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The joint fluids of 37 patients with rheumatoid arthritis, eight patients with traumatic injuries to their joints, two patients with Reiter's syndrome and three patients with psoriatic arthritis were tested for the presence of B cell colony stimulating activity (B cell CSA). B cell CSA was found in all of the joint fluids from the patients with rheumatoid arthritis but in none of the joint fluids from patients with traumatic injuries to their joints or in the joint fluids from the patients with Reiter's syndrome. A trace of B cell CSA was found in the joint fluid of one of the three patients with psoriatic arthritis. There was a positive correlation (r = 0.796) between the amount of rheumatoid factor present in the joint fluids and the titre of B cell CSA. This correlation was highly significant (P less than 0.001). The B cell CSA was localized to component(s) with molecular weight ranges 115-129 kD and 64-72 kD and an isoelectric point of 6.8. Its activity was sensitive to reduction with 2-mercaptoethanol and to the oxidising action of potassium periodate.

Four amines, galactosamine, mannosamine, histamine and arginine were studied for their effects on platelet aggregation, platelet morphological changes, platelet protein phosphorylation and platelet secretion. Galactosamine inhibited platelet aggregation in response to arachidonic acid and ionophore A23187 but did not inhibit changes in platelet morphology, or in platelet protein phosphorylation in response to these agents and only partially inhibited platelet secretion. The results suggest that galactosamine can be used as a selective inhibitor of platelet-platelet attachment without having a significant effect on intracellular processes. Mannosamine was similar to galactosamine except that it partially suppressed phosphorylation of myosin light chain. Histamine was similar to mannosamine except that some platelet damage was seen in platelets exposed to histamine and arachidonic acid or ionophore A23187. Arginine was non-selective: it suppressed platelet aggregation, secretion and phosphorylation of myosin light chain and a 40 kDa protein (40P) in response to arachidonic acid and ionophore A23187. Arginine was also potent in suppressing platelet morphological changes. When the same four amines were evaluated for their effects on thrombin-induced aggregation; secretion was inhibited concomitantly with inhibition of aggregation. Inhibition of myosin light chain and 40P phosphorylation was evident with galactosamine, suggesting that when thrombin is used as the agonist, galactosamine is not a specific inhibitor of platelet-platelet attachment. These amines therefore have various effects on platelet responses. Under some conditions and with arachidonic acid or ionophore A23187 as agonist, one of them, galactosamine, can be used as a selective inhibitor of platelet-platelet attachment.

The detection and recording of vibration emission from human joints, a technique which we have termed "vibration arthrography", is a sensitive, non-invasive method for the objective study of the locomotor system. Using vibration sensors attached to bony prominences around the knee, we studied the joints of both normal and symptomatic subjects. Normal subjects produced three signal types--physiological patellofemoral crepitus, patellar clicks, and the lateral band signal. In symptomatic subjects we identified and categorised many signal types and related them to pathology. Lesions of the menisci produced distinctive signals, and it was possible not only to lateralise the tear, but in many cases to determine the type of meniscal injury present. Vibration arthrography promises to be a useful tool in the non-invasive diagnosis of knee disorders.

Platelet responses to halothane in normal individuals and in patients susceptible to malignant hyperthermia were evaluated. Platelets in platelet-rich plasma from both normal controls and patients underwent aggregation in response to halothane. There was no significant difference in the degree of aggregation between normal subjects and patients. Aggregation by halothane was associated with a change in platelet shape, centralization of platelet granules, and phosphorylation of platelet actin binding protein, myosin light chain, and a 40 000-dalton protein. Aggregation induced by halothane could be inhibited by EGTA, PGE1, adenosine and verapamil, but not by aspirin. Aggregation induced by halothane could be potentiated by small doses of adrenaline or ADP and in some individuals by caffeine. However, previous exposure of platelets to halothane made them subsequently less aggregable to ADP. The results of these studies do not support a use of halothane-induced aggregation of platelets to detect an abnormality in individuals susceptible to malignant hyperthermia, but do provide new evidence of the effects of halothane on cellular function.

As an intermediate stage in the development of an expert system to support undergraduate teaching in rheumatology, a decision tree incorporating the diagnostic criteria to be used in the expert system was produced by a team of rheumatologists. In a controlled trial, 119 final-year medical students each diagnosed 10 rheumatology cases, drawn from a pool of 96 cases, with or without the aid of the decision tree. Students who used the decision tree correctly diagnosed the following conditions more frequently than the control group: polymyalgia rheumatica (p less than 0.05), myopathies (p less than 0.01), systemic lupus erythematosus (p less than 0.05), pyrophosphate arthropathy (p less than 0.05), seronegative spondylarthropathies (p less than 0.01), intra-articular bleeding (p less than 0.05) and traumatic synovitis (p less than 0.05). The overall diagnostic accuracy of the students who used the decision tree was 81% compared with 68% for the control group (p less than 0.001).

As can be seen from this review, protein phosphorylation appears involved in both positive and negative regulation of platelets. To date, good evidence has been presented for the involvement of protein phosphorylation in the regulation of granule centralization (i.e. myosin light chain phosphorylation). It is probable that protein phosphorylation may also be involved in granule labilization, pseudopod formation and ATP synthesis. Protein phosphorylation in association with platelet activation appears mediated through calcium flux, in the case of myosin light chain phosphorylation, and through diglyceride or other substances in the case of 47P phosphorylation. A summary scheme is shown in Figure 1.

