Biomedical subjects
Publications and source records attributed to A Martini.
A macrophage activation syndrome, possibly related to methotrexate toxicity, developed in a boy with systemic juvenile rheumatoid arthritis. Corticosteroid administration was ineffective, whereas a prompt response to cyclosporine was observed. Two months later, Pneumocystis carinii pneumonia developed.
We report the results of a systematic study on the association of antiphospholipid antibodies (aPLs) with some neurological disease other than stroke in a childhood population. Patients affected by migraine, benign intracranial hypertension (BIH) or unilateral movement disorders, such as hemichorea and hemidystonia with acute-subacute onset, were screened for aPLs. None of them had clinical or serological evidence of Systemic Lupus Erythematosus (SLE) or other connective tissue disease. Moderate to high levels of anticardiolipin antibodies (aCL) and/or positive Lupus Anticoagulant (LA) were demonstrated in 6 out of 17 patients with migraine, in 3 out of 4 patients with BIH and in all of the 5 patients showing unilateral movement disorders. The association between aPLs and these neurological conditions, usually regarded as cryptogenic, may suggest a possible pathogenetic mechanism.
A three-generation BO family is presented: the proband showed, in addition to branchio-oto malformations, a severe condition with growth retardation, mandibular hypoplasia and vertebral anomalies resembling the oculo-auriculo-vertebral (OAV) phenotype. This family study supports the hypothesis of Rollnick and Kaye that the OAV spectrum may represent, in some cases, an extreme component of the BOR syndrome. The finding has relevant implications for genetic counselling regarding both conditions.
BACKGROUND: Abnormalities of pulmonary function have been found in children with systemic lupus erythematosus (SLE) even in the absence of clinical or radiographic evidence of pulmonary involvement. It is unknown whether these abnormalities represent an early sign of progressive lung disease or whether they are associated with disease activity. METHODS: After a mean of 4.5 years, respiratory function (forced vital capacity (FVC) and single breath gas transfer factor (TLCO)) and disease activity were reexamined in 13 of 15 previously studied children with SLE. Disease activity was assessed by a validated index of SLE activity (SLE activity measure (SLAM)). RESULTS: In spite of the high prevalence of abnormalities of respiratory function at the baseline investigation, no chest radiographic abnormalities or overt clinical signs of lung disease were found at baseline, in the interval between the two investigations, or at the re-evaluation in any patient. From baseline to the second investigation the mean value of SLAM decreased and there was a trend toward an improvement in FVC and TLCO. TLCO was more severely impaired than FVC, being found as an isolated abnormality in a high percentage of patients (45% at baseline and 35% at follow up). There was a relationship between baseline TLCO and disease activity, expressed as a SLAM score. Moreover, there was a correlation between the changes in the SLAM score from baseline to the second investigation and the corresponding changes in the TLCO value, but not with the corresponding changes in the FVC value. CONCLUSIONS: In this series of patients the decrease in SLE activity from the first to the second investigation was associated with an improvement in pulmonary function. The presence of early isolated functional abnormalities was not associated with subsequent development of lung disease.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Application of clofilium to the endolymphatic side of the isolated frog semicircular canal abolished the transepithelial potential and produced increased K and mannitol outfluxes from the lumen to the dark cells or the basolateral perilymph, with no apparent effect on active K secretion. These results suggest an increased permeability of the paracellular pathway. When applied to the perilymphatic side in the intact labyrinth, clofilium reduced the rates of quantal transmitter release (miniature EPSP frequency), an effect that might arise from a decrease in the transduction current intensity secondary to the reduced transepithelial electrochemical potential for K+. Moreover, afferent spike rates were almost completely abolished at rest as well as during mechanical stimulation. This effect together with a decreased mEPSP amplitude points to a further direct action of clofilium on the afferent postsynaptic terminal. These results suggest a multi-factorial effect of clofilium that would reduce the sensitivity of the vestibular function.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A modified procedure is proposed for chromosomal DNA extraction based on a cell-wall lytic enzyme never applied before in pulsed field gel electrophoresis. Protoplasting efficiency is retained under very challenging conditions for enzyme activity, such as those required for non-Saccharomyces yeasts often characterized by cell walls highly resistant to lysis.
The effects of 1-[2-(4-fluorophenyl)cyclohexyl]-2-[4-(3-phenylalkyl)-piperazin -1-yl]- ethanol, LU52396, on a) Ca2+ influx across the plasma membrane and b) Ca2+ mobilization from intracellular rapidly-exchanging Ca2+ stores were investigated in HeLa cells and in isolated microsomal fractions derived from the cerebellum and the skeletal muscle. LU52396 was found to be a potent inhibitor (Ki of about 2 microM) of the Ca2+ influx activated by depletion of intracellular Ca2+ stores, a phenomenon referred to as store-dependent or capacitative Ca2+ influx. Such an effect, which was reversed by cell washing, was mediated neither by a depolarization of the cell, with decrease in the driving force for cation influx, nor by a change of the intracellular pH, and might therefore be due to a direct action of the drug on either the responsible channel in the plasma membrane or, less likely, on its regulatory mechanisms. Additional effects, i.e. inhibition of receptor-mediated Ca2+ influx, of Ca2+ release from intracellular stores via either inositol 1,4,5-trisphosphate or ryanodine receptors, and of Ca2+ reuptake into the stores via sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPases, were also induced by the drug, however at concentrations 20-fold or more than those effective on the store-dependent influx. To our knowledge LU52396 is the first pharmacological tool that is found to be addressed with some preference to the store-dependent Ca2+ influx. It promises, therefore, to be useful for the characterization of the process, the identification of the responsible channel and, possibly, also of the molecular mechanisms through which these channels operate.
