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Biomedical subjects

P Georgiou

Publications and source records attributed to P Georgiou.

At least 19 recordsLinked to original sources
PubMed2006

Autoantibodies against aggrecan in systemic rheumatic diseases.

OBJECTIVE: This study was undertaken to investigate the presence of autoantibodies against the main cartilage proteoglycan, aggrecan, in systemic rheumatic disease sera, and to identify substructure(s) responsible for the autoimmune response. METHODS: Sera were obtained from 86 patients with various systemic rheumatic diseases, 14 with osteoarthritis (OA), 18 with cancer and 40 healthy individuals. The presence of autoantibodies against aggrecan was examined by a solid phase assay and by Western blotting, using proteoglycan aggregates treated with proteolytic enzymes. The positive bands were subjected to nanohigh performance liquid chromatography (nanoHPLC)-MS, in order to identify the aggrecan substructures involved in the autoimmune response. RESULTS: Autoantibodies against aggrecan were identified in all systemic rheumatic disease sera at a high titre, almost three times that observed in healthy controls. OA and cancer sera produced a reaction equal to that of the healthy. Western blotting analysis of aggrecan proteolytic fragments revealed the presence of a triple band, reacting with the patients' sera, of about 37 kDa, which also reacted with a polyclonal antibody against hyaluronan-binding region. NanoHPLC-MS analysis suggested that this band belonged to the G2 domain of aggrecan. CONCLUSION: At least a part of the autoimmune reaction to aggrecan, displayed by the systemic disease sera, involves the G2 domain. The significant difference observed between these sera and those from other diseases, especially cancer, may suggest a possible discriminatory role of anti-aggrecan antibodies. This may help in the differential diagnosis in complicated clinical cases. However, for this to be confirmed, studies in larger cohorts of patients should be performed.

Adult↗
PubMed2005

Reconstructive surgery for kidney transplant recipients.

Many decades have passed since the first kidney transplantation, which is now the most common organ transplant performed worldwide. Despite the impressive advances, some patients may develop posttransplant complications that require proper management and treatment. The plastic and reconstructive surgeon, among others, may be called on to help resolve a number of reconstructive problems present in the immunosuppressed kidney recipients. This study presents our experience with 41 kidney recipients who needed plastic surgical treatment. Patients were placed into one of three study groups according to the type of posttransplant surgical condition. Group 1 included 17 patients with posttraumatic wound healing problems; group 2, 17 patients with skin tumors; and group 3, 7 patients with other posttransplant surgical complications. Only two of these patients had early posttransplant wound dehiscence; the remaining patients suffered late complications. In conclusion, the kidney recipient can successfully undergo minor or major reconstructive procedures. The possibility of surgical problems arising during the early posttransplant period presents increased complication rates, possibly due to high immunosuppressive drug levels.

Cadaver↗
PubMed2000

Upper eyelid island orbicularis oculi myocutaneous flap for periorbital reconstruction.

PURPOSE: To describe the upper eyelid island orbicularis oculi myocutaneous flap, medially or laterally based, for reconstruction of periorbital defects. METHODS: During the past three years we have used the island orbicularis oculi myocutaneous flap in 62 patients with tumors of the periorbital area, with the following indications: (a) anterior lamellar defects of the medial aspect of the upper eyelid, when the peripheral arcade is intact; (b) up to 2/3 anterior lamellar lower eyelid defects; (c) inner and outer canthus defects; and (d) defects of the peripalpebral area (the lateral half of the eyebrow, bridge of the nose and suprazygomatic areas). RESULTS: The flap proved to be flexible, safe, relatively simple, and provided good functional and aesthetic results. Complications were minimal. CONCLUSIONS: The upper eyelid island orbicularis oculi myocutaneous flap may be a useful tool for periorbital reconstruction.

Eyebrows↗
PubMed1999

Upper eyelid orbicularis oculi flap with tarsoconjunctival island for reconstruction of full-thickness lower lid defects.

The reconstruction of full-thickness defects of the lower eyelid after tumor resection is a challenging operation. The great number of techniques for these defects shows that none of them is the operation of choice. The method of reconstruction will be chosen according to the extent of the defect, the missing components of the eyelid structure, the age of the patient, and the quantity and the quality of the surrounding tissues. In this article, we propose, under specific indications, the use of a pedicled myocutaneous orbicularis oculi flap with a tarsoconjunctival island from the upper eyelid to reconstruct full-thickness lower lid defects. The more choices in a surgeon's armamentarium, the more easily the difficult problems of periorbital surgical oncology will be resolved.

