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C F Johnston

Publications and source records attributed to C F Johnston.

At least 37 records · Page 2Linked to original sources
PubMed1997

Expression of apoptosis-suppressing gene bcl-2 in human carotid body tumours.

That carotid body tumours have a genetic aetiology is suggested by the familial occurrence of the neoplasm. Environmental influences are also implied by the fact that the tumour is more common in those living at high altitudes. However, the mechanism of development of sporadic tumours occurring at sea level, which account for the majority of cases, remains unknown. It has become increasingly clear that the deregulation of programmed cell death is a critical component in multistep tumourigenesis. Previous studies have demonstrated a high frequency of bcl-2 expression in the tumours arising from cells derived from the neural crest and tumour cell lines of neural origin. This investigation was undertaken to determine whether similar molecular events occur in human carotid body tumours. Western and Northern analysis revealed that the tumours expressed the 26 kD protein and bcl-2 transcripts. Immunoperoxidase staining, using a monoclonal anti-bcl-2 antibody, revealed that 11 out of 13 specimens stained positively for bcl-2. These results suggest that the deregulation of programmed cell death may be a critical component in the multistep tumourigenesis of carotid body tumours and that the expression of oncoprotein bcl-2 may contribute to the generation of such tumours.

Adolescent↗
PubMed1997

Ontogenetic expression of chromogranin A and its derived peptides, WE-14 and pancreastatin, in the rat neuroendocrine system.

The ontogenetic expression of chromogranin A (CgA) and its derived peptides, WE-14 and pancreastatin (PST), was studied in the rat neuroendocrine system employing immunohistochemical analysis of fetal and neonatal specimens from 12.5-day embryos (E12.5), to 42-day postnatal (P42) rats. CgA immunostaining was first detected in endocrine cells of the pancreas, stomach, intestine, adrenal gland and thyroid at E13.5, E14.5, E15.5, E15.5 and E18.5, respectively. PST-like immunoreactivity was detected in endocrine cells of the pancreas at E13.5, stomach, intestine at E15.5, adrenal gland at E17.5 and thyroid at E18.5. WE-14 immunoreactivity was first observed in the immature pancreas at E15.5, mucosal cells of the stomach at E15.5, scattered chromaffin cells in the immature adrenal gland and mucosal cells of the intestine at E17.5 and thyroid parafollicular cells at E18.5. These data confirm that the translation of the CgA gene is regulated differentially in various neuroendocrine tissues and, moreover, suggests that the post-translational processing of the molecule is developmentally controlled.

Adrenal Medulla↗
PubMed1997

Cholinergic, serotoninergic and peptidergic components of the nervous system of Haematoloechus medioplexus (Trematoda, Digenea), characterised by cytochemistry.

Cholinergic, serotoninergic and peptidergic neuronal pathways have been demonstrated in whole-mount preparations of the frog-lung digenean trematode, Haematoloechus medioplexus, using enzyme cytochemical methodologies and indirect immunocytochemical techniques in conjunction with confocal scanning laser microscopy. All 3 classes of neuroactive substance were found throughout both central and peripheral elements of a well-developed orthogonal nervous system. Peptidergic immunoreactivity was particularly strong, using antisera directed to native flatworm neuropeptides, neuropeptide F, and FMRF amide-related peptides (FaRPs), and there was significant overlap in the staining with that for cholinergic components. The serotoninergic system appeared quite separate, with the staining localised to a different set of neurons.

Animals↗
PubMed1997

Comparative analysis of the distribution of bradykinin-, GYIRFamide- and neuropeptide F-like immunoreactivities in the monogenean, Diclidophora merlangi.

