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Biomedical subjects

A Hartmann

Publications and source records attributed to A Hartmann.

At least 145 records · Page 8Linked to original sources
PubMed2000

The Influence of Hyperbaric Oxygenation (HBO) on Proliferation and Differentiation of Human Keratinocyte Cultures In Vitro.

A drop in tissue oxygen partial pressure below 30 mm Hg as a result of reduced perfusion in an extensive area of acute skin damage, or where a large number of chronic skin defects occur, inhibits collagen synthesis and neoangiogenesis in the various phases of wound healing. Subsequent granulation and epithelialisation are correspondingly impaired.Hyperbaric oxygenation is now recognised as a valuable supplementary method of treatment for problematic wounds. Stimulation of fibroblast and endothelial cell proliferation through Hyperbaric oxygenation has been demonstrated in numerous studies.The aim of this study was to investigate the effect of hyperbaric oxygen treatment on the proliferation and differentiation of human keratinocyte cultures.The influence of hyperbaric oxygenation on the proliferation of human keratinocyte cultures was demonstrated using flow-through cytometry and a fluorescence activated cell sorter, which detects fluorescence intensity following incorporation of 5-bromo-2'-deoxyuridine in cell DNA.The degree of cell differentiation was deduced from the expression of various components of the cytoskeleton, such as cytokeratin 10 and involukrin, the production of which was quantified through the determination of monoclonal antibodies against cytokeratin 10 and involukrin from measurements of fluorescence activity in a flow-through cytometer.Hyperbaric oxygenation of cell cultures in vitro did not produce a significantly higher rate of cell proliferation, so that no increase in vitality was observed.An interesting observation following exposure to hyperbaric oxygen was the marked increase in expression of both cytokeratin 10 and involukrin, as an indication of accelerated cell differentiation.

Journal Article↗
PubMed2000

Predictive value of clinical lacunar syndromes for lacunar infarcts on magnetic resonance brain imaging.

OBJECTIVE: We prospectively investigated the predictive value of clinical and CT-supported lacunar syndromes for lacunar infarcts on magnetic resonance (MR) brain imaging. PATIENTS AND METHODS: The 54 prospective, consecutive patients had clinical lacunar syndromes of acute onset and early computed tomography (CT; on admission day, i.e. < or =48 h after onset of symptoms) showing either a small deep infarct or no corresponding lesion. Taking MR (at day 2 to 4 after admission) as the gold standard, the positive predictive value of the CT-supported clinical syndrome for corresponding lacunar lesions was calculated. RESULTS: In 27 (50%) patients, early CT showed a lacunar infarct corresponding to the clinical syndrome, a further 27 (50%) patients had no fresh ischemic lesion. In 51 patients (94%), MR showed a recent lacunar infarct (hyperintense lacune in T2-weighted scans, no demarcation on T1-weighted scans and/or positive gadolinium-enhancement) corresponding to the clinical syndrome (positive predictive value 0.94, 95%, CI: 0.88 to 0.98). In 3 (6%) patients MR was normal. Aside from old unrelated ischemic (macro- and/or microangiopathic) lesions, MR revealed no acute non-lacunar infarct. CT and MR sites of lacunar lesions were matching. Compared to gold standard MR, the sensitivity of early CT for suspected lacunar lesions was 0.53 (95% CI: 0.38 to 0.67). CONCLUSION: Lacunar syndromes were highly predictive for small deep infarcts on MR. Magnetic resonance brain imaging may be redundant in the setting of a lacunar syndrome supported by a CT that excludes non-ischemic causes of stroke; it may therefore be abandoned in order to reduce costs in the health care system.

Adult↗
PubMed2000

Clonality and genetic divergence in multifocal low-grade superficial urothelial carcinoma as determined by chromosome 9 and p53 deletion analysis.

