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Biomedical subjects

A Sharif

Publications and source records attributed to A Sharif.

At least 19 recordsLinked to original sources
PubMed2006

Transforming growth factor alpha promotes sequential conversion of mature astrocytes into neural progenitors and stem cells.

An instability of the mature cell phenotype is thought to participate to the formation of gliomas, primary brain tumors deriving from astrocytes and/or neural stem cells. Transforming growth factor alpha (TGFalpha) is an erbB1 ligand overexpressed in the earliest stages of gliomas, and exerts trophic effects on gliomal cells and astrocytes. Here, we questioned whether prolonged TGFalpha exposure affects the stability of the normal mature astrocyte phenotype. We first developed astrocyte cultures devoid of residual neural stem cells or progenitors. We demonstrate that days of TGFalpha treatment result in the functional conversion of a population of mature astrocytes into radial glial cells, a population of neural progenitors. TGFalpha-generated radial glial cells support embryonic neurons migration, and give birth to cells of the neuronal lineage, expressing neuronal markers and the electrophysiological properties of neuroblasts. Lengthening TGFalpha treatment to months results in the delayed appearance of cells with neural stem cells properties: they form floating cellular spheres that are self-renewing, can be clonally derived from a single cell and differentiated into cells of the neuronal lineage. This study uncovers a novel population of mature astrocytes capable, in response to a single epigenetic factor, to regress progressively into a neural stem-like cell stage via an intermediate progenitor stage.

Animals↗
PubMed2006

Scaling and organization of electroencephalographic background activity and alpha rhythm in healthy young adults.

The coexistence of the broad-band fluctuation and alpha rhythm of the brain dynamics is studied based on the zero-crossing property of the local electroencephalographic (EEG) recording in eyes closed and eyes open. A two-component zero-crossing scenario, consisting of a broad-band fractal and narrow-band rhythm components, is assumed. Scaling is found in the power law distribution p(tau) approximately tau(-nu) of the crossing time interval tau of the broad-band fluctuation. In alpha dominant brain state, the alpha rhythm interval L also exhibits scaling in the form of power law distribution: p(L) approximately L(phi). Our main result is the relationship nu + phi approximately 3 that characterizes the organization of these two prominent features of the brain dynamics. The possible role of self-organized criticality of punctuated equilibrium in this organization is discussed.

Adult↗
PubMed2006

Transforming growth factor alpha acts as a gliatrophin for mouse and human astrocytes.

Astrocyte death has been implicated in several neuropathological diseases, but the identification of molecules susceptible of promoting astrocyte survival has been elusive. We investigated whether transforming growth factor alpha (TGFalpha), an erbB1/EGFR ligand, which promotes glioma progression and affects astrocyte metabolism at embryonic and adult stages, regulates astrocyte survival. Primary serum-free astrocyte cultures from post-natal mouse and fetal human cortices were used. Transforming growth factor alpha protected both species of astrocytes from staurosporine-induced apoptosis. In serum-free medium, mouse astrocytes did not survive beyond 2 months while TGFalpha-treated astrocytes survived up to 12 months. Transforming growth factor alpha also promoted long-term survival of human astrocytes. We additionally extended TGFalpha proliferative effects to human astrocytes. After 3 days of permanent application, TGFalpha induced a major downregulation of both erbB1 and erbB2. This downregulation did not impair the functional activation of the receptors, as ascertained by their tyrosine phosphorylation and the continuous stimulation of both ERK/MAPK and PI3K/Akt pathways up to 7 days, the longest time examined. The full cellular effects of TGFalpha required activation of both transduction pathways. Enhanced proliferation and survival thus define TGFalpha as a gliatrophin for mammalian astrocytes. These results demonstrate that in normal, non-transformed astrocytes, sustained and functional erbBs activation is achieved without bypassing ligand-induced receptors downregulation.

Aging↗
PubMed2006

Proteomic analysis of cytochromes P450: a mass spectrometry approach.

