The prevalence and clinical impact of fibromyalgia in systemic lupus erythematosus

OBJECTIVE: To ascertain the prevalence of fibromyalgia syndrome (FMS) in systemic lupus erythematosus (SLE) and to evaluate its clinical impact and relationship to SLE disease activity. METHODS: A cross-sectional analysis of 102 patients from a public hospital SLE clinic. Information was obtained on symptoms of FMS, disability, tender points, pain thresholds, and SLE disease activity. RESULTS: Twenty-two SLE patients (22%) met the American College of Rheumatology criteria for FMS, and another 24 (23%) had clinical FMS but did not meet the classification criteria. The patients who met the criteria for FMS had a significantly increased frequency and severity of symptoms commonly associated with FMS, and were much more likely to be unable to perform daily activities. The FMS patients also were less likely to be employed, and more likely to be divorced and to be receiving welfare or medical disability benefits. However, patients with and those without FMS did not differ in measures of SLE activity. CONCLUSION: FMS is very common in SLE patients, and accounts for many of the symptoms and much of the disability in these patients.     

Expression of an activated erythropoietin or a colony-stimulating factor 1 receptor by pluripotent progenitors enhances colony formation but does not induce differentiation

Whether the presence of specific receptors on the surface of developing cells is the cause or consequence of lineage restriction is not known. If activation of specific receptors is the driving event in differentiation, the premature expression of specific receptors would promote differentiation along that pathway. In this study pluripotent progenitors, obtained from blast cell colonies (pooled or individual) of 5-fluorouracil-treated mice, were infected with retroviral vectors containing either an activated receptor for erythropoietin (EPO), an erythroid progenitor growth factor, or the receptor for colony-stimulating factor 1 (CSF-1), a macrophage growth factor. These receptors exhibit expression patterns restricted to committed progenitors. The developmental potential of infected pluripotent progenitors was not changed, although they expressed the exogenous genes, suggesting that in these cells activation of lineage-specific receptors does not induce differentiation. Acquisition of a constitutively activated EPO receptor allowed erythroid development in mixed colonies in the absence of EPO, as expected. Infection of progenitors with a virus containing the CSF-1 receptor promoted the development of granulocyte/macrophage (GM) colonies but did not alter the differentiation potential of either colony-forming unit (CFU)-GM or CFU-mix.     

Binaural processing in the dorsal nucleus of the lateral lemniscus

We studied the binaural properties of 72 neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the mustache bat. There are six main findings: 1) Conventional EI neurons that were excited by stimulation of the contralateral ear and inhibited by ipsilateral stimulation, comprise the majority (80%) of binaural DNLL cells. 2) For most EI neurons the quantitative features of their interaural intensity disparity (IID) functions, maximum inhibition, dynamic range and 50% point IIDs, were largely unaffected by the absolute intensity at the contralateral ear. 3) Although the net effect of the inhibition evoked by ipsilateral stimulation was to suppress discharges evoked by contralateral stimulation, our results indicate that the inhibitory inputs can act in three different ways. The first was a time-intensity trade, where increasing the intensity at the ipsilateral ear evoked inhibitory effects with progressively shorter latencies. The second way was that the latency of inhibition did not appear to decrease with ipsilateral intensity, but rather increasing ipsilateral intensity appeared only to increase the strength of the inhibition. The third way was that the lowest effective ipsilateral intensity suppressed the first spikes evoked by the contralateral stimulus and higher ipsilateral intensities then suppressed the later discharges of the train. Each of these inhibitory patterns was seen in about a third of the cells. 4) Neurons that had more complex binaural properties, such as the facilitated EI neurons (EI/F) and neurons that were driven by sound to either ear (EE neurons), represented about 20% of the binaural population. There were two types of EE neurons; those in which there was a simple summation of discharges evoked with certain IIDs, and those in which the spike-counts to binaural stimulation at certain IIDs were greater than a summation of the monaural counts and thus were facilitated. 5) All binaural neurons were strongly inhibited with IIDs that favored the ipsilateral ear. Our findings indicate that the more complex binaural types, the facilitated EI neurons (EI/F) as well as the two types of EE neurons, may be constructed from conventional EI neurons by adding inputs from several sources that impart the more complex features to these neurons. We propose four circuits that could account for the different binaural response properties that we observed. The circuits are based on the known connections of the DNLL and the neurochemistry of those connections. Finally, we compared the binaural properties of neurons in the mustache bat DNLL with those of neurons in the mustache bat inferior colliculus and lateral superior olive.(ABSTRACT TRUNCATED AT 400 WORDS)     

Duration of Borrelia burgdorferi infectivity in white-footed mice for the tick vector Ixodes scapularis under laboratory and field conditions in Ontario