Multifocality and recurrence are clinically important features of urothelial carcinomas of the urinary bladder. Recent molecular genetic studies have suggested that multifocal urothelial carcinomas are monoclonally derived from an identical transformed progenitor cell. However, most of these studies investigated advanced and poorly differentiated tumors. The study presented focuses on early papillary tumors, including 52 superficial well-differentiated multifocal and recurrent bladder carcinomas from 10 patients. Microdissection separating urothelium from stromal cells was considered essential to obtain pure tumor cell populations. Genetic analysis was carried out by applying two different methods. Dual color fluorescence in situ hybridization (FISH) with centromeric probes for chromosomes 9 and 17 and gene-specific probes for chromosome loci 9q22, 9p21, and 17p13 was carried out in parallel to loss of heterozygosity (LOH) analyses applying 5 microsatellite markers on these chromosomes. Overall, deletions on chromosome 9p were found in 47 tumors (90%), at chromosome 9q in 36 tumors (69%) and at chromosome 17p in 3 tumors (6%). There was a very high correlation of the results between FISH and LOH analysis. Ten early superficial papillary tumors showed deletion of chromosome 9p without deletion of 9q, suggesting 9p deletions as a very early event in the development of papillary urothelial carcinoma. Although in four patients, all investigated tumors showed identical genetic alterations and one patient showed no genetic alterations at the loci investigated, in five patients, two or more clones with different deletions were found. In four of these patients, the results are compatible with clonal divergence and selection of different cell subpopulations derived from a common progenitor cell. However, in one patient different alleles in two markers at chromosome 9 were deleted, favoring an independent evolution of two recurring tumor cell clones. In summary, we could show that there is considerable genetic heterogeneity in early multifocal and recurring urothelial carcinoma and demonstrated the occurrence of two independent clones in at least one patient as an indicator of possible initial oligoclonality of bladder cancer.

Aged↗
PubMed2000

A trans-acting factor, isolated by the three-hybrid system, that influences alternative splicing of the amyloid precursor protein minigene.

Two clones were isolated in a three-hybrid screen of a rat fetal brain P5 cDNA library with an intronic splicing enhancer of the amyloid precursor protein (APP) gene as RNA bait. These clones represent the rat homologues of the previously described genes CUG-binding protein (CUG-BP) and Siah-binding protein (Siah-BP). Both interact in a sequence-specific manner with the RNA bait used for library screening as well as with the CUG repeat. In contrast, no interactions were observed in the three-hybrid assay with other baits tested. In two-hybrid assays, Siah-BP interacts with U2AF65 as well as with itself. EWS, an RGG-type RNA-binding protein associated with Ewing sarcoma, was identified as an interacting partner for the CUG-BP homologue in a two-hybrid assay for protein-protein interactions performed with various factors involved in RNA metabolism. Splicing assays performed by RT-PCR from cells cotransfected with certain cDNAs and an APP minigene, used as a reporter, indicate exclusion of exon 8 if the CUG-BP homologue is present. We conclude that clone AF169013 and its counterpart in human CUG-BP could be the trans-acting factors that interact with the splicing enhancer downstream of exon 8, and in this way influence alternative splicing of the APP minigene.

Alternative Splicing↗
PubMed2000

Taxonomic characterization of Ochrobactrum sp. isolates from soil samples and wheat roots, and description of Ochrobactrum tritici sp. nov. and Ochrobactrum grignonense sp. nov.

A large collection of bacterial strains, immunotrapped from soil and from the wheat rhizoplane, was subjected to polyphasic taxonomy by examining various pheno- and genotypic parameters. Strains were grouped on (inter) repetitive extragenic palindromic DNA (REP) PCR profiles at the intraspecies level. Pheno- and genotypic characters were assessed for representatives from 13 different REP groups. Strains of nine REP groups constituting two physiological BIOLOG clusters fell in the coherent DNA-DNA reassociation group of Ochrobactrum anthropi. Strains of two REP groups constituting a separate BIOLOG cluster fell in the coherent DNA-DNA reassociation group of Ochrobactrum intermedium. Additional phenotypic characters differentiating O. anthropi and O. intermedium were found. REP group K strains constituted a different BIOLOG cluster, a separate DNA-DNA reassociation group and a distinct phylogenetic lineage in 165 rDNA homology analysis, indicating that REP group K strains represent a new species. Diagnostic phenotypic characters were found. Closest relatives were Ochrobactrum species. The name Ochrobactrum grignonense sp. nov. is proposed (type strain OgA9aT = LMG 18954T = DSM 13338T). REP group J strains again constituted a different BIOLOG cluster, a separate DNA-DNA reassociation group and showed, as a biological particularity, a strict preference for the rhizoplane as habitat. Diagnostic phenotypic characters were found. This indicated that REP group J strains represent a further new species, although phylogenetic analyses using 16S rDNA homology were not able to separate the cluster of REP group J sequences significantly from 16S rDNA sequences of Ochrobactrum anthropi. The name Ochrobactrum tritici sp. nov. is proposed (type strain SCII24T = LMG 18957T = DSM 13340T).

