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Biomedical subjects

M K Jones

Publications and source records attributed to M K Jones.

At least 91 records · Page 5Linked to original sources

Structure and diversity of cestode epithelia.

Eucestodes have a simple aceolomate body structure and are conservative in terms of the numbers and nature of their cell types. Nevertheless, the cestodes form a diverse group with many strikingly different forms distinguished by the structure of their holdfasts, sexual tissues and embryos. These morphological adaptations have their origins in subtle variations in the structure of their cells and extracellular matrices. This review is concerned with the biology of eucestode epithelia and examines their structure and functions, interrelationships with other tissues, and gives insight into how their components are modified among the many taxa. Three features of cestode epithelia, namely, the occurrence of regional specialisation, microtriches and secretory components, are described. In addition, evidence is presented to suggest that some cestode epithelia are involved in developmental processes such as the nurture of embryos and maintenance of surrounding tissues.

Animals↗

Ultrastructural analysis of the adult Schistosoma japonicum by lectin cytochemistry.

Eight lectin probes were used to detect a range of carbohydrate residues in the tegument matrix of Schistosoma japonicum. In addition, other areas of the parasite, such as the gut, vitelline glands and flame cells, were examined for carbohydrate residues. Some minor differences in the carbohydrate residue composition between tegument orientations and between the sexes were identified. Differences between the distribution of carbohydrate residues of S. japonicum examined in this study and previous reports of Schistosoma mansoni were also noted. This study further illustrates the high level of complexity within the tegument of the adult S. japonicum and has demonstrated differences between this species and the widely studied S. mansoni.

Animals↗

The uterine epithelium of Gyrodactylus kobayashii (Monogenea: Gyrodactylidae): ultrastructure of basal matrices, cytoplasmic membranes and the birth plug, and comparison with other reproductive epithelia.

Ultrastructural details of reproductive epithelia in the viviparous monogenean Gyrodactylus kobayashii are described. Specimens of G. kobayashii were fixed for transmission electron microscopy in glutaraldehyde in sodium cacodylate buffer followed by either 1% aqueous osmium tetroxide or 1% aqueous osmium tetroxide reduced with 1.5% potassium ferricyanide. All reproductive epithelia are underlain by a fibrillar basal matrix. The uterine basal matrix is electron-opaque after potassium ferricyanide reduced osmium tetroxide fixation suggesting the presence of carbohydrate-containing materials. With potassium ferricyanide reduced osmium tetroxide fixation, two prominent membrane systems were distinguished in the uterine epithelium. Basal invaginations are short infoldings of the basal membrane. The basal invaginations are common in other reproductive epithelia and tegument and probably enhance transport of materials by these epithelia. Laminated membranes are membrane stacks, resembling endoplasmic reticulum stacks. These membranes were abundant at the apical membrane. The birth plug is a solid cytoplasmic layer, lacking a lumen, and rich in cytoplasmic vesicles. This layer connects the tegument and the uterine epithelium.

Animals↗

Reversible pituitary enlargement in the syndrome of resistance to thyroid hormone.

We report pituitary enlargement after radioiodine ablation in a patient with elevated thyroid hormones and features of hyperthyroidism. Serum thyrotropin (TSH) levels were elevated despite normal circulating thyroid hormones, suggesting inappropriate TSH secretion associated either with a TSH secreting pituitary adenoma or resistance to thyroid hormone (RTH). Normal serum glycoprotein alpha-subunit levels and a preserved TSH response to thyrotropin-releasing hormone (TRH) favored RTH and this diagnosis was confirmed by showing the patient to be heterozygous for a missense mutation (R438H) in the thyroid hormone beta receptor (TRbeta) gene. Thyroxine replacement in supraphysiological doses were required to normalize TSH levels and resulted in regression of the pituitary enlargement, suggesting hyperplasia rather than coincident tumor. This case illustrates the need to avoid thyroid ablation in RTH patients and the importance of supraphysiological thyroxine replacement to prevent pituitary hyperplasia.

Female↗

The role of epidermal growth factor (EGF) and its receptor in mucosal protection, adaptation to injury, and ulcer healing: involvement of EGF-R signal transduction pathways.

