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Biomedical subjects

G Gabriel

Publications and source records attributed to G Gabriel.

At least 19 recordsLinked to original sources

The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host.

Mammalian influenza viruses are descendants of avian strains that crossed the species barrier and underwent further adaptation. Since 1997 in southeast Asia, H5N1 highly pathogenic avian influenza viruses have been causing severe, even fatal disease in humans. Although no lineages of this subtype have been established until now, such repeated events may initiate a new pandemic. As a model of species transmission, we used the highly pathogenic avian influenza virus SC35 (H7N7), which is low-pathogenic for mice, and its lethal mouse-adapted descendant SC35M. Specific mutations in SC35M polymerase considerably increase its activity in mammalian cells, correlating with high virulence in mice. Some of these mutations are prevalent in chicken and mammalian isolates, especially in the highly pathogenic H5N1 viruses from southeast Asia. These activity-enhancing mutations of the viral polymerase complex demonstrate convergent evolution in nature and, therefore, may be a prerequisite for adaptation to a new host paving the way for new pandemic viruses.

Adaptation, Physiological↗

Dystrophinopathy presenting as congenital muscular dystrophy.

We report a 3 1/2-year-old boy with congenital hypotonia, calf pseudohypertrophy, markedly delayed motor milestones and joint contractures. He was initially diagnosed to have congenital muscular dystrophy on the basis of the age of onset, a myopathic EMG, an elevated creatine kinase and a dystrophic muscle biopsy. Subsequently, dystrophin immunocytochemistry and immunoblot analysis showed complete absence of dystrophin. We suggest that male cases of CMD should undergo dystrophin analysis, if there is calf hypertrophy and markedly elevated CK (> 2000 U/l).

Biopsy↗

Murine mast cells synthesize basement membrane components. A potential role in early fibrosis.

Mast cells are resident in tissues, particularly in association with endothelial and epithelial cell basement membranes, and increase at sites of inflammation, injury, and fibrosis. Although mast cells are known to both release and generate proinflammatory molecules in response to inflammatory stimuli, little is known about their normal biologic function. Here we demonstrate that IL-3-dependent mouse PT18 mast cells, mouse bone marrow-derived mast cells, and rat basophilic leukemia cells express large amounts of mRNA for collagen IV, laminin, and heparan sulfate proteoglycan. Western blot analysis confirmed that mast cells synthesize and secrete significant amounts collagen IV and laminin B1 and B2 chains. These data suggest that mast cells may contribute to normal tissue repair and/or the early overproduction of basement membrane components seen in a variety of fibrotic conditions.

Actins↗

Response of serum p24 antigen and antibody to p24 antigen in patients with AIDS and AIDS-related complex treated with zidovudine.

In an open study of the treatment of patients with AIDS-related complex (ARC) and AIDS with zidovudine, we evaluated the response of serum p24 antigen (p24Ag) and antibody to p24Ag (anti-p24) levels. Before treatment, serum from 49 out of 73 (67%) patients was p24Ag-positive, and of these patients 42 received zidovudine 800-1200 mg daily for greater than 4 weeks and had a baseline mean serum level of p24Ag of 119 pg/ml (s.e. 15.7). On zidovudine there was a reduction of p24Ag to 21.12% (s.e. 4.76) of pretreatment values at 3 months; however, there was a subsequent trend for levels after 6 months to increase to greater than 50% of pretreatment levels at 12 months. Serum levels of anti-p24 were measured in 26 patients. Of 16 patients whose serum contained p24Ag and 10 whose serum did not, four and nine, respectively, had detectable levels of anti-p24. There was no significant change in the serum anti-p24 with zidovudine therapy.

AIDS-Related Complex↗

Morphometric and freeze-fracture studies on peripheral nerve in shiverer mice.

Observations have been made on the peripheral nerves of shiverer (shi/shi) mice in comparison with control animals. Although this mutant lacks P1 myelin basic protein in peripheral and central myelin, myelin is defective only in the central nervous system. No ultrastructural abnormalities were observed in the shiverer nerves. Myelin spacing was normal. The density and distribution of intramembranous particles on the E and P faces of myelin and in the axolemma of myelinated and unmyelinated axons did not differ between the shiverer and control mice. Morphometric studies showed that external myelinated fiber diameter was significantly less and that myelin thickness was slightly but significantly greater in relation to axon diameter in the shiverer mice, suggesting a minor degree of axonal atrophy. It is concluded that P1 protein is not necessary for the formation and maintenance of the normal structure of peripheral myelin. The failure to detect differences in intramembranous particle density in myelin between shiverer and control mice indicates that P1 protein is not detected in freeze-fracture preparations.

