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Biomedical subjects

M Khalil

Publications and source records attributed to M Khalil.

At least 19 recordsLinked to original sources

Vibrational anharmonicities revealed by coherent two-dimensional infrared spectroscopy.

Two-dimensional infrared photon echo spectroscopy has been used to describe the anharmonic nuclear potential of two coupled molecular vibrations. The two-dimensional spectrum shows diagonal and off-diagonal features, each composed of two peaks. The splitting between these peaks is directly related to the anharmonicity, while the relative amplitude of the diagonal and off-diagonal features describes the projection angle between interacting dipoles.

Journal Article↗

T cell studies in a peptide-induced model of systemic lupus erythematosus.

We have previously reported that immunization with a peptide mimetope of dsDNA on a branched polylysine backbone (DWEYSVWLSN-MAP) induces a systemic lupus erythematosus-like syndrome in the nonautoimmune BALB/c mouse strain. To understand the mechanism underlying this breakdown in self tolerance, we examined the role of T cells in the response. Our results show that the anti-foreign and anti-self response induced by immunization is T cell dependent and is mediated by I-E(d)-restricted CD4(+) T cells of the Th1 subset. In addition, generation of the critical T cell epitope requires processing by APCs and depends on the presence of both DWEYSVWLSN and the MAP backbone. The breakdown in self tolerance does not occur through cross-reactivity between the T cell epitope of DWEYSVWLSN-MAP and epitopes derived from nuclear Ags. In this induced-model of SLE, therefore, autoreactivity results from the activation of T cells specific for foreign Ag and of cross-reactive anti-foreign, anti-self B cells. Despite the fact that tissue injury is mediated by Ab, the critical initiating T cell response is Th1.

Animals↗

Effects of charged water-soluble polymers on the stability and activity of yeast alcohol dehydrogenase and subtilisin Carlsberg.

Remarkable increases in enzyme catalytic stability resulting from addition of charged water-soluble polymers have recently been reported, suggesting that use of these polymers may be an attractive general strategy for enzyme stabilization. To test the proposed hypothesis that coulombic forces between water-soluble polymers and enzymes are primarily responsible for enzyme stabilization, we examined the catalytic stability and activity of two enzymes in the presence of polymers differing in net charge. All polymers tested increased enzyme lifetimes, regardless of their net charge, suggesting that stabilization of these enzymes by water-soluble polymers is not solely dependent on simple electrostatic interactions between the polymers and enzymes.

Acrylic Resins↗

Hematologic complications of alternative remedies.

The use of alternative therapies increased dramatically over the last decade with a wide variety of methods and interventions. Dietary supplements are a very common form of alternative therapy used by healthy people as well as patients with serious health problems. The use of these untested, unregulated therapies may carry inherent risks. Hematologic complications are known side effects of these remedies and may present potentially life-threatening events. This manuscript discusses the clinical manifestations and mechanisms of action of these remedies and provides recommendations for patients' evaluation and counseling.

Complementary Therapies↗

Human hepatocyte cell lines proliferating as cohesive spheroid colonies in alginate markedly upregulate both synthetic and detoxificatory liver function.

BACKGROUND/AIMS: Bio-artificial liver support systems for treatment of hepatic failure require maintained expression of hepatocyte function in vitro. We studied cultures of human hepatocyte cell-lines proliferating within alginate beads, investigating the hypothesis that 3-dimensional cohesive colonies of hepatocyte cell-lines would achieve polarity and cell-to-cell contact resulting in upregulation of function. METHODS: HepG2 and HHY41 human cell lines in alginate beads were cultured for >20 days. RESULTS: Proliferation was maintained for 20 days. Production of albumin, prothrombin, fibrinogen, alpha-1-acid glycoprotein and alpha-1-antitrypsin was maintained throughout, maximal at days 8-10, when upregulation was 300-1100% compared with monolayer cultures at similar cell number per unit volume. Detoxificatory functions: ethoxyresorufin deethylase activity, androstenedione metabolism, and urea synthesis from arginine was also increased several-fold. Function returned to pre-freezing levels within 18 h of thawing after cryopreservation of cells in alginate. Electron microscopy revealed spherical colonies of cells of cuboidal shape, with cell-to-cell contact via desmosomes and junctional complexes, abundant microvilli, and cytoplasmic appearances suggesting transcriptionally active hepatocytes. CONCLUSION: Hepatocyte cell-lines, proliferating in alginate express a range of liver-specific functions at levels approaching those found in vivo, relevant to their use in liver support systems.

