Prognostic values of galectin-3 and the macrophage migration inhibitory factor (MIF) in human colorectal cancers.

This study aims to investigate whether the immunohistochemical levels of expression of galectin-3 and the macrophage migration inhibitory factor (MIF) are associated with prognostic values in human colorectal tumors. This was performed on 99 specimens including 69 colorectal tumors (17 Dukes A, 19 Dukes B, 15 Dukes C and 18 metastatic tumors that we labeled as D), 10 hepatic metastases from colorectal cancers and 20 normal specimens (biopsies). The immunohistochemical levels of expression of MIF and galectin-3 were quantified on routine histological slides by means of computer-assisted microscopy. Separate analyses were performed on epithelial and connective tissue. The levels of expression of both MIF and galectin-3 were very significantly higher in epithelial tumor tissue when compared with normal epithelial specimens. A positive and significant correlation between MIF and galectin-3 expression was evidenced in connective tumor tissue, and in particular in the cases associated with short survival periods (less than 5 years). In the case of the Dukes A or B tumors, we established two new prognostic groups (labeled I and II) on the basis of the levels of galectin-3 expression measured in the tumor epithelium. In the case of the Dukes C or D tumors, we established two other prognostic groups (labeled III and IV) on the basis of the levels of MIF expression measured in the connective tissue. Kaplan-Meyer analyses confirmed the additional prognostic values (as compared with conventional clinical staging) given by this new classification (groups I to IV). They show that the Dukes A or B tumors characterized by low levels of galectin-3 expression in the tumor epithelium are associated with significantly better prognoses than those characterized by high levels. In addition, the Dukes C or D tumors characterized by high levels of MIF expression in the connective tumor tissue are associated with significantly better prognoses than those characterized by low levels. In conclusions, MIF and galectin-3 expression levels in colorectal tumors are related to their levels of biological aggressiveness. These markers could be used to identify patients at risk, for whom more aggressive adjuvant therapy seems to be indicated.     

Na-K-ATPase activity along the rabbit, rat, and mouse nephron.

Na-K-ATPase activity along the rabbit, rat, and mouse nephron was determined with a micromethod that measures directly labeled phosphate released by the hydrolysis of [gamma-32P]ATP. Na-K-ATPase activity was highest in the rat, intermediate in the mouse, and lowest in the rabbit nephron. With the exception of rabbit cortical thick ascending limb, the enzyme profile was similar in the three species: Na-K-ATPase activity per millimeter tubule length was highest in the distal convoluted tubule and thick ascending limb of Henle's loop, intermediate in the proximal convoluted tubule, and lowest in the pars recta and collecting tubule. The enzyme was present in the thin limbs of Henle's loop, but its activity was very low and measurements were close to the sensitivity limit of the method. Both the absolute activity and the fraction of the total enzyme represented by Na-K-ATPase were severalfold higher than in kidney homogenates. Finally, the Na-K-ATPase activity measured in certain segments of the rat and rabbit nephron in this study seems sufficient to account in theory for the active component of the net sodium transport found in the corresponding region of the nephron with either in vivo or in vitro single tubule microperfusion techniques.     

Callus characteristics following intramedullary nailing with stainless steel or epoxy-carbon nails

Summary Biological mechanical improvements of osteosynthesis make intramedullary nailing an attractive alternative to bone plate fixation. However, little is known about stress shielding induced by intramedullary implantation of a nail. To evaluate the effect of the nail rigidity on bone healing, mid-metatarsal osteotomies were performed in sheep and fixed with either stainless steel or epoxy-carbon composite V-shaped nails. Mechanical and histomorphometric features of the callus were evaluated 4 months postoperatively. No statistical difference between the two groups were demonstrated for either mechanical or microstructural characteristics. The presence of a fibrous membrane filling the bone/nail interface and allowing sliding micromotions of the implants and the much smaller effect of nail rigidity, as compared to bone plate after implantation, were assumed to be the main reason for this uniformity. At this stage of healing, bone characteristics were more related to a non-specific (vascular) bone remodeling phenomenon than to a stress-shielding effect.

