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Biomedical subjects

N B Ibrahim

Publications and source records attributed to N B Ibrahim.

At least 37 records · Page 2Linked to original sources
PubMed1991

Topographical localisation of endothelin mRNA and peptide immunoreactivity in neurones of the human brain.

The distribution of endothelin mRNA and immunoreactivity in the human brain was investigated using the technique of in situ hybridization and immunocytochemistry. Cryostat sections from 22 cases of neurologically normal adult human brain, collected 3-7 h post-mortem were hybridized with 35S-labelled complementary (c)RNA probes prepared from the 3' non-coding region of endothelin-1 cDNA, and the chromosomal genes encoding endothelin-2 and -3. In situ hybridization with all three cRNA probes revealed labelled neuronal cell bodies in laminae III-VI of the parietal, temporal and frontal cortices. Labelled cells were also seen, scattered throughout the para- and periventricular, supraoptic and lateral hypothalamic nuclei, the caudate nucleus, amygdala, hippocampus, basal nucleus of Meynert, substantia nigra, raphe nuclei, Purkinje cell layer of the cerebellum and in the dorsal motor nuclei of the vagus of the medulla oblongata. The distribution of neurones immunoreactive to endothelin was similar to that of endothelin mRNA, although fewer immunoreactive cells throughout the brain, were noted. Immunoreactive fibres were present mainly in the cortex and hypothalamus, and to a lesser extent in the brain stem. Combined in situ hybridization and immunocytochemistry on the same section revealed the presence of endothelin-1 mRNA and immunoreactivity in the same cortical neuronal cell. Colocalisation studies in the cortex revealed endothelin-1 mRNA and immunoreactivity in a number of cells which also expressed neuropeptide Y mRNA and immunoreactivity. In the hypothalamus and basal nucleus of Meynert endothelin immunoreactivity was colocalised to a subset of neurophysin- and galanin-immunoreactive cell bodies respectively. Endothelin mRNA and immunoreactivity was also seen in some blood vessel endothelial cells. The findings of endothelin mRNAs and immunoreactivity in heterogenous neuronal populations further emphasises the potential role of endothelin as a neuropeptide, probably having diverse actions in the nervous system of man.

Adult↗
PubMed1990

Substance P-, calcitonin gene-related peptide- and C-flanking peptide of neuropeptide Y-immunoreactive fibres are present in normal synovium but depleted in patients with rheumatoid arthritis.

By means of antisera to cytoplasmic components of nerve fibres and neuropeptides which are known to be present in sensory or sympathetic nerves we have examined the distribution of both total and different types of nerve fibres in normal and inflamed human synovial tissue. Samples of synovia were obtained at surgery from five normal and five rheumatoid patients (age range 10-77 years). In order to map the overall neural innervation of the synovium, antiserum to the general neuronal marker protein gene product 9.5 was employed. Substance P and calcitonin gene-related peptide antisera were employed to identify sensory fibres and antisera to the C-flanking peptide of neuropeptide Y to distinguish sympathetic nerves. In normal synovium protein gene product 9.5-immunoreactive fibres were numerous, in particular, the vasculature was densely innervated. Free protein gene product 9.5-immunoreactive fibres were less numerous but were present in all synovia examined, and in many cases these extended to the intimal layer. Neuropeptide immunostaining was predominantly found in perivascular networks. Fibres immunoreactive for the C-flanking peptide of neuropeptide Y were exclusively located around blood vessels whereas free fibres were immunoreactive for substance P or calcitonin gene-related peptide. As with free protein gene product 9.5-immunoreactive fibres, fibres expressing substance P or calcitonin gene-related peptide immunoreactivity were often seen in the intimal cell layer. In rheumatoid arthritis a similar innervation to that seen in normal synovium was apparent in the deep tissue but fibres immunoreactive for protein gene product 9.5, the C-flanking peptide of neuropeptide Y, substance P or calcitonin gene-related peptide were not visible in the more superficial tissues or the intimal cell layer. In addition, immunostaining of neuropeptides in the deep tissue was weaker in the diseased tissues than in normal controls. The data unequivocally demonstrate that synovial tissues are richly innervated and confirm the presence of both sensory and sympathetic nerves. The absence of nerves which innervate the superficial synovium in rheumatoid arthritis might suggest that there is increased release of substance P, calcitonin gene-related peptide and the C-flanking peptide of neuropeptide Y, reducing the stores in the nerves to levels below that detectable by immunocytochemistry. However, since protein gene product 9.5-immunoreactive nerves were not seen in the inflamed tissue it is probable that synovial growth outflanks neural growth and consequently as the disease progresses neural structures become restricted to deeper tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Localisation of mRNA and co-expression and molecular forms of GRP gene products in endocrine cells of fetal human lung.

