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C H Rickert

Publications and source records attributed to C H Rickert.

At least 19 recordsLinked to original sources
PubMed2007

Frequent but borderline methylation of p16 (INK4a) and TIMP3 in medulloblastoma and sPNET revealed by quantitative analyses.

Certain risk groups among tumors of the central nervous system (CNS) in children take an almost inevitably fatal course. The elucidation of molecular mechanisms offers hope for improved therapy. Aberrant methylation is common in malignant brain tumors of childhood and may have implications for stratification and therapy. Methylation of p16 (INK4A), p14 (ARF), TIMP3, CDH1, p15 (INK4B )and DAPK1 in medulloblastoma (MB) and ependymoma has been discussed controversially in the literature. DUTT1 and SOCS1 have not previously been analyzed. We examined methylation in MB, sPNET and ependymoma using methylation-specific PCR (MSP), quantitative Combined Bisulfite Restriction Analysis (COBRA) and direct and clone sequencing of bisulfite PCR products. We detected methylation of p16 (INK4A) (17/43), p14 (ARF) (11/42) and TIMP3 (9/44) in MB and others by MSP. CDH1 was not only methylated in MB (31/41), but also in normal controls. Evaluation of MSP results by quantitative COBRA and sequencing yielded methylation between the detection limits of COBRA (1%) and MSP (0.1%). Only p16 (INK4A )and TIMP3 were methylated consistently in medulloblastomas (p16 (INK4A ) 14%, TIMP3 11%) and p16 (INK4A) also in anaplastic ependymomas (1/4 tumors). Methylation ranged from 1-5%. Evaluation of methylation using MSP has thus to be supplemented by quantitative methods. Our analyses raise the issue of the functional significance of low level methylation, which may disturb the delicate growth factor equilibrium within the cell. Therapeutic and diagnostic implications urge into depth analyses of methylation as a mechanism, which might fill some of the gaps of our understanding of brain tumor origin.

Adolescent↗
PubMed2007

Chromosomal imbalances and NF2 mutational analysis in a series of 10 spinal nerve sheath myxomas.

AIMS: To report the demographic, clinical and molecular profile of a series of intraspinal nerve sheath myxomas. Nerve sheath myxomas are diagnostically challenging, mainly cutaneous spindle cell neoplasms exhibiting Schwann cell differentiation. They are frequently mistaken for neurothekeomas and their genetic features are essentially unknown. METHODS AND RESULTS: Ten spinal nerve sheath myxomas with a preferential location in the lumbar spine (70%) were investigated. Presenting symptoms consisted of sciatic pain (100%), muscle weakness and paraesthesia (60% each). Intraoperatively, all tumours were attached to a spinal nerve. Chromosomal imbalances by comparative genomic hybridization were found in 8/10 cases, consisting of -22q (80%) and -19 (30%). Polymerase chain reaction analysis of the NF2 gene (exons 1-16) revealed two tumours with mutations in exon 8 and 14, respectively. CONCLUSIONS: Although these 10 nerve sheath myxomas exhibited Schwann cell differentiation and frequently showed loss of chromosome 22q typically encountered in peripheral nerve tumours, only two cases demonstrated mutations of the NF2 gene. This may indicate involvement of other tumour suppressor genes on 22q in nerve sheath myxomas and shows that they are more closely related at the molecular level to sporadic schwannomas, underscoring the presumption that they are true nerve sheath tumours.

Adult↗
PubMed2006

Evidence for specific phases in the development of human neuromelanin.

