Biomedical subjects
Publications and source records attributed to A Kamal.
Many cases of uveitis are thought to be autoimmune in nature. We report two cases of panuveitis, one of which was associated with chronic active hepatitis and the other with primary biliary cirrhosis. This suggests that the autoimmune disturbance may have been responsible for the development of the intraocular inflammation.
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A broadly conserved membrane-associated protein required for the functional interaction of kinesin-I with axonal cargo was identified. Mutations in sunday driver (syd) and the axonal transport motor kinesin-I cause similar phenotypes in Drosophila, including aberrant accumulations of axonal cargoes. GFP-tagged mammalian SYD localizes to tubulovesicular structures that costain for kinesin-I and a marker of the secretory pathway. Coimmunoprecipitation analysis indicates that mouse SYD forms a complex with kinesin-I in vivo. Yeast two-hybrid analysis and in vitro interaction studies reveal that SYD directly binds kinesin-I via the tetratricopeptide repeat (TPR) domain of kinesin light chain (KLC) with K(d) congruent with 200 nM. We propose that SYD mediates the axonal transport of at least one class of vesicles by interacting directly with KLC.
Azido carbonyl compounds on reaction with trimethylsilyl iodide (in situ prepared from TMSCl/NaI) led to the formation of diazepine imines in good yields under mild conditions. This methodology has been applied to the parent unsubstituted pyrrolobenzodiazepine, the natural product DC-81 and its dimers.
A series of 4beta-arylamino-4'-O-demethylepipodophyllotoxins and 4beta-arylaminoepipodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF. W-68 and other DNA topoisomerase II inhibitors are prepared in good to excellent yields by this method and these are active or more active than etoposide in their inhibition of the human DNA topoisomerase II.
OBJECTIVE: To compare the effectiveness of touch screen system with information leaflet for providing women with information on prenatal tests. DESIGN: Randomised controlled trial; participants allocated to intervention group (given access to touch screen and leaflet information) or control group (leaflet information only). SETTING: Antenatal clinic in university teaching hospital. SUBJECTS: 875 women booking antenatal care. INTERVENTIONS: All participants received a leaflet providing information on prenatal tests. Women in the intervention arm also had access to touch screen information system in antenatal clinic. MAIN OUTCOME MEASURES: Women's informed decision making on prenatal testing as measured by their uptake of and understanding of the purpose of specific tests; their satisfaction with information provided; and their levels of anxiety. RESULTS: All women in the trial had a good baseline knowledge of prenatal tests. Women in the intervention group did not show any greater understanding of the purpose of the tests than control women. However, uptake of detailed anomaly scans was significantly higher in intervention group than the control group (94% (351/375) v 87% (310/358), P=0.0014). Levels of anxiety among nulliparous women in intervention group declined significantly over time (P<0.001). CONCLUSIONS: The touch screen seemed to convey no benefit over well prepared leaflets in improving understanding of prenatal tests among the pregnant women. It did, however, seem to reduce levels of anxiety and may be most effective for providing information to selected women who have a relevant adverse history or abnormal results from tests in their current pregnancy.
AIMS/HYPOTHESIS: Diabetes mellitus leads to functional and structural changes in the brain which appear to be most pronounced in the elderly. Because the pathogenesis of brain ageing and that of diabetic complications show close analogies, it is hypothesized that the effects of diabetes and ageing on the brain interact. Our study examined the effects of diabetes and ageing on learning and hippocampal synaptic plasticity in rats. METHODS: Young adult (5 months) and aged (2 years) rats were examined after 8 weeks of streptozotocin-diabetes. Learning was tested in a Morris water maze. Synaptic plasticity was tested ex vivo, in hippocampal slices, in response to trains of stimuli of different frequency (0.05 to 100 Hz). RESULTS: Statistically significant learning impairments were observed in young adult diabetic rats compared with controls. These impairments were even greater in aged diabetic animals. In hippocampal slices from young adult diabetic animals long-term potentiation induced by 100 Hz stimulation was impaired compared with controls (138 vs 218% of baseline). In contrast, long-term depression induced by 1 Hz stimulation was enhanced in slices from diabetic rats compared with controls (79 vs 92%). In non-diabetic aged rats synaptic responses were 149 and 93% of baseline in response to 100 and 1 Hz stimulation, compared with 106 and 75% in aged diabetic rats. CONCLUSION/INTERPRETATION: Both diabetes and ageing affect learning and hippocampal synaptic plasticity. The cumulative deficits in learning and synaptic plasticity in aged diabetic rats indicate that the effects of diabetes and ageing on the brain could interact.
We analyzed the mechanism of axonal transport of the amyloid precursor protein (APP), which plays a major role in the development of Alzheimer's disease. Coimmunoprecipitation, sucrose gradient, and direct in vitro binding demonstrated that APP forms a complex with the microtubule motor, conventional kinesin (kinesin-I), by binding directly to the TPR domain of the kinesin light chain (KLC) subunit. The estimated apparent Kd for binding is 15-20 nM, with a binding stoichiometry of two APP per KLC. In addition, association of APP with microtubules and axonal transport of APP is greatly decreased in a gene-targeted mouse mutant of the neuronally enriched KLC1 gene. We propose that one of the normal functions of APP may be as a membrane cargo receptor for kinesin-I and that KLC is important for kinesin-I-driven transport of APP into axons.
