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Biomedical subjects

A Ali

Publications and source records attributed to A Ali.

At least 109 records · Page 6Linked to original sources
PubMed2000

Assembly of Sendai virus: M protein interacts with F and HN proteins and with the cytoplasmic tail and transmembrane domain of F protein.

Sendai virus matrix protein (M protein) is critically important for virus assembly and budding and is presumed to interact with viral glycoproteins on the outer side and viral nucleocapsid on the inner side. However, since M protein alone binds to lipid membranes, it has been difficult to demonstrate the specific interaction of M protein with HN or F protein, the Sendai viral glycoproteins. Using Triton X-100 (TX-100) detergent treatment of membrane fractions and flotation in sucrose gradients, we report that the membrane-bound M protein expressed alone or coexpressed with heterologous glycoprotein (influenza virus HA) was totally TX-100 soluble but the membrane-bound M protein coexpressed with HN or F protein either individually or together was predominantly detergent-resistant and floated to the top of the density gradient. Furthermore, both the cytoplasmic tail and the transmembrane domain of F protein facilitated binding of M protein to detergent-resistant membranes. Analysis of the membrane association of M protein in the early and late phases of the Sendai virus infectious cycle revealed that the interaction of M protein with mature glycoproteins that associated with the detergent-resistant lipid rafts was responsible for the detergent resistance of the membrane-bound M protein. Immunofluorescence analysis by confocal microscopy also demonstrated that in Sendai virus-infected cells, a fraction of M protein colocalized with F and HN proteins and that some M protein also became associated with the F and HN proteins while they were in transit to the plasma membrane via the exocytic pathway. These studies indicate that F and HN interact with M protein in the absence of any other viral proteins and that F associates with M protein via its cytoplasmic tail and transmembrane domain.

Animals↗
PubMed2000

Glycogen synthase kinase 3beta negatively regulates both DNA-binding and transcriptional activities of heat shock factor 1.

Stress activation of heat shock factor (HSF1) involves the conversion of repressed monomers to DNA-binding homotrimers with increased transcriptional capacity and results in transcriptional up-regulation of the heat shock protein (hsp) gene family. Cells tightly control the activity of HSF1 through interactions with hsp90 chaperone complexes and through integration into a number of different signaling cascades. A number of studies have shown that HSF1 transcriptional activity is negatively regulated by constitutive phosphorylation in the regulatory domain by glycogen synthase kinase (GSK3) isoforms alpha/beta. However, previous studies have not examined the ability of GSK3 to regulate the DNA-binding activity of native HSF1 in vivo under heat shock conditions. Here we show that GSK3beta inhibits both DNA-binding and transcriptional activities of HSF1 in heat-shocked cells. Specific inhibition of GSK3 increased the levels of DNA binding and transcription after heat shock and delayed the attenuation of HSF1 during recovery. In contrast, the overexpression of GSK3beta resulted in significant reduction in heat-induced HSF1 activities. These results confirm the role of GSK3beta as a negative regulator of HSF1 transcription in cells during heat shock and demonstrate for the first time that GSK3beta functions to repress DNA binding.

Amino Acid Sequence↗
PubMed2000

Relaxation of rat distal colon by activation of muscarinic, neuronal receptors: possible involvement of P(2y)-purinoceptors.

McN-A-343, which is a ligand at muscarinic receptors on myenteric ganglia, was found to concentration-dependently (1-44 microM) elicit non-adrenergic relaxation of the longitudinal muscle of rat distal colon, having been precontracted with carbachol (1 microM). This effect was partly antagonized by the muscarinic receptor antagonist, pirenzepine (0.3 microM), the nerve blocker, tetrodotoxin (1 microM), or by drugs which interfere with purinergic neurotransmission (apamin [0.5 microM], reactive blue 2 [50 microM]). Blockade of nitric oxide synthase (L-NNA [100 microM]), or of the cAMP (H-89 [1 microM]), or cGMP (ODQ [10 microM]) second messenger pathways did not affect the relaxatory response to McN-A-343 (14 microM). An additional, non-neurogenic component of the relaxation to this compound on carbachol induced tone is suggested to reflect a partial antagonism of the muscarinic receptors on the gut muscle by McN-A-343.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed2000

Convergence of the secretory pathways for cholera toxin and the filamentous phage, CTXphi.

