Acute Inflammatory Syndrome Induced by Mycophenolate Mofetil in a Patient Following Kidney Transplantation

Mycophenolate mofetil (MMF) is increasingly used to prevent acute and chronic rejection following kidney transplantation and in autoimmune diseases. Here, we report on a patient after kidney transplantation, who developed an acute inflammatory syndrome characterized by fever and oligoarthritis within 1 week after increasing the MMF dosage. MMF was discontinued resulting in a complete resolution of the syndrome within 48 h. We demonstrated in vitro that the patient's phorbol myristate acetate (PMA-) and formyl Met-Leu-Phe (fMLP-) stimulated polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MMF. This report demonstrates that MMF can also induce acute inflammatory syndrome in patients following kidney transplantation and that this syndrome might be due to a paradox, pro-inflammatory reaction of PMNs.     

PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes.

5-Amino-4-imidazolecarboxamide (AICA) riboside, the nucleoside corresponding to AICA ribotide (AICAR or ZMP), an intermediate of the de novo pathway of purine biosynthesis, was found to exert a dose-dependent inhibition on gluconeogenesis in isolated rat hepatocytes. Production of glucose from lactate-pyruvate mixtures was half-maximally inhibited by approximately 100 microM and completely suppressed by 500 microM AICA riboside. AICA riboside also inhibited the production of glucose from all other gluconeogenic precursors investigated, i.e., fructose, dihydroxyacetone, and L-proline. Measurements of intermediates of the glycolytic-gluconeogenic pathway showed that AICA riboside provoked elevations of triose phosphates and fructose-1,6-bisphosphate and decreases in fructose-6-phosphate and glucose-6-phosphate. The effects of AICA riboside persisted when the cells were washed 10 min after its addition but were suppressed by 5-iodotubercidin, an inhibitor of adenosine kinase. AICA riboside provoked a dose-dependent buildup of normally undetectable Z nucleotides. After 20 min of incubation with 500 microM AICA riboside, ZMP, ZTP, and ZDP reached 3, 0.3, and 0.1 mumol/g cells, respectively. Concentrations of ATP were not significantly modified by addition of up to 500 microM AICA riboside when the cells were incubated with lactate-pyruvate but decreased with fructose or dihydroxyacetone. The activity of rat liver fructose-1,6-bisphosphatase was inhibited by ZMP with an apparent Ki of 370 microM. It is concluded that AICA riboside exerts a suppressive effect on gluconeogenesis because it provokes an accumulation of ZMP, which inhibits fructose-1,6-bisphosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flow cytometric characterization of rat thymus cells in a radiation-dominated model of combined injury

Thymuses of rats that had been: a) gamma-irradiated [500 cGy whole-body radiation (R)], or b) thermally injured [20% BSA dorsal, scald burn (TI)], or c) combined injured [irradiation followed by burn (CI)] were studied for involution and recovery processes after sublethal treatments. The expression of surface antigens on thymic cells before and after injuries was evaluated using the monoclonal antibodies (mcAB) MRC OX4, MRC OX7, MRC OX8, W3/13 HLK, and W3/25 and flow cytometric analysis. Thymic cellularity decreased to less than 1% of normal (N), age-matched rats by 4 days after R or CI. Recovery reached 60% to 70% of N by 28 days post treatments. TI caused a biphasic thymic recovery pattern with nadirs of 40% of N on days 7 and 21. Recovery at day 28 was similar to that after R and CI. Expression of OX7, OX8, W3/13, and W3/25 antigens all reached nadirs of 40% of N by day 4 after R and CI. Recovery of antigen expression, except for W3/25, was near completion by day 7 after R and CI. Changes in antigen expression after TI were less pronounced for all mcAB tested. Decreases in labeling of thymocytes with the helper T-cell marker, W3/25, observed after TI, could not be correlated with elevated expressions of the suppressor/cytotoxic T-lymphocyte antigen, OX8. Variations in relative labeling of nonlymphoid thymic cells with OX4 (Ia-antigen) reflected the disappearance and recovery of radiosensitive lymphoid thymocytes. The similarity of results after R and CI demonstrate that the model of CI is 'radiation-dominated.' The addition of burn injury to radiation trauma had no synergistically damaging effect on the parameters studied.     