The presence of bombesin (gastrin-releasing peptide, GRP)-like immunoreactivity in mucosal endocrine cells of human fetal lung is well established. In this study we have investigated the localisation of pro-GRP mRNA and GRP gene products and compared the distribution and levels of extractable GRP- and C-terminal flanking peptide of human pro-GRP-like immunoreactivity in order to verify synthesis and to investigate their coexistence and molecular forms. Human fetal lungs (14 to 23 weeks gestation) were immunostained, and extracts were assayed using region-specific antisera to pro-GRP. Additional antisera to chromogranin and protein gene product 9.5 (PGP 9.5) were used for immunostaining by the peroxidase anti-peroxidase technique and for double immunofluorescence staining using antisera raised in two species. Immunoreactivity for both bombesin (GRP) and flanking peptide was seen mainly in the same endocrine cells, but more cells were stained with antisera to flanking peptide than with antiserum to bombesin (GRP). In situ hybridisation showed that pro-GRP mRNA was present and thus synthesis of the peptides was taking place. Endocrine cells and nerve fibres were PGP 9.5-immunoreactive, and a subset of cells was immunoreactive for bombesin gene products. Radioimmunoassay and chromatography show that pro-GRP is present in both the uncleaved and cleaved forms, and, in agreement with immunocytochemistry results, that an excess of C-terminal peptide of pro-GRP is detectable. It is therefore concluded that GRP-like peptides and flanking peptide are co-localised in human pulmonary endocrine cells, but the latter is found in larger concentrations than free GRP. Thus GRP-like peptides may be secreted separately from the flanking peptide(s) of pro-GRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Gel↗
PubMed1987

Extraadrenal paragangliomas. An immunocytochemical and ultrastructural report.

Although the majority of extraadrenal paragangliomas are nonfunctional, some of these tumors are associated with hormone production and clinical symptoms, notably hypertension. The authors have investigated 22 paragangliomas, five of which were diagnosed as clinically functional in a light microscopic immunocytochemical and electron microscopic study (nine cases). Histologically, all the paragangliomas exhibited similar features, with a "Zellballen" pattern of polygonal cells. All 22 cases were strongly immunoreactive to protein gene product 9.5 (PGP 9.5) antisera and moderately reactive to antineuron-specific enolase (NSE) sera. Ten cases (five functional) were focally immunoreactive to antichromogranin sera. Seven cases (four functional) were immunoreactive to neuropeptide Y and enkephalin antisera, and six (five functional) to tyrosine hydroxylase antisera. The clinically functional tumors expressed at least two of the antigens, enkephalin, neuropeptide Y, or tyrosine hydroxylase, whereas none of the 17 nonfunctional possessed more than one of these. Electron microscopic study revealed cells from all the nine cases studied to contain secretory granules. Granule sizes ranged from 100 to 280 nm and the morphologic examination of the secretory granules generally showed a dense core with a membrane-bound halo of variable size. Secretory granules were observed in the five functional cases and these were larger (220-280 nm) than those seen in the nonfunctional tumor cells (100-180 nm). Also, tumor cells from the functional cases contained numerous dilated mitochondrial profiles.

Adult↗
PubMed1987

Immunohistochemical markers of small cell carcinoma and related neuroendocrine tumours of the lung.

