β-N-Acetylhexosaminadases in human cerebrospinal fluid and serum of patients with multiple sclerosis

β-N-Acetylhexosaminidase activity and isoenzyme have been investigated in normal human cerebrospinal fluid and that of patients with multiple sclerosis. β-N-acetylhexosaminidase activity in normal cerebrospinal fluids has been resolved into five components. The major component was in a form that eluted from DEAE cellulose at the same salt concentration as hexosaminidase As, the isoenzyme previously identified in human serum. Cerebrospinal fluid from patients exhibited a different isoenzyme profile, showing a remarkable increase in a form having a pI which was more acidic than that of As. These changes have a potential use in the diagnosis and further biochemical characterization of multiple sclerosis.     

MR findings in pituitary haemosiderosis

A girl with Diamond-Blackfan syndrome and hypopituitarism was suspected of having pituitary haemosiderosis because of the clinical picture and the long history of blood transfusions. On T1-weighted MR images the pituitary exhibited a markedly hypointense anterior lobe (mimicking the empty sella), suggesting iron deposition, while on T2W MRI the low signal of the pituitary was surrounded by the high signal of the CSF. MR may be considered the examination of choice for detecting iron overload in the pituitary. Received: 10 November 1997 Accepted: 21 November 1997     

Laparoscopic Treatment of Gallbladder and Common Bile Duct Stones: A Prospective Study

n = 2), port site infection ( n = 2), and subumbilical hematoma ( n = 1). Major morbidity was bile leakage from the cystic duct stump in two cases due to clips or transcystic duct drainage displacement, respectively. One elderly, high risk patient died after being referred for several failed attempts of endoscopic clearance; she died from cardiogenic shock 3 days after successful laparoscopic treatment. Laparoscopic CBD exploration is feasible and safe in most patients, with short-term results that compare favorably with the results of sequential ES/LC reported in the literature.     

Dopamine receptors on human T- and B-lymphocytes

The presence of functional dopamine receptors on differentiated cells of the mammalian immune system is still under discussion. This study has utilized (-)-[³H]sulpride as a ligand to detect the presence of recognition sites of the dopamine D₂ receptor family on human T- and B-lymphocytes. The (-)-[³H]sulpiride binding was of high affinity (K_d 0.9 nM ± 0.2 nM, specific, saturable (B_max 10.2 ± 1.4 fmol/10⁶ cells) and reversible. The pharmacological characterization of the recognition site suggests, similarities mainly with the D₂ and D₄ rather than D₃ subtype of dopamine receptor. Furthermore, dopamine treatment was able to reduce the intracellular cAMP levels of lymphocytes stimulated with forskolin, thus suggesting a potential functional significance of this dopamine receptor in mediating neural-immune interactions.     

Prevalence of hereditary ataxias and spastic paraplegias in Molise,a region of Italy

Summary An epidemiological survey of hereditary ataxias and paraplegias was conducted in Molise, a region of Italy (335, 211 inhabitants on 1 January 1989). Total prevalence was 7.5 x 10^–5 inhabitants (95% confidence limits 4.8–11.1). There were 7 patients with Friedreich's disease, 5 with early onset cerebellar ataxia with retained tendon reflexes, 4 with ataxia-telangiectasia, 9 with hereditary spastic paraplegias (2 autosomal dominant and 7 autosomal recessive cases). There was no patient with autosomal dominant cerebellar ataxia.     

Profile of in Vitro Binding Affinities of Neuroleptics at Different Rat Brain Receptors: Cluster Analysis Comparison with Pharmacological and Clinical Profiles

A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds.     

Search for poliovirus long-term excretors among patients affected by agammaglobulinemia

Patients with agammaglobulinemia may excrete enteroviruses, including vaccine-derived poliovirus, for prolonged periods of time. This poses a risk to the patients but it also may pose a risk to the population after eradication of poliovirus and the cessation of routine vaccination. To assess this risk, a pilot study was performed to identify potential poliovirus long-term excretors in a cohort of 38 patients with a definite/presumptive diagnosis of X-linked agammaglobulinemia (XLA). Stool samples were analyzed to detect any polio or other enteroviruses replicating in the gut and neutralizing antibodies against polioviruses were measured in the sera. No viruses were isolated from the stool samples and most sera had neutralizing antibody levels against all three poliovirus serotypes considered by the WHO to be protective in immunocompetent individuals. This suggests that long-term excretion of enteroviruses in patients with agammaglobulinemia is relatively uncommon.     

Effect of interferon-alpha therapy on epitope-specific cytotoxic T lymphocyte responses in hepatitis C virus-infected individuals.

The majority of hepatitis C virus (HCV)-infected individuals fail to resolve the infection and become chronically infected despite the presence of HCV-specific CTL responses directed to different HCV-derived peptide antigens. Only a minority of individuals is able to clear the virus by mounting efficient CTL responses early after acute infection, but at present it is not clear whether viral clearance is associated with CTL responses of defined specificity. To elucidate those responses associated with improvement of the disease, we analyzed CTL responses to 16 different HLA-A2-presented, HCV-derived epitopes in 12 chronically infected patients, 14 chronically infected patients treated with interferon-alpha, and in one patient with acute symptomatic disease. We show here that the majority of chronically infected individuals present CTL responses directed to an NS4-derived peptide antigen (amino acids 1789-1797). Treated patients presented stronger HCV-specific CTL responses and therapy-induced changes in CTL target choice. In particular, 13 out of 14 individuals responded to an NS3-derived epitope (amino acids 1073-1081). By longitudinal analysis we show that five individuals responding to IFN-alpha therapy with decreases in alanine aminotransferase levels presented a strong CTL activity directed to the NS3-derived epitope. One patient that spontaneously resolved the infection presented a generally strong CTL activity specific for HCV-derived epitopes with a dominant response to the NS3-derived peptide antigen. This suggests that CTL responses directed to this NS3-derived antigen may be beneficial for the control of HCV infection. Improvement of these responses may represent a therapeutic intervention in chronic HCV infection.