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Biomedical subjects

A Aguzzi

Publications and source records attributed to A Aguzzi.

At least 163 records · Page 9Linked to original sources
PubMed1996

Tyrosinase is a new marker for cell populations in the mouse neural tube.

Tyrosinase, the key enzyme in melanin synthesis, is expressed in pigment cells derived from both neural crest and neuroectoderm. The present study was performed to detect tyrosinase promoter activity and tyrosinase gene expression during murine brain development. Mouse tyrosinase 5' region (6.1 Kb) was used to direct lacZ expression in transgenic mice. During embryogenesis, the transgene reproduced tyrosinase expression in pigment cells but was also observed in embryonic neuroectoderm and migrating neural crest cells. Both tyrosinase and lacZ were detected in cell populations often organized in columnar arrangements and found throughout the entire neural tube, in the cranial region as well as in the spinal chord. In the developing brain, the highest density of positive cells was localized to ventricular and subventricular zones and to evaginations of the neural tube such as optic vesicle, pineal gland, and olfactory bulbs. These results demonstrate that tyrosinase promoter activity and tyrosinase expression are not restricted to differentiated pigment cells. We suggest that tyrosinase is a new marker for cell populations in the neural tube, and that expression is correlated to regions undergoing rapid cell proliferation.

Animals↗
PubMed1996

Transgenic and knockout mice in the study of neurodegenerative diseases.

Accurate animal models are essential for detailed analysis of the mechanisms underlying human neurodegenerative diseases. In addition, they can offer useful paradigms for the development and evaluation of new therapeutic strategies. We review the most popular techniques for modification of the mammalian genome in vivo, and provide a critical evaluation of the available transgenic mouse models for several neurological conditions of humans, including prion diseases, human retroviral diseases, Alzheimer's disease, and motor neuron diseases.

Animals↗
PubMed1996

Disseminated encephalitis following streptococcal infection.

Various neurological disorders have been related to Streptococcus pyogenes infection. Only recently, and for the first time, it has been suggested that acute disseminated encephalitis may also complicate a streptococcal infection. The case reported in this paper seems to confirm this hypothesis.

Adolescent↗
PubMed1996

Total removal of a primary intracranial squamous cell carcinoma invading the brain stem.

BACKGROUND: Primary intracranial squamous cell carcinomas are extremely rare, and commonly manifest as malignant transformations of intracranial epidermoid cysts. METHODS: A case of primary squamous cell carcinoma invading the ventral brain stem and the trigeminal entry zone is described. The tumor was microsurgically totally removed via a paramedian supracerebellar approach. Three years after the operation the tumor recurred, and was again totally removed using the same approach. RESULTS: The patient showed no postoperative neurologic deterioration except for a transient deterioration of gait disturbances. The pathologic diagnosis was a recurrence of the squamous cell carcinoma. CONCLUSIONS: Since primary intracranial squamous cell carcinomas grow slowly and have a well demarcated capsule, total removal should be considered whenever possible.

Brain Neoplasms↗
PubMed1996

Tubular adenoma of the choroid plexus: evidence for glandular differentiation of the neuroepithelium.

A case of tubular adenoma arising in the right ventricular choroid plexus of a 4-month-old boy is described. A basic pattern of neoplastic glandular epithelium and lack of papillary architecture distinguished this tumor from a papilloma. Coexpression of S -100 protein, transthyretin and cytokeratin identified the neoplastic cells as being of choroid plexus origin. Immunohistochemical detection of MIB-1 showed a proliferation rate (16%) similar to adenomas in more conventional locations, but not encountered in benign brain tumors. In situ detection of DNA-derived oligonucleosomal fragments by TUNEL analysis, on the other hand, detected apoptotic activity in 5-8% of tumor cells. The indolent course of the disease in the present case, thus, might suggest a compensatory elimination of proliferating cells by apoptosis. This possibly points to mechanisms of neoplastic transformation different from those involved in choroid plexus papillomas.

Adenoma↗
PubMed1996

The standard isoform of CD44 is preferentially expressed in atypical papillomas and carcinomas of the choroid plexus.

