Therapy of human cervical carcinoma with monoclonal antibody-Pseudomonas exotoxin conjugates.

Pseudomonas exotoxin A (PE) linked to the F(ab')2 fragment of 1H10, a murine monoclonal antibody recognizing a carbohydrate epitope of a glycoconjugate expressed on the surface of human cervical carcinoma tumor cells, was evaluated for in vitro and in vivo activity. PE can kill cells by ADP-ribosylating elongation factor 2 thus inhibiting protein synthesis. Disulfide- as well as thioether-linked immunotoxins (1H10-PE) killed cervical carcinoma cells in vitro and were 20-160 times more inhibitory to target than to control cells. Cell killing was antibody mediated as demonstrated by the reduction of 1H10-PE growth inhibition to target CaSki cells by free 1H10 F(ab')2. In addition, a control antibody immunotoxin was nontoxic to CaSki cells. Thioether-linked 1H10-PE administered either i.v. or i.p. suppressed the growth of established solid s.c. cervical carcinoma tumors xenografted in nude mice for over 30 days. Treatment with antibody alone or a control immunotoxin had no significant effect on tumor growth. Administration of immunotoxin i.p. was associated with less toxicity than administration i.v., but i.v. injections were more effective at suppressing the growth of established solid tumors.     

Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

An etiological and clinicopathological study of early syphilis in oropharynx]

OBJECTIVE: To investigate the characteristics of the early stage treponema pallidum infected tissue in ear, nose, oropharynx and larynx and to raise relevance ratio of syphilis in nose and oropharynx and enhance doctor's self-protection awareness. METHODS: The histopathologic characteristics were studied by using HE staining, Warthin-Starry (W-S) staining was adopted to examine the treponema pallidum(TP) in lesion issue and its exudates smear for 12 cases biopsy tissues of suspicious syphilis. The diagnosis was confirmed by venereal disease research laboratory (VDRL), rapid plasma reagin circle test(RPR), treponema pallidum hemagglutination test(TPHA) and fluorescent treponemal antibody-absorption test (FTA-ABS). Treat with curing syphilis methods which published by nation. RESULTS: In the 12 cases mucous membrane specimen, the squamous epithelium proliferated, neutrophilic granulocyte infiltrated, within inherent membrane generous plasmacyte and lymphocyte infiltrated. W-S staining: plenty of treponema pallidum were found inside mucous membrane epithelium and exudate smear. Serology examination: 11 cases VDRL(++++), 7 cases RPR (+), 11 cases TPHA(+), 1 case FTA-ABS(+). After systemic treatment, 11 cases are clinically recovered. All patients serology become negative. CONCLUSION: W-S staining method can directly demonstrate histopathologic characteristics in early syphilis, in intrinsic membrane numerous plasmacyte infiltration. Combining with specific syphilis serology examination could increase diagnosis rate of syphilis in nose and oropharynx.     

后SARS时期对公共卫生与健康的再思考

在人们印象中“公共卫生”是一个很模糊的领域，它比较形象的载体可能就是爱国卫生运动或预防接种。美国1932年提出的公共卫生的定义，对现在依然有指导意义：公共卫生就是预防疾病，延长寿命，通过有组织的社会共同努力来改变环境卫生，从而促进身体的健康，提高工作效率，控制社区传染病的流行，教育个人形成良好的卫生习惯，组织医护人员对疾病进行早期的诊断和预防性治疗。简而言之，“公共卫生”就是关注公众健康的科学。公共卫生学不能脱离临床医学，后是对某种疾病的个体的治疗，而前则着眼对某种疾病做群体防护。     

Dry skin in dermatology: a complex physiopathology

Dry skin (xerosis) is a common dermatosis affecting people of varying skin types and ages and various areas of the body. It is associated with both skin thickening and skin thinning and is triggered by both exogenous (e.g. climate, environment, lifestyle) and endogenous (e.g. medication, hormone fluctuations, organ diseases) factors. Skin requires a water content of 10–15% to remain supple and intact. This water is either ‘static’ (i.e. bound) or ‘dynamic’. The predominance of hydrophobic substances in intercellular constituents is a means of regulating the humidity of the skin. Emollients, highly effective treatment adjuncts in the management of all dry skin disorders, help to restore damaged intercorneocyte lipid structures and increase the water content of the skin, helping to reduce scaling and improving its barrier function.     

In vivo PET imaging of cardiac presynaptic sympathoneuronal mechanisms in the rat.

The sympathetic nervous system of the heart plays a key role in the pathophysiology of various cardiac diseases. Small-animal models are valuable for obtaining further insight into mechanisms of cardiac disease and therapy. To determine the translational potential of cardiac neuronal imaging from rodents to humans, we characterized the rat sympathetic nervous system using 3 radiotracers that reflect different subcellular mechanisms: (11)C-meta-hydroxyephedrine (HED), a tracer of neuronal transport showing stable uptake and no washout in healthy humans; (11)C-phenylephrine (PHEN), a tracer of vesicular leakage and intraneuronal metabolic degradation with initial uptake and subsequent washout in humans; and (11)C-epinephrine (EPI), a tracer of vesicular storage with stable uptake and no washout in humans. METHODS: We used a small-animal PET system to study healthy male Wistar rats at baseline, after desipramine (DMI) pretreatment (DMI block), and with DMI injection 15 min after tracer delivery (DMI chase). The rats were kept under general isoflurane anesthesia while dynamic emission scans of the heart were recorded for 60 min after radiotracer injection. A myocardial retention index was determined by normalizing uptake at 40 min to the integral under the arterial input curve. Washout rates were determined by monoexponential fitting of myocardial time-activity curves. RESULTS: At baseline, HED showed high myocardial uptake and sustained retention, EPI showed moderate uptake and significant biphasic washout, and PHEN showed moderate uptake and monoexponential washout. The average (+/- SD) left ventricular retention index for HED, PHEN, and EPI was 7.38% +/- 0.82%/min, 3.43% +/- 0.45%/min, and 4.24% +/- 0.59%/min, respectively; the washout rate for HED, PHEN, and EPI was 0.13% +/- 0.23%/min, 1.13% +/- 0.35%/min, and 0.50% +/- 0.24%/min, respectively. The DMI chase resulted in increased washout only for HED. DMI block decreased myocardial uptake of all tracers by less than 90%. CONCLUSION: Kinetic profiles of HED in the rat myocardium were similar to those of HED in humans, suggesting comparable neuronal transport density. Unlike in humans, however, significant washout of EPI and faster washout of PHEN were encountered, consistent with high intraneuronal metabolic activity, high catecholamine turnover, and reduced vesicular storage. This evidence of increased neuronal activity in rodents has implications for translational studies of cardiac neuronal biology in humans.