An indirect immunocytochemical technique combined with confocal scanning laser microscopy has been used to demonstrate immunoreactivities to the nonapeptide, RPPGFSPFR (bradykinin, BK) and the endogenous flatworm regulatory peptide, GYIRFamide in the nervous system of the monogenean, Diclidophora merlangi. In addition, a simultaneous double-labelling technique was employed to examine possible co-localization of GYIRFamide- and neuropeptide F (NPF) immunoreactivities, using antisera to the C-terminal nonapeptide-amide of NPF (Moniezia expansa, FAIIGRPRF. NH2). BK immunostaining was restricted to a small population of nerve cells and associated fibres within the ventral nerve cords and to 2 pairs of nerve cells innervating the cirrus and the pharynx, respectively. No immunopositive nerve cells and fibres were identified within the brain or in association with the female reproductive apparatus. In contrast, GYIRFamide staining was abundant throughout the central and peripheral nervous systems, and appeared similar to the staining pattern revealed using an FMRFamide antiserum. GYIRFamide immunoreactivity was localized to nerve cells and fibres within the paired cerebral ganglia and the longitudinal ventral, dorsal and lateral nerve cords and their numerous interconnecting transverse commissures. The plexuses of the buccal suckers, pharynx and clamps of the haptor were strongly immunopositive for GYIRFamide, as were nerve cells innervating the ootype, the oviduct and the vitelline reservoir of the reproductive apparatus. Double-labelling experiments indicated an apparent co-localization of GYIRFamide and NPF immunoreactivities.

Animals↗
PubMed1997

Carcinoma of the bronchus in the Yorkshire region of England 1976-1990: trends since 1984.

We wished to confirm that, in patients with lung cancer, trends in demography and histology, together with modest improvements in survival, first seen in the 1976-1983 cohorts, continued to 1990. All lung cancer patients resident in Yorkshire are notified to the Cancer Registry, whose database was analysed for this report. A total of 38,275 patients were notified. There was no change in annual notification for males but an increase from 513 to 815 annual notifications in females between 1976 and 1990. Mean age increased by 3 yrs, in males to 67.4 yrs and in females to 67.2 yrs. Histological confirmation rate increased from 43% to 60% (mean age from 60.8 to 64.5 yrs). Annual notifications of adenocarcinoma increased consistently from 108 to 253. Two year surgical survival improved from 37.4 to 44.3%, doubling in subjects aged > or = 70 yrs to 43.8%. Over the 15 year period, there was no improvement in survival aged < 60 yrs, but a significant improvement in the 60-69 and > or = 70 yrs age groups. Analysis of survival by quartiles showed significant improvement at all levels (first interval 20 to 24 days, median 79 to 91 days, third interval 224 to 266 days). The modest improvement in outlook was confirmed, confined to older subjects after 1983, and partially masked by increasing age. Survival after surgery is now independent of age.

Adenocarcinoma↗
PubMed1997

Expression of the apoptosis-suppressing gene BCL-2 in pheochromocytoma is associated with the expression of C-MYC.

It has become increasingly clear that deregulation of programmed cell death is a critical component in multistep tumorigenesis. Previous studies have demonstrated a high frequency of Bcl-2 expression in tumors arising from cells derived from the neural crest and in tumor cell lines of neural origin. The present investigation was undertaken to determine whether similar molecular events occur in human pheochromocytoma. With the aim of determining the potential role of apoptosis in the pathogenesis of this tumor, we assessed proto-oncogene Bcl-2 and c-myc protein products as well as Bcl-2 messenger RNA levels in a collection of such tumors. Western blot analysis revealed that such tumors expressed the 26 kDa Bcl-2 (5 of 8 cases) and the 64 kDa c-Myc (7 of 8 cases) proteins. Northern blot analysis detected the Bcl-2 transcripts in 6 of 8 tumors. Immunoperoxidase staining, using a monoclonal anti-Bcl-2 antibody, was positive in 18 (82%), including 5 malignant tumors, of the 22 specimens examined. This Bcl-2 immunoreactivity was seen in 14 of 18 (78%) sporadic tumors, including 2 that were extra-adrenal, and all familial tumors. Of the 22 tumor samples examined for c-Myc protein, 20 (91%) tumors were positive. Our results suggest that deregulation of programmed cell death may be a critical component in the multistep tumorigenesis of human pheochromocytoma. The genetic complementation of simultaneously deregulated Bcl-2 and c-myc may be implicated in this process.

