Homology of the NH2-terminal amino acid sequences of the heavy and light chains of human monoclonal lupus autoantibodies containing the dominant 16/6 idiotype.

The NH2-terminal amino acid sequences have been determined by automated Edman degradation for the heavy and light chains of five monoclonal IgM anti-DNA autoantibodies that were produced by human-human hybridomas derived from lymphocytes of two patients with systemic lupus erythematosus. Four of the antibodies were closely related to the idiotype system 16/6, whereas the fifth antibody was unrelated idiotypically. The light chains of the 16/6 idiotype-positive autoantibodies (HF2-1/13b, HF2-1/17, HF2-18/2, and HF3-16/6) had identical amino acid sequences from residues 1 to 40. Their framework structures were characteristic of VKI light chains. The light chain of the 16/6 idiotype-negative autoantibody HF6-21/28 was characteristic of the VKII subgroup. The heavy chains of the 16/6 idiotype-positive autoantibodies had nearly identical amino acid sequences from residues 1 to 40. The framework structures were characteristic of the VHIII subgroup. In contrast, the GM4672 fusion partner of the hybridoma produced small quantities of an IgG with a VHI heavy chain and a VKI light chain. The heavy chains of the lupus autoantibodies and the light chains of those autoantibodies that were idiotypically related to the 16/6 system had marked sequence homology with WEA, a Waldenstrom IgM that binds to Klebsiella polysaccharides and expresses the 16/6 idiotype. These results indicate a striking homology in the amino termini of the heavy and light chains of the lupus autoantibodies studied and suggest that the V regions of the heavy and light chains of the 16/6 idiotype-positive DNA-binding lupus auto-antibodies are each encoded by a single germ line gene.

Fine resolution mapping of population age-structures for health and development applications.

The age-group composition of populations varies considerably across the world, and obtaining accurate, spatially detailed estimates of numbers of children under 5 years is important in designing vaccination strategies, educational planning or maternal healthcare delivery. Traditionally, such estimates are derived from population censuses, but these can often be unreliable, outdated and of coarse resolution for resource-poor settings. Focusing on Nigeria, we use nationally representative household surveys and their cluster locations to predict the proportion of the under-five population in 1 × 1 km using a Bayesian hierarchical spatio-temporal model. Results showed that land cover, travel time to major settlements, night-time lights and vegetation index were good predictors and that accounting for fine-scale variation, rather than assuming a uniform proportion of under 5 year olds can result in significant differences in health metrics. The largest gaps in estimated bednet and vaccination coverage were in Kano, Katsina and Jigawa. Geolocated household surveys are a valuable resource for providing detailed, contemporary and regularly updated population age-structure data in the absence of recent census data. By combining these with covariate layers, age-structure maps of unprecedented detail can be produced to guide the targeting of interventions in resource-poor settings.

Linking remote sensing, land cover and disease.

Land cover is a critical variable in epidemiology and can be characterized remotely. A framework is used to describe both the links between land cover and radiation recorded in a remotely sensed image, and the links between land cover and the disease carried by vectors. The framework is then used to explore the issues involved when moving from remotely sensed imagery to land cover and then to vector density/disease risk. This exploration highlights the role of land cover; the need to develop a sound knowledge of each link in the predictive sequence; the problematic mismatch between the spatial units of the remotely sensed and epidemiological data and the challenges and opportunities posed by adding a temporal mismatch between the remotely sensed and epidemiological data. The paper concludes with a call for both greater understanding of the physical components of the proposed framework and the utilization of optimized statistical tools as prerequisites to progress in this field.

A rapid chromogenic method for the determination of prothrombin precursor in plasma.

A method was described for the quantitation of precursor prothrombin using a chromogenic substrate S2238 and Dispholidus typus venom. Prothrombin precursor was detected in the adsorbed plasma of all 65 patients on coumadin therapy tested, but was absent in 20 controls. The technic offered a rapid and sensitive method for determining if a prolonged prothrombin time is due to vitamin K antagonism or deficiency.

Inhibition of platelet aggregation by ketamine hydrochloride.

Ketamine hydrochloride, 10 mg/kg by intramuscular injection, inhibited aggregation of platelets from three out of three baboons. Aggregation to ADP, arachidonic acid, epinephrine, and collagen was inhibited but aggregation to ristocetin was normal. Two baboons anaesthetised with the related drug phencyclidine, 1.0 mg/kg intramuscularly, had delayed aggregation. Ketamine inhibition of human platelets was irreversible in that aggregation could not be restored by either gel filtration of inhibited platelets and the re-addition of normal plasma, or by increasing the concentrations of agonists. Mixtures of human ketamine inhibited and aspirinised platelets failed to aggregated. Thromboxane B2 production was reduced to 3% of the amount produced by non inhibited platelets but the oxygen burst was not inhibited.

