Search PubMed⌕ Search

Biomedical subjects

S Brandner

Publications and source records attributed to S Brandner.

At least 19 recordsLinked to original sources
PubMed2006

Prion infectivity in variant Creutzfeldt-Jakob disease rectum.

BACKGROUND: Disease-related prion protein (PrP(Sc)) is readily detectable in lymphoreticular tissues in variant Creutzfeldt-Jakob disease (vCJD), but not in other forms of human prion disease. This distinctive pathogenesis, with the unknown population prevalence of asymptomatic vCJD infection, has led to significant concerns that secondary transmission of vCJD prions will occur through a wide range of surgical procedures. To date PrP(Sc):prion infectivity ratios have not been determined in vCJD, and it is unknown whether vCJD prions are similar to experimental rodent prions, where PrP(Sc) concentration typically reflects infectious prion titre. AIM: To investigate prion infectivity in vCJD tissue containing barely detectable levels of PrP(Sc). METHODS: Transgenic mice expressing only human PrP (Tg(HuPrP129M(+/+)Prnp(o/o))-35 and Tg(HuPrP129M(+/+)Prnp(o/o))-45 mice) were inoculated with brain or rectal tissue from a previously characterised patient with vCJD. These tissues contain the maximum and minimum levels of detectable PrP(Sc) that have been observed in vCJD. RESULTS: Efficient transmission of prion infection was observed in transgenic mice inoculated with vCJD rectal tissue containing PrP(Sc) at a concentration of 10(4.7)-fold lower than that in vCJD brain. CONCLUSIONS: These data confirm the potential risks for secondary transmission of vCJD prions via gastrointestinal procedures and support the use of PrP(Sc) as a quantitative marker of prion infectivity in vCJD tissues.

Animals↗
PubMed2003

Extensive spherical amyloid deposition presenting as a pituitary tumor.

A 71-yr-old man was admitted for further evaluation and trans-sphenoidal surgery of a pituitary tumor. He complained of impotence and decreased libido over a period of about 40 yr. Thirty-eight yr ago he was treated for bilateral gynecomastia with galactorrhea. Endocrinological investigation at presentation revealed only mild hyperprolactinemia and hypogonadotropic hypogonadism. Pituitary magnetic resonance imaging (MRI) showed a tumor up to 2.5 cm in diameter with infiltration of the sphenoid sinus and right cavernous sinus. The tumor exhibited a heterogeneous hyperintense signal on T1-weighted images and hypointense signal on T2-weighted images. Standard trans-sphenoidal surgery was performed and a brownish mass was found inside the sella, which was removed. Histological examination of the mass revealed extensive spherical amyloid deposits with strongly positive immunohistochemical staining for prolactin. Therefore, a prolactinoma with extensive spherical amyloid deposition was diagnosed. Extensive spherical amyloid deposition is a rare finding in prolactin-secreting pituitary adenomas. So far, characteristic radiological findings by MRI have been described only twice. Due to characteristic MRI findings, the diagnosis of extensive intrasellar amyloid deposition can be entertained pre-operatively. Trans-sphenoidal surgical resection is essential to confirm the diagnosis histologically and because of the potential lack of tumor shrinkage under dopaminagonist therapy in this type of prolactinoma.

Aged↗
PubMed2003

Lhermitte-Duclos disease in 3 children: a clinical long-term observation.

We report three boys in whom a diagnosis of Lhermitte-Duclos disease (LDD) was assumed from characteristic neuroimaging findings. LDD was confirmed by an open biopsy in patient 1, while a biopsy in patient 2 was inconclusive. Histologic confirmation in patient 3 was deliberately not attempted. However, a follow-up observation of stable clinical and neuroimaging findings over 2, 5 and 11 years, respectively, support the diagnosis of LDD. Despite extensive expansion of the lesion with brainstem involvement, clinical signs in two boys were minimal, while one patient has cognitive impairment and a complex oculomotor disturbance. So far we found no evidence for an association with Cowden disease (CD). No germline PTEN mutations were detected in these children, but the amount of available biopsy tissue in patients 1 and 2 was insufficient for a complete genetic analysis of tumor tissue. In conclusion, LDD can usually be diagnosed by MRI. In view of the favourable natural history, a conservative "wait and see" strategy is justified, particularly if radical tumor resection is not possible. LDD is often not associated with CD and germline PTEN mutations seem not to be present in isolated LDD.

Cerebellar Neoplasms↗
PubMed2001

Germline SDHD mutation in paraganglioma of the spinal cord.

Hereditary paraganglioma of the head and neck is associated with germline mutations in the SDHD gene, which encodes a mitochondrial respiratory chain protein. Paragangliomas of the central nervous system are very rare, occur almost exclusively in the cauda equina of the spinal cord and are considered non-familial. In the present study, we screened 22 apparently sporadic paragangliomas of the cauda equina for SDHD mutations. One spinal paraganglioma and similar cerebellar tumours that developed 22 years later in the same patient contained a missense mutation at codon 12 (GGT-->AGT, Gly-->Ser) and a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). There was no family history of paragangliomas but DNA from white blood cells of this patient showed the same sequence alterations, indicating the presence of a germline mutation. All other cases of spinal paraganglioma had the wild-type SDHD sequence, except one case with a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). This is the first observation indicating that inherited SDHD mutations may occasionally cause the development of paragangliomas in the central nervous system.