In human, the CYP (cytochrome P450) superfamily comprises 57 genes arranged in 18 families and 42 subfamiles. These genes encode for enzymes involved in the metabolism of drugs, foreign chemicals, fatty acids, eicosanoids and cholesterol. Additionally, they play roles in bile acid biosynthesis, steroid synthesis and metabolism, and vitamin D(3) synthesis and metabolism. Mutations in many CYP genes cause inborn errors of metabolism and contribute to increased risk of cancer. MS provides a convenient method for the identification and quantification of CYP enzymes, and in the present paper we will review the current state of the technology for such an analysis.

Amino Acid Sequence↗
PubMed2006

[Holt-Oram syndrome: characterization of a novel mutation].

INTRODUCTION: Cardiomyelic syndromes encompass congenital heart disease and skeletal malformations of the upper limbs and are related to mutations in transcription factors with T-Box domains. Holt-Oram syndrome is caused by a dominant mutation in the TBX5 gene that alters the three-dimensional structure of the protein and its DNA binding function. Several point mutations and deletions in TBX5 have been reported in patients with the Holt-Oram syndrome phenotype. PATIENTS AND METHODS: The proband was a boy with a large atrial septal defect ostium secundum type and a ventricular septal defect, diagnosed by clinical findings (heart murmur) and echocardiography. He also presented slightly hypoplastic thumbs with distal bilateral placement and an implantation index of 0.19 (compared with an average of 0.50 for his gestational age at birth). The boy was referred to the department of medical genetics to rule out 22q11.2 microdeletion syndrome. RESULTS: Karyotype and fluorescence in situ hybridization at locus D22S75 were both normal. Because of his clinical findings, molecular study for Holt-Oram syndrome was indicated, leading to the finding of a mutation at intron 7 of TBX5, probably producing a splicing alteration of the gene and resulting in a protein truncated at its C-terminal end. The proband's parents presented the wild type sequence of the gene, thus indicating that the mutation was produced de novo, although a possible germinal mosaicism in the parents could not be ruled out. CONCLUSIONS: Holt-Oram syndrome is the most frequent cause of cardiomyelic syndrome. All children with heart malformations and abnormalities of the upper limbs such as absent, hypoplastic, distally placed or triphalangic thumbs should undergo molecular studies for this syndrome.

Abnormalities, Multiple↗
PubMed2006

Unusual perforating foreign body in the neck.

Penetrating injury in the neck is not an uncommon condition, but a perforating foreign body like bamboo in the neck is uncommon. A 36 years old young man was admitted in Otolaryngology and Head Neck surgery department, Mymensingh Medical College hospital, with a history of accidental perforating injury in the neck with a bamboo, while driving a vehicle (tempo). Clinical examination revealed a bamboo measuring 4.6 X 0.09 ft. perforated in his neck from left to right. Surprisingly great vessels and air way spared. Due to difficult intubation, elective tracheostomy was done. Neck was explored and foreign body removed under general anesthesia. Haemostasis ensured and wound closed in layers after putting drain tubes. Recovery was uneventful and was discharged after three weeks.

Adult↗
PubMed2004

The expression of PEA-15 (phosphoprotein enriched in astrocytes of 15 kDa) defines subpopulations of astrocytes and neurons throughout the adult mouse brain.

Phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) is an abundant phosphoprotein in primary cultures of mouse brain astrocytes. Its capability to interact with members of the apoptotic and mitogen activated protein (MAP) kinase cascades endows PEA-15 with anti-apoptotic and anti-proliferative properties. We analyzed the in vivo cellular sources of PEA-15 in the normal adult mouse brain using a novel polyclonal antibody. Immunohistochemical assays revealed numerous PEA-15-immunoreactive cells throughout the brain of wild-type adult mice while no immunoreactive signal was observed in the brain of PEA-15 -/- mice. Cell morphology and double immunofluorescent staining showed that both astrocytes and neurons could be cellular sources of PEA-15. Closer examination revealed that in a given area only part of the astrocytes expressed the protein. The hippocampus was the most striking example of this heterogeneity, a spatial segregation restricting PEA-15 positive astrocytes to the CA1 and CA3 regions. A PEA-15 immunoreactive signal was also observed in a few cells within the subventricular zone and the rostral migratory stream. In vivo analysis of an eventual PEA-15 regulation in astrocytes was performed using a model of astrogliosis occurring along motor neurons degeneration, the transgenic mouse expressing the mutant G93A human superoxyde-dismutase-1, a model of amyotrophic lateral sclerosis. We observed a marked up-regulation of PEA-15 in reactive astrocytes that had developed throughout the ventral horn of the lumbar spinal cord of the transgenic mice. The heterogeneous cellular expression of the protein and its increased expression in pathological situations, combined with the known properties of PEA-15, suggest that PEA-15 expression is associated with a particular metabolic status of cells challenged with potentially apoptotic and/or proliferative signals.

