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Biomedical subjects

L M Levy

Publications and source records attributed to L M Levy.

At least 19 recordsLinked to original sources
PubMed2000

Cancer incidence in the African population of Harare, Zimbabwe: second results from the cancer registry 1993-1995.

The data of the population-based cancer registry in Harare, Zimbabwe, for 1993-1995 are presented and compared with those from 1990-1992. The most significant change in rates is the striking increase in the incidence of Kaposi's sarcoma (KS) in both men and women, compatible with the evolution of the AIDS epidemic in sub-Saharan Africa. The incidence of KS doubled in both sexes and now accounts for 31.1% of registered cancers. It has overtaken breast cancer to become the second most common tumour in African women, after cervical cancer, and is now one of the leading childhood tumours, accounting for 10. 3% of cancers recorded in children (ages 0-14). With the exception of KS, the incidence and pattern of occurrence of the other malignant neoplasms changed little during the observed 6 years.

Adolescent↗
PubMed2000

Indole alkaloids from a culture of the fungus Aporpium caryae.

In a screening for antifungal metabolites, two indole compounds of mixed biogenesis, 1H-indole-3-carboxylic acid, 1-(1,1-dimethyl-2-propenyl) methyl ester and 1H-indole-3-carboxylic acid, 1-(2,3-dihydroxy-1,1-dimethylpropyl) methyl ester were isolated from a culture of the basidiomycete Aporpiums caryae. The structural elucidation of these compounds was accomplished by spectroscopic methods.

Alkaloids↗
PubMed1999

Aids and cancer in Africa: the evolving epidemic in Zimbabwe.

BACKGROUND: Zimbabwe is severely affected by the AIDS epidemic, and many cancers in African populations are related to infectious agents. OBJECTIVE: To study the current pattern, and short-term changes in incidence, of cancers related to infectious agents (and especially to HIV), with respect to the evolving epidemic of AIDS. METHODS: Analysis of data on the African population of Harare, Zimbabwe, from the Zimbabwe Cancer Registry, for the period 1990-1995. Comparison with data on prevalence of HIV seropositivity, and notifications of AIDS. RESULTS: Comparing results from 1993-1995 with those for 1990-1992 shows a continuing increase in the incidence of Kaposi's sarcoma with a doubling of the rates in both men and women. A dramatic increase in the incidence of squamous cell tumours of the conjunctiva was also observed, as well as a significant increase in the incidence of non-Hodgkin's lymphoma in women. There was no apparent increase in risk for Hodgkin's disease, myeloma, liver cancer, or cancer of the cervix. CONCLUSIONS: The AIDS epidemic has had a dramatic effect on the profile of cancer. The changes in incidence involve several cancers previously linked to AIDS in North America and Europe.

Acquired Immunodeficiency Syndrome↗
PubMed1999

The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid.

The stiff-person syndrome, a rare and disabling disorder, is characterized by muscle rigidity and episodic spasms that involve axial and limb musculature. Continuous contraction of agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the hallmark clinical and electrophysiologic signs of the disease. Except for global muscle stiffness, results of neurologic examination are usually normal. Results of conventional computed tomography and magnetic resonance imaging of the brain are also normal. The cause of the stiff-person syndrome is unknown; however, an autoimmune pathogenesis is suspected because of 1) the presence of antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA); 2) the association of the disease with other autoimmune conditions; 3) the presence of various autoantibodies; and 4) a strong immunogenetic association. Anti-GAD antibodies, which are found in high titers in most patients, seem to be directed against conformational forms of GAD. New evidence suggests that these antibodies may be pathogenic because they interfere with the synthesis of GABA. In addition, a reduction in brain levels of GABA, which is prominent in the motor cortex, has been demonstrated with magnetic resonance spectroscopy in patients with the stiff-person syndrome. The stiff-person syndrome is clinically elusive but potentially treatable and should be considered in patients with unexplained stiffness and spasms. Drugs that enhance GABA neurotransmission, such as diazepam, vigabatrin, and baclofen, provide mild to modest relief of clinical symptoms. Immunomodulatory agents, such as steroids, plasmapheresis, and intravenous immunoglobulin, seem to offer substantial improvement. Results of an ongoing controlled trial will elucidate the role of these agents in the treatment of the disease.

