Biomedical subjects
L Toole
Publications and source records attributed to L Toole.
Homeotic transformation of branchial arch identity after Hoxa2 overexpression.
Overexpression of Hoxa2 in the chick first branchial arch leads to a transformation of first arch cartilages, such as Meckel's and the quadrate, into second arch elements, such as the tongue skeleton. These duplicated elements are fused to the original in a similar manner to that seen in the Hoxa2 knockout, where the reverse transformation of second to first arch morphology is observed. This confirms the role of Hoxa2 as a selector gene specifying second arch fate. When first arch neural crest alone is targeted, first arch elements are lost, but the Hoxa2-expressing crest is unable to develop into second arch elements. This is not due to Hoxa2 preventing differentiation of cartilages. Upregulation of a second arch marker in the first arch, and homeotic transformation of cartilage elements is only produced after global Hoxa2 overexpression in the crest and the surrounding tissue. Thus, although the neural crest appears to contain some patterning information, it needs to read cues from the environment to form a coordinated pattern. Hoxa2 appears to exert its effect during differentiation of the cartilage elements in the branchial arches, rather than during crest migration, implying that pattern is determined quite late in development.
The effects of hibernation on the myenteric plexus of the golden hamster small and large intestine.
We have examined the effects of hibernation on the neurochemical composition of myenteric neurones in the small and large intestine of the golden hamster using immunohistochemical and histochemical techniques. Hibernation was induced in golden hamsters by altering the photoperiod and external ambient temperature. Age-matched hamsters kept at room temperature and those kept at 5 degrees C but which failed to hibernate were used as controls. Cell counts were carried out to examine possible changes in the numbers of cell bodies immunoreactive to all of the markers examined. The results demonstrated a significant increase during hibernation in the number of neurones immunoreactive to vasoactive intestinal polypeptide, substance P and calcitonin gene-related peptide; cell bodies positive for tyrosine hydroxylase, which were largely absent in the control animals, were prominent in the hibernating animals. There was a significant decrease in the number of neurones immunoreactive to 5-hydroxytryptamine, and no significant changes in the numbers of neurones immunoreactive to protein gene-product and nitric oxide synthase. It is suggested that selective upregulation and downregulation of myenteric neurones containing certain neurotransmitters may occur as a protective mechanism during hibernation to maintain the integrity of the muscular and mucosal layers of the intestine in the absence of luminal contents.
A neurochemical characterisation of the golden hamster myenteric plexus.
The neurochemical composition of nerve fibres and cell bodies in the myenteric plexus of the proventriculus, stomach and small and large intestines of the golden hamster was investigated by using immunohistochemical and histochemical techniques. In addition, the procedures for localising nitric-oxide-utilising neurones by histochemical (NADPH-diaphorase) and immunohistochemical (nitric oxide synthase) methods were compared. The co-localisation of vasoactive intestinal polypeptide and nitric oxide synthase in the myenteric plexus of all regions of the gut was also assessed. The results demonstrated the presence of nerve fibres and nerve cell bodies immunoreactive to protein gene product, vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide, tyrosine hydroxylase, 5-hydroxytryptamine and nitric oxide synthase in all regions of the gastrointestinal tract examined. The pattern of distribution of immunoreactive nerve fibres and nerve cell bodies containing the above markers was found to vary in different regions of the gut. Myenteric neurones and nerve fibres containing immunoreactivity to nitric oxide synthase and NADPH-diaphorase reactivity, however, were shown to have an identical distribution throughout the gut. In contrast to some studies on the guinea-pig and rat, the co-existence of vasoactive intestinal polypeptide and nitric oxide synthase was seen in only a small population of myenteric neurones.
Neurochemical coding in the myenteric plexus of the upper gastrointestinal tract of hibernating hamsters.
As part of our investigation of the plasticity of autonomic nerves in physiological and pathological conditions, we have examined the effect of hibernation on the neurochemical content of myenteric nerves and nerve cell bodies of the upper gastrointestinal tract of the non-seasonal hibernator, the golden hamster. Age matched hamsters kept at room temperature and those kept at 5 degrees C but which failed to hibernate, were used as controls. Possible changes in nerve fibres and nerve cell bodies containing the general neuronal marker, protein gene product 9.5, the peptides, vasoactive intestinal polypeptide, substance P (SP) and calcitonin gene-related peptide (CGRP), the catecholamine synthesizing enzyme tyrosine hydroxylase and the enzyme responsible for synthesizing nitric oxide, nitric oxide synthase, were examined in the oesophagus, proventriculus and proximal and distal stomach of the golden hamsters using immunohistochemical techniques. The results of the present study revealed a significant increase in the number of nerve cell bodies and density of nerve fibres containing SP-immunoreactivity and increased number of CGRP-immunoreactive cell bodies but not the other markers examined in the proximal stomach and proventriculus. In contrast, there was no change in the distribution of any of the neuroactive substances examined in the myenteric plexus of the oesophagus and distal stomach. It is suggested that the change in the environment of the hibernating hamsters perturbs the normal digestive physiology in the proximal stomach and proventriculus that is reflected by the selective changes in SP- and CGRP-containing enteric nerves; these changes may be part of protective reflex mechanisms to the environmental changes resulting from hibernation, where upgrading of nerve cell bodies expressing CGRP and SP has occurred.
Using a choice assessment to predict reinforcer effectiveness.
A choice assessment has been found to be a more accurate method of identifying preferences than is single-item presentation. However, it is not clear whether the effectiveness of reinforcement varies positively with the degree of preference (i.e., whether the relative preference based on the results of a choice assessment predicts relative reinforcer effectiveness). In the current study, we attempted to address this question by categorizing stimuli as high, middle, and low preference based on the results of a choice assessment, and then comparing the reinforcing effectiveness of these stimuli using a concurrent operants paradigm. High-preference stimuli consistently functioned as reinforcers for all 4 clients. Middle-preference stimuli functioned as reinforcers for 2 clients, but only when compared with low-preference stimuli. Low-preference stimuli did not function as reinforcers when compared to high- and middle-preference stimuli. These results suggest that a choice assessment can be used to predict the relative reinforcing value of various stimuli, which, in turn, may help to improve programs for clients with severe to profound disabilities.