Isolation and characterization of a distinct immunoregulatory isoform of alpha-fetoprotein produced by the normal fetus

In this report, we examine the functional significance of the molecular microheterogeneity of alpha-fetoprotein (AFP). In doing so, we have taken the direct approach of purifying the naturally occurring isomeric forms of fetal-derived AFP using a preparative anion exchange column linked to an automated fast protein liquid chromatography (FPLC) system followed by parallel testing of each isolated molecular variant for in vitro immunoregulatory activity. The data obtained demonstrate the presence of seven distinct variants of AFP as defined by their retention volumes on FPLC elution profiles, by their pIs on analytical IEF gels, and by Western blot analysis. Molecular mass determination by SDS-PAGE showed each isomer to be equivalent in size to 69,000-dalton native unfractionated AFP molecules. All the immunosuppressive activity of AFP was localized to a single variant representing only 6% of the total composition of native AFP. The immunoregulating isomer termed AFP-1 was the least acidic of the seven isolated variants with a pI of 5.1 and displayed a sialic acid content of 1 mol/mol of protein. The inhibitory activity of AFP-1 could be readily measured on T cell-dependent antibody synthesis, Con A-induced stimulation of Lyt-1+23- thymocyte DNA synthesis, and lymphokine-activated NK cell activity. All other isomers were without effect in these test systems. The immunosuppressive AFP-1 isomer also displayed the strongest growth-promoting influence on cultured bone marrow lymphocytes. There was no correlation between functional activity and degree of expression of sialic acid residues on the AFP molecules. These findings demonstrate that the immunoregulating function of AFP is confined to a distinct and relatively small subpopulation of native AFP molecules and should therefore contribute to the resolution of outstanding questions regarding the structure/function relationship of this onco-fetal glycoprotein.     

Five‐Year Follow‐up After Sacral Neuromodulation: Single Center Experience

Objective. We studied long‐term clinical efficacy of sacral neuromodulation (SNM) therapy in patients with refractory urgency incontinence (UI), urgency/frequency (UF) and voiding difficulty (VD), together with urodynamic data at baseline and six   months postimplant. Materials and Methods. Twenty‐two patients were implanted with a neurostimulator after a positive response to a percutaneous nerve evaluation test defined as a greater than 50% improvement in symptoms. Results. At five‐year follow‐up, the number of incontinent episodes and pad usage per day decreased significantly in 10 out of 15 UI patients. Two of five UF patients were successfully treated with SNM; the number of daily voids for all UF patients decreased from 25 to 19 and average voided volume increased from 98 to 212 mL. One of the two VD patients was able to void to completion. Mean first sensation of filling at the six‐month urodynamic investigation for the UI and UF patients increased from 78 to 241 mL and 141 to 232 mL, respectively, and the maximum bladder capacity increased from 292 to 352 mL and 223 to 318 mL, respectively. Five of 22 patients underwent device explant and one patient still has an inactive stimulator implanted. Conclusion. SNM is an effective treatment modality that offers sustained clinical benefit in the majority of patients with refractory UI, UF, and VD that do not respond to other, more conservative therapies.     

Mycobacterium ulcerans infection in Ashanti region, Ghana

We describe a series of 96 cases of Mycobacterium ulcerans infection (Buruli ulcer) from a new endemic focus in the Afram valley, north of Agogo, in Ghana. 63 cases were children under 13 years old. Active treatment by excision and skin grafting necessitates long stays in hospital and repeated procedures. Scarring and contracture are frequent. Eyes and other vital organs may be destroyed. In its endemic foci Buruli ulcer is a serious health burden on rural populations. Research is urgently needed, especially in prevention and non-surgical management.     

Descriptive and comparative analysis of geometrical properties of neuronal tree structures

The morphology of neurons is an important factor for the identification and the study of the changes that occur in the nervous system during development or as a result of disease or an experimental treatment. A number of methods to describe the topological aspects of neuronal morphology is discussed. Furthermore it is illustrated how different groups of neurons can be compared. Although both topological and metrical aspects are considered in the comparative sections emphasis is put on counting instead of measuring. Our intention is to present quick and easy methods that are applicable to camera lucida drawings.     

Stage line diagram: An age‐conditional reference diagram for tracking development

This paper presents a method for calculating stage line diagrams, a novel type of reference diagram useful for tracking developmental processes over time. Potential fields of applications include: dentistry (tooth eruption), oncology (tumor grading, cancer staging), virology (HIV infection and disease staging), psychology (stages of cognitive development), human development (pubertal stages) and chronic diseases (stages of dementia). Transition probabilities between successive stages are modeled as smoothly varying functions of age. Age‐conditional references are calculated from the modeled probabilities by the mid‐P value. It is possible to eliminate the influence of age by calculating standard deviation scores (SDS). The method is applied to the empirical data to produce reference charts on secondary sexual maturation. The mean of the empirical SDS in the reference population is close to zero, whereas the variance depends on age. The stage line diagram provides quick insight into both status (in SDS) and tempo (in SDS/year) of development of an individual child. Other measures (e.g. height SDS, body mass index SDS) from the same child can be added to the chart. Diagrams for sexual maturation are available as a web application at http://vps.stefvanbuuren.nl/puberty . The stage line diagram expresses status and tempo of discrete changes on a continuous scale. Wider application of these measures scores opens up new analytic possibilities. Copyright © 2009 John Wiley & Sons, Ltd.