Growth factors and their receptors are known to play important roles in normal cell proliferation, morphogenesis, tissue repair, and ulcer healing. Epidermal growth factor (EGF) inhibits acid secretion, exerts a trophic effect on gastroduodenal mucosa, protects gastric mucosa against injury, mediates mucosal adaptation, and accelerates gastroduodenal ulcer healing by stimulating cell migration and proliferation. EGF exerts its actions by binding to its receptor, EGF-R, a transmembrane protein tyrosine kinase, which triggers receptor dimerization, autophosphorylation, and recruitment of kinase substrates. These events result in Ras (GTP-binding protein) activation of the Ras/Raf/MAP kinase pathway, leading to phosphorylation of regulatory proteins and transcription factors and culminating in cell proliferation. Other pathways potentially activated by EGF include the phosphatidylinositol pathway and the JAK/STAT signaling pathway. Recent studies demonstrated that EGF-R-associated tyrosine kinase plays an essential role in regulating gastric mucosal cell proliferation after acute injury and further demonstrated activation of the EGF-R gene, EGF-R phosphorylation, and increased MAP kinase activity during early stages of experimental gastric ulcer healing. Finally, experimental data indicate that Helicobacter pylori vacuolating cytotoxin inhibits healing of experimental gastric ulcers, cell proliferation, binding of EGF to its receptor, EGF-induced EGF-R phosphorylation, and MAP kinase (ERK-2) activation. These H. pylori actions can explain its interference with the ulcer healing process.

Epidermal Growth Factor↗

Apolipoprotein B-100: conservation of lipid-associating amphipathic secondary structural motifs in nine species of vertebrates.

Development of a computer program called LOCATE allowed us to show that human apolipoprotein B-100 is composed of five domains, NH2-alpha1-beta1-alpha2-beta2-alpha3-COOH, enriched, alternately, in amphipathic alpha helixes and amphipathic beta strands. Using updated versions of this program, here we compare the complete sequence of human apolipoprotein B-100 with partial sequences from eight additional species of vertebrates (chicken, frog, hamster, monkey, mouse, pig, rat, and rabbit). The lipid-associating amphipathic alpha helixes cluster in domains alpha2 (between residues 2075 +/- 25 and 2575 +/- 25) and alpha3 (between residues 4100 +/- 100 and 4550 +/- 50) in all species for which those regions have been sequenced but with little conservation of individual helixes. Lipid-associating amphipathic beta strands cluster in domains beta1 (approximately residues 827-2000) and beta2 (approximately residue 2571 to residue 4000 +/- 50) in all species for which these regions have been sequenced, with conservation of several individual amphipathic beta strands. Hydrophobic segments are present in apolipoprotein B-100 sequences of all nine species but the frequency of occurrence is no greater than generally found in beta sheet-containing proteins. We conclude that four alternating lipid-associating domains, -beta1-alpha2-beta2-alpha3-COOH, are common supramolecular features of apolipoprotein B-100 in nine vertebrate species.

Amino Acid Sequence↗

Expression of adrenomedullin in portal hypertensive gastric mucosa of rats.

We examined the expression and localization of adrenomedullin (AM) mRNA, AM receptor (AM-R) mRNA and AM protein in normal and portal hypertensive (PHT) rat gastric mucosa. Methods included competitive reverse transcription-polymerase chain reaction (RT/PCR), in situ hybridization and Western blot analysis. Both AM mRNA and AM-R mRNA were strongly expressed not only in normal rat gastric mucosa but also PHT rat gastric mucosa. While total AM and AM-R mRNA abundance was similar in both normal and PHT stomachs, in the superficial mucosa-where major defense mechanisms are located-their expression was significantly reduced in PHT rats by 33% (AM mRNA) and 25% (AM-R mRNA) (both p .0.05). AM protein was also expressed similarly in both normal and PHT gastric mucosa. We conclude that AM and its receptor play a role in regulation of gastric mucosal microcirculation and thus gastric mucosal defense.

Adrenomedullin↗

Role of perceived danger in the mediation of obsessive-compulsive washing.

The role of danger expectancies in sub-clinical Obsessive-Compulsive Disorder (OCD) was examined in 18 undergraduate students who had displayed washing/contamination concerns. The perceived level of danger in a Behavioural Avoidance Test (BAT) involving a compound stimulus of potting soil, animal hair, food scraps, and raw meat was manipulated by varying the instructions participants were given at the commencement of the BAT. Participants were randomly allocated into a high-danger instruction condition or a low-danger instruction condition. Participants in the higher-danger instruction condition had higher mean ratings for anxiety and urge in wash, showed greater avoidance, and spent longer washing their hands at the completion of the task than participants in the low-danger instruction condition. However, only the differences in avoidance scores and post-BAT washing were statistically significant. These findings are discussed in relation to danger-based models of OCD.