A selected group of 263 pulmonary neuroendocrine tumours comprised 156 small cell carcinomas, five combined cell carcinomas, nine atypical carcinoid/small cell carcinomas, 32 atypical carcinoids, ten large cell/small cell carcinomas, and 51 carcinoid tumours. These were compared with a group of 109 non-small cell carcinomas, using four markers of neuroendocrine differentiation to determine differences in reactivity between the two groups and among the variants of neuroendocrine tumour. The antibodies used were neuron-specific enolase (NSE), protein gene product (PGP) 9.5, human bombesin, and the C-terminal flanking peptide of human bombesin (CTP). Most small cell carcinomas, carcinoid tumours, and atypical carcinoid variants showed immunoreactivity for both NSE and PGP 9.5 but a significant number of non-small cell carcinomas, mainly squamous cell carcinomas, were also positive (11 and 35 per cent, respectively). Bombesin was specific for neuroendocrine tumours, being demonstrable in 35 per cent carcinoids and 24 per cent small cell carcinomas, but staining was focal and often confined to scattered cells. Diffuse strongly positive immunoreactivity for CTP was seen in the majority of malignant neuroendocrine tumours, but only 12 per cent of carcinoid tumours were positive and non-small cell carcinomas were negative. CTP is therefore of potential value as a specific marker of malignant neuroendocrine tumours, particularly if the amount of biopsy material is limited and the tumour is an unusual variant, such as atypical carcinoid or large cell-small cell carcinoma.

Biomarkers, Tumor↗
PubMed1987

Expression of the C-terminal peptide of human pro-bombesin in 361 lung endocrine tumours, a reliable marker and possible prognostic indicator for small cell carcinoma.

Small cell carcinoma of the lung is a highly malignant tumour. Its known biological products which include bombesin, do not allow the prediction of tumour behaviour. Molecular biology has revealed the amino acid sequence of human pro-bombesin, which consists of a signal peptide, the bioactive bombesin molecule and a C-terminal peptide. We have raised a rabbit antiserum to the first (N-terminal) 21 amino acids of the predicted C-terminal peptide. A total of 505 (361 neuroendocrine) surgically resected pulmonary tumours were evaluated for the presence of immunoreactive bombesin and C-terminal peptide. Strong immunostaining was obtained with the antiserum to the C-terminal peptide of human pro-bombesin in 70% of the small cell carcinomas (175/250), in 63% of atypical (aggressive) carcinoids (31/49) but only in 16% of benign carcinoids (10/62). In contrast, bombesin immunostaining was focal and only moderately strong and the relative proportion of positive cases was quite evenly distributed amongst the neuroendocrine tumours: 35% of carcinoids (22/62), 22% of atypical carcinoids (11/49) and 25% of small cell carcinoma (62/250). None of the squamous, adeno, or large cell undifferentiated carcinomas were immunoreactive for bombesin or the C-terminal peptide. Radioimmunoassay and chromatography of extracts of tumours recovered from wax blocks revealed high concentrations of C-terminal peptide immunoreactivity (241 +/- 66 pmol/g of tissue) in all 12 small cell carcinomas studied, moderate concentrations in carcinoid tumours (50 +/- 7 pmol/g) and none in non-small cell carcinomas. Patients with tumours showing immunoreactivity to the C-terminal peptide of human pro-bombesin had a significantly shorter survival time than those without immunoreactive peptide (185 +/- 16.49 days, mean +/- SEM, and with 1128 +/- 226 days, respectively P greater than 0.02). The apparent presence of the C-terminal peptide of human pro-bombesin in higher concentrations than bombesin in the more malignant class of endocrine tumours, mainly small cell carcinomas associated with the poorest prognosis, suggests that the antiserum to this C-terminal peptide is not only a useful pathological marker but may prove to be of value in investigating the biological behaviour of small cell carcinomas and predicting the clinical course of the disease.

Bombesin↗
PubMed1986

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↗
PubMed1985

Lymphangiosarcoma of the hand arising in a pre-existing non-irradiated lymphangioma.

Lymphangioma is an uncommon lesion which is widely believed not to undergo malignant change. Lymphangiosarcoma is even rarer and most of the cases reported in the literature were encountered in the setting of chronic lymphoedema, although occasional cases have been reported in irradiated lymphangiomata. This brief communication describes a case of multifocal lymphangiosarcoma arising in a non-irradiated, long standing lymphangioma of the hand. To our knowledge no similar case has been reported previously in the English literature, which is briefly reviewed.

