Atypowe cechy fenotypowe u nosicieli nowej mutacji nonsens Q248X w genie HNF1B

Introduction: Hepatocyte transforming factor 1B-maturity onset diabetes mellitus of the young (HNF1B-MODY) is an autosomal dominant type of monogenic diabetes caused by a mutation in the gene encoding hepatocyte nuclear factor 1beta (HNF-1beta). The aim of this study was to determine if a HNF1B gene mutation was responsible for a dominantly inherited form of diabetes mellitus among the members of a three-generation Polish family. Material and methods: The index subject was a 13-year-old boy with metabolic syndrome, spina bifida occulta, posterior urethral valves, congenital ureteropelvic junction obstruction, and a family history of diabetes of autosomal dominant trait of inheritance. We performed clinical and laboratory examinations of his family and sequenced the HNF1B gene. Results: A novel Q248X mutation (nucleotide C to T transition at position 742 of the exon 3 of HNF1B gene, resulting in stop codon formation) was identified. Phenotypes of family members sharing this mutation are highly variable, and include previously known abnormalities of the urinary system and pancreas, diabetes mellitus of variable onset and severity, hyperinsulinaemia, insulin resistance, metabolic syndrome, elevated aminotransferases, hyperbilirubinemia, hyperamylasemia, short stature and cataracts. To the best of our knowledge, spina bifida occulta, pectus carinatum, and splenomegaly have not been previously reported. Conclusions: Our results broaden the spectrum of HNF1B gene mutations and HNF1B-MODY-related phenotypes. Wstęp: Cukrzyca HNF1B-MODY dziedziczona w sposób autosomalnie dominujący jest rodzajem cukrzycy monogenowej, którą powoduje mutacja w genie HNF1B (hepatocyte transforming factor 1B). Celem pracy było zbadanie czy mutacja w HNF1B jest przyczyną występowania cukrzycy w trzech pokoleniach polskiej rodziny. Materiał i metody: Przeprowadzono ocenę kliniczną i laboratoryjną oraz sekwencjonowanie genu HNF1B trzynastoletniego chłopca z zespołem metabolicznym, rozszczepem kręgosłupa, zastawkami cewki tylnej i wrodzonym zwężeniem moczowodu oraz obciążonym wywiadem rodzinnym w kierunku cukrzycy. Ze względu na wywiad rodzinny o autosomalnie dominującym sposobie dziedziczenia cukrzycy zbadano również członków jego rodziny. Wyniki: Stwierdzono obecność nowej mutacji Q248X będącej skutkiem przeniesienia nukleotydu C na miejsce T w pozycji 742 eksonu 3 genu HNF1B i powstaniem kodonu stop. Cechy fenotypowe członków rodziny będących nosicielami tej mutacji okazały być się bardzo zróżnicowane, a niektóre z nich takie jak spina bifida occulta, pectus carinatum i splenomegalia nie były dotychczas opisywane. Wnioski: Wyniki poszerzają spectrum mutacji genu HNF1B oraz związanych z nimi cech fenotypowych cukrzycy HNF1B-MODY

Changes in the bronchial epithelia in patients with immotile cilia syndromes

Immotile cilia syndromes is a cause of recurrent infection of the airways and recurrent bronchopneumonias. Among the ciliary abnormalities are found changes in the structure of the microtubules, unco-ordinated ciliary movements caused by the absence of inner or outer or both dynein arms, and abnormalities of the kinetosomes and/or rete ridges. In patients with ciliary dyskinaesia bronchitis occurs early in life (during infancy) and usually has a recurrent tendency, so that bronchial biopsy is frequently undergone for diagnostic purposes. In this study we include 127 bronchial biopsies from patients (from 2 months to 49 years) unsuccessfully treated for recurrent respiratory tract infections. When performing regular diagnostic procedures on the light and electron microscopic level, we have looked for cilia abnormalities and also focused on changes within the mucosa and submucosa. The most common abnormality recorded was absence of the inner dynein arms, but in 40 cases neither of the dynein arms were present. Only a few patients had classical Kartagener’s syndrome. Special attention is drawn to biopsies from elderly patients, in whom long-standing infections were followed by extensive damage to the bronchial epithelium, including even a total absence of ciliated cells. In some cases enhanced regenerative processes and some foci of squamous metaplasia were found. In two cases even foci of low-grade dysplasia were diagnosed

