Cell surface phenotype of in vitro proliferating lymphocytes in HTLV-I-associated myelopathy (HAM/TSP)

The in vitro proliferation of peripheral blood lymphocytes (PBLs) without any mitogenic stimulation is one of the hallmarks of human T lymphotropic virus type I (HTLV-I) infection. Recent evidence suggests a difference in the degree of the phenomenon between HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-I carriers (AC). In this article, we demonstrated several alterations in the features of the in vitro transformed lymphocytes between patients with HAM/TSP (n = 16) and AC (n = 8). The percentages of total CD8+ and CD8+CD28+ cells were significantly increased in the in vitro proliferating T lymphocytes derived from the patients with HAM/TSP when compared to those from AC. HAM/TSP was segregated from AC by the high degree of the proliferation of CD8+CD28+ cells. The expression of HTLV-I-specific antigens on the cultured PBLs was detected only in the subjects which showed low CD8+CD28+/CD4+ ratio of the in vitro proliferating lymphocytes. These findings suggest that this phenomenon distinguishes HAM/TSP from AC, not only in quantity but also in quality.     

三个统一:21世纪中医学发展取向的思考

21世纪中医学的发展，面临着理顺民族性表述方式与国际性科学内涵关系的问题，因此必须辩证地把握结构与机能、实证科学手段与人文精神、过程与结果之间的谐调统一，这样既符合中医学术体系特征，又能与当代生命科学研究保持一致。     

Serologic evidence for human ehrlichiosis in Africa

Human ehrlichiosis is a recently recognized rickettsial disease. It is caused byEhrlichia chaffeensis, an intraleucocytic Gram-negative, obligate intracellular bacterium, grouped within the genusEhrlichiae. Most human cases of ehrlichiosis have been diagnosed in the USA. Two cases have been reported outside of the USA, one in Europe and one in Africa. From 1 January to 30 June 1992, 765 sera from blood donors or other asymptomatic subjects in 8 African countries, including Ivory Coast, Burkina Faso, Mali, Central African Republic, Angola, Zimbabwe, Mozambique and Commores Islands, were tested by indirect immunofluorescence for the presence ofE. chaffeensis antibodies. Positive sera were confirmed by Western immunoblotting. Only two of 765 sera tested were positive. One serum obtained from Burkina Faso had an IgG titer of 1:200 and one from Mozambique had an IgG titer of 1:80. Human ehrlichiosis seems to occur infrequently in Africa, although many more sera from additional African countries need to be evaluated.     

Expansion of CD3+CD56+ lymphocytes correlates with induction of cytotoxicity by interleukin-2 gene transfer in human breast tumor cultures

Background: Mice immunized with murine mammary carcinoma cells genetically engineered to secrete interleukin-2 (IL-2) are rendered resistant to subsequent challenge with unmodified tumor cells, and in the case of mice bearing established tumors, the rate of development of pulmonary metastases is reduced. Despite these encouraging animal results, little is known about the induction of antitumor immunity by IL-2 gene transfer in human breast cancer. Methods: Adenovirally mediated IL-2 gene transfer was performed in 12 tumor fragment cultures established from seven primary breast cancers. Autologous tumor infiltrating lymphocytes (TILs) or peripheral blood mononuclear cells (PBMCs) were cocultured with transduced tumor fragments, and changes in phenotype and cytotoxicity were measured. Results: IL-2 was never detectable in the untransduced cultures, but it peaked at 5.0—1,324.8 ng/ml in the transduced cultures. Lymphocyte counts declined in all untransduced cultures, but they increased two- to sevenfold in four transduced cultures. CD4:CD8 ratios decreased from a mean of 2.11 at baseline to 1.27 after stimulation in coculture (p=0.03). Expansion of lymphocytes expressing the natural killer cell phenotype (CD3⁻CD56⁺) occurred in only one culture, but the CD3⁺CD56⁺ population increased in four of six cultures. Lymphocytes from four of 10 cocultures generated significant cytotoxicity against allogeneic breast cancer cells. Induction of cytotoxicity correlated with expansion of the CD3⁺CD56⁺ phenotype (R²=0.805, p=0.02). Conclusions: IL-2 gene expression by human breast cancer causes expansion of CD3⁺CD56⁺ cytotoxic lymphocytes. This phenotype is consistent with that of a non-major histocompatibility complex (MHC)-restricted cytokine induced killer cell population previously described. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the U.S. Army. Presented at the 49th Annual Cancer Symposium of The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

抗人精浆蛋白McAb的制备及其特性研究

本文报道用杂交瘤技术建立了２株分泌抗人精浆蛋白单克隆抗体的细胞株Ｄ１和Ｃ１２。Ｄ１株分泌的抗体为ＩｇＭ，Ｃ１２株为ＩｇＧ３。这两株均能与正常人精浆和无精子症患者的精浆产生特异性免疫反应。Ｄ１株单抗具有补体依赖性制动人精子的作用，间接免疫荧光试验表明，它能结合到人精子颈部和顶体后区。这充分说明２株单抗是特异性抗人精浆的，Ｄ１是精子制动抗体，其相应的精子抗原属于精子外套抗原成分之一。     