The duration of Borrelia burgdorferi infectivity in white-footed mice (Peromyscus leucopus) experimentally inoculated or infested with infected Ixodes scapularis nymphs was evaluated. Infectivity was assessed by infesting these mice with unfed I. scapularis larvae at 7, 21, 35 and 49 days post-inoculation (DPI) or post-infestation (PI). At 7 DPI, B. burgdorferi was transmitted from 18 of 24 syringe-inoculated mice and all three tick-infected mice to I. scapularis larvae which fed upon them. However, at 21, 35 and 49 DPI, significantly fewer mice were infective. Borrelia burgdorferi was isolated from tissues of 14 of 22 syringe-inoculated mice about 56 DPI, and from all three tick-infected mice. However, the level of agreement between xenodiagnosis and bacterial culture was no greater than would be expected by chance alone. We also determined if B. burgdorferi infectivity of mice varied in relation to periods of tick feeding in the field. White-footed mice were trapped during April, July and August 1993 from two habitats on Long Point peninsula (Ontario, Canada), where B. burgdorferi is endemic. Mice from each habitat were infested with laboratory-reared I. scapularis larvae. Ticks from each mouse were subsequently examined by immunofluorescent assay for B. burgdorferi infection and mice were cultured for B. burgdorferi. None of 3577 I. scapularis larvae fed on 62 mice captured within the cottonwood dune habitat were infected with B. burgdorferi, although it was isolated from six of these mice. Within the maple forest habitat, 0/24, 8/21 (38%) and 1/21 (5%) mice transmitted B. burgdorferi to I. scapularis larvae during April, July and August, respectively. Most mice from the maple forest with B. burgdorferi-positive tissues (14/21) were collected during July, although the level of agreement between xenodiagnosis and tissue culture was poor. Because B. burgdorferi infectivity in mice appears to be of short duration, overwintered I. scapularis larvae and nymphs may have to feed upon infected hosts at the same time of year in order for a cycle of B. burgdorferi infection to be maintained on Long Point. Infected I. scapularis nymphs, rather than persistently infected vertebrate hosts, likely serve as the overwintering "reservoir" for B. burgdorferi on Long Point.     

CD40 mediated activation of gingival and periodontal ligament fibroblasts

Lipids and lipoproteins have been associated with breast cancer risk; however, published results have been inconsistent. To clarify these associations, we measured fasting lipids in women undergoing breast biopsies. A case-control study examined the association of fasting levels of lipids with histologically defined breast cancer risk. Four groups of premenopausal women were assembled on the basis of histological appearance of breast tissue: 1) no epithelial proliferation (n = 102), 2) proliferation without atypia (n = 53), 3) atypical hyperplasia or carcinoma in situ (n = 53), and 4) node-negative invasive cancer (n = 102). A postoperative fasting blood specimen was analyzed for cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Demographics, risk factors, diet, physical activity, fasting weight, and skin-fold thickness were measured. Triglyceride levels were significantly higher in women with node-negative invasive cancer (0.94 +/- 1.04 mg/ml) than in those with no epithelial proliferation (0.83 +/- 1.04 mg/ml, p = 0.03). This association persisted after adjustment for age, body size, lipids, reproductive and familial risk factors, and previous benign breast problems (p < 0.01), in keeping with an independent association of elevated triglycerides with breast cancer risk.     

Diapause-specific gene expression in pupae of the flesh fly Sarcophaga crassipalpis

Several cDNAs isolated from brains of diapausing pupae of the flesh fly, Sarcophaga crassipalpis, show expression patterns unique to diapause. To isolate such cDNAs a diapause pupal brain cDNA library was screened by using an elimination hybridization technique, and cDNAs that did not hybridize with cDNA probes constructed from the RNA of nondiapausing pupae were selected for further screening. The 95 clones that did not hybridize in the initial library screen were selected for further characterization. These clones were then screened against diapause and nondiapause pupal poly(A)+ Northern blots. The secondary screen identified 4 diapause-up-regulated clones, 7 diapause-down-regulated clones, 8 clones expressed equally in both diapause and nondiapause, and 75 clones without detectable expression. The diapause-up-regulated and down-regulated clones were further characterized by partial DNA sequencing and identity searches by using GenBank. Identities between our cloned cDNAs and other genes included those linked to cell cycle progression, stress responses, and DNA repair processes. The results suggest that insect diapause is not merely a shutdown of gene expression but is a unique, developmental pathway characterized by the expression of a novel set of genes.     