Adipose Tissue↗
PubMed1985

Leiomyomas of the lower respiratory tract.

Leiomyomas account for about 2% of benign tumours of the lower respiratory tract. From the relatively few cases reported in the literature, it appears that these tumours most commonly occur in the fourth decade, although one third of patients are under the age of 20 years. The distribution of leiomyomas favours the distal part of the tracheobronchial tree and the most common site for tracheal lesions is the membranous portion of the lower third. Over 90% of pulmonary parenchymal leiomyomas, which themselves are more common in women, are incidental findings on chest radiographs whereas bronchial lesions are important causes of irreversible lung damage. Tracheal lesions may present as bronchial asthma. Accurate early diagnosis rests on a high index of clinical suspicion and histological examination of bronchoscopic biopsy specimens or frozen section material obtained at exploratory thoracotomy. Treatment could be conservative surgery, but 65% of reported cases have been managed by lobectomy or pneumonectomy as a result of advanced irreversible lung disease or unawareness of the benign nature of the lesion.

Bronchial Neoplasms↗
PubMed1984

Extrapulmonary oat cell carcinoma.

Primary extrapulmonary tumors with histologic features indistinguishable from bronchogenic oat cell carcinoma are appearing with increasing frequency in the literature. These tumors have been described in the esophagus, stomach, pancreas, larynx, hypopharynx, salivary glands, nasal cavity and paranasal sinuses, thymus, small and large bowel, uterine cervix, endometrium, breast, prostate, urinary bladder, and skin. It is now widely believed that oat cell carcinoma is a poorly differentiated counterpart of carcinoid tumor and that both originate from an endocrine cell system. In this article, the authors review all cases of extrapulmonary oat cell carcinomas, which they were able to find in the English literature, and report personally studied examples of these tumors, occurring in the esophagus, stomach and urinary bladder. A closely related, if not identical, tumor arising in the skin is also described. It is emphasized that a wider recognition of these tumors is likely to lead to their more frequent diagnosis and possible treatment.

Adult↗
PubMed1984

Experience of thin cutaneous melanomas (less than 0.76 mm and less than 0.85 mm thick) in a large plastic surgery unit: a 5 to 17 year follow-up.

The detailed histological findings of 728 melanoma patients treated at Frenchay Hospital during the period 1967 to 1978 have been fully reviewed and analysed. Of these, 75 patients with lesions less than 0.76 mm thick and 15 with lesions greater than 0.75 mm and less than 0.85 mm thick have been identified using a computerised data base. The general practitioners of all the patients in the series have been approached and the clinical histories found in nearly every case (69/75 and 15/15) thus providing a follow-up period of 5 to 17 years. A number of fatal melanomata have been found in these two groups. The histopathological features have been related to the known prognosis in an attempt to characterise the lethal lesions. No statistically significant relationship could be found between prognosis and any histological feature, including specifically the amount of regression within the lesion. However, it was found that assessment of the ratio of the uninvolved dermis beneath the tumour to tumour thickness itself might prove helpful in future case evaluation.

Adolescent↗
PubMed1984

A Melanoma Registry based on a computer-run word and data processing system.

A Melanoma Register, previously organised on a filing card system, has been largely transferred to a computer which utilises both word and data processing programs. This transfer has revolutionised not only the analytical potential of the material, but the follow up of all patients, both old and new. The system is applicable to many other tumours and diseases.

Computers↗
PubMed1983

Oat cell carcinomas of the oesophagus: a clinico-pathological study of 23 cases.

A review of 955 patients with primary oesophageal carcinoma treated with this hospital revealed 23 cases of small cell anaplastic carcinoma of the oat cell type. Fifteen were females and eight were males. In each case the histological appearances were identical to those of the oat cell carcinoma which is much more commonly encountered in the lung. In none of these cases was there any evidence of a primary oat cell carcinoma outside the oesophagus. Argyrophilic granules were seen in three cases and granules of the neurosecretory type were present in five. We conclude that neither of these findings is a prerequisite for making a diagnosis of oesophageal oat cell carcinoma. The histogenesis of this tumour is reviewed and briefly discussed.

APUD Cells↗