Inherited haemoglobin variants in a South African population.

We present the findings of a survey to determine the prevalence of inherited haemoglobin disorders in the Coloured (mixed ethnic origin) population of South Africa. A variety of haemoglobins was found. Of the structural variants, Hb E and Hb S were the most common, the former probably originating from South-East Asia and the latter from East Africa and possibly Madagascar. The alpha+ (-alpha) thalassaemia haplotype is particularly common with an observed frequency of 0.023. Beta thalassaemia was rather less common, while hereditary persistence of fetal haemoglobin was found for the first time in this population group, occurring in two subjects.     

Computer-Assisted Detection of Pulmonary Nodules: Preliminary Observations Using a Prototype System with Multidetector-Row CT Data Sets

The continued revolution in multidetector-row CT (MDCT) scanning increases the quality of lung imaging but at the cost of a greater burden of data for review and interpretation. This article discusses our preliminary experience with prototype software for lung nodule detection and characterization using MDCT data sets. We discuss the potential role of computer-assisted detection (CAD) as applied to the automatic detection of lung nodules. We also review the process of CAD, outline its potential results, and explore how it may fit into existing radiology practice. Finally, we discuss MDCT data-acquisition parameters and how they may affect the performance of CAD.     

Gradient moment nulling for steady-state free precession MR imaging of cerebrospinal fluid

Steady-state free precession (SSFP) pulse sequences can produce magnetic resonance (MR) images rapidly, in which cerebrospinal fluid (CSF) is several times more intense than the other tissues. However, motion in the presence of magnetic field gradients reduces the intensity of CSF drastically, unless the time integral of the gradient waveform between each radio-frequency (rf) pulse vanishes. The consequences of motion on SSFP are explored here in detail theoretically and experimentally. The principle of gradient moment nulling is applied with the objective of giving CSF in SSFP images uniformly high intensity everywhere, in spite of motion. Theoretical analysis of the phase of the transverse magnetization from a group of isochromats, with a trajectory described by a Taylor series, reveals how motion along each direction disrupts SSFP and also causes ghost artifacts. Images of CSF in the cervical spine are found to have less extensive flow voids and weaker ghosts from pulsation if the first moment calculated from the rf pulse to the center of the gradient echo vanishes for both the frequency encoding and slice selection gradient waveforms. However, first-order moment nulling of the phase encoding gradient waveform is unnecessary for SSFP imaging of CSF.     

Presentation of antigen to suppressor cells by a dimethylbenz (a) anthracene-resistant, Ia-positive, Thy-1-negative, I-J-restricted epidermal cell

The epidermal layer of the skin contains class II major histocompatibility (MHC)-positive antigen-presenting cells (APC), the most well characterized population being Langerhans' cells (LC). The chemical carcinogen 7,12 dimethylbenz (a) anthracene (DMBA) depletes about two-thirds of these cells from murine epidermis, and contact sensitizers applied to DMBA-treated skin induce specific immunological tolerance. This tolerance results from epidermal cells migrating to local lymph nodes within 3-6 hr after contact with antigen where they present the antigen to suppressor cells. Here we demonstrate that this epidermal cell which activates suppressor cells is a class II MHC-positive. Thy-1-negative, I-J-restricted APC. Hence at least two types of class II MHC-positive epidermal cells migrate to local lymph nodes and present antigen to lymphocytes; LC, which are sensitive to the effects of DMBA and activate helper lymphocytes, and another, which is resistant to DMBA and activates suppressor cells in an I-J-restricted manner. During the early stages of carcinogenesis any antigen present in the epidermis would be presented only by the cells which activate suppressor lymphocytes, resulting in tolerance induction. This may enable neoplastic cells to avoid the initiation of anti-tumour immunity.     

Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization

Retinal vasculogenesis and ischemic retinopathies provide good model systems for study of vascular development and neovascularization (NV), respectively. Vascular endothelial cell growth factor (VEGF) has been implicated in the pathogenesis of retinal vasculogenesis and in the development of retinal NV in ischemic retinopathies. However, insulin-like growth factor-I and possibly other growth factors also participate in the development of retinal NV and intraocular injections of VEGF antagonists only partially inhibit retinal NV. One possible conclusion from these studies is that it is necessary to block other growth factors in addition to VEGF to achieve complete inhibition of retinal NV. We recently demonstrated that a partially selective kinase inhibitor, PKC412, that blocks phosphorylation by VEGF and platelet-derived growth factor (PDGF) receptors and several isoforms of protein kinase C (PKC), completely inhibits retinal NV. In this study, we have used three additional selective kinase inhibitors with different selectivity profiles to explore the signaling pathways involved in retinal NV. PTK787, a drug that blocks phosphorylation by VEGF and PDGF receptors, but not PKC, completely inhibited retinal NV in murine oxygen-induced ischemic retinopathy and partially inhibited retinal vascularization during development. CGP 57148 and CGP 53716, two drugs that block phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on retinal NV. These data and our previously published study suggest that regardless of contributions by other growth factors, VEGF signaling plays a critical role in the pathogenesis of retinal NV. Inhibition of VEGF receptor kinase activity completely blocks retinal NV and is an excellent target for treatment of proliferative diabetic retinopathy and other ischemic retinopathies.     

