Neonatal spinal muscular atrophy type 1 with bone fractures and heart defect.

The authors present the case of an infant girl with severe generalized weakness, multiple bone fractures, and heart defect. She needed mechanical ventilation from birth. Radiographs showed mid-diaphyseal fractures of both humeri and of the right femur as well as generalized osteopenia. Electroneuromyography showed spontaneous fibrillations at rest with no active movements. Motor response to a stimulus could not be registered. A systolic heart murmur was detected, and echocardiography showed a large atrial septal defect and an additional membrane in the left atrium. DNA analysis confirmed the diagnosis of spinal muscular atrophy on the third day of life. Histology of the muscle showed both hypertrophic and atrophic fibers. Degenerating swollen neurons were found in the ventral horns of the spinal cord and also in the mesencephalic red nucleus, which has not been described before. Humeral bone showed only partly formed cortical bone. The spectrum of spinal muscular atrophy is very diverse, and atypical clinical findings do not always rule out 5q spinal muscular atrophy. The SMN1 gene should still be investigated.

Sarcoidosis (Heerfordt syndrome): a case report.

We report the case of a 22-year-old woman who is suspected of having primary Sjögren s syndrome. She complaining of bilateral swelling of eyelids and the parotid glands of three weeks duration. Physical examination revealed a bilateral enlargement of both parotid glands, which were solid and painful. Sjögren s syndrome was suspected at that stage, and the serologic and specific analysis were done. All these tests didn t find any autoimmune or visceral features typical of Sjögren s syndrome and autoantibodies were negative. During follow-up time the right facial nerve palsy developed. Pulmonary radiography revealed bihilar lymphadenopathy and labial salivary gland biopsy revealed non-caseating granuloma. The patient was classified as having stage I sarcoidosis. This case demonstrates the importance of being aware of the leading clinical signs and symptoms in case of Heerfordt syndrome.

Tissue plasminogen activator and neuroserpin are widely expressed in the human central nervous system.

Tissue plasminogen activator (tPA) is increasingly recognized to play important roles in various physiological and pathological processes in the central nervous system (CNS). Much of the data on the involvement of plasminogen activators in neurophysiology and -pathology have been derived from studies on experimental animals. We have now performed a systematic characterization of the expression of tPA and its inhibitor, neuroserpin, in normal human CNS. Brain and spinal cord samples from 30-36 anatomic locations covering all major brain regions were collected at 9 autopsies of donors with no neurological disease. Tissues were embedded in paraffin and tissue arrays were constructed. In two cases parallel samples were snap-frozen for biochemical analysis. Expression and activity profiling of tPA and neuroserpin were performed by immunohistochemistry, in situ hybridization, immunocapture and zymography assays. In the adult CNS, tPA was expressed at the mRNA and protein levels in many types of neurons, in particular in thalamus, cortex of cerebellum, pontine nuclei, neocortex, limbic system, and medulla oblongata. Interestingly, tPA was often co-expressed with its CNS inhibitor, neuroserpin. Despite overlapping expression of tPA and neuroserpin, zymography and immunocapture assays demonstrated that human neural tissue is a rich source of active tPA. Our analysis documents a detailed map of expression of tPA and its inhibitor in the human CNS and is compatible with the view that tPA is a key player in CNS physiology and pathology.

Identification of the immunodominant regions of the melanoma antigen tyrosinase by anti-tyrosinase monoclonal antibodies.

Tyrosinase, the critical enzyme in melanin synthesis, is also found to be expressed in most malignant melanomas and can serve as a target for the immune response by both CD4+ and CD8+ T-cells. Therefore it could be used as a potential target for therapeutic intervention in tyrosinase-positive melanomas. In order to develop serological reagents for the immunodetection of human tyrosinase and to find the most immunogenic region of the protein, we have raised a panel of monoclonal antibodies (MAbs) against recombinant tyrosinase expressed and purified from bacteria. Epitope mapping revealed the 79 amino acid long stretch between 163 and 241 residues to be the most immunodominant region of the tyrosinase. This region could be further divided into three parts by binding different MAbs. These MAbs were very useful tools for the detection of tyrosinase expression from different constructs in tissue culture cells by immunocytochemistry and in melanocytes by immunohistochemistry. Some of the MAbs that recognized epitopes between 163 and 204 amino acids also recognized an additional distinct protein of about 70 kDa seen on Western blot analysis of transfected and non-transfected COS-7 cells. One of these, the MAb 4B1, was used in immunohistochemistry, and cross reaction with the basement membrane of the human tissue was observed. The analysis of the 4B1 MAb epitope showed that the C-terminal part of that region almost entirely overlaps with the sequence of the recently reported basement membrane protein beta-netrin.

Odontogenic tumours, a collaborative retrospective study of 75 cases covering more than 25 years from Estonia.

