Differential sensitivity of selected rat brain areas to excitatory neurotransmitters released by K+ depolarization

When injected intrathecally in mice in a volume of 5 microliter, adenosine had no effect on tail-flick or hot-plate reaction latencies at dosages up to 1 mM concentration. There were no other behavioral effects observed either. Injecting 1 mM of the adenosine receptor agonist, 5'-N-ethylcarboxamide adenosine (NECA) caused both motor paralysis of the hind-legs with a duration of approximately 4 h and simultaneous antinociception. A slight weakness of the hindlegs, but a profound antinociceptive effect, was observed after the 100 microM dose only. After 10 microM, there was no effect on motor behavior but still a prolongation of the tail-flick and hot-plate reaction latencies. Pretreatment with the adenosine receptor antagonist theophylline attenuated the antinociceptive effect of NECA. Activation of spinal adenosine receptors thus appears to selectively elicit analgesia.     

A new syndrome of triphalangeal thumbs and brachy-ectrodactyly

Two Mexican families in which a total of 17 persons exhibited the same pattern of limb malformations are described. The syndrome is characterized by triphalangeal thumbs and brachydactyly affecting the index fingers and the third toes. The clinical findings are variable and the inheritance is autosomal dominant. The syndrome, to the best of our knowledge, has not been described before.     

"Tissue" transglutaminase in AIDS

Apoptosis or programmed cell death (PCD) is an active process of cellular self-destruction, essential for embryonic development and maintenance of homeostasis of multicellular organisms. Programmed cell death induction can serve as a defence mechanism of the host against intracellular microbes. Virus infections trigger host cell apoptosis, which can either limit virus production or contribute directly to viral pathogenesis.Several independent laboratories have identified "tissue" transglutaminase (tTG) as a potentially important player of the cell death program(s). This gene is specifically expressed in cells dying during mammalian development as well as in those undergoing apoptosis in various patho-physiological and experimental settings [Eur. J. Cell Biol. 56 (1991) 170; Piacentini, M., Davies, P.J.A., Fesus, L., 1994. Tissue transglutaminase in cells undergoing apoptosis. In: Tomei, L.D., Cope, F.O. (Eds.), Apoptosis II: The molecular basis of apoptosis in disease. Cold Spring Harbor Lab. Press, pp. 143-165.]. This chapter reviews recent studies concerning the expression and the possible role of "tissue" transglutaminase (tTG) in apoptotic cells; particular emphasis is given to its expression in the cell death pathways associated with HIV infection in the immune system.We propose here that the induction of the tTG gene in cells of the immune system, as well as the detection of the isodipeptide epsilon(gamma-glutamyl)lysine in plasma, are useful markers of apoptosis and might make it possible to monitor disease progression in HIV-infected individuals.     

Mechanisms of MHC class I-restricted antigen processing and cross-presentation

Summary: In this review, we discuss recent data from our laboratory that address two aspects of major histocompatibility complex (MHC) class I‐restricted antigen processing. First, we consider the nature of the peptide‐loading complex, which is the assembly of proteins in the endoplasmic reticulum (ER) into which newly synthesized MHC class I‐β₂ microglobulin (β₂m) heterodimers are incorporated, and the mechanisms involved in MHC class I assembly and peptide loading that are facilitated by the peptide‐loading complex. Second, we discuss mechanisms of cross‐presentation, the phenomenon whereby extracellular and luminal protein antigens can be processed by antigen‐presenting cells, particularly dendritic cells, and presented by MHC class I molecules to CD8⁺ T cells. The focus of the discussion is mainly on the human MHC class I system.     

Vestibular and audiological findings in the Alport syndrome

Alport syndrome (AS) is caused by mutations in collagen IV, which is widespread in the basement membranes of many organs, including the kidneys, eyes, and ears. Whereas the effects of collagen IV changes in the cochlea are well known, no changes have been described in the posterior labyrinth. The aim of this study was to investigate both the auditory and the vestibular function of a group of individuals with AS. Seventeen patients, aged 9–52, underwent audiological tests including pure‐tone and speech audiometry, immittance test and otoacoustic emissions and vestibular tests including video head impulse test, rotatory test, and vestibular evoked myogenic potentials. Hearing loss affected 25% of the males and 27.3% of the females with X‐linked AS. It was sensorineural with a cochlear localization and a variable severity. 50% of the males and 45.4% of the females had a hearing impairment in the high‐frequency range. Otoacoustic emissions were absent in about one‐third of the individuals. A peripheral vestibular dysfunction was present in 75% of the males and 45.4% of the females, with no complaints of vertigo or dizziness. The vestibular impairment was compensated and the vestibulo‐ocular reflex asymmetry was more evident in rotatory tests carried out at lower than higher speeds; a vestibular hypofunction was present in all hearing impaired ears although it was also found in subjects with normal hearing. A posterior labyrinth injury should be hypothesized in AS even when the patient does not manifest hearing disorders or evident signs of renal failure.     

Diltiazem impairs maturation and functions of human dendritic cells

The aim of this study was to define the effects of diltiazem, a calcium antagonist drug used in cardiology and in clinical transplantation, on the differentiation and maturation of human dendritic cells (DC). Herein, we demonstrate that diltiazem, in association with granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), induces monocytes to differentiate into cells with many of the characteristic of DC. However, diltiazem-induced DC express high levels of mannose receptor and Fc gamma RII and, consequently, manifest a higher endocytic activity compared with GM-CSF+IL-4-induced DC. Importantly, diltiazem-induced DCs have an impaired responsiveness to lipopolysaccharide and CD40 ligand because they produce decreased levels of IL-12 and reveal a reduced ability to stimulate alloreactive T-cell responses as well as in inducing interferon-gamma producing Th1 cells. These effects may contribute to a decreased DC-dependent T-cell activation and may help to explain the immunoregulatory function of diltiazem and its effectiveness in preventing transplant rejection.     

Interphase fluorescence in situ hybridization analysis of del(11)(q23) and del(17)(p13) in chronic lymphocytic leukemia. a study of 40 early-onset patients

Although B-cell chronic lymphocytic leukemia (B-CLL) is the most common form of leukemia in Western countries, little is known about its underlying molecular abnormalities and their prognostic significance, particularly for use in early therapeutic interventions in young patients. As TP53 tumor suppressor gene abnormalities and 11q23 deletions are reported to be prognostically adverse in hematologic malignancies, we used interphase fluorescence in situ hybridization to analyze their incidence and prognostic significance in young B-CLL patients. Bone marrow samples from 40 untreated B-CLL patients at diagnosis were studied using five yeast artificial chromosome clones from the 11q23.1 approximately q23.3 chromosomal region and a probe specific for the 17p13.1 locus. Twenty-three patients (58%) carried 11q deletions. Interestingly, 16 of 17 patients (94%) who showed early disease progression exhibited this chromosomal abnormality, suggesting that 11q deletions may help to identify more aggressive disease in early stage patients. In contrast, monoallelic TP53 deletions were found in all of the patients. The TP53 and 11q deletions were only present in a proportion of the clonal B-cells, which suggests that they are secondary events in B-CLL.