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Biomedical subjects

G Chejfec

Publications and source records attributed to G Chejfec.

At least 55 records · Page 3Linked to original sources

Hereditary pituitary prolactinomas: a new rat model.

Pituitary adenomas are known to occur spontaneously in several rat strains, especially during aging. Here we report the occurrence of adenomas (prolactinomas) in a new rat model at an early age. The adenomas were characterized by light and electron microscopy and histochemically by immunoperoxidase methods using specific antisera. Of the 53 pituitaries examined, one was normal, two were hyperplastic and the remainder were adenomas. Among the latter, there were 37 prolactinomas (70%), 3 GH-producing tumours and 2 ACTH-containing neoplasms. One microadenoma produced both PRL and GH. The remaining 8 adenomas were histochemically negative for all pituitary hormones. Serum PRL levels were elevated in both sexes while serum testosterone was high in females and low in the males. The serum estrogen levels were elevated in the males with prolactinomas. The prolactinomas appear to be transmitted as an autosomal dominant characteristic with incomplete penetrance and a greater incidence in the male.

Animals↗

Neuroendocrine background of the pathology of the islets of Langerhans. A minireview with particular reference to synaptophysin and chromogranin A as neuroendocrine markers and to the ontogeny of argyrophil insulin immunoreactive cells in the rabbit.

As in diseases of other (neuro)endocrine glands, the pathology of the islets of Langerhans comprises both states of hypofunction, notably hypoinsulinism,--diabetes mellitus--and those of hyperfunction, such as hyperinsulinism from either nesidiodysplasia ("nesidioblastosis") or genuine islet-cell neoplasms. The pathogenesis of some characteristic structural lesions of these diseases of the islet parenchymal cells is reviewed against their neuroendocrine background, both phylogenetically and ontogenetically. A preliminary report is given of the appearance of argyrophil insulin cells during the normal foetal development of the islet parenchyma of the rabbit. In addition, the distribution of the newly discovered neuroendocrine markers synaptophysin and chromogranin A has been reviewed immunohistochemically in normal and neoplastic islet parenchyma cells; the insulin cells do not seem to contain chromogranin A.

Animals↗

Synaptophysin. A new marker for pancreatic neuroendocrine tumors.

Synaptophysin (SYP) is a glycoprotein recently isolated from presynaptic vesicles of bovine neurons. Initial studies have demonstrated its presence in neurons in the brain, spinal cord and retina, and in adrenal medullary cells. A subsequent study demonstrated it in pancreatic islet cells and certain neuroendocrine (NE) neoplasms, including several pancreatic islet cell tumors. Based on these preliminary observations, we examined, by immunohistochemistry, conventionally fixed, paraffin sections of 57 pancreatic endocrine tumors with a monoclonal antibody to SYP. Furthermore, we compared the SYP immunoreactivity of 30 of these same tumors with that of neuron-specific enolase (NSE) and of chromogranin (CG). SYP was demonstrated in all but one of the 57 tumors. In the comparative study, for which material was available in only 30 cases, SYP and NSE were present in 29 of the tumors, whereas CG was seen in only 15 cases. We conclude that SYP is a highly sensitive and useful marker for pancreatic NE neoplasms. Moreover, in view of the increasingly evident limited specificity of NSE, SYP should be considered the marker of choice for pancreatic NE neoplasms.

Adenoma, Islet Cell↗

Is gastroesophageal reflux a factor in some asthmatics?

We performed antireflux surgery on 13 adults with both gastroesophageal reflux (GER) and asthma. The duration of asthma ranged from 7 months to 43 yr. Twelve patients had chronic heartburn, 10 had nocturnal cough and wheezing, eight had chest pain, and one was asymptomatic for GER. GER was determined by a combination of esophagoscopy with biopsy, manometry, and esophageal pH testing. Postoperative follow-up ranged from 13 months to 5 yr. Six patients were completely free of all wheezing episodes, six still had wheezing but the frequency and severity had markedly decreased, and one remained unchanged. Of 11 patients who required chronic bronchodilator therapy, four were able to completely stop and six decreased the dose by more than half; one required the same amount of therapy. Of the seven corticosteroid-dependent patients, two were weaned completely, three were being tapered, one remained unchanged, and one required a smaller dose for nasal polyps although he was free of wheezing and had stopped bronchodilators. Three patients, all of whom dramatically improved after surgery, died during their follow-up course: one died suddenly 8 months postoperatively during a walk after dinner from apparent status asthmaticus; one died 9 months postoperatively of refractory congestive heart failure; and one died 30 months postoperatively of metastatic adenocarcinoma of unknown source. We conclude that surgical correction of GER in selected adults with both asthma and GER may significantly decrease or eliminate pulmonary symptoms and the need for asthmatic medications.

Adult↗

Pseudomyxoma peritonei associated with colloid carcinoma of the pancreas.

