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Biomedical subjects

A M Fleming

Publications and source records attributed to A M Fleming.

10 recordsLinked to original sources
PubMed1998

Novel sites of adrenomedullin gene expression in mouse and rat tissues.

Adrenomedullin (AM) was originally identified in pheochromocytoma tissue and was characterized as a hypotensive peptide. The tissue distribution and cellular localization of AM messenger RNA (mRNA) were determined in mouse and rat tissues by in situ hybridization. Three probes were used: two nonoverlapping probes to the pro-AM N-terminal 20 peptide (PAMP) and AM peptide regions of mouse pro-AM, and a larger complementary DNA (cDNA) probe spanning both the PAMP- and AM peptide-coding regions. The most intense expression of AM mRNA was in endometrium and epithelial cells lining the uterus and mouse adrenal medulla. Moderate levels of expression were detected in kidney glomerulus and cortical distal tubules, ovarian corpus luteum and follicles, epithelial cells lining the bronchioles, cardiac atrium and ventricle, posterior pituitary (particularly in female rats), stomach, small intestine (microvilli, mucosa and submucosa), spleen, and pancreas. Lower levels were observed in pulmonary alveoli, anterior pituitary, and submandibular gland. No expression was detected in the testis, thymus, skeletal muscle, or liver. The localization of AM mRNA in epithelial cells lining the uterus, bronchioles, and gastrointestinal tract indicates novel roles for AM, possibly as an antimicrobial agent. The strong expression of AM in uterus, ovary, and posterior pituitary suggests that AM plays a role in female reproduction.

Adrenal Glands↗
PubMed1993

The syntaxin family of vesicular transport receptors.

Syntaxins A and B are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. A family of syntaxin-related proteins from rat has been identified that shares 23%-84% amino acid identity. Each of the six syntaxins terminate with a carboxy-terminal hydrophobic domain that anchors the protein on the cytoplasmic surface of cellular membranes. The syntaxins display a broad tissue distribution and, when expressed in COS cells, are targeted to different subcellular compartments. Microinjection studies suggest that the nervous system-specific syntaxin 1A is important for calcium-regulated secretion from neuro-endocrine PC12 cells. These results indicate that the syntaxins are a family of receptors for intracellular transport vesicles and that each target membrane may be identified by a specific member of the syntaxin family.

Amino Acid Sequence↗
PubMed1993

A rab protein regulates the localization of secretory granules in AtT-20 cells.

Low molecular weight (LMW) GTP-binding proteins are hypothesized to play a role in the vectorial transport of intracellular vesicles. Mutational studies in yeast and subcellular localization in mammalian cells suggest that a family of LMW GTP-binding proteins, termed rab, target intracellular vesicles to their appropriate acceptor compartment. In this report, we demonstrate that an elasmobranch homologue of rab3A, o-rab3, plays a significant role in the sequestration of regulated secretory vesicles. When transfected into the murine endocrine cell line AtT-20, the wild-type o-rab3 protein is localized exclusively to the tips of the processes, a region of the cell known to accumulate proteins associated with regulated secretory vesicles. Two mutations, Gln81 to Leu (Q81L) and Asn135 Ile (N135I), which alter GTP binding or rate of hydrolysis, blocked the localization of the o-rab3 protein to the tips of cell processes. These mutations also hindered the sequestration of ACTH-containing secretory vesicles to the process tips but did not affect the basal or stimulated release of ACTH. Moreover, the sequestration of the protein VAMP to the process tip was also hindered by the mutation. The results demonstrate a role for the rab3 proteins in localization, sequestration, and storage of secretory vesicles near their release site.

Adrenocorticotropic Hormone↗
PubMed1981

Peripheral nerve function in patients with bronchial carcinoma. Comparison with matched controls and effects of treatment.

Clinical examination of 80 patients with bronchial carcinoma showed minor neurological abnormalities but in only a few cases were these considered to be due to neuromyopathy. Spontaneous activity in the EMG was shown in 35%, consistent with a mild degree of partial denervation; when 50 of the patients were matched with 50 controls the patients showed a small but significant impairment of nerve conduction velocity in comparison with the controls. These findings accord with subclinical neuropathy in a high proportion of patients with bronchial carcinoma consistent with primary axonal change. Thirty patients participated in a prospective study of the effects of treatment. Of these nine were reassessed following surgery or radiotherapy. Although there was a trend towards improvement in sensory conduction there was no consistent change in the electromyographic findings.

Bronchial Neoplasms↗
PubMed1977

Urinary monoamine metabolite excretion in disorders of movement. Effects of amantadine and levodopa.

We have studied the urinary excretion of 1,4-methylhistamine (1,4-MeHm), 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in patients with Parkinson's disease, choreiform movements and essential tremor. The effect of amantadine on urinary excretion has been measured in each group of patients as well as the effect of levodopa in patients with Parkinson's disease. In patients with Parkinson's disease, excretion of 1,4-MeHm and HVA was significantly lower than in controls. Patients with choreiform movements had a reduced excretion of HVA but trends toward low levels of 1,4-MeHm and, in patients with Huntington's chorea, elevated excretion of 5-HIAA, were not significant. In patients with essential tremor, urinary excretion of the amine metabolities studied did nof differ significantly from controls. Administration of amantadine to patients with Parkinson's disease was not followed by increased excretion of monoamine metabolites except in those patients who were already receiving anticholinergic drugs. This increase is not significant and there was no effect in other groups of patients. These findings lend no support to the view that amantadine has a general amine-releasing action although there is limited evidence for such an effect in Parkinson's disease. In addition to the expected increase in HVA excretion, administration of levodopa to Parkinsonian patients was followed by significantly reduced excretion of 1,4-MeHm and 5-HIAA. However, if amantadine and levodopa were given together, excretion of 5-HIAA was still reduced, but that of 1,4-MeHm was normal. Levodopa may thus modify the turnover of histamine, which appears to be reduced in Parkinson's disease, and this effect may be modified by amantadine.

Amantadine↗
PubMedDate not supplied

Evaluation of dosage adjustment in patients with renal impairment.

AIMS: To determine whether appropriate dosage adjustments are made in patients with significant renal impairment for drugs with a high fractional renal clearance. METHODS: Evaluation of dosage adjustment was performed in patients who were admitted to a 480-bed metropolitan hospital (Princess Alexandra Hospital, Brisbane, Australia) with an estimated creatinine clearance of < or =40 mL/min. All drugs had a high fractional renal excretion. A prescribed dose within 30% of the calculated dose was considered appropriate. RESULTS: Doses were found to be inappropriately high in 111 (44.8%) of 248 admission prescriptions of the targeted drugs. Doses were appropriately reduced in hospital in 26 patients (23.4%). Seventy-three (29.3%) prescriptions were continued with excessive doses. Only 34 prescriptions for the target drugs were initiated in hospital, of which 88.2% were appropriately dosed. CONCLUSIONS: A significant percentage of patients with renal impairment are admitted to hospital on inappropriately high doses of drugs, with a high fractional renal excretion and low therapeutic index. Doses are appropriately reduced in hospital in some patients but there is still room for improvement [corrected].

Administration, Oral↗