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Biomedical subjects

J Rode

Publications and source records attributed to J Rode.

At least 73 records · Page 4Linked to original sources

Vasitis nodosa and associated clinical findings.

To establish the prevalence of vasitis nodosa in patients who had undergone vasectomy segments of vas deferens resected from 40 patients at the time of vasectomy reversal were examined histologically and immunohistochemically. The findings were correlated with clinical history and postoperative outcome. Controls comprised segments of normal vas deferens excised at vasectomy. Twenty of the 40 vasovasostomy specimens showed vasitis nodosa; in 13 this was associated with sperm granulomas and in two with spermatocoeles. The vasitis nodosa was characterised by multiple small ductules extending from the central lumen of the vas into the muscle layers and adventitia. In 14 cases there was mucinous metaplasia of the epithelium lining the ductules. The number of nerve fibres in the submucosa and muscle layers was reduced after vasectomy. In patients with vasitis, however, hyperplasia of nerve fibres in the adventitia (16 of 20 cases) and formation of neuromas were seen. Nerve fibre hyperplasia was seen in only one, and sperm granulomas and spermatocoeles in none of the 20 specimens without vasitis nodosa. The development of vasitis nodosa was independent of the patients' age or the interval between vasectomy and reversal. The restoration of fertility did not seem to be affected by previous vasitis nodosa.

Adult↗

Biliary stent blockage with bacterial biofilm. A light and electron microscopy study.

Clogging of endoscopic stents necessitates their replacement in many patients with malignant obstructive jaundice and limits their use in benign strictures. We studied the basic mechanism of clogging to find ways to prevent it. We did light and electron microscopy studies of blocked and functioning stents, which were prepared so that organic structures would be preserved. The material blocking the lumina was composed of a matrix of bacterial cells and their fibrillar anionic extracellular products. Crystals of calcium bilirubinate, calcium palmitate, and cholesterol were embedded within this matrix. Bacterial cells were attached to the stent surface by a fibrillar matrix, suggesting that the initial event in stent clogging is the development of an adherent bacterial biofilm. Bacterial enzyme activity (beta-glucuronidase and phospholipase) leads to the deposition of crystals. The use of antibacterial plastics in the manufacture of stents may reduce bacterial adhesion and stent clogging.

Bacteria↗

The immunolocalization of protein gene product 9.5 using rabbit polyclonal and mouse monoclonal antibodies.

In order to assess the potential of protein gene product (PGP) 9.5 as a marker of the nervous and neuroendocrine systems, we examined its immunolocation in human, rat and guinea-pig tissues, using a rabbit polyclonal antiserum and two new mouse monoclonal antisera, I3C4 and 3IA3. Our results demonstrate immunoreactive PGP 9.5 in neurons and nerve fibres at all levels of the central and peripheral nervous system, in many neuroendocrine cells, in part of the renal tubule, in spermatogonia and Leydig cells of the testis, and in ova and in some cells of the pregnant and non-pregnant corpus luteum. In routinely processed tissues, standard immunohistochemical techniques using the polyclonal antibody demonstrated peripheral nerve fibres of all sizes with striking clarity.

Animals↗

[The prognosis of carcinoid tumors of the stomach].

Follow-up examinations were carried out in 55 patients with small carcinoid tumours in the stomach (diameter 0.5-1.7 cm). For the most part, the tumours were located within the body and fundus of the stomach, with only 3 being found in the antrum. Thirty-five of the 55 patients (63.6%) had multiple gastric carcinoids, while in 46 patients (83.6%) concomitant chronic atrophic gastritis was also present. Eight patients were treated surgically, while 47 patients were merely kept under endoscopic/bioptic surveillance. In 34 out of 40 patients in whom the diagnosis had been established more than 6 months previously (longest observation period 13 years), follow-up findings were available (7 surgical patients, 27 non-operated patients). The patients submitted to surgery (average follow-up period 3.5 years) are alive and free of complaints between 1 and 9 years post-op; no metastases have occurred, but a recurrent tumour has developed in a single patient. Among the 27 non-operated patients (average follow-up period 3.6 years), 3 have died of diseases unrelated to the carcinoid tumours, in none of the other patients has there been any change in the findings. On the basis of these results it is concluded that, in carcinoid tumours of the stomach with a diameter of less than 1.0 cm, surgical treatment is not absolutely necessary, and that, in comparison with the risks represented by surgical mortality and post operative morbidity, regular endoscopic/bioptic follow-up can be considered to be adequate.

