Chromosome 22q11.2 deletion and phenotypic features in 30 patients with conotruncal heart defects

This report describes the dysmorphic features and frequency of 22q11.2 deletion (del22q11) in 30 Turkish patients with conotruncal heart defects (CTHDs). Fluorescence in situ hybridization (FISH) analysis revealed deletions in the 22q11.2 region in nine (30%) individuals. The CTHDs in this group were tetralogy of Fallot (four cases), double-outlet right ventricle (DORV) (two cases), transposition of great arteries (two cases), and ventricular septal defect (VSD) associated with other CTHDs (one case). The frequency of del22q11 in the study group was relatively high because many of the patients with dysmorphic findings also had cardiac anomalies involving the pulmonary artery, ductus arteriosus, or the aortic arch and its main branches. Twenty of the 30 patients exhibited several dysmorphic findings. Two of the nine patients with del22q11 exhibited no apparent dysmorphic features other than sacral dimple. Interestingly, one of the patients with del22q11 had a phenotypic appearance similar to that seen in oculo-auriculo-vertebral spectrum (OAVS). This individual had left microtia, atresia of the external meatus, mandibular asymmetry, and peripheral facial nerve paralysis. His mental development was normal and there were no abnormalities on ophthalmological examination. The CTHDs in this patient were situs inversus dextrocardia, DORV, pulmonary stenosis, and VSD. Radiographs of this patient showed platybasia, complete fusion of C2-C3, and posterior fusion of the T1-T2 vertebrae. This particular case indicates that the phenotypic features of del22q11 and OAVS may overlap.     

Evaluation of fractionated total body irradiation and dose rate on cataractogenesis in bone marrow transplantation

PURPOSE: To assess dose rate effect on cataractogenesis in allogeneic or autologous bone marrow transplanted patients conditioned with fractionated total-body irradiation (FTBI). MATERIALS AND METHODS: Between 1987 and 2001, a total of 105 patients have received TBI conditioning for Bone Marrow Transplantation (BMT) for hematological malignancies at Gulhane Military Medical School. 12 Gy FTBI was applied in 6 fractions over 3 consecutive days with a Co60 teletherapy machine. 46 patients who have survived and were followed up after more than one year were evaluated for cataractogenesis in relation to dose rate. Conditioning therapy included only cyclophosphamide (60 mg/kg/day for two days) + TBI with no steroid and veno-occlusive disease prophylaxis. RESULTS: The median follow-up is 32 months. Posterior subcapsular cataract developed in 5 eyes of three patients out of 46 patients. The 5-year and 10-year estimated cataract incidence in the high-dose rate (> 0.04 Gy/min) group was 29% and 43% respectively while no cataracts occurred in the low-dose rate (< or = 0.04 Gy/min) group. Cataract development in the high-dose rate group versus low-dose rate group was statistically significant (p < 0.039). CONCLUSION: Cataract is a late side effect of TBI. Low-dose rate fractionated TBI is a reliable conditioning program in BMT with effective lens sparing to avoid cataractogenesis.     

Inhibition of chemokines prevents intraperitoneal adhesions in mice

BACKGROUND: The present study evaluates the efficacy of a broad-spectrumchemokine inhibitor, NR58-3.14.3, in the prevention of adhesionformation after i.p. surgery in mice. METHODS: A total of 110eight week old female Balb/c mice underwent laparotomy. Fortyanimals were randomly assigned to receive daily i.p. injectionsof either vehicle (control) or NR58-3.14.3. Time-course of adhesionformation was assessed. A titration of NR58-3.14.3 was conductedfor i.p. and s.c. administrations. The effectiveness of a singleintra-operative dose of NR58-3.14.3 was evaluated. Number, extent,location and type of adhesions were recorded. Immunohistochemistryof adhesions was done with leukocyte common antigen, CD45. RESULTS:Adhesion scores peaked on post-operative days 6–8. Onboth days 6 and 8, there were smaller adhesion size and lowercumulative adhesion scores in NR58-3.14.3-treated group. Moreover,on day 8, there were significantly fewer adhesions in NR58-3.14.3-treatedgroup compared to controls. The least effective dose for i.p.administration of NR58-3.14.3 was 0.45 mg/animal. Subcutaneousand single intra-operative i.p. administrations were also effectivein the prevention of i.p. adhesions. Although NR58-3.14.3 decreasedthe number of CD45⁺ inflammatory cells in the adhesions by 22.5%compared to control group, this was not significant. CONCLUSIONS:Our results show that this broad-spectrum chemokine inhibitorprevents post-operative adhesions in mice and may have a potentialclinical use.     