3T3 Cells↗
PubMed2004

Evaluation of CO laser efficacy in the treatment of cutaneous leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis is a common disease in Iran, especially in the north-east, central and southern parts of the country. Many treatments have been suggested for this disease but none is completely effective and without side-effects such as pain, arthralgia and renal or cardiac complications. Lasers have been used for treatment of several skin diseases since 1970, and CO(2) lasers are now being used for treatment of leishmaniasis. In this study, a CO(2) laser (Sonic 500 machine) was used as a source of a continuous CO(2) laser wave. METHODS: A total of 123 patients (68 female and 55 male) with 183 lesions were treated with the CO(2) laser. The maximum power was 100 W and the pulse width was 0.5-5 s. For the control group, 110 patients (with 250 lesions) were treated with glucantime 50 mg/kg/day for 15 days and, after 15 days of rest, this treatment was repeated (Glucantime Amps, 1.5 g in a 50-mL solution, was used). For follow-up, the patients were visited 1, 3, 4, 8, 12 and 24 weeks after treatment and any complications, recurrences or other wound characteristics were recorded. In the second group, Finally, all collected data were analyzed statistically. RESULTS: Statistical analysis with the chi(2) test showed that treatment with the CO(2) laser was more effective than treatment with glucantime (P = 0.0007). Complications were also seen less often with the laser treatment than with glucantime and were limited to the ulcer site. The CO(2) laser was more effective in treating cutaneous leishmaniasis than glucantime (1.12 times), had fewer side-effects (4.5% vs. 24%) and resulted in a shorter healing time (1 month vs. 3 months), and treatment could be applied in a single session. CONCLUSIONS: The results of this and previous studies suggest that cutaneous leishmaniasis can be treated effectively with CO(2) laser if those providing the treatment are sufficiently experienced. Laser treatment is more cost-effective than other treatments and can be used as first-line therapy for cutaneous leishmaniasis (wet and dry types).

Adolescent↗
PubMed2001

Expression of Ol-KIP, a cyclin-dependent kinase inhibitor, in embryonic and adult medaka (Oryzias latipes) central nervous system.

From an expression screen in a fish model, the medaka, we have isolated Ol-KIP (Oryzias latipes-kinase inhibitor protein), a new member of the KIP subfamily of cyclin-dependent kinase (Cdk) inhibitors. We have analysed its expression in the developing and adult brain by in situ hybridization and by double labeling with Ol-KIP mRNA and proliferating cell nuclear antigen (PCNA) antibodies. Ol-KIP presents a complex expression pattern in several areas of the embryonic central nervous system, most often in close vicinity to proliferative neuroepithelia. We studied in great detail its expression in the optic tectum: Ol-KIP is expressed in a ring-shaped domain lying exactly between the proliferative and the postmitotic zones of this structure and is, therefore, potentially involved in cell cycle exit. In the adult CNS, Ol-KIP expression persists in numerous nuclei, both close and distant from proliferative ventricular areas. So, Ol-KIP expression is in part compatible with a sustained "stop signal" role for proliferation, but its expression in postmitotic zones suggests that KIP proteins may have late neuronal function(s), in addition to inhibiting Cdks. This first detailed study of the expression profile of a KIP gene in a nonmammalian vertebrate, thus, opens perspectives for analysing the role of these regulators in brain development and function.

Animals↗
PubMed2001

Hormone replacement therapy menopause with a better future--a survey of views on hormone replacement therapy (HRT).

