Involvement of the Subplate Zone in Preterm Infants with Periventricular White Matter Injury

Studies of periventricular white matter injury (PWMI) in preterm infants suggest the involvement of the transient cortical subplate zone. We studied the cortical wall of non‐cystic and cystic PWMI cases and controls. Non‐cystic PWMI corresponded to diffuse white matter lesions, the predominant injury currently detected by imaging. Glial cell populations were analyzed in post‐mortem human frontal lobes from very preterm [24–29 postconceptional weeks (pcw)] and preterm infants (30–34 pcw) using immunohistochemistry for glial fibrillary acidic protein (GFAP), monocarboxylate transporter 1 (MCT1), ionized calcium‐binding adapter molecule 1 (Iba1), CD68 and oligodendrocyte lineage (Olig2). Glial activation extended into the subplate in non‐cystic PWMI but was restricted to the white matter in cystic PWMI. Two major age‐related and laminar differences were observed in non‐cystic PWMI: in very preterm cases, activated microglial cells were increased and extended into the subplate adjacent to the lesion, whereas in preterm cases, an astroglial reaction was seen not only in the subplate but throughout the cortical plate. There were no differences in Olig2‐positive pre‐oligodendrocytes in the subplate in PWMI cases compared with controls. The involvement of gliosis in the deep subplate supports the concept of the complex cellular vulnerability of the subplate zone during the preterm period and may explain widespread changes in magnetic resonance signal intensity in early PWMI.     

Oral lichen planus – retrospective study of 563 Croatian patients

Objectives: To investigate the epidemiological and clinical characteristics of oral lichen planus (OLP) in a group of Croatian patients seen between 2006 and 2012. Study Design: A group of 563 patients with a diagnosis of OLP was retrospectively reviewed in our clinic. Data regarding age, gender, medical history, drugs, smoking, alcohol, chief complaint, clinical type, localization, histology, treatment and malignant transformation were registered. Results: Of the 563 patients, 414 were females and 149 were males. The average age at the diagnosis was 58 (range 11-94). The most common site was buccal mucosa (82.4%). Most of our patients did not smoke (72.5%) or consume alcohol (69.6%). Patients reported oral soreness (43.3%), mucosal roughness (7%), xerostomia (3%), gingival bleeding (2%) and altered taste (0.5%) as the chief complaint, while almost half of them were asymptomatic (44.2%). The most common types of OLP were reticular (64.8%) and erosive (22.9%). Plaque-like (5.7%) atrophic/erythemtous (4.3%) and bullous (2.3%) type were also observed. Malignant transformation rate of 0.7% was recorded. Conclusions: OLP mostly affects non-smoking middle-aged women. Buccal mucosa is the most commonly affected site. In almost half of the cases patients are asymptomatic. In spite of the small risk for malignant transformation all patients should be regularly monitored. Key words:Oral lichen planus, malignant transformation, epidemiology, retrospective study.     

Prognostic significance of bone morphogenetic protein 6 (BMP6) expression,clinical and pathological factors in clinically node-negative oral squamous cell carcinoma (OSCC)

Bone morphogenetic protein 6 (BMP6) has unique properties regarding structure and function in supporting bone formation during development and adult life. Despite its known role in various malignant tumors, the prognostic significance of BMP6 expression in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the study was to investigate immunohistochemical expression of BMP6 in OSCC in correlation with clinical and pathological parameters, disease recurrence and survival. In addition, we investigated other parameters in order to identify prognosticators of neck metastases and final outcome. The study included 120 patients with clinically T1-3N0 OSCC who were primarily surgically treated between 2003 and 2008. There were 99 (82.5%) male and 21 (17.5%) female patients. The five-year disease-specific survival for the whole cohort was 79.7%. Tumors smaller than 2 cm in diameter showed higher incidence of strong BMP6 expression. No statistical correlation was observed between other clinico-pathological factors and BMP6 expression. Expression of BMP6 was not associated with disease recurrence and survival. BMP6 may not serve as prognosticator of final outcome or recurrence in clinically node-negative OSCC subjects. In multivariate analysis predictors of poorer survival were positive surgical margin, moderate tumor cell differentiation and pathological involvement of levels IV and/or V.     