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Zusammenfassung Biologische und mechanische Fortschritte auf dem Gebiet der Osteosynthese lassen die Marknagelung zu einer attraktiven Alternative zur Plattenosteosynthese wurden. Es ist jedoch wenig bekannt über die Abschirmung des Knochens gegenüber der mechanischen Beanspruchung durch die Implantation eines Marknagels. Um den Einfluß der Steifigkeit des Nagels auf die Knochenheilung zu überprüfen, wurden beim Schaf Metatarsalosteotomien in Schaftmitte durchgeführt und entweder mit einem rostfreien Stahlnagel oder mit einem Epoxy-Kohlenstoff-Nagel mit V-Profil stabilisiert. Mechanische und histomorphometrische Eigenschaften des Knochens wurden 4 Monate postoperativ ermittelt. Für beide Gruppen wurden bei den mechanischen und mikrostrukturellen Befunden keine statistisch signifikanten Unterschiede gefunden. Für these Überein-stimmung wurde eine fibröse Membran in der Kontaktfläche zwischen dem Marknagel und dem umgebenden Knochengewebe, die feine Bewegungen des Implantates erlaubt, verantwortlich gemacht. Ein wesentlich geringerer Effekt wurde der Steifigkeit des Nagels im Vergleich zu einer Plattenosteosynthese beigemessen. In diesem Heilungsstadium waren die Befunde am Knochen mehr mit einer unspezifischen (vaskulären) Umbaureaktion als mit einer Abschirmung gegenüber mechanischer Beanspruchung in Zusammenhang zu bringen.

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Abbreviations M bending moment - D bone outside diameter - y distance nail edge-global center of inertia - I _xxB bone moment of inertia - I _xxN nail moment of inertia - _B maximal bending stress in bone - _N maximal bending stress in the nail Supported in part by grant no. 79-0162 from DGRST     

Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.     

The origin of human B and T cells from multipotent stem cells: a study of the Tn syndrome

The Tn (or polyagglutinability) syndrome corresponds to a human nonmalignant acquired condition which results from a somatic mutation occurring at the level of bone marrow stem cells. This model offers therefore a unique opportunity to study the contribution of multipotential stem cells to the maintenance of cells from the lymphoid lineage. We found that the Tn mutation is expressed by both myeloid and lymphoid mature blood cells. Whereas a large proportion of surface IgM-bearing B cells carry the Tn mutation, only a small percentage of T cells and IgA- or IgG-bearing B cells are defective, showing that under physiological conditions the penetration of stem cells into the various myeloid and lymphoid compartments is variable.     

Follow-up of soluble interleukin-2 receptor levels after thymectomy in patients with myasthenia gravis.

Soluble interleukin-2 receptor (sIL-2R) levels were followed up after thymectomy by a quantitative immunoradiometric assay in 59 patients with myasthenia gravis (MG). Increased levels of sIL-2R were found in 30.5% of the patients before thymectomy. Serum levels were significantly higher in severely affected patients. Sequential sampling after thymectomy indicated a significant and progressive decline of sIL-2R levels within 2 years after surgery, which was well associated with clinical improvement or remission. The sIL-2R purified from sera of patients with MG had a molecular mass of 45 kDa as the normal sIL-2R. The decline after thymectomy of sIL-2R titers suggests a possible role of the thymus in the occurrence of sIL-2R in the periphery. Soluble IL-2R levels may represent a marker of disease severity in MG, which might be useful in the follow-up of individual patients.     

HIV-1感染者外周血单个核细胞缺损病毒基因的研究

目的:研究HIV-1感染者缺损HIV-1 DNA的特性.方法:用长片段PCR法(LD-PCR)研究分析HIV-1感染者外周血单个核细胞(peripheral blood mononuclear, PBMCs)和体外培养感染淋巴细胞中HIV-1基因特征,使用位于HIV-1 DNA链两端的LTR(U5)、LTR(R)为引物,插入有全长HIV-1基因片段的大肠杆菌质粒PNL4-3等为标准对照,并对部分标本克隆测序.结果:经扩增9.1 kb是LD-PCR的主要产物,但在10例HIV-1感染者中有9例PBMCs检测出大小不一、范围较广的缺失HIV-1基因片段,经用基因探针杂交,发现近HIV-1基因中心部位缺失频率增加,缺失结合点常存在3～4个核苷酸短片段直接重复,体外培养中HIV-1基因缺损量减少,完整和缺失基因的存在与培养中病毒分离的时间密切相关.结论:HIV-1感染者PBMCs中存在大量HIV-1基因重组和缺损片段.     

