Toll-like receptor 7 stimulation promotes autoimmune diabetes in the NOD mouse.

AIMS/HYPOTHESIS: The role of Toll-like receptor 7 (TLR7), a sensor of viral and self RNA, in promoting autoimmune diabetes remains unclear. Our goal was to determine the effect of TLR7 stimulation on the priming and activation of diabetogenic CD8(+) T cells. METHODS: We explored the effects of CL097 (TLR7/8 agonist) and immunoregulatory sequence 661 (IRS661, TLR7 inhibitor) on bone marrow-derived dendritic cells (BMDCs), diabetogenic CD8(+) T cell function and autoimmune diabetes onset in NOD and 8.3 NOD T cell receptor transgenic mice (8.3 NOD mice). RESULTS: TLR7 stimulation of NOD BMDCs increased activation and production of proinflammatory cytokines. In vivo administration of CL097 activated T cells and dendritic cells and increased levels of proinflammatory cytokines and type 1/2 IFNs in NOD mice. In vivo antigen-specific cytotoxicity studies revealed enhanced cytotoxicity against islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP, an islet autoantigen) peptide pulsed targets in NOD mice treated with CL097 plus CD40 agonist. This combination treatment accelerated the onset of autoimmune diabetes in 8.3 NOD mice. Likewise, topical treatment of NOD mice with a TLR7 agonist accelerated diabetes onset. Spontaneous disease in 8.3 NOD mice and accelerated disease in CL097+CD40 agonist-treated 8.3 NOD mice were delayed by IRS661 treatment, which is associated with inhibition of the endogenous upregulation of IFN-α levels within the pancreatic lymph nodes. CONCLUSIONS/INTERPRETATION: TLR7 stimulation accelerates the spontaneous onset of autoimmune diabetes in 8.3 NOD and NOD mice. Conversely, TLR7 inhibition prevents the early events associated with diabetogenesis.

Creutzfeldt-Jakob disease with initial right hemiparesis masquerading as a stroke.

The early stage of sporadic Creutzfeldt-Jakob disease is generally characterised by progressive changes in behaviour and intellectual function. While only a few patients have stroke-like onset, Creutzfeldt-Jakob disease with initial monoparesis has been described. In this report, a patient with an unusual sporadic Creutzfeldt-Jakob disease with typical magnetic resonance imaging findings, positive cerebrospinal fluid 14-3-3 brain protein, sharp-wave complexes in electroencephalogram, and initial right hemiparesis is reported.

Chromosome lesions produced with an argon laser microbeam without dye sensitization.

Improvements in the argon laser microbeam have made it possible to cause damage to chromosomes of tissue culture cells without prior treatment of the cells with a photosensitizing agent. These results have been confirmed independently in two laboratories.

Urgent biliary decompression after endoscopic retrograde cholangiopancreatography.

Acute cholangitis complicating diagnostic endoscopic retrograde cholangiopancreatography (ERCP) is potentially fatal. Among 323 consecutive patients with proved biliary obstruction, 21 (7 percent) developed acute cholangitis after examination. Four patients underwent emergency surgery for the control of sepsis with two deaths. Of the 21 parameters chosen for evaluation, malignant obstruction, fever (higher than 37.5 degrees C) within 72 hours before the procedure or when afebrile, and an increased aspartate transaminase level of 70 IU or more were the independent predictive factors identified by multivariate analysis. An increased temperature should be regarded as an absolute contraindication to examination unless followed by immediate ductal drainage. Since the risk of septic complications is minimal when none of the risk factors are present, routine urgent biliary decompression after ERCP is probably unnecessary for these selected patients. For patients with malignant obstruction or other risk factors, early elective surgical drainage is advisable. When surgery is not feasible, nonoperative drainage of the obstructed biliary system as a preventive measure might be considered.

Classification of sleep patterns by means of markov modeling and correspondence analysis.

Shown is how correspondence analysis can be used to track changes in an individuals' sleep pattern. Correspondence analysis was applied to sleep stage transition matrices computed from all-night sleep of normal, obese, and apnoetic subjects. Differences between the groups, and intraindividual changes in sleep patterns could be visualized better than with a x2-based clustering approach.

