Macrophages and CD4+ T lymphocytes from two multiply exposed, uninfected individuals resist infection with primary non-syncytium-inducing isolates of human immunodeficiency virus type 1

Despite multiple, high-risk sexual exposures, some individuals remain uninfected with human immunodeficiency virus type 1 (HIV-1). CD4+ lymphocytes from these individuals are less susceptible to infection in vitro with some strains of HIV-1, suggesting that the phenotype of the virus may influence its ability to interact with certain CD4+ cells. In the present study, we examined the susceptibility of CD4+ T lymphocytes and macrophages from two exposed uninfected individuals (EU2 and EU3) to infection with a panel of biologically cloned isolates of HIV-1 having either a non-syncytium-inducing (NSI) or a syncytium-inducing (SI) phenotype. Our results indicate that CD4+ T lymphocytes from EU2 and EU3 are resistant to infection with NSI isolates of HIV-1 but are susceptible to infection with primary SI isolates. In addition, we found that macrophages from EU2 and EU3 are resistant to infection with both NSI and SI isolates. The latter finding was confirmed by using several uncloned NSI and SI isolates obtained from patients during acute HIV-1 infection. In further experiments, env clones encoding glycoproteins characteristic of NSI or SI viruses were used in single-cycle infectivity assays to evaluate infection of CD4+ lymphocytes and macrophages from EU2 and EU3. Consistent with our previous results, we found that macrophages from these individuals are resistant to infection with NSI and SI env-pseudotyped viruses, while CD4+ T lymphocytes are resistant to NSI, but not SI, pseudotyped viruses. Overall, our results demonstrate that CD4+ cells from two exposed uninfected individuals resist infection in vitro with primary, macrophage-tropic, NSI isolates of HIV-1, which is the predominant viral phenotype found following HIV-1 transmission. Furthermore, infection with NSI isolates was blocked in both CD4+ T lymphocytes and macrophages from these individuals, suggesting that there may be a common mechanism for resistance in both cell types.     

Glucose repression/derepression in budding yeast: SNF1 protein kinase is activated by phosphorylation under derepressing conditions, and this correlates with a high AMP:ATP ratio

BACKGROUND: Genetic studies of Saccharomyces cerevisiae have shown that Snf1p and Snf4p, which together form the SNF1 complex, are essential for gene derepression on removal of glucose from the medium. However the metabolic signal(s) involved, and the exact role of SNF1, have remained enigmatic. Recently, the AMP-activated protein kinase (AMPK) was shown to be the mammalian homologue of SNF1. AMPK is activated by the elevation of the cellular AMP:ATP ratio, which occurs during cellular stress in mammalian cells. The mechanism of activation involves phosphorylation of AMPK by an upstream protein kinase (AMPKK). We have investigated whether a similar mechanism might explain the role of SNF1 in yeast in the response to the stress of glucose starvation. RESULTS: The protein kinase activity of SNF1 was dramatically and rapidly activated by phosphorylation on removal of glucose from the medium. SNF1 was not activated directly by AMP, but could be inactivated by protein phosphatases and reactivated by mammalian AMPKK. We also demonstrated that an endogenous SNF1-reactivating factor, most likely an upstream protein kinase, is present in yeast extracts. Under a variety of different growth conditions, there was a correlation between cellular adenine nucleotide levels and the activation state of SNF1. CONCLUSIONS: Apart from the lack of direct allosteric activation of SNF1 by AMP, the regulation of the mammalian AMPK and yeast SNF1 protein kinase cascades is highly conserved. Adenine nucleotides are now good candidates for metabolic signals which indicate the lack of glucose in the medium, triggering activation of SNF1 and derepression of glucose-repressed genes.     

Soluble tumour necrosis factor receptor release after anti-CD3 monoclonal antibody treatment in mice is independent of tumour necrosis factor-alpha release

The involvement of TNF-alpha in the release of soluble TNF receptors was assessed in mice, treated with anti-CD3 monoclonal antibodies. After treatment with three different anti-CD3 mAb, we simultaneously studied serum levels of TNF-alpha, soluble TNF receptor P55 and P75. All three anti-CD3 mAb triggered the release of both of the soluble TNF receptors, whereas only one of the anti-CD3 mAb triggered TNF-alpha release. These data demonstrate that in our model soluble TNF receptor release is independent of TNF-alpha release.     