Identification of a heparin activated amidolytic enzyme in carp (Cyprinus carpio) plasma.

A heparin activated amidolytic enzyme capable of cleaving synthetic thrombin sensitive chromogenic substrates was identified from the plasma of the carp (Cyprinus carpio). Activation was inhibited by KCl, protamine sulphate and human plasma. Heparin was not required for the continued action of the enzyme. Active enzyme was irreversibly inhibited by DFP. The pH and temperature optima was studied and the enzyme semi purified by Sephadex G100 superfine and Sephadex A50 chromatography. An approximate MW of 62,000 was found. Activity generated by as little as 0.002 units of heparin per ml carp plasma was detected. The trivial name carpamidase is proposed for the enzyme.

Spatial analysis for epidemiology.

Remote sensing, geographical information systems (GIS) and spatial analysis provide important tools that are as yet under-exploited in the fight against disease. As the use of such tools becomes more accepted and prevalent in epidemiological studies, so our understanding of the mechanisms of disease systems has the potential to increase. This paper introduces a range of techniques used in remote sensing, GIS and spatial analysis that are relevant to epidemiology. Possible future directions for the application of remote sensing, GIS and spatial analysis are also suggested.

Fatty acid composition of human milk from South African black mothers consuming a traditional maize diet.

Fatty acid composition of mature human milk of rural and urban black South African mothers was determined by gas-liquid chromatography. Rural mothers consumed traditional diets low in animal protein and fat, and high in carbohydrate and fibre. Urban mothers consumed more varied, partially westernized diets, and two-thirds were overweight. Plasma cholesterol concentrations were significantly lower in the rural group (3.64 vs 4.75 mmol/l, P less than 0.01). Milk of rural mothers contained significantly higher percentages of C10:0, C12:0, and total saturated fatty acids. Fatty acids C8:0-C14:0 synthesized de novo in the mammary gland were substantially higher in the milk of the rural mothers (24.7 vs 15.9 per cent). Conversely, the milk of the urban group contained higher percentages of monounsaturated fatty acids, 18:3 omega 3 and 20:2 omega 6. The ratio of polyunsaturated to saturated fatty acids in rural samples was 0.36 +/- 0.13 compared to 0.41 +/- 0.15 in urban samples (P greater than 0.1). It is concluded that maternal dietary intake significantly affects milk composition, as demonstrated by the high percentages of fatty acids synthesized de novo in the mammary gland of rural mothers habituated to low-fat, high-carbohydrate intakes.

Disturbances of blood coagulation associated with Salmonella typhi infections.

Disturbances of blood coagulation were studied in 32 consecutive patients with typhoid fever on their admission to hospital. Estimations of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation products (FDPs), factors VII, VIII and XII, alpha I antitrypsin, plasminogen, CI esterase inhibitor, and platelet counts were performed as well as liver function tests and blood counts. Five patients had laboratory evidence of disseminated intravascular coagulation (DIC) and two had a generalised bleeding disorder which in the other three was inapparent. The platelet count in the group as a whole was low (P less than 0.05) and the FDPs in most cases were mildly elevated. The pre-kallikrein values were depressed in three of the five with DIC, whereas factor XII was not reduced. These results indicate that bleeding disorders in typhoid fever are uncommon. The depression of pre-kallikrein indicates that the DIC is probably triggered by activation of the intrinsic coagulation pathway. Most patients had lymphopenia and monocytopenia but only two had neutropenia.

Pregnancy induced hypertension: will treatment with dietary eicosapentaenoic acid be effective?

The current understanding of endothelial membrane prostaglandin metabolism is presented together with an explanation of how this may be altered in pregnancy induced hypertension (PIH). A hypothesis is proposed to explain why dietary supplementation with eicosapentaenoic acid (EPA) may reverse abnormal prostaglandin metabolism, increase membrane fluidity and lower blood pressure in PIH.

Hypothesis: a central role for platelet activating factor in the pathogenesis of pre-eclampsia.

The pathophysiology of pre-eclampsia is uncertain, though many mechanisms have been postulated. These include an immune response to fetal or placental antigens, a thromboxane-prostacyclin system imbalance and an increase in levels of or responsiveness to angiotensin. We propose the hypothesis that platelet activating factor (PAF), a mediator of inflammatory and allergic responses, may be an important link between these pathophysiological events.

