Cutaneous allergy.

Cutaneous allergy encompasses a broad spectrum of clinical presentations with complex underlying immunological mechanisms. Allergy may be considered to play a role in disorders that include atopic dermatitis, contact dermatitis, urticaria, angioedema, anaphylaxis and adverse drug reactions. The skin phenotypes associated with allergy are more commonly exhibited in non-allergic disease and so a high proportion of patients who consider themselves allergic in truth have other, nonallergic explanations for their presentation. Investigations may help to delineate those individuals who are more likely to have true allergy, but tests currently available have significant limitations and are open to easy misinterpretation. As a consequence, any investigations are best carried out by someone experienced in managing patients with potentially allergic disorders.

Production of a recombinant form of early pregnancy factor that can prolong allogeneic skin graft survival time in rats.

Early pregnancy factor (EPF), an extracellular chaperonin 10 homologue, has immunosuppressive and growth factor properties. In order to carry out more extensive studies on the in vivo characteristics of EPF, a recombinant form of the molecule has been prepared. Recombinant human EPF (rEPF) was expressed in Escherichia coli using the plasmid pGEX-2T expression system. Potency of rEPF in vitro in the rosette inhibition test, the bioassay for EPF, was equivalent to that of native EPF (nEPF), purified from human platelets, and synthetic EPF (sEPF). However, the half-life of activity (50% decrease in the log value) in serum, following i.p. injection, was significantly decreased (3.2 h, compared with nEPF 6.2 days, sEPF 5.8 days). This was thought to be due to modification of the N-terminus of the recombinant molecule inhibiting binding to serum carrier proteins. Because EPF can modify Th1 responses, the ability of the recombinant molecule to suppress allogeneic graft rejection was investigated. Following skin grafts from Lewis rats to DA rats and vice versa, rEPF was delivered locally at the graft site and the effect on survival time of the allografts noted. Results demonstrated that rEPF treatment significantly prolonged skin graft survival time by as much as 55% in stringent models of transplantation across major histocompatibility barriers.

Early pregnancy factor in liver regeneration after partial hepatectomy in rats: relationship with chaperonin 10.

Early pregnancy factor is not only a product of dividing embryonic and neoplastic cells, as demonstrated previously, but also of normal proliferating cells. Eight hours after partial hepatectomy in rats, early pregnancy factor was detected in serum. It rose to a peak by 48 hr. Neutralization of early pregnancy factor in vivo by passive immunization with specific antibodies, 18 hr after partial hepatectomy, resulted in a significant decrease in the uptake of [3H]thymidine by the liver remnant, measured 4 to 6 hr later. These results suggest that during liver regeneration, early pregnancy factor is essential to the sequence of events that culminates in DNA synthesis and cell division. Recently we purified early pregnancy factor from human platelets and determined by mass spectrometry a precise molecular mass of 10,843 Da. Amino acid sequencing (approximately 72% of the molecule) demonstrated that early pregnancy factor is highly homologous with chaperonin 10, a stress-inducible mitochondrial protein, and that platelet-derived early pregnancy factor and rat chaperonin 10 share similar biochemical and immunological properties. In this study we show that early pregnancy factor, purified from regenerating rat liver and from serum taken 24 hr after hepatectomy, shares these properties. In addition, antibodies to early pregnancy factor, effective in passive immunization studies, recognize chaperonin 10, whereas chaperonin 10 antibodies bind to early pregnancy factor from regenerating liver and posthepatectomy serum. We propose that early pregnancy factor/chaperonin 10 is selectively released from proliferating cells and, in an autocrine or paracrine mode (or both) is involved in DNA synthesis.

Topical retinoic acid inhibits changes in Langerhans cell density during carcinogenesis.

Ultraviolet radiation (UVR), chemical carcinogens and contact sensitisers all reduce the density of Langerhans cells (LC) in murine epidermis; UVR also lowers the number of Thy-1 dendritic epidermal cells (Thy-1+ dEC). Topical application of all-trans retinoic acid (RA) renders these cells insensitive to UVR and the tumour promoter 12-0-tetradecanoylphorbol 13-acetate (TPA) but does not inhibit LC migration from the epidermis in response to a contact sensitiser. Additionally, when the diet of mice was supplemented with the retinoid temarotene, UVR was unable to reduce the number of LC or Thy-1+ dEC. Hence one of the anti-carcinogenic mechanisms of retinoids may be to protect LC from carcinogens.