Aged↗
PubMed1997

Island mucochrondrocutaneous flap for reconstruction of total loss of the lower eyelid.

The methods usually employed for reconstruction of total lower eyelid loss include (1) tarsoconjunctival flaps from the upper eyelid and skin-graft cover and (2) chondromucosal grafts and local skin-flap cover. We report a technique for coverage of these defects with an island flap involving the full thickness of the ipsilateral nasal wall based on the dorsal (external) nasal vessels, terminal branches of the ophthalmic vessels. The advantages of this method are (1) the main components of the eyelid (skin, tarsus, conjunctiva) are reconstructed in a single short operation, even under local anesthesia, (2) there is one donor area that can be closed primarily without significant deformity, (3) the upper lid remains intact, and ectropion is improbable, and (4) the procedure involves a short hospitalization. As disadvantages we might mention bulkiness of the new eyelid and difficult dissection of the (subcutaneous) pedicle.

Aged↗
PubMed1997

Effect of pranlukast, an oral leukotriene receptor antagonist, on leukotriene D4 (LTD4) challenge in normal volunteers.

BACKGROUND: There is increasing evidence to show that leukotrienes are important mediators in asthma. Leukotriene receptor antagonists protect against antigen and exercise challenges in patients with chronic asthma. A study was undertaken to investigate the activity of the leukotriene receptor antagonist pranlukast (SB 205312, ONO-1078) in blocking bronchoconstriction induced by leukotriene D4 (LTD4) inhalation. The selectivity of pranlukast was evaluated using histamine challenge. METHODS: Pranlukast, 450 mg twice daily, was given to eight healthy non-smoking men for five days in a randomised, double blind, placebo controlled, crossover study. The specific airways conductance (sGaw) was measured before and after bronchial provocation with inhaled LTD4 at 3.5 hours after the first dose and at 3.5 and 9.5 hours after the last dose of pranlukast on the morning of day 5. The concentration of LTD4 required to produce a fall in sGaw of 35% (PC35) was calculated. Subjects also underwent a histamine challenge 3.5 hours after a single dose of pranlukast, 450 mg, or placebo. RESULTS: A single dose of pranlukast produced a 10.6 fold increase in PC35sGaw (95% confidence interval (CI) 4.4 to 25.5; p < 0.001) for LTD4 at 3.5 hours after dosing compared with placebo. Three and a half hours after the morning dose of pranlukast on day 5 the PC35sGaw for LTD4 was increased 25.9 fold (95% CI 10.8 to 62.2; p < 0.001) and was still increased sevenfold (95% CI 2.9 to 16.7; p < 0.001) relative to placebo 9.5 hours after administration of the morning dose. No significant differences were noted for the PC35sGaw to histamine for pranlukast compared with placebo. CONCLUSIONS: This study shows that pranlukast is a potent and selective LTD4 receptor antagonist in humans which blocks LTD4 challenge after initial and repeated administration when given twice daily for five days.

Administration, Inhalation↗
PubMed1996

Tear and saliva ferning tests in Sjögren's syndrome (SS).

The purpose of this study was to evaluate the tear ferning test (TFT) and the saliva ferning test (SFT) as diagnostic tests for xerophthalmia and xerostomia respectively in patients with SS. Dried samples of freshly produced tears and saliva from: (A) 36 healthy controls without sicca symptoms, (B) 61 patients with primary SS, (C) 53 patients with secondary SS and (D) 22 patients with psychiatric disorders receiving antidepressants, were examined by polarizing light microscopy. All individuals included in the study were postmenopausal women. The crystallization was classified into 4 types according to the ferning phenomenon: uniformity, branching, spreading and integrity (type I normal and II, III, IV abnormal). Abnormal TFT was found in tear samples of: (A) 8/72 normal control eyes, (B) 110/122 prim SS eyes, (C) 86/106 sec SS eyes and (D) 30/44 psychiatric patients' eyes. Abnormal SFT was found in: (A) 6/36 of normal controls, (B) 59/61 of prim SS, (C) 51/53 of sec SS patients and (D) 16/22 of psychiatric patients. The differences of both TFT and SFT of patients with prim SS and sec SS versus controls were significant (p < 0.001). The sensitivity of TFT was found to be high both in prim SS (90%) and in sec SS (81%). In addition the specificities of TFT and SFT were high 89% and 83% respectively. On the other hand the differences of TFT and SFT in psychiatric patients receiving antidepressants versus normal controls were also significant (p < 0.05 and p < 0.025 respectively). According to our data TFT and SFT are simple, sensitive and specific tests to evaluate xerophthalmia and xerostomia in SS and probably in other conditions characterized by mucous membrane dryness.

