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Biomedical subjects

A Logan

Publications and source records attributed to A Logan.

At least 91 records · Page 5Linked to original sources

A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury.

Traumatic injury to the CNS initiates transient and unsuccessful regeneration of damaged neural pathways, accompanied by reactive gliosis, angiogenesis, and deposition of a dense fibrous glial/meningeal scar at the wound site. Basic fibroblast growth factor (basic FGF) is a CNS protein with potent effects on neurons, glia, fibroblasts, and vascular endothelial cells. Hybridization and immunocytochemical methods were used to examine temporal and spatial changes in distribution and levels of basic FGF protein and mRNA and also of its receptor mRNA (flg), following a defined wound to the cerebral cortex of adult rat brains. In the injured brain, a rapid, transient increase in basic FGF mRNA and protein is readily detectable within 7 d of surgery and thereafter declines in the tissues bordering the lesion. The increased expression is localized to multiple cell types including macrophages, neurons, astrocytes, and vascular endothelial cells. The changes in immunoreactive basic FGF parallel changes in the bioactivity of extracted heparin-binding proteins, which include basic FGF. Focal increases in flg mRNA appear 7 d after injury and subside by 14 d. The changes in local basic FGF synthesis, concentration, localization, and bioactivity suggest that this growth factor may contribute to the cascade of cellular events that occur in CNS wound repair.

Animals↗

Studies on the mechanisms of signalling and inhibition by pertussis toxin of fibroblast growth factor-stimulated mitogenesis in Balb/c 3T3 cells.

Basic fibroblast growth factor (bFGF) stimulates mitogenesis of Balb/c 3T3 fibroblast cells. This stimulation may be mediated by multiple signal pathways as it is accompanied by the formation of inositol phosphates, activation of PKC (protein kinase C) and a decrease in intracellular cAMP levels. The multiple positive and negative pathways implicated for FGF-induced mitogenesis may interact and each may contribute in varying degrees to the final cellular response. At least two types of G-proteins may be involved in the intracellular signalling pathways of FGF. Pertussis toxin blocks FGF and TPA (12-O-tetradecanoylphorbol-13-acetate) induced. PKC-mediated mitogenesis and also the associated fall in intracellular cAMP levels. However, pertussis toxin has no effect upon FGF-induced inositol phosphates formation. Thus, inhibition of mitogenesis by pertussis toxin may involve pertussis toxin sensitive G-proteins which may affect at least two separate putative signal pathways involving adenylate cyclase and protein kinase C. Pertussis toxin insensitive G-proteins may also be involved in coupling the FGF receptor to phosphoinositidase C.

Adenylate Cyclase Toxin↗

Production of inositol phosphates in BALB/C 3T3 cells stimulated with basic fibroblast growth factor.

When quiescent 3T3 fibroblast cells were pre-labelled with [3H]inositol and stimulated with basic fibroblast growth factor there was a stimulation of the hydrolysis of membrane lipids and the rapid production of [3H]inositol polyphosphates. Rapid and transient peaks of isomers of inositol phosphates with the chromatographic properties of inositol trisphosphates and inositol tetrakisphosphates were detectable by anion-exchange HPLC between 5 and 10 s after stimulation. These data suggest that upon stimulation the receptor for fibroblast growth factor is coupled to a phosphoinositidase C and that one of its signal-transducing pathways involves hydrolysis of inositol lipids and the production of inositol polyphosphates, some of which may act as intracellular signals mediating the cellular response. Chronic stimulation with basic fibroblast growth factor is associated with desensitization of the inositol lipid signaling pathway.

Animals↗

Basic fibroblast growth factor affects DNA synthesis and cell function and activates multiple signalling pathways in rat thyroid FRTL-5 and pituitary GH3 cells.

We have used a recombinant human basic fibroblast growth factor (basic FGF) to study its effects on cell proliferation, gene expression and accumulation of cyclic AMP (cAMP) and inositol phosphates in two well-characterized endocrine cell lines, FRTL-5 rat thyroid and GH3 rat pituitary cells. Basic FGF induced a dose-dependent increase in mitogenesis (assessed by measuring incorporation of [3H]thymidine) in FRTL-5 cells (40 ng basic FGF/ml increased mitogenesis above the control value by 2148 +/- 108% (mean +/- S.E.M.), but inhibited mitogenesis in GH3 cells at all doses (85 +/- 4% of control with 40 ng basic FGF/ml]. Thyroglobulin mRNA concentration was increased in FRTL-5 cells (126 +/- 6% of control with 40 ng basic FGF/ml) as was prolactin mRNA in GH3 cells (246 +/- 11% of control with 40 ng basic FGF/ml), but GH mRNA in GH3 cells was not significantly affected by any dose of basic FGF. Intracellular cAMP was reduced by basic FGF in both FRTL-5 and GH3 cells (40 ng bFGF/ml giving 80 +/- 5% of the control value in FRTL-5, and 67 +/- 15% of the control value in GH3 cells) despite increased levels when FRTL-5 cells were stimulated with 150 microU TSH/ml (5645 +/- 484% of control) or GH3 cells were stimulated by 10 mumol forskolin/l (3347 +/- 396% of control). In both FRTL-5 and GH3 cells, accumulation of [3H]inositol phosphates were increased by 40 ng basic FGF/ml (201 +/- 6 and 330 +/- 51% of control values respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

CNS growth factors.

The fundamental importance of polypeptide growth factors in regulating growth and maintaining viability within the CNS is now widely acknowledged. Although the physiological roles of individual growth factors remain to be defined, increasing evidence suggests involvement within the CNS in development, maintenance of neurones, injury responses, the pathogenesis of degenerative diseases and possibly oncogenesis. This review focuses on nerve growth factor and the fibroblast growth factors.