OBJECTIVE: To assess the views and prescribing practices of doctors regarding hormone replacement therapy (HRT). METHODS: In April 1999, 103 doctors from a teaching hospital participated in a survey. Using a self-administered questionnaire, subjects were contacted at the departments of Internal Medicine, Family Medicine, Obstetrics and Gynaecology, and Orthopaedics. RESULTS: Seventy-two percent were below 40 years of age and 67% of the respondents were male. Most doctors believed that HRT decreases the risk of subsequent osteoporosis (97%), ischaemic heart disease (77%) and depression associated with menopause (64%). Doctors generally considered menopausal symptoms (90%), premature menopause (87%), surgical menopause (85%) and osteoporotic fracture (77%) as clear indications for hormone replacement therapy. Absolute contraindications to the therapy were stated as recent breast cancer (82%) and recent endometrial cancer (84%). Among the specialities covered, there were differing views on proposed duration of HRT. It was generally believed that a pelvic examination, cervical smear and mammography were pre-requisites when initiating and monitoring HRT. Majority (69%) felt that HRT should be offered to all menopausal women, assuming no contraindications and most (73%) did discuss HRT with their patients. However, less than 10% of the menopausal patients under their care were using HRT. Those doctors not in favor of universal offering of HRT (31%) considered unreliable patient follow up to be the main reason. Females were two times more likely to discuss HRT with their patients (p = .08). Doctors who discussed HRT with their patients were four times more likely to consider HRT for themselves or their spouses (p = .13). Gynecologists were eight times more likely to prescribe HRT than non-gynecologists (p = .001). CONCLUSION: Doctors are positively disposed to the universal offering, and use of HRT. Further studies are needed to understand a possible gap between perceived and actual prescribing practice.

Adult↗
PubMed1998

Enhancement of aspirin-induced gastric damage by cholestasis in rats.

In this study the severity of aspirin-induced gastric mucosal damage was investigated in rats with obstructive cholestasis. Cholestasis was induced by ligation and resection of the bile duct under general anesthesia. Two weeks after operation, the rats were fasted for 24 hours. Aspirin was administered orally in doses of 0, 128, 192, 266 and 335 mg/kg, and the animals were killed four hours after dosing. The dose of 266 mg/kg was chosen for a study of the time-dependency; other groups of animals were killed at time intervals of one, three, five, seven and nine hours after aspirin administration. The results showed that aspirin induces more severe gastric damage in bile duct resected rats compared with sham-operated and control animals. Salicylate levels of serums were also measured but there was no significant difference in serum salicylate levels between bile duct resected, sham-operated and control rats. It can be concluded that cholestasis can potentiate aspirin-induced gastric damage in rats.

Animals↗
PubMed1997

Involvement of septal muscarinic receptors in cholinergically mediated changes in rat rearing activity.

We tested the hypothesis that septal muscarinic receptors of the rat are involved in exploratory behavior control, at least as reflected in the measure of rearing activity. At a dose capable of inducing hippocampal theta rhythm, carbachol injection into the septum significantly increased the number of rearings from the 2nd to the 5th min postinjection. The increase was maximal in the 3rd min and gradually declined until the 9th min postinjection, when it was near the control level. This behavioral effect was blocked by prior injection of atropine. These data, when considered with other findings showing a similar motor response caused by the hippocampal injection of the cholinergic agonist, strongly suggest that the cholinoceptive cholinergic components of the septohippocampal system play a role in the release of exploratory behavior. This role might be mediated via muscarinic receptors at the septal level. Moreover, the time course of behavioral action of carbachol injected into the septum is of particular importance for studies on the effect of the drug on performance of the rat in learning and memory tests requiring contribution of exploratory behavior.

Animals↗
PubMed1997

Relations between acetylcholine release and electrophysiological characteristics of theta rhythm: a microdialysis study in the urethane-anesthetized rat hippocampus.