Alginates↗

Isolation and properties of two forms of thrombin inhibitor from the nymphs of the camel tick Hyalomma dromedarii (Acari: Ixodidae).

Two forms of the nymphal thrombin inhibitors (NTI) 3.2 kDa and 14.9 kDa were purified by chromatography on CM-cellulose. Sephacryl S-300 and Sephadex G-50 columns and designated NTI- 1 and NTI-2 respectively. The NTI-2 turned out to be homogenous monomeric protein in both native-PAGE and denatured SDS-PAGE with M(r) value of 14.9 kDa approximately and its pI value ranged from 7.2 to 7.5. The NTI-1 and NTI-2 displayed anticoagulant activity since they prolonged both the activated partial thromboplastin time (APTT) and the prothrombin time (PT) of the camel plasma in a concentration-dependent manner. The potency of NTI-I toward thrombin was 5-fold higher than that toward FXa, while NTI-2 was 3-fold active toward FXa than thrombin. However, both of them did not inhibit any of the other examined proteases. The types of inhibition of thrombin by NTI-1 and NTI-2 were non-competitive and competitive with inhibition constants (Ki) values of 11.7 microM and 211 nM respectively. One binding site was deduced on thrombin for each inhibitor.

Animals↗

Glc7p protein phosphatase inhibits expression of glutamine-fructose-6-phosphate transaminase from GFA1.

Inhibitor-1 (I-1) is a specific inhibitor of protein phosphatase-1 (PP1). We assayed the ability of I-1 to inhibit Saccharomyces cerevisiae PP1, Glc7p, in vivo. Glc7p like other PP1 catalytic subunits associates with a variety of noncatalytic subunits, and Glc7p holoenzymes perform distinct physiological roles. Our results show that I-1 inhibits Glc7p holoenzymes that regulate transcription and mitosis, but holoenzymes responsible for meiosis and glycogen metabolism were unaffected. Additionally, we exploited a genetic screen for mutants that were dependent on I-1 to grow. This scheme can identify processes that are negatively regulated by Glc7p-catalyzed dephosphorylation. In this paper I-1-dependent gfa1 mutations were analyzed in detail. GFA1 encodes glutamine-fructose-6-phosphate transaminase. One or more phosphorylated proteins activate GFA1 transcription because the pheromone response and Pkc1p/mitogen-activated protein kinase pathways positively regulate GFA1 transcription. Our findings show that an I-1-sensitive Glc7p holoenzyme reduces GFA1 transcription. Therefore, GFA1 is a member of a growing list of genes that are negatively regulated by Glc7p dephosphorylation.

Catalysis↗

Nonpenetrating deep sclerectomy versus trabeculectomy in bilateral primary open-angle glaucoma.

OBJECTIVE: To establish the efficacy and safety of nonpenetrating deep sclerectomy versus trabeculectomy in primary open-angle glaucoma. DESIGN: Prospective randomized trial. PARTICIPANTS: Thirty-nine patients (78 eyes) with bilateral primary open angle glaucoma were included in the study. INTERVENTION: Eyes were randomly assigned to receive deep sclerectomy in one eye and trabeculectomy in the other eye. MAIN OUTCOME MEASURES: Mean intraocular pressure (IOP), postoperative medications, visual acuity, success rate, and complications. RESULTS: At 12 months, mean IOP reduction was 12.3 +/- 4.2 (sclerectomy) versus 14.1 +/- 6.4 mmHg (trabeculectomy) (P = 0.15), and an IOP </= 21 mmHg was achieved in 36 (92.3%) and 37 eyes (94.9%) (P = 0.9), respectively. Complications included three (7.7%) flat/shallow anterior chambers and one (2.6%) hypotony (trabeculectomy), whereas internal iris incarceration was encountered in two eyes (5.1%) (sclerectomy). CONCLUSIONS: Deep sclerectomy may provide comparable IOP reduction with fewer complications in management of primary open angle glaucoma.

Adult↗

Basal cell adenocarcinoma of the lacrimal gland.