Virulence of Vibrio cholerae depends on secretion of cholera toxin (CT), which is encoded within the genome of a filamentous phage, CTXphi. Release of CT is mediated by the extracellular protein secretion (eps) type II secretion system. Here, the outer membrane component of this system, EpsD, was shown to be required for secretion of the phage as well. Thus, EpsD plays a role both in pathogenicity and in horizontal transfer of a key virulence gene. Genomic analysis suggests that additional filamentous phages also exploit chromosome-encoded outer membrane channels.

Bacterial Outer Membrane Proteins↗
PubMed2000

Major histocompatibility complex class I peptide-pulsed host dendritic cells induce antigen-specific acquired thymic tolerance to islet cells.

BACKGROUND: As T-cell receptor-major histocompatibility complex (MHC) class I/self peptide interaction regulates T-cell development in the thymus, we reasoned that presentation of peptides by self dendritic cells (DC) to developing T cells in the thymus might induce acquired thymic tolerance. This hypothesis is based on the finding that intrathymic injection of allopeptides in the adult animal induces acquired tolerance. To examine this hypothesis, we studied the effects of intrathymic (IT) injection of a single immunodominant Wistar-Furth (WF) MHC class I (RT1.Au) peptide-pulsed host DC on islet allograft survival in the WF-to-ACI rat combination. METHODS: Bone marrow-derived ACI DC expressing MHC class I and II, OX62, and ED2 present allopeptides to naive and specifically peptide-primed syngeneic T cells in mixed lymphocyte reaction. Host DC pulsed with RT1.Au peptide 5 (residues 93-109) were injected into the thymus of streptozotocin-induced diabetic ACI that were transplanted 7 days later with donor-type (WF) or third-party (Brown Norway [BN]) islets. RESULTS: Whereas IT injection of 300 microg of peptide 5 alone led to normoglycemia and permanent islet survival in three of six diabetic ACI recipients, similar treatment combined with simultaneous intraperitoneal injection of 0.5 ml of anti-lymphocyte serum (ALS) on day -7 led to 100% permanent islet allograft survival (>200 days) compared to a mean survival time of 15.0+/-2.3 days in controls treated with ALS alone. In contrast, similarly prepared animals rejected the third-party (BN) islets in an acute fashion. To address the question of indirect allorecognition in acquired thymic tolerance, we examined the effect of peptide-pulsed host DC on graft survival. Whereas IT injection of peptide-pulsed host DC alone resulted in permanent islet survival in two of five animals, IT injection of peptide-pulsed host DC combined with 0.5 ml of ALS induced 100% donor-specific permanent islet allograft survival in the WF-to-ACI rat combination. These results suggest that thymic DC take up, process, and present the administered peptide to the developing T cells by the indirect allorecognition pathway in the induction of acquired thymic tolerance. CONCLUSION: We have demonstrated a novel approach to inducing transplant tolerance to islet allografts with IT injection of allopeptide-pulsed host DC. This finding suggests that immunization strategies using DC expressing MHC allopeptides or peptide analogue might be potentially useful in the treatment of autoimmune diabetes mellitus.

Animals↗
PubMed2000

Stereotactically guided laser therapy of occult breast tumors: work-in-progress report.

HYPOTHESIS: Mammographically detected breast tumors can be completely ablated with laser energy. DESIGN: Nonrandomized control trial. SETTING: A university hospital ambulatory care center. PATIENTS: Thirty-six patients with mammographically detected well-defined breast tumors were selected. INTERVENTIONS: The diagnosis of malignant neoplasms and determination of prognostic factors were established by image-guided needle-core biopsy. Patients were treated on a stereotactic table, using a 16- to 18-gauge laser probe, with an optic fiber transmitting a predetermined amount of laser energy. A multisensor thermal probe was inserted into the breast adjacent to the laser probe to monitor treatment. In the last 10 patients, the tumor blood flow was evaluated before and after laser therapy with contrast-enhanced color Doppler ultrasound. One to 8 weeks after laser therapy, the tumors were surgically removed and serially sectioned. MAIN OUTCOME MEASURE: Complete necrosis in 66% of tumors. RESULTS: Total tumor ablation with negative margins was observed whenever 2500 J/mL of tumor was given or the thermal sensors recorded 60 degrees C. Microscopic examination at 1 week showed disintegration of malignant cells, with peripheral acute inflammatory response and at 4 to 8 weeks extensive fibrosis. Contrast-enhanced color Doppler ultrasound revealed loss of tumor circulation after therapy, and positron emission tomography scan correlated well with histologic findings. There were no systemic adverse effects. Two patients sustained 3 x 4-mm skin burns around the laser needle. CONCLUSION: A stereotactically guided minimally invasive technique may be effective for the treatment of mammographically detected breast cancer.

