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M Kidd

Publications and source records attributed to M Kidd.

At least 55 records · Page 3Linked to original sources
PubMed1996

Neurohormonal modulation of rat enterochromaffin-like cell histamine secretion.

BACKGROUND & AIMS: Gastric mucosal cells and nerve terminals contain at least acetylcholine, adrenergic agents, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, serotonin, gamma-amino-butyric acid, neurokinins A and B, neurotensin, neuropeptide Y, peptide YY, gastrin-releasing peptide, somatostatin, and [Met5]enkephalin. Although some of these agents have been implicated as regulators of gastric acid secretion, their site and mechanism of action is not well understood. The aim of this study was to investigate whether local gastric neurotransmitters modulate acid secretion by regulating basal and gastrin-driven enterochromaffin-like (ECL) cell histamine release. METHODS: The effects of the above agents were investigated in a short-term 90%-95% pure ECL cell culture system. Cells were incubated with either the neuromodulator alone or in combination with gastrin for 10-40 minutes, and histamine secretion was measured by enzyme immunoassay. RESULTS: Acetylcholine, isoproterenol, and vasoactive intestinal polypeptide significantly stimulated basal and gastrin-driven histamine secretion, whereas calcitonin gene-related peptide and somatostatin inhibited basal and gastrin-driven histamine secretion. The M1 muscarinic receptor antagonist pirenzepine dose dependently inhibited the action of acetylcholine, whereas the M3 receptor antagonist 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride had no effect. the rest of the evaluated agents had no effect on ECL cell histamine secretion. CONCLUSIONS: These data are consistent with the hypothesis that substantial neurohormonal modulation of ECL cell function exists.

Acetylcholine↗
PubMed1996

The role of transforming growth factor alpha in the enterochromaffin-like cell tumor autonomy in an African rodent mastomys.

BACKGROUND & AIMS: Gastric carcinoids evolved from enterochromaffin-like (ECL) cell hyperplasia are usually associated with high pH and hypergastrinemia. The Mastomys species exhibits a genetic propensity to gastric carcinoid formation that can be accelerated by acid inhibition-induced hypergastrinemia. Although gastrin is critical in the initiation of the ECL cell transformation, the role of other growth factors involved in the evolution of the tumor autonomy has not been established. The aim of this study was to evaluate the role of transforming growth factor (TGF) alpha in the regulation of ECL cell transformation. METHODS: Mastomys were orally administered an irreversible H2-receptor antagonist loxtidine for 0, 8, and 16 weeks, and ECL cell transformation was monitored by assessing gastrin levels, mucosal histamine content, and chromogranin immunoreactivity. The ECL cells were purified, and cell proliferation at each stage in response to gastrin and TGF alpha was measured by bromodeoxyuridine uptake. TGF-alpha expression was evaluated by radioimmunoassay and Northern blot, and epidermal growth factor (EGF) receptor expression was determined by Western blot, immunoprecipitation, and immunocytochemistry. RESULTS: Although the response to gastrin decreased during hypergastrinemia, the proliferative effect of TGF-alpha on ECL cells was specifically amplified during the development of hyperplasia. TGF-alpha and EGF receptor expression increased steadily in the transformed cells. CONCLUSIONS: During low acid-induced hypergastrinemia, the expression of TGF-alpha and EGF receptor may constitute an autocrine regulatory mechanism in ECL cell tumor transformation.

Animals↗
PubMed1996

Evidence for a regulatory role for histamine in gastric enterochromaffin-like cell proliferation induced by hypergastrinemia.