PURPOSE: Basal cell adenocarcinoma is a recently recognized entity among malignant tumors of the salivary glands. This entity has not received enough attention among ophthalmologists and ophthalmic pathologists. We recommend that basal cell adenocarcinoma be included in the differential diagnosis of lacrimal gland tumors. DESIGN: Case report. METHODS: In 1988 a lacrimal gland tumor was incompletely removed from the left orbit of a 36-year-old woman and diagnosed as "solid basaloid adenoid cystic carcinoma". Soon after, an exenteration of the orbit was performed. In 1998, upon review of the initial histopathology, the diagnosis of solid adenoid cystic carcinoma was changed to basal cell adenocarcinoma. RESULTS AND MAIN OUTCOME MEASURE: The pathologic findings included nests of basaloid cells with minimal atypia and incomplete palisading around the periphery. The cells were of two types. The first type were large, pale cells with round or oval nuclei, scanty cytoplasm, and ill-defined borders. The other type were smaller cells with hyperchromatic nuclei situated mainly near the periphery of the nests. There was no necrosis or perineural invasion. Mitotic figures were present. Cysts within the nests showed Alcian blue negative contents. Immunohistochemistry showed a positive reaction to cytokeratin and a negative reaction with smooth muscle actin (SMA). CONCLUSIONS: The Alcian blue negative stain, the negative reaction to SMA, and the fact that the patient is still alive 10 years after exenteration favored the diagnosis of basal cell adenocarcinoma. It is essential to differentiate a basal cell adenocarcinoma of the lacrimal gland from the solid basaloid type of adenoid cystic carcinoma, because the former has a better prognosis. Patients with basal cell adenocarcinomas of the lacrimal gland should be closely monitored for local recurrences because this tumor has the tendency to show perineural invasion.

Adenocarcinoma↗

Simultaneous subconjunctival and subscleral mitomycin-C application in trabeculectomy.

OBJECTIVE: To establish the efficacy and safety of simultaneous subconjunctival and subscleral application of mitomycin-C in trabeculectomy. DESIGN: A prospective, randomized study. PARTICIPANTS: Sixty-eight patients (68 eyes) with refractory glaucomas were included in the study. INTERVENTION: Eyes were randomly assigned to receive intraoperative mitomycin-C (0.3 mg/ml) applied under the conjunctival flap (group 1), scleral flap (group 2), or under both flaps (group 3). MAIN OUTCOME MEASURES: Mean intraocular pressure (IOP), postoperative medications, visual acuity, filtering bleb appearance, and complications. RESULTS: There was a significant difference in IOP at 6, 9, and 12 months after surgery among the three groups (P = 0.021, 0.026, and 0.033, respectively ANOVA). At 12 months, the mean IOP in group 3 was 9.8+/-3.7 mm Hg compared with 13.4+/-5.5 mm Hg in group 2. (P = 0.015) and 12.4+/-4.4 mm Hg in group 1 (P = 0.039). Success rate (21 mm Hg or less), number of antiglaucoma medications, and complications showed no statistical significant difference between the three groups at each postoperative visit. CONCLUSIONS: Mitomycin-C applied under the scleral flap may have an additional beneficial effect when combined with simultaneous subconjunctival exposure.

Adult↗

Uterine EMG analysis: a dynamic approach for change detection and classification.

Toward the goal of detecting preterm birth by characterizing events in the uterine electromyogram (EMG), we propose a method of detection and classification of events in this signal. Uterine EMG is considered as a nonstationary signal and our approach consists of assuming piecewise stationarity and using a dynamic change detector with no a priori knowledge of the parameters of the hypotheses on the process state to be detected. The detection approach is based on the dynamic cumulative sum (DCS) of the local generalized likelihood ratios associated with a multiscale decomposition using wavelet transform. This combination of DCS and multiscale decomposition was shown to be very efficient for detection of both frequency and energy changes. An unsupervised classification based on the comparison between variance-covariance matrices computed from selected scales of the decomposition was implemented after detection. Finally a class labeling based on neural networks was developed. This algorithm of detection-classification-labeling gives satisfactory results on uterine EMG: in most cases more than 80% of the events are correctly detected and classified whatever the term of gestation.

Algorithms↗

Three dimensional culture upregulates extracellular matrix protein expression in human liver cell lines--a step towards mimicking the liver in vivo?