A case of pseudomyxoma peritonei associated with a mucin-rich, "colloid" adenocarcinoma of the pancreas is described. This previously unreported association was characterized by an extremely rapid clinical course, transerosal spread of the neoplastic process, and the consistent presence of intracytoplasmic lumina in all cells, an ultrastructural feature thought to characterize malignant lesions.

Adenocarcinoma, Mucinous↗

Malignant mesotheliomas. Improved differential diagnosis from lung adenocarcinomas using monoclonal antibodies 44-3A6 and 624A12.

Forty-three malignant pleural mesotheliomas and 10 known metastatic pulmonary adenocarcinomas to the pleura were studied by immunohistochemistry using monoclonal antibodies 44-3A6 and 624A12. Monoclonal antibodies 44-3A6 and 624A12 were raised against human pulmonary carcinoma cell lines; they recognize a membrane-associated protein of 40,000 mol wt and a specific sugar sequence of lacto-N-fucopentose III, respectively. Samples were also studied with a broad-spectrum antikeratin antibody and a polyclonal antibody to carcinoembryonic antigen (CEA). These investigations were performed on formalin-fixed and paraffin-embedded tissues. The mesotheliomas comprised only grossly evident, pleurectomized, or pneumonectomized cases; they included 22 epithelial, 15 biphasic, and 6 spindle cell types. Electron-microscopic study was also done on 9 cases. None of the mesotheliomas was immunoreactive to 624A12, while 9/10 metastatic pulmonary adenocarcinomas were convincingly immunoreactive. Monoclonal antibody 44-3A6 immunostained all of the metastatic adenocarcinomas strongly, whereas only 10/43 mesotheliomas were focally and weakly immunoreactive. The latter included 5 epithelial and 4 biophasic mesotheliomas and 1 spindle cell mesotheliomas; the immunoreaction was confined to scattered single cells, and the staining pattern was readily discernible from that of adenocarcinomas. Forty of 43 mesotheliomas were strongly immunoreactive with the broad-spectrum anti-keratin antibody, whereas 8/10 metastatic pulmonary adenocarcinomas showed focal and rather weak staining. Seven of 10 metastatic adenocarcinomas were immunoreactive to anti-CEA antibody, while only 15/43 mesotheliomas displayed weak immunoreactivity. It is concluded that monoclonal antibodies 44-3A6 and 624A12 are excellent phenotypic markers of metastatic pulmonary adenocarcinomas to the pleura and thus are useful for the differential diagnosis of pleural mesotheliomas. Given conventionally fixed and processed tissues, it appears that the combined use of these monoclonal antibodies may be more effective for that differential diagnosis than anti-CEA and anti-keratin antibodies.

Adenocarcinoma↗

Amphicrine cells, dysplasias, and neoplasias.

The existence of epithelial cells displaying synchronous features of exocrine and endocrine differentiation has been well established. Sporadic descriptions of neoplasms comprising or including such cells have also been recorded. The authors investigated eight carcinomas (lung, two; stomach, two; colon, one; appendix, one; esophagus, one; and pancreas, one). By conventional light microscopy, all eight neoplasms appeared as moderately to well-differentiated adenocarcinomas. Mucosubstance stains showed positive material within well-defined lumina and as intracytoplasmic droplets. Argyrophil stains were positive in seven of the eight neoplasms. The esophageal tumor was a predominantly solid carcinoma; it compromised small to intermediate cells with focal mucosubstance positivity and squamous pearls. By electron microscopy, all these carcinomas including cells displaying variable complements of neurosecretory granules, which were concentrated in the basal pole or in cytoplasmic processes. The granule population was often heterogeneous. The pancreatic carcinoma also showed typical zymogen granules. In all cases, many of the neoplastic cells had true lumina or intracytoplasmic lumina, as well as arrays of filaments; secretory granules were also observed in cells with true or intracytoplasmic lumina. Immunohistochemical studies revealed in all cases either serotonin or one of a spectrum of neuropeptides. Five tumors contained more than one immunoreactive material. The authors conclude that synchronous exocrine and endocrine differentiation may be comparatively frequent in a spectrum of tumors that may be properly termed "amphicrine" carcinomas. This demonstrable heterogeneity of malignant cell populations, however variably expressed, may prove to have considerable significance in the diagnosis and management of these neoplasms.

Adenocarcinoma↗

Barrett's oesophagus and colonic tumours.

Of 65 patients with Barrett's oesophagus, all of whom were white, 29 (44.6%) had colonic tumours; 19 were benign and 10 were malignant. The frequency of colonic cancer was especially high (38%) in patients with Barrett's oesophagus aged 64 years or older. 7 of the 65 patients had had previous colonic resections for cancer and 3 were found prospectively to have malignant tumours. Benign tumours had been removed by colonoscopic polypectomy in 3 of the 19 patients; in 16 patients the tumours were diagnosed prospectively. In comparison with two other high risk groups, malignant tumours were found in 7.7% of 325 symptomatic patients admitted for colonoscopy and in 11.3% of 120 symptom-free patients with occult blood in the stools. The probability of finding this number of malignant tumours in an age-matched random sample of the general population is less than one in a million.

