The role of muscle strength on tendon adaptability in old age.

PURPOSE: The purpose of the study was to determine: (1) the relationship between ankle plantarflexor muscle strength and Achilles tendon (AT) biomechanical properties in older female adults, and (2) whether muscle strength asymmetries between the individually dominant and non-dominant legs in the above subject group were accompanied by inter-limb AT size differences. METHODS: The maximal generated AT force, AT stiffness, AT Young's modulus, and AT cross-sectional area (CSA) along its length were determined for both legs in 30 women (65 ± 7 years) using dynamometry, ultrasonography, and magnetic resonance imaging. RESULTS: No between-leg differences in triceps surae muscle strength were identified between dominant (2798 ± 566 N) and non-dominant limb (2667 ± 512 N). The AT CSA increased gradually in the proximo-distal direction, with no differences between the legs. There was a significant correlation (P < 0.05) of maximal AT force with AT stiffness (r = 0.500) and Young's modulus (r = 0.414), but only a tendency with the mean AT CSA. However, region-specific analysis revealed a significant relationship between maximal AT force and the proximal part of the AT, indicating that this region is more likely to display morphological adaptations following an increase in muscle strength in older adults. CONCLUSIONS: These findings demonstrate that maximal force-generation capabilities play a more important role in the variation of AT stiffness and material properties than in tendon CSA, suggesting that exercise-induced increases in muscle strength in older adults may lead to changes in tendon stiffness foremost due to alterations in material rather than in its size.

Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL).

TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18-64) were included. Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. The toxicity was moderate, resulting in a cumulative incidence of non-relapse mortality (NRM) at 1 year of 8% (90% confidence interval: 2-15%). Acute GvHD grade II-IV and grade III/IV was noted in 53% and 14%, respectively. Chronic GvHD at one year was seen in 41%. After a median follow-up of 24 months the cumulative incidence of relapse was 36% (90% confidence interval: 24-48) and 51% (90% confidence interval: 37-65) at 1 and 2 years, respectively. The estimated 2-year disease-free and overall survivals were 36 and 48%, respectively. Treosulfan, etoposide and cyclophosphamide followed by AHSC has a favorable toxicity profile with low NRM and therefore represents a potential alternative regimen for ALL in 1. CR (NCT00682305).

Functional cooperation of Epstein-Barr virus nuclear antigen 2 and the survival motor neuron protein in transactivation of the viral LMP1 promoter.

Epstein-Barr virus nuclear antigen 2 (EBNA2) is essential for viral transformation of B cells and transactivates cellular and viral target genes by binding RBPJkappa tethered to cognate promoter elements. EBNA2 interacts with the DEAD-box protein DP103 (DDX20/Gemin3), which in turn is complexed to the survival motor neuron (SMN) protein. SMN is implicated in RNA processing, but a role in transcriptional regulation has also been suggested. Here, we show that DP103 and SMN are complexed in B cells and that SMN coactivates the viral LMP promoter in the presence of EBNA2 in reporter gene assays and in vivo. Subcellular localization studies revealed that nuclear gems and/or coiled bodies containing DP103 and SMN are targeted by EBNA2. Protein-protein interaction experiments demonstrated that DP103 binds to SMN exon 6 and that both EBNA2 and SMN interact with the C terminus of DP103. Furthermore, a DP103 binding-deficient SMN mutant was released from nuclear gems and/or coiled bodies and further enhanced coactivation. In addition, impaired transactivation of a DP103 binding-deficient EBNA2 mutant was rescued by overexpression of SMN. Testing different promoter constructs in luciferase assays showed that RBPJkappa is required but not sufficient for coactivation by EBNA2 and SMN. Overall, our data suggest that EBNA2 might target spliceosomal complexes by binding to DP103, thereby releasing SMN which subsequently exerts a coactivational function within the RNA-polymerase II transcription complex on the LMP1 promoter.

Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) ORF54 encodes a functional dUTPase expressed in the lytic replication cycle.

The complete ORF54 of the Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpesvirus-8; HHV-8) was cloned and expressed in E. coli. The results show that KSHV/HHV-8 ORF54 encodes a functional dUTPase which specifically hydrolyses dUTP to dUMP. Monoclonal antibodies against the HHV-8 dUTPase detected a protein with the expected molecular mass of 35 kDa in HHV-8-infected BCBL-1 cells. Induction of the lytic replication cycle of HHV-8 by treatment of BCBL-1 cells with the phorbol ester TPA resulted in an increased expression of the protein which was not inhibited by phosphonoacetic acid, indicating that the protein is expressed early in the lytic replication cycle. Moreover, the sporadic expression of the HHV-8 dUTPase in tissue sections of Kaposi's sarcoma was detected by immunohistochemistry.

Glucocorticoids inhibit stress-induced phosphorylation of CREB in corticotropin-releasing hormone neurons of the hypothalamic paraventricular nucleus.