Discrimination of an infected brain tumor from a cerebral abscess by combined MR perfusion and diffusion imaging.

The aim of this study was to investigate the signal characteristics of the abscess wall and tumor wall on diffusion-weighted and perfusion-weighted images and thus to evaluate the feasibility of using combined MR diffusion and perfusion imaging to differentiate pyogenic cerebral abscess from infected brain tumor. The tumor wall of various types of cystic or necrotic brain tumor was significantly hyperintense relative to that of cerebral abscess wall on both diffusion-weighted images and regional cerebral blood volume maps. Sixteen patients who had cerebral masses with large cystic or necrotic cavities were imaged to generate diffusion-weighted images and regional cerebral blood volume maps using single-shot echoplanar imaging (EPI) pulse sequences. Apart from qualitative analysis, apparent diffusion coefficients (ADC) as well as regional cerebral blood volume (rCBV) ratios were calculated from the abscess wall and peripheral tumor wall and comparison was made by using Student's t-test. The tumor wall of various types of cystic or necrotic brain tumor had significantly lower ADCs relative to those of the abscess wall (P<0.005) and thus appeared relatively hyperintense on diffusion-weighted images. The mean rCBV ratio relative to normal white matter (2.90+/-0.62) of the peripheral tumor wall of various types of cystic or necrotic brain tumor were significantly larger than the mean rCBV ratio (0.45+/-0.11) of the pyogenic cerebral abscess wall (P<0.001) by Student's t-test. It is concluded that the combined MR diffusion and perfusion imaging might be capable of differentiating an infected brain tumor from a pyogenic cerebral abscess.

An epidemiological study of motor neuron disease in Hong Kong.

Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality. We identified the subjects from the computer database of the government hospital system between 1 January 1997 and 31 January 2002 by searching the ICD code starting from 335.xx. Every retrieved case or their records were reviewed and validated by neurologist(s) of the responsible regional hospitals which the patients attended. One hundred and twenty cases from seven regional hospitals (serving 48.05% of the HKSAR population) were identified, validated and confirmed to be MND or related diseases. Ninety-eight new cases were diagnosed during the study period. Average age of onset was 58.76 years; SD 14.12 (28-89) years. Male to female ratio was 1.72:1. Peak age of onset was 60-64 years without sex difference. The adjusted incidence rate was 0.60/100,000/year. The adjusted point prevalence at the prevalence date (31 January 2001) was 3.04/100,000. Despite the incidence and prevalence of MND among Hong Kong Chinese, it remained low compared to worldwide figures, and our data suggested a significant rise of MND or related disease in the last decade. A territory-wide prospective epidemiological study is indicated.

Structural EEG analysis: an explorative study.

A method is described to detect (subtle) changes in an EEG (electroencephalogram) by means of a Markovian modeling approach. This method, termed structural EEG analysis, treats the non-stationary EEG as a sequence of a finite number of short elementary patterns. Subtle changes in an EEG may be detected by studying the transition probabilities between the different patterns. By viewing the patterns as states in a Markov chain, a representation of the EEG structure based on a state transition probability matrix emerges. Various techniques to estimate the state transition probability matrices have been investigated. A number of experiments were performed with artificially generated data to determine the data length required to obtain a reliable estimate of the transition matrices. It appeared that a data length of approximately five to eight times the number of entries in the matrices is needed to accurately estimate the matrices. It was determined that the data length required to reliably estimate the transition probability matrix is dependent on the number of states and the number of non-zero entries of the matrix. Also, the data length appears independent of the values of the probabilities. The structural analysis approach was applied to actual EEG data, recorded from normal volunteers and epileptic subjects. It was demonstrated that visually confirmable changes in the EEG could be detected by the structural analysis method more accurately than by a more conventional approach.

Changes in composition of the porcine zona pellucida during development of the oocyte to the 2- to 4-cell embryo.

