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G Cann

Publications and source records attributed to G Cann.

4 recordsLinked to original sources

SF/HGF is a mediator between limb patterning and muscle development.

Scatter factor/hepatocyte growth factor (SF/HGF) is known to be involved in the detachment of myogenic precursor cells from the lateral dermomyotomes and their subsequent migration into the newly formed limb buds. As yet, however, nothing has been known about the role of the persistent expression of SF/HGF in the limb bud mesenchyme during later stages of limb bud development. To test for a potential role of SF/HGF in early limb muscle patterning, we examined the regulation of SF/HGF expression in the limb bud as well as the influence of SF/HGF on direction control of myogenic precursor cells in limb bud mesenchyme. We demonstrate that SF/HGF expression is controlled by signals involved in limb bud patterning. In the absence of an apical ectodermal ridge (AER), no expression of SF/HGF in the limb bud is observed. However, FGF-2 application can rescue SF/HGF expression. Excision of the zone of polarizing activity (ZPA) results in ectopic and enhanced SF/HGF expression in the posterior limb bud mesenchyme. We could identify BMP-2 as a potential inhibitor of SF/HGF expression in the posterior limb bud mesenchyme. We further demonstrate that ZPA excision results in a shift of Pax-3-positive cells towards the posterior limb bud mesenchyme, indicating a role of the ZPA in positioning of the premuscle masses. Moreover, we present evidence that, in the limb bud mesenchyme, SF/HGF increases the motility of myogenic precursor cells and has a role in maintaining their undifferentiated state during migration. We present a model for a crucial role of SF/HGF during migration and early patterning of muscle precursor cells in the vertebrate limb.

Animals↗

The alpha4 subunit of integrin is important for neural crest cell migration.

We identify the alpha4 subunit of integrin as a predominant integrin expressed by neural crest cells in both avian and murine embryos. Using degenerate primers, we obtained a PCR fragment of the chick integrin alpha4 subunit that was subsequently used to clone the full-length subunit with a predicted amino acid sequence 60% identical to human and mouse alpha4 subunits. In situ hybridization demonstrates that chick integrin alpha4 mRNA is expressed at high levels by migrating neural crest cells and neural crest-derived ganglia at both cranial and trunk levels. An antibody against the murine alpha4 subunit revealed similar distribution patterns in mouse to chick. In addition to neural crest cells, the integrin alpha4 subunit was later observed on the muscle masses of the limb, the apical ectodermal ridge, and the developing liver. To examine the functional role of the integrin alpha4 subunit in neural crest cell migration, we used an explant preparation that allows visualization of neural crest cells in their normal environment with or without perturbing reagents. In the presence of a blocking antibody against the mouse integrin alpha4 subunit, there was a profound abrogation of neural crest cell migration at trunk and hindbrain levels. Both the numbers of migrating neural crest cells and the total distance traversed were markedly reduced. Similarly, avian embryos injected with synthetic peptides that contain the integrin alpha4 binding site in fibronectin displayed abnormal neural crest cell migration. Our results suggest that the integrin alpha4 subunit is important for normal neural crest cell migration and may be one of the primary alpha subunits used for neural crest cell migration in vivo. Furthermore, the integrin alpha4 subunit represents a useful neural crest marker in the mouse.

Amino Acid Sequence↗

What happens to patients following open access gastroscopy? An outcome study from general practice.

BACKGROUND: Open access gastroscopy allows general practitioners to request a gastroscopy without prior referral to a specialist. The effect of open access gastroscopy upon patient management is poorly explored. Most studies have been hospital based and have focused on diagnostic yields and on means of tightening requests to reduce inefficient use. A user evaluation can only be made by measuring outcomes in primary care. AIM: A study was undertaken to determine the impact of open access gastroscopy in general practice and in particular, the value of a normal result. METHOD: All general practices in South Tees District Health Authority were asked to participate. Any of their patients who had had open access gastroscopy in the year prior to July 1990 were identified from the hospital computer and their general practitioner notes examined. Patient management during the year prior to the open access gastroscopy was compared with the year after. The main outcome measures were: detection rate and grade of lesion, change in graded score of prescribed drugs, consultation rate for dyspepsia and non-dyspepsia problems, and further hospital referral and investigations. Outcomes among those with normal and abnormal gastroscopy results were compared. RESULTS: The study sample comprised 715 patients, 36% of whom had a normal gastroscopy result, 34% a major abnormality and 26% a minor abnormality (4% of patients had miscellaneous diagnoses). It was found that 39% of all patients, and 60% of those with normal findings on open access gastroscopy had their drug treatment stopped or reduced in grade after the investigation. Of those with a major endoscopic abnormality 58% increased their treatment score. Consultations for dyspepsia in the year before and after gastroscopy fell by 57% overall among those with a normal gastroscopy result, by 37% among those with a minor finding and by 33% in those with a major finding. There was a 21% fall in consultations for all reasons among those with a normal gastroscopy result but those with a minor abnormality had a 23% increase in non-dyspepsia consultations. Of all patients 19% were referred to hospital subsequently. CONCLUSION: Open access gastroscopy has a major effect upon patient management in general practice, and a normal endoscopy result has an important an impact as an abnormal one. Open access gastroscopy is associated with a rationalization of drug therapy, reduced consultations and a low hospital referral rate.

Dyspepsia↗