Primary Budd–Chiari syndrome in a 3-year-old boy with homozygous factor V Leiden G1691A mutation

Budd–Chiari syndrome (BCS) is an uncommon disorder characterized by obstruction of hepatic venous outflow. The primary BCS is a rare disease with an incidence about 0.2 per million inhabitants per year. We present a 3-year-old boy with intrahepatic inferior vena cava clot. Because of decreased levels of protein C (38.7 %), F II (69.1 %), and activated protein C resistance (1.43), a mutational gene analysis was performed. The patient was found to be homozygous for the FV G1691A mutation. Conclusion: The primary BCS is a rare disease especially in childhood. Activated protein C resistance caused by the factor V Leiden mutation may be responsible for primary BCS. Prompt recognition of underlying prothrombotic disease and early initiation of their specific therapy might translate into rapid improvement of liver disease.     

Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages

Multicellular animals use a three-part molecular toolkit to mediate phospho-tyrosine signaling: Tyrosine kinases (TyrK), protein tyrosine phosphatases (PTP), and Src Homology 2 (SH2) domains function, respectively, as “writers,” “erasers,” and “readers” of phospho-tyrosine modifications. How did this system of three components evolve, given their interdependent function? Here, we examine the usage of these components in 41 eukaryotic genomes, including the newly sequenced genome of the choanoflagellate, Monosiga brevicollis, the closest known unicellular relative to metazoans. This analysis indicates that SH2 and PTP domains likely evolved earliest—a handful of these domains are found in premetazoan eukaryotes lacking tyrosine kinases, most likely to deal with limited tyrosine phosphorylation cross-catalyzed by promiscuous Ser/Thr kinases. Modern TyrK proteins, however, are only observed in two lineages, metazoans and choanoflagellates. These two lineages show a dramatic coexpansion of all three domain families. Concurrent expansion of the three domain families is consistent with a stepwise evolutionary model in which preexisting SH2 and PTP domains were of limited utility until the appearance of the TyrK domain in the last common ancestor of metazoans and choanoflagellates. The emergence of the full three-component signaling system, with its dramatically increased encoding potential, may have contributed to the advent of metazoan multicellularity.     

Sequence structure and intragenomic variability of ribosomal ITS2 in monozoic tapeworms of the genus Khawia (Cestoda: Caryophyllidea), parasites of cyprinid fish

The sequence structure of the ribosomal internal transcribed spacer 2 (ITS2) was determined for six species of Khawia (Cestoda: Caryophyllidea), parasites of cyprinid fish in the Holarctic Region. Homologous intragenomic ITS2 structure was found in Khawia armeniaca, Khawia baltica, and Khawia rossittensis; whereas divergent intragenomic ITS2 copies were detected in Chinese, Japanese, and Slovak isolates of Khawia sinensis and in Khawia japonensis, both parasitic in common carp, and in Khawia saurogobii, recently described from Chinese lizard gudgeon in China. Despite distinct morphological differences between K. saurogobii and K. sinensis, both species display very high level of molecular homogeneity. Variation in number of short repetitive motifs [(GCCT)( n ) (GCCC)( n )], [(GTG)( n )], [(ATAC)( n )], [ACGTGT (TCGTGT)( n )], [(GT)( n )], [(GT)( n )], and [(ACCT)( n ) (GCCT)( n )] resulted in assortment of ITS2 sequences in four ITS2 variants in K. saurogobii from China, three in Chinese and Japanese isolates of K. sinensis, and five ITS2 variants in K. sinensis from Slovakia. In K. japonensis, the structure and arrangement of microsatellites was different from those of K. sinensis and K. saurogobii. The heterogeneity in the number of two microsatellite regions [(TG)( n ); (TTG)( n )] divided ITS2 clones into two variants-first ITS2 variant (472?bp) with (TG)(5) and (TTG)(6), and second variant with (TG)(7) and (TTG)(2) (465?bp). Sequence identity of K. saurogobii with all but one (K. sinensis) congeneric species ranged between 49.5 and 69.2?%, which corresponds to the interspecific differences. In contrast, sequence identity of K. saurogobii and K. sinensis (87.6-95.0?%) failed into the range of intraspecific variation determined for K. sinensis samples. This close genetic similarity indicates that recently described K. saurogobii may have undergone morphological divergence as a result of ongoing sympatric speciation by host switching.