Software for the quantitative evaluation of in vitro monoclonal antibody production from ELISA data

Software has been developed which permits the quantitation of monoclonal antibodies secreted by B cell hybridomas. This program does not require the user to enter a large number of complex parameters and can be easily used without any previous computer experience. It fits all the experimental and standard curves by determining overlapping linear domains using the linear least-squares method. The program is based on logarithmic interpolations for determining Ig concentrations comparing experimental samples to Ig concentrations in standards. It provides a complete print-out of the data with editing options and is written in BASIC EDEX 4.0 Commodore computer language. It permits the accurate quantification of minute amounts of monoclonal antibodies and can be used to detect the inhibitory or enhancing effects of lymphokines or cytokines on Ig secretion by hybridoma B cells.     

Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice

The cytokine thymic stromal lymphopoietin (TSLP) has been linked to human allergic inflammatory diseases. We show here that TSLP expression was increased in the lungs of mice with antigen-induced asthma, whereas TSLP receptor-deficient mice had considerably attenuated disease. Lung-specific expression of a Tslp transgene induced airway inflammation and hyperreactivity characterized by T helper type 2 cytokines and increased immunoglobulin E. The lungs of Tslp-transgenic mice showed massive infiltration of leukocytes, goblet cell hyperplasia and subepithelial fibrosis. TSLP was capable of activating bone marrow-derived dendritic cells to upregulate costimulatory molecules and produce the T helper type 2 cell-attracting chemokine CCL17. These findings suggest that TSLP is an important factor necessary and sufficient for the initiation of allergic airway inflammation.     

Over-diagnosed prostate cancer in solid organ recipients: lessons from the last 3 decades

Introduction

Prostate cancer (PC) is the most common neoplasia in men. With aging of solid organ transplant recipients (SOTR), its incidence is likely to increase. The aim of this study was to analyze PC screening results retrospectively in renal transplant recipients (RTR), hepatic transplant recipients (HTR) and cardiac transplant recipients (CTR).

Patients and methods

A retrospective monocentric study of PC diagnosed in renal, hepatic or cardiac transplanted patients since 1989 was performed. All the patients were followed annually by digital rectal examination and prostate serum antigen (PSA) dosage.

Results

57 PC were diagnosed in 1565 SOTR male patients (3.6%): 35 RTR, 15 HTR, and 7 CTR. Standard incidence ratio (SIR) was 41.9. Mean age at the time of diagnosis was 64.5 (60.5–69.2). Mean time between transplantation and PC diagnosis was 95.7 (39.0–139.5) months. Median PSA rate was 7.0 (6.2–13) ng/mL. Clinical stages were T1, T2, and T3, respectively, for 29, 22 and 6 patients. Diagnosis was done by screening in 52 patients, after prostatitis in 1 and bone pain in another. Three PC were discovered on prostate chips after transurethral resection. Two patients were treated by active surveillance. 39 (68%) patients (25 RTR, 11 HTR and 3 CTR) were treated by radical prostatectomy. Histological results were 30 pT2 and 9 pT3 tumors, with 7 positive surgical margins. Gleason score was 5, 6, 7, 8 and 9 in, respectively, in 2, 24, 11, 1 and 1 patients. One patient with positive pelvic nodes was treated with hormonal therapy (HT). One had a biochemical relapse at 10 months and underwent salvage radiotherapy. Median follow-up was 85.2 months (46.1–115.0). 23 (40.4%) patients died. Two (3.6%) RTR and 1 (1.8%) CTR died from their PC. Standard incidence ratio were, respectively, 42.4, 48.2 and 39 in RTR, HTR and CTR.

Conclusion

Systematic screening in male SOTR after 50 years old could not be recommended. In the last 3 decades, we diagnosed too many low-risk prostate cancers strongly increasing the SIR but failing to decrease prostate cancer related mortality. SOTR should undergo individual screening with prior MRI when PSA rates are high. Management should not be different from that of the general population.

     

Attenuation of fear-like response by escitalopram treatment after electrical stimulation of the midbrain dorsolateral periaqueductal gray

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) has frequently been shown to induce escape and freezing/decreased locomotion responses which mimic panic- and fear-like behaviour. In the present study we tested whether such spontaneous fear-like behaviour could be observed in an open-field test 12 h after dlPAG stimulation. Further, we tested whether this fear-like behaviour could be attenuated by acute or chronic administration of buspirone and escitalopram. Our data demonstrate for the first time that animals showed fear-like behaviour 12 h after dlPAG stimulation, which may possibly reflect panic disorder with anticipatory anxiety/agoraphobic symptoms. Acute and chronic escitalopram, but not buspirone, treatment attenuated the fear-related behaviour. Besides, our data also showed that the stimulation intensities to evoke an escape reaction, a panicogenic response, were significantly higher after chronic buspirone and escitalopram treatment. These results suggest that the fear-like response, which was observed 12 h after dlPAG stimulation, could be considered as a relevant animal model for panic disorder with anticipatory anxiety/agoraphobic symptoms.     

