The activation of the contact phase of coagulation by physiologic surfaces in plasma: the effect of large negatively charged liposomal vesicles

The endogenous, negatively charged surface that induces activation of the contact coagulation factors was investigated in plasmas taken from women in late pregnancy and control subjects of child-bearing age. The plasmas from the two groups of subjects were incubated at 4 degrees C for 24 hours either in plastic or in glass tubes and the factor VII coagulant activity (VIIc) was assayed in the treated plasmas. The activation of factor VII under these conditions involves the generation of enzymes derived from factor XII (XIIa). The contact surface is rate- limiting for the activation of factor VII in the plasmas in both groups of subjects and can be supplemented by large multilamellar liposomal vesicles carrying the appropriate density of negative charge. The size of these vesicles is within the range of sizes of the large lipoprotein particles (chylomicrons, very low and intermediate-density lipoproteins). The relationship between the density of negative charge on the liposomal vesicles and VIIc was similar in the late pregnancy and the control plasmas incubated in plastic tubes. At a saturating density of negative charge the observed relative VIIc was similar in both sets of plasmas. The incubation of late pregnancy or control plasma in plastic tubes in the presence of sodium stearate caused VIIc to increase with increasing concentration of the added fatty acid. These results suggest that large lipoprotein particles carrying the appropriate free fatty acid at a sufficient density of negative charge could provide the contact surface that induces the generation of factor XIIa and the subsequent activation of factor VII. Moreover, plasmas from women in late pregnancy have a higher concentration of potential surface and a higher density of negative charge than the plasmas from nonpregnant women.     

Production of cytokines by bone marrow cells obtained from patients with multiple myeloma

Previous work with continuously cultured multiple myeloma lines suggested that cytokine production by tumor cells may mediate some of the medical complications of this disease. To further investigate this issue, we assayed freshly obtained bone marrow (BM) cells from myeloma patients for the in vitro production of cytokines and the presence of cytokine RNA. Production of cytokine protein was assessed by bioassays with the aid of specific neutralizing anticytokine antibodies. These assays detected interleukin-1 (IL-1) and tumor necrosis factor (TNF) secretion by myeloma BM cells, which was significantly greater than secretion from similarly processed BM cells of control individuals. In contrast, lymphotoxin and interleukin-2 (IL-2) production could not be detected. The levels of IL-1 and TNF produced in vitro peaked at 24 hours of culture and correlated with stage and the presence (or absence) of extensive osteolytic bone disease. Northern blot analysis demonstrated the presence of IL-1 beta and TNF RNA in uncultured myeloma BM cells but no detectable IL-1 alpha or lymphotoxin RNA. In addition, the amount of cytokine RNA correlated with protein production, being significantly greater in patients' BM cells than in control marrow. These data suggest a role for IL-1 beta and/or TNF in the pathophysiology of multiple myeloma and argue against a role for lymphotoxin or IL-2.     

X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features

The radiologic studies of 38 essentially untreated adults with X-linked hypophosphatemia (XLH) were reviewed to determine the prevalence of radiologic features, to compare the findings in men and in women, and to elucidate the natural history of the disease by comparing the findings in young, intermediate-age, and older patients. Bone-reinforcement lines were common, but no characteristic mineral mass alteration was established. Looser zones were more prevalent in older subjects. Osteoarthritis was common, occurring in the ankles, knees, feet, sacroiliac joints, and wrists. Enthesopathy was infrequent in the younger group but was present in every member of the intermediate and older groups and was often accompanied by extra ossicles. Curvatures of the lower-extremity long bones were common in all age groups. Three new skeletal alterations in XLH were found to be common: flaring of the iliac wings, trapezoidal distal femoral condyles, and alterations in talar morphology, including shortening of the talar neck and flattening of the talar dome. Technetium-99m methylene diphosphonate scintigrams of 17 subjects were often abnormal, depicting bowing deformity and focal tracer accumulation in diaphyseal cortices and in periarticular and extraarticular regions. The mean metabolic index was moderately elevated (4.0). Both radiographic and scintigraphic findings were more severe in men, consistent with hemizygosity. The natural history of untreated XLH in both sexes is characterized by the development of a variety of age-related skeletal abnormalities during adulthood.     