Neuromelanin is a dark-coloured pigment which forms in the dopamine neurons of the human midbrain. Here we describe the age-related development and regulation of neuromelanin within these dopamine neurons. 10 microm sections from formalin-fixed midbrain from 29 people spanning the ages of 24 weeks to 95 years old were either stained with a basic Nissl substance stain (0.5% cresyl violet), or processed unstained. After locating the substantia nigra using the stained sections, digital photos were taken of individual ventral substantia nigra neurons in the unstained sections, and the cellular area occupied by pigment, and optical density were measured using computer software. These measurements demonstrated three developmental phases. Neuromelanin was not present at birth and initiation of pigmentation began at approximately 3 years of age, followed by a period of increasing pigment granule number and increasing pigment granule colouration until age 20. In middle and later life the colour of the pigment granules continued to darken but was not associated with any substantial growth in pigment volume. The identification of three phases and changes in the rate of neuromelanin production over time suggests the regulation of neuromelanin production and turnover, possibly through enzymatic processes.

Adolescent↗
PubMed2006

Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood.

Supratentorial primitive neuroectodermal tumors (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of the CNS represent a biological and clinical enigma, despite advances in both molecular techniques and clinical management for these two rare embryonal brain tumors of childhood. Epigenetic changes hold great potential as possible disease mechanisms and may be manipulated therapeutically. We thus studied aberrant methylation of the genes RASSF1A and CASP8 and its consequence on expression in cell lines and primary tumors using a combination of semiquantitative methylation specific PCR (MSP), bisulfite sequencing and RT-PCR. In all, 17 samples of autopsy-derived normal appearing brain served as controls. Opposed to control tissues 19/24 sPNET and 4/6 AT/RT demonstrated aberrant methylation for the RASSF1A promoter region. Treatment of cell lines using 5-Aza-2'-deoxycytidine (5AZA) alone or in combination with trichostatin A (TSA) succeeded in re-establishing expression of RASSF1A in cell lines derived from a renal rhabdoid, an AT/RT and a medulloblastoma. A 5' CpG-rich region of CASP8 was methylated in normal tissues and in tumors. However, CASP8 showed inconsistent expression patterns in normal and tumor tissues. Our results indicate that aberrant methylation of the RASSF1A promoter region may be of importance in the origin and progression of sPNET and AT/RT while the analysed 5'-CpG rich region of the CASP8 gene does not seem to play an important role in these tumors. Further studies of epigenetic changes in these rare tumors are warranted as their biology remains obscure and treatment efforts have been rather unsuccessfull.

Adolescent↗
PubMed2006

Evidence for specific phases in the development of human neuromelanin.

Neuromelanin is a dark-coloured pigment which forms in the dopamine neurons of the human midbrain. The age-related development and regulation of neuromelanin within these dopamine neurons has not been previously described. Optical density and area measurements of unstained neuromelanin in ventral substantia nigra neurons from 29 people spanning the ages of 24 weeks to 95 years old, demonstrated three developmental phases. Neuromelanin was not present at birth and initiation of pigmentation began at approximately 3 years of age, followed by a period of increasing pigment granule number and increasing pigment granule colouration until age 20. In middle and later life the colour of the pigment granules continued to darken but was not associated with any substantial growth in pigment volume. The identification of three phases and changes in the rate of neuromelanin production over time suggests the regulation of neuromelanin production and turnover, possibly through enzymatic processes.

Adolescent↗
PubMed2006

Immunohistochemical profile and chromosomal imbalances in papillary tumours of the pineal region.

The histopathology of papillary tumours of the pineal region (PTPR) closely resembles that of ependymomas and choroid plexus tumours. Therefore, immunohistochemical staining profiles were investigated in a series of 15 PTPR. In addition to cytokeratin, synaptophysin and glial fibrillary acidic protein expression, PTPR were examined for the presence of dot- or ring-like epithelial membrane antigen (EMA) immunoreactivity typically encountered in ependymoma, staining for inwardly rectifying potassium channel Kir7.1 and stanniocalcin-1 (specifically expressed in choroid plexus tumours) as well as microtubule-associated protein-2 (MAP-2). Furthermore, comparative genomic hybridization was performed in five PTPR. Cytokeratin was expressed in all PTPR examined, whereas glial fibrillary acidic protein and synaptophysin staining were absent. Dot- or ring-like EMA immunoreactivity was only observed in 1 out of 15 PTPR. Membranous Kir7.1 and cytoplasmic stanniocalcin-1 staining were present in the minority of PTPR (3/15 and 4/15, respectively). In contrast, MAP-2 immunoreactivity was encountered in 13 out of 15 PTPR, but was significantly less frequently observed in a series of choroid plexus tumours (7/37). PTPR mainly presented with chromosomal losses affecting chromosomes 10 (4/5 cases) and 22q (3/5 cases) as well as gains on chromosomes 4 (4/5 cases), 8 (3/5 cases), 9 (3/5 cases) and 12 (3/5 cases). To conclude, the majority of PTPR can be distinguished from ependymomas and choroid plexus tumours by absent staining for epithelial membrane antigen, Kir7.1 and staniocalcin-1 as well as the presence of distinct MAP-2 immunoreactivity. Antibodies directed against these antigens are thus expected to be valuable markers in the diagnosis of papillary tumours located in the vicinity of the third ventricle.

