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Biomedical subjects

D F McLaughlin

Publications and source records attributed to D F McLaughlin.

12 recordsLinked to original sources
PubMed2001

Disruption of layers 3 and 4 during development results in altered thalamocortical projections in ferret somatosensory cortex.

The precision of projections from dorsal thalamus to neocortex are key toward understanding overall cortical organization and function. To identify the significance of layer 4 cells in receiving the bulk of thalamic projections in somatosensory cortex, we disrupted layer 4 genesis and studied the effect on thalamic terminations in ferrets. Second, we ascertained the result of layer 4 disruption on functional responses and topographic organization. Methylazoxy methanol (MAM) was injected into pregnant ferrets on embryonic day 33 (E33), when most layer 4 neurons of somatosensory cortex are generated. This treatment resulted in dramatic reduction in the thickness of targeted layer 4. E38 MAM treatment was used as a control, when layer 2-3 neurons are generated. The projections of ventrobasal thalamus into somatosensory cortex were studied using DiI injections. We found only subtle differences between groups (normal, E33, or E38 MAM-treated) in the thalamic afferent pattern on postnatal day 1 (P1) and P7. On P14, thalamic terminations distribute almost equally throughout the remaining cortical layers in the E33 MAM-treated group compared with normal and E38 MAM-treated animals, in which the ventrobasal thalamus projects primarily to central layers. Electrophysiological recordings conducted on mature ferrets treated with MAM on E33 demonstrated that somatotopic organization and receptive field size are normal. These findings emphasize the importance of layer 4 in determining the normal laminar pattern of thalamic termination and suggest that, although its absence is likely to impact on complex neocortical functional responses, topographic organization does not arise from the influence of layer 4.

Animals↗
PubMed2000

Secreted and membrane attractin result from alternative splicing of the human ATRN gene.

Attractin, initially identified as a soluble human plasma protein with dipeptidyl peptidase IV activity that is expressed and released by activated T lymphocytes, also has been identified as the product of the murine mahogany gene with connections to control of pigmentation and energy metabolism. The mahogany product, however, is a transmembrane protein, raising the possibility of a human membrane attractin in addition to the secreted form. The genomic structure of human attractin reveals that soluble attractin arises from transcription of 25 sequential exons on human chromosome 20p13, where the 3' terminal exon contains sequence from a long interspersed nuclear element-1 (LINE-1) retrotransposon element that includes a stop codon and a polyadenylation signal. The mRNA isoform for membrane attractin splices over the LINE-1 exon and includes five exons encoding transmembrane and cytoplasmic domains with organization and coding potential almost identical to that of the mouse gene. The relative abundance of soluble and transmembrane isoforms measured by reverse transcription-PCR is differentially regulated in lymphoid tissues. Because activation of peripheral blood leukocytes with phytohemagglutinin induces strong expression of cell surface attractin followed by release of soluble attractin, these results suggest that a genomic event unique to mammals, LINE-1 insertion, has provided an evolutionary mechanism for regulating cell interactions during an inflammatory reaction.

Alternative Splicing↗
PubMed2000

The perceptions and aspirations illicit drug users hold toward health care staff and the care they receive.

Over the 30 years of conflict, Northern Ireland escaped the worst excess of illegal drug trafficking and usage. However, the recent 'peace dividend' has brought with it an unprecedented rise in the availability and use of illicit drugs. With this, new problems and pressures have been brought to bear on the health service. The literature would suggest that drug users are loathed and feared by health care staff. Staff will also admit to be lacking in the knowledge and skills necessary for the delivery of appropriate support and treatment for this client group. Further, the literature has little to offer on the experiences and aspirations of drug users in relation to their treatment and the staff who care for them. In order to understand the drug users' experiences of health care and health staff, focus group methodology was employed to obtain qualitative data. A total of 20 illicit drug users from across Northern Ireland took part. Supporting the literature, all had experienced 'care' that they felt was filled with judgement, hostility and loathing. They recognized clearly the challenge they pose to health care staff. These findings indicate that there is obvious dissonance between those tasked to care for drug users and drug users themselves, with little respect being shown on either side. Results suggest that action needs to be taken to address the deficits in the knowledge, skills and values of health care professionals in relation to illicit drug users. The findings will be of interest to service providers within and outside the United Kingdom.

Attitude↗
PubMed1999

Functional interaction of DFF35 and DFF45 with caspase-activated DNA fragmentation nuclease DFF40.

DNA fragmentation factor (DFF) functions downstream of caspase-3 and directly triggers DNA fragmentation during apoptosis. Here we described the identification and characterization of DFF35, an isoform of DFF45 comprised of 268 amino acids. Functional assays have shown that only DFF45, not DFF35, can assist in the synthesis of highly active DFF40. Using the deletion mutants, we mapped the function domains of DFF35/45 and demonstrated that the intact structure/conformation of DFF45 is essential for it to function as a chaperone and assist in the synthesis of active DFF40. Whereas the amino acid residues 101-180 of DFF35/45 mediate its binding to DFF40, the amino acid residues 23-100, which is homologous between DFF35/45 and DFF40, may function to inhibit the activity of DFF40. In contrast to DFF45, DFF35 cannot work as a chaperone, but it can bind to DFF40 more strongly than DFF45 and can inhibit its nuclease activity. These findings suggest that DFF35 may function in vivo as an important alternative mechanism to inhibit the activity of DFF40 and further, that the inhibitory effects of both DFF35 and DFF45 on DFF40 can put the death machinery under strict control.

Amino Acid Sequence↗
PubMed1998

Attractin (DPPT-L), a member of the CUB family of cell adhesion and guidance proteins, is secreted by activated human T lymphocytes and modulates immune cell interactions.