Adjuvants, Immunologic↗
PubMed1999

Metabolic abnormalities detected by 1H-MRS in dyscalculia and dysgraphia.

Proton MRS was performed in a patient with developmental acalculia. The results indicated a focal, wedge-shaped defect in the left temporoparietal brain region near the angular gyrus, with differential decreases in N-acetyl-aspartate, creatine, and choline. These results support the hypothesis that developmental acalculia, like acquired acalculia, is associated with left posterior hemisphere lesions.

Adolescent↗
PubMed1999

Pancytopenia in Zimbabwe.

BACKGROUND: There has been little systematic study of the clinical spectrum of pancytopenia, and the optimal diagnostic approach to pancytopenia remains undefined. METHODS: The authors studied 134 hospitalized pancytopenic patients in Zimbabwe in both consecutive and nonconsecutive fashion. RESULTS: The most common cause of pancytopenia was megaloblastic anemia, followed by aplastic anemia, acute leukemia, acquired immunodeficiency syndrome (AIDS), and hypersplenism. Severe pancytopenia was usually due to aplastic anemia. Patients with aplastic anemia and acute leukemia were usually children, whereas those with megaloblastic anemia were adults. Moderate to severe anemia was noted throughout the series, but was most striking in patients with megaloblastic anemia, aplastic anemia, and acute leukemia. The mean corpuscular volume (MCV) was elevated in most patients with megaloblastic hematopoiesis, aplastic anemia, and acute nonlymphocytic leukemia. Normal or low MCV values were noted in almost one third of patients with megaloblastic anemia. Anisocytosis, poikilocytosis, macroovalocytosis, microcytosis, fragmentation, and teardrop erythrocytes were more prominent on the blood films of patients with megaloblastic anemia. CONCLUSIONS: Megaloblastic anemia, aplastic anemia, and AIDS are the most common causes of pancytopenia in Zimbabwe. Aplasia is the most frequent cause of severe pancytopenia. The authors have formulated tentative guidelines for the evaluation of pancytopenic patients in this setting.

Acquired Immunodeficiency Syndrome↗
PubMed1999

MR imaging of cerebrospinal fluid flow and spinal cord motion in neurologic disorders of the spine.

In summary, MR imaging of CSF and cord motion helps to evaluate diseases affecting cord and CSF motion and to identify the specific pathophysiology involved. A number of significant points have been made. First, MR imaging flow studies can be useful in evaluating CSF spaces and cystic diseases. Second, longitudinal and transverse motions occur in the spinal cord and CSF. Traveling wave motion occurs along the length of the spinal cord. Third, spinal cord tethering is associated with decreased cord velocity and loss of cord displacement at tethering site. Decreased transverse velocities occur with lateral cord tethering to the spinal canal. Fourth, in spinal dysraphism, longitudinal cord velocity is decreased by tethering, and is normal in asymptomatic patients with low conus. Normal cord motion helps to rule out possible tethering in symptomatic dysraphism with hydromyelia. Fifth, in acquired and nonmyelodysplastic symptomatic tethering, spinal cord motion is decreased. Sixth, in symptomatic cord compression, CSF flow and cord motion decrease, but recover after surgical decompression and after compensatory atrophy. Seventh, in asymptomatic spinal stenosis, cord motion is normal or increased. Diffuse spinal stenosis with cord atrophy leads to diffuse cord acceleration and prolonged cord caudal velocity, possibly related to the loss of the transverse mobility of the cord. Finally, focal spinal stenosis leads to focal dynamic cord deformation and can be associated with prominent intramedullary deformations. When compression is severe or symptomatic, cord motion is significantly decreased. Postoperative cases demonstrate good recovery of cord and CSF motion, unless compression or obstruction is still present.

Cerebrospinal Fluid↗
PubMed1998

Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake.

