A de novo loss-of-function DYNC1H1 mutation in a patient with parkinsonian features and a favourable response to levodopa.

Graphical summary of 'A de novo loss-of-function DYNC1H1 mutation in a patient with parkinsonian features and a favourable response to levodopa' by Szczaluba et al..

A novel interaction between HER2/neu and cyclin E in breast cancer.

HER2/neu (HER2) and cyclin E are important prognostic indicators in breast cancer. As both are involved in cell cycle regulation we analyzed whether there was a direct interaction between the two. HER2 and cyclin E expression levels were determined in 395 breast cancer patients. Patients with HER2-overexpression and high levels of cyclin E had decreased 5-year disease-specific survival compared with low levels of cyclin E (14% versus 89%, P<0.0001). In vitro studies were performed in which HER2-mediated activity in HER2-overexpressing breast cancer cell lines was downregulated by transfection with HER2 small interfering RNA or treatment with trastuzumab. Cyclin E expression levels were determined by western blot analysis, and functional effects analyzed using kinase assays, MTT assays were used to assess cell viability as a marker of proliferation and fluorescence-activated cell sorting analysis was used to determine cell cycle profiles. Decreased HER2-mediated signaling resulted in decreased expression of cyclin E, particularly the low molecular weight (LMW) isoforms. Decreased HER2 and LMW cyclin E expression had functional consequences, including decreased cyclin E-associated kinase activity and decreased proliferation, because of increased apoptosis and an increased accumulation of cells in the G1 phase. In vivo studies performed in a HER2-overexpressing breast cancer xenograft model confirmed the effects of trastuzumab on cyclin E expression. Given the relationship between HER2 and cyclin E, in vitro clonogenic assays were performed to assess combination therapy targeting both proteins. Isobologram analysis showed a synergistic interaction between the two agents (trastuzumab targeting HER2 and roscovitine targeting cyclin E). Taken together, these studies show that HER2-mediated signaling effects LMW cyclin E expression, which in turn deregulates the cell cycle. LMW cyclin E has prognostic and predictive roles in HER2-overexpressing breast cancer, warranting further study of its potential as a therapeutic target.

Post-translational activation of human phenylalanine 4-monooxygenase from an endobiotic to a xenobiotic enzyme by reactive oxygen and reactive nitrogen species.

An investigation into the post-translational activation of cDNA-expressed human phenylalanine 4-monooxygenase and human hepatic cytosolic fraction phenylalanine 4-monooxygenase activity with respect to both endobiotic metabolism and xenobiotic metabolism revealed that the reactive oxygen species (hydrogen peroxide and hydroxyl radical) and reactive nitrogen species (nitric oxide and peroxynitrite) could elicit the post-translational activation of the enzyme with respect to both of these biotransformation reactions. In virtually all instances, the K(m) values were decreased and the V(max) values were increased; the only exceptions observed being with hydrogen peroxide and L-phenylalanine. These effects were shown to occur at activator concentrations known to exist in physiological situations and, hence, suggest that reactive oxygen and reactive nitrogen species may cause, and may be involved with, the post-translational activation of phenylalanine 4-monooxygenase within the human body. This mechanism, in response to free-radical bursts, may enable the enzyme to expand its substrate range and to process certain xenobiotics as and when required.

[Lymphocyte subpopulations of peripheral blood in children with Schönlein-Henoch purpura and IgA nephropathy]. / Subpopulacje limfocytów krwi obwodowej u dzieci z choroba Schönleina-Henocha i nefropatia IgA.

The main lymphocytes' subpopulations of peripheral blood in 21 children (mean age--9.8 +/- 3.3 y) with permanent proteinuria and haematuria, 11 with IgA nephropathy (IgA) and 10 with nephropathy in course of Schonlein-Henoch purpura (Sch-H) during intensification of symptoms were assessed on flow cytometer f. Coultier, using monoclonal antibodies. The control group consisted of 21 healthy children at the same age. The results showed decreased percentage of CD4 and increased percentage of CD8 with decreased CD4/CD8 ratio in both groups of examined children. In most cases also increased percentage of B lymphocytes (CD19) were noticed and especially in children from N IgA group increased concentration of immunoglobulin A in serum. Only in some patients increased percentage of natural cytotoxic cells NK were noticed. The results were similar either in N IgA or Sch-H groups.

[The course of post-streptococcal glomerulonephritis depending on methods of treatment for the preceding respiratory tract infection]. / Przebieg popaciorkowcowego klebuszkowego zapalenia nerek w zaleznosci od sposobu leczenia poprzedzajacego zapalenia dróg oddechowych.