Variable telomere length across post-mortem human brain regions and specific reduction in the hippocampus of major depressive disorder

Stress can be a predisposing factor to psychiatric disorders and has been associated with decreased neurogenesis and reduced hippocampal volume especially in depression. Similarly, in white blood cells chronic psychological stress has been associated with telomere shortening and with mood disorders and schizophrenia (SZ). However, in previous post-mortem brain studies from occipital cortex and cerebellum, no difference in telomere length was observed in depression. We hypothesized that in psychiatric disorders, stress-driven accelerated cellular aging can be observed in brain regions particularly sensitive to stress. Telomere length was measured by quantitative-PCR in five brain regions (dorsolateral prefrontal cortex, hippocampus (HIPP), amygdala, nucleus accumbens and substantia nigra (SN)) in major depressive disorder (MDD), bipolar disorder, SZ and normal control subjects (N=40, 10 subjects per group). We observed significant differences in telomere length across brain regions suggesting variable levels of cell aging, with SN and HIPP having the longest telomeres and the dorsolateral prefrontal cortex the shortest. A significant decrease (P<0.02) in telomere length was observed specifically in the HIPP of MDD subjects even after controlling for age. In the HIPP of MDD subjects, several genes involved in neuroprotection and in stress response (FKBP5, CRH) showed altered levels of mRNA. Our results suggest the presence of hippocampal stress-mediated accelerated cellular aging in depression. Further studies are needed to investigate the cellular specificity of these findings.     

Characterization of non-human primate antisera to acute lymphoblastic leukemia (ALL): evidence for unique antigen(s) on childhood ALL of "T" phenotype

A non-human primate antiserum was prepared to acute lymphoblastic leukemia of T-cell phenotype (T-ALL) and, after absorptions with normal blood elements, reacted by immunofluorescence and microcytotoxicity to all the T-ALL tested. In addition, the antiserum reacted with cells from about 70% of the common ALL studied and immunoprecipitated the common ALL antigen of 100,000 daltons. However, when the anti-T-ALL serum was absorbed with with lymphoblasts from common ALL, it failed to react with common ALL lymphoblasts, yet reacted significantly with cells from patients with T-ALL phenotype and defined a 100,000-dalton membrane component not found on common ALL lymphoblasts. In addition, sequential immunoprecipitation of 125I-labeled T-ALL membranes by anti- common-ALL serum followed by anti-T-ALL serum detected the T-ALL membrane component of 100,000 daltons that was not found on common ALL. Thus, our results demonstrate the presence of of a unique human T-ALL antigen present on all T-ALL distinct from the common ALL antigen.     

诱导化疗在局部晚期头颈癌中的作用

作为标准化的非手术治疗,诱导化疗(ICT)在治疗局部晚期头颈鳞癌已有几十年的历史,但是关于其作用尚存争议。同期放化疗(CRT)是目前标准化的非手术治疗,然而由于ICT能够使肿瘤体积缩小,提高放疗的可行性,改善患者对放疗的耐受力,增加放疗后器官功能保留的可能性及降低远处转移率。所以,对ICT的研究从未停止。该文对近期随机试验进行回顾分析,与手术或单独CRT比较,评估ICT中紫杉醇的价值。Meta分析比较ICT中紫杉醇和顺铂及5氟尿嘧啶的作用。之前的随机试验中,并没有ICT提高生存率的报道。但     

The impact of periodontitis on oral health‐related quality of life: a review of the evidence from observational studies

Modern population based oral health management requires a complete understanding of the impact of disease in order to provide efficient and effective oral health care and guidance. Periodontitis is an important cause of tooth loss and has been shown to be associated with a number of systemic conditions. The impact of oral conditions and disorders on quality of life has been extensively studied. However, the impact of periodontitis on quality of life has received less attention. This review summarizes the literature on the impact of periodontitis on oral health‐related quality of life (OHRQoL). Relevant publications were identified after searching the MEDLINE and EMBASE electronic databases. Screening of titles and abstracts and data extraction was conducted. Only observational studies were included in this review. Most of the reviewed studies reported a negative impact of periodontitis on OHRQoL. However, the reporting standards varied across studies. Moreover, most of the studies were conducted in developed countries.