Crystallization↗
PubMed1996

The single and multiple dose pharmacokinetics of pranlukast in healthy volunteers.

OBJECTIVE: The pharmacokinetics of pranlukast, a leukotriene LTD4 antagonist, were studied in 48 young, healthy subjects after single and repeated oral doses (given every 12 h) ranging from 112.5 to 675 mg. The doses were administered 30 minutes after a light breakfast. RESULTS: Maximal drug concentrations generally occurred between 2 and 6 h after dosing, and there was some evidence of an absorption lag-time. Secondary peaks were observed in the plasma concentration vs. time profiles of many of the study subjects after both single and repeated doses, particularly during the period of maximum drug absorption. In general, after both single and repeated doses, there were related increases in the corresponding Cmax and AUC with a rise in dose, although the increase was diminished at doses above 450 mg. With repeated dosing of pranlukast the mean AUC was generally higher (up to 1.6-fold), and the higher plasma concentrations allowed characterisation of a longer mean t 1/2 than after single dose administration. The mean steady-state trough plasma concentrations attained after evening doses were considerably higher (up to 14-fold) than those obtained after the morning dose. CONCLUSION: The data suggested that the pharmacokinetics of pranlukast are influenced by the time of dosing. Based on analysis of urinary 6 beta-hydroxycortisol excretion, there was no evidence that pranlukast modified the metabolic activity of cytochrome P-450 3A isoenzymes.

Adolescent↗
PubMed1996

A double blind, placebo-controlled study to assess the effect of famciclovir on virus replication in patients with chronic hepatitis B virus infection.

This is the first double-blind controlled study of famciclovir, an oral antiviral agent, as potential therapy for chronic hepatitis B virus (HBV) carries. A fall of more than 90% in HBV DNA levels was noted in six of 11 evaluable patients treated with a 10 day course of oral famciclovir. Further studies with more prolonged therapy are ongoing.

2-Aminopurine↗
PubMed1995

Role of ETS1 in IL-2 gene expression.

The ETS1 gene encodes a sequence-specific transcription factor binding to purine-rich DNA sequences (-GGAA-) present in the transcriptional regulatory regions of many cellular and viral promoters/enhancers, including many lymphokine genes. The ETS1 gene is expressed at high levels in resting T cells and at very low levels after T cell activation, suggesting it may suppress the expression of genes induced during T cell activation. To find out if ETS1 regulates expression of the IL-2 gene, we have ectopically expressed antisense (AS) ETS1 in Jurkat T cells to block the formation of ETS1 proteins. AS ETS1 transfectants produce higher levels of IL-2 compared with sense ETS1 transfectants. Expression of ETS1 DNA binding domain in Jurkat T cells also decreased the production of IL-2. In AS ETS1 transfectants, IL-2 formation was completely inhibited by cyclosporin A and FK590. The IL-2 promoter linked to a chloramphenicol acetyl transferase reporter gene has high activity in AS ETS1 transfectants, indicating that increased IL-2 production seems to be a result of transcriptional induction. Taken together, these results suggest the possibility that ETS1 may act as a negative regulator of IL-2 gene transcription and provide a rational approach toward engineering the endogenous expression of IL-2 in T cells.

Cell Line↗
PubMed1994

Regenerative and non-regenerative calcium transients in hamster eggs triggered by inositol 1,4,5-trisphosphate.

