Wall effects in sucrose density gradient centrifugation of viruses

Summary The depletion of sedimenting particles to be expected from wall effects in the course of sucrose gradient centrifugation, was computed for various types of swing-out rotors on the assumption that particles hitting the tube wall are lost from the gradient.This assumption was roughly verified for heat-denatured, but not for native poliovirus. Tween 20 reduced the depletion, and prevented tight sticking of heat-denatured virus particles to tube walls.     

Neocortical and hippocampal EEG in normal and lateral hypothalamic-damaged rats

Cortical and hippocampal EEG were correlated with behavior in rats before and after bilateral hypothalamic (LH) damage. In Stage 1 of recovery (aphagia and adipsia), the neocortex showed continuous large amplitude slow activity. It did not desynchronize during spontaneous acts such as grooming as well as during tail pinch-induced struggling or orienting, even though a slow form of hippocampal theta accompanied these acts. However, during Stage 2 (anorexia), the neocortical EEG did desynchronize when such theta appeared. Therefore, as behavioral recovery progresses after LH damage, there appears to be a concomitant recovery of cortical participation in such behavior. Early in recovery, LH rats, unlike normals, showed slow (3–4.5 Hz) atropine-sensitive hippocampal theta during automatisms such as grooming as well as during immobility. Thus, LH damage, while temporarily abolishing fast. noncholinergic theta, appears to release slow cholinergic theta. Later in recovery, faster atropine-resistant (noncholinergic) theta becomes functional again.     

大鼠眶皮质的间脑和脑干的传入投射

目的：研究间脑和脑干对眶皮质的传入投射。方法：ＨＲＰ逆行示踪法。结果：将ＨＲＰ分别导入１８只大鼠的内侧及腹侧眶区、腹外侧内和外侧区后，在同侧丘脑背内侧核中可见密集的标记细胞，并有一定的局部定位，其次在内丘脑的胶状核、前内侧核、菱形核、腹我侧和腹内侧核中可见大量标记细胞。在同侧下丘脑餐侧区、背侧区、未定带和背内侧核中可见少量标记细胞。在脑干的黑质致密部、腹侧被盖区、中缝背核、导水管周灰质中也可见标记     

Differential activation of mouse hepatitis virus-specific CD4+ cytotoxic T cells is defined by peptide length.

In this study we have characterized the core epitope recognized by the MHV-A59-specific CD4+ cytotoxic T lymphocyte (CTL) clones HS1 and B6.1, derived from BALB/c and C57/BL6 mice, respectively. These CD4+ clones respond to the promiscuous peptide fragment S-329-343 of the glycoprotein S of MHV-A59. The results indicate that the core peptides of both clones overlap but are not identical. The core region of the HS1 clone is an 8-mer, and comprises the amino acid residues S-332-339, whereas the minimal epitope for clone B6.1 is a 9-mer and comprises the amino acid residues S-334-342. The peptide fragment S-329-343 activates all T-cell effector functions, including proliferation, cytokine secretion and cytolysis. However, in the present study we show that T-cell activation is not an all-or-none phenomenon, in which T-cell stimulation leads to activation of all T-cell effector functions. It appears that changes in the length of a peptide ligand can differentially activate the cytolytic machinery from proliferation and cytokine secretion. Furthermore, the results indicate that, in our case, modulation of the flanking residues of the core epitopes did not convert the cytokine profile of polarized T-helper type-1 (Th1) clones into a Th2-type pattern.     

A microiontophoretic study of the action of kainic acid and putative neurotransmitters in the rat mesencephalic trigeminal nucleus

The ‘excitotoxic’ hypothesis proposes that neurotoxic amino acids exert their effect through neuronal excitation (Olney, Ho &;Rhee, 1971).Colonnier, Steriade &;Landry (1979) have found that trigeminal mesencephalic neurons in the cat are resistant to the neurotoxic effect of kainic acid. In the present study it was found that the same neurons in the rat also resist the cytotoxic action of this amino acid. In addition, kainic acid, applied iontophoretically onto these neurons failed to alter their firing frequency. The resistance of these neurons to both neurotoxic and excitatory actions of kainic acid is consistent with the ‘excitotoxic’ hypothesis.Other putative neurotransmitters were applied by microiontophoresis on these neurons and none were found to alter their rate of discharge. Procaine however applied with relatively low ejecting currents consistently reduced their firing rates. The failure of the putative neurotransmitters tested to influence the rate of discharge of the trigeminal mesencephalic neurons suggests that the chemical synapses present on these neurons in the rat (Hinrichsen &;Larramendi, 1970) utilize another neurotransmitter from those tested. Alternatively the synapses might have a role other than the direct regulation of the firing frequency of these primary afferent neurons.     

Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases and pathologies of the central nervous system

In this review we focus on peptide- and peptidomimetic-based approaches that target autoimmune diseases and some pathologies of the central nervous system. Special attention is given to asthma, allergic rhinitis, osteoarthritis, and Alzheimer's disease, but other related pathologies are also reviewed, although to a lesser degree. Among others, drugs like Diacerhein and its active form Rhein, Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed against the common beta-chain of cytokine receptors, are described below as well as attempts to target beta-amyloid peptide aggregation. Parts of the review are also dedicated to targeting of pathologic conditions in the brain and in other tissues with peptides as well as methods to deliver larger molecules through the "blood--brain barrier" by exploring receptor-mediated transport, or elsewhere in the body by using peptides as carriers through cellular membranes. In addition to highlighting current developments in the field, we also propose, for future drug targets, the components of the inflammasome protein complex, which is believed to initiate the activation of caspase- 1 dependent signaling events, as well as other pathways that signal inflammation. Thus we discuss the possibility of targeting inflammasome components for negative or positive modulation of an inflammatory response.     

Risk factors for antibiotic-resistant Escherichia coli isolated from hospitalized patients with urinary tract infections: a prospective study

From November 1998 to February 1999 we prospectively evaluated the prevalence of resistance to penicillins, cephalosporins, carbapenem, quinolones, aminoglycosides, and trimethoprim-sulfamethoxazole (SXT) in 320 Escherichia coli isolates isolated from hospitalized patients with acute urinary tract infections (UTIs). We also studied for these strains risk factors for resistance to amoxicillin-clavulanic acid (AMC), fluoroquinolones (FQs), and SXT. Resistance rates were consistent with those from major recent studies reported in the literature. Multivariate analyses selected the following factors as being significantly associated with E. coli resistance: (i) for resistance to AMC, prior (1 year) UTI (odds ratio [OR] = 2.71, P = 0.006), prior (1 year) urinary catheter (OR = 2.98, P = 0.0025), and prior (6 months) antibiotic exposure (OR = 2.68, P = 0.005); (ii) for resistance to FQs male sex (OR = 3.87, P = 0.03), with a trend toward significance for age >65 years (OR = 7.67, P = 0.06) and prior (1 year) UTI (OR = 2.98, P = 0.07); and (iii) for resistance to SXT, male sex (OR = 1.91, P = 0.046), hospitalization in an intermediate-term-care unit (OR = 2.18, P = 0.008), and prior (1 year) UTI (OR = 2.03, P = 0.03). Ours results suggest that prior UTI is a common risk factor for resistance to the different antibiotics tested. Although few studies on risk factors for E. coli resistance to antibiotics have been published, careful interpretation of their findings, taking into consideration the population, infection site, and period studied, should contribute to the formulation of a better strategy that can be used to overcome antibiotic resistance.     

Detection of human immunodeficiency virus type 1 (HIV-1) in heel prick blood on filter paper from children born to HIV-1-seropositive mothers.

The human immunodeficiency virus type 1 (HIV-1) DNA PCR results of 94 dried blood spot (DBS) samples on filter paper and corresponding venous blood in EDTA obtained from infants born to HIV-1-seropositive mothers were compared. In addition, the results of HIV-1 DNA PCR on DBS and the HIV-1 RNA PCR from plasma of 70 paired samples were compared. A 100% specificity and a 95% sensitivity for HIV-1 DNA PCR on DBS compared with results for venous blood were observed for the 94 paired samples. The results of the DBS HIV-1 DNA PCR and HIV-1 RNA PCR of 70 corresponding plasma samples correlated perfectly (100%). The DBS HIV-1 DNA PCR method proved reliable for HIV-1 detection.