Adult↗

Proteins C and NS4B of the flavivirus Kunjin translocate independently into the nucleus.

The subcellular locations in infected Vero cells of Kunjin (KUN) virus core protein C and NS4B were analyzed by immunofluorescence (IF) and by immunoelectron microscopy using monospecific antibodies. Selection of appropriate fixation methods for IF showed that both proteins were associated at all times with perinuclear membranes spreading outward in a reticular pattern and they entered the nucleus late during the latent period. Subsequently NS4B was also dispersed through the nucleoplasm, while C appeared in the nucleolus and the nucleoplasm. These nuclear locations were confirmed by immunogold labeling of cryosections of infected cells at 24 hr postinfection. Labeling of NS4B in cryosections was especially enriched in the perinuclear membranes of the endoplasmic reticulum. When C and NS4B were each expressed separately in stably transformed cell lines, both cytoplasmic and nuclear localization was observed by IF and confirmed by immunoelectron microscopy. Thus the two proteins translocated to the nucleus independently of each other and of other viral proteins. Dual IF with antibodies to double-stranded RNA showed that cytoplasmic locations of C and NS4B were apparently associated in part with the sites of viral RNA synthesis which were resistant to solubilization by Triton X-100.

Animals↗

The cognitive mediation of obsessive-compulsive handwashing.

The potential mediating roles of danger expectancies, responsibility, perfectionism, anticipated anxiety and self-efficacy on obsessive-compulsive handwashing were examined. Ratings were obtained from 27 obsessive-compulsive patients before and during a behavioural avoidance test involving a compound stimulus of potting soil, animal hair, food scraps and raw meat. Correlation and partial correlation analyses were conducted to examine the relationships between the cognitive predictor variables and anxiety, urge to wash, time in task and duration of post-test washing. Large and significant relationships between danger expectancies and the dependent measures were obtained, even when alternative mediators were held constant. No other variable remained significantly related to any of the dependent measures when severity of disease ratings were held constant. Results suggest that of the cognitive variables examined, danger expectancies are the most likely mediator of washing-related behaviour in obsessive-compulsive disorder.

Adult↗

Danger ideation reduction therapy (DIRT): preliminary findings with three obsessive-compulsive washers.

Three obsessive-compulsive patients received Danger Ideation Reduction Therapy (DIRT) in an initial treatment trial. All three subjects presented with contamination/washing concerns but refused to participate in exposure and response prevention. DIRT is solely directed at decreasing danger-related expectancies concerning contamination. DIRT procedures do not attempt to address inflated personal responsibility. In addition, DIRT does not involve direct or filmed exposure to contamination-related stimuli, or behavioural experiments. Components of DIRT include corrective information cognitive restructuring, filmed interviews, microbiological experiments, attentional focusing and Hoekstra's (1989) probability of catastrophe estimation task. Treatment consisted of between six and ten 1-hr weekly sessions. At post-treatment, substantial reductions in scores on the Padua Inventory, Maudsley Obsessional-Compulsive Inventory and two global rating scales were apparent for all subjects. These improvements were maintained at a 3-month follow-up. The theoretical and clinical implications of these preliminary findings are discussed.

Adult↗

Variation in the egg cell forming region of Gyrodactylus kobayashii Hukuda, 1940 (Monogenea:Gyrodactylidae).

The egg cell forming region of Gyrodactylus kobayashii from goldfish (Carassius auratus) is a thin nucleated cytoplasmic layer surrounding the developing egg cell (= oocyte). The cytoplasm contains numerous elougate membranes. As parasites age, the egg cell forming region becomes electron lucent. The apical membrane of the egg cell forming region becomes disrupted in places. A basal matrix is indistinct in new-born and young worms, becoming more evident as worms grow older. Numerous pits (= basal pits) are found along the basal plasma membrane of worms with a mature male system. These pits appear to be stable components of the membrane and resemble hemidesmosomes. Basal pits were co-incident with sperm in the egg cell forming region in 3 of 5 worms examined. The function of the basal pits of G. kobayashii could not be determined. It is postulated, however, that they either assist sperm to traverse the egg cell forming region to fertilize the egg cell or stabilize the egg cell forming region against damage by sperm traversing this layer. The egg cell forming region encloses a large egg cell and 1 or more smaller differentiating egg cells. The ripening egg cell has a large nucleus and extensive cytoplasm. The cell has a thickened membrane. Large vacuoles and invaginations at the periphery of the egg cell appear to engulf cytoplasm of the egg cell forming region.