Archaic speculations and firmly established legends regarding the origin of the yeast Saccharomyces cerevisiae and related species are revisited in light of past and recent ecological evidence pointing to a strict association with artificial, man-made environments such as wineries and fermentation plants. The nomenclature within this industrially important group is also discussed in view of the modifications imposed from application of molecular techniques to classification.
In juvenile chronic arthritis (JCA) the indices of disease activity, such as joint swelling, pain, tenderness, and limitation of motion, may poorly correlate with the degree of functional impairment. Since the improvement of functional capacity is one of the main objectives of treatment, we evaluated the effect of methotrexate (MTX) in 29 children with JCA by assessing both the articular indices and a functional status measure. After 6 months of therapy, 15 of the 29 patients had a significant (> or = 50%) reduction in the number of joints with active arthritis and/or the articular severity score and were then judged as responders, while 14 did not respond to MTX. In the responder group, the median functional index score decreased from 17 (range: 13-27) at baseline to 13 (range: 13-15) at 6 months (p < 0.001); the median score of the non-responder group was 20 both at baseline and at 6 months (ranges: 14-27, and 13-36, respectively). These results show an improvement of functional impairment in those patients who respond to MTX according to the conventional indices of articular inflammation.
We report here a glycogen storage myopathy type V associated with multifocal encephalopathy. The patient, a 43-year-old male with increased serum CK, a heavy drinker and smoker, had been affected by generalized epilepsy since age 24, after a cranial injury. He had had a right hemiparesis 2 years before coming to our observation and a transient left hemiparesis the following year. CT and MRI of the brain showed multiple hemispheric lesions consistent with an ischemic process, as suggested by single photon emission tomography of the brain. Muscle biopsy showed a vacuolar myopathy, and myophosphorylase activity was 13% of the normal mean. Phosphorus magnetic resonance spectroscopy (31P-MRS) performed on resting calf muscles showed increased PCr to ATP and decreased PCr to P(i) ratios. During both aerobic and ischemic exercise 31P-MRS failed to show any cytosolic acidification and phosphomonoesters (PME) accumulation, two MRS findings in agreement with McArdle's syndrome diagnosis. Mitochondrial respiration was also affected as shown by a low PCr to P(i) ratio at rest and by a low rate of PCr re-synthesis during recovery from aerobic exercise. This latter finding in McArdle's disease can be explained by decreased mitochondrial substrate availability, which in turn can contribute to the phenotypic manifestations of the disease.
A novel 'multistep molecular mimicry' mechanism for induction of rheumatoid arthritis (RA) by bacterial antigens that activate T lymphocytes previously 'educated' by peptides derived from a class of human histocompatibility antigens is reported here. These antigens have the amino acid sequence QKRAA, which is also present on the Escherichia coli heat-shock protein dnaJ. Synovial fluid cells of early RA patients have strong immune responses to the bacterial antigen, but cells from normal subjects or controls with other autoimmune diseases do not. The activated T cells may cross-react with autologous dnaJ heat-shock proteins that are expressed at synovial sites of inflammation. Our findings may have direct relevance to new strategies for the immune therapy of RA.
Isoenzymatic characterization was done on 100 isolates obtained from visceral leishmaniasis (VL) patients coinfected with human immunodeficiency virus (HIV); isolates had been received between 1986 and 1993 at the International Leishmania Cryobank and Identification Centre in Montpellier, France. Electrophoresis was done with 15 isoenzymes using the starch gel technique combined, where appropriate, with isoelectrofocusing. Nine Leishmania infantum zymodemes were identified; L. infantum zymodeme MON-1, the most common parasite of human VL in the Mediterranean basin, was the most frequent in coinfections. It could also occasionally be responsible for localized cutaneous leishmaniasis lesions. Several dermotropic zymodemes, which were responsible for localized cutaneous leishmaniasis in immunocompetent patients, caused VL in HIV-positive patients. In addition, in 10 patients, a second isolate obtained during relapses occurring between 1.5 and 9.0 months after treatment was identical to the original isolate.
This study aimed to measure IgG reactivities to DNA-free nucleosome subparticles (H2AH2B, H3H4) and nucleosome subparticles (H2AH2B-DNA, H3H4-DNA) and to evaluate the temporal relation of these reactivities, as well as those to single core histones, with iridocyclitis (IC) in patients with antinuclear antibody positive (ANA+) pauciarticular juvenile chronic arthritis (JCA). Reactivities to nuclear substrates were determined by enzymatic immunoassays in 120 sera from 45 children with ANA+ pauciarticular JCA. Significantly elevated IgG levels to H3 and H4, to DNA-free nucleosome subparticles, and to the nucleosome subparticle H3H4-DNA were present in patients with ANA+ pauciarticular JCA; no evidence of recognition of conformational epitopes was found. In both horizontal and follow-up studies, no relation between the reactivities studied and the development, presence, or history of IC was found. Our results show the absence of a relation of antibodies to histone molecules or to nucleosome subparticles with IC in patients with ANA+ pauciarticular JCA.
Behçet's disease and Takayasu's disease in children are uncommon and may have an insidious course leading to a delayed diagnosis. Both diseases usually occur in late childhood, although disease onset in the first year of life has been reported. Compared with adults, Behçet's disease in children appears to be characterized by a lower incidence of ocular and vascular involvement, and Takayasu's disease by a higher incidence of systemic symptoms. The reported characteristics of both diseases in children are reviewed.