Human polymorphonuclear neutrophils express a B7-1-like molecule.

Polymorphonuclear neutrophils (PMN) are part of the innate immune system and are first-line effector cells in acute inflammatory responses. On activation PMNs secrete cytokines and oxygen metabolites that might be involved in the regulation of the acquired immune response. We show here that peripheral blood PMNs constitutively express a B7-1-like molecule as detected by immunostaining with several B7-1 antibodies. Reverse transcriptase-polymerase chain reaction using three sets of primers spanning different regions of B7-1 indicate dissimilarities at the mRNA level. B7-1 mRNA is expressed in bone marrow cells and lipopolysaccharide (LPS)-stimulated but not in unstimulated PMNs. The B7-1-like molecule is localized to the cytoplasmic granules and translocated to the cell surface after stimulation with LPS or interleukin-12 in some donors. Binding of CTLA4-Ig suggests that the B7-1-like molecule can interact with functional B7 ligand and might be important in the immunobiology of PMNs.

Immunological and clinical response to immunosuppressive treatment in paraneoplastic cerebellar degeneration.

OBJECTIVE: To report the clinical and immunological response to immunosuppressive treatment with cyclophosphamide in two patients with paraneoplastic cerebellar degeneration. DESIGN: Case reports. Clinical and immunological follow-up data available for 4 1/2 years in the first patient and for 2 years in the second patient. SETTING: A 1500-bed university hospital and a 1200-bed university teaching hospital. INTERVENTION: Cyclophosphamide intermittent treatment. MAIN OUTCOME MEASURE: Clinical disability. RESULTS: One of the patients, who was treated from an early stage, recovered completely. The other patient showed a partial clinical response. While the two patients were receiving a maintenance regimen with cyclophosphamide, the conditions of both patients remained stable for at least 2 years. In both patients, intrathecal antibody synthesis declined considerably. CONCLUSION: Early induction of immunosuppressive therapy with cyclophosphamide should be tried in treating patients with paraneoplastic cerebellar degeneration.

Protein gradients in the cerebrospinal fluid and the calculation of intracerebral IgG synthesis.

When six successive samples of 2.5 ml cerebrospinal fluid (CSF) were withdrawn from eight multiple sclerosis (MS) and 12 other neurological disease (OND) patients, the IgG index rose continuously between 2.9 and 24.0%, while both the Tourtellotte as well as the Reiber/Felgenhauer formulas were less affected.

Expression of matrix metalloproteinase-9 and its inhibitors in mononuclear blood cells of patients with multiple sclerosis.

Inflammatory mononuclear cells invading the nervous system in demyelinating diseases are supposed to be a major source of matrix metalloproteinases which are involved in damaging the blood-brain barrier and facilitating cellular migration through the extracellular matrix. Several studies revealed a crucial role of 92 kDa gelatinase (matrix metalloproteinase-9, MMP-9) in these processes. In this study, we determined MMP-9, TIMP-1 and TIMP-2 (tissue inhibitor of metalloproteinase) mRNA in peripheral blood mononuclear cells of multiple sclerosis (MS) patients by competitive reverse transcription PCR and plasma protein levels by ELISA. In active MS patients, both with relapsing-remitting and chronic progressive disease MMP-9 mRNA and plasma protein levels were significantly increased compared to healthy controls. No significant changes in mRNA expression were found for TIMP-1 and TIMP-2. However, unbound TIMP-2 in plasma was significantly higher in MS patients compared to healthy controls. MMP-9 and TIMP-1 expression was significantly correlated in MS with a significantly higher MMP-9/TIMP-1 ratio in active MS than in healthy controls. These results are in support of an important pathogenic role of MMP-9 activity in MS.

Elevated endogenous cannabinoids in schizophrenia.

Evidence suggests that cannabinoid receptors, the pharmacologcial target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia. To test this hypothesis, we examined whether endogenous cannabinoid concentrations in cerebrospinal fluid of schizophrenic patients are altered compared to nonschizophrenic controls. Endogenous cannabinoids were purified from cerebrospinal fluid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quantified by isotope dilution gas-chromatography/mass-spectrometry. Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were significantly higher in schizophrenic patients than non-schizophrenic controls (p < 0.05). By contrast, levels of 2-arachidonylglycerol, another endogenous cannabinoid lipid, were below detection in both groups. The findings did not seem attributable to gender, age or medication. Elevated anandamide and palmitylethanolamide levels in cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia.

