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Biomedical subjects

D G Jones

Publications and source records attributed to D G Jones.

At least 91 records · Page 5Linked to original sources

Cytochrome-oxidase blobs in cat primary visual cortex.

Cytochrome-oxidase blobs are central to two of the most influential ideas in contemporary visual neuroscience--cortical modularity and parallel processing pathways. In particular, the regular 2D array of cytochrome-oxidase-rich blobs in primate visual cortex is arguably the most compelling evidence for cortical modularity and has been hypothesized to mark a separate processing stream through the visual cortex. Although previously a variety of mammals have been studied, blobs have only been demonstrated in the visual cortex of primates, which has led to the conclusion that blobs represent a primate-specific feature of visual cortical organization. Here we demonstrate the presence of cytochrome-oxidase blobs in a nonprimate species. Throughout the full tangential extent of layers II-III in cat visual cortex the cytochrome-oxidase staining pattern is distinctly patchy, with the darkly stained blobs forming a regular 2D array. In addition, the blobs in cat visual cortex are functionally related to the underlying ocular dominance columns. The presence of cytochrome-oxidase blobs in the cat clearly demonstrates that they no longer can be considered a primate-specific feature of visual cortical organization.

Animals↗

Cross-reactivity amongst recombinant haematopoietic cytokines from different species for sheep bone-marrow eosinophils.

The potentiating effects of a variety of recombinant cytokines on the survival or proliferation (or both) of sheep bone marrow eosinophils in vitro were assessed by means of cell-specific enzyme microassays for eosinophil peroxidase (EPO) and eosinophil arylsulphatase (EAS). In this system recombinant human and mouse interleukin 5 (rhIL5 and rmIL5, respectively) had potent eosinophil potentiating activity (EPA) that was reciprocally inhibited by polyclonal anti-rhIL5 and anti-rmIL5 antibodies and by a specific monoclonal anti-rmIL5 (TRFK5). Recombinant ovine granulocyte-macrophage colony-stimulating factor (rovGM-CSF) and interleukin 3 (rovIL3) also had marked EPA for sheep cells, and the activity of the former was blocked by a mouse monoclonal anti-rovGM-CSF. The equivalent human and murine recombinant GM-CSFs and IL3s had no detectable effect on sheep eosinophils, nor did antibodies against them influence the EPA of any of the ovine cytokines. The evidence presented provides further support to the concept that the structure, biological reactivity and cell specificity of IL5 is highly conserved in mammals, whereas other eosinopoietins such as IL3 and GM-CSF are more species-specific.

Animals↗

Effects of cadaver dissection on the attitudes of medical students.

A study was conducted to determine whether the attitudes of medical students to death and caring changed during the 3 months following exposure to cadaver dissection. All first-year students were invited to complete a questionnaire immediately before their initial cadaver dissection experience, after 6 weeks, and after a further 3 months. The questionnaire reflected attitudes to death, violent death, death of someone known to the respondent and caring when someone known to the respondent is seriously injured. Ethnicity and previous exposure to dying has no effect on responses, but overall men students' reactions were significantly less than for women (P < 0.001). The responses given on the final part of the questionnaire after 3 months were significantly lower than those to most questions in the first part of the questionnaire. The exceptions were those questions where the subject in the given scenario was known to the respondent, where reactions were rated significantly greater (P < 0.001) in the follow-up questionnaire and can be explained on the basis that they were a personal referent. Students rapidly develop a coping mechanism which enables them to view cadaver dissection as an occupation quite divorced from living human beings. During these early months of training solicitude decreases for those who die who are unknown to them, but concern for personal referents increases. Educators should be aware of the dramatic change of attitudes among students and the process of professionalization which might influence their caring of future patients.

Adaptation, Psychological↗

Local eosinophil- and mast cell-related responses in abomasal nematode infections of lambs.

Eosinophil numbers in peripheral blood and eosinophil potentiating activity (EPA) and sheep mast cell protease (SMCP) in efferent gastric lymph were monitored in lambs during infections with Ostertagia circumcincta. Worm burdens, eosinophil numbers in bone marrow, abomasal mucosa and gastric lymph node, as well as mast cell numbers and SMCP concentrations in mucosa and mucus, were determined in post mortem samples. In naive lambs, high and relatively uniform worm burdens were present 10 days after primary infection and these were associated with only mild blood and tissue eosinophilia. By day 21 worm burdens were markedly lower and more variable. There was more evidence of eosinophil and mast cell accumulation in mucosa, and numbers in bone marrow were also higher than on day 10. However, neither EPA nor SMCP were detectable in lymph. By contrast, EPA and SMCP were present in substantial amounts in draining lymph within 48 h of challenge (secondary) infection of previously exposed lambs. EPA was inversely related to worm burdens recovered on day 10, as were abomasal mucosal and mucus SMCP concentrations. Elevated eosinophil numbers were also consistently detected in blood, bone marrow, mucosa and gastric lymph node. The results suggest that host immune defence against secondary, but not primary, exposure to O. circumcincta involves a rapidly mobilised local inflammatory component.