Alphaproteobacteria↗
PubMed2000

Ecology and evolution of bacterial microdiversity.

Using high resolution molecular fingerprinting techniques like random amplification of polymorphic DNA, repetitive extragenic palindromic PCR and multilocus enzyme electrophoresis, a high bacterial diversity below the species and subspecies level (microdiversity) is revealed. It became apparent that bacteria of a certain species living in close association with different plants either as associated rhizosphere bacteria or as plant pathogens or symbiotic organisms, typically reflect this relationship in their genetic relatedness. The strain composition within a population of soil bacterial species at a given field site, which can be identified by these high resolution fingerprinting techniques, was markedly influenced by soil management and soil features. The observed bacterial microdiversity reflected the conditions of the habitat, which select for better adapted forms. In addition, influences of spatial separation on specific groupings of bacteria were found, which argue for the occurrence of isolated microevolution. In this review, examples are presented of bacterial microdiversity as influenced by different ecological factors, with the main emphasis on bacteria from the natural environment. In addition, information available from some of the first complete genome sequences of bacteria (Helicobacter pylori and Escherichia coli) was used to highlight possible mechanisms of molecular evolution through which mutations are created; these include mutator enzymes. Definitions of bacterial species and subspecies ranks are discussed in the light of detailed information from whole genome typing approaches.

Bacteria↗
PubMed2000

Middle cerebral artery (MCA) susceptibility sign at susceptibility-based perfusion MR imaging: clinical importance and comparison with hyperdense MCA sign at CT.

PURPOSE: To describe the radiologic findings of susceptibility changes in acute middle cerebral artery (MCA) thromboembolism detected with three-dimensional (3D) susceptibility-based perfusion magnetic resonance (MR) imaging and to compare the detectability and clinical value of this sign with those of the hyperdense MCA sign at computed tomography (CT). MATERIALS AND METHODS: Twenty-three patients (mean age, 55 years) underwent CT and MR imaging within the first 6 hours after the onset of acute MCA stroke. The hyperdense MCA sign at CT and the presence of susceptibility changes in acute thromboembolism as depicted on T2*-weighted 3D perfusion MR images were assessed. The presence of each sign was correlated with clinical presentation. RESULTS: The sensitivity of the hyperdense MCA sign at CT was 54% (negative predictive value, 71%) compared with 82% (negative predictive value, 86%) for the susceptibility changes at MR imaging. There were no false-positive CT or MR readings. The presence of the MCA susceptibility sign correlated positively with the initial clinical presentation (chi(2) = 7.987, P =.009, Spearman rho = 0.589). However, neither of the signs was a predictor for clinical outcome in cases of spontaneous MCA stroke. CONCLUSION: In addition to the information traditionally provided with reconstructed perfusion parameter maps, 3D susceptibility-based perfusion MR images allow the identification of acute MCA thromboembolism with a sensitivity higher than that of CT.

Acute Disease↗
PubMed2000

Intracerebral abscess caused by Nocardia otitidiscaviarum in a renal transplant patient--cured by evacuation plus antibiotic therapy.

We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rifampicin for 2 months. Due to pharmacokinetic interaction with rifampicin, the prednisolone dose was doubled, and the dose of tacrolimus had to be tripled for maintenance of adequate trough concentrations. Five months following cessation of antibiotic treatment, the patient has regained normal strength and function in her left-sided extremities and has a serum creatinine level of about 160 micromol/l (1.8 mg/dl).

Anti-Bacterial Agents↗
PubMed2000

Oligoclonality of early lesions of the urothelium as determined by microdissection-supported genetic analysis.

