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Biomedical subjects

J Husain

Publications and source records attributed to J Husain.

12 recordsLinked to original sources

Giant-cell tumor of bone arising from the falx cerebri. A case report.

The histological and ultrastructural features of a giant-cell tumor of bone arising in the falx cerebri of a 27 year-old man are described. The tumor was embedded in the medial aspect of the left frontal lobe and was not attached to any of the bones of the skull. At surgery, the tumor was lightly adherent to the falx and was easily extracted. Histologically, the tumor was composed of mononuclear spindle-shaped and ovoid stromal cells, multinuclear giant cells containing 20-30 nuclei, and foci of osteoid and bone production. Hemorrhagic and cystic areas were also present within the tumor. Ultrastructurally, the spindle-shaped cells resembled fibroblasts and were surrounded by small bundles of collagen fibrils. The ovoid cells contained numerous mitochondria, abundant rough endoplasmic reticulum, vesicles, lysosomes, phagosomes and osseous material in the cytoplasm suggesting their monocyte-macrophage lineage. These cells were closely apposed and displayed evidence of fusion in the form of focal and linear subplasmalemmal densities to form multinucleated giant cells with similar organelles and multiple nuclei. It is suggested that the primary giant cell tumor of the one arose from the metaplastic ossification of the falx. To our knowledge, a giant-cell tumor of bone arising from the falx cerebri has not been previously described.

Adult↗

Extracorporeal shock wave therapy in the management of Peyronie's disease: initial experience.

OBJECTIVE: To evaluate prospectively the efficacy of extracorporeal shock wave therapy (ESWT) as a conservative treatment for Peyronie's disease. PATIENTS AND METHODS: After obtaining ethical committee approval, 37 patients with Peyronie's disease were treated using ESWT. Before treatment the degree of angulation was assessed by artificially inducing an erection with a vacuum device. The severity of pain on erection was assessed using a visual analogue scale (0-5). Each patient was treated with a minimum of three sessions of ESWT (3000 shock waves at an energy density of 0.11-0.17 mJ/mm2) at 3-week intervals. The results were analysed using the Wilcoxon signed-rank test. RESULTS: Of the 37 patients, 34 completed the protocol; the mean (range) duration of the disease was 19.43 (4-60) months and the mean follow-up 7.5 (5-11) months. Almost half (47%) of the patients reported an improvement in angulation, with a mean reduction of 29.3 degrees (10 degrees -60 degrees ) (P < 0.001); 12 of the 20 (60%) patients with pain on erection reported immediate relief, the mean reduction being 2.3 (1-4) on the visual analogue scale (P < 0.001). There was only minimal bruising at the site of treatment and no major side-effects were reported. CONCLUSION: ESWT is an effective and safe treatment for Peyronie's disease; the long-term follow-up and results are awaited.

Adult↗

Combinatorial expression patterns of individual TLE proteins during cell determination and differentiation suggest non-redundant functions for mammalian homologs of Drosophila Groucho.

The Drosophila protein Groucho is involved in the regulation of cell-determination events during insect neurogenesis and segmentation. A group of mammalian proteins, referred to as transducin-like Enhancer of split (TLE) 1 through 4, share with Groucho identical structures and molecular properties. The aim was to determine whether individual TLE proteins participate in the regulation of cell determination in mammals like their Drosophila counterpart. It is here reported that TLE family members are expressed in combinatorial ways during the in vitro differentiation of mouse P19 embryonic carcinoma cells (a model for neural determination) and rat CFK2 cells (a model for chondrocytic determination). TLE1 is up-regulated and TLE2 and TLE4 are down-regulated to different extents during early stages of differentiation. In contrast, later stages correlate with up-regulation of TLE2 and TLE4, and decreased expression of TLE1. Individual TLE proteins are also expressed in combinatorial as well as complementary patterns during the development of the cerebral cortex and spinal cord of mouse embryos. In particular, TLE1 is robustly expressed in both neural progenitor cells and postmitotic neurons of the outer layers of the cortical plate, whereas TLE4 expression marks preferentially postmitotic neurons of the inner layers. Taken together, these results strongly suggest non-redundant roles for individual TLE proteins during both cell-determination and cell-differentiation events.