In urethane-anesthetized rats, recording electrodes were implanted in the left dorsal hippocampus and a dialysis probe was placed in the contralateral dorsal or ventral hippocampus. Samples of extracellular acetylcholine (ACh) levels were assessed at 10-min intervals over a period of 30 min using microdialysis with high-performance liquid chromatography with electrochemical detection. EEG was recorded during the same period and amplitude, frequency, and duration of theta rhythm were calculated for each of the three 10-min intervals. Data were analyzed using the two-tailed Spearman rank-order correlation test. A positive and high rank correlation coefficient (rho = 0.90, p < 0.01, n = 8) was seen between the average ACh outflow in the dorsal hippocampus and the average theta amplitude, both being calculated for the entire collection period. A lower but statistically significant positive correlation (rho = 0.59, p < 0.01) between dorsal hippocampus ACh output and theta amplitude was also found when the couples of values collected for the 30-min period were pooled (n = 20). In contrast, frequency and duration of theta were not significantly correlated with dorsal hippocampus ACh release. Also, no statistically significant correlation (p > 0.05) was found between ACh output in the ventral hippocampus and theta parameters. Because changes in hippocampal ACh outflow are believed to be the reflection of changes in number and/or level of activity of cholinergic afferents to the dorsal hippocampus, our present findings support the view that, at least in the dorsal hippocampus of the urethane-anesthetized rat, the septohippocampal cholinergic projection regulates the theta amplitude but not frequency. Finally, the possibility that ACh outflow increase and tonic release in the hippocampus is not a sufficient condition to induce and maintain theta in the urethane-anesthetized rat is discussed.

Acetylcholine↗
PubMed1996

Intraseptal infusion of selective and competitive glutamate receptor agonist NMDA and antagonist D-2-amino-5-phosphonopentanoic acid spectral implications for the physostigmine-induced hippocampal theta rhythm in urethane-anesthetized rats.

Theta (theta) rhythm may be mediated, at least in part, by a glutamate neurotransmitter. Thus, in the present study, it was hypothesized that the septum glutamatergic NMDA receptor subtype may be involved in the modulation of physostigmine-induced theta rhythm. To test this hypothesis, we analyzed, in the urethane-anesthetized rat, the effects of septum application of NMDA and D-2-amino-5-phosphonopentanoic acid (AP5), selective and competitive NMDA agonist and antagonist, respectively, on the spectral characteristics of hippocampal theta rhythm elicited by intravenous injection of a anticholinesterase agent, physostigmine. A low dose (16 nmol) of AP5 did not significantly affect EEG recordings, whereas a high dose (50.75 nmol) resulted in significant decreases in phase (-61.8%) at theta frequency, peak theta power (-64.2%), and absolute power of the low-frequency theta band (-67%). These electroencephalographic alterations, which appeared at 50.75 nmol AP5, were amplified following application of massive doses of the drug (121.8 nmol, n = 1, and 162 nmol, n = 1). Amplification, however, was slight and the theta waves remained clearly detectable. On the other hand, the infusion of NMDA resulted in a significant increase in frequency (+25%) of this rhythm, but this effect was completely antagonized by prior local administration of 16 nmol AP5. Our data suggest that the septal NMDA receptors exert subtle modulatory influences on the septohippocampal cells involved in physostigmine-induced theta wave production, which has not been reported elsewhere: tonic with respect to both low-frequency theta band power and theta phase, and phasic with respect to theta frequency. Our data also indicate that the septum may be a sensitive action site for exogenously administered glutamatergic drugs.

2-Amino-5-phosphonovalerate↗
PubMed1994

Involvement of M2 and non-M2 muscarinic receptors in hippocampal theta rhythm induced by carbachol infusion into the septum of the rat.

Binding and autoradiographic studies have shown the presence of a rather high density of M2 muscarinic subtype receptors and the apparent absence or low density of the M1 subtype in the septum. We tested the hypothesis that, in the urethane-anesthetized rat, septal M2 receptors are involved in the generation of the hippocampal theta (theta) rhythm induced by intraseptal administration of carbachol, a potent cholinomimetic agent. Carbachol-induced theta was blocked by local infusion of the unspecific muscarinic antagonist agent, atropine (20 micrograms (29.55 nM)), given 10 min prior to carbachol. The intraseptal administration of low to high doses of gallamine (range: 20-180 micrograms (22.43-201.90 nM)), a specific M2 antagonist which displays high affinity for the septal region, resulted in significant changes in the electrophysiological characteristics of carbachol-induced theta but failed to abolish this rhythm. It is suggested that the latter may have resulted from a combined activation of both M2 and non-M2 receptors at septal level.

Animals↗