Glutamate transport across the plasma membrane of neurons and glia is powered by the transmembrane electrochemical gradients for sodium, potassium, and pH, but there is controversy over the number of Na+ cotransported with glutamate. The stoichiometry of glutamate transporters is important because it determines a lower limit to the extracellular glutamate concentration, [glu]o, in both normal and pathological conditions. We used whole-cell clamping to study the stoichiometry of the glial transporter GLT-1, the most abundant glutamate transporter in the brain, expressed under control of the Tet-On system in a Chinese hamster ovary (CHO) cell line selected for low endogenous glutamate transport. After the induction of GLT-1 expression with doxycycline, glutamate evoked a Na+-dependent inward current with the voltage dependence and pharmacology of GLT-1 and acidified the cell cytoplasm. Raising [K+]o around cells clamped with electrodes containing sodium and glutamate evoked an outward reversed uptake current. These responses were reduced by the specific GLT-1 blocker dihydrokainate (DHK). DHK evoked an outward current with NO3-, but not with Cl-, as the main intracellular anion, suggesting that the anion conductance of the transporter is active even without external glutamate but generates little current in the absence of highly permeable anions like NO3-. Measuring the reversal potential of the transporter current in various ionic conditions suggested that the transport of one glutamate anion is coupled to the cotransport of three Na+ and one H+ and to the countertransport of one K+. This suggests that in ischemia, when [K+]o rises to 60 mM, the reversal of glutamate transporters will raise [glu]o to >50 microM.

ATP-Binding Cassette Transporters↗
PubMed1998

Inducible expression of the GLT-1 glutamate transporter in a CHO cell line selected for low endogenous glutamate uptake.

Inducible expression of the mammalian glial cell glutamate transporter GLT-1 has been established in a CHO cell line selected for low endogenous Na+-dependent glutamate uptake by [3H]aspartate suicide selection. Culturing the cells in doxycycline-containing medium, to activate GLT-1 expression via the Tet-On system, increased uptake of the GLT-1 substrate D-aspartate 280-fold, and increased cell size. Applying glutamate to whole-cell clamped, doxycycline-treated cells evoked a transporter-mediated current with characteristics appropriate for GLT-1. This cell line provides a useful tool for further examination of the electrical, biochemical and pharmacological properties of GLT-1, the most abundant glutamate transporter in the brain.

ATP-Binding Cassette Transporters↗
PubMed1997

Expression of glial glutamate transporters GLT-1 and GLAST is unchanged in the hippocampus in fully kindled rats.

In situ hybridization techniques and quantitative western blotting were used to study the expression of the glial glutamate transporter GLT-1 and GLAST in the brains of normal (implanted, non-kindled) and fully kindled rats. Wistar rats were implanted with stimulating electrodes in the basolateral amygdala, and killed 28 days after the stimulated group had shown stage 5 seizures on five occasions. The brains were processed for in situ hybridization of messenger RNA for GLT-1 using 35S-labelled oligonucleotide probes or digoxigenin-labelled riboprobes. Paired (kindled and non-kindled) sections were used for qualitative and quantitative analyses. Image analysis of autoradiograms showed no change in expression of GLT-1 messenger RNA in any region of the hippocampus or in the cortex. An increase in expression of GLT-1 messenger RNA (expressed as percentage difference of control) was observed bilaterally in the striatum in kindled animals (16-21%, P<0.05). Nuclear emulsion-dipped sections showed predominant glial cell labelling in the hippocampus. Particle density analysis revealed reduced cell labelling in some kindled vs control pairs but overall there was no significant reduction in labelling in CA1. Equivalent results were found in CA1 using digoxigenin-labelled riboprobes. Quantitative immunoblotting also revealed no change in GLT-1 or GLAST transporter protein in the hippocampus of kindled animals. From these data we conclude that the enduring seizure susceptibility associated with the fully kindled state is unlikely to involve alterations in hippocampal GLT-1 messenger RNA or GLT-1 and GLAST transporter protein expression.

ATP-Binding Cassette Transporters↗
PubMed1997

Primary cerebral lymphoma in Zimbabwe: a report of three patients.

Primary central nervous system lymphoma (PCNSL) is steadily increasing. Immunosuppressed individuals are at particular risk. In AIDS patients a clinical diagnosis of PCNSL is made in 0.5 to 8.4%, and a post mortem diagnosis in up to 11% of cases. In spite of the extensive HIV epidemic in parts of Africa, a literature search revealed only one African report of this condition. The reasons for this apparent infrequency are not clear. Possibilities include under diagnosis or early demise of patients due to other AIDS related illnesses of earlier onset. Three patients with primary cerebral lymphoma from Zimbabwe are presented. All were young, with tumours of high grade showing typical features.

Adult↗
PubMed1996

Brain glutamate transporter proteins form homomultimers.