A follow-up study of surgically treated cryptorchid patients.

A group of 112 adult patients were traced who had had childhood orchiopexies at an average age of 9 yr at two childrens' hospitals. Sixty-seven per cent of all married patients had sired children although only 44% of the married bilateral cryptorchid patients had done so. The percentage paternity of the unilaterally cryptorchid patients was normal when compared with the general population. There appeared to be no difference in the eventual results of the two types of orchiopexy performed on this series of patients.

Plasma gonadotropins and androgens in surgically treated cryptorchid patients.

Plasma LH, FSH, and total 17betaOH androgen levels were measured in a group of 40 adult patients who underwent orchiopexy for either unilateral or bilateral cryptorchism during childhood. Gonadotropin abnormalities were found in 15 of 40 patients and thereby appeared to be a much more sensitive indicator of testicular malfunction than the androgens which were abnormal in only four patients. In the postpubertal phase, the estimation of gonadotropins and androgens appeared valuable, first, as an additional help in the prognosis of fertility, where combined raised levels of LH and FSH were found to indicate a poor prognosis; second, to detect in infertile patients gonadotropin deficiency which, if previously missed, can still be expected to respond to gonadotropin therapy; third, for the detection of the subclinically hypogonad group who may require follow-up, and finally for the detection of the low-androgen group who may require some form of hormonal therapy. As several patients in this study were found to have low gonadotropins, it is postulated that low levels of gonadotropin may play a role in the production of cryptorchism. The finding of high gonadotropin levels in another group may indicate a feedback mechanism sensitive to a damaged testis, but alternatively it is possible that there might be a primary resistance to the action of gonadotropins and it is postulated that such a resistance may be an additional factor of the causation of cryptorchism in some cases.

Issues of scale and uncertainty in the global remote sensing of disease.

Scale and uncertainty are important issues for the global prediction of disease. Disease mapping over the entire surface of the Earth usually involves the use of remotely sensed imagery to provide environmental covariates of disease risk or disease vector density. It further implies that the spatial resolution of such imagery is relatively coarse (e.g., 8 or 1km). Use of a coarse spatial resolution limits the information that can be extracted from imagery and has important effects on the results of epidemiological analyses. This paper discusses geostatistical models for (i) characterizing the scale(s) of spatial variation in data and (ii) changing the scale of measurement of both the data and the geostatistical model. Uncertainty is introduced, highlighting the fact that most epidemiologists are interested in accuracy, aspects of which can be estimated with measurable quantities. This paper emphasizes the distinction between data- and model-based methods of accuracy assessment and gives examples of both. The key problem of validating global maps is considered.

Long-term ultra-low-dose aspirin therapy and platelet function.

The effect of ultra-low-dose aspirin on platelet aggregation and thromboxane B2 (TXB2) production was studied in two groups of normal subjects. Group 1 received 162 mg/d and group 2 received 20 mg/d for 4 weeks. For the first 2 weeks the effects were similar in the two groups, namely inhibition of aggregation and inhibition of TXB2 production. However, after 4 weeks there was significantly less inhibition of platelet aggregation in those receiving 20 mg/d. Inhibition of TXB2 production in the two groups was not significantly different. Two of 9 individuals receiving 20 mg/d showed an escape from the aspirin effect by the 4th week. When 40 mg/d was given to these 2 individuals they again responded. A daily dose of 20 mg aspirin is therefore too small to maintain adequate inhibition of platelet function in normal subjects.

Case report: splenic-gonadal fusion--the ultrasound appearances.

We report the ultrasound appearances, with pathological correlation, of splenic-gonadal fusion in a patient who presented with an asymptomatic scrotal swelling. Ultrasound examination showed an echo-poor 2 cm diameter lesion in the upper pole of the left testicle. Histologically the lesion was normal spleen. Splenic-gonadal fusion should be considered in the differential diagnosis of scrotal swellings.

Normal haematological reference values in the adult black population of the Witwatersrand.

Normal haematological reference values for healthy adult blacks residing on the Witwatersrand are given. The haemoglobin concentration was 13.95 +/- 0.8 g/dl for women and 15.82 +/- 1.05 g/dl for men. Leucocyte counts were lower than those found in whites, being 5.60 +/- 1.51 X 10(9)/l for both sexes. Platelet counts were 280 +/- 59.4 X 10(9)/l for men and 317 +/- 64.0 X 10(9)/l for women. The differential counts and other parameters are given in the text.