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.     

The effect of follow-up on limiting non-participation bias in genetic epidemiologic investigations

The use of a comprehensive follow-up strategy to limit non-participation bias was evaluated in a population-based case-control study of orofacial clefts. Birth parents were requested to provide exposure data, and index children and parents were asked to provide blood specimens. Follow-up included telephone or postal reminders every two weeks for up to three months. Consent to participate was received from 281 (76.6%) case mothers and 246 (72.4%) case fathers. The corresponding totals for controls were 279 (54.7%) and 245 (49.8%). Evaluation of participation rates by intensity of follow-up showed that 23% of case and 18% of control families consented without reminders (first stage); 81% of cases and 83% of controls agreed following one or two reminders (second stage); and the remainder of participants consented following three or more reminders (final stage). Cumulative distributions of sociodemographic characteristics differed little between second and final stage participants. Odds ratios for maternal multivitamin use were similar between second and final stage participants, whereas those for maternal and paternal smoking tended to decline. Although follow-up measures were necessary to enroll most families, use of more than two reminders did not appear to increase the representativeness of the sample; however, termination of recruitment after only two reminders would have led to different conclusions. Future studies require data collection protocols that encourage participation from all population subgroups, and one alternative is presented.     

Visualization of the ribosome-lamella complex in plastic-embedded biopsy specimens as an aid to diagnosis of hairy-cell leukemia.

Hairy-cell leukemia is a lymphoid leukemia of B-cell lineage, the cells of which are characteristically tartrate resistant acid phosphatase positive on blood and bone marrow smears. However, because hairy-cell leukemia is frequently associated with abundant marrow stroma, dry marrow taps, and peripheral pancytopenia, the diagnosis may rest on the appearance of the bone marrow biopsy specimen alone. The ribosome-lamella complex has been associated with hairy-cell leukemia, and can be visualized by light microscopy using l-micron sections of plastic-embedded bone marrow specimens stained with toluidine blue. We describe the findings in a case in which bone marrow and liver biopsy specimens were positive for hairy cells containing ribosome-lamella complex, which were visualized with both electron microscopy and light microscopy. Reliable light microscopic identification of ribosome-lamella complex may provide an easy and inexpensive method of aiding in the diagnosis of hairy-cell leukemia when aspirate material is not available for tartrate-resistant acid phosphatase stain.     

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。     

Diabetes mellitus in the guinea pig.

Spontaneous diabetes mellitus has been documented in a colony of guinea pigs. The contagious nature of the disease has been verified, but the nature of the infectious agent is not known. Animals from the original colony or animals exposed to the colony with normal glucose tolerance tests (GTT) became diabetic, as evidenced by elevated one- and four-hour GTT values, and in most cases have significant glycosuria. The severity of pathologic changes in the pancreatic islets parallel, in general, the severity of the clinical symptoms (glycosuria and abnormal GTT). Those animals with severe glycosuria and elevated FBS as well as one- and four-hour GTT values had the most pronounced degranulation and most prominent cytoplasmic inclusions in islet B cells. The severity of scarring in the islets can be correlated with the duration of the overt diabetic state. The other clinical parameters of note were elevated serum triglycerides, normal serum but elevated aortic cholesterol, and absence of ketonemia or ketonuria. The reproductive capacity of diabetic females was compromised. While the clinical manifestations are mild or variable, the presence of significant islet pathology is reminiscent of human juvenile diabetes mellitus. These findings lend support to the concept that infectious and/or immune mechanisms could be operative in the etiology and pathogenesis of human diabetes mellitus.     

File arrangement and maintenance executive (FAME). A general purpose schema driven file maintenance system

FAME is a data base maintenance system featuring dictionary driven access to items, handling of repeating groups, and a compression scheme. FAME can create and update files and utilities are provided to give programmers total access to these files through the dictionary. Other utilities aid the programmer in writing reports. In addition, there is a linkage to general retrieval and reporting packages and the statistical package SPSS which make these systems usable on a FAME data base by a non-programmer.