Peripheral blood mononuclear cell human immunodeficiency virus type 1 proviral DNA quantification by polymerase chain reaction: relationship to immunodeficiency and drug effect.

Human immunodeficiency virus type 1 (HIV-1) proviral DNA from peripheral blood mononuclear cells (PBMCs) was quantitated in 61 HIV-1-seropositive individuals by a nonisotopic polymerase chain reaction assay. Primers from the gag region (SK38, SK39) were used to determine the log10 HIV-1 proviral copy number per 10(6) CD4+ T lymphocytes (peripheral blood proviral load). A standard curve was generated for each assay by using ACH-2 cell DNA. The peripheral blood proviral load was followed in 15 individuals in a longitudinal study and was measured in 45 individuals in a cross-sectional analysis. Three of four untreated patients who were followed for 14 months had stable PBMC proviral loads and CD4+ T lymphocyte counts; one untreated patient had a sustained increase in PBMC proviral load followed 5 months later by a significant decline in the CD4+ T lymphocyte count. Eleven previously untreated individuals were monitored for 1 year following initiation of zidovudine and/or 2',3'-dideoxyinosine therapy. The mean log10 number of proviral HIV-1 copies per 10(6) CD4+ T cells decreased from 4.3 +/- 0.4 at the baseline to 3.5 +/- 0.6 after 2 to 4 months of therapy (P < 0.01). This initial 0.8 log10 fall in the PBMC proviral load after the initiation of therapy was followed by a rise in the PBMC proviral load by the sixth month of therapy. The PBMC proviral load in 45 subjects, both treated (n = 25) and untreated (n = 20), correlated inversely with the CD4+ T lymphocyte count (P < 0.01, R = 0.49). PBMC proviral DNA quantification by a nonisotopic polymerase chain reaction assay correlates with HIV-1 disease progression and could be used to monitor the effect of antiretroviral therapy.     

Treatment of bipolar affective illness with zimeldine, a 5-HT uptake inhibitor

A small group of patients who had been successfully treated with lithium for a number of years were treated with zimeldine in order to determine whether this antidepressant could be substituted for lithium in patients with a bipolar affective illness. The proposed treatment period of 6 months was not reached by any patient due to depression, hypomania, mania or unusual adverse symptoms. The results of this pilot study suggest that bipolar patients being treated with lithium should not then be treated by antidepressants including those which are potent and selective inhibitors of 5-HT uptake.     

The hydrational effect of alkali metal and halide ions on the Rh-anti-Rh system

An examination has been made of the action of alkali metal and halide ions on the Rh-anti-Rh system.

Under conditions in which differences due to electrostatic effects are minimal, there is appreciable variation in the experimental response measured by the Race score. This variation is attributed to hydrational effects of the ions and it is noted that the erythrocyte permeability of halide ions complicates their behaviour.

It is suggested that ionic hydration is an important factor governing the magnitude of the entropy change that accompanies Rh-anti-Rh combination in the first stage reaction.

     

In vitro calcification and in vivo biocompatibility of the cross-linked polypentapeptide of elastin

The in vitro calcifiability and molecular weight dependence of calcification of the polypentapeptide, (L X Val1-L X Pro2-Gly3-L X Val4-Gly5)n, which had been gamma-irradiation cross-linked have been determined when exposed to dialyzates of normal, nonaugmented fetal bovine serum. The material was found to calcify: calcifiability was found to be highly molecular weight dependent and to be most favored when the highest molecular weight polymers (n approximately equal to 240) had been used for cross-linking. The in vivo biocompatibility, biodegradability, and calcifiability of the gamma-irradiation cross-linked polypentapeptide were examined in rabbits in both soft and hard tissue sites. The material was found to be biocompatible irrespective of its physical form and to be biodegradable but with n of 200 or less it was not shown to calcify or ossify in the rabbit tibial nonunion model.