Characterization of a new HLA-B39 allele, B*3913, in a Brazilian Caucasian

We report a case of paraplegia in the immediate postoperative period following right bilobectomy for carcinoma of the lung. An epidural catheter had been inserted following induction of anaesthesia and an infusion of bupivacaine 0.15% was used for postoperative pain relief. Magnetic resonance imaging failed to reveal any spinal or epidural haematoma or spinal cord ischaemia. The patient developed respiratory failure on the third postoperative day and required assisted ventilation. He was weaned from the ventilator on day 15. Two days later he sustained a cardiac arrest and died. Post-mortem examination demonstrated spinal cord infarction and severely stenosed spinal arteries. The thoracotomy position and/or intra-operative hypotension might have compromised the blood flow to the spinal cord and although suspected as a possible cause, the use of epidural analgesia was not implicated.     

The development of novel and selective p56lck tyrosine kinase inhibitors

Early T-cell receptor mediated signal transduction involves the activation of several tyrosine protein kinases. One of these tyrosine kinases, p56lck, is expressed primarily in T-cells and Natural Killer (NK) cells and has been shown to be critical for their proliferative and effector functions. Indandiones have been identified as a potent and selective chemical class that inhibits p56lck.     

Sonographic incidence of deep venous thrombosis contralateral to hip or knee replacement surgery

PURPOSE: This study assesses the sonographic incidence of deep venous thrombosis (DVT) contralateral to and the venographic incidence ipsilateral to hip or knee replacement surgery and the role of sonography in routine surveillance. METHODS: We prospectively evaluated 178 consecutive patients with sonography of the femoropopliteal venous systems of the contralateral lower extremity and venography of the ipsilateral lower extremity on days 3 and 4, respectively, after total hip or knee replacement surgery. RESULTS: No cases of acute DVT and only 1 case of chronic DVT isolated to the popliteal system were identified by sonography in the contralateral extremity. In the ipsilateral extremity, venography identified 26 patients with acute DVT (3 femoropopliteal, 21 calf, and 2 concurrent femoropopliteal and calf). CONCLUSIONS: Routine sonographic evaluation of the lower extremity contralateral to hip or knee replacement surgery is not cost-effective because of the extremely low incidence of detectable acute thrombus.     

The effects of a health promotion-health protection intervention on behavior change: the WellWorks Study

OBJECTIVES: This study assessed the effects of a 2-year integrated health promotion-health protection work-site intervention on changes in dietary habits and cigarette smoking. METHODS: A randomized, controlled intervention study used the work site as the unit of intervention and analysis; it included 24 predominantly manufacturing work sites in Massachusetts (250-2500 workers per site). Behaviors were assessed in self-administered surveys (n = 2386; completion rates = 61% at baseline, 62% at final). Three key intervention elements targeted health behavior change: (1) joint worker-management participation in program planning and implementation, (2) consultation with management on work-site environmental changes, and (3) health education programs. RESULTS: Significant differences between intervention and control work sites included reductions in the percentage of calories consumed as fat (2.3% vs 1.5% kcal) and increases in servings of fruit and vegetables (10% vs 4% increase). The intervention had a significant effect on fiber consumption among skilled and unskilled laborers. No significant effects were observed for smoking cessation. CONCLUSIONS: Although the size of the effects of this intervention are modest, on a populationwide basis effects of this size could have a large impact on cancer-related and coronary heart disease end points.     

Neutralizing antibodies from the sera of human immunodeficiency virus type 1-infected individuals bind to monomeric gp120 and oligomeric gp140

Antibodies that neutralize primary isolates of human immunodeficiency virus type 1 (HIV-1) appear during HIV-1 infection but are difficult to elicit by immunization with current vaccine products comprised of monomeric forms of HIV-1 envelope glycoprotein gp120. The limited neutralizing antibody response generated by gp120 vaccine products could be due to the absence or inaccessibility of the relevant epitopes. To determine whether neutralizing antibodies from HIV-1-infected patients bind to epitopes accessible on monomeric gp120 and/or oligomeric gp140 (ogp140), purified total immunoglobulin from the sera of two HIV-1-infected patients as well as pooled HIV immune globulin were selectively depleted of antibodies which bound to immobilized gp120 or ogp140. After passage of each immunoglobulin preparation through the respective columns, antibody titers against gp120 and ogp140 were specifically reduced at least 128-fold. The gp120- and gp140-depleted antibody fraction from each serum displayed reduced neutralization activity against three primary and two T-cell line-adapted (TCLA) HIV-1 isolates. Significant residual neutralizing activity, however, persisted in the depleted sera, indicating additional neutralizing antibody specificities. gp120- and ogp140-specific antibodies eluted from each column neutralized both primary and TCLA viruses. These data demonstrate the presence and accessibility of epitopes on both monomeric gp120 and ogp140 that are specific for antibodies that are capable of neutralizing primary isolates of HIV-1. Thus, the difficulties associated with eliciting neutralizing antibodies by using current monomeric gp120 subunit vaccines may be related less to improper protein structure and more to ineffective immunogen formulation and/or presentation.     