Animals↗

Affinity for the nuclear compartment and expression during cell differentiation implicate phosphorylated Groucho/TLE1 forms of higher molecular mass in nuclear functions.

The Drosophila protein Groucho is involved in embryonic segmentation and neural development, and is implicated in the Notch signal transduction pathway. We are investigating the molecular mechanisms underlying the function of Groucho and of its mammalian homologues, the TLE ('transducin-like Enhancer of split') proteins. We show that Groucho/TLE1 proteins are phosphorylated. We also show that two populations of phosphorylated Groucho proteins can be identified based on their interaction with the nuclear compartment. More slowly migrating proteins with an apparent molecular mass of roughly 110 kDa interact strongly with the nuclei, while faster migrating proteins displaying molecular masses roughly 84-85 kDa show lower affinity for the nuclear compartment. Similarly, TLE1 proteins with an apparent molecular mass of roughly 118 kDa exhibit higher affinity for the nuclear compartment than do faster migrating forms with apparent molecular masses of 90-93 kDa. Moreover, we show that the nuclear, more slowly migrating, TLE1 proteins are induced during neural determination of P19 embryonic carcinoma cells. These results implicate phosphorylation in the activity of Groucho/TLE1 proteins and suggest that phosphorylated forms of higher molecular mass are involved in nuclear functions. Finally, we show that different TLE proteins respond in different ways to the neural commitment of P19 cells, suggesting that individual members of this protein family may have non-redundant functions.

Animals↗

Oligodendroglial precursor cell susceptibility to hypoxia is related to poor ability to cope with reactive oxygen species.

Oligodendrocyte precursors and astrocytes in 2-week-old rat primary glial cultures survived 24 h of anoxia, suggesting both cell types could survive using glycolysis for ATP synthesis; however, when the hypoxia developed gradually, the majority of oligodendrocyte precursor cells died within 24 h of the beginning of the experiment but astrocytes survived. Similarly when cultures were exposed to an atmosphere of 1% oxygen, but not 2% or greater, oligodendrocyte precursors died within 24 h. Much more lipid peroxidation was seen under conditions of hypoxia than under conditions of anoxia suggesting that oligodendrocyte precursors died under the former condition because of free radical-induced damage. Using 5-(and -6)-carboxy-2',7'-dichlorodihydrofluorescein (DCFH) as an intracellular probe of oxidative stress, we have demonstrated directly on living cells that oligodendrocyte precursors have a poorer ability to scavenge free radicals than astrocytes. Furthermore, when free radicals were induced to form in the cells either by cysteine auto-oxidation or menadione redox cycling, oligodendrocyte precursors were more readily damaged than astrocytes. We conclude that oligodendroglial precursor cells are exquisitively sensitive to reactive oxygen species.

Animals↗

TLE expression correlates with mouse embryonic segmentation, neurogenesis, and epithelial determination.

The TLE proteins are the mammalian homologues of Groucho, a member of the Drosophila Notch signaling pathway. Notch signaling controls the differentiation of a variety of tissues in invertebrates and vertebrates. We are investigating the role of the TLE genes during mammalian development. We show that TLE 1 and TLE 3 are expressed during a number of cell-determination events, including embryonic segmentation, central and peripheral neurogenesis, and epithelial differentiation. This expression pattern is in agreement with the involvement of Groucho in similar fate choices in Drosophila and suggests that Groucho and TLE proteins perform similar developmental roles. Our results also show that TLE genes are co-expressed during a variety of cell-fate choices with several vertebrate homologues of genes implicated in the Drosophila Notch cascade, suggesting a role for the TLE proteins in mammalian Notch signaling.

Animals↗

Hyperthermic injury of oligodendrocyte precursor cells: implications for dysmyelination disorders.

Although 6 h of exposure to 41 degrees C did not affect the viability of oligodendrocyte precursors in culture, a 2-h exposure to 42 degrees C caused them to die. In contrast, astrocytes could tolerate 42 degrees C for at least 6 h. There was an increase in lipid peroxidation following the 42 degrees C insult, particularly in the oligodendrocyte precursors. These findings may be of relevance in understanding certain dysmyelination disorders in humans.