Cauda Equina↗
PubMed2001

Kell and XK immunohistochemistry in McLeod myopathy.

The McLeod syndrome is an X-linked neuroacanthocytosis manifesting with myopathy and progressive chorea. It is caused by mutations of the XK gene encoding the XK protein, a putative membrane transport protein of yet unknown function. In erythroid tissues, XK forms a functional complex with the Kell glycoprotein. Here, we present an immunohistochemical study in skeletal muscle of normal controls and a McLeod patient with a XK gene point mutation (C977T) using affinity-purified antibodies against XK and Kell proteins. Histological examination of the affected muscle revealed the typical pattern of McLeod myopathy including type 2 fiber atrophy. In control muscles, Kell immunohistochemistry stained sarcoplasmic membranes. XK immunohistochemistry resulted in a type 2 fiber-specific intracellular staining that was most probably confined to the sarcoplasmic reticulum. In contrast, there was only a weak background signal without a specific staining pattern for XK and Kell in the McLeod muscle. Our results demonstrate that the lack of physiological XK expression correlates to the type 2 fiber atrophy in McLeod myopathy, and suggest that the XK protein represents a crucial factor for the maintenance of normal muscle structure and function.

Amino Acid Transport Systems, Neutral↗
PubMed2001

Normal neurogenesis and scrapie pathogenesis in neural grafts lacking the prion protein homologue Doppel.

The agent that causes prion diseases is thought to be identical to PrPSc, a conformer of the normal prion protein PrPC. Recently a novel protein, termed Doppel (Dpl), was identified that shares significant biochemical and structural homology with PrPC. To investigate the function of Dpl in neurogenesis and in prion pathology, we generated embryonic stem (ES) cells harbouring a homozygous disruption of the Prnd gene that encodes Dpl. After in vitro differentiation and grafting into adult brains of PrPC-deficient Prnp0/0 mice, Dpl-deficient ES cell-derived grafts contained all neural lineages analyzed, including neurons and astrocytes. When Prnd-deficient neural tissue was inoculated with scrapie prions, typical features of prion pathology including spongiosis, gliosis and PrPSc accumulation, were observed. Therefore, Dpl is unlikely to exert a cell-autonomous function during neural differentiation and, in contrast to its homologue PrPC, is dispensable for prion disease progression and for generation of PrPSc.

Animals↗
PubMed2001

Second primary glioblastoma.

Although characterized by a highly variable phenotype and multiple genetic alterations, glioblastomas are considered monoclonal in origin. We here report on a 64-yr-old patient who developed a second glioblastoma in the left frontal lobe 10 yr after surgical resection of a glioblastoma of right frontal lobe. The first tumor contained 2 p53 mutations, in codon 213 (CGA-->TGA, Arg-->stop) and codon 306 (CGA-->TGA, Arg-->stop), further, 1 missense PTEN mutation (codon 257, TTC-->TTA, Phe-->Leu) and a silent PTEN mutation (codon 154, TTC-->TTT, Phe-->Phe). The second glioblastoma also contained multiple, but different mutations: p53 mutations in codons 158 (CGC-->CAC, Arg-->His) and 273 (CGT-->TGT, Arg-->Cys), and a PTEN mutation in codon 233 (CGA-->TGA, Arg-->Stop). Both neoplasms had a homozygous p16 deletion. The discordant pattern of mutations indicates that the second glioblastoma was not a recurrence but an independent second glioblastoma. The presence in these neoplasms of multiple mutations in tumor suppressor genes suggests the involvement of a novel disease mechanism but there was no indication of a DNA mismatch repair deficiency or of an inherited tumor syndrome.

Chromosomes, Human, Pair 10↗
PubMed2001

Neuroimaging of cerebellar liponeurocytoma. Case report.

Cerebellar liponeurocytoma is a newly recognized, rare clinicopathological entity. It manifests with posterior fossa symptoms in adults and is characterized histopathologically by advanced neuronal and focal lipomatous differentiation with a low level of mitotic activity. The authors analyzed the computerized tomography (CT) and magnetic resonance (MR) imaging findings in two patients with histopathologically proven cerebellar liponeurocytomas and review the literature. Cerebellar liponeurocytoma may be suspected on the basis of neuroimaging findings that demonstrate an intraaxial neoplasm with the propensity for exophytic growth into the adjacent subarachnoid spaces. On CT scans, the tumor commonly presents as a hypointense mass with intermingled areas exhibiting the attenuation values of fatty tissue. On T1-weighted MR images, the tumor is hypointense with scattered foci of hyperintense signal and displays moderate contrast enhancement. On T1-weighted MR images, the tumor is slightly hyperintense to cortex, and edema is usually absent. Areas of fat density as assessed on CT scans and of T1 hyperintensity seen on MR images help to distinguish this rare neoplasm from the more common adult medulloblastomas or ependymomas. The available follow-up data indicate a favorable clinical prognosis; therefore, knowledge and precise characterization of this tumor is important to avoid unnecessary adjuvant radio- or chemotherapy.

