HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.     

Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes

meta-Iodobenzylguanidine, an adrenal imaging agent used for the scintigraphic detection of human pheochromocytoma, is a substrate for the monoamine uptake system of chromaffin granules. It is accumulated by bovine chromaffin granule membrane vesicles in the presence of ATP, and it can be released by an osmotic shock. The uptake is dependent upon the generation of an H+-electrochemical gradient by an ATP-dependent H+ pump since it is blocked by an H+ ionophore and since meta-iodobenzylguanidine uptake can be driven by imposing an artificial pH gradient (inside acidic) on the membrane vesicles. The transport is saturable and its Km value (2.0 microM at pH 8.0) is similar to that of noradrenaline (5.3 microM). Transport occurs through the monoamine transporter since it is blocked by the same inhibitors, tetrabenazine and reserpine, and also by the transporter substrates noradrenaline and serotonin. Noradrenaline inhibits meta-iodobenzylguanidine uptake competitively (Ki = 13 microM). In addition, meta-iodobenzylguanidine displaces dihydrotetrabenazine and reserpine from their binding sites on chromaffin granule membranes. It is thus likely that, after in vivo administration, [131I] meta-iodobenzylguanidine is ultimately stored in chromaffin granules and that it is translocated by the monoamine transporter.     

The effects of shivering on oxygen consumption and carbon dioxide production in patients rewarming from hypothermic cardiopulmonary bypass

Oxygen consumption (VO2), carbon dioxide production (VCO2), end-tidal carbon dioxide partial pressure (PETCO2), mixed venous oxygen saturation (SvO2) and haemodynamic variables were recorded every 30 min for four hours in 15 patients recovering from hypothermic cardiopulmonary bypass (CPB). All patients had been anaesthetised with fentanyl 40 micrograms.kg-1, supplemented with isoflurane, and pancuronium 0.15 mg.kg-1 for muscle relaxation. Three of the 15 patients (20 per cent) shivered, defined as intermittent or continuous, vigorous movements of chest or limb muscles. Patients who shivered had a VO2 of 159 +/- 16.4 ml.min-1.m-2 on arrival in the ICU which rose to a maximum value of 254 +/- 28.3 ml.min-1.m-2 by 150 min post-CPB. In contrast, patients who did not shiver had a significantly lower VO2 of 93.1 +/- 6.9 ml.min-1.m-2 on arrival in the ICU which rose to a maximal value of only 168 +/- 11.5 ml.min-1.m-2 by 180 min post-CPB. Maximal VO2 in both groups was reached when the nasopharyngeal temperature (NPT) was approaching normal. VCO2 paralleled the increase in VO2 in both groups. By four hours there was no significant difference between the two groups; however, the VO2 in both groups (160.5 +/- 21.3 ml.min-1.m-2 and 173.9 +/- 12.3 ml.min-1.m-2 respectively) was approximately twice values commonly measured in anaesthetized patients. Patients who shivered had a significantly higher heart rate and cardiac index and significantly lower SvO2. We conclude that the high VO2 and VCO2 associated with shivering causing increased myocardial work may be detrimental to patients who have impaired cardiac function post-coronary artery surgery (CAS).     

Three highly polymorphic microsatellites at the human myelin oligodendrocyte glycoprotein locus, 100 kb telomeric to HLA-F : Characterization and relation to HLA haplotypes

The MOG locus, located on chromosomal bands 6p21.3-p22 and mapped about 100 kb telomeric to HLA-F, was isolated from cosmid ICRFcl09A2434 and shown to contain three microsatellites. These CA-repeat polymorphic markers were characterized in a sample of 173 healthy unrelated individuals and 84 DNAs from the HLA Workshop reference panel, by a method combining fluorescence labeling of PCR products and use of an automated DNA sequencer. For the three markers, frequencies of heterozygotes are well predicted from allele frequencies by the Hardy—Weinberg rule, which suggests that problems of allele nonamplification are unlikely. Typing of cell lines homozygous in the HLA region allowed unambiguous definition of 81 HLA-MOG haplotypes and showed that several HLA ancestral haplotypes extended to the MOG region. The high degree of polymorphism (59%, 51%, and 81% at the three loci, respectively, and 87% at the haplotype level) makes these new markers informative for association or linkage studies with diseases such as hemochromatosis or multiple sclerosis, and for studies aimed at precisely delineating the site of crossover in chromosomes in which recombination occurred in the distal part of the HLA class I region.     

Ontogeny of B lymphocytes in mice. Quantification of surface membrane immunoglobulins by immunoperoxidase assay.

Surface membrane immunoglobulins (SmIg) of splenic lymphocytes were investigated by immunoperoxidase assay in newborn Swiss mice, their mothers and adult controls. The mean number of SmIg + cells in adult mice was 45-8% and the mean number of antigenic sites per positive cells was 108,500. In newborn mice during the first 7 days of life, values for both parameters were low (24-25--28-5% and 38,000-45,773 respectively) and began to rise after the 10th day to reach adult levels between the ages of 2 and 3 weeks. A peak above adult levels for the mean number of sites per cell was observed on day 21 with a subsequent drop to adult levels on day 28. Post-partum females were found to have consistently fewer sites per positive cell (69,000-86,600) during the 14 days following delivery than their adult control counterparts, though the difference was not statistically significant.     