Animals↗

Schistosoma japonicum: immunolocalization of paramyosin during development.

This paper describes the localization of paramyosin immunoreactivity in Schistosoma japonicum and represents the first comparative immunolocalization study among schistosome adult, cercariae and lung schistosomula by electron microscopy. A polyclonal antibody was utilized to immunolabel paramyosin or paramyosin-like proteins. Paramyosin was localized within the muscle layer of all 3 developmental stages. Furthermore, paramyosin was localized within granules of the post-acetabular glands of cercariae, and within the tegument matrix and surface of lung schistosomules. Adults and cercariae did not display any detectable paramyosin on the surface or within the tegument. The possible functions of paramyosin within S. japonicum and the relevance of these findings in relation to the reported protective properties of paramyosin as an anti-schistosome vaccine target molecule are discussed.

Animals↗

The cysteine proteinases of Schistosoma mansoni cercariae.

Based on substrate preferences, cercariae of Schistosoma mansoni were seen to express both cathepsin L and cathepsin B cysteine proteinases, although the former activity was many-fold greater. Two cathepsin L activities identified in cercarial extracts by zymography co-migrated with activities in extracts of 3 h and 24 h schistosomula and in extracts of adult worms. Since these enzymes have been implicated in haemoglobin digestion by adult worms, they may perform a similar function in schistosomula. Immunolocalization using scanning electron micrographs showed that cathepsin L and cathepsin B proteinases were present in the cercarial post-acetabular glands. In addition, cercarial serine proteinase activities considered to facilitate skin penetration efficiently cleaved the substrates Z-Gly-Pro-Arg-NHMec and Z-Gly-Pro-Lys-NHMec. Cercariae release most of this serine proteinase activity when induced to secrete the contents of their acetabular glands. In contrast, newly transformed 3 h and 24 h schistosomula did not express this activity.

Animals↗

Immunolocalization of the fatty acid-binding protein Sj-FABPc within adult Schistosoma japonicum.

This paper describes the first localization study of the 14.7 kDa fatty acid-binding protein in Schistosoma japonicum (SjFABPc) using transmission electron microscopy. A polyclonal antibody raised against recombinant Sj-FABPc was used in combination with a colloidal gold marker to determine the distribution of the protein within adult parasites. Sj-FABPc was localized within lipid droplets below the subtegumental region of the male parasite. Additionally, Sj-FABPc was present in the vitelline droplets of the vitelline glands of female parasites. There were no detectable levels of Sj-FABPc on the surface or within the tegument of male or female parasites. Possible functions of Sj-FABPc within S. japonicum and the relevance of these immunolocalization findings in light of the recent reports that the homologue Sm-FABPc is an important anti-S. mansoni vaccine target molecule are also discussed.

Animals↗

Ultrastructure of Kunjin virus-infected cells: colocalization of NS1 and NS3 with double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures.

The subcellular location of the nonstructural proteins NS1, NS2B, and NS3 in Vero cells infected with the flavivirus Kunjin was investigated using indirect immunofluorescence and cryoimmunoelectron microscopy with monospecific antibodies. Comparisons were also made by dual immunolabelling using antibodies to double-stranded RNA (dsRNA), the putative template in the flavivirus replication complex. At 8 h postinfection, the immunofluorescent patterns showed NS1, NS2B, NS3, and dsRNA located in a perinuclear rim with extensions into the peripheral cytoplasm. By 16 h, at the end of the latent period, all patterns had changed to some discrete perinuclear foci associated with a thick cytoplasmic reticulum. By 24 h, this localization in perinuclear foci was more apparent and some foci were dual labelled with antibodies to dsRNA. In immuno-gold-labelled cryosections of infected cells at 24 h, all antibodies were associated with clusters of induced membrane structures in the perinuclear region. Two important and novel observations were made. First, one set of induced membranes comprised vesicle packets of smooth membranes dual labelled with anti-dsRNA and anti-NS1 or anti-NS3 antibodies. Second, adjacent masses of paracrystalline arrays or of convoluted smooth membranes, which appeared to be structurally related, were strongly labelled only with anti-NS2B and anti-NS3 antibodies. Paired membranes similar in appearance to the rough endoplasmic reticulum were also labelled, but less strongly, with antibodies to the three nonstructural proteins. Other paired membranes adjacent to the structures discussed above enclosed accumulated virus particles but were not labelled with any of the four antibodies. The collection of induced membranes may represent virus factories in which translation, RNA synthesis, and virus assembly occur.

Animals↗