INTRODUCTION: The aim of the present collaborative study was to analyse retrospectively the character of odontogenic tumours in Estonia, involving the entire Estonian population (1.4 million), and to compare their prevalence with the figures presented in similar reports from other countries. MATERIAL AND METHODS: All material for the retrospective study was retrieved from the files of the Departments of Maxillofacial Surgery in Tartu and Tallinn, Estonia, where all in/out-patients are treated from the whole country. The final diagnosis in each case of odontogenic tumour was based on the 1992 WHO histological criteria. RESULTS: A total of 75 odontogenic tumours was found, 74 (98.6%) of which were benign, and 1 (1.3%) was malignant. The frequency of odontogenic tumours in this study was the lowest ever reported. The most common tumours were odontoma (34.3%), followed by ameloblastoma with different subtypes (25.3%), ameloblastic fibroma (16%), odontogenic myxoma (12%) and benign cementoblastoma (8%). CONCLUSION: Odontogenic tumours are relatively rare in Estonia compared with the data from other countries.

Mandibular ameloblastoma and maxillary adenoid cystic carcinoma: case report.

We report the case of a 74-year-old woman who developed a follicular ameloblastoma of the right mandible and 22 months later developed a cribriform adenoid cystic carcinoma of the soft palate on the right maxilla. The ameloblastoma was treated by hemimandibulectomy, and the adenoid cystic carcinoma was managed by resection of the soft palate and the surrounding tissue and bone followed by a 6-week course of radiotherapy. Our review of the literature indicates that only one similar case has been previously reported where an odontogenic tumor and a salivary gland tumor involved two different anatomic locations in the same patient at nearly the same time.

Neoplastic meningitis as the presenting manifestation of gastric adenocarcinoma.

A middle aged man presented with clinical signs of chronic meningitis, including bilateral hearing loss and progressive blindness. Lumbar puncture revealed a mild elevation in lymphocyte number, an elevation in protein levels, and diminished glucose levels, without malignant cells. Magnetic resonance imaging (MRI) T2 weighted seqeunces showed bilateral enhancement of the acoustic nerves. The aetiology of the chronic meningitis was revealed gastric cancer by gastroscopy, and micrometastasis by bone marrow trephine biopsy. Although cerebrospinal fluid (CSF) cytology was negative, neoplastic meningitis (NM) was diagnosed based on clinical and MRI data. The patient's condition worsened rapidly and he died shortly thereafter. Autopsy confirmed the presence of advanced gastric cancer (adenocarcinoma of signet-ring cell type) with pancreatic involvement, and NM with cancer cells on the meninges, but without infiltration tumour cells into underlying brain parenchyma. We conclude that NM as an initial symptom of gastric cancer is rare and ultimately fatal.

Descriptive epidemiology of spinal muscular atrophy type I in Estonia.

Spinal muscular atrophy is the second most frequent autosomal-recessive disorder in Europeans. There are no published epidemiological data on SMA in Estonia and other Baltic countries. The aim of this study was to estimate the incidence of SMA I in Estonia. All patients with SMA I diagnosed between January 1994 and December 2003 were included in the study. The diagnosis was established on the basis of neurological evaluation, ENMG findings, molecular studies and muscle biopsy. PCR and restriction enzyme analysis was used to detect the homozygous deletion of the SMN1 gene. A total of 9 cases of SMA I were identified during this 10-year period. The incidence of SMA I in Estonia is 1 in 14,400 live births, which is similar to the result from Hungary but lower than average incidence in the world. Only one of the patients was female. Typical SMN1 gene deletion was found in all cases.

Analysis of the TP53 gene in laser-microdissected glioblastoma vasculature.

Malignant transformation of human gliomas is accompanied by extensive proliferation of stromal blood vessels. Recent data suggest mesenchymal transdifferentiation of neoplastic cells in various human cancers, including colon and breast cancer as well as gliosarcoma. In this study, we have analyzed proliferating stromal blood vessels in glioblastoma multiforme for the presence of mutations in the tumor suppressor gene TP53. Using tissue arrays derived from glioblastoma specimens, cases with significant immunohistochemical p53 accumulation were selected for molecular genetic detection of TP53 mutations in exons 5 to 8. None of the tumors included in this series displayed properties of gliosarcoma. Proliferating glomeruloid stromal vessels were isolated by laser microdissection from paraffin sections. In six cases, single-strand conformation polymorphism analysis for mutations of the TP53 gene in stromal blood vessels compared with adjacent tumor cells and subsequent DNA sequencing of the resulting DNA fragments were carried out. Glioblastoma cells of these cases exhibited TP53 mutations in exons 5, 7 and 8. None of these tumors showed TP53 mutations in microdissected samples from glomeruloid vessels. The absence of TP53 mutations in vascular stromal components of glioblastoma multiforme supports the hypothesis that microvascular proliferations originate from the tumor stroma and are not derived from transdifferentiated glioblastoma cells.