealed small clusters of haphazardly oriented, mildly pleomorphic cells. Their larger nuclei had thickened membranes, evenly dispersed chromatin and occasional multiple nucleoli. The cytologic differentiation of histologically graded low- and high-grade dysplasia was difficult. The carcinoma cases displayed numerous isolated cells exhibiting flagrant malignant features. We conclude that BE lesions are cytologically distinctive and suggest that BC may play a role in surveillance.

Adenocarcinoma

The induction of esophageal tumors in mice: dose and time dependency.

Three hundred and forty eight C57Bl mice were killed after diethyl-nitrosamine (DEN) treatment at various time intervals ranging from one day to six months. No esophageal tumors occurred in the first three months after DEN treatment; They occurred, however, at four months and increased in number at six months of DEN treatment. Other groups of animals under the same initial DEN treatment were allowed to survive seven or nine months without treatment. One esophageal tumor was recorded at observations made seven months after one single day of DEN administration. A significant increase in the number of esophageal tumors occurred at seven months in mice treated with DEN for two weeks, and for one, two, three or four months; the highest tumor frequency was found in mice treated for six months and surviving three additional months on a carcinogen-free diet. These results suggest that clones of esophageal cells had been "programmed" for tumor growth at an early stage of DEN treatment. The tumors had, however, remained undetected at macroscopical and microscopical examination several months previously. It is apparent that not only the dose administered, but also the post-carcinogen interval is an important factor in esophageal carcinogenesis in the mouse.

Animals