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Biomedical subjects

S Byrne

Publications and source records attributed to S Byrne.

43 records · Page 3Linked to original sources

Current concepts and recent advances in the management of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the Western World in those aged 65 and older. At present, several treatment modalities are utilised and several more are undergoing investigation in an attempt to retard the occurrence and progression of this devastating condition. AIMS: To provide the non-ophthalmologist with an understanding of the current treatment options available to patients suffering from all variants of AMD. METHODS: Medline and Embase search. RESULTS: Several treatment modalities have been investigated and utilised in the treatment of all variants of this condition. While promising results have been reported, no treatment is ideal. CONCLUSION: While no curative treatment for this condition currently exists, early recognition and treatment, if indicated, have been shown to reduce the risk of severe vision loss in patients with this condition.

Aging↗

Localization and distribution of tissue type and urokinase type plasminogen activators and their inhibitors Type 1 and 2 in human and rhesus monkey fetal membranes.

Fetal membranes consist of 10 distinct layers including components of amnion, chorion and decidua, the latter being of maternal origin. They form mechanically integrated sheets capable of retaining amniotic fluid and play an essential role in protecting fetal growth and development in the pregnant uterus. The extracellular matrix, substrate for plasminogen activators (PAs), is an important supportive framework of the fetal membranes. Fetal membranes from women with preterm premature rupture of membranes may differ in their protease activity compared with normal membranes. To identify the presence of PAs and their inhibitors (PAI) and their possible role in the process of fetal membrane rupture, this study investigated the distribution and localization of both protein and mRNA for tissue (t) and urokinase (u) PA and their inhibitors type 1 (PAI-1) and type 2 (PAI-2) in amniochorion of human and rhesus monkey using conventional and confocal immunofluorescence microscopy. In situ hybridization analysis showed that the distribution and localization of mRNAs for tPA, uPA, PAI-1 and PAI-2 were similar in the fetal membranes of human and rhesus monkey; no obvious species difference was observed. Evidence of tPA mRNA was detected in amniotic epithelium, trophoblast cells and nearly all cells of the decidual layer. Strong expression of uPA mRNA was noted in the decidual cells which increased in intensity as the abscission point was approached. Weak staining in chorion laeve trophoblast was also detected. In situ hybridization experiments showed PAI-1 mRNA to be concentrated mainly in the decidual cells, some of which were interposed into the maternal-facing edge of the chorion laeve. Maximal labelling of the decidua occurred towards the zone of abscission. Weak expression of PAI-1 mRNA was also noted in some cells of the chorion laeve. The distribution of PAI-2 mRNA in amniochorion was also concentrated in the cells of the decidual layer, maximum expression of the mRNA was in the level of abscission. No detectable amount of mRNAs for tPA, uPA, PAI-1 and PAI-2 was found in the fibroblast, reticular and spongy layers. Distribution of the proteins of tPA, uPA and PAI-1 in the fetal membranes of these two species was consistent with the distribution of their mRNA. Anti-PAI-2 immunofluorescence was found to be strongly concentrated in the amniotic epithelium, but PAI-2 mRNA was negative in this layer, suggesting that the epithelium-associated PAI-2 is not of epithelial origin. These findings suggest that a local fibrinolysis in fetal membranes generated by precisely balanced expression of PAs and their inhibitors via paracrine or autocrine mechanisms may play an essential role in fetal membrane development, maturation and in membrane rupture. Following an analysis of the distribution and synthesis of activators and inhibitors it was found that they may play a role in abscission during the third stage of labour.

Adult↗

Expression of urokinase, plasminogen activator inhibitors and urokinase receptor in pregnant rhesus monkey uterus during early placentation.