Animals↗

Peripheral nerve intramembranous particle density and distribution in chronic streptozotocin-induced diabetes in rats.

Freeze-fracture studies have been made on the sciatic nerve of rats with chronic streptozotocin-induced diabetes mellitus. The density of intramembranous particles was reduced in both P and E faces of the axolemma of myelinated and unmyelinated axons, in myelin and in the perineurial cells. This may reflect a general reduction in protein synthesis, or excessive protein degradation, related to the diabetic state. The perineurial cells also showed gap junctions which are not normally present in adult rat peripheral nerve. These may represent a reaction to changes in perineurial activity consequent to alterations in the endoneurial tissue fluid.

Animals↗

Freeze-fracture observations on human peripheral nerve.

A study has been made on the appearances in normal human sural nerve using freeze-fracture replication techniques. These have included qualitative observations on the major membrane systems and quantitative assessments of the density of intramembranous particles in the perineurial cell membranes, myelin, the nodal and internodal axolemma of myelinated nerve fibres and the axolemma of unmyelinated axons. The results have been compared with those obtained in other species.

Adolescent↗

Distribution of particle aggregates in the internodal axolemma and adaxonal Schwann cell membrane of rodent peripheral nerve.

Freeze-fracture studies on myelinated fibres from the internodal regions of rat and mouse sciatic nerve show symmetrical particle aggregates within the adaxonal Schwann cell plasmalemma and particle clusters in the axolemma. These are mainly confined to the vicinity of the internal mesaxon and the Schmidt-Lanterman incisures. The Schwann cell particle aggregates are concentrated as bands over the cytoplasmic pockets of Schmidt-Lanterman incisures and the paramesaxonal pockets. In the axolemma there are linear rows of particle aggregates along the groove related to the inner mesaxon and in bands to either side of it. The morphological features suggest the possibility of metabolic coupling between the axoplasm and the Schwann cell cytoplasm via the periaxonal space.

Animals↗

Seizures in relation to head injury.

Seizures have a two-fold relationship with head injury: they can cause a head injury, or they can be the result of a head injury. We compare these two groups in terms of cause, severity, likelihood of sequelae, outcome, radiological investigation, and surgical intervention. Of 702 patients admitted with a head injury to Cook County Hospital (CCH), 25 patients (3.6%) had seizures causing a head injury (Group 1). Another 29 patients (4.1%) experienced a head injury which caused a seizure (Group 2). The remaining 648 patients (Group 3) had no seizure involvement in relation to their injury. Group 1 and Group 3 were similar in terms of severity and sequelae. Group 2, in which a statistically significant increase in both was noted, was dramatically different. It thus appears that seizures indicate increased severity and sequelae in a head injury only when they result from that injury, and not when they cause it. The emergency physician must thus be prepared to distinguish these two situations, for patients in Group 2 have an increased need for neuroradiologic procedures and neurosurgical intervention.

Craniocerebral Trauma↗

The activity of miokamycin (MOM) against Chlamydia trachomatis and mycoplasmas in vitro.

The activity of miokamycin, a new macrolide, was investigated against Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis, in vitro. Miokamycin was found to be similar in activity to doxycycline and erythromycin against Chlam. trachomatis and U. urealyticum. Against Mycopl. hominis, miokamycin had an activity clearly superior to erythromycin.

Anti-Bacterial Agents↗

Reinforcement and protection with polystyrene of freeze-fracture replicas during thawing and digestion of tissue.

An improved method for reinforcing freeze-fracture replicas, which is especially suitable for tough tissues, is described. For this purpose, polystyrene dissolved in chloroform is used to produce a solid protecting layer of plastic on top of the replica, enabling it to withstand the stresses associated with the thawing and digestion of the tissue with strong acids. The method results in production of large clean replicas from tissues such as skin or peripheral nerve which are difficult to process. The method can also be used profitably for reinforcing other softer and more homogeneous tissues.

Axons↗