Częstość wybranych polimorfizmów pojedynczych nukleotydów związanych z osteoporozą u Polaków zakażonych i niezakażonych HIV

Introduction: Osteoporosis poses significant risk for HIV infected subjects in the era of the long-term antiretroviral treatment. For this study frequency of the selected 11 single nucleotide polymorphisms (SNP single nucleotide polymorphism) previously associated with osteoporosis risk in HIV infected and uninfected cohorts was analysed. Association with the SNP variation and the risk of osteoporosis in the entire study and in HIV-infected cases was investigated. Material and methods: The study included 568 patients (226 women and 342 men): 315 HIV-infected patients and 253 anti-HIV negative cases. Osteoporosis was confirmed using dual energy absorptiometry ionizing radiation (DXA) in eight HIV infected patients and three controls [odds ratio (OR): 7.66, 95% CI: 1.98–29.6; p = 0.001; relative risk (RR): 7.04, 95% CI: 1.98–25.97, p = 0.0019]. SNP assays performed for collagen type 1 (COL1A1) rs1800012, parathyroid hormone (PTH) rs9630182, estrogen receptor gene (ER1) rs2077647, rs3020314 and rs1884051, Vitamin D receptor (VDR) rs1544410 and rs731236, Osteoprotegerin rs4355801, LDL receptor protein (LRP5) rs3736228, RANK rs3018362 and CYP19A1 (aromatase) rs700518 using TaqMan SNP Genotyping Assay (Applied Biosystems) according to the manufacturer’s protocol. For statistics Statistica 12 software was used. Results: Majority of allele frequencies for the studied polymorphisms were consistent with the Hardy-Weinberg equilibrium. CC homozygotes for ER1 rs2077647 were notably more common in HIV (+) cases compared to controls [OR: 2.29, 95%CI: 1.25–4.19, p = 0.003; RR: 2.11, 1.22–3.68, p = 0.0072]. Also GG homozygotes for ER1 rs1884051 were more common both in HIV(+) [OR: 2.57, 1.33–4.94, p = 0.0016; RR: 2.37, 1.29–4.36, p = 0.002] and in all patients with osteoporosis [OR 5.04, 1.24–20.4, p = 0.025; RR 3.94, 1.38–11.24, p = 0.043] . Additionally, in HIV (+) patients parathyroid hormone rs9630182 T allele was notably more common [OR: 1.4, 1.0–1.97, p = 0.024; RR: 1.15, 0.99–1.33, p = 0.029]. Conclusions: Genetic variability for the osteoporosis-associated SNPs was similar in HIV-infected patients and uninfected persons. ER1rs1884051 variants may be associated with the increased osteoporosis risk, but increased incidence of osteoporosis in HIV-infected compared to uninfected people seems to be weakly associated with investigated single nucleotide polymorphisms. Variation in the gene for the estrogen receptor ER1rs1884051 was significantly more frequent in patients with osteoporosis and more common in HIV infection.Wstęp: Osteoporoza staje się