We have investigated plasmin mediated proteolysis associated with trophoblast invasion during early stages of pregnancy in the rhesus monkey. In situ hybridization and immunocytochemical localization were used to define the cellular and tissue distribution of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and 2 (PAI-2) and urokinase receptor in early monkey placenta and uterus. Our results indicate: (1) uPA is expressed in proliferating and invasive cytotrophoblast located in chorionic villi as well as in extravillous trophoblast associated with uterine arterioles. This raises the possibility that urokinase may play an important role in trophoblast invasion. (2) PAI-1 mRNA is specifically localized in two areas where invasive trophoblast cells encounter maternal tissue directly. The extravillous cytotrophoblast cells at the maternofetal junction express PAI-1 mRNA. The invasive endovascular trophoblast cells within the uterine arterioles also express PAI-1 mRNA. The location sensitive expression of PAI-1 mRNA at the maternofetal junction may imply a protective function of this protease inhibitor that might be induced through interaction with decidual cells. (3) Urokinase receptor antigen has also been found at the maternofetal junction and in endovascular trophoblast cells of the invaded maternal blood vessel. (4) PAI-2 immunoreactivity is found in association with cytotrophoblast cells in anchoring choronic villi suggesting its association with early placentation. In conclusion, we propose that the plasmin/plasminogen activator system may not only regulate extracellular matrix degradation, but also modify migration and invasive behaviour of extravillous trophoblast cells, during early placentation.

Animals↗

Plasminogen activators and inhibitors are transcribed during early macaque implantation.

Plasminogen activators and inhibitors may be important early in primate implantation but evidence for this is sparse in non-human primates. We define the expression of urokinase type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) and type 2 (PAI-2), the receptor for uPA (uPAR) and fibrin/fibrinogen in monkey implantation sites. In situ hybridization and immuno-histochemical localization of rhesus monkey implantation sites (day 15-16 postovulation) indicate: (1) uPA mRNA is localized to placental trophoblast, epithelial plaque and endometrial stroma. (2) tPA mRNA is mainly expressed in glandular cells of endometrium. (3) PAI-1 expression is linked to a specific population of trophoblasts that confront maternal cells, adding support to our view that it has a regulatory role in trophoblast invasion. (4) Localization of tPA antigen confirms that uterine glands are the major source of tPA and that it is also closely associated with fibrin(ogen) suggesting its possible function during implantation is fibrinolysis. (5) Unlike uPA mRNA, however, the distribution of uPA protein and its cell surface receptor uPAR suggests that it mediates trophoblast invasion and plays a significant role in angiogenesis. (6) PAI-2, the inhibitor associated with pregnancy in humans, was found in unidentified cells located specifically along the maternofetal junction. This localization adjacent to areas of cell death at the maternofetal junction implies that it may have a role as a protective curtain with anti-apoptotic function. In conclusion our results suggest that gene expression of PAs and PAIs in early implantation sites are tissue-specific, location-sensitive and function-related.

Animals↗

Management of the child with cystic fibrosis.

The association between salty skin and early death has been recognized since medieval times but the first description of cystic fibrosis was not published until 1938 by Anderson. Over teh last 53 years attitudes to the disease have changed radically and modern aggressive care involving a wide variety of professionals has contributed to the improved life expectancy.

Anti-Bacterial Agents↗

Parasuicide and general practice: a pilot study.

General Practitioners from Cork City and its environs were sent a questionnaire regarding their experience of parasuicide in the previous twelve months. Replies were received from 133 of the 185 GPs. 189 individuals, accounting for 212 episodes of parasuicide, were seen by 78 doctors, indicating a lower level of repetition than that found in hospital-referred cases. Almost a third of doctors saw no cases, just over one fifth saw one episode and the same proportion dealt with two. A small number of general practitioners saw many cases. Regarding management, 128 (60%) were referred to Casualty, 31 of whom were also referred for psychiatric care. Thirty percent were referred directly for psychiatric care. While only fourteen were retained within general practice without referral, 40% of the GPs felt that, ideally, acts of parasuicide should be retained with more specialised advice being obtained. Furthermore, 88.1% believed that management of parasuicide should form part of an integral part of post-graduate or continued general practitioner medical training. Clearly, GPs are willing to play a more active role in the management of parasuicide.

Family Practice↗