The influence of cytomegalovirus infection, confirmed by pp65 antigen presence, on the development of cardiac allograft vasculopathy

AIM: We sought to determine the impact of cytomegalovirus (CMV) infection on cardiac allograft vasculopathy (CAV) development in the long term after orthotopic heart transplantation (OHT). MATERIALS AND METHODS: We enrolled 144 patients in this retrospective study including 128 men with an overall age at transplantation of 48.4 +/- 9.3 years. Before OHT, 45% exhibited ischemic heart disease (IHD). The mean follow-up was 62 months. Detection of CMV antigenemia was performed by identification of pp65-antigen on peripheral blood leukocytes. The first diagnostic coronary angiography was routinely performed at 1 year after heart transplantation and thence every second year. We evaluated every incidence of change in the coronary arteries, of significant stenosis (requiring percutaneous coronary intervention), acute myocardial infarction, of death or of transplantation. All patients were followed to the incidence of a cardiovascular event, death, or the end of observation. RESULTS: Of 144 patients, 33 were pp65 positive, namely 29 men with overall mean age at transplantation of 48 +/- 10.3 years. Before OHT, 52% had IHD. The incidence of CAV during follow-up was 24% (n = 8) in the pp65(+) and 22% (n = 24) in the pp65(-) group. It was significant in 3 (9%) versus 8 (24%) patients. There were 4 (12%) deaths in pp65(+) and 9 (8%) deaths in the pp65(-) groups. Kaplan-Meier survival curves to estimate the time for CAV development and death showed no significant differences by log-rank tests. CONCLUSION: No impact of CMV infection on CAV development was observed in first 5 years after OHT.     

Evaluation of coccygeal bone variability, intercoccygeal and lumbo-sacral angles in asymptomatic patients in multislice computed tomography

The coccyx is a highly variable structure in the human caudal spine. Previous studies have revealed a significant correlation between coccyx shape and the pain syndrome coccygodynia. The aim of this study was to carry out a complex morphological evaluation of the coccyx in a group of asymptomatic patients of different sex and age examined by multislice computed tomography (MSCT) of the pelvis for different clinical reasons. MSCT pelvis examinations from various nontraumatic clinical conditions from consecutive adult patients (250 males and 250 females of comparable age, mean 54.9 ± 14.8 years) were used. Based on middle sagittal plane reconstructions: coccyx configuration (types I–IV according to Postacchini and Massobrio classification, each successive type characterized by a more pronounced anterior position of coccyx), number of segments, length and angles (intercoccygeal and lumbo-sacral) were measured. The results obtained were analyzed statistically. The following types of coccyx were observed in the study group: type I in 16.2 %, type II 40.0 %, type III 32.4 %, and type IV 11.4 % cases. In most cases (50.8 %), three segments were noted. Lumbo-sacral angle varied from 15.6° to 66.4° (average 41.6° ± 7.7°), and intercoccygeal angle from 0° to 107° (average 51° ± 23.3°). A significant negative correlation between age and number of segments as well as age and intercoccygeal angle was observed. In males, the coccyx was significantly longer, while in females the intercoccygeal angle was significantly wider. Type I was significantly more frequent in males, while type IV was found more often in females. The results obtained differ from other results in the literature. Our research could be useful to determine population standards, and help (together with clinical history) future studies of associations between idiopathic coccygodynia and coccyx morphology.     

Reversal by insulin of concanavalin A inhibition of myotube formation and evidence for common binding sites

Concanavalin A (Con A) inhibits fusion of trypsin-treated myoblasts. This inhibition is reversed by the addition of supraphysiological concentrations (4 micrograms/ml) of insulin either during continuous presence in culture or by pulse additions at 36 and 48 h of culture, just before the time that cultures not treated with Con A undergo myoblast fusion. This reversal is not due to the mitogenic effects of insulin. Under reversal conditions, no specific displacement of bound [125I]iodo-Con A was detected nor did insulin stimulate metabolite uptake. Cell surface replicas of hemocyanin-tagged Con A showed that insulin reversal of the inhibition of myotube formation correlated with the alteration of Con A-binding sites from a clustered configuration present in the inhibited cells to a dispersed state correlated with normal myotube formation. Although a causal relationship has yet to be shown, the data suggest that insulin-mediated reversal of Con A inhibition of myoblast fusion may be related to the ability of insulin at supraphysiological levels to alter the translational mobility of cell surface components containing glucose and/or mannose residues capable of binding Con A. Evidence is presented which suggests that insulin and Con A share common binding sites, since in the physiological range of insulin concentrations (1 ng/ml), Con A pretreatments results in an inhibition of specific [125I]iodo-insulin binding, and antagonistic interactions of insulin and Con A on metabolite uptake and cell proliferation occur. Thus, it appears that the insulin receptors of developing skeletal muscle are glycoproteins containing glycopyranosides.     

