Codon 178 mutation of the human prion protein gene in a German family (Backer family): sequencing data from 72-year-old celloidin-embedded brain tissue

Familial Creutzfeldt-Jakob disease was first described in a family from northern Germany in the 1920s (Backer family). PCR amplification of DNA extracted from brain tissue embedded in celloidin 72 years ago shows a GAC to AAC substitution at codon 178 of the prion protein gene. This mutation is associated with fatal familial insomnia and familial Creutzfeldt-Jakob disease in a number of families of diverse ethnic background.     

Aneuploidy of chromosome 20 in invasive breast cancer correlates with poor outcome

Breast carcinoma is a genetically and phenotypically heterogeneous disease and is frequently associated with nonrandom chromosomal alterations. The aim of this study was to investigate the numerical aberrations of chromosome 20 in breast cancer. The observed chromosome-specific numerical abnormalities were evaluated along with the established clinicopathological parameters, the immunohistochemical expression of ER, PR, p53, c-erbB-2, Ki-67 and patients' survival. Nonisotopic in situ hybridization was applied to interphase cell nuclei on paraffin embedded tissue sections. Polysomy of chromosome 20 was the prevalent alteration in 45 of 50 (90%), monosomy in 2 of 50 (4%) and disomy in 3 of 50 (6%) cases. Invasive ductal carcinomas displayed a higher percentage of polysomy than lobular ones. A statistical significant association was demonstrated between Ki-67 immunohistochemical expression and polysomy of chromosome 20. Disomy was inversely correlated with Ki-67, while monosomy was suggestively associated with PR positive expression. Among the patients, those with the highest levels of polysomy showed the worst survival. In conclusion, the gain of chromosome 20 is the prevalent aberration in patients with breast carcinomas and may be useful prognostic marker in breast cancer.     

September 2002: 24-year-old female with a 6-month history of seizures

The September 2002 COM. A 24-year-old female presented with a history of 3 generalized seizures, the first of which had occurred 6 months before admission. Her neurological examination was normal, but upon admission her MRI showed a small cystic lesion in the left parieto-occipital region. The lesion was hyper-intense on T-2 weighted images and did not show contrast enhancment. At surgery, the tumor was found to be deep to the cortex and was a cyst with amber fluid surrounded by gliotic brain. Microscopically, the tumor was well-demarcated from the surrounding tissues, which showed reactive changes, including Rosenthal fibers. The tumor was composed of GFAP-positive glial cells, which were arranged in a pseudopapillary fashion around blood vessels. In between, the tumor cells were positive for neuronal markers. The diagnosis was papillary glioneuronal tumor (PGNT), a relatively recently described lesion that may be a variant of ganglioglioma. The current literature on PGNTs is reviewed.     

Enhanced mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in breast carcinomas is correlated with adverse prognosis

Tissue inhibitor of metalloproteinase-1 (TIMP-1) has emerged as a multifunctional protein with the contrasting activities of inhibiting tissue-degrading enzymes and promoting cellular growth. In an attempt to elucidate the clinical significance of TIMP-1 in breast cancer, the expression of TIMP-1 mRNA was evaluated in 117 invasive breast carcinomas by mRNA in situ hybridization, in correlation with clinicopathological parameters, immunohistochemical prognostic factors (Ki-67, c-erb-B-2, bcl-2) and clinical outcome. TIMP-1 was detected in stromal cells in areas within the tumours and at the tumour margin. High TIMP-1 mRNA expression in the marginal portion of the tumours was significantly correlated with lymph node metastasis (p<0.05) and c-erbB-2 expression (p<0.05). On the other hand, increased TIMP-1 mRNA expression within the tumours showed a statistically significant correlation with ER detection (p<0.01). Multivariate analysis revealed worse survival for patients with high TIMP-1 mRNA expression in the marginal portion of the tumours; the subgroup of these patients co-expressing high levels of TIMP-1 mRNA within the tumours as well had even worse survival (p=0.042). In conclusion, our data support the multifunctional role of TIMP-1, particularly its growth-promoting activity, on the basis of its significant correlation with lymph node metastasis and adverse prognosis. In addition to the latter property, a probable association of TIMP-1 with tumour cell differentiation is suggested by its topographical correlation with ER detection.     

