Interleukin-6 regulates the cytotoxic effect of tumour necrosis factor on U937 cells.

In this study, we demonstrate that low but not high concentrations of interleukin-6 (IL-6) potentiate the cytotoxic effect of tumour necrosis factor-alpha (TNF-alpha) on U937 cells, in a dose-dependent manner. Killing of U937 cells by 100 U/ml of TNF-alpha, was maximally potentiated by 50 U/ml of IL-6. No potentiation of cell killing was observed when the concentration of IL-6 was increased to 4000 U/ml. At a concentration of 50 U/ml, IL-6 up-regulated TNF receptor expression but no change in TNF receptor number was observed when the concentration of IL-6 was increased to 4000 U/ml. Low concentrations of IL-6 can also induce sub-cytotoxic doses of TNF-alpha (0.1 and 0.33 U/ml) to kill U937 cells. Up-regulation of TNF receptors by IL-6 is dependent on de novo protein synthesis since receptor induction is abolished in the presence of cycloheximide. Taken together the data suggest that the potentiation of cell killing observed by a combination of these lymphokines is mediated in part by IL-6-induced changes in TNF receptor expression.     

Safety and efficacy of a monomeric, functionally intact intravenous IgG preparation in patients with primary immunodeficiency syndromes

Results of an open, phase II clinical trial on therapy with an iv IgG preparation in patients with primary antibody-deficiency syndromes are reported. Three hundred infusions of the product, an intact monomeric IgG preparation, were given to 16 patients for an average of 14 (+/- 0.7) months, the dose being 220 (+/- 26.9) mg/kg/month. Only two minor adverse reactions occurred. This preparation did not produce transient leukopenia on infusion. Preinfusion serum IgG levels increased continuously in the course of treatment (average values: 325 +/- 51 at the beginning of therapy, 438 +/- 59 at 6 months, 568 +/- 75 at 12 months, 631 +/- 52 at the end of treatment). The infusions were well accepted and well tolerated by the patients, and the clinical efficacy was highly superior to intramuscular immunoglobulin.     

Relation between extracellular [K+], membrane potential and contraction in rat soleus muscle: modulation by the Na+-K+ pump

An increased extracellular K⁺ concentration ([K⁺]₀) is thought to cause muscle fatigue. We studied the effects of increasing [K⁺]₀ from 4 mM to 8–14 mM on tetanic contractions in isolated bundles of fibres and whole soleus muscles from the rat. Whereas there was little depression of force at a [K⁺]₀ of 8–9 mM, a further small increase in [K⁺]₀ to 11–14 mM resulted in a large reduction of force. Tetanus depression at 11 mM [K⁺]_o was increased when using weaker stimulation pulses and decreased with stronger pulses. Whereas the tetanic force/resting membrane potential (E _M) relation showed only moderate force depression with depolarization from –74 to –62 mV, a large reduction of force occurred whenE _M fell to –53 mV. The implications of these relations to fatigue are discussed. Partial inhibition of the Na⁺-K⁺ pump with ouabain (10^–6 M) caused additional force loss at 11 mM [K⁺]₀. Salbutamol, insulin, or calcitonin gene-related peptide all stimulated the Na⁺-K⁺ pump in muscles exposed to 11 mM [K⁺ ₀] and induced an average 26–33% recovery of tetanic force. When using stimulation pulses of 0.1 ms, instead of the standard 1.0-ms pulses, force recovery with these agents was 41–44% which was significantly greater (P < 0.025). Only salbutamol caused any recovery ofE _M (1.3 mV). The observations suggest that the increased Na⁺ concentration difference across the sarcolemma, following Na⁺-K⁺ pump stimulation, has an important role in restoring excitability and force.     

Nucleolar organizer regions in transitional cell tumors of the bladder

The traditional silver staining technique that identifies nucleolar organizer region-associated proteins has recently been adapted and applied to paraffin sections, and used to examine changes in nucleolar organizer region numbers in a variety of benign and malignant conditions. We describe herein the enumeration of nucleolar organizer regions in a variety of benign and malignant conditions of the transitional epithelium of the urinary bladder. While there is a statistical separation between normal and neoplastic groups, there is a degree of overlap between normal, inflammatory, dysplastic, and neoplastic urothelium.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

Differential effect of nerve fiber structure on block by local anesthetic

The incidence of conduction block by lidocaine 0.3 mmol/l (8.1 mg/dl) in several successive lengths of individual afferent axons of rabbit was compared. The conduction velocity of the axons was either "slow," "intermediate" (1.3-4 m/s), or "fast." The "intermediate" group showed a higher incidence of proximal acceleration of conduction (P less than 0.001) and a greater incidence of block (P less than 0.001) than the "slow" and "fast" fiber groups. The results were interpreted as indicating that the fibers of the "intermediate" group had an unmyelinated peripheral and a myelinated proximal length, with a junctional heminodal region that was the seat of the high sensitivity to block. The potential clinical significance of the observation is discussed in terms of the known distribution of heminodes in the peripheral nervous system.     