The corticotropin-releasing hormone (CRH) gene contains a perfect palindromic motif in its promoter region that allows binding of the cyclic adenosine monophosphate response element binding protein, CREB. Since previous studies suggest that the CRH gene can be activated by cyclic adenosine monophosphate, we determined whether stress and feedback inhibition by glucocorticoids in CRH-producing neurons in the hypothalamic paraventricular nucleus could be mediated by changes in the phosphorylation of CREB. Antisera to CREB and phospho-CREB Ser133 (PCREB), the active phosphorylated form of CREB, were used for immunohistochemical studies on rat brain. In nonstressed animals CREB immunostaining was confined to the nucleus of cells ubiquitously throughout the hypothalamus, while PCREB immunostaining was discretely localized in magnocellular neurons and only a few cells in the medial parvocellular subdivision of the paraventricular nucleus. Ether and handling stress markedly increased the number of PCREB-labeled neurons in the parvocellular subdivision. Double immunolabeling with CRH antiserum revealed that the majority of hypophysiotropic CRH neurons in stressed animals expressed PCREB. Following systemic administration of dexamethasone (100 micrograms/day) for 2.5 days, PCREB immunostaining was completely abolished in parvocellular CRH-producing neurons after ether or handling stress. Dexamethasone had no apparent effect on CREB immunostaining. These results demonstrate that glucocorticoids suppress CREB phosphorylation in hypophysiotropic CRH neurons and suggest that prevention of CREB phosphorylation is a possible mechanism for feedback inhibition of CRH biosynthesis by glucocorticoids.

[Results of percutaneous kidney cyst sclerosing]. / Ergebnisse der perkutanen Nierenzystenverödung.

The results of the percutaneous obliteration of the renal cysts in 68 renal cysts (6 cases of recidivation) are discussed. The use of an obliteration remedy is superior to the only submaximal depletion of cysts. The results after the sclerosation treatment with ethoxysclerol 2% were essentially better than after varicocid instillation. The sclerosation therapy may be performed only after a preliminary thorough angiographical clarification including renocystography. The excretion urograms are sufficient for the control examination.

[Quantitative angiographic studies for the differential diagnosis of early acute kidney failure of ischemic and rejection-damaged grafts]. / Quantitative angiographische Undersuchungen zur Differentialdiagnose des frühen akuten Nierenversagens ischämie- und rejektionsgeschädigter Transplantate.

On 22 auto- or homotransplanted kidneys of dogs a quantitative angiographic evaluation of the corticalis perfusion was carried out. For this purpose four special parameters were evaluated. With the help of the linear discriminance analysis we succeed in a sufficient secure separation between autografts impaired by ischaemia or shock on the one hand and homografts impaired by rejection on the other. It is referred to the prognostic significance of angiography in human graft kidneys with disturbed function.

[Planimetric measurement of kidney size in patients with stenosis of the renal artery (author's transl)]. / Planimetrische Nierengrössenbestimmungen bei Patienten mit Nierenarterienstenosen (prä- und postoperative Kontrolluntersuchungen).

Comparison of pre- and postoperative angiograms reveals no significant statistical difference concerning kidney size after successful reconstruction of the renal artery. This examination is based on planimetric data of 10 patients with haemodynamical important stenoses of the renal artery (including one patient with bilateral stenosis).

Comparison of DES vs DES + chlorambucil in women with first recurrence of breast cancer.

Thirty-four women with first recurrence of breast cancer were randomized into two groups, and received either Diethylstilbestrol (DES) 5 mg orally (PO) t.i.d. alone, or in combination with Chlorambucil (CB) 0.1--0.2 mg/kg/day PO. All patients randomized were greater than 5 years postmenopausal at the time of the study and had no prior chemical or hormonal therapy. Estrogen receptors were not available. There was no significant difference between Groups A and B with respect to frequency of objective response or mean duration of that response, with the values for Group A being 46.2% and 4.8 months, respectively, and for Group B, 46.7% and 4.8 months (P greater than 0.05). The most common toxicities noted for both groups were nausea and vomiting, edema, weakness, and thrombophlebitis. The risk of major toxicity necessitating withdrawal from the study was greater in Group B due to the added danger of thrombocytopenia/pancytopenia. The addition of CB to DES does not appear to offer any significant advantage over DES alone in women with first recurrence of breast cancer.

[Surgical treatment of renovascular hypertension (author's transl)]. / Ergebnisse der Nierenarterienrekonstruktion zur Behandlung des vasorenalen Hypertonus.

Renal artery stenosis was corrected in 50 patients suffering from renovascular hypertension. In 32 cases hypertension returned to normal, 11 patients were improved and hypertension was unchanged in seven cases.

[Vascular changes in experimental renal ischemia and after renal homotransplantation (experimental angiographic study on animals)]. / Gefässveränderungen bei experimenteller Nierenischämie und nach Nierenhomotransplantation (Eine tierexperimentelle angiographische Studie).

Which consequences result from these experimental results from practice? In the acute angiography in postoperative functional distrubance after transplantation of a human kidney is at first probably always to be reckoned with a rejection process, though this immunological process by no means must be in the foreground of the causal connection of several pathogenetic factors. Therefore, in our opinion it would then be assumed an ischaemia-conditioned cell damage of the tubulus by a longer lasting prefinal circulatory depression or due to a not optimal preservation, when there is in the angiogramme a clear discrepancy to the severity of the postoperative functional distrubance, i.e. when angiographically exists only a slight cortical ischaemia in an otherwise good arterial filling picture and a widely normal capillary filling phase.

[Diagnosis of a nonparasitic splenic cyst]. / Zur Diagnostik einer nichtparasitären Milzzyste.

It is reported on a case of the infrequent non-parasitic cyst of the spleen. Here the difficulties of the diagnostics due to the poorness of clinical and laboratory-chemical symptoms are emphasized. After the radiological exclusion of the belonging of the spacial demand to the gastrointestinal canal and to the uropoietic system it is recommended to strive for the angiographical clarification and, when a cyst of the spleen is to be proven, for the splenectomy.