AIM: To contribute to the ongoing discussion of clonality of human urothelial cancer it was considered a valuable approach to analyze multiple areas from cystectomy specimens for deletions of chromosomes known to be involved early in bladder cancer development. MATERIAL AND METHODS: Thus, in 86 biopsies of 4 human cystectomies with different histological findings (maximal diagnosis: pT1G2, pTaG3, pT2G2, normal) loss of heterozygosity (LOH) was investigated as a deletion marker using markers of chromosomes 8p, 9p, 9q and 17p. Findings were compared to histology of the lesion. RESULTS: Findings indicate: (1) no changes in the markers investigated in the bladder with histologically normal urothelium in contrast to detection of LOH in normal urothelium of tumour-bearing bladders; (2) an accumulation of the number of LOH with increasing malignancy of lesions within one bladder, and (3) indications of oligoclonal neoplastic lesions in two of the urinary bladders investigated. CONCLUSIONS: The investigation of multiple lesions within one bladder presents a snapshot of genetic changes in differently advanced tumour stages. The hypotheses of tumour evolution and oligoclonality as derived from our LOH data need to be supported by deletion-independent clonality studies as X-chromosomal inactivation analysis.

Carcinoma in Situ↗
PubMed2000

Laser microdissection and microsatellite analyses of breast cancer reveal a high degree of tumor heterogeneity.

Carcinomas with productive fibrosis are the most common forms of breast cancer. Analysis of tumor-specific genomic alterations can be compromised by the presence of normal cells, demanding microdissection of small tumor areas to detect loss of heterozygosity (LOH) and microsatellite instability (MSI). The aim of this study was to evaluate the importance of precise laser microdissection for microsatellite analyses and investigation of tumor heterogeneity in breast cancer. 39 primary breast tumor samples were analyzed for MSI and LOH by PCR followed by polyacrylamide gel electrophoresis and silver staining using 15 microsatellite markers. Different tumor areas were processed separately in 30 patients. Both intraductal and invasive breast cancer regions were investigated in 11 patients. The following results were obtained: (1) accurate microdissection revealed MSI in 3 or more of the investigated markers (> or =20%) in 33% of the patients, a higher frequency than reported previously; (2) laser microdissection was 43% more sensitive in detection of LOH compared to manual microdissection due to a reduction of contamination by normal cells, and (3) 29 of 30 investigated tumors showed heterogeneity of genetic alterations in different tumor regions. Laser-based microdissection is a valuable tool in genetic analysis of desmoplastic tumors and allows an accurate determination of genetic alterations in histologically different tumor regions.

Adult↗
PubMed2000

Microsatellite instability in tumor and nonneoplastic colorectal cells from hereditary non-polyposis colorectal cancer and sporadic high microsatellite-instable tumor patients.

Genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) have been frequently studied in various tumor types. Genetic heterogeneity of nonneoplastic cells has not yet been sufficiently investigated. However, genomic instability in normal cells could be a potentially important issue, in particular when these cells are used as reference in LOH and MSI analyses of tumor samples. In order to investigate possible genetic abnormalities in normal colorectal cells of tumor patients, MSI analyses of normal colonic mucosa were performed. Up to 15 different laser-microdissected normal regions containing 50-150 cells were investigated in each of 15 individual microsatellite-stable, sporadic high microsatellite-instable (MSI-H) and hereditary non-polyposis coli cancer (HNPCC) colorectal cancer patients. Frequent MSI and heterogeneity in the MSI pattern were found both in normal and tumor cells from 10 HNPCC and sporadic MSI-H tumor patients whose tumors had defect mismatch repair protein expressions. This observation shows that MSI can also occur in nonneoplastic cells which has to be considered in MSI analyses for molecular HNPCC screening. In addition, considerable genetic heterogeneity was detected in all MSI-H (sporadic and HNPCC) tumors when analyzing five different regions with less than 150 cells, respectively. These differences were not detectable in larger tumor regions containing about 10,000 cells. Thus, heterogeneity of the MSI pattern (e.g. intratumoral MSI) is an important feature of tumors with the MSI-H phenotype.

Cell Separation↗
PubMed2000

Determinants of neurological outcome after surgery for brain arteriovenous malformation.