Human B cell colonies were grown from peripheral blood of 12 patients with systemic lupus erythematosus (SLE) and from 12 healthy control subjects. The SLE group showed a large increase (p less than 0.001) in the number of colony forming cells (CFC) present in peripheral blood as compared with controls. The CFC were of the pre-B cell type. There was also a loss of OKT8+ cell inhibition of B cell colony growth in the SLE group compared with control subjects.

Fifty patients whose sera contained a speckled antinuclear antibody (ANA) were interviewed and examined to determine if there was any relationship between their clinical manifestations and the presence of certain serological markers. The results suggest that speckled ANA is usually found in patients with definite connective tissue diseases, but a significant minority have incomplete or early stages of these diseases. Characterisation of the antibody to extractable nuclear antigen (ENA) and other serological markers does not normally assist in making a clinical diagnosis, but the detection of a speckled ANA should prompt further investigation and careful follow-up.

We describe the development of a simple and highly sensitive double antibody sandwich enzyme-linked immunosorbent assay (ELISA) for measuring IgG and IgM anticardiolipin antibodies (ACA). Microtitre plates were coated with cardiolipin at a concentration of 45 micrograms/ml by evaporation under nitrogen. Non-specific binding of diluted sera was eliminated by blocking of plates with 10% fetal calf serum in phosphate buffered saline (PBS/FCS) for 2 h. Then sera (100 microliters) at a dilution of 1:100 were incubated in the wells for 1 h. Affinity purified goat anti-human IgG or IgM (100 microliters) at a concentration of 1 microgram/ml was subsequently added and allowed to incubate for 1 h; detection of ACA was achieved using an alkaline phosphatase conjugated rabbit anti-goat IgG reagent by reading the colorimetric yield at 405 nm after incubation with substrate. Reference serum pools were established to study reproducibility of the assay throughout its sensitivity range, and Standard curves were established. The quantitative normal range was 0-9.0 Anticardiolipin ELISA Units (AEU) for IgG and 0-8.0 (AEU) for IgM-ACA. A strong correlation was found between the ELISA and radioimmunoassay methods for measuring ACA of both IgG and IgM classes. Results from 65 patients with systemic lupus erythematosus (SLE) and 45 patients with seropositive rheumatoid arthritis are also reported. The advantages of the ELISA method for quantitative determination of ACA levels, should make it a useful and reliable method for clinical and experimental monitoring of patients with SLE and associated autoimmune disorders.

The detection of sounds from the human body for diagnostic purposes has a long history. In the respiratory and circulatory systems such auscultation is a precise science yielding much useful information. The detection and interpretation of joint sounds, however, has been much less successful in its development. In this paper we outline the history of joint auscultation, of phonoarthrography, and of their modern equivalent: vibration arthrography. The relative merits of acoustic and vibration based systems are discussed and these are illustrated with data from simultaneous recordings of several joint phenomena. Finally, we concluded that the future of phonoarthrography as a clinical test is based on its further development using accelerometers rather than microphones as detectors.

In this paper, the principles of vibration arthrography are briefly described and the analysis of the resulting signals is explained. Using such a system, localisation of signals from within the joint is possible. Finally, the development of a vibration-based arthrographic system is proposed as a safe, relatively inexpensive, and totally non-invasive aid to the diagnosis of internal disease of the knee.

Antipyrine is a pyrazole derivative used extensively as a marker for hepatic drug metabolizing enzyme activity. A subject participating in a clinical trial employing antipyrine experienced an acute allergic reaction to the drug which was characterized by diaphoresis, flushing, swelling of the throat, difficulty in breathing, vomiting, swelling of the upper lip, and a diffuse urticarial rash. Intravenous administration of diphenhydramine markedly improved the symptomatology. Clinical investigators as well as study participants should be alerted to the potential for antipyrine to cause an acute allergic reaction.

Bacterial endotoxin at concentrations of 0.03 mug/ml enhanced the following responses, each of which reflects calcium influx: (1) contraction of spiral intestine retractor muscle of dogfish; (2) amplitude of postsynaptic potential of squid giant synapse as a function of presynaptic depolarization; (3) membrane responses of deep abdominal extensor muscle of crayfish, stimulated intracellularly; and (4) slow transient (calcium) current in trabeculae of frog atrium under voltage clamp. Corticosteroid antagonized the endotoxin effect on the smooth muscle, not on the frog atrial current. One mechanism of action of endotoxin may be to increase transmembrane calcium currents.

The absorption of the low-energy radiation from iodine-125 under certain circumstances may be a serious disadvantage in its use as a radioisotopic tracer.

Vaccinia virus was irradiated in vacuo with low-voltage electrons of restricted ranges. It was found that the pock-forming ability of the virus was not decreased after bombardment with electrons penetrating 100 A beneath the virus surface. There was very slight reduction in titer with large doses of electrons penetrating 330 A, but a sudden marked drop in infectivity occurred after exposure to electrons penetrating 500 to 700 A. Electrons of higher energies, including those capable of penetrating the virus particle completely, did not produce significant further fall in infectivity titer. It is concluded that a highly radiation-sensitive unit essential for pock formation is situated 500 to 700 A beneath the surface of the virus particle, possibly in the form of a shell. The relation of this finding to the known structure of the virus and to other radiation data on the dimensions of the infectious unit is discussed.