Changes of cerebrovascular response to visual stimulation in migraineurs after repetitive sessions of somatosensory stimulation (acupuncture): a pilot study.

OBJECTIVES: To evaluate the effect of repetitive somatosensory stimulation (acupuncture) on cerebrovascular response in migraineurs by functional transcranial Doppler. METHODS: Changes of cerebral blood flow velocity in the right posterior and left middle cerebral arteries were measured by functional transcranial Doppler during visual stimulation (flickering light over 57 seconds) in 10 migraineurs before and after 10 acupuncture sessions. The same stimulation paradigm was performed in 10 control subjects. Cerebral blood flow velocity data were analyzed with a previously validated technique based on automated stimulus-related averaging. To evaluate the clinical effect of the treatment, a headache diary monitored the frequency and intensity of the migraine attacks. A positive treatment effect was defined as a reduction of at least 50% in the attack frequency or the mean headache intensity (or both). RESULTS: Before treatment, migraineurs showed overshooting cerebral blood flow velocity changes at the beginning and at the end of the stimulation and a delayed decline to baseline compared with control subjects. After treatment, this response pattern was significantly diminished (P

Disturbance in the serum IgG subclass distribution in patients with anti-Hu positive paraneoplastic neurological syndromes.

Autoantibodies in patients with paraneoplastic neurological syndromes (PNS) have been reported to be predominantly IgG1 and IgG3 isotypes. However, no data are available about the IgG subclass distribution of the total serum IgG in these patients. Therefore, we investigated the IgG subclass distribution (given as percentage of total IgG) in 15 anti-Hu positive PNS patients, 15 patients with small cell lung cancer (SCLC) without PNS and 23 healthy controls using a commercial enzyme-linked immunosorbant assay test. Although IgG1 (and to a lower extent IgG3) are the predominant subclasses of the anti-Hu antibodies, PNS and SCLC showed a significant decrease in IgG1 and a concomitant increase in IgG2 compared with healthy controls (P < 0.05, respectively). In contrast, only SCLC patients, but not PNS patients, had higher IgG3 and IgG4 values compared with controls (P < 0.05, respectively). There was no correlation between IgG subclass levels and the titre or the predominant isotype of the antineuronal antibodies. PNS patients with autonomic disturbances had lower IgG4 levels than PNS patients without autonomic disturbances (P < 0.05). Our study demonstrates a disturbance in the IgG subclass distribution in PNS patients which is partly different from SCLC patients. The isotype regulation of the anti-Hu antibody seems to be independent from this phenomenon.

Altered cerebrovascular response pattern in interictal migraine during visual stimulation.

A dysbalance of the cerebrovascular response during functional activation of the brain has been postulated as a factor in the pathophysiology of migraine. To determine the dynamic pattern of the cerebrovascular response in migraineurs compared with a control group, changes of the cerebral perfusion during cerebral activation were studied with high temporal resolution by functional transcranial Doppler sonography (fTCD). The cerebral blood flow velocity (CBFV) in the right posterior cerebral artery (PCA) and the left middle cerebral artery (MCA) was measured simultaneously during visual stimulation in 19 interictal migraineurs and in 19 age- and sex-matched control subjects. Data were analysed with a previously validated technique based on automated stimulus-related averaging of the CBFV. The MCA migraineurs exhibited a steady increase of CBFV during the stimulation, while normal subjects showed a habituation of the CBFV response. The lack of habituation in migraineurs was significantly (P < or = 0.05) more pronounced across patients with a high attack frequency (> or = 4 per month) compared with migraineurs with a low attack frequency (< 4 per month). In the PCA, compared with normal subjects, migraineurs showed significantly (P < or = 0.05) stronger CBFV changes at the beginning and after the end of stimulation, with a slower decline to baseline. Data are in accordance with electrophysiological findings in migraineurs. It is assumed that a lack of habituation of the cerebrovascular response in migraineurs might contribute to a disturbance of the metabolic homeostasis of the brain that might induce migraine attacks.

Shift in the IgG subclass distribution in patients with lung cancer.