Isoforms of the CD44 adhesion molecule have been assigned a pivotal role in tumor invasion and metastasis. CD44 splice variants may be selectively expressed in various normal and neoplastic tissues. We investigated immunohistochemically the presence of the standard (H) and two variant (v3, v6) isoforms of the CD44 molecule in a series comprising 13 choroid plexus papillomas (WHO grade I) and 8 carcinomas (WHO grade III). In the papilloma group, 5 tumors showed variable cellular pleomorphism and foci of infiltrative growth, and were tentatively classified as atypical papillomas. Autopsy specimens of normal pediatric and adult choroid plexus were used as control. Western-blot analysis of CD44H was carried out on 4 carcinomas, 1 papilloma and on normal choroid plexus. The proliferation rate was assessed by MIB-1 immunoreactivity. The normal choroid plexuses and 9 papillomas were negative for the standard as well as the variant CD44 molecules investigated. Four atypical papillomas and 5 carcinomas expressed CD44H. CD44v3 and CD44v6 were only detected in one of the atypical papillomas also positive for CD44H. These data indicate that CD44H is preferentially expressed on atypical papillomas and carcinomas and may correlate with the infiltrative growth of these tumors.

Adolescent↗
PubMed1996

Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria.

Acute intermittent porphyria (AIP) is a human disease resulting from a dominantly inherited partial deficiency of the heme biosynthetic enzyme, porphobilinogen deaminase (PBGD). The frequency of the trait for AIP is 1/10,000 in most populations, but may be markedly higher (1/500) in psychiatric patients. The clinical expression of the disease is characterized by acute, life-threatening attacks of 'porphyric neuropathy' that include abdominal pain, motor and sensory neurological deficits and psychiatric symptoms. Attacks are frequently precipitated by drugs, alcohol and low caloric intake. Identical symptoms occur in other hepatic porphyrias. To study the pathogenesis of the neurologic symptoms of AIP we have generated Pbgd-deficient mice by gene targeting. These mice exhibit the typical biochemical characteristics of human AIP, notably, decreased hepatic Pbgd activity, increased delta-aminolevulinic acid synthase activity and massively increased urinary excretion of the heme precursor, delta-aminolevulinic acid after treatment with drugs such as phenobarbital. Behavioural tests reveal decreased motor function and histopathological findings include axonal neuropathy and neurologic muscle atrophy.

Aminolevulinic Acid↗
PubMed1996

Pathogenesis of spongiform encephalopathies: an update.

In the last 40 years, the pathogenesis of transmissible spongiform encephalopathies of humans and animals have been the subject of exciting discoveries and also of passionate controversies. Although the human forms of these diseases are rare, the recent epidemics of bovine spongiform encephalopathy has most dramatically raised the issue of the transmissibility from affected animals to humans. This review summarizes some current hypotheses on the nature of the infectious agent causing these diseases, and on the pathogenetic pathways which produce histologically detectable damage to the central nervous system. The main focus is on the use of transgenic and knockout mice which, combined with organ transplantation and bone marrow reconstitution techniques, have provided powerful tools for dissecting the pathogenesis of these diseases.

Animals↗
PubMed1996

[Consensus report: tissue handling in suspected Creutzfeldt-Jakob disease and other spongiform encephalopathies (prion diseases) in the human. European Union Biomed-1 Concerted Action].

Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion diseases) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. The autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for safe performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories experienced in handling tissue from transmissible spongiform encephalopathies. In essence, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potentially infectious material must be adequately decontaminated by specific means. The full English text of this Consensus Report was published in Brain Pathology 5: 319-322 (1995).

Autopsy↗
PubMed1996

Telencephalic transplants in mice: characterization of growth and differentiation patterns.