Abomasum↗

Generation and screening of an oligonucleotide-encoded synthetic peptide library.

We have prepared a library of approximately 10(6) different peptide sequences on small, spherical (10-microns diameter) beads by the combinatorial chemical coupling of both L- and D-amino acid building blocks. To each bead is covalently attached many copies of a single peptide sequence and, additionally, copies of a unique single-stranded oligonucleotide that codes for that peptide sequence. The oligonucleotide tags are synthesized through a parallel combinatorial procedure that effectively records the process by which the encoded peptide sequence is assembled. The collection of beads was screened for binding to a fluorescently labeled anti-peptide antibody using a fluorescence-activated cell sorting instrument. Those beads to which the antibody bound tightly were isolated by fluorescence-activated sorting, and the oligonucleotide identifiers attached to individual sorted beads were amplified by the PCR. Sequences of the amplified DNAs were determined to reveal the identity of peptide sequences that bound to the antibody with high affinity. By combining the capacity for information storage in an oligonucleotide code with the tremendous level of amplification possible through the PCR, we have devised a means for specifying the identity of each member of a vast library of molecules synthesized from both natural and unnatural chemical building blocks. In addition, we have shown that the use of flow cytometry instrumentation permits facile isolation of individual beads that bear high-affinity ligands for biological receptors.

Amino Acid Sequence↗

2'-substituted chalcone derivatives as inhibitors of interleukin-1 biosynthesis.

A series of 2'-substituted chalcone derivatives has been found to show potent inhibition of the production of IL-1 beta from human peripheral blood monocytes stimulated with lipopolysaccharide (LPS), with IC50 values in the 0.2-5.0-microM range. Some members of the series have also shown inhibition of septic shock induced in mice by injection of LPS, although with low potency. Qualitative structure-activity relationships have shown that the enone is required for activity, which may be mediated by conjugate addition of a biological nucleophile to the chalcone. Electron-poor aromatic rings beta to the ketone give enhanced potency. Although electronic effects in the other ring (directly attached to the ketone) are minimal, this ring must possess an ortho substituent for good activity without cytotoxicity, suggesting a degree of selectivity which would not be expected for simple, nonspecific alkylating agents.

Animals↗

Morphological characteristics of perforated synapses in the latter stages of synaptogenesis in rat neocortex: stereological and three-dimensional approaches.

Over recent years attention has been focused on perforated synapses (PSs), on account of their possible involvement in synaptic plasticity in the nervous system. The mechanism invoked has involved the conversion of conventional (non-perforated) synapses into perforated ones, with the latter subsequently splitting to form new daughter synapses. Data challenging this mechanism have emerged from studies using unbiased stereological and three-dimensional reconstruction procedures in early synaptogenesis and also in early- to mid-adulthood. The present study is an attempt to complement these earlier studies by concentrating on the latter part of synaptogenesis and early adulthood in rats (7-60 days postnatal). Using the disector method, the frequency of perforated synapses increases with age from 12% at seven days to 33% at 60 days. Reconstruction of the perforated synapses has led to the description of three sub-types, while quantitation of the reconstructions has highlighted major differences between perforated and non-perforated synapses over this developmental period. For instance, the postsynaptic density of perforated synapses increases in size with age, but remains static in the non-perforated variety; in addition, it is 2-3 times larger in perforated synapses. The proportion of the synaptic contact zone occupied by the postsynaptic density increases in perforated synapses with increasing age, but is static in non-perforated synapses. No evidence has been found to support a perforated synapse splitting model, since perforated synapses are present from early in synaptogenesis, the frequency of non-perforated synapses reaches a peak prior to, but not following, that of perforated synapses, and the size of the postsynaptic density of non-perforated synapses remains constant throughout the period of the study.

Animals↗

Determination of neuronal number and process surface area in organotypic cultures: a stereological approach.

Preparation of nervous tissue as an organotypic culture permits examination of nervous system development and interactions between neurons and with their environment. In order to evaluate the statistical significance of morphological changes, it is necessary to quantify tissue populations and parameters. Recent advances in stereology facilitate the gathering of morphometric data, while eliminating sources of error associated with traditional methods. Unfortunately, the new stereology has been perceived as complex and, therefore, has been slow to gain acceptance within neuroscience investigations in general and in vitro applications in particular. Here, we present a detailed application of the new, unbiased stereology to organotypic hippocampal cultures. These methods allow assessment of neuronal survival and morphological plasticity to culture conditions with increasing culture age. Neuronal number was assessed from point-sampled intercepts of cells sampled without bias by the selector procedure in vertical sections through hippocampal cultures. Surface area was estimated from profile intersects of neuronal processes with a cycloid array. The reference volume was determined by the Cavalieri method; this permitted expression of results as absolute values rather than as component densities. The importance of absolute values to valid interpretation of quantitative data is demonstrated by the results for neuronal number. The methods applied here provide a powerful approach to quantitation of organotypic cultures, and represent an important extension of qualitative studies of cultured nervous tissue.