Animals↗

Crystal structure of momordin, a type I ribosome inactivating protein from the seeds of Momordica charantia.

A type I ribosome-inactivating protein, extracted and purified from M. charantia seeds, was crystallised by vapour diffusion with polyethylene glycol at pH 7.2. X-ray data were collected to 2.1 A resolution and the structure solved by molecular replacement using the A-chain coordinates of ricin. The overall fold of the protein is similar to ricin but there are differences in secondary structure, on the surface and in the active site cleft. These differences are probably due in part to the evolution of the protein without a B-chain partner. The most extensive reorganisation occurs at the C-terminus whereas Tyr70 shows the greatest change in the active site cleft.

Binding Sites↗

The conformation of deamino-oxytocin: X-ray analysis of the 'dry' and 'wet' forms.

Two crystal structures of (1 beta-mercaptopropionic acid) deamino-oxytocin are reported. The 'dry form' in space group C2 has cell dimensions a = 27.08 +/- 0.03, b = 9.06 +/- 0.01, c = 22.98 +/- 0.02 A, beta = 102.06 +/- 0.03 with one deamino-oxytocin and six water molecules per asymmetric unit. The 'wet form' in space group P2(1) has cell dimensions a = 27.27 +/- 0.02, b = 9.04 +/- 0.01, c = 23.04 +/- 0.02 A, beta = 102.24 +/- 0.02, with two deamino-oxytocin and 13 water molecules per asymmetric unit. A local twofold parallel to the monoclinic axis gives a pseudo C2 packing. Initial phases of the 'dry form' were calculated by the heavy-atom method from the isomorphous and anomalous difference Pattersons and anomalous difference Fouier synthesis. The structure was refined by using restrained least-squares at 1.2 A resolution to a crystallographic R = 0.10. The molecular replacement method yielded the P2(1) structure that was refined with geometric restraints to R less than 0.09, by using all data to 1.09 A resolution. Deamino-oxytocin consists of a cyclic tocin ring formed by six amino acids, closed by a disulphide bridge, S1-S6, and held by two trans-annular hydrogen bonds N2-O5 and N5-O2 with a type II turn at residues 3 and 4. A flexible tripeptide tail has a loosely hydrogen-bonded type I beta-turn between N9 and O6. The sulphur of cysteine at position 1 is disordered in all the molecules leading to alternative hands of disulphide. The conformational flexibility of Ile 3, Asn 5, Pro 7 side chains and the disulphide bridge is consistent with previous models of oxytocin in which flexibility is necessary for biological activity.

Amino Acid Sequence↗

Severity of nursing-bottle syndrome and feeding patterns in Kuwait.

On the basis of extensive clinical experience, a classification scheme for nursing-bottle syndrome (NBS) has been empirically constructed to reflect the progression and severity of the disease. Patients who do not have NBS are assigned a score of zero. Patients with NBS are given a score of 1 if they have caries on the facial or lingual surface of at least one of the primary maxillary incisors and optionally the primary maxillary first molars, a 2 if the buccal surface of one or both of the primary mandibular first molars are also involved, or a 3 if specific multiple surfaces are involved. The feeding pattern classification is as follows: 0 = non abusive, 1 = mildly, 2 = moderately, and 3 = severely abusive. The scoring depends upon the number of feeding times/day, the frequency with which the bottle or breast feeding is given during the might, and the duration of the feeding pattern (in months). Eighty-six cases were reviewed for classification. A chi-square test of a two-way contingency table showed a strong and significant relationship between disease severity and degree of feeding abuse. The findings support the validity of the classification schemes, illustrate the general pattern of NBS progression, and indicate that disease severity is a function of specific combinations of factors.

Bottle Feeding↗

Management of the unerupted incisor.

Failure of eruption of incisors can cause problems in the adult dentition. Early diagnosis is vital, and a number of options are available for treatment. This article sets out guidelines for general dental practitioners managing such teeth.

Adult↗