The development of excitatory transmitter amino acid-containing neurons in the rat visual cortex

The excitatory amino acids l-glutamate and l-aspartate are believed to be utilized as neurotransmitters by the pyramidal neurons in the mammalian cerebral cortex. These cells can be recognized early in development, while glutamate might play an important part in the maturation and plasticity of the cortex. Here, we used light and electron microscopic immunocytochemistry to study the time of appearance and maturation of glutamate and aspartate in neurons of the rat visual cortex. Glutamate- and aspartate-immunoreactive cells were first detected in deep cortical layers at postnatal day 3. During the next 3 weeks, labelled neurons were observed progressively in more superficial layers, but did not demonstrate their adult pattern of distribution until postnatal week 4. Electron microscopic analysis showed that glutamate- and aspartate-labelled neurons gradually develop their cytological and synaptic features during the first 4 postnatal weeks, with this process of differentiation originating in the deep cortical layers and progressively extending to the superficial layers. These findings suggest that cortical pyramidal neurons begin to express detectable levels of transmitter glutamate and/or aspartate after they have completed their migration. Their neurochemical differentiation follows an inside-out pattern similar to the pattern described for the genesis and morphological differentiation of this population of cortical neurons.     

Case report: Role of hepatitis E virus in the etiology of community-acquired non-A,non-B hepatitis in greece

The aim of this study was to determine the frequency of hepatitis E virus (HEV) infection in a population of Greek adults with community-acquired (sporadic) non-A, non-B hepatitis found to be seronegative for antibodies to hepatitis C virus (anti-HCV). All patients admitted to the Liver Unit of Western Attica General Hospital and diagnosed as having acute community-acquired non-A, non-B hepatitis between February, 1986, and May, 1990, were enrolled in follow up studies (n = 66). Nineteen patients with HCV infection and 11 patients with acute non-A, non-B, non-C hepatitis that progressed to chronicity were excluded. Convalescent sera were tested for antibody to HEV (anti-HEV) by a fluorescent antibody blocking assay in 33 of 36 eligible patients. One of the 33 (3%) patients was found to be positive for anti-HEV. Anti-HEV testing of all 20 available serum specimens from this patient showed evidence of anti-HEV seroconversion at the fourth week after the onset of hepatitis. The patient had not travelled abroad or within Greece or had not had apparent contact with people from foreign countries for the previous 3 months. These data show that HEV infection is not a major cause of community-acquired non-A, non-B hepatitis in Greece. However, the reported case of HEV hepatitis suggests that HEV may retain a low endemicity in Greece. More extensive seroprevalence studies are needed for an accurate estimation of the extent of HEV infection in the southeastern European countries. © 1994 Wiiey-Liss, Inc.     

Birth of a healthy infant following trophectoderm biopsy from blastocysts for PGD of beta-thalassaemia major

PGD is a well accepted reproductive choice for couples at genetic risk and involves the diagnosis and transfer of unaffected IVF embryos. PGD for monogenetic diseases is most commonly accomplished by the biopsy of one or two blastomeres from cleavage stage embryos, followed by PCR-based protocols. However, PCR-based DNA analysis of one or two cells is subject to several problems, including total PCR failure, or failure of one allele to amplify. Trophectoderm biopsy at the blastocyst stage enables the removal of more than two cells for diagnosis while being non-invasive to the inner cell mass which is destined for fetal development. The aim of this study was to develop a safe, reliable technique for the biopsy of trophectoderm cells from human blastocysts. This case report demonstrates that removal of trophectoderm cells prior to blastocyst transfer is compatible with implantation and development to term. Here we report successful PGD for beta-thalassaemia following trophectoderm cell biopsy from blastocysts and the birth of a healthy infant.     

“Aggressive” Feeding of Very Preterm Neonates and Body Mass Index at School Age

Introduction: The effects of “aggressive” neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our “aggressive” nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years. Materials and Methods: Eighty four VPN, who received “aggressive” nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula; A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180–210 mL/kg/day; A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts. Results: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4. Conclusions: “Aggressive” and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results.