The cytoskeleton is crucial for the efficient and polarized transport of vesicles in intracellular membrane-sorting pathways. Recent studies have identified specific kinesin, dynein, and myosin motor proteins that mediate defined membrane transport steps. Important clues have also been uncovered about the nature of motor-protein receptors on vesicular cargoes and the molecular mechanisms of motor-protein regulation.
PURPOSE: To investigate the effect of indocyanine green in enhancing the effect of diode laser for treatment of circumscribed choroidal haemangioma. METHODS: Intravenous indocyanine green was used to enhance uptake of heat energy during transpupillary diode thermotherapy of circumscribed choroidal haemangioma. RESULTS: In a series of 6 patients treated in this manner, response to treatment was much improved compared with results without the use of indocyanine green. All patients retained the same or better visual acuity after treatment, and 67% of eyes improved visual acuity by more than 2 lines on Snellen testing. Ultrasonographic and angiographic evidence of improvement was seen in all patients. Treatment complications were minimal, comprising transient worsening of preexisting cystoid macular oedema in one case, and a small macular branch vein occlusion in the retina overlying the treated area. CONCLUSIONS: The use of indocyanine green as a contrast medium during transpupillary thermotherapy allows consistent uptake of diode laser energy, and shortens the duration of laser burn required. It is a cost-effective, easily performed outpatient procedure, with lower morbidity than other treatment modalities.
Assisted zona hatching (AZH) has been used in IVF programmes for several years. Recently one group has reported successful pregnancies after transfer of zona-free blastocysts. The aim of our study was to evaluate outcomes after transfer of zona-free day 3 embryos. Two groups of women undergoing intracytoplasmic sperm injection (ICSI) were included in the study. Group A consisted of 52 women under the age of 40 years undergoing their first ICSI attempt. They were alternately randomized to receive zona-free embryos (27 women) and zona-intact embryos (25 women). The second group (group B) included 71 women with a poor prognosis, as defined by age 40 years or more, and/or at least two previous failed IVF/ICSI attempts. They were randomized in a 3:4 ratio (30 zona-free, 41 zona-intact). Acid Tyrode's solution was used to remove the zona pellucida before embryo transfer on day 3 after oocyte collection. The pregnancy rate in group A was not significantly improved when the zona pellucida was removed. However, in the poor prognosis group B, zona removal resulted in a significantly higher pregnancy rate when compared with controls (23 versus 7.3%). We conclude that complete removal of the zona pellucida can improve pregnancy rates in women with poor IVF/ICSI prognosis.
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Recent studies suggest that the mobility of clathrin-coated pits at the cell surface are restricted by an actin cytoskeleton and that there is an obligate reduction in the amount of spectrin on membranes during coated pit budding. The spectrin-actin cytoskeleton associates with membranes primarily through ankyrins, which interact with the cytoplasmic region of numerous integral membrane proteins. We now report that the fourth repeat domain (D4) of ankyrin(R) binds to the N-terminal domain of clathrin heavy chain with high affinity. Addition of peptides containing the D4 region inhibited clathrin-coated pit budding in vitro. In addition, microinjection of D4 containing peptides blocked the endocytosis of fluorescent low density lipoprotein (LDL). Ankyrin(R) peptides that contained repeat domains other than D4 had no effect on either in vitro budding or internalization of LDL. Finally, immunofluorescence shows that ankyrin is uniformly associated with endosomes that contain fluorescent LDL. These results suggest that ankyrin plays a role in the budding of clathrin-coated pits during endocytosis.
Conventional kinesin, kinesin-I, is a heterotetramer of two kinesin heavy chain (KHC) subunits (KIF5A, KIF5B, or KIF5C) and two kinesin light chain (KLC) subunits. While KHC contains the motor activity, the role of KLC remains unknown. It has been suggested that KLC is involved in either modulation of KHC activity or in cargo binding. Previously, we characterized KLC genes in mouse (Rahman, A., D.S. Friedman, and L.S. Goldstein. 1998. J. Biol. Chem. 273:15395-15403). Of the two characterized gene products, KLC1 was predominant in neuronal tissues, whereas KLC2 showed a more ubiquitous pattern of expression. To define the in vivo role of KLC, we generated KLC1 gene-targeted mice. Removal of functional KLC1 resulted in significantly smaller mutant mice that also exhibited pronounced motor disabilities. Biochemical analyses demonstrated that KLC1 mutant mice have a pool of KIF5A not associated with any known KLC subunit. Immunofluorescence studies of sensory and motor neuron cell bodies in KLC1 mutants revealed that KIF5A colocalized aberrantly with the peripheral cis-Golgi marker giantin in mutant cells. Striking changes and aberrant colocalization were also observed in the intracellular distribution of KIF5B and beta'-COP, a component of COP1 coatomer. Taken together, these data best support models that suggest that KLC1 is essential for proper KHC activation or targeting.