Effects of chronic chlorpromazine or lithium administration on ageing-related lipopigment in rat Purkinje neurones

Ageing-related accumulation of neuronal lipopigment is considered to be debris from processes of renewal of cellular constituents, but can also reflect cell damage and certain diseases. Chlorpromazine (an example of a class of drug chronically administered in psychiatric practice) has been reported to reduce neuronal lipopigment accumulation, and the present study investigated the effects of 28 weeks of chlorpromazine administration on lipopigment in rat Purkinje neurones. The effects of 26 weeks of lithium administration (also chronically administered in psychiatric practice) were also studied. Lipopigment was identified by fluorescence microscopy and the area enclosed by an outline of each discrete region of lipopigment was measured. While lithium administration was not associated with significant changes in lipopigment variables, chlorpromazine administration was associated with a significant (p=0.001) reduction in the number of discrete lipopigment regions and with significant (p=0.001) differences in the numbers of discrete lipopigment regions in various size categories. The findings are similar to those associated with the administration of acetyl-L-carnitine (which has been reported to reduce some morphological and behavioural associations of brain ageing) and are compatible with a reduction in the rate of lipopigment formation. This could reflect an adverse effect of chlorpromazine administration (i.e. reduced functional activity of neurones) or a beneficial effect (i.e. a reduction in ageing-related changes).     

Evaluating the hazard of dodecyl alkyl sulphate to natural ecosystems using indigenous protistan communities

The effect of the surfactant dodecyl alkyl sulphate (C12AS) on the structure and function of lotic protistan assemblages was examined using the Experimental Stream Facility (ESF) operated by the Procter and Gamble Company. Population- and community-level responses to C12AS were monitored on introduced substrates placed in the channels 28 days prior to dosing (mature communities) as well as those placed in the channels on day 0 of dosing (immature communities), to allow for a broad assessment of the effect of the chemical on processes contributing both to community development and maintenance. C12AS appeared to elicit a subsidy response from the native protistan assemblage which may have resulted from both positive and negative responses at trophic levels above and below the assemblage. Protistan responses to the surfactant tended to occur more rapidly and be more sensitive than those documented for invertebrates and fish. C12AS elicited a modest response (i.e. a 20% change) from several reliable parameters including community respiration (reduced dissolved oxygen at 289 g per L), protozoan species richness (increased at 63 g per L) and protozoan community composition (increased dissimilarity at 1254 g per L). Responses to C12AS exceeded expected exposures in the real world by a factor of six or greater thereby indicating that the hazard of exposure to C12AS to stream communities is low. The results of this study support the use of mesocosms as decisive tools for evaluating the hazard posed by consumer product chemicals to natural communities and ecosystems     

Development of inflammation after application of mustard oil or glutamate to the rat temporomandibular joint

Application of the small-fibre excitant and inflammatory irritant mustard oil or the excitatory amino-acid receptor agonist glutamate to the rat temporomandibular joint (TMJ) region evokes similar changes in jaw-muscle activity, suggesting that peripheral application of glutamate may be nociceptive. Application of mustard oil to the TMJ region is also inflammatory, but, it is not clear if application of glutamate is equally inflammatory. In this study the extent of plasma-protein extravasation and oedema induced by mustard oil application to the TMJ region was compared with that induced by glutamate. Application of mustard oil resulted in plasma-protein extravasation into the TMJ tissues and oedema of the TMJ region. In contrast, glutamate did not cause plasma-protein extravasation or oedema.     

Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat

Ischemic preconditioning has been shown to ameliorate injury due to subsequent ischemia in several organs. However, relatively little is known about preconditioning and the kidney. To address this, rats were randomized to control (C, N = 14), 2 min of ischemic preconditioning (P2 N = 10), 3 periods of 2 min of ischemia separated by 5 min periods of reflow (P2,3 N = 7), or three 5 min periods of ischemia separated by 5 min of reflow (P5,3 N = 6) prior to 45 min of bilateral renal ischemia followed by 24 hours of reperfusion. We observed a lower serum creatinine after 24 hours of reflow in P2, P2, 3 but not P5, 3 rats compared with C. Histology was examined in the C and P2, 3 groups and demonstrated less severe injury in the P2, 3 group. To gain insight into the mechanism by which preconditioning ameliorated ischemic injury, we performed near IR spectroscopy and 31P NMR spectroscopy. Based on near IR spectroscopy, the P2, 3 group had closer coupling of cytochrome aa3 redox state with that of hemoglobin during reflow. In the 31P NMR studies, the changes in ATP and pHi were similar during ischemia, but the P2, 3 group recovered ATP and pHi faster than C. These data suggest that ischemic preconditioning may ameliorate ischemic renal injury as assessed by functional, metabolic and morphological methods. The mechanism(s) by which this occurs requires additional study.