Animals↗

The eosinophil.

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Animals↗

Characterization of proteinases in extracts of adult Haemonchus contortus, the ovine abomasal nematode.

The degradation of several protein substrates, including the blood proteins haemoglobin, albumin and fibrinogen, by proteinases present in extracts of adult Haemonchus contortus was examined over a broad pH range. These proteinases were further characterized on the basis of substrate specificity, inhibitor sensitivity and molecular size by spectrophotometric and substrate gel analysis. The majority of the proteinases capable of degrading the blood proteins tested were active at acidic pH and could be ascribed to the cysteine proteinase class. In addition, evidence is presented that these proteinases are differentially recognized and inhibited by immune sera and that parasites capable of withstanding protective host immune responses exhibit modified expression of proteinases.

Abomasum↗

Sarcoidosis--the way ahead.

The cause(s) of sarcoidosis is likely to be a combination of a conducive soil or sarcoid diathesis invaded by an antigen-driven cell-mediated immune response. The antigenic invasion may be mycobacteria and other organisms and/or their chemical constituents. A ten-point plan of management is set out so that early diagnosis allows early treatment and to prevent complicating pulmonary, ocular or renal fibrosis and to prevent failure of these vital organs.

Adult↗

Synaptic plasticity and perforated synapses: their relevance for an understanding of abnormal synaptic organization.

Perforated synapses refer to a synaptic type found in the central nervous system, and characterized by a discontinuous postsynaptic density when viewed in transverse sections; they are doughnut-shaped or horseshoe-shaped when viewed in en face views. They are large, and are considered to represent single synapses. In this review the evidence for their being intermediates in synaptic turnover is examined. In particular, the view that they originate from conventional, non-perforated synapses, enlarge, and subsequently split to give rise to a new generation of non-perforated synapses, is critically assessed. It is concluded that all the necessary stages in such a scheme have not been unequivocally demonstrated, and an alternative is considered. According to this, perforated and non-perforated synapses constitute separate populations from early in their development, each representing complementary forms of synaptic plasticity. It is further argued that the perforated synapse population can be subdivided into synapses with simple, discrete perforations, those with re-entrant zones, and those with a more complex fragmented form of organization. There is evidence that it is synapses of the latter type that are implicated in synaptic plasticity. An attempt is also made to discover whether the results of synaptic studies on both the normal ageing human brain and the brain in Alzheimer's disease, throw light on the role of perforated synapses in synaptic plasticity. It is suggested that there may be a loss of perforated synapses in Alzheimer's disease, although definitive data are required to test this possibility.

Age Factors↗

The bequest of human bodies for dissection: a case study in the Otago Medical School.

AIMS: To explore why and by whom body bequests to the Otago Medical School have been made since the 1960s. METHODS: We sent out a questionnaire to people who have bequeathed their bodies to the medical school, the people being randomly selected on the basis of the inclusion of the initial J in a forename. The questionnaire sought information on sex, marital status, age, occupation at the time of bequest and bequest information source, as well as reasons for the bequest, expectations of cadaver use and attitudes towards organ donation. RESULTS: The most common reasons for making a bequest were--to aid medical science, and gratitude to the medical profession. There was, however, widespread confusion between cadaver use for medical teaching and for research. CONCLUSIONS: These center around the ethical implications of our findings for organ donation and attitudes towards usage of the dead body.

Adult↗

Bad language?

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Animals↗

Perforated synapses are present during synaptogenesis in rat neocortex.

It has been known for some time that perforated synapses increase in number and size with increasing age. Initially, these trends were used to support the concept that nonperforated synapses enlarge until an optimal size is reached, at which point they perforate and may subsequently split. More recent stereological and three-dimensional reconstruction investigations, however, suggest that this may not be the case and that perforated and nonperforated synapses constitute separate synaptic populations. In order to test the separate population hypothesis, synapses have been studied ultrastructurally in the parietal cortex of rats aged 19 and 20 days gestation, and 1 and 4 days postnatal. By examining synapses serially, and also by studying three-dimensional reconstructions, it has been demonstrated that perforated synapses are present at each of these ages. Some are relatively simple in organization, resembling previously described perforated synapses at 14 days of age, although others appear to consist of two or more separate PSD components. These findings demonstrate that perforated synapses are present from early on in synaptogenesis and that developing perforated synapses may have distinct characteristics that cast light on their developmental course.

Animals↗