The influence of disease activity on the number of blood cells of multiple sclerosis patients.

The influence of disease activity on blood cell counts was studied in over 100 multiple sclerosis patients examined at regular intervals of 4-8 weeks over an 18-month period. T-lymphocytes were assessed by the cytochemical alpha-naphthyl-acetate-esterase (ANAE) stain in addition to conventional differentials. In all patients as a group as well as in individual patients studied sequentially, an exacerbation was marked by a striking reduction in both the relative and absolute numbers of ANAE-positive cells. Simultaneously, a strong increase in granulocytes and a slight augmentation of ANAE-negative cells occurred. Similar changes related to disease activity in leucocytes and lymphocytes were also detected in conventional blood smears. Fluctuations in the number of blood cells with disease activity persisted under therapy with corticosteroids and to a lesser degree also with azathioprine.

Reactivity of sera and isolated monoclonal IgM from patients with Waldenström's macroglobulinaemia with peripheral nerve myelin.

Sera of 23 patients with Waldenström's macroglobulinaemia and six monoclonal IgM paraproteins, which had been isolated from these sera, were examined for reactivity against peripheral nerve tissue. Of these 23 patients, 12 had clinical signs of peripheral polyneuropathy (PN). Using an indirect immunofluorescence method, all sera and monoclonal IgM preparations reacted with peripheral nerve structures, displaying a distinct granular fluorescence pattern with anti-IgM sera. The Waldenström sera reacted mainly with structures at the border of the myelin sheath, as well as between myelin and axon, and occasionally with the axon itself. There was no difference between sera of patients with PN and those without. Negative results were obtained in a complement fixation assay. Of the 23 sera, 15 reacted in an antibody-dependent lymphocyte-mediated cytotoxicity reaction (ADLC) with peripheral nerve myelin, and to a much lesser extent with myelin basic protein from CNS. Five of the six isolated monoclonal IgM preparations also gave positive ADLC reactions. These results constitute additional evidence for an immunological mechanism in the pathogenesis of PN in Waldenström's macroglobulinaemia.

Positron emission tomography and magnetic resonance imaging for cerebral involvement in patients with systemic lupus erythematosus.

Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains difficult to diagnose, particularly since structural abnormalities may not be revealed by magnetic resonance imaging (MRI). Glucose utilisation was measured by positron emission tomography (PET) in 35 SLE patients to detect signs of CNS involvement. The patients were examined by a standardised neurological examination, a battery of tests to evaluate neuropsychological performance and MRI. Antineuronal antibodies were determined to investigate their putative role in CNS involvement in SLE. Twenty patients had distinct neurological (17) and/or psychiatric (3) symptoms. Ten patients had pronounced cognitive impairment. Neurological and cognitive deficits were thus found to be unrelated disorders in SLE. Global glucose utilisation of SLE patients did not differ significantly from that of normal controls, nor were differences found between SLE patients with or without neurological or cognitive abnormalities. On MRI of the brain, the number and size of white matter lesions correlated with the presence of neurological deficits but were unrelated to the severity of cognitive impairment. Within the normal range, lower global glucose utilisation tended towards lower values with increasing number and size of white matter lesions. Patients with lesions larger than 8 mm also showed distinctly increased IgG anticardiolipin antibody titres, whereas measuring antineuronal antibodies did not reveal any relation to the variables investigated. We conclude that the demonstration of CNS lesions by MRI can contribute confirmatory evidence for CNS involvement in SLE, but PET or the presence of antineuronal antibodies adds little if any information beyond that obtained by clinical examination, neuropsychological testing, and MRI.

Two-month follow-up of the changes in vitreal constituents after argon laser coagulation of the retina in rabbits.

The response of the vitreous after panretinal argon laser photocoagulation was followed over a period of 60 days. Two phases can be discerned. An an immediate reaction to the disturbance of the blood-retinal barrier at the site of the pigment epithelium the total protein content and malate dehydrogenase activity rise sharply within 3 days, 4- to 5-fold above a normal. The more protracted increase of lysosomal enzyme activities which reach their peak heigh after 14 days only, can be attributed to the action and proliferation of phagocytic cells. 2 months after treatment all parameters have returned to their normal levels.