The effects of a low or high concentration of glucose in the perfusion medium on synaptic activity and plasticity were studied in hippocampal slices from rats. Low-glucose medium depressed the field excitatory post-synaptic potentials (fEPSP) significantly, whereas high-glucose medium had little effect on the fEPSP. Tetanization of the afferent fibres elicited significant potentiation (LTP) of synaptic activity irrespective of the glucose concentration in the medium. This may indicate that LTP induction does not depend on optimal neural transmission. Paired-pulse facilitation (PPF) experiments showed that the medium glucose concentration did not significantly influence potentiation of the second response.
OBJECTIVE: Our purpose was to evaluate a protocol for the management of long-standing unexplained infertility. STUDY DESIGN: A prospective study was conducted at an in vitro fertilization-embryo transfer center with 485 patients with the diagnosis of long-standing unexplained infertility. Patients were treated by means of controlled ovarian hyperstimulation and intrauterine insemination for a maximum of 3 cycles. Those who did not become pregnant underwent in vitro fertilization and intracytoplasmic sperm injection on sibling oocytes. RESULTS: Among 485 patients, 921 cycles of controlled ovarian hyperstimulation and intrauterine insemination were performed. The pregnancy rate was 15.7% per cycle and 29.8% per patient. Among those who did not become pregnant, 131 patients underwent in vitro fertilization and intracytoplasmic sperm injection into sibling oocytes; 48 women became pregnant (36.7%). There was total failure of the in vitro fertilization oocytes in 23 cycles (17.6%). CONCLUSION: Management of long-standing unexplained infertility with controlled ovarian hyperstimulation and intrauterine insemination resulted in a reasonable pregnancy rate. Treatment by means of in vitro fertilization and intracytoplasmic sperm injection into sibling oocytes among patients who did not become pregnant resulted in a good pregnancy rate. The overall results showed that the proposed protocol for management of unexplained infertility is satisfactory.
OBJECTIVE: To modify the technique of multifetal pregnancy reduction and to study the outcome of reduced twins in comparison with nonreduced twins and high-order multiple gestations. DESIGN: Prospective controlled study. SETTING: The Egyptian IVF-ET Center, Cairo. PATIENT(S): Seventy-five patients with high-order multiple pregnancies resulting from assisted reproduction. Controls were 40 nonreduced twin pregnancies and 22 high-order multiple gestations. INTERVENTION(S): Transvaginal ultrasonically guided multifetal pregnancy reduction was performed. The first 30 cases were done using KCl as a cardiotoxic agent. The modified technique was used for the last 45 cases at an earlier gestational age (approximately 7 weeks) by eliminating the use of KCI and by aspirating the embryonic parts. MAIN OUTCOME MEASURE(S): Miscarriage rate, gestational age at delivery, birth weight, and pregnancy complications. RESULT(S): Using the modified technique, the miscarriage rate was 8.8% and 41 patients delivered between 32 and 39 weeks of gestation (mean+/-SD, 36.9+/-2.45 weeks). The mean (+/-SD) birth weight was 2,450.51+/-235.44 g. The miscarriage rate, fetal wastage rate, mean gestational age, and mean birth weight were similar in reduced and nonreduced twins and were significantly better than in nonreduced triplets and quadruplets. CONCLUSION(S): The modified technique of multifetal pregnancy reduction significantly improved outcomes, which were similar to those of nonreduced twins resulting from assisted reproduction and significantly better than those of nonreduced triplets and quadruplets.
Streptozotocin-diabetic rats, an animal model for diabetes mellitus, show learning deficits and impaired long-term potentiation in the CA1-field of the hippocampus. The present study aimed to further characterize the effects of streptozotocin-diabetes on N-methyl-D-aspartate receptor-dependent long-term potentiation in the CA1-field, to extend these findings to N-methyl-D-aspartate receptor-dependent and independent long-term potentiation in other regions of the hippocampus and to examine effects on long-term depression. First, the effect of diabetes duration on long-term potentiation in the CA1-field was determined. A progressive deficit was observed after a diabetes duration of six to eight weeks, which reached a maximum after 12 weeks of diabetes and remained stable thereafter. Next, long-term potentiation was examined in the dentate gyrus and in the CA3-field after 12 weeks of diabetes. Both were found to be impaired compared to controls. Finally, long-term depression was examined in the CA1-field of the hippocampus after 12 weeks of diabetes and found to be enhanced in slices from diabetic rats compared to controls. Changes in synaptic plasticity were observed in hippocampal slices from streptozotocin-diabetic rats. Expression of N-methyl-D-aspartate receptor-dependent long-term potentiation was impaired in the CA1-field and dentate gyrus and expression of N-methyl-D-aspartate receptor-independent long-term potentiation was impaired in the CA3-field. In contrast, expression of long-term depression was facilitated in CA1. It is suggested that this combination of changes in plasticity may reflect alterations in intracellular signalling pathways.