Breast Neoplasms↗
PubMed2000

Diffuse alveolar hemorrhage following administration of tirofiban or abciximab: a nemesis of platelet glycoprotein IIb/IIIa inhibitors.

We describe three patients who developed severe pulmonary hemorrhage following administration of tirofiban (one patient) and abciximab (two patients). Pulmonary hemorrhage associated with abciximab use has been described, but to the best of our knowledge there has been no previous reports of this complication with tirofiban. Cathet. Cardiovasc. Intervent. 49:181-184, 2000.

Abciximab↗
PubMed2000

An anemic patient with phenotypical beta-thalassemic trait has elevated level of structurally normal beta-globin mRNA in reticulocytes.

Of the numerous beta-thalassemic mutations linked or unlinked to the beta-globin gene, all invariably cause a decrease in or an absence of structurally normal beta-globin mRNA when assayed. Here we report an anemic patient with an elevated alpha-/beta globin synthesis ratio of 2.0 in his reticulocytes. The patient's blood film showed marked red cell anisopoikilocytosis, microcytosis, and hypochromia, consistent with a typical beta-thalassemic trait phenotype. Acid-eluted erythrocytes contained numerous Heinz bodies. Molecular analysis of the patient's reticulocyte mRNA indicated that, compared to normal controls, there was a 3-fold elevation of beta-globin mRNA when assayed by RT-PCR and a 1.5-fold elevation of beta-globin mRNA when assayed by RNA slot blotting. The level of alpha-globin mRNA was normal when compared to that of normal adult controls. Extensive structural analysis of the beta-globin mRNA and gene by sequencing of RT-PCR and PCR products, respectively, did not detect any mutations. Tryptic mapping of purified beta-globin chains also did not show any abnormal tryptic fragments. These data indicated that a relative insufficiency of structurally normal beta-globin mRNA was not a cause of this beta-thalassemic phenotype. Therefore, the lesion that caused this particular thalassemic phenotype is not linked to the beta-globin allele.

Anemia↗
PubMed2000

Extracellular expression, purification, and characterization of a winter flounder antifreeze polypeptide from Escherichia coli.

HPLC6 is the major component of liver-type antifreeze polypeptides (AFPs) from the winter flounder, Pleuronectes americanus. To facilitate mutagenesis studies of this protein, a gene encoding the 37-amino acid mature polypeptide was chemically synthesized and cloned into the Tac cassette immediately after the bacterial ompA leader sequence for direct excretion of the AFP into the culture medium. Escherichia coli transformant with the construct placIQpar8AF was cultured in M9 medium. The recombinant AFP (rAFP) was detected by a competitive enzyme-linked immunosorbent assay (ELISA). After IPTG induction, a biologically active rAFP was expressed. The majority of the rAFP was excreted into the culture medium with only trace amounts trapped in the periplasmic space and cytoplasm. After 18 h of induction, the accumulated rAFP in the culture medium amounted to about 16 mg/L. The excreted AFP was purified from the culture medium by a single-step reverse-phase HPLC. Mass spectrometric and amino acid composition analyses confirmed the identity of the purified product. The rAFP, which lacked amidation at the C-terminal, was about 70% active when compared to the amidated wild-type protein, thus confirming the importance of C-terminal cap structure in protein stability and function.

Amino Acid Sequence↗
PubMed2000

Transdermal glyceryl trinitrate in the management of primary dysmenorrhea.