Brainstem evaluation in children with primary nocturnal enuresis

We investigated the brainstem integrity in children with primary nocturnal enuresis (PNE) using auditory brainstem responses (ABR), blink reflex and exteroceptive suppression of the masseter muscle. We examined 23 children with PNE (16 male, 7 female; mean age: 10.4 years) and 19 control subjects (11 male, 8 female; mean age: 11.8 years). ABR parameters such as wave latencies, amplitudes and interpeak latencies and blink reflex parameters such as R1 and R2 amplitude and latencies were not significantly different between the 2 groups. Although S2 parameters of the exteroceptive suppression of the masseter muscle were easily and completely obtained from the control subjects, in the PNE group S2 onset latency and duration were not recorded in 26% of the study children (n = 6) (P = 0.01). S2 duration time was significantly lowered in the enuretic group (left side: P = 0.001 and right side: P = 0.003). S2 duration time changes in the enuretic group supports a possible brainstem dysfunction in children with PNE.     

Determination of allelic deletion of multiple endocrine neoplasm type 1 (MEN1) gene in acute myeloid leukemia (AML) by application of FISH-TSA technique

We have used the single and dual color fluorescence in situ hybridization (FISH) technique combined with a new detection system, tyramide signal amplification (TSA), by using the multiple endocrine neoplasm type 1 (MEN1) gene and chromosome 11 specific alpha satellite DNA probes for the study of the allelic deletion of the MEN1 gene. The MEN1 gene is a new tumor suppressor gene and has been recently cloned on chromosome 11q13. FISH combined with the TSA detection system was performed on bone marrow interphase nuclei of 22 patients with acute myeloid leukemia (AML). The FISH-TSA analysis revealed the mono allelic deletion of the MEN1 gene in 4 out of 22 patients (18.18%), 2 of 9 AML-M2 patients (22.2%), 1 of 6 AML-M4 patients (16.6%), and 1 of 4 AML-M5 patients (25.0%). Our study indicates that allelic deletion of the MEN1 gene is not a major cause or a primary event in tumorigenesis of AML, although the long arm (q13 region) of chromosome 11 involves a chromosomal rearrangement in AML.     

BAG1 over-expression in brain protects against stroke

The co-chaperone BAG1 binds and regulates 70 kDa heat shock proteins (Hsp70/Hsc70) and exhibits cytoprotective activity in cell culture models. Recently, we observed that BAG1 expression is induced during neuronal differentiation in the developing brain. However, the in vivo effects of BAG1 during development and after maturation of the central nervous system have never been examined. We generated transgenic mice over-expressing BAG1 in neurons. While brain development was essentially normal, cultured cortical neurons from transgenic animals exhibited resistance to glutamate-induced, apoptotic neuronal death. Moreover, in an in vivo stroke model involving transient middle cerebral artery occlusion, BAG1 transgenic mice demonstrated decreased mortality and substantially reduced infarct volumes compared to wild-type littermates. Interestingly, brain tissue from BAG1 transgenic mice contained higher levels of neuroprotective Hsp70/Hsc70 protein but not mRNA, suggesting a potential mechanism whereby BAG1 exerts its anti-apoptotic effects. In summary, BAG1 displays potent neuroprotective activity in vivo against stroke, and therefore represents an interesting target for developing new therapeutic strategies including gene therapy and small-molecule drugs for reducing brain injury during cerebral ischemia and neurodegenerative diseases.     

