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Biomedical subjects

G Hassan

Publications and source records attributed to G Hassan.

At least 19 recordsLinked to original sources
PubMed2005

Immunomodulation of autoimmune and inflammatory diseases with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over two decades. Since the early 1980s, the therapeutic efficacy of IVIg has been established in idiopathic thrombocytopenic purpura, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, dermatomyositis and Kawasaki syndrome, and the prevention of graft versus host disease in recipients of allogeneic bone marrow transplants. Its use has also been reported in a large number of other autoimmune and systemic inflammatory conditions. In this review, we discuss the mechanisms by which IVIg exerts immunomodulatory effects in immune pathologies.

Antigen-Presenting Cells↗
PubMed2004

Postoperative alopecia areata: is pressure-induced ischemia the only cause to blame?

INTRODUCTION: Postoperative alopecia areata (PAA) following surgery has been reported, especially after certain gynecologic and cardiac procedures; however, no cases have been reported after liver transplant (LT). Localized pressure associated with prolonged anesthesia is usually blamed. Herein we report a few cases of PAA encountered especially in relation to LT procedures. OBJECTIVE: To report our PAA cases, identifying possible contributing risk factors. METHODS: Between April 2001 and May 2003 the data on eight PAA cases were analyzed for age, sex, type of surgery, duration of anesthesia, type of head support, periods of hypotension, and psychiatric comorbidity. RESULTS: Median age of affected patients was 27 years (10 to 44) and the male/female ratio 3/5. The type of surgery included: two LT recipients, two LT donors, three cardiac valve replacements, and one coronary bypass surgery. Median anesthesia time was 6 hours (3 to 12). Sponge or jelly donut was used for head support with frequent change of its position as per protocol. There were no significant periods of hypotension. Surprisingly, almost all patients had a documented psychiatric comorbidity, mainly anxiety, adjustment/adaptation, or mood disorders. CONCLUSIONS: PAA is a rare complication following certain surgeries including both donor and recipient LT procedures. Although pressure-induced ischemia is the most likely etiological factor, we believe that psychiatric comorbidity plays a major role in its development. Therefore, preoperative thorough psychiatric counseling in addition to frequent intraoperative head repositioning will help to avoid this minor but distressing postoperative complication.

Adolescent↗
PubMed2003

Salmonella typhi endocarditis: a case report.

Salmonella are a rare cause of infective endocarditis. This report describes a case where Salmonella typhi was isolated from the blood and urine of a patient with echocardiographically documented aortic valve disease and endocarditis. The patient was treated with two weeks of ceftriaxone (3 g/day) and amikacin (15 mg/kg/day), followed by a further two weeks of ceftriaxone (3 g/day) alone. He made a complete recovery.

Adult↗
PubMed2000

Presence of functional endothelin-1 receptors in nuclear membranes of human aortic vascular smooth muscle cells.

Our previous work showed that the nucleus plays a role in excitation-contraction coupling and that the channels and receptors could be present at the nuclear membrane. In the study reported here, the objective was to test the hypothesis that endothelin-1 (ET-1) receptors are functional at the level of the nuclear membranes and that their stimulation importantly regulates free nucleoplasmic Ca2+ level. Using a Fluo-3 Ca2+ measurement technique in human vascular smooth muscle cells (HVSMC), superfusion with increasing concentrations of extracellular ET-1 induced a dose-dependent sustained increase of free cytosolic ([Ca]c), nuclear ([Ca]n) Ca2+ and contraction with an EC50 near 3 x 10(-10) M. Like the extracellular ET-1, the cytosolic application of ET-1 using the perforated sarcolemma membrane technique, induced a dose-dependent increase of nuclear free calcium of HVSMC with an EC50 of 2 x 10(-11) M. These results strongly suggest that ET-1 receptors are functional at the level of the nuclear membranes. Furthermore, the sensitivity of ET-1 receptors at the nuclear membrane level seems to be higher than that of the receptors at the sarcolemma membrane. Finally, our results suggest that cytosolic ET-1 may play a role in preventing HVSMC nuclear calcium overload, thus protecting the cells from apoptosis.

Adult↗
PubMed2000

Neuropeptide Y induced increase of cytosolic and nuclear Ca2+ in heart and vascular smooth muscle cells.