Adenocarcinoma, Papillary↗
PubMed2005

O-(2-[18F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours.

PURPOSE: The aim of this study was to evaluate the differential uptake of O-(2-[18F]fluorethyl)-L-tyrosine (FET) in suspected primary brain tumours. METHODS: Positron emission tomography (PET) was performed in 44 patients referred for the evaluation of a suspected brain tumour. Acquisition consisted of four 10-min frames starting upon i.v. injection of FET. Tumour uptake was calculated as the ratio of maximal tumour intensity to mean activity within a reference region (FETmax). RESULTS: FET uptake above the cortical level was observed in 35/44 lesions. All histologically confirmed gliomas and many other lesions showed FET uptake to a variable extent. No uptake was observed in nine lesions (one inflammatory lesion, one dysembryoplastic neuroepithelial tumour, one mature teratoma, six lesions without histological confirmation). An analysis of uptake dynamics was done in the patients with increased FET uptake (22 gliomas, three lymphomas, three non-neoplastic lesions, three lesions with unknown histology and four other primaries). Upon classification of tumours into low (i.e. WHO I and II) and high grade (i.e. WHO III and IV), a significant difference in FETmax between the two categories was observed only in the first image frame (0-10 min p.i.), with FETmax=2.0 in low-grade and 3.2 in high-grade tumours (p<0.05); no significant differences were found in frame 4 (30-40 min p.i.), with FETmax=2.4 vs 2.7. Similar results were obtained when the analysis was applied only to astrocytic tumours (2.0 vs 3.1 in the first frame; 2.4 vs 2.6 in the fourth frame). CONCLUSION: These initial results indicate that FET PET is a useful method to identify malignant brain lesions. It appears that high- and low-grade brain tumours exhibit a different uptake kinetics of FET. A kinetic analysis of FET PET may provide additional information in the differentiation of suspected brain lesions.

Adolescent↗
PubMed2005

[Clinical value of amino acid imaging in paediatric brain tumours. Comparison with MRI].

PURPOSE: To evaluate single photon emission computed tomography (SPECT) using the amino acid l-3-[123I]-alpha-methyl tyrosine (IMT) and contrast enhanced magnetic resonance imaging (MRI) as diagnostic tools in primary paediatric brain tumours in respect of non-invasive tumour grading. Patients, materials, methods: 45 children with primary brain tumours were retrospectively evaluated. IMT uptake was quantified as tumour/nontumour-ratio, a 4-value-scale was used to measure gadolinium enhancement on contrast enhanced MRI. Statistical analyses were performed to evaluate IMT uptake and gadolinium enhancement in low (WHO I/II) and high (WHO III/IV) grade tumours and to disclose a potential relationship of IMT uptake to disruption of blood brain barrier as measured in corresponding MRI scans. RESULTS: IMT uptake above background level was observed in 35 of 45 patients. IMT uptake was slightly higher in high grade tumours but the difference failed to attain statistical significance. Grading of individual tumours was neither possible by IMT SPECT nor by gadolinium enhanced MRI. CONCLUSION: IMT is accumulated in most brain tumours in children. Tumour grading was not possible using IMT or contrast enhancement as determined by MRI. Neither morphological nor functional imaging can replace histology in paediatric brain tumours.