Attractin is a normal human serum glycoprotein of 175 kDa that is rapidly expressed on activated T cells and released extracellularly after 48-72 hr. We have cloned attractin and find that, as in its natural serum form, it mediates the spreading of monocytes that become the focus for the clustering of nonproliferating T lymphocytes. There are two mRNA species with hematopoietic tissue-specific expression that code for a 134-kDa protein with a putative serine protease catalytic serine, four EGF-like motifs, a CUB domain, a C type lectin domain, and a domain homologous with the ligand-binding region of the common gamma cytokine chain. Except for the latter two domains, the overall structure shares high homology with the Caenorhabditis elegans F33C8.1 protein, suggesting that attractin has evolved new domains and functions in parallel with the development of cell-mediated immunity.

Amino Acid Sequence↗
PubMed1998

Organization of the forepaw representation in ferret somatosensory cortex.

Little is known about the function and structure of ferret somatosensory cortex. We used anatomical methods and multi-unit recordings to characterize the cytoarchitecture, functional responses and topography of the forepaw representation in ferret somatosensory cortex. The representation of the cutaneous ferret forepaw encompasses approximately the caudal half of the posterior sigmoid gyrus. The posterior sigmoid gyrus and coronal sulcus contain unique cytoarchitectonic fields that conform in large part to earlier descriptions of somatosensory regions in the cat. The cytoarchitectonic regions form mediolateral bands that comprise areas 4, 3a, 3b, 1, and 2 (from rostral to caudal). We studied most extensively areas 3a and 3b for functional responses to somatic stimuli; our data indicate that ferret somatosensory cortex contains at least two representations of the forepaw in these two areas. Our data also suggest that within ferret somatosensory cortex, the morphological and submodality features gradually, rather than abruptly, distinguish themselves as unique cortical fields.

Animals↗
PubMed1996

Frequency-domain measurement of vibrotactile driving responses in first-order afferent populations.

Surface recordings made at the wrist during moderate vibrotactile stimulation of a digit display rhythmic activity at the frequency of the driving stimulus. This activity is abolished by local anesthesia of the stimulated digit and by substitution of the corresponding digit of the opposite hand with the recording geometry and the load on the stimulator unchanged. Several additional features of the response are similarly incompatible with an artifactual origin in properties of the stimulus motion or the associated electromagnetic field, but consistent with previous neurophysiological observations. The frequency-domain analysis extends readily to the single-trial level, making the technique potentially useful for a variety of basic research and clinical purposes.

Adult↗
PubMed1991

Directional sensitivity along the upper limb in humans.

The capacity of four neurologically healthy young adults to distinguish opposing directions of cutaneous motion was determined at five different sites along the proximal-distal axis of the upper limb. Constant-velocity brushing stimuli (ranging from 0.5 to 32.0 cm/sec) were delivered through an aperture in a Teflon plate that was securely positioned in light contact with the skin. In one series of experiments, directional sensitivity in d' units was assessed at each site, using an aperture length of 0.75 cm. In a second series of experiments, the aperture length required to obtain the same criterion level of directional sensitivity at each site was determined. To attain the sensitivity reached at distal sites, a proximal stimulus had to traverse a longer chord of skin. Specifically, chords 5.9 times longer on average (range = 5.4-6.2) were required on the proximal forearm than on the index finger pad. This finding suggests that relative directional sensitivity increases sixfold from the proximal forearm to the finger pad. Moreover, relative directional sensitivity on the shoulder was comparable to that observed on the proximal forearm for two of the subjects, and approximately one-half that observed on the proximal forearm for the other two subjects. In addition to such a prominent spatial gradient in relative directional sensitivity, the velocity of stimulus motion at which directional sensitivity was highest increased systematically as the test site was shifted from the finger pad to the proximal forearm. Specifically, the optimal velocity on the finger pad varied among subjects from 1.5 to 9.4 cm/sec (mean = 5.4 cm/sec), and on the proximal forearm from 11.5 to 31.2 cm/sec (mean = 18.6 cm/sec). The optimal velocity on the shoulder was not significantly different from that observed on the proximal forearm. The results suggest that effective and informed clinical testing of patients' capacity to distinguish opposing directions of motion on cutaneous regions that differ in peripheral innervation density requires appreciation of the sensitivities of different skin regions, as well as the unique velocity dependency of direction discrimination at each skin site.

Adolescent↗
PubMedDate not supplied

Evoked potentials as indices of adaptation in the somatosensory system in humans: a review and prospectus.

Population-level behavior of large neural aggregates can be efficiently monitored by corresponding population-level indices such as somatosensory evoked potentials (SEPs). The literature reviewed clearly indicates that SEPs undergo systematic and often marked changes under conditions of repetitive stimulation. Similar results have been reported for several mammalian species and with a diversity of stimulation, recording and analysis protocols. The most characteristic finding is a loss of SEP component amplitude as a function of decreasing time between stimulus presentations. The effects become larger and appear at longer ISIs at higher levels of the somatosensory pathway, are more readily evoked by stimulus trains than by stimulus pairs and are most pronounced for response components generated in the upper cortical layers. These findings are consistent with a recently proposed neurophysiological model of short-term plasticity in somatosensory cortex, which incorporates detailed and current information on cortical microcircuitry, receptor and neurotransmitter characteristics, topographical organization and dynamic response to repetitive sensory drive. Recommendations are provided for further research, emphasizing the potential of frequency-domain analysis methods in conjunction with mechanical vibrotactile stimuli as a vehicle for more detailed testing of the proposed neurophysiological model and for closer integration with psychophysical studies of vibrotactile adaptation.

Adaptation, Physiological↗