BACKGROUND AND PURPOSE: We sought to define determinants of neurological deficit after surgery for brain arteriovenous malformation (AVM). METHODS: One hundred twenty-four prospective patients (48% women, mean age 33 years) underwent microsurgical brain AVM resection. Patients were examined by 3 study neurologists immediately before surgery, postoperatively in-hospital, by in-person long-term follow-up, and with a structured telephone follow-up. They were classified according to the 5-point Spetzler-Martin grading system, with its 3 elements: size, venous drainage pattern, and location. The functional neurological status was classified with the modified Rankin scale. Multivariate logistic regression models were applied to test the effect of patient age, gender, and the 3 Spetzler-Martin elements on early and long-term postoperative neurological complications. RESULTS: Twelve patients (10%) were classified as Spetzler-Martin grade 1; 36 (29%) as grade 2; 47 (38%) as grade 3; 26 (21%) as grade 4; and 3 (2%) as grade 5. Postoperatively, in-hospital, 51 patients (41%) showed new neurological deficits (15% disabling [ie, Rankin scale score >2] and 26% nondisabling [ie, Rankin 1 or 2]). At long-term follow-up (mean follow-up time 12 months), 47 patients (38%) revealed surgery-related neurological deficits (6% disabling; 32% nondisabling). The rate of neurological complications increased by Spetzler-Martin grade. Female gender, AVM size, and deep venous drainage were significantly associated with neurological deficits at in-hospital and long-term evaluation. For patient age and AVM location, no significant association was found. CONCLUSIONS: The findings suggest that female gender, AVM size, and AVM drainage into the deep venous system may be determinants of neurological deficit after microsurgical AVM resection.

Adolescent↗
PubMed2000

Incident hemorrhage risk of brain arteriovenous malformations located in the arterial borderzones.

BACKGROUND AND PURPOSE: We sought to assess the relative risk of hemorrhagic presentation of brain arteriovenous malformations (AVMs) located in the arterial borderzone territories. METHODS: The 464 consecutive, prospectively enrolled patients from the New York AVM Databank were analyzed. AVM borderzone location was coded positive when the malformation was supplied by branches of at least 2 of the major circle of Willis arteries (anterior, middle, and/or posterior cerebral arteries). AVMs fed by branches of only 1 major pial or any other single artery served as a comparison group. Clinical presentation (diagnostic event) was categorized as (1) intracranial hemorrhage, proven by brain imaging, or (2) seizure, focal neurological deficit, headache, or other event with no signs of AVM hemorrhage on brain imaging. RESULTS: In 48% (n=222) of the patients, AVMs were located in the arterial borderzone territories; in 52% (n=242) a non-borderzone location was found. Hemorrhage was the presenting symptom in 44% (n=205); 28% (n=132) presented with seizures, 11% (n=52) with headaches, 7% (n=34) with a neurological deficit, and 9% (n=41) with other or no AVM-related symptoms. The frequency of incident AVM hemorrhage was significantly lower in borderzone AVMs (27%, n=61) than in non-borderzone malformations (60%, n=144; P:<0.001). This difference remained significant in a multivariate model controlling for age, sex, AVM size, deep venous drainage, and presence of aneurysms (odds ratio, 0.4; 95% CI, 0.25 to 0.66). CONCLUSIONS: Our findings suggest that borderzone location is an independent determinant for a lower risk of AVM hemorrhage at initial presentation.

Adult↗
PubMed2000

Demographic, morphological, and clinical characteristics of 1289 patients with brain arteriovenous malformation.

