MIR204 n.37C>T variant as a cause of chorioretinal dystrophy variably associated with iris coloboma,early-onset cataracts and congenital glaucoma

Four members of a three-generation Czech family with early-onset chorioretinal dystrophy were shown to be heterozygous carriers of the n.37C>T in MIR204. The identification of this previously reported pathogenic variant confirms the existence of a distinct clinical entity caused by a sequence change in MIR204. Chorioretinal dystrophy was variably associated with iris coloboma, congenital glaucoma, and premature cataracts extending the phenotypic range of the condition. In silico analysis of the n.37C>T variant revealed 713 novel targets. Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants. Haplotype analysis excluded relatedness with the original family reported to harbour the n.37C>T variant in MIR204. Identification of a second independent family confirms the existence of a distinct MIR204-associated clinical entity and suggests that the phenotype may also involve congenital glaucoma.     

Dose-dependent effect of histamine on liver function markers in immunized rabbits

ObjectiveThe present study was designed to delineate the hepatotoxicological roles of histamine dose-dependently in immunized rabbits.MethodsThe cohort comprised of three groups (II, III and IV), containing 18 rabbits each, and received subcutaneous histamine 50 μg/kg, 100 μg/kg and 200 μg/kg, respectively for 10 days (b.i.d., starting from 3 days prior to immunization until 7 days after immunization). Group I (control, n = 18) received subcutaneous sterile distilled water for 10 days. They were subsequently immunized at day 3 with intravenous injection of SRBC (1 × 10⁹ cells/ml). Blood samples were collected on pre-immunization (pre-I) day 0, as well as on days 7-, 14-, 21-, 28- and 58-post-immunization (post-I). Biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin [total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB)] were determined.ResultsGroups II and IV revealed a significant decrease (on day 0-pre-I) and a significant increase (on days 7-, 14-, 21-, 28- and 58-post-I) in ALT and AST levels, when compared with the corresponding values of groups I and III while group II showed a significant increase in ALT and AST levels as compared to group IV. ALP levels in groups II, III and IV showed a significant enhancement when compared with group I. Moreover, results of TB, DB and IB demonstrated increased levels in group III when compared with groups I, II and IV. The results were found statistically significant (p < 0.05).ConclusionShort-term treatment of histamine produces dose-dependent differential patterns of hepatic dysfunctions suggestive mild liver degeneration warranting further long-term studies.     

Subclinical atherosclerosis in psoriatic arthritis: a case-control study

OBJECTIVE: To investigate the prevalence of subclinical atherosclerosis among patients with psoriatic arthritis (PsA). METHODS: Forty patients with PsA were enrolled. Controls were matched by age, sex, and atherosclerotic risk factors. All patients and controls underwent duplex scan of the carotid arteries. Carotid intima-media thickness (IMT) was evaluated and the presence of atherosclerotic plaques was recorded. The plaques were graded and carotid plaque index was calculated. RESULTS: Patients with PsA had a higher IMT (mean +/- standard deviation, 1.04 +/- 0.35 mm vs 0.88 +/- 0.29 mm in controls; p = 0.03), and had a higher carotid plaque index than did matched controls (2.3 +/- 2.6, compared to 1.12 +/- 2.09; p = 0.03). Multivariate analysis demonstrated that PsA status as well as age and triglyceride levels were associated with the presence of carotid plaque. Other traditional risk factors were more prevalent among patients with PsA; however, they were not statistically significant. CONCLUSION: Our study demonstrates that patients with PsA may have an increased prevalence of subclinical atherosclerosis. These findings may not be solely attributable to traditional risk factors alone. Special attention and strict control of atherosclerotic risk factors in patients with PsA is warranted.     

The modular architecture of protein-protein binding interfaces

Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few interactions between the modules. The boundaries between modules are defined by clustering the contact map of the interface. We show that mutations in one module do not affect residues located in a neighboring module. As a result, the structural and energetic consequences of the deletion of entire modules are surprisingly small. To the contrary, within their module, mutations cause complex energetic and structural consequences. Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography. Replacing an entire module of five interface residues with Ala created a large cavity in the interface, with no effect on the detailed structure of the remaining interface. The modular architecture of binding sites, which resembles human engineering design, greatly simplifies the design of new protein interactions and provides a feasible view of how these interactions evolved.     