Adult↗

Appendicitis revisited: a comparative study of Malawian and English appendices.

The incidence of appendicitis shows a marked variation between populations which has been attributed to dietary differences. Neural mechanisms and serotonin discharge from subepithelial neurosecretory cells have been previously implicated in pain referable to the appendix and appendicitis. Forty consecutive appendicectomy specimens from Malawi were studied by staining with haematoxylin and eosin, an alcian blue - PAS diastase sequence coupled with lead haematoxylin (PbH) and immunohistology for serotonin and NSE. The findings were compared with those in appendices removed at the Middlesex Hospital, London, to see if there were any differences between a population with a low risk of appendicitis (Malawi) and a high risk population (England). Acute transmural appendicitis was seen in fewer appendices from Malawi (27.5 per cent) than in English appendices (58 per cent). Subepithelial neurosecretory cells identified with PbH were present in 20 per cent of appendices from Malawi and 69 per cent of English appendices. These cells in both series showed immunohistochemical staining for serotonin. Nerve hyperplasia identified by staining for NSE in the appendix was present in 17.5 per cent and 81 per cent of non-inflamed appendices from Malawi and England respectively. Appearance of subepithelial neurosecretory cells and hyperplasia appear to be concomitants of an increased risk of appendicitis. Neural mechanisms may participate in adapting to a low residue diet and in some cases may generate appendicitis.

Appendicitis↗

Expression of the C-terminal flanking peptide of human progastrin in human gastroduodenal mucosa, G-cell hyperplasia and islet cell tumours producing gastrin.

Three antisera to the C-terminally extended form of gastrin or the C-terminal flanking peptide of progastrin were used in an attempt to investigate the post-translational processing of progastrin at the cellular level by light and electron microscopical immunocytochemistry. In the normal human gastric antrum, the G-cell secretory granules were found to contain both gastrin and the C-terminal progastrin determinants (progastrin 87-93, 87-95 and 93-101). Immunostaining of serial sections at the light microscopical level revealed that duodenal gastrin-containing cells also express the C-terminal progastrin determinants, as well as gastrin-34. In foetal tissue, cells containing C-terminal gastrin and the C-flanking peptide of progastrin were first seen at 8 weeks of gestation, in the duodenum. They were not found in the stomach until the 11th week. In hyperplastic G-cells and in gastrin-producing tumour cells, the level of C-terminal peptide immunoreactivity was variable and often lower than that seen in normal antrum and only minimal immunoreactivity could be detected using electron immunocytochemistry. This was interpreted as representing altered post-translational processing of progastrin in modified G-cells.

Adenoma, Islet Cell↗

Carcinoid tumour of stomach and primary hyperparathyroidism: a new association.

Three cases of carcinoid tumour of the stomach associated with primary hyperparathyroidism had the clinical and pathological features of a pluriglandular syndrome. Two of the patients showed multiple small polypoid carcinoids in the non-antral stomach, in conjunction with a parathyroid adenoma in one and parathyroid hyperplasia in the other case. One of these patients was also suffering from pernicious anaemia. A third patient had a large metastasising carcinoid arising in the gastric body and a parathyroid adenoma. Immunohistochemical stains for PGP 9.5 were positive in the carcinoids of all three cases. In all cases the carcinoids showed immunoreactivity for gastrin. A positive family history of endocrine hyperplasia and neoplasia was established in one case. It is suggested that patients with gastrointestinal carcinoids and their families should be evaluated for hyperparathyroidism, and patients with hyperparathyroidism presenting with upper gastrointestinal symptoms should undergo endoscopy to rule out gastric carcinoid tumours.

Adult↗

Endocrine differentiation of extra-pulmonary small cell carcinoma demonstrated by immunohistochemistry using antibodies to PGP 9.5, neuron-specific enolase and the C-flanking peptide of human pro-bombesin.

Several recent studies have confirmed the endocrine nature of small cell carcinoma of the lung. In extra-pulmonary sites, small cell 'undifferentiated' carcinomas have classical morphological features similar to their pulmonary counterpart. We therefore investigated, using immunocytochemistry, the possibility that the non-pulmonary neoplasms may also be endocrine in nature. Sections of 29 small cell carcinomas from oesophagus, stomach, larynx, colon and urinary bladder were immunostained using antisera to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), cytokeratin, leucocyte common antigen and peptides including bombesin, the C-flanking peptide of human probombesin, adrenocorticotrophic hormone, neurotensin, calcitonin and pancreatic polypeptide. All the tumours showed immunoreactivity for at least one of the two general endocrine markers PGP 9.5 and NSE. Twenty-three of the 29 cases were immunoreactive for PGP 9.5, 27 for NSE. All were positive for cytokeratin and negative for leucocyte common antigen. Of the regulatory peptides, immunoreactivity was obtained with antisera to bombesin (one case), the C-flanking peptide of human pro-bombesin (14 cases), adrenocorticotrophic hormone (one case) and calcitonin (three cases). No PGP 9.5-, NSE- or peptide-like immunoreactivity was detected in 25 control tumours from similar sites, including lymphomas and poorly differentiated tumours. These results suggest that non-pulmonary small cell carcinoma has an endocrine character.