Neurectodermal differentiation of extraskeletal myxoid chondrosarcoma: a classical feature?

Extraskeletal myxoid chondrosarcoma (EMC) is a phenotypically and genotypically distinct entity with a protracted course. A documented case of an extraskeletal myxoid chondrosarcoma characterized by a t(9; 17) (q22; q11) translocation with a neuroendocrine and neural differentiation is reported.     

Recombination pattern of the TCR γ locus in human peripheral T-cell lymphomas

The recombination events of the γ and β T-cell receptor (TCR) loci were analysed in a series of 39 peripheral T-cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR αβ PTCLs, 22/23 cases showed a γ-gene rearrangement while only 18/23 showed a concomitant β-gene rearrangement. The germline configuration of the β locus was found in angioimmunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three γδ PTCLs rearranged both γ and β genes. TCR silent PTCLs showed three different patterns of γ- and β-gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged γ and a germline β locus; and five cases had the two loci rearranged. Regarding the variable genes in the γ-rearranged alleles, members of the VγI subgroup were the most frequently presented (39/50), followed by VγII, VγIII, and VγIV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the γ locus is more frequently rearranged whatever the TCR expression. The γ-locus analysis provides a better diagnostic yield than the β locus in the study of PTCL clonality.     

Mycoplasma pneumoniae-associated nephritis in children

 Mycoplasma pneumoniae infection is a rare cause of acute nephritis. Six children (2 girls) aged 5–10 years, admitted for nephritis, had serological tests showing recent Mycoplasma pneumoniae infection. The diagnosis of Mycoplasma pneumoniae infection was based on the presence of serum IgM, detected either by immunofluorescence (IF) (n=1) or enzyme-linked immunosorbent assay (n=5). Four children had a renal biospy, with analysis of parenchymal Mycoplasma pneumoniae components by indirect IF and polymerase chain reaction. Extrarenal symptoms were: respiratory (n=3), ear, nose, and throat (n=2), gastrointestinal (n=3), hepatic (n=1), neurological (n=1), articular (n=1), and hematological (n=3). The patients presented with acute nephritis (1 had a nephrotic syndrome) or with acute renal failure and proteinuria. Pathological findings included type 1 membranoproliferative glomerulonephritis (MPGN, n=1), proliferative endocapillary glomerulonephritis (n=2), and minimal change disease (n=1). The patient with type 1 MPGN progressed rapidly towards end-stage renal failure because of a congenital solitary kidney. Among the patients with endocapillary glomerulonephritis, 1 relapsed 6 months later and remained proteinuric, while the other recovered, as did the child with minimal change disease. The search for Mycoplasma pneumoniae antigens and nucleic acids in renal tissue was negative. However, the absence of the microorganism in the kidney is a common feature of post-streptococcal glomerulonephritis. We conclude that Mycoplasma pneumoniae is a rare yet potential cause of acute glomerulonephritis. Received: 13 September 1996 / Revised: 16 June 1998 / Accepted: 18 June 1998     

Increased dopamine receptor sensitivity in the rat following acute administration of sufentanil,U50,488H and d-Ala2-d-Leu5-enkephalin

Summary The effects of acutely administered opioid receptor agonists sufentanil, U50,488H and [d-Ala², d-Leu⁵]-enkephalin (DADL) were observed upon dopamine D₁ and D₂ binding site density in the striatum of the rat. In addition, the functional implications of opioid-induced changes in dopamine receptor sensitivity were studied using the behavioural profile elicited by apomorphine in the rat. The -agonist sufentanil (1 or 20 Erg/kg, i. p.), the -agonist U50,488H (10 mg/kg, i. p.) and DADL (1 g/animal, i. c. v.) all significantly elevated D₂ but not D₁ binding site density in rat striatum. Pretreatment with sufentanil (1 g/kg, i. p.) induced an elevation in apomorphine-induced sterotyped behaviour, but attenuated locomotor activity. Following administration of U50,488H (10 mg/kg, i. p.), both the degree of stereotypy and the intensity of the locomotor activity were enhanced. Contralateral rotation was observed in animals pretreated with DADL (1 g/animal, i. c. v.) following challenge with apomorphine. It is concluded that the opioid agonists studied induce a significant elevation in functional D₂ sites to the exclusion of D₁ sites. However, the precise mechanism by which this effect is elicited remains to be established. Send offprint requests to R. D. E. Sewell at the above address     

Shifting Cerebral Dominance in a Woman with Schizoaffective Psychosis: A Case Study

We describe a case of an intelligent, artistic 50-year-old woman with schizoaffective disorder with a long history of delusional preoccupation with laterality and episodes of reported shifts in handedness. Investigations including dichotic listening and lateralised visual imagery tasks indicated unusual patterns of asymmetry. Executive functions were found to be intact, and EEG and CT scan were normal. Interview schedules revealed high scores for schizotypy, and no evidence of a dissociative disorder, whereas psychotic symptoms with mood lability were evident on mental status examination. The subject's preoccupations are illustrated with a selection of her artistic productions. The case is discussed in the context of reports of a relationship between schizophrenia and ambiguous handedness. A cognitive neuropsychiatric formulation briefly explores the possibility of alternative cerebral hemispheres affecting cognitive-perceptual operations.