The milk-alkali syndrome caused by betelnuts in oyster shell paste

We report anesthetic management of 6 cases (5 patients) with dilated cardiomyopathy for noncardiac surgery. The severity of their cardiomyopathy evaluated by left ventricular ejection fraction (LVEF) utilizing echocardiography was different in each case. The management of anesthesia was divided into 3 steps according to the LVEF. In cases with LVEF over 0.45, it was possible to perform regular anesthetic management by carefully selecting and controlling anesthetic agents. In 2 cases with LVEF from 0.2 to 0.4, anesthetic management was difficult. Some vasoactive drugs (e.g. dopamine) and intensive monitoring devices (e.g. pulmonary artery catheter) were needed to optimize anesthetic course. In one case with LVEF less than 0.2, we discussed much about surgical indication. Because of the malignant nature of the tumor, we agreed to proceed. IABP was inserted preoperatively and this proved to be life-saving during the procedure. It is important to have an inter-departmental discussion on these severely compromised cases.     

Color coded ultrasound--quantification of perfusion in a perfusion model

One patient with acute and transient functional psychosis was assessed repeatedly using a brief neuropsychological assessment during his recovery from the psychotic episode. The psychotic features of the patient were characterized by perplexed behavior, attentional disturbance and emotional turmoil. Characteristic findings, including impairment of attention tests, dysgraphia and constructional disturbances, were seen. Findings improved in accordance with recovery on a behavioral level. We discussed the similarity of neuropsychological and behavioral abnormalities of this patient and those of patients in an acute confusional state.     

Effects of pyriproxyfen on engorged females and newly oviposited eggs of the lone star tick (Acari:Ixodidae)

Engorged females and 1- to 3-d-old eggs of the lone star tick, Amblyomma americanum (L), were exposed to 9 treatments of pyriproxyfen (4, 8, and 16 micrograms/cm2) in glass vials at exposure periods of 7 d, 14 d, and continuous at each dosage level. Treatment of newly engorged females did not affect the number of females ovipositing, but the number of eggs oviposited decreased as dosage and exposure time increased. Complete inhibition of egg hatch occurred at all treatment levels except that of the lowest dosage and exposure time where 99.9% inhibition was observed. Egg masses from treated females contained eggs that turned a dark amber color and imploded, retained normal shape and color without visible evidence of embryogenesis, or had developed embryos that were unable to emerge. Treatments of 1-to 3-d-old eggs were effective in reducing hatch and larval survivorship to 25 d after emergence only at the continuous exposures of dosages of 4, 8, and 16 micrograms/cm2. Larvae emerging from eggs treated at the lower dosage rates of 0.2 and 0.02 microgram/cm2 were as successful in feeding on chickens and subsequently molting as acetone treated control ticks.     

Accuracy of direct signs of tears of the anterior cruciate ligament

OBJECTIVE: To evaluate the accuracy of direct magnetic resonance imaging (MRI) signs of tears of the anterior cruciate ligament. PATIENTS AND METHODS: Over the period April 1991 to February 1994, 92 consecutive MRI studies of the knee were obtained for which arthroscopic data were also available. The MRI studies were retrospectively evaluated for course, continuity, signal intensity, morphologic features, contour and visualization of the anterior cruciate ligament. Arthroscopic findings were correlated with individual primary signs and the overall MRI diagnosis. RESULTS: Among the cases studied were 4 partial and 32 complete tears of the anterior cruciate ligament (as determined by arthroscopy). Because of the low number of partial tears, it was not possible to draw any meaningful conclusions about the MRI diagnosis of this type of tear. For complete tears, the criteria with the highest accuracy were abnormal course of the ligament (96.0%) and high signal intensity (89.3%). The overall diagnostic accuracy of MRI was 98.8%. CONCLUSIONS: The most accurate direct MRI finding in patients with a complete tear of the anterior cruciate ligament was abnormal course of the ligament, followed by abnormally high signal intensity.