The functional characterization of interleukin-10 receptor expression on human natural killer cells

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.     

Smoking habits in relapsed subjects from a smoking cessation trial after one year

Reports of smoking cessation studies often claim that many relapsed subjects reduce their smoking. We investigated the smoking habits of relapsers 1 year after quitting in a smoking cessation trial using nicotine or placebo patches. All 289 participants in that study were summoned to a 1-year follow-up visit–148 (57%) of 259 relapsers attended, as did all 30 sustained abstainers. Fewer than 1% of the subjects had quit spontaneously after the primary relapse. Daily cigarette consumption, standard nicotine yield per cigarette, saliva cotinine concentration, expired carbon monoxide level and two nicotine dependency scales were assessed at entry and at the 1-year follow-up. In five of these six smoking-related characteristics, there was a small but significant mean reduction of 7%-27%. A significant weight gain of 0.5 ± 2.9 kg (mean ± SD) was recorded in the relapsers compared with 4.8 ± 4.2 kg for abstainers (p < 0.001). It is concluded that smoking habits in relapsers are relatively unchanged, and thus the most important outcome measure in smoking cessation trials is abstinent subjects.     

Die Knochenbank Richtlinien - Probleme - Anwendung

Bone banks, which, due to problems concerning transmission of infectious diseases, had been shut down in many places over the last 10 years, are becoming increasingly popular all over the world again. Using different methods of virus inactivation either osteoconductivity is dramatically reduced or sterility of the transplant cannot be guaranteed. Synthetic bone replacement materials, which in addition to finally being bioresorbable also get better in terms of biomechanical stability all the time (SRS®, ?fracture grout®” [Norian], alpha BSM® [Merck]) will not be able to take place neither for allogenous nor autogenous bone transplants during the next couple of years, until patient and material outcome has been evaluated over an adequate time frame. Autogenous bone transplantation therefore remains the golden standard, whereas allogenous transplantation has to be considered if cancellous bone explant sites have been exploited. In this case the guidelines of the Bundesärztekammer from 1996 have to be applied. In the following these guidelines will be explained, occurring problems and possible solutions will be described and compared to the experiences made in other countries. Finally the use of such a bone bank will be analyzed together with a case history of polyostotic fibrous dysplasia in McCune-Albright's syndrome.     

Exposure to various benzene derivatives differently induces cytochromes P450 2B1 and P450 2E1 in rat liver

Benzene (B), toluene (T), ethylbenzene (EB), styrene (S) and xylene isomers (oX, mX, pX) are important environmental pollutants and B is a proved human carcinogen. Their inhalation by male Wistar rats (4 mg/1,20 h/day, 4 days) caused cytochrome P450 (P450) induction. The degree of P450 2B1 induction increased and that of 2E1 decreased in the series B, T, EB, S, oX, mX and pX, as estimated by Western blots, while neither solvent was as effective for 2B1 induction as phenobarbital and B was more effective for 2E1 than ethanol. The levels of several other P450s decreased after exposure to these solvents, B being most effective. Exposure to these solvents increased in vitro hepatic microsomal oxidation of B and aniline (AN) (2E1 substrates) 3 to 6-fold, indicating induction of this P450. T oxidation was increased 2 to 4-fold and chlorobenzene (ClB) oxidation 3-fold. Sodium phenobarbital (PB, 80 mg/kg/day, 4 days, i.p.) did not increase ethylmorphine (EM) and benzphetamine (BZP) demethylation (2B1 substrates), neither of the B derivatives did so, and oX decreased it; however, pentoxyresorufin O-dealkylation was well related to the immunochemically detected 2B1 levels in control, PB and B microsomes. PB did not increase B, but increased T and C1B oxidation 2–4 and 3-fold, respectively, indicating possible 2B1 role in their oxidation. B oxidation after various inducers was related to immunochemical 2E1 levels, T and C1B oxidation to both 2B1 and 2E1 and AN oxidation to 2E1 and 1A2 levels. Very efficient B oxidation by 2E1 at low B levels indicates that induction of 2E1 may contribute to B myelotoxicity in vivo more than any other P450 enzyme tested, especially considering the fact that B is the most efficient inducer of its metabolism.     

Solid Aneurysmal Bone Cyst of the Metacarpal Bone

Background: A solid aneurysmal bone cyst is a rare tumor-like lesion of bone. As conventional aneurysmal bone cyst it is a benign, although locally destructive lesion. While the aneurysmal bone cyst is characterized by cyst-like walls of predominantly fibrous tissue filled with free-floating blood, the solid variant shows essential findings identical to those seen in the walls of conventional aneurysmal bone cysts, except that the lesion almost completely lacks the blood-filled spaces and the cyst walls. Differential Diagnosis: Aneurysmal bone cysts and solid aneurysmal bone cysts may easily be mistaken for a malignant tumor, both radiologically and histologically, due to their great rate of growth, tremendous destruction of bone, and marked cellular exuberance in the early to mid phase of development. Case Study: A case of solid aneurysmal bone cyst of the fourth metacarpal is presented. In spite of the relatively unusual location it allows to clearly demonstrate both, the task of correct differential diagnosis and the surgical spectrum of therapy including local recurrence.     

喉癌患者无癌侵及的喉内肌与正常喉内肌的组织学差异

目的：通过对喉癌患者未被癌组织侵及的喉内肌及正常人的喉内肌肌纤维形态、结构的比较分析，从组织学角度揭示二者之间的差异。方法：将5例喉癌患者未被癌组织侵及的肌纤维和1例使康成人的甲杓肌、环杓侧肌及环杓后肌经HE染色，于镜下观察肌纤维的形态，并采用显微图像分析仪测量肌纤维的横截面积和最大宽度。结果：喉癌患者与使康成人相比，各喉内肌肌纤维形态差异较大；肌纤维横截面积、最大宽度有显著增加(P＜0．01)，增加的幅度均为环杓后肌＞环杓侧肌＞甲杓肌。结论：喉癌患者未被癌组织侵及的肌纤维不仅在形态上有很大的不同，而且肌纤维横截面积及最大宽度明显增大，可能是癌变增加了呼吸道的阻力，各喉内肌代偿性活动的结果。