Adrenocorticotropic Hormone↗

Duodenal gangliocytic paragangliomas: a study of 10 cases with immunocytochemical neuroendocrine markers.

Ten cases of duodenal paraganglioma were studied by conventional histologic and immunocytochemical techniques at both light and electron microscopic levels. Histologically, mixtures of epithelial, ganglion, and spindle cells were seen. In all of the cases immunoreactivity for neuron-specific enolase (NSE) and protein gene product (PGP) 9.5 was seen in each component. Pancreatic polypeptide immunoreactivity was detected in eight cases, mainly in epithelial cells. Somatostatin immunoreactivity was present in epithelial and ganglion cells in nine cases. In seven cases immunoreactivity for neurofilaments, a marker for neurons, was seen in ganglion and spindle cells. However, immunoreactivity for chromogranin, a protein found in endocrine storage granules, was found in only two cases, and the staining was confined to well-granulated epithelial cells. The spindle cells were immunostained only for neuronal markers, NSE and neurofilaments, and the glial marker S-100 protein.

Duodenal Neoplasms↗

Pernicious anaemia and mucosal endocrine cell proliferation of the non-antral stomach.

There is a recognised association between pernicious anaemia and the development of gastric carcinoma, endocrine cell hyperplasia, and carcinoid tumour. Multiple endoscopic biopsies from the body mucosa of seven patients with pernicious anaemia showed small intestinal metaplasia with varying degrees of inflammation, fibrosis, and expansion of the lamina propria. Using conventional silver and lead stains, endocrine cells were inconspicuous. Staining for the general neural and neuroendocrine markers NSE and PGP 9.5 revealed a proliferation of endocrine cells in the epithelium and isolated clumps of endocrine cells in the lamina propria. The clumps were composed of two cell types, either small or large. Some of these endocrine cells showed gastrin, 5HT, VIP and substance P immunoreactivity of varying intensity. Ultrastructurally nine morphologically distinct types of granules were found some of which correlated with the immunohistochemistry. Some separate islands were composed solely of endocrine cells while others had a definite neural component, suggesting that the former arise from 'budding off' of enteroendocrine cells and the latter originate from the neuroendocrine cells of the lamina propria plexus. Thus there may be a dual origin of carcinoid tumours. Carcinoid tumours associated with pernicious anaemia tend to be multifocal and are infrequent. Less than 50 such cases have hitherto been reported. Our findings of endocrine cells proliferations in seven cases of pernicious anaemia indicate that this may be an adaptive change that occurs frequently and provides the basis on which carcinoids, less frequently, develop.

Adult↗

Measuring S100 protein and neurone specific enolase in melanocytic tumours using video image analysis.

Using a computed video image analysis system, the staining intensity for both neurone specific enolase (NSE) and S100 protein was measured in sections from 19 malignant melanomas and 16 benign melanocytic lesions. The results of this study confirm previous reports that NSE and S100 protein are useful markers for malignant melanoma. NSE staining intensity in the cases of malignant melanoma was significantly higher than that in benign naevi (p = 0.011). Intensity of staining for S100 protein was not significantly higher in the malignant melanomas. There was, however, a significant S100 gradient when comparing superficial and deep intradermal portions of these tumours (p = 0.003). This feature was not seen in benign naevi. The greatest intensity of S100 protein staining was found in the deeper portions of the malignant melanomas. This gradient difference was not seen with staining for NSE. Although it seems that the overall intensity of staining for NSE is more effective in differentiating between benign and malignant lesions, the difference in staining intensity between the superficial and deep portions of the tumour may be the better indicator of adverse behaviour in lesions in which the diagnosis of malignancy is uncertain.

Humans↗

Granular cell tumour of the common bile duct.