Estimated Prevalence and Care Pathway of Feeding and Eating Disorders in a French Pediatric Population

Feeding and Eating Disorders (FED) are mostly described in infants and adolescents but are less well-known in children. Information on the prevalence of FED in the general pediatric population is still limited. The aim of this study was to estimate the prevalence and the care pathway of FED in a population aged 0–18 years old, using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 classification. Two physicians interviewed 401 families using a questionnaire including demographics, BMI, dietary behavior data, and age-appropriate screening tools. Qualitative and quantitative variables were compared using the Chi² test and Student’s t-test, respectively. After a headcount adjustment based on the French population by age group, the estimated prevalence rate was 3% [95%CI (1.7–5.1)] for Avoidant and Restrictive Food Intake Disorder (ARFID), and 9.7% [95%CI (7.2–13.0)] for Unspecified FED (UFED), which included other restrictive and compulsive FED. The median age for ARFID was 4.8 years (0.8–9 years), and 7.5 years (0.6–17 years) for UFED. The interviews did not identify cases of anorexia, bulimia, binge eating disorder, other specified FED, pica or rumination. Only 15.2% of children with an FED were receiving medical care. The development of validated pediatric screening tools, as well as the training of health professionals in children FED is necessary.     

Synthesis and biological studies of a new ginkgolide C derivative: Evidence that the cardioprotective effect of ginkgolides is unrelated to PAF inhibition

Ginkgolides have been demonstrated to protect the myocardium in experimental ischemia‐reperfusion, but the extent to which this property is not related to platelet‐activating factor (PAF) inhibition remains debated. This study was undertaken to determine whether a ginkgolide devoid of any anti‐PAF activity could retain a cardioprotective activity. For this purpose, a new ginkgolide C ( 3 ) analogue, 7‐O‐(4‐methylphenyl) ginkgolide C ( 4 ), was obtained from 3 with retention of configuration, using, in the key step, a copper‐catalyzed arylation with tris‐(4‐methylphenyl) bismuth diacetate. No PAF inhibition on rabbit platelets in vitro was found for 4 up to 1.2.10^–4 M. However, 4 was found a significantly better preserving agent than 3 or ginkgolide B, a potent PAF inhibitor (all drugs at 0.35 μM), on hemodynamic and metabolic (i.e., myocardial ATP contents and enzymatic activities) indices measured in rat isolated hearts undergoing ischemia‐reperfusion. The data provide additional support to a PAF‐unrelated pharmacological activity for ginkgolides. Because the water solubility of 4 , estimated by high‐performance liquid chromatography analysis, was significantly lower than that of the parent molecule 3 , a likely mechanism for the protective action of 4 involves its increased affinity for the myocardium, as compared to the relatively more hydrophilic 3 . Drug Dev. Res. 54:191–201, 2001. © 2002 Wiley‐Liss, Inc.     

Management of major blunt renal lacerations: is a nonoperative approach indicated?

OBJECTIVES: The aim of the study was to determine whether a nonoperative approach is able to reduce renal parenchymal loss after renal trauma. METHODS: Sixty-four consecutive patients with major blunt renal lacerations were treated from 1988 to 1999. Initial management was conservative. In group 1 (35 patients) delayed hemorrhage, persistent urinoma or hemodynamic instability were dealt with by open surgery. In group 2 (29 patients), most complications were dealt with using endoscopic procedures; open surgery was reserved exclusively for major complications. RESULTS: In group 1, 7 patients were not operated and 28 patients were managed surgically. Twenty (57%) patients underwent total (8) or partial (12) nephrectomy. In 8 patients the surgical intervention was open drainage of perinephric collection (6) and/or renorrhaphies (2). Four patients in this group developed urinary fistulae treated successfully with ureteral stents. Length of hospital stay was 9.6 days (3-25 days). In group 2, persistent hemodynamic instability led to nephrectomy in 1 case. The remaining 28 patients were managed conservatively, with endoscopic ureteric stenting in 5 cases. A persistent urinary extravasation with hyperthermia led to open drainage of perinephric urinoma (5) and renorrhaphy (2). No delayed nephrectomy was necessary. Average hospital stay was 12 days (5-21 days). Only 1 patient in this group developed hypertension. CONCLUSION: For most patients and with close follow-up available, conservative treatment represents a real alternative to open surgery in major blunt renal lacerations. In our experience, open surgery usually results in loss of renal parenchyma.