Adolescent↗
PubMed2004

[Correlation between clinical apparatus-based differential diagnosis and neuropathological diagnosis in patients with AIDS].

BACKGROUND: During the course of HIV infection, the majority of patients develop opportunistic cerebral neuro-manifestations. If conventional diagnostic tools are not sufficient, a stereotactic biopsy is often necessary. PATIENTS AND METHODS: In order to evaluate the correctness of the clinical diagnosis of cerebral neuro-manifestations in HIV-infected patients, we compared the results of cerebral biopsy or autopsy with the previous clinical diagnosis. A total of 19 biopsies and 49 autopsies could be analyzed. RESULTS: Except for HIV-associated encephalopathy, we detected a very high conformity between the clinical and the neuropathological diagnoses. We obtained the best sensitivity for progressive multifocal leukoencephalopathy (PML), whereas for cerebral toxoplasmosis the worst sensitivity and specificity was identified. CONCLUSION: We conclude that the diagnosis of PML can be made on clinical grounds alone, whereas the diagnosis of cerebral toxoplasmosis and lymphoma often requires a biopsy, which should be performed early.

AIDS Dementia Complex↗
PubMed2003

Plasma cell granuloma involving the brain and the lung.

BACKGROUND: Symptomatic plasma cell granulomas (PCG) of the central nervous system (CNS) are a rare entity, especially in association with an extracranial manifestation. CLINICAL PRESENTATION: A 13 years old boy was operated on for a symptomatic plasma cell granuloma of the lower lobe of the left lung. Four years later, he suffered his first generalized seizure. CT and MRI scans revealed a small hyperdense lesion, which was located in the right frontal lobe, adjacent to the motor strip. Intervention. Stereotactic guided surgery was performed. A plasma cell granuloma was found, which histopathologically resembled the intrapulmonary lesion, which had been removed four years ago. CONCLUSION: Histological findings, differential diagnosis and specific treatment are reviewed and discussed. Patients with PCG should be radiologically staged. Long term prognosis of PCG is good in cases surgically resectable. Nevertheless, patients require lifelong follow up.

Adolescent↗
PubMed2003

Lack of chromosomal imbalances in adamantinomatous and papillary craniopharyngiomas.

Craniopharyngiomas are among the most common paediatric tumours and are thought to arise from embryonic remnants of Rathke's pouch. The molecular mechanisms involved in their formation remain elusive and little is known about chromosomal imbalances that could suggest the locations of tumour suppressor or proto-oncogenes involved in the pathogenesis. The paucity of published data on the molecular basis of such tumours prompted this investigation of 20 adamantinomatous and nine papillary craniopharyngiomas for genetic abnormalities by comparative genomic hybridisation (CGH). CGH revealed no DNA copy number changes in any of the 29 primary craniopharyngiomas, regardless of their histological subtype. These data suggest that chromosomal imbalances are a rare event in both adamantinomatous and papillary craniopharyngiomas.

Adolescent↗
PubMed2002

Immunoglobulin deposition in sural nerves of AIDS patients with distal-symmetric HIV-associated polyneuropathy.

The most frequent neurological diagnosis in peripheral nerve function of HIV-positive individuals is distal-symmetric polyneuropathy (DSPN). In this study we investigated the histopathology as well as the immunohistochemical expression of immunoglobulins IgA, IgG and IgM in post-mortem sural nerve tissue gained from 11 patients who had suffered from DSPN in the clinical course of AIDS (CDC 3C). We found that all 11 sural nerves showed signs of demyelination while in 6 out of 11 cases axonal degeneration could also be detected. Immunohistochemical expression of at least one immunoglobulin was found in all but two cases with deposits uniformly being located immediately beneath the basement membrane of capillary blood vessels and within the perineurium while endoneurial staining was discernable in three cases. The most commonly expressed immunoglobulin was IgA which was identified in 7 cases, followed by IgG and IgM which were positive in 6 and 5 cases, respectively. All three immunoglobulins were found to be expressed simultaneously in only two cases. Thus, our study shows that immunoglobulin deposits among other factors may be implicated in altering the function of sural nerves or enhance their vulnerability. In peripheral nerves they may be responsible for some of the common alterations in the development of AIDS-associated distal symmetric polyneuropathy.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Mycotic cerebral vasculitis in a paediatric cardiac transplant patient excludes misadventure.