BACKGROUND AND PURPOSE: The purpose of this study was to assess demographic, clinical, and morphological characteristics of patients with brain arteriovenous malformations (AVMs). METHODS: Prospectively collected data of 1289 consecutive AVM patients from 3 independent databases (1 multicenter [Berlin/Paris/Middle and Far East, n=662] and 2 single centers [New York, n=337, and Toronto, n=290]) were analyzed. The variables assessed were age at diagnosis, sex, AVM size, AVM drainage pattern, AVM location in functionally important brain areas ("eloquence"), and type of presentation (hemorrhage, seizure, chronic headache, or focal neurologic deficit). Comparisons were made by ANOVA, contingency tables, and log-linear models. RESULTS: Overall, mean age at diagnosis was 31.2 years (95% CI 30.2 to 32.2 years), and 45% of the patients were female (95% CI 42% to 47%). AVM maximum diameter was <3 cm in 38% (95% CI 35% to 41%). Deep venous drainage was present in 55% (95% CI 52% to 59%). An eloquent AVM location was described in 71% (95% CI 69% to 74%). AVM hemorrhage occurred in 53% (95% CI 51% to 56%). Generalized or focal seizures were described in 30% (95% CI 27% to 33%) and 10% (95% CI 8% to 12%), respectively. Chronic headache was recorded in 14% (95% CI 12% to 16%). Persistent neurological deficits were found in 7% (95% CI 6% to 9%), and progressive neurological deficits in 5% (95% CI 4% to 6%). Significant differences between centers were found for age (P<0.001), sex (P=0.04), eloquence (P=0.04), size (P<0.001), hemorrhage (P=0.006), persistent neurological deficit (P<0.001), and reversible neurological deficit (P=0.013). The intercenter difference found for hemorrhage frequency did not remain after adjustment for AVM size. CONCLUSIONS: Baseline characteristics differed considerably between centers. The differences found in patient age and AVM size may be explained by center-specific referral patterns and the influence of access to treatment resources, whereas those found for other characteristics may be attributable to center-specific definitions. Analysis of natural history data from tertiary referral center databases may be improved by consistent definitions applicable to the entire population of AVM patients.

Adolescent↗
PubMed1999

[Cardiovascular disease after kidney transplantation].

Norwegian renal transplant recipients have a high prevalence of cardiovascular disease. In this group of patients cardiovascular disease causes three out of four deaths. Well-known risk factors such as hypertension, dyslipidemia, impaired glucose tolerance and diabetes mellitus are common in renal transplant recipients, but these factors cannot fully explain the high cardiovascular morbidity and mortality. Atherosclerotic disease and left ventricular hypertrophy are highly prevalent in uremic patients before transplantation. Hyperhomocysteinemia, elevated levels of advanced glycosylated end products, and immunosuppressive medication may also accelerate the atherosclerotic process. Until results from controlled trials on the effect of lipid-lowering therapy in renal transplant recipients are available, treatment decisions must be based on studies in non-transplanted patients. Every patient should be treated individually with the overall risk pattern taken into account.

Cardiovascular Diseases↗
PubMed1999

Dysarthria during basilar artery balloon occlusion.

A 49-year-old woman presenting with recurrent, reversible brainstem symptoms and a distal basilar artery aneurysm underwent balloon test occlusion. Five minutes after balloon inflation she developed a reversible isolated dysarthria. Despite failing the test occlusion (and after an additional brainstem event), the patient underwent surgery with placement of a clip across the basilar artery. The operation was tolerated without complication. The authors conclude that 1) pure dysarthria may be a symptom of temporary basilar artery occlusion and 2) balloon testing may overestimate the risk of basilar artery clipping.

Angioplasty, Balloon↗
PubMed1999

FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells.

Oxidative stress is thought to be involved in the mechanism of nerve cell death in Parkinson's disease (PD). Among several toxic oxidative species, nitric oxide (NO) has been proposed as a key element on the basis of the increased density of glial cells expressing inducible nitric oxide synthase (iNOS) in the substantia nigra (SN) of patients with PD. However, the mechanism of iNOS induction in the CNS is poorly understood, especially under pathological conditions. Because cytokines and FcepsilonRII/CD23 antigen have been implicated in the induction of iNOS in the immune system, we investigated their role in glial cells in vitro and in the SN of patients with PD and matched control subjects. We show that, in vitro, interferon-gamma (IFN-gamma) together with interleukin-1beta (Il-1beta) and tumor necrosis factor-alpha (TNF-alpha) can induce the expression of CD23 in glial cells. Ligation of CD23 with specific antibodies resulted in the induction of iNOS and the subsequent release of NO. The activation of CD23 also led to an upregulation of TNF-alpha production, which was dependent on NO release. In the SN of PD patients, a significant increase in the density of glial cells expressing TNF-alpha, Il-1beta, and IFN-gamma was observed. Furthermore, although CD23 was not detectable in the SN of control subjects, it was found in both astroglial and microglial cells in parkinsonian patients. Altogether, these data demonstrate the existence of a cytokine/CD23-dependent activation pathway of iNOS and of proinflammatory mediators in glial cells and their involvement in the pathophysiology of PD.

Aged↗