BACKGROUND/AIMS: Hypergastrinemia, induced by sustained suppression of gastric acid secretion, is associated with gastric enterochromaffin-like (ECL) cell hyperplasia and carcinoid tumor formation. We examined the effect of a selective H1-histamine antagonist, terfenadine, on gastric mucosal cell proliferation to determine whether histamine might modulate ECL cell generation. METHODS: The rodent mastomys received the H2-antagonist loxtidine (2 g/l drinking water) alone or in combination with terfenadine (0.5 g/l or 35 mg/l drinking water) for 120 days. Controls received water or terfenadine alone. Serum gastrin levels and tissue histamine content were assayed by radioimmunoassays, and tissue chromogranin levels determined (Western blot analysis). In vivo cell proliferation was measured by bromodeoxyuridine (BrdU, 200 mg/kg/day, 3 days) incorporation. Gastric mucosal thickness was determined, ECL cell number was assessed, and the percentage of proliferating ECL cells quantitated. To evaluate the direct action on ECL cells we then studied the effect of terfenadine on histamine secretion and DNA synthesis (BrdU uptake) in an isolated preparation (approximately 90% pure) of ECL cells. RESULTS: Loxtidine increased serum gastrin levels, mucosal thickness, tissue chromogranin levels, tissue histamine content, BrdU incorporation, ECL cell number, and proliferating ECL cells (all parameters p < 0.05). Terfenadine alone, irrespective of dosage, had no significant effect. The high dose in combination with loxtidine significantly inhibited the increase in tissue chromogranin levels, tissue histamine content, ECL cell number and proliferating ECL cells (p < 0.05), but did not alter other parameters, compared to loxtidine alone. The low does did not alter the loxtidine-induced changes. In pure isolated ECL cells, terfenadine did not alter histamine secretion either alone or in combination with gastrin (10 nM). DNA synthesis was significantly inhibited by terfenadine (IC50 10(-10) M). CONCLUSIONS: Terfenadine specifically inhibited the effect of loxtidine-induced ECL cell proliferation in vivo and significantly inhibited ECL cell DNA synthesis in vitro. We postulate that histamine, through an H1 receptor, positively modulates gastric ECL cell proliferation.

Animals↗
PubMed1996

Pathophysiology of the fundic enterochromaffin-like (ECL) cell and gastric carcinoid tumours.

The genesis of human gastric carcinoma is ill understood but is invariably related to achlorhydria. Gastrin secretion is negatively regulated by luminal acid and hypergastrinaemia is thus associated with low acid states which may be natural (atrophic gastritis) or owing to acid inhibitory therapy. Apart from its acid secretory activity, gastrin is trophic to the mucosa, via stimulation of the fundic enterochromaffin-like (ECL) cells to secrete histamine. In conditions of elevated gastrin levels, ECL cell hyperplasia and even neoplasia have been noted. The relationship between low acid, hypergastrinaemia, ECL cell hyperplasia, and neoplasia may be of relevance since ECL cells secrete histamine and TGF alpha which are both recognised mitogens. We studied the rodent mastomys, which spontaneously develop gastric carcinoid tumours, which can be generated in 4 months under conditions of drug-induced acid inhibition and inhibited by octreotide administration. A pure (90-95%) cell preparation was used to evaluate ECL cell physiology and trophic regulation. A gastrin/CCKB receptor responsible for histamine secretion and DNA synthesis was identified, cloned and sequenced. Octreotide lowers plasma gastrin levels, decreases ECL cell neoplasia and, in vitro, inhibits ECL cell DNA synthesis. H1 receptor antagonists inhibited DNA synthesis in vitro and ECL neoplasia in vivo without altering gastrin levels. Hypergastrinaemia increased TGF alpha/EGF receptor and TGF alpha production and TGF alpha massively stimulated ECL cell DNA synthesis. Since ECL cells produce both histamine and TGF alpha and regulate parietal cells which produce TGF alpha, it is possible that achlorhydria-generated ECL cell dysfunction may play an initiative role in the pathobiology of gastric adenocarcinoma. The long-term clinical consequences of drug-induced sustained acid inhibition are worthy of further consideration.

Animals↗
PubMed1996

A guide to computer-generated prescriptions.

The use of computer systems to produce prescriptions offers many benefits at a reasonable cost. This article summarises the benefits and costs and the steps recommended for general practitioners who wish to start using a computer to generate their prescriptions.

Australia↗
PubMed1995

Informatics in family practice--an Asia-Pacific perspective.

Recent advances in computer hardware, software and telecommunications, and particularly in the development of the electronic medical record, mean that family practitioners around the world now have access to a multiplicity of tools which offer the potential for significant time savings and improved quality of health care provision. Areas such as practice management medication management and prescription generation, clinical record keeping, decision support, medical research and continuing medical education can all be aided through the use of information technology in a family practice setting. Yet family medicine, or general practice, has largely been slow to take up the challenge of implementing information technology in most parts of the Asia-Pacific region. This contrasts sharply with many other areas of medicine which have been very active in embracing this technology. This paper examines the potential advantages and the difficulties of computerisation for general practitioners and their patients in the Asia-Pacific region. It is hoped that the lessons already learned in some countries in this region can be adapted and applied elsewhere.

Asia↗
PubMed1994

How to prepare for the FRACGP exam.