1. Inositol 1,4,5-trisphosphate (InsP3) injected into unfertilized golden hamster eggs elicits a hyperpolarizing response (HR) that is due to stimulation of calcium-activated potassium channels in the egg plasma membrane. 2. A single injection of InsP3 gave a single HR above a threshold value of 0.3 nM. At 5 nM and above, InsP3 induced HRs with no detectable latency. At concentrations between these two values a latency was observed. The amplitude of the HR was independent of InsP3 concentration. 3. A second HR could be elicited by injection of InsP3, but five times more InsP3 was required to trigger a second HR, and 10-100 times more to give an HR of similar magnitude to the first, and there was no latency. 4. The increase in [Ca2+]i in response to an initial injection of 1 nM InsP3 could be resolved into two distinct components: a slow, early rise immediately after InsP3 injection (phase I) followed by a larger and more rapid increase (phase II). The initiation of an HR coincided with the second component of the [Ca2+]i increase. 5. Further injection of InsP3 resulted only in slow, smaller increases in [Ca2+]i that resembled phase I and often did not cause an HR. Phase II appeared to be absent. However, 100-fold greater InsP3 concentrations gave slow, larger Ca2+ transients (and HRs) with no detectable latency. 6. If large amounts of InsP3 were allowed to leak into the eggs constantly from a pipette, repetitive calcium transients were seen. Unlike the sustained repetitive responses seen at fertilization, they were often smaller than the initial transient and less well sustained. However, a subsequent transient could still be elicited on injection of very large concentrations of InsP3. 7. InsP3 can induce regenerative, all-or-none [Ca2+]i increase (CICR) in hamster eggs, often with a long latency, as well as non-regenerative increases. InsP3 injections desensitize CICR and cannot mimic all the features of Ca2+ signalling at fertilization in the hamster egg, in particular, the sensitization of CICR caused by the sperm.

Animals↗
PubMed1994

Tear mucus ferning in patients with Sjögren's syndrome.

The purpose of this study is to evaluate the possibility of using the mucus ferning phenomenon of the tears as a diagnostic test for Keratoconjunctivitis sicca in patients with Sjögren's syndrome. Using a polarising light microscope dried samples were tested for ferning phenomenon collected from (1) 36 healthy controls, (2) 21 patients with primary Sjögren's syndrome, and (3) 15 patients with secondary Sjögren's syndrome. Patients with Sjögren's had xerostomia, abnormal salivary gland biopsy and at least two positive tests for Kerato-conjunctivitis sicca. Patterns of mucus crystallization were classified into 5 types according to uniformity, branch spreading and integrity (types I, II normal, types III, IV, V abnormal). Abnormal ferning was found in tear samples of 8 out of 72 normal control eyes, 38 out of 42 with primary Sjögren's syndrome and 25 out of 30 with secondary Sjögren's syndrome. The differences between both primary and secondary Sjögren's syndrome, in comparison to healthy controls, were significant (p < 0.001). The sensitivity of the method was found 90% for primary Sjögren's syndrome and 80% for secondary Sjögren's syndrome. According to our data, tear mucus ferning test is a simple, sensitive and specific test to estimate Keratoconjunctivitis sicca in patients with Sjögren's syndrome.

Humans↗
PubMed1994

Epitope mapping of human ETS1 monoclonal antibody.

The epitope for E44 monoclonal antibody (mAb) was mapped using mutated ETS1 proteins lacking different carboxy-terminal regions and by the employment of synthetic oligopeptides spanning the epitope region. This epitope lies around Arg211 of the human ETS1 protein since substitution of Arg211 by Gln211 in the epitope region results in the loss of recognition of the mouse ETS1 protein by E44 mAb. Substitution of Leu214 by valine214 in the epitope region (as is found in the chicken ETS1 and viral Ets proteins) does not alter the capacity of the E44 mAb to recognize this antigen. Taken together, these results suggest that a specific ionic interaction is able to play a pivotal role in the recognition of the ETS1 protein by the E44 mAb.

Amino Acid Sequence↗
PubMed1994

Linear pharmacokinetics of penciclovir following administration of single oral doses of famciclovir 125, 250, 500 and 750 mg to healthy volunteers.

Twenty healthy male volunteers received single oral doses of famciclovir (125-750 mg), in a randomized, single-blind, crossover study. Plasma and urine concentrations of penciclovir and its 6-deoxy precursor, BRL 42359, were determined and penciclovir plasma concentration-time data submitted to model-independent pharmacokinetic analysis. Peak plasma concentrations of penciclovir were obtained at median times of 0.5-0.75 h after dosing. The areas under the concentration versus time curves (AUC) and the peak penciclovir concentration (Cmax) increased linearly with dose of famciclovir. Time to Cmax, elimination half-life, urinary recovery and renal clearance of penciclovir did not change with increasing dose. Famciclovir was excreted via the kidneys as penciclovir (60%) and BRL 42359 (5%), respectively. Famciclovir was well tolerated by all subjects with a low incidence of adverse effects. In conclusion, penciclovir thus displays linear pharmacokinetics in the anticipated therapeutic dose range of famciclovir.

2-Aminopurine↗