Adrenergic Fibers↗

A role for nerve growth factor in collateral reinnervation from sensory nerves in the guinea pig.

We have investigated whether chronic nerve growth factor (NGF) depletion affects the development of a transmedian collateral reinnervation. The extent of transmedian innervation of the skin supplied by the left inferior alveolar nerve (IAN) was determined either immediately, 2 days or 7-9 weeks after sectioning and preventing regeneration of the contralateral IAN and in another group of animals left to recover for 7-9 weeks but also autoimmunised against NGF. Transmedian innervation was measured by recording the area from which a jaw-opening reflex could be evoked and by recording activity in the left IAN during mechanical and electrical stimulation of the skin. Nerve recording during electrical stimulation revealed extensive transmedian collateral reinnervation 7-9 weeks after denervation but this was prevented by NGF autoimmunisation. No change in transmedian innervation could be detected in any of the groups by nerve recording during mechanical stimulation and reflex responses revealed changes in the anaesthetic area which could not be attributed to collateral reinnervation. These results suggest that NGF plays an important role in collateral reinnervation from high-threshold sensory nerves.

Action Potentials↗

Recovery of elevated atrial natriuretic peptide in pressure-overload right heart failure.

Elevation of the plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) was observed in canine chronic right heart failure (RHF) secondary to right ventricular (RV) pressure overload. Pressure overload on the right heart was gradually increased using an inflatable cuff. The interval between banding and the onset of RHF was 152 +/- 52 days. Seventeen RHF dogs were produced and divided into Group I (n = 11) and Group II (n = 6). At the onset of RHF, Group I dogs were either sacrificed for study of the heart, or unbanded to allow recovery from RHF. The dogs in Group II were maintained in RHF for 3 additional months before being either sacrificed or unbanded. Following unbanding, the ANP level of Group I recovered from 108 +/- 36 (n = 11) to 20 +/- 6 pg/ml (n = 6) at 1 month and was maintained at 27 +/- 7 pg/ml (baseline, 21 +/- 5 pg/ml, n = 11) at 4 months. ANP levels of Group II declined from 165 +/- 55 (n = 6) to 87 +/- 2 pg/ml (n = 3) at 1 month and further decreased to 42 +/- 14 pg/ml (n = 3) 4 months after unbanding. Thus, compared to Group I, Group II had a high ANP level before unbanding and a delay in recovery of the ANP levels despite normalization of the right atrial pressure (RAP). Four months after release of pressure overload, the right atrial hypertrophy persisted in the unbanded dogs; however, Group I unbanded dogs showed a better reversal of the right atrial hypertrophy than Group II unbanded dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Full thickness grafts taken from the plantar instep for syndactyly release.

Thirteen digital clefts (eight patients) were reviewed in which full-thickness plantar instep skin was used in syndactyly release. The results are presented, emphasising the good colour match of plantar instep skin with digital skin. There was a surprising lack of morbidity in the thirteen donor sites.

Adolescent↗

Critically ill polyneuropathy associated with burns: a case report.

A severe sensorimotor peripheral neuropathy is reported in a patient with burns covering 35 per cent of the body surface area, severe sepsis and acute renal failure. It presented as difficulty in wearing the patient from a ventilator. Attention is drawn to the condition of critically ill polyneuropathy which has been recently noted in severe illnesses and sepsis. From a search of the literature we believe this to be the first report of this condition in association with thermal injury.

Adult↗

Isokinetic testing in young nonathletic able-bodied subjects.

Isokinetic strength testing has been widely used to assess athletic populations. The purpose of this study was to measure isokinetic strength in nonathletic able-bodied subjects to provide a subsequent comparison with nonathletic injured patients. Using a standard isokinetic protocol, with continuous verbal encouragement, a single investigator tested 16 women and nine men aged 20 to 30 years on an isokinetic dynamometer. Subjects had minimal athletic experience, and none were varsity performers. Peak torque as a percentage of body weight was statistically greater for men than for women in most joints tested both at 60 degrees and 180 degrees per second. The ratio of the last five to the first five of 25 repetitions at 180 degrees/second (Endurance Ratio = ER) rarely (ie, 5/154 tests) fell below the commonly accepted value of 50%. Many subjects had an endurance ratio of 100% or greater (range 4% to 171%). Peak torques were well below and endurance ratios well above those published for similarly aged athletes. The results suggest that before isokinetic testing is considered as a possible way to distinguish malingerers among injured patients, normal values in an age-matched, nonathletic, working population should be clearly defined. The endurance ratio may reflect the level of athletic training or the level of vigorous participation in an exercise program.

Adult↗

Elevation of acidic fibroblast growth factor mRNA in lesioned rat brain.

A 40-base oligodeoxynucleotide probe is described which has been prepared corresponding to the amino acid sequence 9-22 of acidic fibroblast growth factor. Following electrophoretic separation of rat brain mRNA under denaturing conditions the probe hybridizes to a major polyadenylated mRNA species of approximately 4.8 kb. This mRNA is the same size as that reported for acidic fibroblast growth factor mRNA. The relative abundance of the hybridizing 4.8 kb mRNA species increases in rat brain 3 days after cortical lesion indicating increased expression of the gene for acidic fibroblast growth factor.

Animals↗

Distribution of fibroblast growth factor in the central and peripheral nervous systems of various mammals.

Fibroblast growth factor (FGF) is a potent, mesodermal cell mitogen which has been identified throughout the central nervous system of various mammals and shown to display no regional concentration differences within the brain. An FGF-like mitogen of similar specific activity is also identified in the peripheral nervous system. Although not myelin-derived, these factors may arise from some component, of neuronal or glial origin, common to the central and peripheral nervous systems.

Animals↗