Array CGH - A Powerful Tool in Molecular Diagnostic of Pathogenic Microdeletions - Williams-Beuren Syndrome - A Case Report.

Williams-Beuren syndrome (WBS) (OMIM 194050) is caused by interstitial deletions or duplications of the 7q11.23 chromosomal region and characterised through a complex phenotype. We described a case diagnosed clinically and genetically confirmed through aCGH. Genetic assessment identified three microdeletions with a total size of 1.35 Mb located at 7q11.23. The deleted regions encompasses more than 30 genes including several protein coding genes such as ELN, LIMK1, FZDS, WBSCR22, WBSCR27, WBSCR28, STX1A, CLDN3, CLDN4, LAT2, ABHD11 or EIF4H .

Autophagy and Neovascularization in Colorectal Cancer.

PURPOSE: This study aims to determinate the microvessel density at the base of the tumor, as well in tumor's mass, in order to determinate the number of neovascularization vessels (marked with CD105) in comparison with presence or absence of autophagy puncta. MATERIAL/METHODS: Standard immunohistochemistry was performed on 38 samples of colorectal adenocarcinoma, in order to determinate the presence of autophagy and neovascularization blood vessels with the help of LC3, CD34, CD31 and CD105 antibodies. RESULTS: The autophagy process was observed in the cancerous cells and was noted as present in both regions of interest from the tumor. The mean number of blood vessels market with CD105 is higher in tumor mass then at its base, p value of the Student t test being highly significant (p<0.0001). CONCLUSIONS: The presence of autophagy puncta was notice in every case, both in the mass of the tumor and at its base. Microvascular density of new-grown blood vessels is higher in the mass of the tumor compared with the base of the tumor.

Correlation between High Endothelial Vessels and Histopathological Features of Different Pigmented Lesions.

PURPOSE: Tumor infiltrating lymphocytes are playing an important role in cutaneous melanoma being a strong prognostic parameter. Our goal was to study the presence of high endothelial vessels in correlation with the histopathological features in different pigmented skin lesions. MATERIAL AND METHODS: our study group included 60 patients (20 cases with dysplastic nevi, 20 thin melanoma and 20 thick melanoma). For each patient we noted epidemiological and clinico-pathological characteristics including: age, gender, anatomic sites, regression, Breslow thickness, mitoses, Clark level and lymphocytic infiltration. Using immunohistochemistry staining we identified the presence of high endothelial vessels in our groups. RESULTS: the most common localization of primary melanoma was trunk 57,5%, followed by extremities 35% and head 7,5%. We found positive MECA-79 vessels in 67% of primary melanoma samples and in 30% of dysplastic nevi. Lymphocytic infiltration was present in 80% samples of dysplastic nevi and 75% of primary melanomas. Using Kruskal Wallis non-parametric test we found a positive association between MECA-79+ vessels and different anatomic sites (p<0,01). We have also found a significant correlation between MECA-79+ vessels and the presence of regression in melanoma samples. In conclusion a better understanding of tumor microenvironment and mechanisms involved in anti-tumor response might play an important role in development of future melanoma therapeutic strategies.

VEGF-A and VEGF-B mRNA expression in gastro-oesophagela cancers

INTRODUCTION: Angiogenesis is essential for the local growth, invasion and metastasis of the tumours. Vascular endothelial growth factors (VEGFs) play a crucial role in tumour angiogenesis. The aim of our study was to quantify the expression of several VEGF family molecules in human gastro-oesophageal cancers and to analyse possible correlations between genes expression and clinico-pathological features. MATERIALS AND METHODS: Gene expression was quantified in 43 gastro-oesophageal paired samples using qRT-PCR with TaqMan probes specific to VEGF-A, including soluble transcript variants and VEGF-B genes. RESULTS: VEGF-A, including the studied splice variants and VEGF-B mRNAs were expressed in both tumour and peritumour mucosa. The expression of VEGF-A and its isoforms was higher in tumour compared with paired peritumour mucosa, while no significant difference was observed in VEGF-B expression. VEGF-A expression tended to correlate with tumour invasion. CONCLUSION: VEGF-A has a tendency to over-express in gastro-oesophageal cancers, while VEGF-B does not seem involved in these tumours. Further studies are required to establish the utility of anti-VEGF-A therapy and to find biomarkers for pathogenesis or response to therapy in gastro-oesophageal tumours (AU)

Holt-Oram syndrome.