It was reported that neuropeptide Y (NPY) affects cardiac and vascular smooth muscle (VSM) function probably by increasing intracellular Ca2+. In this study, using fura-2 microfluorometry and fluo-3 confocal microscopy techniques for intracellular Ca2+ measurement, we attempted to verify whether the action of NPY receptor's stimulation in heart and VSM cells modulates intracellular Ca2+ and whether this effect is mediated via the Y1 receptor type. Using spontaneously contracting single ventricular heart cells of 10-day-old embryonic chicks and the fluo-3 confocal microscopy Ca2+ measurement technique to localize cytosolic ([Ca]c) and nuclear ([Ca]n) free Ca2+ level and distribution, 10-10 M of human (h) NPY significantly (P < 0.05) increased the frequency of cytosolic and nuclear Ca2+ transients during spontaneous contraction. Increasing the concentration of hNPY (10(-9) M) did not further increase the frequency of Ca2+ transients. The L-type Ca2+ channel blocker, nifedipine (10(-5) M), significantly (P < 0.001) blocked the spontaneous rise of intracellular Ca2+ in the absence and presence of hNPY (10(-10) and 10(-9) M). However, the selective Y1 receptor antagonist, BIBP3226 (10(-6) M), significantly decreased the hNPY-induced (10(-10) and 10(-9) M) increase in the frequency of Ca2+ transients back to near the control level (P < 0.05). In resting nonworking heart and human aortic VSM cells, hNPY induced a dose-dependent sustained increase of basal resting intracellular Ca2+ with an EC50 near 10(-9) M. This sustained increase was cytosolic and nuclear and was completely blocked by the Ca2+ chelator EGTA, and was significantly decreased by the Y1 receptor antagonist BIBP3226 in both heart (P < 0.05) and VSM (P < 0.01) cells. These results strongly suggest that NPY stimulates the resting basal steady-state Ca2+ influx through the sarcolemma and induces sustained increases of cytosolic and nuclear calcium, in good part, via the activation of the sarcolemma membrane Y1 receptor type in both resting heart and VSM cells. In addition, NPY also increased the frequency of Ca2+ transients during spontaneous contraction of heart cells mainly via the activation of the Y1 receptor type, which may explain in part the active cardiovascular action of this peptide.

Animals↗
PubMed2000

Cockayne syndrome.

We report four cases of Cockayne Syndrome in a family of seven children. Apart from the usual clinical and laboratory features, sparse eye lashes and high arched palate in two patients, conjunctival and corneal edema in one, and proximal muscle weakness in one patient were noticed as additional findings.

Adolescent↗
PubMed1998

Nuclear targeting by growth factors, cytokines, and their receptors: a role in signaling?

The role of membrane receptors is regarded as being to transduce the signal represented by ligand binding from the external cell surface across the membrane into the cell. Signals are subsequently conveyed from the cytoplasm to the nucleus through a combination of second-messenger molecules, kinase/phosphorylation cascades, and transcription factor (TF) translocation to effect changes in gene expression. Mounting evidence suggests that through direct targeting to the nucleus, polypeptide ligands and their receptors may have an important additional signaling role. Ligands such as those of the platelet-derived and fibroblast growth factor classes, as well as cytokines such as interferon-gamma and interleukins-1 and -5, have been found to localize in the nucleus through the action of nuclear localization sequences (NLSs). Where tested, these NLSs appear to be essential for full signaling activity and may be responsible for cotranslocating receptors to the nucleus in complexes with their ligands. The implication is that, subsequent to endocytosis at the membrane, particular polypeptide ligands or their receptors, or both, may translocate to the nucleus to participate directly in gene regulation.

Cell Nucleus↗
PubMed1998

Drug-related hospitalization at a tertiary teaching center in Lebanon: incidence, associations, and relation to self-medicating behavior.

OBJECTIVE: In Lebanon there is very limited restriction on drug use. Accordingly, self-medication is highly prevalent. This study examined the influence of these factors on the development of drug-related illnesses that lead to hospitalization. METHODS: Patients admitted to the medical and pediatric wards of a tertiary teaching center in Beirut, Lebanon, over a period of 6 months were interviewed and their charts were reviewed. Admissions attributable to adverse drug reactions or therapeutic failures were identified and characterized with respect to demographic factors, medical history, drug intake, and self-medicating behavior. The influence of these variables on the development of drug-related illnesses was examined by logistic regression. RESULTS: Of 1745 adults and 457 children, there were 177 (10.2%) and 36 (7.9%) drug-related illnesses, respectively. Adverse drug reactions accounted for 7.0% and 5.7% and therapeutic failures for 3.2% and 2.2% of adult and pediatric admissions, respectively. Self-medication was commonly practiced (52.6% of adults and 41.6% of children). Logistic regression analysis revealed that female sex increased the risk of adverse drug reaction in adults, whereas self-medication decreased the risk. In children, the risk of adverse drug reaction was increased in lower socioeconomic groups, whereas the risk of therapeutic failure was increased by a positive history of atopy or drug reaction. CONCLUSIONS: These results provide the first detailed analysis of the problem of drug-related illnesses in a developing country and identify a number of related or risk factors. Despite the lack of regulation of drug dispensing and the unchecked access to drugs in Lebanon, the incidence of drug-related illnesses is not different from that in Western nations. This finding may have relevance to policies of drug regulation in other countries.

Adolescent↗
PubMed1997

Interleukin-1-producing plasma cells in close contact with hepatocytes in patients with chronic active hepatitis.

