Outer membrane protein YadA of enteropathogenic yersiniae mediates specific binding to cellular but not plasma fibronectin.

The binding of bacteria or bacterial products to host proteins of tissue extracellular matrix may be a mechanism of tissue adherence. We investigated interactions of the plasmid-encoded outer membrane protein YadA, which confers pathogenic functions on enteropathogenic yersiniae, with fibronectin. Attachment of YadA-positive and YadA-negative recombinant Yersinia enterocolitica strains to cartilage-derived human cellular fibronectin and human plasma fibronectin in the solid phase revealed that YadA mediates binding of yersiniae to cellular fibronectin in a saturable, concentration-dependent manner. The interaction could be inhibited by an anti-YadA-specific anti-serum. An anti-beta 1-integrin antibody and the synthetic peptide G-R-G-D-S-P, representing the binding site for alpha 5 beta 1-integrin on fibronectin, did not block attachment of YadA-positive yersiniae to cellular fibronectin, indicating a binding site for YadA on cellular fibronectin independent of the R-G-D-S-containing site. By contrast, YadA failed to mediate binding to plasma fibronectin immobilized on nitrocellulose or plastic surfaces. These observations provide evidence for the hypothesis that the binding region for YadA in cellular fibronectin is not present in plasma fibronectin. This study is the first report on differential binding of bacteria to splicing variants of fibronectin. Further experiments might answer the question whether binding of YadA to cellular fibronectin contributes to the pathogenesis of yersiniae, both to the initial adhesion of the bacteria to the matrices of the host and to the arthritogenic potential of enteropathogenic yersiniae.     

Comparison of ultrasonographic findings in spontaneous abortions with normal and abnormal karyotypes

To determine whether ultrasonographic findings can predict the karyotype of spontaneous abortions, 137 pregnancies (54 spontaneous, 83 assisted ovulatory cycles) that subsequently aborted and had chromosome analysis performed on the products of conception were studied ultrasonographically. Transvaginal ultrasound was performed using an Acuson 128XP/10 with 7.5 MHz probe. The numbers of empty gestational sacs, small and normal for gestational size, embryonic poles and embryos with documented cardiac activity were calculated. The frequency of each of these findings in pregnancies with normal and abnormal karyotypes was compared. Of the 137 spontaneous abortions, 51 had normal chromosome analyses and 86 had abnormal karyotypes (68 aneuploidies and 18 polyploidies). Ultrasonographic findings in the 51 karyotypically normal pregnancies included 16 (31%) with empty gestational sacs, and 35 (69%) with embryonic poles, of which 24 (69%) were at least 1 week smaller than expected for gestational age and 11 (31%) were the expected size. Embryonic cardiac activity was documented in 22 (63%) of the 35 embryonic poles. Amongst 86 pregnancies with abnormal karyotypes, similar frequencies of ultrasound findings were found: 23 (27%) with empty gestational sacs, 42 (67%) with embryonic poles smaller than expected for gestational age, and 50 (79%) embryos lost after documentation of embryonic cardiac activity. No differences in the frequency of ultrasonographic findings of empty gestational sacs, small embryonic pole and embryonic cardiac activity were observed between karyotypically normal and abnormal spontaneous abortions. Ultrasonographic findings cannot predict the karyotype of spontaneous abortions.      

Cytokines and the chronic inflammation of rheumatic disease. I. The presence of interleukin-1 in synovial fluids

Synovial fluids from patients with rheumatoid arthritis (13 cases), ankylosing spondylitis (six), psoriatic arthritis (two), osteoarthritis (three) and rubella arthritis (four) contain interleukin-1 (Il-1) activity as measured in the CH3/He mouse thymocyte assay. That this activity is Il-1 was shown by: (i) the time course of thymocyte stimulation; (ii) failure of PHA blast cells to absorb out the activity; (iii) molecular weight of 15,000-20,000 daltons, and (iv) ability to stimulate prostaglandin E2 production from synovial cells. These results indicate that IL-1 is an important mediator in the inflammatory pathway of different types of joint disease.     