Role of nitric oxide in the contractile response to 5-hydroxytryptamine of the basilar artery from Wistar Kyoto and stroke-prone rats

1. Isolated basilar arteries from spontaneously hypertensive stroke-prone rats (SHRSP) are more sensitive to the contractile effect of 5-hydroxytryptamine (5-HT) than those from normotensive Wistar Kyoto rats (WKY). This has been attributed to a different proportion of 5-HT receptor subtypes mediating these responses. In the present study we have examined if differences in nitric oxide release could also contribute to this difference in sensitivity to 5-HT.
2. At rest, the normalized internal diameter was significantly smaller in SHRSP (297.4±3.5 μm, n=88) than in WKY (375.1±4.0 μm, n=62, P<0.01) arteries. The contractile response to 100 mM KCl was higher in WKY (3.57±0.15 mN mm⁻¹, n=22) than in SHRSP arteries (2.32±0.20 mN mm⁻¹, n=28, P<0.01).
3. When added on the plateau of contraction to 5-HT (1 μM), acetylcholine (ACh, 3 μM) evoked significant relaxation in all preparations from WKY (n=20), but only in 15 out of 26 preparations from SHRSP. The mean relaxations were 55.4±5.2% in WKY and 20.6±4.6% in SHRSP (as % of the contractile tone evoked by 5-HT; P<0.01).
4. The NO synthase inhibitor N^ω-nitro-L-arginine (L-NOARG, 0.1 mM) produced a similar increase in tone in both WKY and SHRSP. This tone was equal (in % of the contractile response to 100 mM KCl) to 70.8±4.4% in WKY (n=20) and 67.6±5.9% in SHRSP (n=26) and was reversed by L-arginine (1 mM) and by 1,4-dihydropyridine calcium channel blockers (10 nM nisoldipine, 10 nM lacidipine, 100 nM nifedipine). The L-NOARG-induced tone was absent when the arteries were bathed in phosphate-free Krebs (pH 7.4).
5. EC₅₀ values of 5-HT were about four fold smaller in SHRSP than in WKY arteries (P<0.01). The maximal response to 5-HT (E_max) was higher than 100 mM KCl-contraction in SHRSP but not in WKY arteries. Removal of endothelium produced a shift to the left of the 5-HT curve in WKY, but not in SHRSP arteries.
6. When evoked in phosphate-free Krebs, the contractile responses to 5-HT showed tachyphylaxis, but the responses were reproducible by adding the agonist at 30 min intervals. In such conditions, EC₅₀ values of 5-HT were about two fold smaller in SHRSP than in WKY arteries (P<0.01). In phosphate-free Krebs, the blockade of NO synthase did not change the contractile response to 100 mM KCl; it reduced EC₅₀ and increased E_max of 5-HT in WKY, but not in SHRSP.
7. These results confirm that the sensitivity to 5-HT is higher in basilar artery isolated from SHRSP than in those from WKY. They show that endothelium-dependent vasorelaxation to ACh is impaired in SHRSP. The finding that removal of endothelium or blockade of NO synthase augmented the contractile response to 5-HT in WKY, but not in SHRSP basilar arteries indicates that the difference in responsiveness to 5-HT observed between WKY and SHRSP basilar arteries might be, at least in part, related to dissimilarities in NO release. Furthermore, the L-NOARG-induced contraction sensitive to calcium channel blockers indicates that, in basilar arteries, NO production might lower L-type calcium channel opening and thereby control the tone of the vessels.

     

Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - The purpose of this study was to examine the anaesthetic requirement of intrathecal midazolam in a dose-response fashion in...     

Is there still a place for angiography in the management of renal mass lesions?

In recent years, the development of noninvasive imaging modalities for exploration of the kidney has markedly reduced the use of angiography in the evaluation of renal masses. Presently, it is not required in routine practice to evaluate renal masses. Ultrasound is the most efficient procedure in detecting renal tumor. It is acknowledged that arteriography has a limited diagnostic and staging value compared with CT and MRI for the assessment of renal cell carcinomas (RCC). Most urologists recommend partial nephrectomy or tumor enucleation in an effort to preserve as much as possible functioning renal tissue. In such cases a preoperative map of the renal vasculature is not needed. Information on the main renal artery(ies) and segmental renal arteries can be provided with spiral CT or dynamic MR angiography. Arteriography remains useful in exceptional situations. Interventional arteriography is becoming an important part. It is indicated by means of selective embolization for the treatment of potentially bleeding tumor (i. e. angiomyolipoma) or in emergency in cases of acute hemorrhage. Less frequently, it may be proposed as a palliative procedure for inoperable patients with huge renal tumor. Two other indications of interventional arteriography are acknowledged. Some urologists request preoperative embolization of the tumor-harboring kidney to decrease/avoid extensive blood loss during surgery and/or to facilitate surgery with huge renal tumors when the renal vessels are difficult to reach. The complications of nephron-sparing surgery (partial nephrectomy or tumor enucleation) related to bleeding or arteriovenous fistulas may be cured by arterial embolization. Received: 18 May 1998; Revision received: 3 August 1998; Accepted: 6 August 1998