We present the case of a 10-year-old girl with cardiomyopathy who received a heart transplant. Due to organ rejection, the dosage of immunosuppressive agents was increased postoperatively. The patient complained of intermittent headaches in the following days and developed a haemorrhagic necrosis of the left thalamus. A week later, an oral dose of cyclosporin A was accidentally given intravenously, and 2 weeks later a recurrent subarachnoid haemorrhage of unknown origin was diagnosed. The clinical course was then characterised by progressive deterioration resulting in coma, fluctuating brain stem symptoms and the development of a massive cerebral oedema with subsequent brain death. A coroner's autopsy was instigated to investigate a claim of medical misadventure. Neuropathological investigations found a focal infiltration of fungal hyphae in the left posterior cerebral artery resulting in necrosis of the vascular wall and thus explaining the source of the recurrent subarachnoid haemorrhage which eventually resulted in the girl's death. Medical misadventure due to the administration of cyclosporin was not directly responsible for the death of this patient. This case illustrates that it is of paramount importance to copiously sample and investigate the basal cerebral arteries in cases of subarachnoid haemorrhage of unknown origin, in particular in a medico-legal context.

Aspergillosis↗
PubMed2001

Population-based epidemiologic data on brain tumors in German children.

BACKGROUND: Brain tumors are the most common disease group of solid tumors in childhood, and children with brain tumors have a relatively poor survival rate. Epidemiologic data from a population-based cancer registry provide the necessary information to obtain a full picture of the frequency of this disease, which is a great challenge in pediatric oncology. METHODS: The German Childhood Cancer Registry (GCCR) is a population-based registry. The level of completeness of patient registration is 95%, but it is somewhat lower for patients with brain tumors. More than 300 children with newly diagnosed brain tumors are reported every year. Analyses of GCCR data are performed according to the International Classification of Childhood Cancer and the recently published World Health Organization classification of tumors of the nervous system. In addition, incidence rates of childhood brain tumors in Germany are compared with those of other countries, as published by the International Agency for Research on Cancer. RESULTS: In the years 1990-1999, a total of 3268 brain tumors were observed (excluding intracranial and intraspinal germ cell tumors). The respective incidence rate for children age < 15 years was 2.6 per 100,000 children and lies between the rates from other countries, which range between 1.7 and 4.1 per 100,000 children. The most common brain tumors were astrocytomas (41.7%), medulloblastomas (18.1%), ependymomas (10.4%), supratentorial primative neuroectodermal tumors (PNETs; 6.7%), and craniopharyngiomas (4.4%). They were located mainly in the cerebellum (27.9%) and the cerebrum (21.2%). The 5-year survival rate for all brain tumors was 64%, with the poorest prognosis for children with PNET. CONCLUSIONS: The large data base of the GCCR made it possible to present representative data on patients with childhood tumors of the central nervous system in Germany. The data quality was high, not least because of the strong cooperation with corresponding clinical trials. However, for children with central nervous system tumors, the ascertainment of newly diagnosed patients needs further improvement.

Adolescent↗
PubMed2001

Tumors of the choroid plexus.

