Strain differences in mouse cellular responses to Mycobacterium lepraemurium and BCG subcutaneous infections. I. Analysis of cell surface phenotype in local granulomas.

C57BL/6, BALB/c and CBA mice were subcutaneously infected with either Mycobacterium lepraemurium (MLM) or BCG, and studied for bacillary growth, granuloma size of infected footpads and draining lymph nodes (DLN), and DLN cell surface phenotype. Whereas, BCG-infected mice controlled the infection and developed early and large granulomas, MLM-infected mice exhibited major strain variations in their resistance to the infection, as well as in the granuloma size and kinetics. C57BL/6 mice, highly resistant, displayed early and regressive granulomas; BALB/c mice showed lower resistance and early granulomas that grew continuously; CBA mice, highly susceptible, developed late, soft, phagocyte-rich granulomas. Important strain differences in lymph node lymphocyte subset distribution could be observed prior to any infection: C57BL/6 mice displayed higher B cell percentages than both of the other strains and BALB/c mice showed the highest CD4/CD8 ratios, followed by CBA and C57BL/6 mice. BCG and MLM infections both induced similar changes of these parameters in all three strains: that is a decrease of the B cell percentage and a decrease of the CD4/CD8 ratio, and the strain differences observed in uninfected mice persisted. On the other hand, DLN cells stimulated by the infecting bacillus and interleukin 2 also displayed an increase of the CD8 T cell percentage as compared with normal lymph node cells, but this phenomenon was much less pronounced in BALB/c mice, whether infected by MLM or BCG, and in MLM-infected CBA mice, than in BCG- or MLM-infected C57BL/6 (B6) mice. Thus the ability of C57BL/6 mice to generate an early and persistent CD8 T cell response to mycobacteria may contribute to their resistance to MLM.     

Electroencephalogram and cardiovascular responses to noise during daytime sleep in shiftworkers

Summary Intermittent noise occurring during sleep has been found to induce heart rate, peripheral vasomotor and electroencephalogram (EEG) changes. This study analysed these responses during the daytime and night-time sleep of shiftworkers doing a three shift system, to determine the influence of the inversion of the sleep-wake cycle on the sensitivity to noise. A group of 14 shiftworkers [aged 37 (SD 5) years] underwent an habituation daytime sleep, two experimental daytime sleeps and a night-time sleep. Traffic noises were presented during sleep [truck, 71 dB(A); motorbike, 67 dB(A); and car, 64 dB(A)] at a rate of nine each hour. The EEG measurements of sleep, electrocardiogram and finger pulse amplitude were recorded continuously. The results were expressed by computing the percentage of observed cardiac response (%HRR) and vasoconstrictive response (%FPR), magnitude of heart rate variation (heart rate response; HRR), percentage of reduction of the digital blood flow (finger pulse response, FPR), cardiac cost (CC = % HRR x HRR) and vasomotor cost (VC = % FPR x FPR). The results showed that, compared to night-time sleep, there was change in the structure of daytime sleep, that is an increase in slow wave sleep (SWS), especially stage 4 sleep decrease of stage 2 and rapid eye movement (REM) sleep latencies, and an earlier SWS and REM sleep barycentric point. During daytime sleep the % FPR was significantly smaller in SWS than in stage 2 or REM sleep. Large differences were observed in % HRR, HRR and CC between daytime sleep stages (SWS less than stage 2 less than REM sleep). These differences were not observed during night-time sleep. Moreover, compared to night-time sleep, CC was increased during daytime REM sleep and decreased during daytime SWS. The inversion of the sleep-wake cycle in shiftworkers, did not influence the overall cardiovascular reactivity to noise. This was explained by a compensatory effect due to an increase in this reactivity during daytime REM sleep and its decrease in daytime SWS. The second reason is due to an increase in the percentage of stage 4 sleep during daytime sleep (less disturbed by noise than other sleep stages). This increased percentage of stage 4 sleep was probably a consequence of the partial sleep deprivation occurring after a week working on nightshift.     

Cytotoxic activity of human lymphocytes against differentiated intestinal tumour cell lines.

The natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activity of human peripheral blood lymphocytes (PBL) against various human tumour cell lines from intestinal origin (WIDR, HT29, Caco-2) has been investigated. The differentiated Caco-2 cells were then used as a model to investigate the cytotoxic activity against enterocyte-like target cells. Caco-2 were seeded on polycarbonate filters and maintained in culture for at least 15 days to allow the differentiation and formation of tight junctions. The integrity of tight junctions was assayed by measuring [3H]mannitol flux from apical to basolateral compartment. Cytotoxic analysis showed that both differentiated and undifferentiated Caco-2 cells were similarly susceptible to NK and LAK activity. The capacity of cytotoxic lymphocytes to kill enterocyte-like cells with intact junctional complex may suggest a direct role of cytotoxic lymphocytes in causing intestinal lesions under inflammatory conditions.     

Protection from insulin-dependent diabetes mellitus is linked to a peptide transporter gene

HLA class II association with insulin-dependent diabetes mellitus (IDDM) is well established but is still difficult to map to a particular locus. Polymorphism of the genes coding for transporter associated with antigen processing (TAP1 and TAP2), and located in the HLA class II region, was studied in 167 IDDM patients (116 adult-onset and 51 childhood-onset patients) and 98 normal controls using oligotyping after genomic amplification. A dominant protective effect was observed for theTAP2*0201 allele [relative risk (RR)=0.3, corrected probability (pc) < 0.001]. Conversely, susceptibility to IDDM was associated with apparent homozygosity for the TAP2*0101 allele (RR=3.4, pc < 0.001). Protection was independent from but additive to the protection conferred by the DRB1*02 DQB1*0602 haplotype (RR=0.06, pc<0.05), and antagonistic to the DRB1*03 DQB1*0201 and DRB1*04 DQB 1*0302 haplotypes predisposing effect (RR=1.1, not significant), arguing in favor of an absence of linkage disequilibrium between TAP2 and HLA class II genes. This was assessed by x² analysis. TAP1 allelic distribution was not different among diabetics and controls. A significant association was observed between the presence of TAP2*0101 and that of islet cell antibodies (p < 0.05). These data suggest that the TAP2 gene, which encodes protein required for delivery of antigen peptides to class I molecules in the endoplasmic reticulum, could modulate the autoimmune response leading to β cell destruction. From a practical point of view, they make the combined screening of HLA class II and TAP2 loci a highly valuable tool in IDDM prediction.     

Leiomyoma arising from the right seminal duct/seminal vesicle—Report of a rare case and review of the literature

We present a case of a patient with a large, symptomatic abdominal tumour, which finally could be classified as a leiomyoma arising from the right seminal duct/seminal vesicle. In computed tomography (CT) scan, it appeared as a 7.5 × 6.5 cm solid, supravesical mass. A cystoscopy as well as bilateral retrograde studies was normal, a transrectal ultrasound‐guided biopsy and an ultrasound‐guided transabdominal biopsy of the mass were inconclusive. Subsequently, we performed a tumour extirpation through a lower midline laparotomy. Histological examination showed a leiomyoma arising from the right seminal duct or seminal vesicle. In this article, we discuss clinical presentation, findings on imaging and management of this rare benign tumour and review the relevant literature where only 13 similar cases could be identified.     

Effect of highly purified capsaicin on articular cartilage and rotator cuff tendon healing: An in vivo rabbit study

Highly purified capsaicin has emerged as a promising injectable compound capable of providing sustained pain relief following a single localized treatment during orthopedic surgical procedures. To further assess its reliability for clinical use, the potential effect of highly purified capsaicin on articular cartilage metabolism as well as tendon structure and function warrants clarification. In the current study, rabbits received unilateral supraspinatus transection and repair with a single 1 ml injection of capsaicin (R + C), PEG‐only placebo (R + P), or saline (R + S) into the glenohumeral joint (GHJ). An additional group received 1 ml capsaicin onto an intact rotator cuff (I + C). At 18 weeks post‐op, cartilage proteoglycan (PG) synthesis and content as well as cell viability were similar (p > 0.05) across treatment groups. Biomechanical testing revealed no differences (p > 0.05) among tendon repair treatment groups. Similarly, histologic features of both cartilage and repaired tendons showed minimal differences across groups. Hence, in this rabbit model, a single injection of highly purified capsaicin into the GHJ does not induce a deleterious response with regard to cartilage matrix metabolism and cell viability, or rotator cuff healing. These data provide further evidence supporting the use of injectable, highly purified capsaicin as a safe alternative for management of postoperative pain following GHJ surgery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1854–1860, 2015.