UNLABELLED: The aim of our work was to assess the course of post-streptococcal glomerulonephritis (APSGN) in children according to the way of preceding respiratory tract infection treatment. The examinations were carried out in a group of 26 children aged 5-15 years, who were divided into two subgroups: I--12 children, who did not receive antibacterial treatment, and II--14 children who were shortly treated with different antibiotics (3-5 days). All the children had full symptomatic picture of post-streptococcal glomerulonephritis with haematuria, oedemas, hypertension and hypocomplementemia. The etiology was diagnosed retrospectively during observation of ASO titer dynamics and additionally in 18 after finding pathogenic Streptococcus strains in pharyngeal swab. The differences in the course of illness was shown only during first weeks. In children from the group I the course of acute APSGN was a little more serious, because haematuria, proteinuria and hypertension were observed longer. Symptoms of nephrotic syndrome were observed in two children, acute renal insufficiency in two children, and one with hypertensive encephalopathy. After 3 and 12 months no children had pathological signs. Erythrocyturia was observed in 19 of 26 children after 3 months and in 10 of 26 children after 12 months after illness with similar frequency in both groups. In 5 children with proteinuria renal biopsy showed mesangialis proliferative glomerulonephritis--1st degree. CONCLUSION: All observed children with APSGN were not cured properly during the respiratory tract infection preceding the disease, however even short antibacterial treatment caused the moderation of symptoms.

[Use of salazopyrin in Schonlein-Henoch disease]. / Zastosowanie salazopiryny w chorobie Schonleina-Henocha.

A favourable effect was achieved of treatment with salazopyrin of severe abdominal of Schoenlein-Henoch disease (SH). Salazopyrin was used in two children with generalized form of SH, with paroxysmal abdominal pain and bleeding from the gastrointestinal tract.

[Anomalies of the cervical spine in children]. / Anomalie w zakresie kregoslupa szyjnego u dzieci.

Two children are presented with congenital anomalies of the cervical spine and associated malformations of the nervous and urinary systems. The attention is paid to the usefulness of the cervical spine assessment in children in cases of recurrent cerebellar manifestations of unclear aetiology or combined malformations of the urinary system.

[Familial occurrence of central diabetes insipidus]. / Rodzinne wystepowanie moczówki prostej osrodkowej.

Two cases are presented of familial diabetes insipidus with analysis of pedigree involving four generations. The analysis of diabetes insipidus occurrence in this family indicates the autosomal dominant type of inheritance.

[Echocardiographic image of cardial amyloidosis]. / Obraz echokardiograficzny amyloidozy serca.

Heart is involved nearly in 90% of acquired, systemic amyloidosis in a course of plasmocytoma, monoclonal gammapathy, Waldenstrom's disease and others immunological disorders. In classical acquired systemic amyloidosis due to chronic bacterial infection and other inflammatory states heart involvement is observed in 54% of patients. Authors presented a case of cardiac amyloidosis coexisting with hepatomegaly and nephropathy due to plasmocytoma. Diagnosis was based on the echocardiographic examination to which the patient was sent as the unstable postinfarction angina. Echocardiographic image typical of amyloidosis revealed such changes as: concentric both ventricular hypertrophy, generalized contractility impairment, thickness of intraatrial septum and pericardium with minimal effusion. Echocardiographic diagnosis was proved by the anatomopathologic examination.

[A case od rare location of Ewing's sarcoma in a 6-year-old boy]. / Przypadek rzadkiej lokalizacji miesaka Ewinga u 6-letniego chlopca.

A 6 boy is described treated for two months for pneumonia. In view of absent improvement the diagnosis was verified and malignant tumour was recognized. Radiological examination and clinical observation showed presence of a tumour in the 4th rib with pulmonary metastases. Histological examination of a biopsy specimen from the rib demonstrated primary microcellular Ewing's sarcoma. Of importance are: the age of the patient, rarely described location and diagnostic difficulties in the initial stage of the disease.

[Value of two-dimensional and Doppler echocardiography in the diagnosis of rupture of the interventricular septum in myocardial infarction]. / Wartosc echokardiograffii dwuwymiarowej i dopplerowskiej w diagnostyce chorych z peknieciem przegrody komorowej w przebiegu zawalu serca.

Usefulness of two-dimensional and Doppler echocardiography in diagnosis of the ruptured interventricular septum in a course of myocardial infarction was evaluated basing on own material consisted of 6 cases. Ventricular septal defect was visualized in 5 patients. The blood flow through the ventricular septum was detected in all of 6 patients. Obtained results were concordant with intraoperative and anatomicopathologic findings as for as the localization of the rupture is concerned.