Studies of chemotactic factor-induced polarity in human neutrophils. Lipid mobility, receptor distribution and the time-sequence of polarization.

Differences in membrane composition between the anterior and posterior poles of human blood neutrophils on exposure to chemoattractant were studied using a laser microscope, and the effects of attractant concentration and time on the ability of neutrophils to polarize were determined. The findings were as follows. (1) The fluorescein-labelled chemotactic hexapeptide fLeu-Norleu-Phe-Norleu-Tyr-Lys was asymmetrically distributed on polarized cells with the highest concentration at the anterior pole of the cell. (2) Differences in membrane lipid behaviour were studied by fluorescence recovery after photobleaching (FRAP) using the probe 5-N-(octadecanoyl)-aminofluorescein. Recovery curves suggested that the proportion of mobile lipid probe at the anterior pole of the cell was higher than at the posterior. However, no difference was found in the rate of recovery between the two poles. (3) Studies of the time-course of polarization were undertaken using neutrophils in suspension exposed to different isotropic concentrations of fMet-Leu-Phe (fMLP). At low concentrations (less than or equal to 10(-9) M), the cells polarized immediately on exposure to the attractant. At a high concentration (10(-7) M) they assumed multipolar morphologies and polarized very poorly, suggesting that ligand binding was too rapid for the cells to form a dominant pole. At the optimal concentration, 10(-8) M fMLP, the cells assumed irregular, ruffled, morphologies after 30s, but showed an increasing proportion of polarized forms over the next 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Replacement of excised segments of proximal ureters by tubularised bladder grafts vascularised by previously established omental pedicles.

This article reports the final study of experiments in which autologous bladder grafts have been used to replace excised segments of ureters in dogs. The technique described involves the use of bladder grafts on previously established omental pedicles as replacements for proximal ureters. Grafts were tubularised over silastic stents, then completely covered with secondary wrappings of omentum. Operated upper tracts were compared to control sides up to 12 months, then, at one year, intravenous urography was repeated at which time inspection was made of operated upper tracts (and contralateral controls) using an image intensifier prior to recording renal pelvic pressure responses to increasing perfusion rates and, finally, pathological examination. Only two of 14 upper tracts with pedicle grafts were failures radiologically and no upper tract was obstructed urodynamically. This approach is recommended for consideration as a treatment option in managing longitudinal defects in ureters in humans.

The epidemiologic basis for family medicine research.

Epidemiology, historically the study of communicable disease, has evolved to include the use of certain epidemiologic precepts in more diverse studies of human health and disease. Most especially, epidemiology offers a distinctly useful mechanism for research involving clinical, cultural, and economic factors impinging on the health status of individuals, families, and various populations.

Social supports and stress as predictors of illness.

The incidence and pattern of self-reported illness were studied over a six-month period in panels of 292 women and 188 men categorized by their experience of stressful life changes and their perceived supportive relationships. Men and women with more than average stressful changes had a risk of illness 1.6 and 1.8 times that reported by those with below-average changes. Analysis of the interaction of stressful changes with social supports showed that women with a combination of high changes and low supports experienced 2.5 times the rate of illness as those with low changes and high supports. This interaction was not found for men. A monthly rating of perceived life stress was correlated with subsequently recalled life changes for both men and women. The findings for women are consistent with the hypothesis that the interaction of stress with degree of social support is an important predictor of illness experience.

Beyond biology: a curriculum in methods of analysis for clinicians.

Over the past five years a three-month interdisciplinary seminar curriculum for postgraduate physicians entering a Robert Wood Johnson Clinical Scholars Program has been developed. While emphasizing an epidemiologic paradigm of analysis, the format facilitates collegial learning among fellows and faculty from diverse fields in the biometric, social, and management sciences. Questions for discussion are drawn largely from the on-going clinical concerns of the participants. This approach has provided a useful basis for both problem assessment and the development of independent research. Educational strategies and devices from this effort appear to be applicable to other contexts and illustrate ways of exploring beyond the predominantly biological models of contemporary medical education.

A nomograph method for assessing body weight.

The ratio of weight/height emerges from varied epidemiological studies as the most generally useful index of relative body mass in adults. The authors present a nomograph to facilitate use of this relationship in clinical situations. While showing the range of weight given as desirable in life insurance studies, the scale expresses relative weight as a continuous variable. This method encourages use of clinical judgment in interpreting "overweight" and "underweight" and in accounting for muscular and skeletal contributions to measured mass.