Primary germinoma of the brain. Immunocytochemical demonstration of tumour cells in the cerebrospinal fluid.

A patient is presented, who developed a suprasellar tumour. Stereotactical biopsy of the tumour revealed the diagnosis of a dysgerminoma. Immunocytochemical examination of the CSF showed neoplastic cells staining for human chorionic gonadotropin and for alpha-fetoprotein. The authors stress the possibility to diagnose primary intracranial germ cell tumours without operation.

Preparation procedure for cerebrospinal fluid that yields cytologic samples suitable for all types of staining, including immunologic and enzymatic methods.

A new method for the cytologic investigation of the cerebrospinal fluid is described. Preparation of the cells is done by successive centrifugation, resuspension of the cells in a protein-enriched medium and cytocentrifugation. The method provided both good cell yields and morphologic preservation. All stainings, including enzymecytochemical and immunocytochemical, could be performed on the specimens. The cell-free fluid from the first centrifugation is also available for use in other studies.

Monoaminergic neurotransmission is altered in hepatitis C virus infected patients with chronic fatigue and cognitive impairment.

BACKGROUND: The majority of patients with hepatitis C virus (HCV) infection suffer from disabling fatigue, cognitive dysfunction, and quality of life reduction. Meanwhile, there is increasing evidence that HCV infection can affect brain function. Recent studies have shown that fatigue and psychomotor slowing may resolve in patients with hepatitis C after treatment with ondansetron. This observation indicates alteration of serotonergic neurotransmission in HCV infected patients with chronic fatigue. METHODS: Data from 20 HCV infected patients who were referred to our clinic because of disabling fatigue and cognitive decline of unknown cause were analysed retrospectively. Patients had undergone a diagnostic programme, including clinical and psychometric examination, electroencephalogram (EEG), magnetic resonance imaging of the brain, cerebrospinal fluid analysis, and I-123-beta-CIT (2beta-carbomethoxy-3-beta-(4-[(123)I]iodophenyl)tropane) single photon emission computerised tomography (SPECT) studies of serotonin and dopamine transporter binding capacity. RESULTS: All patients had pathological results on the fatigue impact scale. Two thirds of patients showed pathological attention test results. EEG, magnetic resonance imaging, and cerebrospinal fluid analysis were normal. Pathological dopamine transporter binding was present in 12/20 (60%) patients and pathological serotonin transporter binding in 8/19 (50%) patients. Patients with normal SPECT results did not significantly differ from controls with regard to psychometric test results. Interestingly, patients with both decreased serotonin and dopamine transporter binding showed significantly impaired performance in most of the tests applied. Comorbidity that could have impaired cerebral function was excluded in all patients. CONCLUSION: Our findings indicate alteration of serotonergic and dopaminergic neurotransmission in HCV infected patients with chronic fatigue and cognitive impairment.

Enzyme activities and protein concentration in the intraocular fluids of ten mammals.

An attempt was made to establish normal values for the total protein concentrations and the enzyme activities of LDH, MDH and PGI in the intraocular fluids of rats, guinea pigs, rabbits, cats, dogs, sheep, cattle, pigs, horses and humans. Remarkably little species differences were noted in 9 of the 10 mammals with vitreal enzyme activities falling into a narrow range between 8.4 U/l (PGI, horse) and 92.4 U/l (MDH, guinea pig). All species obeyed the sequence aqueous less than vitreous less than serum with exception of the rat, where vitreous activities surpassed serum at least two-fold. The very low enzyme activities in the aqueous and vitreous humors demand special precautions against contaminations which can either derive from post-mortem storage or inadequate sampling procedures. Conversely elevated enzyme activities could be used as probes for pathological processes or as a check for a clean preparation.

[Tobacco-alcohol amblyopia. Clinical course in 33 patients]. / Tabak-Alkohol-Amblyopie. Klinischer Verlauf bei 33 Kranken.

The clinical data of 33 patients with tobacco-alcohol-amblyopia are described. Usually, the visual disturbance concerned both eyes and was not associated neither with headache nor with painful eye movements. The fundus was very often normal. In the static perimetry mostly relative or absolute central scotomas were found, sometimes centrocoecal scotomas and very seldom paracentral scotomas. The colour vision was very often disturbed, usually the red-green discrimination. In the rule the amplitudes of the visual evoked potentials were diminished, the P-100 latency was delayed in 39%. A follow-up of 25 patients revealed that the visus and the results of the static perimetry improved in 72% during vitamin substitution (B1, B2, B6, B12, folic acid). In a few cases this improvement could be observed even though the alcohol drinking was not ceased. In most cases the disturbance of the colour vision and the pathologic visual evoked potentials, however, did not change.