This paper aims to assist candidates in their preparation for the RACGP Fellowship examination. Particular emphasis is placed on what to do before the event and the techniques to use on the day. Explanations about the rating schedules for the various segments are also given.

Australia↗
PubMed1993

Advice to a Moscow children's hospital.

At the request of the largest children's hospital in Moscow, McKenzie and colleagues made recommendations for improving the service. Restrictions on visiting and fears of contracting illness from non-disposable needles have discouraged the local population from using the hospital. Consequently the hospital is underused and overstaffed. Serious shortages of drugs and surgical supplies compromise care. Fundamental changes are needed in nursing and postgraduate education. The authors encouraged their Russian colleagues to address the health care needs of their local population and to develop family centred care, and they offered training in London.

Child↗
PubMed1989

Immunoaffinity chromatographic purification of amyloid-related proteins from Alzheimer's disease brain tissue.

We describe the preparation and characterisation of an immunoaffinity column of immobilised monoclonal antibody 1G10/2/3 which was raised against a synthetic peptide representing residues 8-17 of the A4 amyloid protein (or beta-protein) of Alzheimer's disease (AD). In previous work we have shown that this antibody reacts in formalin-fixed, paraffin-embedded tissue sections with plaque cores, plaque periphery and cerebrovascular amyloid of AD. We have used the column in the immunoaffinity isolation from extracts prepared from AD brain tissue of a protein with an apparent molecular weight of 31,000; this protein is reactive with 1G10/2/3 in Western blots. The same protein is also present, but at lower level, in normal control brain tissue. Possible relationships of this protein to the predicted structures for full-length A4-precursors are discussed. However, in view of the preliminary nature of the observations and potential problems relating to proteolysis occurring post-mortem or during the extraction process, firm conclusions cannot be drawn about any role for this molecule in the normal functioning of A4-precursors or in the conversion of A4-precursor to the deposits of A4 seen in AD brain. Nevertheless, we conclude that we are seeing a stable but truncated form of A4-precursor and it will be of interest to see if further studies can clarify the possible relevance of the protein to normal or pathological processes in human brain tissue.

Alzheimer Disease↗
PubMed1988

Surgical results in iridocorneal endothelial syndrome.

The charts of 83 patients with iridocorneal endothelial (ICE) syndrome were retrospectively reviewed. Forty-two eyes of 42 patients had had filtering surgery, 37 of whom had had a trabeculectomy to reduce uncontrolled intraocular pressure. Twenty-four of these trabeculectomy patients required a second surgery, and 8 required a third surgery. The results are presented using a survival analysis. The success rates at one year of follow-up for the first, second, and third trabeculectomies were 64%, 79%, and 63%, respectively. Patients subclassified as having Chandler's syndrome, essential iris atrophy, and Cogan-Reese syndrome responded with approximately the same success rates within the first two years following their first surgery. The success rates for repeated surgeries are comparable with those of initial surgery in patients with primary open angle glaucoma. On the basis of this study, further surgery is recommended despite initial failure in this group of difficult patients.

Endothelium, Corneal↗
PubMed1988

Regulation of fibrinolysis in aortic surgery.

The existence of inhibitors of plasminogen activator has been shown to play an important role in regulation of fibrinolysis and postoperative thrombosis. Platelets and endothelium are sources of plasminogen activator inhibitor (PAI). This study determines the contribution of platelet-released PAI to perioperative fibrinolytic shutdown. PAI levels were measured in 25 patients having aortic surgery. In nine patients the platelet-released PAI contribution was determined by in vitro activation of platelets with phorbol-myristate-acetate (PMA). Mean preoperative PAI levels (3.78 +/- 1.19 U/ml) were similar to controls (3.01 +/- 1.04 U/ml) (p greater than 0.05). Plasma PAI showed an operative increase to a maximum at 8 hours postoperatively and returning to preoperative values by the second postoperative day. In the nine patients who were subjected to studies with in vitro activation, the preoperative PAI level (4.0 +/- 0.9 U/ml) was elevated to 5.1 +/- 0.7 U/ml (p = 0.001) with PMA induction. Maximum stimulated release of platelet granule contents (platelet releasate) could account for an increase of only 1.0 U/ml compared with a postoperative increase of 2.3 U/ml. Postoperative mean peak plasma PAI (6.3 +/- 0.4 U/ml) could not be further elevated by induced release (6.3 +/- 0.4 U/ml) (p = 0.003). A statistically significant increase in PAI occurred in aortic surgery patients postoperatively. The platelet releasable pool of PAI contributed to the increase and was functionally exhausted postoperatively. Postoperative increases of PAI were twice that induced by platelet in vitro stimulation alone. The perioperative increase in PAI was partly due to platelet release.

