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Biomedical subjects

J Georgiou

Publications and source records attributed to J Georgiou.

18 recordsLinked to original sources
PubMed2002

Use of a highly sensitive quantitative telomerase assay in intracytoplasmic sperm injection programmes for the treatment of 47,XXY non-mosaic Klinefelter men.

We evaluated the role of the sensitive quantitative telomerase assay (SQTA) in the management of men with non-mosaic Klinefelter's syndrome (KS). Diagnostic testicular biopsy (DTB) was performed in 24 men with KS. A part of the DTB was stained and the remaining fragment was processed for the SQTA. After 3-18 months, a therapeutic testicular biopsy (TTB) was performed in the same testicle and the recovered specimens were processed to identify spermatozoa. Men with a SQTA outcome equal to 0.00 Units microg-1 protein (n = 7) demonstrated therapeutic testicular biopsy material that was negative for spermatogenic cells. In five men with a SQTA outcome of 8.11-38.03 Units microg-1, the most advanced germ cell was the spermatogonium/primary spermatocyte. In the remaining 12 men, the most advanced spermatogenic cell in the TTB was the spermatozoon. In these men, the SQTA outcome was equal to 25.76-92.68 Units microg-1 protein. Using 39.00 Units microg-1 protein as a cut-off value, the accuracy of the SQTA in identifying men positive for spermatozoa was 91.6%. It appears that the SQTA has a role for identifying non-mosaic KS men who have testicular spermatozoa.

Adult↗
PubMed2001

The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function.

Members of the Eph family of receptor tyrosine kinases control many aspects of cellular interactions during development, including axon guidance. Here, we demonstrate that EphB2 also regulates postnatal synaptic function in the mammalian CNS. Mice lacking the EphB2 intracellular kinase domain showed wild-type levels of LTP, whereas mice lacking the entire EphB2 receptor had reduced LTP at hippocampal CA1 and dentate gyrus synapses. Synaptic NMDA-mediated current was reduced in dentate granule neurons in EphB2 null mice, as was synaptically localized NR1 as revealed by immunogold localization. Finally, we show that EphB2 is upregulated in hippocampal pyramidal neurons in vitro and in vivo by stimuli known to induce changes in synaptic structure. Together, these data demonstrate that EphB2 plays an important role in regulating synaptic function.

Animals↗
PubMed1999

Muscarinic control of cytoskeleton in perisynaptic glia.

Similar to astrocytes at CNS synapses, perisynaptic Schwann cells (PSCs) surround nerve terminals at the neuromuscular junction (NMJ). These special teloglial cells are sensitive to neurotransmitters and upregulate glial fibrillary acidic protein (GFAP) when deprived of synaptic activity. We found that activation of muscarinic acetylcholine receptors (mAChRs) at PSCs, but not purinergic (ATP and adenosine) or peptidergic [substance P (SP) and calcitonin gene-related peptide (CGRP)] receptors, prevented this upregulation. When applied onto single PSCs, muscarine evoked Ca2+ responses that fatigued but prevented upregulation of this glial cytoskeletal protein. Application of ATP onto single PSCs evoked Ca2+ signals that showed little fatigue, and GFAP upregulation occurred. Thus, Ca2+ signals alone cannot prevent GFAP upregulation in the PSCs. After blockade of cholinergic receptors by gallamine, neuronal activity was not effective in maintaining low GFAP levels in the perisynaptic glia. Last, immunohistochemistry disclosed mAChRs on PSCs and nearby fibroblasts. Thus, acetylcholine secreted by the nerve terminal acts on the PSCs via mAChRs to regulate GFAP. Cytoskeletal changes may influence perisynaptic glial functions, including growth, remodeling, and modulation of the synapse.

Animals↗
PubMed1999

Non-myelin-forming perisynaptic schwann cells express protein zero and myelin-associated glycoprotein.