BACKGROUND/AIMS: In chronic active liver diseases (CALD) with viral aetiology, a population of plasma cells localised in the piecemeal necrosis areas was previously detected by means of autoradiography after in vitro 3H-proline incorporation, a method which proved much more sensitive than conventional immunohistochemical procedures. These plasma cells, characteristically located in niches among hepatocytes, in close contact with collagen fibrils, have been hypothesised to exert a role in fibrogenesis stimulation, and particularly in collagen synthesis, possibly through secretion of lymphokines. Specifically, we investigated the presence of interleukin-1, well known to play a crucial role in inflammation and production of collagen by epithelial cells, and to be present in activated plasma cells of myeloma. METHODS: The immunohistochemical localisation of interleukin-1beta in biopsies of patients suffering from chronic active hepatitis was studied, using an affinity-purified rabbit polyclonal antibody. RESULTS: The strongest interleukin-1beta immunostaining was observed in the above-described plasma cell population, identified by anti-immunoglobulin antibodies, and 3H-proline incorporation. CONCLUSIONS: The ability of plasma cells to produce interleukin-1 during viral CALD suggests that in these pathologies plasma cells play a major role, mainly of paracrine nature. Interleukin-1, possibly together with other mediators, might in turn stimulate the production of collagen. Hepatocytes of the piecemeal necrosis area appear to be possible candidates for this synthesis, as they show a significant labelling after 3H-proline incorporation, which is absent from hepatocytes far from necrotic areas.

Adult↗
PubMed1997

Bradykinin activates R-, T-, and L-type Ca2+ channels and induces a sustained increase of nuclear Ca2+ in aortic vascular smooth muscle cells.

The mechanism(s) fo Ca2+ entry stimulated by bradykinin (BK) and the receptor subtype responsible for this effect were examined in human and rabbit aortic vascular smooth muscle cells (VSMCs). Using the whole-cell voltage clamp technique, BK (10(-6)M) significantly (p < 0.05) increased both T- and L-type Ca2+ currents (ICa) in rabbit aortic VSMCs. Using the fura-2 total intracellular Ca2+ ([Ca]i) measurement technique, BK (10(-6) M) induced a transient increase of [Ca]i followed by a sustained component. Pretreatment of rabbit VSMCs with sarcoplasmic reticulum (SR) Ca2+ releaser caffeine (1-5 mM) significantly decreased the BK-induced transient increase of [Ca]i without affecting the sustained component induced by this hormone. This sustained phase was blocked by extracellular application of the Ca2+ chelator EGTA. Using the fluo-3 confocal microscopy Ca2+ measurement technique to localize cytosolic ([Ca]c) and nuclear ([Ca]n) free Ca2+ distribution, the resting sustained concentration of Ca2+ in the cytoplasm of rabbit and human aortic VSMCs was less than that in the nucleus. BK (10(-7) M) induced a nonsignificant sustained increase of [Ca]c but significant (p < 0.05) sustained increase of [Ca]n that was reversed but not prevented by the specific B1 receptor antagonist R126 (10(-6) M) as well as by the B2 receptor antagonist R817 (10(-6) M). In both VSMC preparations, the specific B1 agonist R211 (10(-9) to 10(-7) M) rapidly induced a nonsignificant increase of [Ca]c but a significant (p < 0.05) sustained increase of [Ca]n that was prevented but not reversed by the B1 selective antagonist R126 (10(-6) M). The sustained increase of [Ca]c and [Ca]n induced by BK and B1 receptor agonist was blocked by extracellular application of EGTA. These results strongly suggest that B1 and probably B2 receptors are functional in human and rabbit aortic VSMCs. BK-induced transient increase of [Ca]i is mainly due to the stimulation of T- and L-type Ica as well as to Ca2+ release from caffeine- and ryanodine-sensitive Ca2+ pools. The sustained component induced by the hormone or the B1 agonist is mainly nuclear and is due to the stimulation of Ca2+ influx through the R-type Ca2+ channels that are present at the sarcolemma and the nuclear membranes.

Animals↗
PubMed1997

The use of confocal microscopy in the investigation of cell structure and function in the heart, vascular endothelium and smooth muscle cells.

In recent years, fluorescence microscopy imaging has become an important tool for studying cell structure and function. This non invasive technique permits characterization, localisation and qualitative quantification of free ions, messengers, pH, voltage and a pleiad of other molecules constituting living cells. In this paper, we present results using various commercially available fluorescent probes as well as some developed in our laboratory and discuss the advantages and limitations of these probes in confocal microscopy studies of the cardiovascular system.

Animals↗
PubMed1989

Proline-incorporating cells in chronic active liver diseases.

The incorporation of 3H-proline in cells of liver biopsy specimens from patients with chronic active liver diseases has been studied by light and electron microscopic autoradiography. The labeled proline is incorporated by hepatocytes of the external rows of the residual liver lobule, by the cells of the proliferating bile ductule and very actively by the plasma cells localized at the boundary between the inflammatory infiltrate and the liver lobule. These plasma cells, which are often in close contact with the hepatocytes at the edge of the liver lobule, appear to be either negative or positive after the immunohistochemical tests for the k and lambda chains of immunoglobulins. Results are discussed in relation to both the synthesis of collagen and the role of the immunocompetent cells during the process of the piecemeal necrosis.

Autoradiography↗