Removal of excitatory amino acids from the extracellular fluid is essential for synaptic transmission and for avoiding excitotoxicity. The removal is accomplished by glutamate transporters located in the plasma membranes of both neurons and astroglia. The uptake system consists of several different transporter proteins that are carefully regulated, indicating more refined functions than simple transmitter inactivation. Here we show by chemical cross-linking, followed by electrophoresis and immunoblotting, that three rat brain glutamate transporter proteins (GLAST, GLT and EAAC) form homomultimers. The multimers exist not only in intact brain membranes but also after solubilization and after reconstitution in liposomes. Increasing the cross-linker concentration increased the immunoreactivity of the bands corresponding to trimers at the expense of the dimer and monomer bands. However, the immunoreactivities of the dimer bands did not disappear, indicating a mixture of dimers and trimers. GLT and GLAST do not complex with each other, but as demonstrated by double labeling post-embedding electron microscopic immunocytochemistry, they co-exist side by side in the same astrocytic cell membranes. The oligomers are held together noncovalently in vivo. In vitro, oxidation induces formation of covalent bonds (presumably -S-S-) between the subunits of the oligomers leading to the appearance of oligomer bands on SDS-polyacrylamide gel electrophoresis. Immunoprecipitation experiments suggest that GLT is the quantitatively dominant glutamate transporter in the brain. Radiation inactivation analysis gives a molecular target size of the functional complex corresponding to oligomeric structure. We postulate that the glutamate transporters operate as homomultimeric complexes.

ATP-Binding Cassette Transporters↗
PubMed1996

Peroxynitrite inhibits glutamate transporter subtypes.

The reuptake of glutamate in neurons and astrocytes terminates excitatory signals and prevents the persistence of excitotoxic levels of glutamate in the synaptic cleft. This process is inhibited by oxygen radicals and hydrogen peroxide (H2O2). Here we show that another biological oxidant, peroxynitrite (ONOO-), formed by combination of superoxide (O2-) and nitric oxide (NO), potently inhibits glutamate uptake by purified or recombinant high affinity glutamate transporters reconstituted in liposomes. ONOO- reduces selectively the Vmax of transport; its action is fast (reaching > or = 90% within 20 s), dose-dependent (50% inhibition at 50 microM), persistent upon ONOO- (or by product) removal, and insensitive to the presence of the lipid antioxidant vitamin E in the liposomal membranes. Therefore, it likely depends on direct interaction of ONOO- with the glutamate transporters. Three distinct recombinant glutamate transporters from the rat brain, GLT1, GLAST, and EAAC1, exhibit identical sensitivity to ONOO . H2O2 also inhibits reconstituted transport, and its action matches that of ONOO- on all respects; however, this is observed only with 5-10 mM H202 and after prolonged exposure (10 min) in highly oxygenated buffer. NO, released from NO donors (up to 10 mM), does not modify reconstituted glutamate uptake, although in parallel conditions it promotes cGMP formation in synaptosomal cytosolic fraction. Overall, our results suggest that the glutamate transporters contain conserved sites in their structures conferring vulnerability to ONOO- and other oxidants.

ATP-Binding Cassette Transporters↗
PubMed1996

Cloning and expression of a neuronal rat brain glutamate transporter.

Glutamate is the major excitatory transmitter in the mammalian central nervous system. Glutamate transporters, which keep the extracellular glutamate concentration low, are required both for normal brain function and for protecting neurons against harmful glutamatergic overstimulation. We have isolated the cDNA for a rat brain glutamate transporter (REAAC1) which has 90% amino acid and 86% nucleotide identity to the rabbit EAAC1. When REAAC1 was expressed in HeLa cells using a recombinant vaccinia-T7 virus expression system, a sodium dependent glutamate uptake was observed. The affinity of the carrier to various substrates was typical of brain "high affinity' glutamate uptake: threo-3-hydroxyaspartate, (R)-aspartate, (S)-glutamate and (S)-trans-pyrrolidine-2,4-dicarboxylic acid were strong inhibitors, but not (R)-glutamate or gamma-aminobutyrate. High resolution, non-radioactive in situ hybridization histochemistry in rat brain revealed the mRNA in several types of glutamatergic as well as non-glutamatergic neurons, but not in glial cells.

ATP-Binding Cassette Transporters↗