OBJECTIVE: Increased intra-uterine pressure due to exaggerated myometrial contractions is an important factor in the pathogenesis of dysmenorrhea, its treatment being associated with uterine muscle relaxation. Diminished synthesis of endogenous nitric oxide has been shown to induce myometrial contractions and, conversely, the administration of exogenous nitric oxide has successfully resulted in uterine relaxation in a variety of obstetrical/gynecological disorders. The objective of this study was to determine the role of transdermal glyceryl trinitrate, as a source of exogenous nitric oxide, in the management of primary dysmenorrhea. METHOD: This was a multi-national, double-blind, randomized and cross-over study in patients with primary dysmenorrhea. Eighty-eight patients from six countries were evaluated during three menstrual cycles while receiving glyceryl trinitrate patches, 0.1 mg/h (x) or matching placebo patches. Pain intensity scores assessed on a visual analog scale and the time-weighted sum of the pain intensity differences (SPID) were evaluated during days 1, 2 and 3 of each cycle using an analysis of variance (ANOVA) model. Overall assessment of efficacy and the incidence of adverse events were analyzed by the Stuart-Maxwell or the McNemar tests as appropriate. RESULTS: Efficacy was determined for the first day of each cycle, all days/all cycles and for patients who completed at least one cycle in each treatment modality. In all three analyses, SPIDs were statistically superior (P<0.01) for the glyceryl trinitrate patches. Pain intensity differences from hours 1 to 6 also showed statistically significant differences in favor of the active treatment. In the overall assessment of efficacy, glyceryl trinitrate patches were statistically superior as well. The incidence of headache was 26% for the active drug and 6.1% for placebo (P<0.01). CONCLUSIONS: The data indicate that transdermal glyceryl trinitrate, as a source of exogenous nitric oxide, is useful as a modulator of uterine contractility representing, therefore, a new and mechanistically different therapeutic alternative for the management of primary dysmenorrhea.

Administration, Cutaneous↗
PubMed2000

Response of Osteosarcoma to Chemotherapy. Evaluation with F-18 FDG-PET Scans.

Objective: Positron emission tomography (PET) using fluorine-18-fluoro-2-D-deoxyglucose (FDG) is increasingly being used to evaluate and manage oncology patients. Several reports have documented its utility in diagnosis, staging, response to treatment, and tumor viability assessment. There is, however, a paucity of literature on PET scanning in patients with osteosarcoma. We report results of serial F-18 FDG-PET scans in 16 untreated patients with osteosarcoma who underwent chemotherapy prior to surgical resection of the primary tumor site.Procedure: Changes in tumor fluoro-2-D-deoxyglucose (FDG) uptake were correlated with percent tumor necrosis on histopathology. PET studies were analyzed by visual assessment of tumor uptake of FDG by 3 independent observers, calculating a tumor to normal background activity ratio (TBR) by drawing regions of interest (ROIs) around the tumor and background activity in the contralateral normal limb, and percent change in TBR values between baseline and presurgical study.Results: All patients had positive baseline scans. Baseline TBRs ranged between 2.5-8.7 and visual assessment of intensity of FDG uptake was 2-3 on a scale of 0-3. At histopathologic examination, 8 patients were classified as good responses with more than 90% tumor necrosis and 8 patients as poor responses with less than 90% necrosis. Tumor necrosis was accurately predicted on PET scan in 15/16 patients by visual assessment, 14/15 patients by final TBR value on presurgery scans, and 7/15 patients using percent change of TBR on serial scans.Conclusions: The results of this small series suggest that FDG-PET scanning is fairly accurate in evaluating the response of osteosarcoma to chemotherapy. Visual assessment and TBR are more accurate in predicting tumor necrosis than percent change in TBR on serial scans.

Journal Article↗
PubMed2000

Three novel monotetrahydrofuran annonaceous acetogenins from Annona montana.

Three new monotetrahydrofuran (mono-THF) acetogenins, anmontanins A-C (1-3) were isolated from the leaves of Annona montana. Anmontanin C (3) is the first stereochemically pure acetogenin reported to have a gamma-hydroxymethyl-gamma-lactone moiety. Two known mono-THF acetogenins, murisolin and annonacin, were isolated from the seeds of the plant. The structures of compounds 1-3 were elucidated by spectral methods and chemical derivatization.

Furans↗
PubMed2000

Pharmacological examination of contractile responses of the guinea-pig isolated ileum produced by mu-opioid receptor antagonists in the presence of, and following exposure to, morphine.