Perisynaptic Schwann cells (PSCs) envelop axonal terminals and are physiologically distinct from the nearby myelinating Schwann cells (MSCs), which surround the same innervating motor axons. PSCs have special functions at the neuromuscular synapse, where they detect and can modulate neurotransmitter release. Although PSCs are similar to non-myelinating Schwann cells in that they do not form multiple myelin wrappings around nerve terminals, they do wrap around single nerve terminals. These differences, as well as others, lead us to question whether PSCs are truly of Schwann cell origin. We thus characterized the expression of molecules, classically associated with myelin and Schwann cells, in PSCs at the frog neuromuscular junction. We wondered whether PSCs express the Schwann cell marker protein zero (P(0)) and whether their lack of myelination was related to an absence of myelin-associated glycoprotein (MAG), a protein found in myelinating cells that is considered important in myelination. Instead, we found that PSCs express both P(0) and MAG, and other myelinating glial markers such as galactocerebroside and 2',3'-cyclic nucleotide 3'-phosphodiesterase. In denervated preparations, P(0) and MAG expression persisted, including at newly formed PSC extensions. Because PSCs do not myelinate, it is clear that expression of these proteins alone is not sufficient for myelin formation. It is possible that factors present at synapses may prevent myelination, while P(0) and MAG may mediate adhesion between nerve terminals and the surrounding PSCs. The results indicate that PSCs are of Schwann cell origin.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1998

In vitro and in vivo evaluation of insulin-producing beta TC6-F7 cells in microcapsules.

In the present study, the insulin secretory capacity of beta TC6-F7 cells in microcapsules was evaluated. The cell mass within capsules was found to expand in a three-dimensional fashion, in contrast to cells seeded on plates that grew as a monolayer. In in vitro studies, both free and encapsulated cells were found to secrete insulin in the absence of glucose, at 13.6 +/- 1.1 and 14.5 +/- 0.9 ng.10(6) cells-1.60 min-1, respectively, with the response rising to a maximum of 26.0 +/- 0.8 and 31 +/- 2.3 ng.10(6) cells-1.60 min-1 in the presence of 16.8 mM glucose. Encapsulated cells were able to produce Ca2+ responses in the presence of KCl (50 mM) and BAY K 8644 (100 microM). In in vivo studies, intraperitoneal transplantation of 3.0 x 10(6) microencapsulated cells into mice (n = 5) with streptozotocin-induced diabetes resulted in the restoration of normoglycemia up to 57 days. Insulin concentrations rose from 0.4 +/- 0.1 ng/ml before the graft administration to 2.2 +/- 0.8 ng/ml after the transplantation in the normoglycemic recipients. An oral glucose challenge in transplant recipients demonstrated a flat glucose response, suggesting extremely high glucose clearance rates. These data demonstrate the potential use of the immunoisolated beta-cell lines for the treatment of diabetes.

Animals↗
PubMed1997

Administration of high doses of recombinant human erythropoietin to patients with beta-thalassemia intermedia: a preliminary trial.

Four patients (1 male, 3 female, age range 16-56 yr) with beta-thalassemia intermedia were given high doses of recombinant human erythropoietin (rHuEpo), iron sulfate and folic acid in an attempt to improve their anemia. The dose schedule was: rHuEpo, 500 U/kg 3 times weekly, iron sulfate, 300 mg/d and folic acid, 5 mg/d. All patients were red blood cell transfusion-dependent. Hematological data and fetal hemoglobin (HbF) were assayed every 2 wk. XmnI polymorphism and beta-thalassemia mutations were identified by PCR. All patients showed a moderate to high increase in hemoglobin values (mean value: 2.5 g/dl) and in 1 patient HbF levels also increased; 3 patients became red blood cell transfusion-independent and 1 patient was able to extend the intervals between transfusions significantly. No side effects were observed during rHuEpo therapy.

Adolescent↗
PubMed1997

Imaging of calcium in Drosophila larval motor nerve terminals.