Our objective was to identify any changes that occur in the composition of the porcine zona pellucida during development of the 2- to 4-cell embryo from the oocyte. Oocytes, unfertilized eggs and single and 2- to 4-cell embryos have been recovered surgically and their zonae pellucidae 125I-labelled and analysed individually by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The zonae from ovulated eggs possessed two major glycoproteins Mr250 000 and 90 000 which were absent from follicular oocytes but present in the fluid from the oestrus, but not luteal, oviduct. The glycoproteins remained on the zona pellucida of 2- to 4-cell embryos whose analysis showed the presence of additional polypeptides of Mr 150 000, 57 000, 50 000 and 25 000. It is concluded (i) that shortly after ovulation, and in spite of the presence around the egg of cumulus oophorus and corona radiata cells, significant amounts of oviducal glycoproteins are able to bind firmly to the zona pellucida, and (ii) that after contact with spermatozoa there is evidence of a limited hydrolysis of the structure by the sperm protease acrosin.

A laboratory evaluation of the accuracy and precision of the photovac snapshot portable gas chromatograph and the Dräger Chip Measurement System monitor for benzene in air measurements.

A laboratory evaluation of the accuracy and precision of two field instruments, the Photovac Snapshot Gas Chromatograph and the Dräger Chip Measurement System (CMS) Monitor, both capable of specific determination of benzene, was carried out. The evaluation was based on the generation of a test atmosphere of known concentration of benzene in a stainless steel calibration chamber and simultaneous sampling of the test atmosphere by each instrument. At the same time, the chamber atmosphere was continuously monitored by one or two data logging photoionization detector (PID) hydrocarbon analysers. A series of six, 10-minute charcoal tube air samples of the test atmosphere was also collected over the 1-hour run and analyzed by gas chromatography. Nine different concentrations ranging from 0.25 ppm to 8 ppm were used. Accuracy was evaluated using National Institute for Occupational Safety and Health (NIOSH) criteria. The Photovac GC consistently met the NIOSH recommended accuracy criteria of +/- 25 percent at or below 1 ppm of benzene, whereas the Drager CMS results generally fell slightly outside this criteria. Compared against less stringent accuracy criteria of +/- 35 percent, all Photovac GC results were acceptable but about 40 percent of Drager CMS results were not. The precision of Photovac GC (CV +/- 10%) is better than Drager CMS (CV = +/- 20% to 40%). Both instruments are, however, good field instruments provided their limitations are taken into account in their use.

Hydrocarbon exposures at petroleum bulk terminals and agencies.

Occupational exposures to the 55 hydrocarbon components of gasoline and petroleum products were measured at the bulk terminals and agencies of six Ontario petroleum companies during the summer of 1986. A total of 82 long-term (full-shift) and 111 short-term personal samples were taken over 3 months. The data, expressed as concentrations in milligrams per cubic meter, were highly variable and appeared to fit the lognormal distribution well. Full-shift exposures of bulk terminal drivers, agency drivers, and plantmen to total hydrocarbons (THC), computed as an n-hexane equivalent, and other hydrocarbon components for which exposure limits exist can be expected to exceed their respective 1986-1987 threshold limit value-time-weighted average (TLV-TWA) no greater than 1% of the time on the basis of the lognormal model. The short-term THC exposures of agency truck drivers can be expected to exceed the 1986-1987 TLV-short-term exposure limits about 7% of the time while top-loading and more than 17% while off-loading. For benzene, the short-term exceedance percentages are 1% and 4% for top- and off-loading operations, respectively. For long-term benzene exposures, up to 69% of the assessments can be expected to exceed the 1990-1991 proposed TLV-TWA of 0.3 mg/m3 (0.1 ppm). The full-shift hydrocarbon exposures of agency drivers were significantly higher than those for bulk terminal drivers. At the bulk terminals, the short-term hydrocarbon exposures during top-loading were significantly higher than during bottom-loading.

Laser Raman sensor for measurement of trace-hydrogen gas.

A new optical hydrogen sensor based on spontaneous Raman scattering of laser light has been designed and constructed for rugged field use. It provides good sensitivity (better than 100 parts in 10(6)), rapid response (several seconds), and the inherent Raman characteristics of linearity and background gas independence of the signal. Efficient light collection and discrimination by using fast optics and a bandpass interference filter compensate for the inefficiency of the Raman-scattering process. A multipass optical cavity with a Herriott-type configuration provides intense illumination from an air-cooled cw gas laser. The observed performance is in good agreement with the theoretical signal and noise level predictions.