Sequence typing of human adenoviruses isolated from Polish patients subjected to allogeneic hematopoietic stem cell transplantation – a single center experience

ABSTRACT

Purpose: Human adenoviruses (HAdV) from species A, B and C are commonly recognized as pathogens causing severe morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. The purpose of the present study was to determine HAdV types responsible for viremia in HSCT recipients at a large tertiary hospital in Poland.

Methods: Analysis of partial nucleotide sequences of HAdV hexon gene was used to type 40 clinical isolates of HAdV obtained from 40 HSCT recipients.

Results: We identified six different HAdV serotypes belonging to species B, C and E. We demonstrated high variability in sequences of detected HAdV types, and patients infected with the same HAdV types were not hospitalized at the same time, which suggests the low possibility of cross-infection. In almost all patients, anti-HAdV antibodies in IgG class were detected, which indicates a history of HAdV infection in the past. Clinical symptoms accompanying HAdV viremia were in 89%, and in 61.5% of individuals, HAdV was a sole pathogen detected. There were no cases with high-level HAdV viremia and severe systemic or organ infections. Graft-versus-host disease (GvHD) was present in patients infected with species B and C, but grade II of GvHD was observed only in patients infected with HAdV-B.

Conclusions: The predominance of HAdV-C and common presence of anti-HAdV antibodies in IgG class may strongly suggest that most infections in the present study were reactivations of HAdV persisting into the patient’s mucosa-associated lymphoid tissues. Variability of HAdV sequences suggests that cross-infections between patients were very rare.

ABBREVIATIONS: GvHD: graft-versus-host disease; HAdV: human adenoviruses; HSCT: hematopoietic stem cell transplantation     

Acute myeloid and T-cell acute lymphoblastic leukaemia with aberrant antigen expression exhibit similar TCRδ gene rearrangements

TCRδ gene recombination patterns were analysed by Southern blot, polymerase chain reaction and nucleotide sequencing in acute myeloid leukaemias with coexpression of lymphoid antigens (Ly⁺ AML, n = 10) as well as in early T-cell acute lymphoblastic leukaemias with (My⁺ T-ALL, n = 10) and without coexpression of myeloid antigens (My^? T-ALL, n = 9). These 29 acute leukaemias exhibiting TCRδ gene rearrangements were selected from 66 Ly⁺ AML, 14 My⁺ T- ALL and 12 My^? T-ALL cases. Similar recombination patterns, namely Dδ2Jδ1 and Vδ1Jδ1 gene rearrangements, were observed in Ly⁺ AML and My⁺ T-ALL. In contrast to Vδ2Dδ3 rearrangements in B-cell precursor ALL, these rearrangements require activation of a T-cell-specific TCRδ enhancer. Comparison of My⁺ T-ALL and Ly⁺ AML with My^? T-ALL exhibited a higher incidence of incomplete Dδ2Jδ1 rearrangements in My⁺ T-ALL and Ly⁺ AML. Since a Dδ2Jδ1 rearrangement is an early event in TCRδ recombination, these leukaemias seem to be arrested at an earlier stage of differentiation. Similar patterns of TCRδ rearrangements in My⁺ T-ALL and Ly⁺ AML suggest existence of a common myeloid/T-lymphoid progenitor cell. Although weak or missing expression of terminal deoxynucleotidyl transferase (TδT) was found in 7/10 Ly⁺ AML cases, no difference was observed in numbers of N-nucleotides inserted in junctional regions when comparing with 3/10 cases exhibiting TdT expression. Since TdT activity is necessary for N-nucleotide addition, this finding suggests down-regulation of TδT expression after rearrangement took place in these Ly⁺ AML cases.     