Asbestos-related benign disease and cancer: symptoms and treatment

Long lasting occupational exposure to asbestos dust may cause skin corns, benign pleural effusion, hyaline plaques of the parietal pleura, diffuse thickening of the pulmonary pleura, and asbestosis, i.e. diffuse interstitial pulmonary fibrosis. Malignant disorders include lung cancer and mesothelioma of the pleura, peritoneum and pericardium. In general, many years elapse from first exposure to the appearance of symptoms. Almost all these diseases are the result of dusty working conditions more than 20 years ago. In spite of the fact that the general public is invariably exposed to small amounts of the material, asbestos is not a public health problem. Even living in a building containing sprayed asbestos is calculated to produce a lifetime risk of death which is negligible. There is no evidence to indicate that ingested asbestos fibres represent a major health problem.     

Effects of sex on differences in awareness, treatment, and control of high blood pressure

Our purpose was to explain the reasons for sex differentials in the awareness, treatment, and control of hypertension by identifying major social and behavioral predictors of these three sequential stages of high blood pressure control. We analyzed data on all 1,433 hypertensive subjects from the First Connecticut Blood Pressure Survey. Hypertensive women were more likely than hypertensive men to be aware of their high blood pressure (odds ratio = 1.40; confidence interval = 1.10-1.79) and to have controlled levels of blood pressure (odds ratio = 1.62; confidence interval = 1.08-2.44). Men and women who were aware of their hypertension were equally likely to be treated. Sex still explained differences in awareness and control of hypertension after adjusting for other significant variables. We conclude that sex is an important predictive covariate for adjustment in explaining differences in awareness and control of high blood pressure. Health care professionals should be aware of the differential role of sex when informing and treating hypertensive patients.     

Precision of three-dimensional CT-assisted model production in the maxillofacial area

Individual skull model fabrication was introduced into preoperative diagnostics in maxillofacial surgery in the mid-1980s. The aim of the present study was to collect information on the reproducibility of a skull model milled from hardened polyurethane foam. This model was based on the CT data of a real skull. Twenty comparative studies were carried out on both the model and the original skull, the model showing an average inaccuracy of 1.6 mm. The deviations ranged between 0.0 and 3.6 mm; the general trend favouring enlargements. The total deviation of the model as compared to the original skull was 1.8%. A convincing aspect of the model, which cannot be obtained by any other method, is its plasticity and the possibility of 3 D orientation on a lifesize model. This new method is already used in preoperative planning of corrections of post-traumatic defects and craniofacial deformities as well as in tumour surgery. Correspondence to: P. Solar     

Antagonism of airway reactivity induced by ovalbumin antigen in guinea pigs by 5-amino-4-imidazolecarboxamide riboside

The effect of 5-amino-4-imidazolecarboxamide riboside (AICA riboside), a modulator of purine metabolism, was studied on antigen-induced bronchospasm in ovalbumin (OA)-sensitized guinea pigs. In separate experiments, sodium cromoglycate (SCG) and terbutaline were used to compare their effectiveness with that of AICA riboside (wt/vol). AICA riboside and SCG were administered as an aerosol daily for a minimum of 2 weeks before OA aerosol challenge. Terbutaline, as an aerosol, was administered once 5 minutes before OA challenge. Airway reactivity was determined through the use of a whole-body plethysmography by monitoring specific airway resistance (SRaw). OA aerosol challenge of 0.05%, 0.1%, and 0.25% (wt/vol), administered for a period of 1 minute, increased SRaw. Each of the three agents attenuated the effect of OA on SRaw, although terbutaline demonstrated more consistency and potency as compared to either AICA riboside or SCG. However, at moderate degrees of OA challenge, AICA riboside appeared to be as effective as either agent. Although the mechanism of action of AICA riboside remains uncertain, it may have therapeutic benefit in the treatment of asthma or allergic diseases.     

Acetylsalicylic acid after iliac-femoro-popliteal interventions?

To determine whether acetyl salicylic acid (ASA) in a daily dose of 1500 mg versus untreated controls is effective in patients with peripheral arterial disease a prospective randomized but not placebo-controlled one single centre trial was undertaken. Patients were assigned to one of two groups by means of multi-dimensional contingency tables whereas the risk factors age, sex, height, body weight, diabetic metabolic state, hypertension, history of myocardial infarction, smoking habits and preoperative clinical status according to the Fontaine classification where found in the state of balance. 298 patients with arterial occlusions in the iliaco-femoro-popliteal level were recruited during 1971-1974, the primary end points were probability of patency and probability of survival. In regard as well as to the probability of patency (p less than 0.56 Breslow, p less than 0.66 Mantel) as to the probability of survival (p less than 0.10 Breslow, p less than 0.70 Mantel) no statistical significant difference was detected. In conclusion ASA, in the doses administered here, was unable to improve patency or prolong patient survival, an outcome, which is at variance with results obtained by others.