We have assessed the potential of several mu-opioid receptor antagonists to elicit a response in the guinea-pig isolated ileum in the presence of, and following overnight exposure to, morphine. Naloxone, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP), (-)-5, 9alpha-diethyl-2-(3-furyl-methyl)-2'-hydroxy-6,7-benzomorphan (MR2266), but not D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP), produced a transient inhibition of electrically-evoked contractions of the guinea-pig ileum. The effect of 1 microM CTOP, but not that to MR2266, was inhibited by 1 microM somatostatin. Naloxone (0.3 microM), CTOP (3 microM), CTAP (3 microM) and MR2266 (0.3 microM) antagonized the inhibitory effect of morphine on electrically-evoked contractions of the guinea-pig to a similar degree and, following 60 min exposure to morphine, produced non-sustained contractions. The response to 3 microM CTOP was significantly smaller than that to 3 microM CTAP. None of the antagonists produced a response in the absence of morphine. Following overnight exposure of the ileum to 0.3 microM morphine (4 degrees C), and repeated washing to remove the agonist, all four antagonists elicited non-sustained contractions. However, the responses to 3 microM CTOP and 0.3 microM MR2266 were significantly smaller than those elicited by 0.3 microM naloxone and 3 microM CTAP. Somatostatin (1 microM) significantly reduced naloxone-induced contractions, but not those to CTAP. While all four mu-opioid antagonists elicited contractions in the presence of, and following prolonged exposure to, morphine, differences between them were noted which may be a consequence of non-opioid actions.

Animals↗
PubMed2000

Intraoperative sestamibi scanning in reoperative parathyroidectomy.

BACKGROUND: Reoperative neck exploration for hyperparathyroidism is often difficult even for experienced surgeons. Recent advances in preoperative and intraoperative localization techniques have improved successful resection rates. This prospective study evaluates the accuracy and clinical utility of intraoperative technetium 99m sestamibi scanning for localizing hyperfunctioning parathyroid tissue in reoperative neck explorations. PATIENTS AND METHODS: Eleven patients underwent reoperative neck exploration for hyperparathyroidism. Two patients had 3 prior neck explorations, 1 had 2 prior neck explorations, and 8 patients had 1 prior neck operation. Preoperative studies included sestamibi scintigraphy and ultrasound in all patients, magnetic resonance imaging in 4, computed tomography scan in 3, parathyroid arteriogram in 1, and selective venous sampling in 1. All patients underwent intraoperative technetium 99m sestamibi scanning and parathyroid hormone assay. RESULTS: Preoperative technetium 99m sestamibi scanning and ultrasound each successfully localized 7 of 11 hyperfunctioning glands (64%). Intraoperative technetium 99m sestamibi scanning correctly localized 10 of 11 hyperfunctioning glands (91%). Intraoperative parathyroid hormone assay confirmed successful excision of hyperfunctioning tissue in all 11 patients. Postoperatively, all 11 patients had low-normal or normal calcium levels. CONCLUSIONS: Intraoperative technetium 99m sestamibi correctly localized 91% of hyperfunctioning glands compared with 64% localization for preoperative technetium 99m sestamibi and preoperative ultrasound. Intraoperative technetium 99m sestamibi scanning and parathyroid hormone monitoring are useful in reoperative neck explorations for hyperparathyroidism.

Adult↗
PubMed2000

Comparison between young and old patients with bronchogenic carcinoma.

The aim of this study was to compare the clinical characteristics, histological type, stage at diagnosis, treatment and survival of young (< or = 45 years) and older patients with bronchogenic carcinoma. The study was designed as a retrospective review of all lung cancer patients referred to the Kuwait Cancer Control Center over a 10-year period from 1985 to 1994. The study comprised 590 patients with primary bronchogenic carcinoma, of whom 72 (12%) were < or = 45 years of age at the time of diagnosis. Median (range) duration of symptoms, percentage of smokers and male to female ratios for the younger and older patients were 8 (2-48) weeks vs. 8 (1-52) weeks (p = 0.9), 74% vs. 83% (p = 0.06) and 5.5 vs. 5.3, respectively. The majority of patients had advanced stage disease at presentation; 91% of the younger patients had stage III or IV compared with 88% of the older patients (p = 0.1). The histological types for the younger and older patients were 32% vs. 20% for adenocarcinoma (p = 0.01) and 33% vs. 45% for squamous cell carcinoma (p = 0.1). There were more patients in the younger group who had surgery (21% vs. 7.5%) than in the older group (p = 0.001). Follow-up data were available for 177 patients out of 190 Kuwaiti national patients (93%). The median (range) survival rates for young and old patients were 8 (3-62) months and 7 (1-174) months, respectively (p = 0.09). Only 6 patients survived for more than 5 years, one (7.6%) from the younger group and 5 (3%) from the older group. Our study shows a relatively high percentage of young patients in our population of lung cancer patients. Apart from the higher incidence of adenocarcinoma in the young group and the fact that these patients had more surgery than the older group, there were no other significant differences between the two groups.

Adult↗