istotnym zagrożeniem dla pacjentów zakażonych HIV, szczególnie w erze długotrwałego leczenia antyretrowirusowego. W badaniu oceniono częstość wybranych 11 polimorfizmów pojedynczych nukleotydów (single nucleotide polymorphism, SNP) związanych z osteoporozą u pacjentów zakażonych HIV i bez tego zakażenia. Zbadano, czy zmienność genetyczna wybranych SNP wpływa na ryzyko osteoporozy w całej badanej populacji i u zakażonych HIV. Materiał i metody: Do badania włączono 568 osób (226 kobiet i 342 mężczyzn): 315 pacjentów zakażonych HIV i 253 osoby anty-HIV ujemne. Osteoporozę potwierdzono w badaniu za pomocą absorpcjometrii podwójnej energii promieniowania jonizującego (Dual-energy X-ray absorptiometry, DXA) u 8 pacjentów zakażonych HIV i 3 z grupy kontrolnej [iloraz szans (odds ratio, OR): 7,66; 95% Cl: 1,98–29,6; p = 0,0010; ryzyko względne (relative risk, RR): 7,04; 95% Cl: 1,98–25,97; p = 0,0019]. Zbadano SNP dla genów: kolagenu typu I (COLIA1) rs1800012, parathormonu (PTH) rs9630182, receptora estrogenów typu 1 (ER1) rs2077647 rs3020314 i rs1884051, receptora witaminy D (VDR) rs1544410 i rs731236, osteoprotegeryny (OPG) rs4355801, białka receptorowego dla LDL (LRP5) rs3736228, RANK rs3018362 i aromatazy (CYP19A1) rs700518 przy użyciu zestawów TaqMan SNP Genotyping Assay (AppliedBiosystems) zgodnie z protokołem producenta. Wyniki uzyskanych badań opracowano statystycznie w programie Statistica 12. Wyniki: Częstości alleli większości badanych polimorfizmów były zgodne z prawem Hardy-Weinberga. Analizując występowanie poszczególnych genotypów, stwierdzono istotnie częstsze wstępowanie u zakażonych HIV w porównaniu z grupą kontrolną homozygoty CC ER1 rs2077647 (OR: 2,29; 1,25–4,19; p = 0,003; RR: 2,11; 1,22–3,68; p = 0,0072). Także częściej występowała homozygota GG ER1 rs1884051 u zakażonych HIV (OR: 2,57; 1,33–4,94; p = 0,0016; RR: 2,37; 1,29–4,36; p = 0,002) oraz u pacjentów z osteoporozą (OR: 5,04; 1,24–20,4; p = 0,025; RR: 3,94; 1,38–11,24; p = 0,043). Dodatkowo u pacjentów zakażonych HIV istotnie częściej (p = 0,047) występował allel T genu parathormonu rs9630182 (OR: 1,4; 1,0–1,97; p = 0,024; RR: 1,15; 0,99–1,33; p = 0,029). Wnioski: Zmienność genetyczna pojedynczych nukleotydów związanych z występowaniem osteoporozy była podobna u pacjentów zakażonych HIV i osób niezakażonych. Warianty ER1 rs1884051 mogą mieć związek ze zwiększonym ryzykiem osteoporozy, ale wyższe ryzyko osteoporozy u pacjentów zakażonych HIV w porównaniu z osobami niezakażonymi wydaje się mieć niewielki związek z badanymi polimorfizmami pojedynczych nukleotydów. Zmienność w genie dla receptora estrogenów ER1rs1884051 istotnie częściej wystąpiła u pacjentów z osteoporozą i u zakażonych HIV