Mass spectrometric characterization of a 2,2-bis[4-(2,3-epoxypropoxy)phenyl]propane-aniline addition polymer and its telechelic prepolymers

Fast-atom bombardment (FAB) and plasma desorption mass spectrometry of high molecular weight addition polymers of 2,2-bis[4-(2,3-epoxypropoxy)phenyl]propane (DGEBA) and aniline show protonated molecular ions of the intact polymer and oligomer molecules. The oligomeric products consist mainly of cyclooligomers. Their formation can be observed during the polymerization reaction. Telechelic prepolymers having epoxide end groups as well as telechelics containing amino end groups were found with lower degree of polymerization in the mass spectra. Side reactions such as ether formation or epoxide polymerization were not observed. Telechelic DGEBA-aniline prepolymers are shown to consist of a series of oligomers as shown by highpressure liquid chromatography (HPLC) analyses. Consequently, the FAB mass spectra of the prepolymers show molecular ions of the different oligomers. Furthermore, under the conditions of the FAB mass spectrometric analysis fragmentation of the prepolymers to iminium fragment ions was observed.     

Synthesis, receptor binding affinities and alpha-MSH releasing activities of TRH analogues

New syntheses of three thyrotropin releasing hormone (TRH) analogues ([Dopa2]THR, [Nic1]TRH, and [Tyr(30NO2)2]TRH) have been reported (Dopa stands for L-3,4-dihydroxyphenylalanine, Nic--for nicotinic acid and Tyr(3-NO2)--for L-3-nitrotyrosine). These three TRH analogues and five already known ones ([Aad1Tca3]TRH, [D-His2]TRH, [D-Pro3]TRH, [Pro-NH-NH2(3)]TRH and [Tyr2]TRH), were studied in vitro for their binding activity to rat pituitary TRH receptors and a-MSH releasing activity in the neuro-intermediate lobe of frogs. Competition of analogues for 3H-TRH binding to rat anterior pituitary membrane fraction was used. One of ten tested analogues ([Aad1, Tca]3 TRH) was as potent as TRH in competing for high-affinity binding sites (Kd = 8.5 nM). The binding activity of diastereoisomers ([D-His2]TRH and [D-Pro3]TRH) was reduced as well as that of analogue [Pro-NH-NH2(3)]TRH. The rest of the analogues were inactive. The binding activities were in good accordance with alpha-MSH releasing activities.     

Effect of stimulation and coagulation of the midbrain reticular formation on the bronchial musculature; a modification of histamine susceptibility

Summary The influence of the midbrain reticular formation on bronchial muscle tonus in the guinea pig was examined. In the midbrain reticular formation functionally interrelated regions were distinguished that play a role in the control of bronchial smooth muscle tonus. The dorso-caudal regions of the midbrain reticular formation activate the constriction of the bronchial tubes, whereas the ventro-rostral regions exert an antagonistic influence. The dorso-caudal regions act on the effector mainly by phasic regulation through the parasympathetic nervous system. The facilitation of the dilatatory reaction is connected with the prepotency of the sympathetic nervous system and an activation of the hypophysio-adrenal system.

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Zusammenfassung Bei Meerschweinchen wurde die Einwirkung der Formatio reticularis des Hirnstammes auf den Tonus der Bronchialmuskulatur untersucht. In der Formatio reticularis wurden die funktionell zusammenhängenden Strukturen, welche den Tonus der Bronchialmuskulatur regulieren, lokalisiert. Die dorso-caudalen Gebiete der Formatio reticularis aktivieren die Verengerung der Atmungswege, die ventrorostralen Gebiete wirken antagonistisch auf die glatte Bronchialmuskulatur. Die dorso-caudalen Gebiete wirken über das parasympathische Nervensystem. Die Aktivierung der Entspannung hängt mit dem überwiegenden Einfluß des sympathischen Nervensystems zusammen und ist an die Aktivierung des hypophysäradrenalen Systems gebunden.

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With 15 Figures