Adult↗
PubMed2000

[Vasculitis and mononeuritis multiplex].

In 1991, a 67 year old patient, suffering from an adenocarcinoma of the colon, had to undergo hemicolectomy. In the five following years, isolated metastases developed in the liver and have been surgically removed. In 1997, acute mononeuritis multiplex appeared and nerve biopsy revealed vasculitis. There were no signs of inflammatory rheumatic illness, collagenosis, cryglobulinemia, infection or hypersensitivity to medication. We have therefore postulated a relation between the vasculitis and the malignancy. Tumorous relapse could however not be detected at that time. Under immunosuppressive therapy, the neurological deficiencies receded partially, though the carcinoma of the colon reappeared with systemic metastases in the wake of the vasculitis. Diagnostic measures and the relationship between malignancy and vasculitis are discussed.

Adenocarcinoma↗
PubMed2000

[Mechanisms of neuroinvasion by prions: molecular principles and present state of research].

The prion was defined by Stanley Prusiner as the infectious agent that causes transmissible spongiform encephalopathies and equated with the prion protein PrPSc. Its cognate gene, Prnp, was identified by Charles Weissmann in Zurich, and shown to encode the host protein PrPC. Since the latter discovery, transgenic mice have contributed many important insights to the field of prion biology, including an understanding of the molecular basis of the species barrier for prions. By disrupting the Prnp gene, it was shown that an organism that lacks PrPC is resistant to infection by prions. Introduction of mutant PrP genes into PrP-deficient mice was used to investigate the structure-activity relationship of the PrP gene with regard to scrapie susceptibility. Ectopic expression of PrP in Prnp-knockout mice provided a useful strategy for the identification of host cells competent for prion replication. Finally, the availability of Prnp-knockout mice and transgenic mice overexpressing PrP allows selective reconstitution experiments aimed at expressing PrP in neurografts or in specific populations of hemato- and lymphopoietic cells. The latter studies have allowed us to clarify some of the mechanisms of prion spread and disease pathogenesis.

Animals↗
PubMed2000

Prions: from neurografts to neuroinvasion.

Spongiform encephalopathies are infectious neurodegenerative diseases caused by pathogens that seem to be devoid of any informational nucleic acids. Histopathologically, these diseases are characterized by spongiform degeneration of the central nervous system. Although the main pathological changes during the course of the disease occur in the brain, the infectious agent accumulates early in lymphoid tissue. The consecutive development of clinical disease depends on the presence of an intact immune system including mature B-cells and follicular dendritic cells. In this article we review the state of knowledge on the routes of neuroinvasion used by the infectious agent in order to gain access to the central nervous system upon entry into extracerebral sites.

Animals↗
PubMed2000

Meningeal hemangiopericytoma in childhood.

Meningeal hemangiopericytoma (MHP) is extremely rare in childhood. Mean age at diagnosis is between 38 and 43 years. We present an 8-year-old boy with MHP of the middle cranial fossa. Imaging findings were indistinguishable from an aggressive bone tumor such as Ewing's sarcoma. Imaging findings are presented and discussed. Our case indicates that MHP should be considered in the differential diagnosis of skull-base tumors despite the fact that MHP is extremely rare in childhood.

Child↗
PubMed2000

Mitochondrial diseases represent a risk factor for valproate-induced fulminant liver failure.

We report on 3 siblings (2 females and 1 male) with chronic progressive external ophthalmoplegia (CPEO), compatible with inherited mitochondrial cytopathy. The younger of the two sisters died at the age of 37 due to progressive respiratory failure. The older one presented with a status epilepticus at the age of 39 and was treated with valproate. Five months after the start of treatment, she developed fulminant liver failure and died. The brother has suffered from CPEO since early childhood but has had so far no other symptoms of a mitochondrial disease. A muscle biopsy from the younger sister revealed ragged-red fibers and decreased activities of complex I and IV of the respiratory chain but no pathogenic mutations in the mitochondrial tRNA genes or in several locations in the coding region of the mitochondrial genome. In the older sister's liver (obtained post-mortem), mitochondrial DNA was fragmented and could not be investigated. The clinical presentation and the biochemical findings suggest that all 3 siblings suffered from a mitochondrial cytopathy. Since mitochondrial cytopathies and valproate-induced fulminant liver failure are both rare events, an association between them is likely. Mitochondrial diseases should therefore be considered as a risk factor for valproate-induced liver failure and be excluded before treatment with valproate.

Adult↗