Investigation of chiral smectic phases and conformationally disordered crystal phases of the liquid crystalline 3F5FPhH6 compound partially fluorinated at the terminal chain and rigid core

Complementary methods are applied to investigate the phase transitions and crystallization kinetics of the liquid crystalline compound denoted as 3F5FPhH6. Two crystal phases are confirmed, and one of them is the conformationally disordered (CONDIS) phase. Complexity of the melt crystallization process is revealed by the analysis with Friedman’s isoconversional method. The melt crystallization of 3F5FPhH6 shows different mechanisms depending on temperature, which is explained by the relation between the thermodynamic driving force and the thermal energy of translational degrees of freedom. The studied compound crystallizes even during fast cooling (30 K/min), unlike similar compounds with different fluorosubstitutions of the benzene ring, which form the smectic glass for moderate cooling rates. The tendency to vitrification of the smectic phase decreases apparently with the decreasing stability width of the $SmC_{A}$* phase and the increasing relaxation time of the collective relaxation process in this phase, at least for homologues differing from 3F5FPhH6 only by the type of fluorosubstitution

Xanthine Oxidoreductase Reference Values in Platelet-Poor Plasma and Platelets in Healthy Volunteers

Introduction. Xanthine oxidoreductase (XOR) is an enzyme belonging to the class of hydroxylases. XOR is stated, inter alia, in the kidneys, liver, and small intestine as well as in leukocytes and platelets and endothelial cells of capillaries. Its main role is to participate in the conversion of hypoxanthine to xanthine and the uric acid. It occurs in two isoforms: dehydrogenase (XD) and oxidase (XO), which is considered one of the sources of reactive oxygen species. Aim of the Study. Determination of reference values of xanthine oxidoreductase activity in PPP and platelets. Materials and Methods. Study group consisted of 70 healthy volunteers. The isoform activities of xanthine oxidoreductase were determined by kinetic spectrophotometry. Results. A statistically significant difference between the activity of the XOR in PPP and platelets (P<0.001). The highest activity of XO was found in both PPP and blood platelets. Significant differences between the activity of the various isoforms in PPP (P=0.0032) and platelets (P<0.001) were also found. Conclusions. The healthy volunteers showed the highest activity XO (prooxidant) and the lowest XD (antioxidant), which indicates a slight oxidative stress and confirmed physiological effects of XOR

Pulmonary metastases of the A549-derived lung adenocarcinoma tumors growing in nude mice : a multiple case study

Lung adenocarcinoma is a leading human malignancy with fatal prognosis. Ninety percent of the deaths, however, are caused by metastases. The model of subcutaneous tumor xenograft in nude mice was adopted to study the growth of control and photodynamically treated tumors derived from the human A549 lung adenocarcinoma cell line. As a side-result of the primary studies, observations on the metastasis of these tumors to the murine lungs were collected, and reported in the present paper. The metastasizing primary tumors were drained by a prominent number of lymphatic vessels. The metastatic tissue revealed the morphology of well-differentiated or trans-differentiated adenocarcinoma. Further histological and histochemical analyses demonstrated the presence of golden-brown granules in the metastatic tissue, similar to these found in the tumor tissue. In contrast to the primary tumors, the electron paramagnetic resonance spectroscopy revealed no nitric oxide - hemoglobin complexes (a source of intense paramagnetic signals), in the metastases. No metastases were found in other murine organs; however, white infarctions were identified in a single liver. Taken together, the A549-derived tumors growing subcutaneously in nude mice can metastasize and grow on site in the pulmonary tissue. Thus, they can represent an alternative for the model of induced metastatic nodule formation, following intravenous administration of the cancerous cells

Quality of marital relationships in patients with diagnosis of psychotic disorders in both partners : case report

Niniejszy artykuł dotyczy jakości relacji partnerskiej w małżeństwie w którym u obojga partnerów zdiagnozowane zostały zaburzenia psychotyczne tj. schizofrenia paranoidalna (F.20.0) oraz zaburzenia schizoafektywne, typ depresyjny (F.25.1). Chociaż w literaturze przedmiotu stosunkowo dokładnie opisane zostały przypadki związków partnerskich w zakresie rozpoznania choroby psychicznej u jednego z partnerów [1,2,3,4] to jednak występowanie tak specyficznych zaburzeń u obojga współmałżonków wciąż należy jeszcze do rzadkości. Niezwykle istotną wydaje się więc dogłębna analiza funkcjonowania wskazanych osób w kontekście subiektywnego postrzegania przez nich własnego związku intymnego wraz z uwzględnieniem obiektywnych, zarówno specyficznych jak i niespecyficznych objawów psychopatologicznych rzutujących bezpośrednio na jakość oraz trwałość relacji partnerskiej. Opisany w niniejszej pracy przypadek stanowi więc próbę uzupełnienia luki w zakresie istniejącej problematyki oraz przybliża interpersonalny wymiar funkcjonowania osób z zaburzeniami psychotycznymi wraz z uwzględnieniem klinicznych implikacji istotnych dla dalszego przebiegu choroby.This article is about the quality of partner relationships in marriages in which both partners have been diagnosed with psychotic disorders such as paranoid schizophrenia (F 20.0) or schizoaffective disorders of the depressive type (F 25.1). Although within the literature there are relatively precisely descriptions of interpersonal relations in couples with a mental disorder diagnosed in one of the partners [1,2,3,4], much less is known about couples diagnosed with profound psychopathological phenomena in both partners. It seems to be extremely important to analyze the functioning of this patient group with regard to their own perception of their intimate relationship. Moreover, it is as important to understand the effect of both specific and non-specific psychopathological symptoms as these directly project upon the quality and durability of the partner relationship. The case described here is an attempt to fill in the gaps in terms of the aforementioned notions, and bring into the light, the closer interpersonal dimensions of persons with psychotic diagnoses, taking into account as well, clinical implications important for the further course of their illness