Lung cancer patients have been reported to have generalized immune dysfunction of the cell-mediated immune response. In contrast, little is known about the humoral immune function in these patients. Therefore, we examined the IgG subclass distribution (IgG1-lgG4) in 67 lung cancer patients (23 adenocarcinoma, 29 squamous cell carcinoma, 15 small cell carcinoma), 13 patients with inflammatory lung diseases, seven patients with pulmonary metastasis and 23 healthy controls using a commercial available ELISA. We found a significant increase in the percentage of IgG1 in adenocarcinoma, compared with squamous cell and small cell lung carcinoma (P < 0.05). Small cell lung cancer patients showed an increase in IgG2, IgG3 and IgG4 compared with all other groups (P < 0.05, respectively). IgG1/lgG2, IgG1/lgG3 and IgG1/lgG4 ratios in adenocarcinoma were higher than in small cell lung cancer (P < 0.05). In the squamous cell carcinoma there was no difference in IgG subclass distribution compared to controls. Our study demonstrates that the different histological subtypes of lung carcinoma influence the IgG subclass distribution. Whether this phenomenon is the result of a direct influence on B-cell activity by the tumor needs further investigation.

Production, purification and characterization of hemolysins from Listeria ivanovii and Listeria monocytogenes Sv4b.

In culture supernatants of both Listeria ivanovii and Listeria monocytogenes Sv4b, for the first time a hemolysin of molecular weight 58 kDa was identified, which had all the characteristics of an SH-activated cytolysin, and which was therefore identified as listeriolysin O (LLO). In the case of L. ivanovii a second major supernatant protein of molecular weight 24 kDa co-purified with LLO. However, the function of this protein has to be determined. In culture supernatants of L. ivanovii a sphingomyelinase and a lecithinase activity could be detected, both enzymatic activities together contributing to the pronounced hemolysis caused by L. ivanovii. The N-terminal amino acid sequences of LLO and the 24 kDa from L. ivanovii are shown.

Purification and characterization of cytolysins from Listeria monocytogenes serovar 4b and Listeria ivanovii.

Several exoproteins from Listeria monocytogenes serovar 4b (NCTC 10527) and Listeria ivanovii (ATCC) 19119, SLCC 2379), respectively, have been purified to homogeneity by thiol-disulfide exchange chromatography and gel filtration. Both strains produce a haemolytic/cytolytic protein of Mr 58 kDa, which has all the properties of a SH-activated cytolysin, the prototype of which is streptolysin O (SLO), and this protein has therefore been termed listeriolysin O (LLO). In addition a protein of Mr 24 kDa from culture supernatants of L. ivanovii co-purified with LLO. The N-terminal aminoacid sequences of both proteins from L. ivanovii have been determined. By mutagenesis with transposons of Gram-positive origin (Tn916 and Tn1545), which have been introduced via conjugation into L. ivanovii, several phenotypic mutants (altered haemolysis on sheep blood agar or lecithinase-negative) were obtained. Results on the properties of these mutants will be presented.

Hemolysin from Listeria--biochemistry, genetics and function in pathogenesis.

Thiol-activated hemolysins (listeriolysins) from Listeria monocytogenes (Sv4b) and Listeria ivanovii were purified to homogeneity. The N-terminal amino acid sequences of the 58 kDa listeriolysin of L. ivanovii and of a 24 kDa protein which may represent the CAMP-factor of L. ivanovii were determined. Antibodies raised against the L. ivanovii listeriolysin and anti-streptolysin O antibodies were used in Western blot analyses to detect listeriolysin(s) in virulent and avirulent Listeria strains. It was found that all virulent strains of L. monocytogenes synthesize and secrete listeriolysin (Mr 58-59 kDa), albeit in significantly variable quantities. No protein cross-reaction with anti-listeriolysin antibodies or anti-streptolysin O-antibodies was present in the supernatant of Listeria innocua, Listeria welshimeri, Listeria grayi and Listeria murrayi strains. Furthermore, the avirulent but hemolytic Listeria seeligeri did not cross-react with these antibodies. In a L. monocytogenes (strain EGD) gene bank constructed in Escherichia coli two types of hemolytic clones were identified. The first type carried recombinant plasmids with a common 2.0 kb fragment coding for a 23 kDa protein. This hemolytic activity was not activated by DTT and the 23 kDa protein did not cross react with anti-listeriolysin or anti-streptolysin antibodies. The other type of hemolytic clones was detected by using anti-streptolysin O antibodies to screen the gene bank. Some of these clones synthesized a protein of 61 kDa which cross reacted with anti-streptolysin O (or anti-listeriolysin) antibodies. By transposon Tn916 mutagenesis of L. monocytogenes two types of nonhemolytic mutants were obtained. Type I produced no extracellular protein that cross reacted with anti-listeriolysin (or anti SLO) antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)