Blockade of the human cardiac K+ channel Kv1.5 by the antibiotic erythromycin

Erythromycin administration has been associated with a prolongation of cardiac repolarization in certain clinical settings. This could be due to blockade of voltage-dependent K⁺ channels in the human heart. For this reason we examined the effects of erythromycin on a rapidly activating delayed rectifier K⁺ channel (Kv1.5) cloned from human heart and stably expressed in human embryonic kidney cells. When examined using the whole-cell patch clamp technique, erythromycin (100 μM) blocked Kv1.5 current in a time-dependent manner but required prolonged exposure to do so. However, when we examined Kv1.5 current using inside-out macropatches, erythromycin applied to the cytoplasmic surface rapidly (within 1-2 min) inhibited Kv1.5 current with an IC₅₀ value of 2.6 x 10^-5M (1.7 - 3.9 x 10^-5M, 95% C.L.). The main effect of erythromycin was to accelerate the rate of Kv1.5 current decay thereby reducing the current at the end of a prolonged voltage-clamp pulse. Erythromycin also blocked Kv1.5 current in both a voltage- and frequency-dependent manner but had little effect on the activation kinetics, deactivation kinetics, or the steady-state inactivation properties of Kv1.5. These data suggest that erythromycin acts as a blocker of an activated state of the Kv1.5 channel and that it may access its binding site from the intracellular face of the channel. This study is the first to examine the effects of erythromycin on a cloned human cardiac K⁺ channel. It is concluded that erythromycin blocks Kv1.5 at clinically relevant concentrations. Blockade of voltage-dependent K⁺ channels in the heart could contribute to the alterations in cardiac repolarization that have been observed with erythromycin. Received: 22 November 1996 / Accepted: 26 February 1997     

Cancellous Bone Structure in the Growing and Aging Lumbar Spine in a Historic Nubian Population

There is abundant data on cancellous bone in the aging human spine, but little relating to the growing vertebral cancellous bone in childhood and adolescence. The purpose of this study was to map vertebral cancellous bone in a growth and age series of historic skeletal samples and to make comparisons with data published on recent material. Lumbar vertebral bodies were collected from 65 skeletons (0–60 years) from a medieval Nubian population. Ethnohistoric information was collected to interpret conditions that might have influenced bone structure and metabolism. The cancellous bone was studied three dimensionally, using stereophotography and scanning electron microscopy and morphometrically by performing a semiautomatic structural analysis on digitized backscattered electron images of polymethacrylate-embedded material. The cancellous bone structure in the children consisted mainly of a densely packed, uniform network of small rodlike trabeculae. The greatest bone volume fraction with small, more platelike trabeculae was observed during adolescence. In young adults, larger platelike trabeculae were present in the central zone and smaller trabeculae in the superior and inferior zones, as described for modern skeletal material. Structural changes associated with aging were observed much sooner than in modern man. By the estimated age of approximately 50–60 years, the predominant architectural elements were slender rarified rods in both sexes. The ethnohistorical data suggest that this was essentially a black African population of physically active peasants, not likely to suffer Vitamin D insufficiency or deficient calcium intake. Thus an earlier onset of the biological age changes in cancellous bone found in modern populations was probably prevalent. Received: 1 March 1996 / Accepted: 31 December 1996     

An anisotropy of human tactile sensitivity and its relation to the visual oblique effect

Summary The ability of humans to detect striated stimuli on the distal phalanges was found to be highly anisotropic. Observers were much more sensitive to stripes presented in the proximal-distal orientation than to stripes in any other orientation. This tactile anisotropy was contrasted with the well-known visual anisotropy in which sensitivity is greatest for stripes at the horizontal and vertical orientations. We suggest that both the tactile anisotropy and the visual anisotropy are caused by corresponding anisotropies in the distribution of preferred orientations of orientation-selective neurons with in the respective modalities.     

Hyperexcitability associated with localizable lesions in epileptic patients

Intracellular recordings from neurons were carried out in cortical slices obtained from tissue removed from patients suffering from intractable seizures. The patients were divided into two groups based on the presence or absence of an anatomical abnormality that could be imaged preoperatively. The lesion or its surround was the presumptive epileptogenic area. The tissue removed from the patients without lesions was removed either for biopsy purposes or for access to epileptic tissue and was not considered epileptogenic. All neurons from patients without an imageable lesion, and some (19%) from patients with an imageable lesion, responded to orthodromic stimuli with a sequence of synaptic excitation followed by inhibition; these properties resembled those of normal rodent cortical slices. Different responses, classified as abnormal, were observed in 81% of the neurons in tissue specimens obtained near lesions. The most common was prolonged synaptic excitation with no noticeable inhibition, even at high stimulus strengths. In three resections, long latency all-or-none depolarization shifts were observed that resemble the classic paradoxical depolarization shift seen in in vivo extracellular recordings. Loss of specific inhibitory systems within the cortex may contribute in part to these abnormal responses.     

Time course of the effects of diazepam and lorazepam on perceptual priming and explicit memory

The effects of diazepam and lorazepam on explicit memory and perceptual priming were studied 50, 130 and 300 min after drug administration. Sixty healthy volunteers were randomly assigned to one of five parallel groups (placebo, diazepam 0.2 or 0.3 mg/kg, lorazepam 0.026 or 0.038 mg/kg). The corresponding doses of benzodiazepines exerted a similar negative effect on explicit performance. Lorazepam markedly impaired priming performance, whereas the effect of diazepam was intermediate between that of placebo and that of lorazepam 0.038 mg/kg. The impairment was maximal at the theoretical peak plasma concentration. Contamination by explicit memory could account for the decrease in priming performance observed in the diazepam groups.