Aorta↗
PubMed1988

Immunohistochemical evidence for the derivation of a peptide ligand from the amyloid beta-protein precursor of Alzheimer disease.

A monoclonal antibody to a synthetic peptide consisting of residues 8-17 of the amyloid beta protein of Alzheimer disease was used in immunohistochemical studies to reveal binding sites for this peptide in vesicular elements in the islets of Langerhans of the pancreas and the zona reticularis of the adrenal gland. These binding sites may represent a specific membrane receptor. These results, together with similarities in structural features between the precursors for epidermal growth factor and beta protein, suggest that the beta-protein precursor may be processed to release an active peptide ligand rather than acting as a membrane receptor. In Alzheimer disease, abnormal processing of this active peptide precursor may result in the deposition of beta-protein amyloid fibrils in the brain.

Adrenal Glands↗
PubMed1988

CNS amyloid proteins in neurodegenerative diseases.

The amyloid plaques found in neurodegenerative diseases show considerable morphologic diversity. Two amyloidogenic proteins have been isolated from the brains of humans and animals with neurodegenerative diseases--beta-protein from Alzheimer's disease (AD) and Down's syndrome, and prion protein (PrP) from scrapie and Creutzfeldt-Jakob disease (CJD). Using monoclonal antibodies to a synthetic peptide corresponding to a portion of beta-protein and rabbit antiserum to hamster scrapie PrP 27-30, we examined in situ amyloid plaques on sections from cases of neurodegenerative diseases, including cases with a spectrum of plaque types. Anti-beta-peptide stained cerebrovascular and plaque core amyloid in all AD cases as well as cerebrovascular amyloid and senile plaque core amyloid in five elderly CJD cases. Anti-PrP stained plaques in CJD, kuru, and Gerstmann-Sträussler syndrome cases but not cerebrovascular amyloid or plaques in AD. Dual localization experiments showed that in cases with a mixture of plaque types, the antibodies identified different populations of plaques that showed anatomic heterogeneity. Colocalization of the two proteins was not observed in any plaque type. The data suggest that in neurodegenerative diseases two major plaque types exist, which have different etiologic origins. Our results emphasize the need for classification of CNS amyloids based not on their morphology but on the macromolecular components comprising these pathologic polymers.

Alzheimer Disease↗
PubMed1987

Immunogold labeling of cerebrovascular and neuritic plaque amyloid fibrils in Alzheimer's disease with an anti-beta protein monoclonal antibody.

A monoclonal antibody raised to a synthetic peptide consisting of residues 8 to 17 of the amyloid beta protein of Alzheimer's disease was employed for immunogold electron microscopic studies on amyloid fibrils of cerebrovascular walls and neuritic plaques in this disease. Electron microscopy revealed a specific gold labeling of the amyloid fibrils in these structures. This provides ultrastructural evidence that beta protein is intimately associated with the amyloid fibril. With previous chemical evidence, this observation supports the concentration that it is an intrinsic component of the fibril.

Alzheimer Disease↗
PubMed1986

Monoclonal antibodies raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease.

Four monoclonal antibodies (1D2/1/2, 1G10/2/3, 3B6/1/1, 4D12/2/6) were raised against a synthetic peptide consisting of residues 8-17 of a protein reported to be common to senile plaque cores, cerebrovascular amyloid and neurofibrillary tangles in Alzheimer's disease. In an immunoperoxidase study of Alzheimer brain tissue, these antibodies stained plaque and vascular amyloid but not tangles, suggesting that the polypeptide chain in the region of residues 8-17 is exposed in the former two but, if present, inaccessible in the latter. In addition, staining of granular material in the plaque periphery was observed. These antibodies will be useful tools for future work on the origin of this protein.

Alzheimer Disease↗
PubMed1986

Isolated senile plaque cores in Alzheimer's disease and Down's syndrome show differences in morphology.

Frontal and temporal cortical tissue from the brains of elderly cases of Down's syndrome was used to make preparations of neuronal cell bodies containing senile plaque cores. Polarisation microscopy revealed normal "classical" plaque cores, and also a high proportion of unusual "amorphous" plaque cores which we have not seen in Alzheimer's disease. These two forms were easily distinguished by electron microscopy. This suggests that late Down's syndrome may not be an exact model for Alzheimer's disease.

Alzheimer Disease↗