Calcium measurements in the presynaptic terminal are essential in the investigation of mechanisms underlying neurotransmitter release. To enhance the genetic analysis of secretory mechanisms, we have developed Ca2+ imaging techniques for Drosophila larval motor nerve terminals. We studied Ca2+ signals in "big" (type Ib) and "small" (type Is) boutons that innervate ventral longitudinal muscles 6 and 7 in each abdominal segment of Canton-S (CS)-strain 3rd instar larvae. The indicator fluo-3 in conjunction with confocal microscopy was used to detect stimulus-dependent changes in [Ca2+]i. The Ca2+ signals were reliable and reproducible, and the resting fluorescence remained constant throughout the experiments. The Ca2+ signals increased with stimulus frequency from 5 to 20 Hz for both bouton types. No significant differences in the Ca2+ signals were seen between the two bouton types at 5 and 20 Hz, but there was a difference at 10 Hz. The decay of the Ca2+ signal was more prolonged after 20-Hz stimulation than after 5 and 10 Hz. At the single-synapse level, the secretory efficacy of Is synapses is greater than that of Ib synapses, but our data show that factors other than differences in Ca2+ entry may govern the strength of synaptic transmission.

Animals↗
PubMed1995

Functional expression of the rat pancreatic islet glucose-dependent insulinotropic polypeptide receptor: ligand binding and intracellular signaling properties.

Incretins are endogenous peptides released from the gastrointestinal tract into the circulation during a meal that potentiate glucose-stimulated insulin secretion. At present, there are two established incretins: glucose-dependent insulinotropic polypeptide (GIP) and the truncated glucagon-like peptides (tGLPs), which are now being investigated for use in the treatment of diabetes mellitus. In the present study we cloned a rat islet GIP receptor complementary DNA (GIP-R1) to answer several important questions regarding the ligand-binding and intracellular signaling properties of the GP receptor. GIP-R1, when expressed transiently in monkey kidney (COS-7) or stably in Chinese hamster ovary (CHO-K1) cells, demonstrated comparable high affinity binding for either synthetic porcine (sp) GIP or synthetic human (sh) GIP. The IC50 values for displacement of [125I]spGIP in CHO-K1 cells were 2.6 +/- 0.8 and 3.1 +/- 0.9 nM for two different preparations of shGIP, and 3.7 +/- 1.5 and 3.6 +/- 0.4 nM for two preparations of spGIP. Saturation isotherms obtained with both intact cells and membranes gave monophasic binding curves with apparent Kd values of 204 +/- 17 and 334 +/- 94 pM, respectively. Cells expressed 12-15 x 10(3) receptors/cell. In COS-7 cells, spGIP and shGIP also exhibited similar IC50 values (7.6 +/- 1.2 and 8.9 +/- 1.8 nM, respectively). The receptor in CHO-K1 cells bound GIP-(1-30) with lower affinity (IC50 = 39 +/- 17 nM), whereas the fragments GIP-(19-30), GIP-(18-28), and GIP-(21-26) showed no apparent binding. The specificity of the receptor was further examined using several structurally related peptides. Surprisingly, exendin-(9-39) [Ex-(9-39)], a GLP-1 receptor antagonist, and Ex-4-(1-39), a GLP-1 receptor agonist, demonstrated some affinity for the GIP receptor, with 39% and 21% displacement of [125I]spGIP, respectively, at 1 microM. Other members of the secretin/vasoactive intestinal peptide family of peptides tested showed no interaction. GIP-R1 receptor binding correlated with activation of the adenylyl cyclase system, whereby spGIP and shGIP evoked concentration-dependent increases in cAMP accumulation with EC50 values of 8.7 +/- 1.5 x 10(-10)M and 8.1 +/- 1.6 x 10(-10)M for spGIP and shGIP, respectively. Increases in cAMP in the presence of 10 nM spGIP were not dependent on the ambient glucose concentration, with 22- and 18-fold increases in cAMP accumulation at 0.1 and 5.5 mM glucose, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Synaptic regulation of glial protein expression in vivo.