Effects of histamine H1R—H4R—agonist on the airway epithelium of rabbits

ObjectiveTo explore the exact role of histamine receptors in respiratory system.MethodsThe cohort comprised of six groups (group I control and group II-VI treated) containing five rabbits in each group. Control-group received vehicle (sterile distilled water) and treated groups received subcutaneous histamine (100 μg/kg, b.i.d.), and H1R-agonist (HTMT), H2R-agonist (amthamine), H3R-agonist (R-(?)-α-methylhistamine) and H4R-agonist (clobenpropit) each in a dose of 10 μg/kg, b.i.d. for 30 subsequent days. After completion of treatment, animals were euthanized and perfused with 10% buffered formalin. Small tissue blocks of trachea and lungs were processed for paraffin embedding. Observations were recorded in sample photomicrographs taken from 10 μm thick. Haematoxylin and eosin stained sections.ResultsIt was observed that trachea and bronchi from histamine, H1R and H4R groups had only patches of hyperplastic and hypertrophied epithelium and in general, cells in the affected region were taller heaped up. The bronchiolar epithelia from all treated groups showed hypertrophy and hyperplasia throughout with most of the cells having rounded profile and appeared to bud out from the basal cells.ConclusionsIt is concluded that histamine receptors on induction via its specific agonist can induce hypertrophy, hyperplasia of respiratory tract epithelia suggesting its role akin to growth stimulating factor and warranting further long-term study.     

Telomerase activity in patients with transitional cell carcinoma: a preliminary study

BACKGROUND: Telomerase activity is not detectable in normal cells, and their telomers shorten until the chromosome is unable to replicate. Immortal cells have short but stable chromosomes and increased telomerase activity. Transitional cell carcinoma (TCC) has only a few useful markers of diagnostic or prognostic importance. The objective of this study was to determine whether there was a correlation between telomerase activity and the grade or stage of TCC, and whether the enzyme's activity could serve as a biochemical marker of this tumor. METHODS: The study included 29 patients with TCC. From each patient, samples of urine cells were obtained, and a cup biopsy was taken from an apparently normal area as well as from a part of the bladder tumor resected transurethrally. Control uroepithelial biopsies were taken from normal transitional cell sites from non-TCC patients. Biopsies or cells were subjected to either histologic examination or telomerase activity determination. RESULTS: Twenty-six of 29 (90%) of the tumor biopsies exhibited telomerase activity. Most of the cup biopsies were categorized as metaplastic or dysplastic, and 20 of 29 (69%) of these exhibited telomerase activity. Telomerase activity was found in 17 of 21 (81%) of the urine cells but in only 3 of 14 (21%) of control urine cells. All (10 of 10) of the uroepithelial biopsies taken from non-TCC patients did not show any telomerase activity. CONCLUSIONS: In this study, almost all tumor biopsies exhibited telomerase activity. The high incidence of telomerase activity found in cup biopsies of the malignant field uroepithelial cells from cup biopsies of TCC patients may suggest that telomerase could be activated early in carcinogenesis. A high incidence of telomerase activity was found in voided uroepithelial cells of TCC patients; however, no correlation between this activity and the histologic determination of grading and staging of the tumor was found.     

Gross pericardial effusion with tamponade in 2<Superscript>nd</Superscript> trimester of pregnancy

Hypothyroidism in pregnancy is associated with serious maternal and fetal risk. Rarely, it is manifested by life-threatening cardiac complications, such as gross pericardial effusion and tamponade. We present a case of successfully treated gross pericardial effusion and tamponade in a 22-week pregnant woman with hypothyroidism. The patient was treated by pericardial drainage with further treatment of hypothyroidism with levothyroxine. During the follow-up pregnancy was uncomplicated without recurrence of pericardial effusion and successful delivery of full-term baby. We conclude that careful monitoring of thyroid functional tests and proper management should be performed in pregnant women with hypothyroidism to prevent cardiac complications of the disease, like pericardial effusion and tamponade.