Adolescent↗
PubMed1997

Regulatory peptides and other neuroendocrine markers in medullary carcinoma of the thyroid.

Medullary thyroid carcinoma (MTC) is an APUDoma (APUD refers to amine precursor uptake and decarboxylation) arising from the parafollicular cells. Diarrhoea has been reported in some 30% of patients, variously attributed to excess production of calcitonin (CT), serotonin (5-HT), vasoactive intestinal peptide (VIP) or other factors. The regulatory factors in MTC were examined employing immunocytochemistry and RIA to tumours and their extracts. The patients were followed up for more than 15 years. CT and calcitonin gene-related peptide were universally expressed in all the tumours. The neuroendocrine markers chromogranin A (and its fragments pancreastatin and WE-14), neurone-specific enolase, protein gene product 9.5 and carcino-embryonic antigen were found in the majority of MTCs and might be useful as immunocytochemical markers. 5-HT, substance P, neurokinin A, glucagon and VIP could not be detected, excluding them as candidates in the diarrhoea of MTC.

Apudoma↗
PubMed1996

The peptidergic nervous system of the triclad turbellarian, Bdelloura candida (Maricola, Bdellouridae): an immunocytochemical study using an antiserum raised to an endogenous neuropeptide, GYIRFamide.

The organisation of the nervous system of Bdelloura candida (Tricladida, Maricola, and Bdellouridae) was studied by immunocytochemistry, by using an antiserum raised to the authentic B. candida FMRFamide-related peptide (FaRP), GYIRFamide. Immunostaining was intense and abundant throughout both the central and peripheral nervous systems, being localised to the brain, the longitudinal nerve cords and their transverse and lateral connections, the pharyngeal plexus, the extensive sub-epidermal and sub-muscular plexuses, and elements of the reproductive apparatus. Compared to an earlier anatomical investigation of this species, and also to the neuroanatomy of other triclad turbellarians, the pattern of GYIRFamide-immunoreactivity reveals differences in the following aspects: the shape and structure of the brain, the distribution of longitudinal nerve cords and their relationships with the peripheral nervous system, the structure and distribution of the lateral nerves and the transverse connectives between the longitudinal nerve cords, organisation of the pharyngeal nervous system, and innervation of the eyespots and epidermal sensory structures. Although this study focuses on a descriptive account of the neuroanatomy of Bdelloura candida, by using anti-GYIRFamide as a neuronal marker, the possible functions of the native peptide are also discussed. The quality and reproducibility of the immunostaining obtained during this work highlights the effectiveness of the GYIRFamide antiserum in the neuroanatomical study of flatworms, and also the suitability of B. candida as a model species in studies of the turbellarian nervous system.

Animals↗
PubMed1996

Oncogene expression in carotid body tumors.

BACKGROUND: The genetic etiology of carotid body tumors is suggested by the familial occurrence of the neoplasm. Environmental influences are also implied by the fact that the tumor is more common in those living at high altitudes. However, the development of sporadic tumors occurring at sea level, which account for the majority of cases, remains unknown. METHODS: The clinical and pathologic features of 13 carotid body tumors excised in 13 patients were reviewed. Two patients had bilateral tumors, one with a strong family history, and two patients had recurrent carotid body tumors. All tumors were benign except for one that had local lymph gland metastases. All patients were followed up for a period ranging from 1 to 17 years. Each tumor was examined for the oncoproteins c-myc, bcl-2 c-erbB-2, c-erbB-3 and c-jun and for the proliferating cell nuclear antigen (PCNA) by immunohistochemistry. RESULTS: c-myc immunoreactivity was observed in all tumors and, in 12 of 13 cases, was present in more than 10% of tumor cells, bcl-2 immunoreactivity was found in 11 cases with 6 tumors exhibiting more than 10% immunopositive cells, c-jun expression was found in 5 cases with 3 tumors containing more than 10% immunopositive cells. Only two tumors were positive for c-erb-B2 immunoreactivity with a cytoplasmic staining pattern. One tumor was positive for c-erb-B3. CONCLUSIONS: The oncogenes c-myc, bcl-2 and c-jun, are abnormally expressed in some carotid body tumors. Their expression may contribute to the genesis of carotid body tumors.