We investigated signaling between individual nerve terminals and perisynaptic Schwann cells, the teloglial cells that cover neuromuscular junctions. When deprived of neuronal activity in vivo, either by motor nerve transection or tetrodotoxin injection, perisynaptic Schwann cells rapidly up-regulated glial fibrillary acidic protein. Addition of transcription or translation inhibitors to excised muscles prevented this increase. Stimulation of cut nerves prevented glial fibrillary acidic protein increases even when postsynaptic nicotinic receptors were blocked, but not when neurotransmitter release was blocked with omega-conotoxin GVIA. We conclude that there is a nerve terminal to glial signal, requiring presynaptic neurotransmitter release, which regulates perisynaptic Schwann cell genes. This may be a general principle since many types of glial are sensitive to transmitters applied in vitro or released in situ.

Action Potentials↗
PubMed1994

Molecular basis and haplotype analysis of delta, beta-thalassemic chromosomes in Greece.

The molecular defect was defined in 38 delta beta-thalassemic chromosomes from 30 unrelated heterozygous and 4 homozygous patients of Greek origin. Restriction fragment beta-gene cluster haplotypes were studies in 23 delta beta-thalassemic chromosomes. The molecular lesion was identical in all studied cases and corresponds to the 'Sicilian' type of delta beta-thalassemia. Restriction haplotypes analysis has shown that, with one exception only, all Greek delta beta-thalassemic chromosomes bear the polymorphic sites which characterize haplotypes I or VII, the former being probable by indirect evidence. The striking similarities of the molecular lesion and the underlying haplotypes are consistent with two theories: (1) The deletion occurred once on a chromosome and spread all over Greece and the Mediterranean area thereafter; (2) the 5' subhaplotype +----favors the deletional event in the delta-beta gene area.

Base Sequence↗
PubMed1989

Progress of coronary artery disease: compliance to therapy.

UNLABELLED: From a sample of 1,824 patients with coronary artery disease (CAD) at the time of their interview, 827 males (M) and 251 females (F), had at least one distinct recurrence of their disease--some type of angina (A) or myocardial infarction (MI). In these patients, the age and type of CAD at the first and second manifestations (MSs) were noted, together with the patient's compliance to prescribed therapy. The first MF of CAD in Ms was A in 61% at the age of 59.4 +/- 10.15 years and MI in 39% at a significantly younger age (54.4 +/- 10.54 years, p less than 0.001). In Ms with A, the second MF was again A in 39% at the age of 61.4 +/- 10.14 years and MI in 61% at 62.1 +/- 10.2 years. In Ms with MI, the second MF was A in 85% at 56.5 +/- 10.52 years and MI in 15% at 59.2 +/- 12.0 years. No statistical difference was found between patients with good or poor compliance to therapy in connection with the time of the second MF as A or MI. A significantly lower percentage of MI after A, as the first MF, was found in patients with good compliance (55%) than in patients with poor compliance (69%, p less than 0.01). In Fs the first MF was A in 88% at 61.6 +/- 9.82 years and MI in 12% at 58.1 +/- 9.1 years (p less than 0.05). The second MF for all F patients was MI in 48% at 65.4 +/- 10.02 years, compared with A in 52% at the age of 64.5 +/- 9.78 years. CONCLUSIONS: In Ms a rather quick (approximately equal to 2.5 years) progression of CAD is expected after its initial MF mainly as A (approximately equal to 61%), and in these, MI as the second MF is more common in patients with poor compliance to therapy. In Fs there is a delayed first MF mainly as A (approximately equal to 90%) and a delayed second MF as A and MI in equal proportion.

Coronary Disease↗
PubMed1985

Carcinoma of the breast in three siblings.