Extracellular matrix (ECM) in the liver affects the phenotype of both hepatocytes and non-parenchymal cells. To be able to mimic in vivo liver function for extracorporeal hepatic support using human cell lines, a necessary step is to upregulate the function normally seen in monolayer culture. 3-D spheroid colonies were formed by culturing single HepG2 cells encapsulated in alginate beads. ECM expression in these cultures was compared to monolayer Hep G2 cultures. The following ECM proteins were detected immunohistochemically:- collagens 1, III, V and VI, the glycoproteins fibronectin, tenascin and vitronectin, and the basement membrane protein laminin. In 3-D cultures, all proteins except tenascin were strongly expressed, as compared with weak or undetectable expression in monolayer cultures, even with 10-fold increases in the antibody concentration used. In conclusion, we have demonstrated that the 3-D environment created by alginate encapsulation of cell lines leads to cell behaviour mimicking that in vivo.

Cells, Cultured↗

Laparoscopic extraperitoneal inguinal hernia repair. A safe approach based on the understanding of rectus sheath anatomy.

We have devised a reproducible approach to the preperitoneal space for laparoscopic repair of inguinal hernias that is based on an understanding of the abdominal wall anatomy. Laparoscopic totally extraperitoneal herniorrhaphy was performed on 99 hernias in 90 patients at the Los Angeles County-University of Southern California Medical Center, using a standardized approach to the preperitoneal space. Operative times, morbidity, and recurrence rates were recorded prospectively. The median operative time was 37 min (range, 28-60) for unilateral hernias and 46 min (range, 35-73) for bilateral hernias. There were no conversions to open repair, and there was only one conversion to a laparoscopic transabdominal approach. Complications were limited to urinary retention in two patients, pneumoscrotum in one patient, and postoperative pain requiring a large dose of analgesics in one patient. All patients were discharged within 23 h. There were no recurrences or neuralgias on follow-up at 2 years. A standardized approach to the preperitoneal space based on a thorough understanding of the abdominal wall anatomy is essential to a satisfactory outcome in hernia repair.

Adolescent↗

Role of interferon-alpha in the treatment of primary glomerulonephritis.

Interferon-alpha (IFN-alpha) is a naturally occurring cytokine. It was the first cytokine used with clinical benefit in the treatment of viral hepatitis and malignancies. Patients with viral hepatitis B or C may have complications with glomerulonephritis (GN). Improvement in proteinuria with or without clearing of viral markers after IFN-alpha therapy has been reported. This encouraged us to offer IFN-alpha therapy to four patients with GN. These patients refused treatment with steroids and/or cyclophosphamide because of concerns about side effects. One patient with membranous GN and two patients with mesangial GN (MesGN) had a remission of nephrotic syndrome. In one patient with type II diabetes and MesGN, renal insufficiency and proteinuria did not subside; however, renal function remained stable. The mechanism of action of IFN-alpha is discussed, with its possible role in the treatment of primary GN.

Adult↗

One-site versus 2-site phacotrabeculectomy: a randomized study.

PURPOSE: To compare 1-site and 2-site combined phacoemulsification with foldable intraocular lens (IOL) implantation and trabeculectomy. SETTING: El-Maghraby Eye Hospital, Jeddah, Saudi Arabia. METHODS: Seventy-six eyes with coexisting cataract and glaucoma were randomly assigned to have a mitomycin-C trabeculectomy in a superior quadrant combined with phacoemulsification and foldable IOL implantation through the same incision (1-site group) or a separate, temporal, clear corneal incision (2-site group). Postoperative evaluation included visual acuity, intraocular pressure (IOP), bleb assessment, and number of antiglaucoma medications. Follow-up ranged from 12 to 18 months. RESULTS: Mean preoperative IOP was 28.1 mm Hg +/- 7.1 (SD) in the 2-site group and 26.2 +/- 6.5 mm Hg in the 1-site group. At 6 months postoperatively, mean IOP was 16.9 +/- 4.3 and 16.8 +/- 3.8 mm Hg, respectively (P = .9) and at 12 months, 17.6 +/- 3.3 and 19.1 +/- 3.1 mm Hg, respectively (P = .044). Twenty-three of 39 eyes (59%) in the 2-site group and 14 of 37 (38%) in the 1-site group had clinically apparent filtering blebs at 12 months (P = .065). Postoperative astigmatic change and complications were comparable. CONCLUSION: Mitomycin-C trabeculectomy superiorly combined with separate temporal clear corneal phacoemulsification provided 1 year IOP control comparable to that with single-incision (1-site) combined cataract and glaucoma surgery.

Adult↗