Choroid plexus tumors are rare intraventricular papillary neoplasms derived from choroid plexus epithelium, which account for only between 0.4-0.6% of all intracranial and 2-3% of pediatric neoplasms. Plexus papillomas outnumber choroid plexus carcinomas by a ratio of 5:1 and around 80% of choroid plexus carcinomas arise in children. Plexus tumors are most common in the lateral and fourth ventricles; while 80% of lateral ventricle tumors present in children, fourth ventricle tumors are evenly distributed in all age groups. Clinically, choroid plexus tumors tend to cause hydrocephalus and increased intracranial pressure. Histologically, choroid plexus papillomas correspond to WHO grade I, choroid plexus carcinomas to WHO grade III. Immunohistochemically, cytokeratins and vimentin are expressed by virtually all choroid plexus papillomas and most choroid plexus carcinomas while transthyretin and S-100 protein are present in 80-90% of cases, less frequently, though, in choroid plexus carcinomas. Glial fibrillary acidic protein can be found focally in about 25-55% of choroid plexus papillomas and 20% of choroid plexus carcinomas. The mean Ki67/MIB1 labeling index for choroid plexus papillomas is 1.9%, for choroid plexus carcinomas 13. 8%. Choroid plexus papillomas typically show hyperdiploidy with gains particularly on chromosomes 7, 9, 12, 15, 17, and 18 while one choroid plexus carcinoma showed rearrangements of chromosomes 7p11-12, 9q11-12, 15q22, and 19q13.4. Choroid plexus papillomas can usually be cured by surgery alone with a 5-year survival rate of up to 100% with occasional recurrences while choroid plexus carcinomas grow more rapidly and have a less favorable outcome with a 5-year survival rate of 26-40%.

Animals↗
PubMed2001

Comparative genomic hybridization in pineal parenchymal tumors.

Nine pineal parenchymal tumors were studied by comparative genomic hybridization. These consisted of three pineocytomas (WHO grade II), three pineal parenchymal tumors of intermediate differentiation (WHO grade III), and three pineoblastomas (WHO grade IV). An average of 0 chromosomal changes per pineocytoma, 5.3 per pineal parenchymal tumor of intermediate differentiation (3.3 gains vs. 2.0 losses), and 5.6 per pineoblastoma (2.3 gains vs. 3.3 losses) were found. The most frequent DNA copy number changes among pineal parenchymal tumors of intermediate differentiation and pineoblastomas were gains of 12q (3/6 cases), 4q, 5p, and 5q (2/6 cases each), as well as losses of 22 (4/6 cases), 9q, and 16q (2/6 cases each). Among pineal parenchymal tumors of intermediate differentiation, the most common chromosomal imbalances were +4q, +12q, and -22 (2/3 cases each), and in pineoblastomas -22 (2/3 cases). Five high level gains were identified, all of them in pineoblastomas; these were found on 1q12-qter, 5p13.2-14, 5q21-qter, 6p12-pter, and 14q21-qter. Clinically, all patients with pineocytomas and pineal parenchymal tumors of intermediate differentiation were alive after a mean observation time of 142 and 55 months, respectively, whereas all patients with pineoblastomas had died after an average of 17 months. Our findings suggest that pineal parenchymal tumors of intermediate differentiation are cytogenetically more similar to pineoblastomas and prognostically more similar to pineocytomas. Furthermore, imbalances in higher-grade pineal parenchymal tumors mainly affect gains of 12q and losses of chromosome 22.

Adult↗
PubMed2001

[Primary central nervous system lymphoma as a neurological manifestation of AIDS stage].

In patients infected with human immunodeficiency virus (HIV), the risk of developing non-Hodgkin's lymphoma is over 100 times greater than with noninfected persons. Primary central nervous system lymphoma as a complication of the acquired immunodeficiency syndrome (AIDS) occurs in up to 2.4% of all cases and is strongly associated with the Epstein-Barr virus. The prognosis is very poor, with a mean survival time of 21 to 27 days without therapy and up to 119 days with radiation therapy. We describe the course of seven AIDS patients with histologically proven primary central nervous system lymphoma and present a review of clinical symptoms, diagnosis, and therapy. The main criteria for differential diagnosis from other secondary neuromanifestations such as cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, abscesses, and infarctions are described.

AIDS-Related Opportunistic Infections↗