Granular cell tumors are a rare cause of benign biliary stricture. A case is reported which is unusual in that the diagnosis was made before the onset of jaundice. We emphasize the importance of accurate histology of biliary strictures, to eliminate confusion between those of benign and malignant nature and to ensure that the appropriate management is undertaken. Immunohistochemical evidence for the neural origin of this rare tumour is presented.

Adult↗

Neural markers in carcinoma of the lung.

Small cell carcinoma (SCC) is considered to be of neuroendocrine origin. Neurone specific enolase (NSE) and PGP 9.5 are markers of neural and neuroendocrine differentiation. S-100 protein is a marker of glial differentiation. The expression of these markers in endobronchial biopsy and lung tumour resection specimens was studied to see if any diagnostic, prognostic or therapeutic implications would emerge. Zamboni fixed endobronchial tumour biopsy specimens from 20 patients were examined. Twelve of these were cases of SCC and 8 were non-SCC. Of the 12 SCC, 7 were positive for NSE, 6 for PGP 9.5 and 5 for S-100 protein. Cases which showed a positive reaction for NSE had a mean survival of 9.1 months compared with 3.9 months for those with a negative reaction, but the number of cases is too small to assign any statistical significance. There was no difference in survival times between positive and negative reactors for PGP 9.5 and S-100 protein. All 8 cases of non-SCC showed positive reactions to all three markers. Of 32 formalin fixed lung tumour resection specimens 6 were cases of SCC, 25 non-SCC and 1 a chemodectoma. Three of the 6 cases of SCC showed positive staining for NSE, 3 for PGP 9.5 and 1 for S-100 protein. Of the 25 non-SCC, 10 were positive for NSE, 12 for PGP 9.5 and 6 for S-100 protein. The 1 chemodectoma stained positively for all three markers. Neuroendocrine markers are of little value in differentiating SCC from non-SCC. Positive staining for NSE in SCC may be an indicator of prolonged survival but further investigation is required.

Adenocarcinoma↗

PGP 9.5, a new marker for human neuroendocrine tumours.

PGP 9.5 is a soluble protein isolated from brain and is a general marker for neuronal and neuroendocrine tissue. Its function is not known. Until now neurone specific enolase (NSE) has been the only general marker for the paracrine system and tumours derived from it. Seventy-four neuroendocrine tumours, 17 melanocytic naevi, 51 melanomas and four granular tumours were stained immunohistochemically for PGP 9.5 and NSE. A variety of pulmonary and non-neuroendocrine tumours were also stained. Two so-called goblet cell carcinoids of the appendix were included in the series. Using NSE 59/74 neuroendocrine tumours were positive and 58/74 stained for PGP 9.5. In combination 63/74 of these tumours were positive for either NSE or PGP 9.5 or both. Staining for PGP 9.5 was better for demonstration of nerves in routinely processed material than was staining for NSE. Twenty-one out of 43 primary melanomas stained for PGP 9.5 and 36 showed staining for NSE. Only two of eight metastatic melanomas melanocytic stained for PGP 9.5 while seven of these eight stained for NSE. Six of 17 melanocytic naevi stained for PGP 9.5 and five stained for NSE. All four granular cell tumours stained for PGP 9.5 and NSE. Both "goblet cell carcinoids' of the appendix were negative for NSE and PGP 9.5. Fifteen out of 32 pulmonary cancers showed staining for either marker and no non endocrine tumour showed any specific staining. Staining for PGP 9.5 is a valuable additional probe in the exploration of the paracrine system and the diagnosis of tumours arising from it.

Humans↗

Neurone specific enolase and S100 protein as possible prognostic indicators in melanoma.

Fourteen cases of primary melanoma and 25 of their subsequent metastases were stained for Neurone Specific Enolase (NSE) and S100 protein. Intensity of staining for NSE and S100 protein broadly corresponded in 11 of the primary lesions and was disparate in three. Staining intensity for NSE or S100 was independent of tumour thickness. Primary lesions showing marked or moderate staining for NSE and S100 protein took a shorter time to metastasize than those showing slight or no staining. Assessment of staining intensity for NSE and S100 thus identified prognostic categories corresponding to disease free interval obtained by division according to tumour thickness. Staining intensity for S100 protein appears to give a clearer indication as to expectation of disease free interval. Staining intensity in individual cases showed an increase both for NSE and S100 protein between primary and metastatic lesions. The data presented are not sufficient to assign statistical significance but may lead to the incorporation of functional studies into the pathological assessment of malignant melanocytic lesions. The simultaneous occurrence of a functional neuronal and Schwann cell marker in melanoma is discussed.

Adult↗