Reported are three siblings, a sister and 2 brothers, who had breast cancer. The paternal grandmother of the proband was known to have had breast cancer. It is our belief that this report supports further the genetic etiology of certain breast cancers. The study examines the literature with regard to genetically transmitted female breast cancer and also implies a genetic etiology of male breast cancer. Of special interest is the fact that the female sibling had bilateral breast cancer during her premenopausal years and that one of the two brothers also developed his lesion at an early age, 41 years.

Adult↗
PubMed1985

Coexistence of abdominal aortic aneurysm and carcinoma of the colon: a dilemma.

The incidence of colonic cancer coexisting with an aneurysm of the abdominal aorta is approximately 2%. Such a coexistence presents a true dilemma to the surgeon for it is often difficult to decide whether to treat the carcinoma or the aneurysm first. This report summarizes the opinions of 46 Professors of General Surgery and Vascular Surgery who gave their response as to which condition should receive priority of treatment. Approximately one third of the respondents favored excision of the carcinoma first; one third stated they would excise the aneurysm first; and the remaining third said they would withhold a decision until laparotomy was performed. Two surgeons replied that they would attempt to perform aneurysmectomy and colectomy simultaneously.

Aorta, Abdominal↗
PubMed1985

Intestinal ischemia caused by cocaine ingestion: report of two cases.

Ingested cocaine can be a cause of severe bowel ischemia or gangrene. Two cocaine addicts who ingested large quantities of the drug developed severe abdominal symptoms and signs caused by bowel ischemia. In one patient gangrene of the bowel necessitated repeated resections and was followed, several weeks later, by death. The other patient suffered less severe ischemia and the bowel returned to normal. The diagnosis of bowel ischemia should be suspected whenever a cocaine addict has severe abdominal symptoms and signs. The presence of marked leukocytosis suggests bowel gangrene and demands prompt surgical intervention.

Adult↗
PubMedDate not supplied

Strength of synaptic transmission at neuromuscular junctions of crustaceans and insects in relation to calcium entry.

Crustacean and insect neuromuscular junctions typically include numerous small synapses, each of which usually contains one or more active zones, which possess voltage-sensitive calcium channels and are specialized for release of synaptic vesicles. Strength of transmission (the number of quantal units released per synapse by a nerve impulse) varies greatly among different endings of individual neurons, and from one neuron to another. Ultrastructural features of synapses account for some of the physiological differences at endings of individual neurons. The nerve terminals that release more neurotransmitter per impulse have a higher incidence of synapses with more than one active zone, and this is correlated with more calcium build-up during stimulation. However, comparison of synaptic structure in neurons with different physiological phenotypes indicates no major differences in structure that could account for their different levels of neurotransmitter release per impulse, and release per synapse differs among neurons despite similar calcium build-up in their terminals during stimulation. The evidence indicates differences in calcium sensitivity of the release process among neurons as an aspect of physiological specialization.

Animals↗
PubMedDate not supplied

Germ cell transplantation: a review and progress report on ICSI from spermatozoa generated in xenogeneic testes.

Results from the transplantation of donor male germ cells into xenogeneic recipient seminiferous tubules indicate that donor spermatogonia are capable of differentiating to form spermatozoa morphologically characteristic of the donor species. Germ cell transplantation procedures combined with developments in freezing, culturing or enriching germ cell populations have applications of paramount importance in medicine, basic sciences and animal reproduction. Additionally, these techniques can serve as an alternative approach for gonadal protection and fertility preservation in patients with cancer. This article is a chronological critical review of the technological advances that followed the initial successful transplantation of mouse germ cells into recipient mice. Furthermore, the factors responsible for the immunological privilege properties of the testis and the parameters influencing the potential of mammalian germ cells to undergo mitosis and meiosis within a xenogeneic testis are described. Finally, the role of human germ cell transplantation procedures in the therapeutic management of non-obstructive azoospermia is discussed.

Animals↗