Telencephalic grafting represents a powerful tool for developmental studies and for the investigation of biological features of transgenic brain tissue. The interpretation of grafting experiments, however, requires detailed knowledge of graft biology. Therefore, we have characterized growth rates, graft size, and differentiation of embryonic telencephalic tissue harvested at various developmental stages and grafted into the caudoputamen and lateral ventricles of histocompatible mice. A total of 164 grafts were analysed up to 500 days after transplantation. Of all transplants, 79.3% resulted in the formation of solid neural grafts. Grafted cells were identified by 3H-thymidine labelling and autoradiography. Proliferation was studied by bromodeoxyuridine incorporation and decreased from an initial 35% at 1-3 d after grafting to less than 1.6% after 40 days. The graft size was measured as a function of the embryonic age of the transplanted tissue. Our data indicate that telencephalic tissue harvested at embryonic day E 12.5 reproducibly yields large, fully differentiated neuroectodermal grafts. The parameters defined in this study will be useful for detailed analysis of neuroectodermal tissue from mice undergoing fatal neurodegeneration, such as knockout mice bearing lethal mutations.

Animals↗
PubMed1996

Comparative in vivo and pathological analysis of the blood-brain barrier in mouse telencephalic transplants.

The post-transplantation status of the blood-brain barrier (BBB) is still a matter of debate. In an attempt to define BBB properties after neural transplantation in mice of a defined genetic background, we have used two exogenous markers (horseradish peroxidase and Evans blue), one endogenous marker (immunoglobulins), and in vivo contrast enhanced magnetic resonance imaging (MRI) and compared the results obtained with the different methods. With all four techniques employed, we found the BBB to be reconstituted in 67% of the grafts 3 weeks after grafting, and in more than 90% of all grafts 50 days after grafting. Horseradish peroxidase and contrast enhanced MRI were the most sensitive techniques, the latter offering the unique advantage of repetitive scanning of individual grafts. Our findings provide important information for transplantation studies in mouse models for neurodegenerative diseases.

Animals↗
PubMed1996

MIB-1 immunoreactivity reveals different labelling in low-grade and in malignant epithelial neoplasms of the choroid plexus.

MIB-1 immunohistochemistry was carried out on a retrospective biopsy series of epithelial choroid plexus neoplasms in order to assess the proliferation rate of tumour cells. The material included 14 cases of papilloma (WHO grade I) and five cases of carcinoma (WHO grade III). There was one recurrent tumour in the papilloma group, while three patients with carcinoma experienced recurrence. Choroid plexus obtained at autopsy from paediatric and adult patients with unrelated diseases served as control. The average MIB-1 labelling index of choroid plexus papillomas was 3.7%, while that of carcinomas was 14%, and that of normal choroid plexus was 0.02% to 0.06%. The age and sex of the patients as well as the tumour localization were not found to influence MIB-1 reactivity. The labelling index of recurrent lesions was not significantly different from that of the corresponding primary tumours. High MIB-1 labelling indices were associated with less favourable post-operative outcome in choroid plexus carcinomas and in one papilloma with atypical histology. However, most tumours with atypical histological features did not exhibit distinctive MIB-1 labelling indices. Analysis of growth fraction by MIB-1 immunohistochemistry may prove a useful ancillary method for assessing the malignant potential of choroid plexus neoplasms.

Adolescent↗
PubMed1996

Neuroectodermal grafting: a new tool for the study of neurodegenerative diseases.

Transgenic and knockout mice have contributed much to our current understanding of the role played by single genes during development and in pathological processes of the CNS, such as neuro-degeneration. However, embryonic lethality resulting from the disruption of important genes has often hindered the interpretation of such experiments. Grafting of immature cells from genetically modified organisms into healthy recipients promises to efficiently bypass this problem. We have used neural transplantation techniques which allow us to keep CNS tissue of knockout and transgenic mice viable for a prolonged period of time in the brain or in the kidney capsule of healthy recipients. We have characterized biological parameters such as growth, proliferation and differentiation and also the formation of an intact blood-brain barrier (BBB) after grafting of wild-type telencephalic anlage in this system. We have also employed this technique to study the longterm properties of neuroepithelial tissue derived from knockout mice. The results of our studies are discussed in the context of neurodegenerative diseases.

Adenosine Triphosphatases↗