Hypothalamic synaptogenesis and its relationship with the maturation of hormonal secretion

1. Information obtained during the last decade has demonstrated that hypothalamic neurons release a wide variety of neuroactive substances, such as neurotransmitters, mostly monoamines and amino acids, and neuromodulators such as the peptides vasopressin (AVP) and oxytocin (OXT) and hypophysial releasing hormones. 2. Synapse formation between hypothalamic neurons was followed at different times within a given nucleus and among different nuclei during development of the mouse hypothalamus. 3. The amounts of various neurotransmitters and hormones were determined at various stages of development. 4. A correlation is presented of the biochemical and ultrastructural features and their functional implications during maturation.     

Regulation of action-potential firing in spiny neurons of the rat neostriatum in vivo

Both silent and spontaneously firing spiny projection neurons have been described in the neostriatum, but the reason for their differences in firing activity are unknown. We compared properties of spontaneously firing and silent spiny neurons in urethan-anesthetized rats. Neurons were identified as spiny projection neurons after labeling by intracellular injection of biocytin. The threshold for action-potential firing was measured under three different conditions: 1) electrical stimulation of the contralateral cerebral cortex, 2) brief directly applied current pulses, and 3) spontaneous action-potentials occurring during spontaneous episodes of depolarization ( state). The average membrane potential and the amplitude of noiselike fluctuations of membrane potential in the state were determined by fitting a Gaussian curve to the membrane-potential distribution. All neurons in the sample exhibited spontaneous membrane potential shifts between a hyperpolarized state and a depolarized state, but not all fired action potentials while in the state. The difference between the spontaneously firing and the silent spiny neurons was in the average membrane potential in the state, which was significantly more depolarized in the spontaneously firing than in the silent spiny neurons. There were no significant differences in the threshold, the amplitude of the noiselike fluctuations of membrane potential in the state, or in the proportion of time that the membrane potential was in the state. In both spontaneously firing and silent neurons, the threshold for action potentials evoked by current pulses was significantly higher than for those evoked by cortical stimulation. Application of more intense current pulses that reproduced the excitatory postsynaptic potential rate of rise produced firing at correspondingly lower thresholds. Because the membrane potential in the state is mainly determined by the balance between the synaptic drive and the outward potassium conductances activated in the subthreshold range of membrane potentials, either or both of these factors may determine whether firing occurs in response to spontaneous afferent activity.     

Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina

BACKGROUND: Systemic markers of inflammation have been found in unstable angina. Disruption of culprit coronary stenoses may cause a greater inflammatory response in patients with unstable than those with stable angina. We assessed the time course of C-reactive protein (CRP), serum amyloid A protein (SAA), and interleukin-6 (IL-6) after single-vessel PTCA in 30 patients with stable and 56 patients with unstable angina (protocol A). We also studied 12 patients with stable and 15 with unstable angina after diagnostic coronary angiography (protocol B). METHODS AND RESULTS: Peripheral blood samples were taken before and 6, 24, 48, and 72 hours after PTCA or angiography. In protocol A, baseline CRP, SAA, and IL-6 levels were normal in 87% of stable and 29% of unstable patients. After PTCA, CRP, SAA, and IL-6 did not change in stable patients and unstable patients with normal baseline levels but increased in unstable patients with raised baseline levels (all P<0.001). In protocol B, CRP, SAA, and IL-6 did not change in stable angina patients after angiography but increased in unstable angina patients (all P<0.05). Baseline CRP and SAA levels correlated with their peak values after PTCA and angiography (all P<0.001). CONCLUSIONS: Our data suggest that plaque rupture per se is not the main cause of the acute-phase protein increase in unstable angina and that increased baseline levels of acute-phase proteins are a marker of the hyperresponsiveness of the inflammatory system even to small stimuli. Thus, an enhanced inflammatory response to nonspecific stimuli may be involved in the pathogenesis of unstable angina.     

Potent inhibitors of the MAP kinase p38

The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines TNF-alpha and IL-1. We have developed a novel series of potent p38 inhibitors that could lead to new methods of treatment for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.     

Theory and practice of isoelectric focusing of interacting systems

The theory of mass transport coupled to reversible protein interactions forms the basis for computer simulation of the isoelectric focusing behavior of several model systems. These include pH-dependent conformational transition, carrier ampholyte-induced interactions and protein-ligand interactions. The computational results compare favorably with experimental observations. In addition, a method is formulated for an isoelectric focusing procedure which enables determination of intrinsic ligand-binding constants for statistical binding of a charged ligand, binding to heterogeneous sites, and cooperative binding.