Adolescent↗
PubMed1996

Cellular and subcellular localization of SALMFamide (S1)-like immunoreactivity within the central nervous system of the nematode Ascaris suum (Nematoda, Ascaroidea).

The localization and distribution of SALMFamide (S1)-like immunoreactivity (IR), was determined at both the cellular and subcellular level in the central nervous system (CNS) of the nematode roundworm Ascaris suum. The techniques of indirect immunofluorescence in conjunction with confocal scanning laser microscopy and post-embedding, IgG-conjugated colloidal gold immunostaining were used, respectively. Immunostaining was widespread in the CNS of adult A. suum, with immunoreactivity (IR) being localized in nerve cells and fibres in the ganglia associated with the anterior nerve ring and in the main nerve cords and their commissures. At the subcellular level, gold labeling of peptide was localized exclusively over dense-cored vesicles within nerve cell bodies, nerve axons and nerve terminals of the neuropile of the anterior nerve ring, main ganglia and nerve cords in the CNS. Double-labeling demonstrated an apparent co-localization of S1- and FMRFamide-IR-together with S1- and pancreatic polypeptide (PP)-IR in the same dense-cored vesicles. Antigen preabsorption experiments indicated little cross-reactivity, if any, between the three antisera; indeed, neither FMRFamide nor PP antigens abolished S1 immunostaining.

Animals↗
PubMed1996

Cholinergic, serotoninergic and peptidergic components of the nervous system of Discocotyle sagittata (Monogenea:Polyopisthocotylea).

Cholinergic, serotoninergic (5-HT) and peptidergic neuronal pathways have been demonstrated in both central and peripheral nervous systems of adult Discocotyle sagittata, using enzyme histochemistry and indirect immunocytochemistry in conjunction with confocal scanning laser microscopy. Antisera to 2 native flatworm neuropeptides, neuropeptide F and the FMRFamide-related peptide (FaRP), GNFFRFamide, were employed to detect peptide immunoreactivity. The CNS is composed of paired cerebral ganglia and connecting dorsal commissure, together with several paired longitudinal nerve cords. The main longitudinal nerve cords (lateral, ventral and dorsal) are interconnected at intervals by a series of annular cross-connectives, producing a ladder-like arrangement typical of the platyhelminth nervous system. At the level of the haptor, the ventral cords provide nerve roots which innervate each of the 9 clamps. Cholinergic and peptidergic neuronal organisation was similar, but distinct from that of the serotoninergic components. The PNS and reproductive system are predominantly innervated by peptidergic neurones.

Animals↗
PubMed1996

PC12 cells show immunoreactivity to a number of proteins and peptides, including vasostatin.

N-terminal chromogranin A (CGA) contains peptides with vasoinhibitory properties, called vasostatin I (VST) and II [CGA (1-76) and (1-113) in human and bovine; (1-128) in rat]. Three fragments of VST were synthesized and antisera raised: human CGA (68-76) (VST I) rat CGA (121-128) (VST II fragment 2), and bovine/human CGA (83-91) (VST II, fragment 3). Strong immunoreactivity was observed in PC12 cells with antisera to VST II, fragment 3, VST I, and neuron-specific enolase. Little or no immunoreactivity was observed using antisera to synaptophysin, whole molecule CGA, pancreastatin, protein gene product 9.5, somatostatin, pancreatic polypeptide, or with antibodies 875 and 876 to VST II, fragment 2. Most of the VST antisera cross-reacted, with a species of molecular weight, 61 kDa but one, 874, cross-reacted with two species of molecular weights, 7.2 and 12 kDa. Our results show the presence of N-terminally processed CGA in PC12 cells.

Amino Acid Sequence↗