RNA extraction from virus-diseased sweet potato for reverse transcriptase polymerase chain reaction analysis

Apoptosis occurs in both clinical and experimental alcoholic liver disease. The mechanisms involved in alcohol-induced apoptosis of liver cells are not completely understood. Induction of cytochrome P450 2E1, the alcohol-inducible cytochrome P450, is one of the proposed mechanisms. Exposure of Hep G2 cells expressing cytochrome P450 2E1 to arachidonic acid leads to increased lipid peroxidation and apoptosis. Increased levels of iron in the liver also promote lipid peroxidation and are associated with increased numbers of apoptotic hepatocytes. Tumor necrosis factor (TNF) acting through its receptors can induce apoptosis in hepatocytes. Increased levels of tumor necrosis factor and its receptors have been described in alcoholic liver disease. The liver is also CD95 receptor positive and in liver tissue from patients with alcoholic hepatitis, the CD95 ligand is expressed at high levels in hepatocytes. Cytotoxic T lymphocytes could, through the CD95 receptor-ligand interaction, promote apoptosis.     

Management of patients with unstable angina in a general cardiology unit

AIMS: To review the clinical management of patients with unstable angina and to relate prospectively initial risk stratification, according to the Braunwald criteria, to subsequent cardiovascular events. METHODS: From February to April 1996 we performed a three month prospective review of all patients with a diagnosis of unstable angina admitted to the coronary care unit at Auckland Hospital. RESULTS: One hundred and four patients (61% male), with a mean age of 64 years, were classified as high (58%), intermediate (41%) or low risk (1%) for an adverse cardiac event. Twelve (12%) patients had a documented myocardial infarction, of whom 11 were in the high-risk group (p = 0.038). During hospitalisation there was one death. Twelve (12%) patients underwent inpatient exercise testing, five of whom proceeded to a coronary angiogram prior to hospital discharge. Twenty-two (21%) unstable patients underwent inpatient angiography without prior exercise testing. Twenty-one (20%) patients required revascularisation on the same admission: percutaneous coronary angioplasty (n = 14) or coronary artery bypass grafting (n = 7). Twelve of these 21 patients were in the high-risk group (p = 0.999, NS). CONCLUSION: Patients admitted with unstable angina had low inpatient mortality but a 12% rate of subsequent myocardial infarction. Braunwald low-risk unstable angina patients were not admitted to the coronary care unit. Braunwald high-risk patients were more likely to develop a subsequent myocardial infarction. Stratification of patients into intermediate or high-risk groups did not relate to initial medical management or subsequent revascularisation. Thus, while this method of risk stratification may predict cardiovascular events, it may be of limited clinical use in the New Zealand environment.     

Increased functional load on mouse kidney proximal tubule epithelial cells causes changes in nucleolar 3-D architecture

Ultrastructural 3-D analysis of nucleolar architecture and Ag-NOR protein distribution in mouse kidney-cortex proximal-tubule epithelium has been performed. A principal scheme of structural changes of the nucleolus and organization of its components during the intensification of pre-rRNA synthesis (dynamic model of a nucleolus) based on computer spatial modelling has been advanced. According to the nucleolar composition, three groups of cells, which differ from each other by rRNA synthesis, are defined in normal kidney. Most nephron proximal-section cells (about 52%) are characterized by lower activity of RNA synthesis. Such kind of cells are defined as group I (nucleolar diameter 0.7-1.5 microm) and always contain resting, ring-shaped or close to ring-shaped dense nucleoli, which have 2 or 3 fibrillar centers. Nucleoli of group II cells (about 37%, nucleolar diameter 1.5-2.5 microm) have a higher level of activity, contain 4-7 fibrillar centers, and their structural organization is close to reticulated forms due to the first indications of vacuolar network (identified as prereticulated nucleoli). The most active cells of group III (about 11%, nucleolar diameter 2.5-3.5 microm) include cells with typical reticulated nucleoli with a well expressed vacuolar network and numerous fibrillar centers (18-22). Increased functional load of the epithelium caused by unilateral nephrectomy and diuretic (4-chlor-H [2-furylmethyl] 5-sulphamyl-antranic acid) injection changed the proportion of the different cell groups: group I decreased (about 25%), whereas groups II and III increased (about 8% and 17%, respectively). The increase of nucleolar activity first causes a deformation of the individual fibrillar centers as well as complication and growth of their surface. Further, a progressive fragmentation of the fibrillar centers and the growth of their total volume is observed. The complication and growth of the total volume of Ag-positive zones is another indication of the nucleolar activation. The vacuolar system develops by a gradual fusion of small isolated cavities into a united vacuolar network. Nucleoli with 2-7 fibrillar centers are considered to be intermediate forms reflecting successive stages of its activation or inactivation: from the resting ring-shaped nucleolus via transient stages of increasing functional activity to the active reticulated nucleoli and vice versa. The observed differences in the nucleolar ultrastructure are regarded as evidence of the functional heterogeneity of cell populations within one functional segment of nephron.