T-cell-mediated activation of macrophages

Functionally diverse subpopulations of macrophages and lymphocytes, a wide array of stimulatory signals, and an enormous effector repertoire of activated macrophages keeps this field dynamically active. We review new advances in the identification of cytokines that interact to activate macrophages, and in the discovery of effector molecules used by activated macrophages to destroy their targets.     

The effect of neuroleptics and other psychotropic drugs on negative symptoms in schizophrenia

It has been hypothesized that the negative symptoms of schizophrenia are related to structural brain abnormalities and respond poorly to treatment with neuroleptics and other drugs since they are persistent, if not irreversible. Because this issue has important clinical and theoretical implications, the authors reviewed the relevant literature on the effect of neuroleptics, L-dopa, and other psychotropic agents on these symptoms. Contrary to the above conclusions, several large scale, controlled studies of the therapeutic effects of conventional neuroleptics have reported clinically relevant improvement in negative symptoms in a significant proportion of schizophrenics. The improvement tended to occur early in the course of treatment and was most notable in those patients with relatively shorter durations of illness. A specific class of neuroleptic drugs not studied in these earlier large scale trials, the diphenylbutylpiperidines, has been suggested to be particularly likely to ameliorate negative symptoms, possibly because of their significant calcium channel blocking action. A review of the clinical studies comparing this group of neuroleptics with those from different classes supports the suggestion that they can produce greater improvement in anergia and emotional withdrawal. Six open and four controlled trials of L-dopa treatment of negative symptoms with L-dopa alone or in combination with neuroleptics. As with neuroleptics alone, improvement tended to be greater in those with a shorter duration of illness. The available evidence suggests that negative symptoms, at least in less chronic schizophrenic patients, may be partially responsive to currently available pharmacological intervention in a significant proportion of schizophrenics.     

Increased content of a minor ankyrin in erythrocyte membranes of bipolar subjects

This preliminary study reports on the increased content of a structurally important protein in erythrocyte membranes of bipolar patients treated with lithium carbonate compared with control subjects. The external portion of the erythrocyte membrane is a lipid bilayer into which various integral proteins are inserted; some of these serve as ion channels or energy-dependent transport systems. Another group of proteins, including those termed "ankyrins," link the bilayer to an underlying network of cytoskeletal proteins, and maintain both cell shape and the arrangement of integral proteins within the bilayer. Structural changes resulting from the observed excess of one of the ankyrins in membranes from bipolar subjects could alter several aspects of membrane function. Ankyrins also occur in neurons, where a corresponding increase would alter central nervous system function.     

Inhibition of human immunodeficiency virus infection in monocytes by monoclonal antibodies against leukocyte adhesion molecules.

CD4 is the surface receptor for HIV envelope. Some evidence exists, however, that other cell surface receptors may be involved in viral entry subsequent to the initial binding of gp120 to CD4. Antibodies to leukocyte integrin LFA-1, a major component of intercellular adhesive interactions, have been shown to inhibit HIV-induced syncytia formation. Using a stringent system for in vitro HIV infection of human leukocytes, we examine the ability of some monoclonal antibodies (mAb) against various adhesion-related molecules to block or partially inhibit productive viral replication. HIV-1 infection of target monocytes or T cells by cell-free virus was blocked completely or partially by some mAb that prevent cell-cell interactions (CD4, HLA-DR, LFA-1, LFA-3), but not by others (ICAM-1, MAC-1, gp150.95, CD2, CD3, CD14). The capacity for mAb to block HIV infection appears to be epitope-specific, and does not relate to the ability to block homotypic adhesion. HIV transmission from infected cells was more difficult to block than was infection by cell-free virus. Adhesion molecules may be involved in facilitating early stages of HIV infection, following gp120/CD4 binding but prior to viral integration, in a manner distinct from cell-cell adhesion.     

Separate and variably shaped chromosome arm domains are disclosed by chromosome arm painting in human cell nuclei

Fluorescence in situ hybridization (FISH) with microdissection probes from human chromosomes 3 and 6 was applied to visualize arm and subregional band domains in human amniotic fluid cell nuclei. Confocal laser scanning microscopy and quantitative three-dimensional image analysis showed a pronounced variability of p- and q-arm domain arrangements and shapes. Apparent intermingling of neighbouring arm domains was limited to the domain surface. Three-dimensional distance measurements with pter and qter probes supported a high variability of chromosome territory folding.     

Endocarditis with ruptured cerebral aneurysm caused by Cardiobacterium valvarum sp. nov

A fastidious gram-negative bacterium was isolated from the blood of a 37-year-old man who had insidious endocarditis with a sudden rupture of a cerebral aneurysm. Characterization of the organism through phylogenetic and phenotypic analyses revealed a novel species of Cardiobacterium, for which the name Cardiobacterium valvarum sp. nov. is proposed. C. valvarum will supplement the current sole species Cardiobacterium hominis, a known cause of endocarditis. Surgeries and antibiotic treatment cured the patient's infection and associated complications. During cardiac surgery, a congenital bicuspid aortic valve was found to be the predisposing factor for his endocarditis.     

Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge

Summary The effects of massive destruction of granule cells of the fascia dentata on the spatial and temporal firing characteristics of pyramidal cells in the CA1 and CA3 subfields of the hippocampus were examined in freely moving rats. Microinjections of the neurotoxin colchicine were made at a number of levels along the septo-temporal axis of the dentate gyri of both hemispheres, resulting in destruction of over 75% of the granule cells. By contrast there was relatively little damage to the pyramidal cell fields. As assessed by three different behavioral tests, the colchicine treatment resulted in severe spatial learning deficits. Single units were recorded from the CA1 and CA3 subfields using the stereotrode recording method while the animals performed a forced choice behavioral task on the radial 8-arm maze. Considering the extent of damage to the dentate gyrus, which has hitherto been considered to be the main source of afferent information to the CA fields, there was remarkably little effect on the spatial selectivity of place cell discharge on the maze, as compared to recordings from control animals. There was, however, a change in the temporal firing characteristics of these cells, which was manifested primarily as an increase in the likelihood of burst discharge. The main conclusion derived from these findings is that most of the spatial information exhibited by hippocampal pyramidal cells is likely to be transmitted from the cortex by routes other than the traditional trisynaptic circuit. These routes may include the direct projections from entorhinal layers II and III to CA3 and CA1, respectively.