Effects of concurrent inspiratory and expiratory muscle training on respiratory and exercise performance in competitive swimmers

The efficiency of the respiratory system presents significant limitations on the bodys ability to perform exercise due to the effects of the increased work of breathing, respiratory muscle fatigue, and dyspnoea. Respiratory muscle training is an intervention that may be able to address these limitations, but the impact of respiratory muscle training on exercise performance remains controversial. Therefore, in this study we evaluated the effects of a 12-week (10 sessions week^–1) concurrent inspiratory and expiratory muscle training (CRMT) program in 34 adolescent competitive swimmers. The CRMT program consisted of 6 weeks during which the experimental group (E, n=17) performed CRMT and the sham group (S, n=17) performed sham CRMT, followed by 6 weeks when the E and S groups performed CRMT of differing intensities. CRMT training resulted in a significant improvement in forced inspiratory volume in 1 s (FIV_1.0) (P=0.050) and forced expiratory volume in 1 s (FEV_1.0) (P=0.045) in the E group, which exceeded the S groups results. Significant improvements in pulmonary function, breathing power, and chemoreflex ventilation threshold were observed in both groups, and there was a trend toward an improvement in swimming critical speed after 12 weeks of training (P=0.08). We concluded that although swim training results in attenuation of the ventilatory response to hypercapnia and in improvements in pulmonary function and sustainable breathing power, supplemental respiratory muscle training has no additional effect except on dynamic pulmonary function variables.     

Heterogeneity in synaptic transmission along a Drosophila larval motor axon

At the Drosophila melanogaster larval neuromuscular junction (NMJ), a motor neuron releases glutamate from 30-100 boutons onto the muscle it innervates. How transmission strength is distributed among the boutons of the NMJ is unknown. To address this, we created synapcam, a version of the Ca2+ reporter Cameleon. Synapcam localizes to the postsynaptic terminal and selectively reports Ca2+ influx through glutamate receptors (GluRs) with single-impulse and single-bouton resolution. GluR-based Ca2+ signals were uniform within a given connection (that is, a given bouton/postsynaptic terminal pair) but differed considerably among connections of an NMJ. A steep gradient of transmission strength was observed along axonal branches, from weak proximal connections to strong distal ones. Presynaptic imaging showed a matching axonal gradient, with higher Ca2+ influx and exocytosis at distal boutons. The results suggest that transmission strength is mainly determined presynaptically at the level of individual boutons, possibly by one or more factors existing in a gradient.     

Brief intense exercise followed by passive recovery modifies the pattern of fuel use in humans during subsequent sustained intermittent exercise

The role of work period duration as the principal factor influencing carbohydrate metabolism during intermittent exercise has been investigated. Fuel oxidation rates and muscle glycogen and free carnitine content were compared between two protocols of sustained intermittent intense exercise with identical treadmill speed and total work duration. In the first experiment subjects (n=6) completed 40 min of intermittent treadmill running involving a work : recovery cycle of 6 : 9 s or 24 : 36 s on separate days. With 24 : 36 s exercise a higher rate of carbohydrate oxidation approached significance (P=0.057), whilst fat oxidation rate was lower (P ≤ 0.01) and plasma lactate concentration higher (P ≤ 0.01). Muscle glycogen was lower post‐exercise with 24 : 36 s (P ≤ 0.05). Muscle free carnitine decreased (P ≤ 0.05), but there was no difference between protocols. In the second experiment a separate group of subjects (n=5) repeated the intermittent exercise protocols with the addition of a 10‐min bout of intense exercise, followed by 43 ± 5 min passive recovery, prior to sustained (40 min) intermittent exercise. For this experiment the difference in fuel use observed previously between 6 : 9 s and 24 : 36 s was abolished. Carbohydrate and fat oxidation, plasma lactate and muscle glycogen levels were similar in 6 : 9 s and 24 : 36 s. When compared with the first experiment, this result was because of reduced carbohydrate oxidation in 24 : 36 s (P ≤ 0.05). There was no difference, and no change, in muscle free carnitine between protocols. A 10‐min bout of intense exercise, followed by 43 ± 5 min of passive recovery, substantially modifies fuel use during subsequent intermittent intense exercise.     

Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection

BACKGROUND AND METHODS. Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. RESULTS. At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. CONCLUSIONS. Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.