Diffuse optical tomography with a priori anatomical information

Diffuse optical tomography (DOT) poses a typical ill-posed inverse problem with a limited number of measurements and inherently low spatial resolution. In this paper, we propose a hierarchical Bayesian approach to improve spatial resolution and quantitative accuracy by using a priori information provided by a secondary high resolution anatomical imaging modality, such as magnetic resonance (MR) or x-ray. In such a dual imaging approach, while the correlation between optical and anatomical images may be high, it is not perfect. For example, a tumour may be present in the optical image, but may not be discernable in the anatomical image. The proposed hierarchical Bayesian approach allows incorporation of partial a priori knowledge about the noise and unknown optical image models, thereby capturing the function-anatomy correlation effectively. We present a computationally efficient iterative algorithm to simultaneously estimate the optical image and the unknown a priori model parameters. Extensive numerical simulations demonstrate that the proposed method avoids undesirable bias towards anatomical prior information and leads to significantly improved spatial resolution and quantitative accuracy.     

Expression of CD138 (Syndecan-1) in renal cell carcinoma is reduced with increasing nuclear grade.

CD138/Syndecan-1 is a cell-surface heparan sulfate proteoglycan expressed on most epithelial cells, and decreased CD138 expression is associated with increased invasive and metastatic potential in carcinomas. CD138 expression has not been investigated previously in renal neoplasms. Formalin-fixed, paraffin-embedded tissue sections of 50 renal cell carcinomas (RCCs) (40 clear-cell RCCs of various nuclear grades, 10 of which harbored metastases; 6 papillary RCCs, 4 chromophobe RCCs) and 4 oncocytomas were stained immunohistochemically for CD138 using the monoclonal antibody B-B4 (CD138). Staining intensity and distribution were scored and results related to histologic type, nuclear grade, and local stage (pT). Immunoreactivity was membranous in all clear-cell RCCs, chromophobe RCCs, and oncocytomas and was located at the basal aspect of cytoplasm in papillary RCCs. In clear-cell RCCs, the extent of CD138 immunoreactivity decreased with increasing nuclear grade (P<0.001). No significant correlation was found between CD138 immunoreactivity and histologic type (P=0.2) or local stage (P=0.7). Metastatic foci showed a mild to moderate decrease in intensity compared with primary tumor. Decreased expression of CD138 may have a role in more aggressive behavior of clear-cell RCC.     

Immunohistochemical localisation of 3β-hydroxysteroid dehydrogenase in<Emphasis Type="Italic"> Sarcocystis</Emphasis> spp.

3-Hydroxysteroid-dehydrogenase (3-HSD) is an isoenzyme that catalyses an essential step in the synthesis of all classes of active steroid hormones. The presence of steroid hormones of the vertebrate type in invertebrates is acknowledged in addition to a group of steroid-like hormones called ecdysteroids that were present in arthropods and helminths. In the present study, 3-HSD was detected in the bradyzoites enclosed in sarcocysts of Sarcocystis spp. with immunohistochemistry. The results suggest that self-originating steroid hormones may play important roles in the development of Sarcocystis spp., and possibly in the regulation of the reciprocal immune interaction between the host and these parasites.     

Molecular epidemiology of macrolide-resistant Streptococcus pneumoniae isolates in Europe

In many European countries, the level of pneumococcal resistance to macrolides has now passed the level of resistance to penicillin G. A total of 82 erythromycin A-resistant isolates of Streptococcus pneumoniae were collected by 11 laboratories in seven European countries. All of the isolates were tested for antimicrobial susceptibility, analyzed for clonal relatedness by multilocus sequence typing, and characterized for macrolide resistance genotypes. The prevalence of the macrolide resistance genotypes varied substantially between countries. In France (87.5% of all strains), Spain (77.3%), Switzerland (80%), and Poland (100%), strains were predominantly erm(B) positive, whereas higher levels of mef(A)-positive strains were reported from Greece (100%) and Germany (33.3%). Macrolide resistance was caused by the oligoclonal spread of some multilocus sequence types, but significant differences in clonal distribution were noted between France and Spain, countries from which high levels of macrolide resistance have been reported. Overall, sequence type 81 (Spain23F-1 clone) was by far the most widespread. The mainly erm(B)-positive serotype 14 clone (sequence type 143), first reported in Poland in the mid-1990s, is now widespread in France.