Adenocarcinoma↗

Bombesin in human neuroendocrine (NE) neoplasms.

Bombesin is a 14 amino acid peptide isolated from amphibian skin which was found to have stimulatory effects upon gastric and pancreatic secretions, release of gastrointestinal hormones, gallbladder contraction and bronchoconstriction. It is present in amphibian gastric endocrine cells, avian proventriculus endocrine cells and avian brain. In mammals it is present mainly in nerve cells and fibers. The only mammalian endocrine cell shown to date to have bombesin is the P-cell in fetal lung. Bombesin is also found in mammalian brain, with its highest concentration in the hypothalamus. We examined several groups of human neuroendocrine neoplasms for the presence of bombesin by immunohistochemistry. Our findings indicate that bombesin is present 68% of bronchial carcinoids, 65% of pulmonary neuroendocrine carcinomas, 62% of neuroendocrine carcinomas of the skin, 5-10% of pheochromocytomas and extraadrenal paragangliomas and 35% of gastrointestinal carcinoids and neuroendocrine carcinomas. Parallel studies in a wide variety of non neuroendocrine neoplasms failed to reveal the presence of bombesin. We conclude that bombesin is a highly specific marker of neuroendocrine differentiation and thus a valuable tumor marker. Furthermore, its specificity compares favorably with another neuroendocrine marker, neuron specific enolase, an enzyme thought to be present only in neural tissues and neuroendocrine cells but recently found in non neural human tissues and non neuroendocrine neoplasms.

Bombesin↗

Postsurgical chylous ascites in sarcoidosis with portal hypertension.

A patient with extensive thromboses of portal and mesenteric veins and sarcoid of the liver developed recurrent pulmonary emboli, which necessitated the insertion of an umbrella into the inferior vena cava. Chylous ascites appeared shortly thereafter; the ascitic fluid fat content was strikingly reduced after reduction of dietary long chain triglycerides, but the ascitic fluid volume was reduced only after insertion of a peritoneovenous shunt (LeVeen). The shunt was found to be nonfunctioning 4 months later, but ascites did not recur. Seven years later, while eating a normal diet and still having a nonfunctioning shunt, he remains free of ascites. We postulate that iatrogenic obstruction of the inferior vena cava in the presence of mesenteric and portal vein thromboses, as well as obstruction of mesenteric lymphatics by sarcoid lymphadenopathy, led to the formation of chylous ascites and that establishment of adequate mesenteric and portal venous and/or lymphatic collateral circulation was responsible for his sustained improvement.

Biopsy↗

Atypias, dysplasias, and neoplasias of the esophagus and stomach.

Our understanding of the origin and evolution of gastrointestinal mucosal dysplasias and neoplasias has been greatly expanded in recent years by the marked increase in the number of endoscopic biopsies, which are facilitated by the use of flexible instruments with a remarkable safety record. The availability of specimens and the development of special procedures to examine them allows the detailed study of the normal and abnormal gastrointestinal mucosa, as determined by histochemical procedures. Similarly, immunocytochemistry has been used to determine the presence of oncofetal antigens as an expression of neoplastic transformation and/or evolution. Finally, the ease of repeat endoscopic procedures has permitted close observation of the natural or therapeutically modified history of mucosal lesions. The majority of the pathologic findings were in specimens obtained during endoscopic procedures ("grasp or pinch biopsies"), which generally yield superficial fragments of mucosa. Suction biopsies have been recently proposed as an alternative since such specimens contain portions of the whole mucosal layer and part of the submucosa. Our institution performs over 3,000 endoscopic procedures per year; the experience gathered with this material constitutes the basis for this review of esophageal and gastric preneoplastic and neoplastic mucosal lesions obtained by endoscopic and suction biopsies. Data obtained from conventional surgical specimens are also included.

Adenocarcinoma↗

Gastric parietal cell carcinoma--a newly recognized entity: light microscopic and ultrastructural features.

Three cases of gastric parietal cell carcinoma are described. Tumour cells are round to polygonal, with abundant eosinophilic, granular cytoplasm reactive with phosphotungstic acid haematoxylin and Luxol Fast Blue. Ultrastructurally the tumour cells are characterized by abundant mitochondria, tubulovesicles, intracellular canaliculi and intercellular lamina filled with undulated microvilli.

Aged↗

Immunocytochemical localization of keratin in normal, dysplastic and neoplastic cervical epithelium.

The PAP immunocytochemical technique utilizing specific keratin antibody was applied to paraffin sections from 36 cervical biopsies. Normal squamous epithelium and condylomas had similar patterns of keratin production with intense staining of intermediate and upper layers, while basal cells remained negative. Dysplasia, carcinoma in situ and infiltrating squamous carcinoma showed uneven distribution of keratin with the least amount seen in the areas with high mitotic rate and anaplasia. All large cell squamous carcinomas demonstrated presence of significant amounts of keratin. Squamous carcinomas of the small cell type were essentially keratin-free.

Adenocarcinoma↗

Amphicrine cells.

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Cell Differentiation↗