Carbohydrate structures of beta-trace protein from human cerebrospinal fluid: evidence for "brain-type" N-glycosylation.

The carbohydrate structures of beta-trace protein from human cerebrospinal fluid have been elucidated. This protein carries exclusively N-linked oligosaccharides at two sites (Asn29 and Asn56). Enzymatically released N-glycans were studied by compositional and methylation analyses, high-pH anion-exchange chromatography, and liquid secondary ion mass spectrometry. All glycans were found to be of the complex type, and most (90%) of them were biantennary with no (40%), one (40%), or two (20%) N-acetylneuraminic acid residues. The rest were triantennary chains or biantennary chains with intact or truncated lactosamine repeats. The innermost N-acetylglucosamine residues of nearly all structures were found to be alpha 1,6-fucosylated. Peripheral fucose (about 20% alpha 1,3-linked to N-acetylglucosamine) was also detected. Seventy percent of the oligosaccharides contained a bisecting N-acetylglucosamine. Especially in the neutral, but also in the monosialylated oligosaccharide fractions, many incomplete antennae consisting of N-acetylglucosamine only were present. At least 20 different N-glycans were identified. Analysis of the site-specific glycosylation patterns at Asn29 and Asn56 revealed only minor differences. According to the structural features (a high degree of fucosylation, high amounts of bisecting N-acetylglucosamine, as well as terminal N-acetylglucosamine and galactose residues, and significant amounts of N-acetylneuraminic acid in alpha 2,3 linkage), this protein can be classified as "brain-type" glycosylated.

Early onset MS under the age of 16: clinical and paraclinical features.

MS in juvenile patients under the age of 16 occurred in 31 (5%) of our whole MS population of 620 patients in the time from 1975-1991. It does not differ clinically from the disease as observed in 72 patients with later onset MS in respect to symptoms at onset, course, progression rate, rate of relapses and abnormalities in CSF and MRI. However, fever, headache, nausea and vomiting with pleocytosis in CSF during the first episode and development of oligoclonal bands with passage of time may be characteristic in some juvenile patients. The presence of oligoclonal bands and MRI results are of high diagnostic value in this special group of patients.

[61-year-old patient with rapidly progressive cerebellar symptoms]. / 61jähriger Patient mit rasch progredienter zerebellärer Symptomatik.

The rare case of a paraneoplastic, cerebellar degeneration is reported. In addition to the valuable early diagnosis of tumor disease, this paraneoplastic occurrence can also lead to false diagnoses in regard to both the underlying disease and the staging of the tumor. In the cases of known tumor disease, the assumption of cerebral metastasis is also possible.

Renal involvement in patients with congenital cyanotic heart disease.

Patients with congenital cyanotic heart disease may develop a glomerulopathy with proteinuria and impaired renal function. In order to investigate this problem we conducted a study on 27 patients with uncorrected cyanotic heart disease who were between 1 day and 25 years old. As a consequence of hypoxaemia haematocrit was elevated to 57%. Proteinuria was above 150 mg/day/1.73 m2 body surface in 12 patients. Only one of 9 children under 10 years of age had pathological proteinuria presenting as isolated albuminuria. Seven out of 10 patients between 11 and 20 years had an elevated proteinuria with a glomerular pattern. Creatinine clearance was normal in these patients. All four patients above 20 years of age had a considerable glomerular proteinuria with a mean excretion of 5.7 g/24 h/1.73 m2 body surface. These patients suffered additionally from chronic cardiac failure and creatinine clearance was below the normal range. There was a clear relationship between pathological proteinuria and age of the patients and thus duration of hypoxaemia. Patients with pathological proteinuria had a significant higher erythrocyte count (7.3 +/- 1.3 vs 5.6 +/- 1.4 10(12)/l p less than 0.01) and a lower mean corpuscular haemoglobin. In summary, children with persistent congenital cyanotic heart disease have substantial risk of developing a glomerulopathy if the cyanosis remains unchanged for more than ten years.