The Holt-Oram syndrome or atriodigital dysplasia is an autosomal dominant disorder with near complete penetrance and variable expression, caused by mutations of the TBX5 gene (12q24.1), affecting one in 100 000 live births. 60% of cases are familial and 40% sporadic. We present the case of a 24 years old male patient with a personal history of bilateral coxa vara surgically corrected on the right at the age of 8 years, complicated by osteochondritis, short stature (160 cm), underweight (37 kg, BMI 14.45 kg/cm(2)), triangular face, micrognathia, down slanting palpebral fissures, hypertelorism, low set ears, scoliosis, narrow shoulders, shortened left arm, left thumb agenesia, limited supination, abnormal toes, hypoplastic muscles, atrial septal defect ostium secundum type, incomplete right bundle branch block, hypoacusia and normal intelligence.

Diabetes mellitus and Turner syndrome.

Noninsulindependent diabetes mellitus is 2-4 times more prevalent in Turner subjects as compared to normal females, and tends to develop at a younger age, but it is usually mild and responsive to weight loss or monotherapy. The primary pathogenic event is beta cell dysfunction, but insulin resistance also plays a central role and is worsened by the presence of hypertension, obesity and dyslipidemia which are common in Turner syndrome. We present the case of a 30 year-old female patient with short stature, 141cm (<-- 2.5 SD), overweight 51kg, waist circumference 79cm, triangular facies, downslanting palpebral fissures, low set ears, short neck, secondary amenorrhea, palpitations, a history of polyuria, polydypsia of three months duration and a fasting morning glucose of 260 mg/dL. Cardiac and renal defects were excluded, hormonologic evaluation was consistent with hypergonadotropic hypogonadism (FSH 65 mUI/mL) and primary hypothyroidism (TSH 5.68 microUI/mL) and karyotype was 45,XO. She also had hypercholesterolemia (247 mg/dL), hypocalcemia (8 mg/dL), mild elevation of hepatic enzymes (ALAT 51 U/L) and osteopenia (Tscore--2.22). Glycaemic control was achieved with diet only; therapy consisted of hormone replacement theraphy, thyroxine and beta blockers.

46,XY hypergonadotropic hypogonadism and myasthenia gravis.

Both hypergonadotropic hypogonadism and myasthenia gravis can be parts of type II autoimmune polyendocrine syndrome and association between the two disorders has been reported in few cases. A 14 year old male patient with a personal history of bilateral cryptorchidism and ptosis was referred for delayed puberty. Clinical examination revealed eunuchoid habitus, small, soft testes, gynecomastia, ptosis, a myasthenic deficit score of 22.5 points and an IQ of 84 points. Decreased testosterone (0.064 ng/mL) and elevated LH (64.5 mUI/mL) were consistent with hypergonadotropic hypogonadism and karyotype was normal: 46,XY. Thyroid function, haematologic evaluation, BUN, electrolytes, and glycemia were in the normal range. Therapy consisted of anticholinesterase inhibitors, immunosuppressants, corticotherapy, testosterone; thoracoscopic thymectomy was performed showing thymic lymphoid hyperplasia on histopathologic examination. Myasthenic score improved (12.5 points), progressive virilization occurred, and a year later the patient presented with cushingoid features and obesity.

Cytogenetic effects of sodium azide encapsulated in liposomes on heteroploid cell cultures.

Lipid vesicles (liposomes) have been shown to be a useful vehicle for the delivery of a variety of compounds to cultured cells. Using multilamellar vesicles (MLV) and small unilamellar vesicles (SUV) we were able to deliver the classical mutagen, sodium azide, into human heteroploid HEp-2 cells. With this method sodium azide is not diluted in culture medium, but it is 'focused' into cells, producing chromosomal aberrations and other major genetic damages. Our results indicate that liposomes are suitable vectors for introducing clastogenic substances into cultured human cells.

Induction of chromosomal aberrations by restriction endonucleases encapsulated in liposomes.

We used liposomes to deliver the restriction endonucleases BamHI and SmaI into human heteroploid HEp-2 cells. With this method very low concentrations of enzymes (2 units/ml) were active in the production of chromosomal aberrations. SmaI, which produces blunt-ended double-strand breaks in the DNA molecule, induces chromosomal aberrations more effectively than BamHI, which produces cohesive ends. Our results indicate that liposomes are suitable vectors for introducing restriction endonucleases into cultured human cells.

[IgA changes in chronic alcoholic hepatopathy]. / Modificari ale IgA în hepatopatia cronica alcoolica.

Chronic alcoholic hepatitis (CAH) has been included, in the last 10 years, among the disease accompanied by particular changes of IgA (primary glomerulonephritis with mesangial deposits of IgA, Berger; Henoch-Schonlein's purpura with IgA deposits in dermatic capillaries and herpetiform dermatitis, with deposits of IgA in dermatic papillae). The characteristics of IgA involvement in CAH are: The whole IgA system is changed, at its 3 levels: circulatory, tissular, formative. at the circulatory level, the IgA2 monomeric fraction increases characteristically; in hepatic parenchyma, perisinusoidal linear deposits of IgA are formed; they have a great significance for the alcoholic etiology, the length of time and seriousness of alcoholism.