Experimental capabilities for liquid jet samples at sub-MHz rates at the FXE Instrument at European XFEL.

The Femtosecond X-ray Experiments (FXE) instrument at the European X-ray Free-Electron Laser (EuXFEL) provides an optimized platform for investigations of ultrafast physical, chemical and biological processes. It operates in the energy range 4.7-20 keV accommodating flexible and versatile environments for a wide range of samples using diverse ultrafast X-ray spectroscopic, scattering and diffraction techniques. FXE is particularly suitable for experiments taking advantage of the sub-MHz repetition rates provided by the EuXFEL. In this paper a dedicated setup for studies on ultrafast biological and chemical dynamics in solution phase at sub-MHz rates at FXE is presented. Particular emphasis on the different liquid jet sample delivery options and their performance is given. Our portfolio of high-speed jets compatible with sub-MHz experiments includes cylindrical jets, gas dynamic virtual nozzles and flat jets. The capability to perform multi-color X-ray emission spectroscopy (XES) experiments is illustrated by a set of measurements using the dispersive X-ray spectrometer in von Hamos geometry. Static XES data collected using a multi-crystal scanning Johann-type spectrometer are also presented. A few examples of experimental results on ultrafast time-resolved X-ray emission spectroscopy and wide-angle X-ray scattering at sub-MHz pulse repetition rates are given.

High-resolution crystal structure and IgE recognition of the major grass pollen allergen Phl p 3.

BACKGROUND: Group 2 and 3 grass pollen allergens are major allergens with high allergenic activity and exhibit structural similarity with the C-terminal portion of major group 1 allergens. In this study, we aimed to determine the crystal structure of timothy grass pollen allergen, Phl p 3, and to study its IgE recognition and cross-reactivity with group 2 and group 1 allergens. METHODS: The three-dimensional structure of Phl p 3 was solved by X-ray crystallography and compared with the structures of group 1 and 2 grass pollen allergens. Cross-reactivity was studied using a human monoclonal antibody which inhibits allergic patients' IgE binding and by IgE inhibition experiments with patients' sera. Conformational Phl p 3 IgE epitopes were predicted with the algorithm SPADE, and Phl p 3 variants containing single point mutations in the predicted IgE binding sites were produced to analyze allergic patients' IgE binding. RESULTS: Phl p 3 is a globular ß-sandwich protein showing structural similarity to Phl p 2 and the Phl p 1-C-terminal domain. Phl p 3 showed IgE cross-reactivity with group 2 allergens but not with group 1 allergens. SPADE identified two conformational IgE epitope-containing areas, of which one overlaps with the epitope defined by the monoclonal antibody. The mutation of arginine 68 to alanine completely abolished binding of the blocking antibody. This mutation and a mutation of D13 in the predicted second IgE epitope area also reduced allergic patients' IgE binding. CONCLUSION: Group 3 and group 2 grass pollen allergens are cross-reactive allergens containing conformational IgE epitopes. They lack relevant IgE cross-reactivity with group 1 allergens and therefore need to be included in diagnostic tests and allergen-specific treatments in addition to group 1 allergens.

Carrier-bound nonallergenic Der p 2 peptides induce IgG antibodies blocking allergen-induced basophil activation in allergic patients.

BACKGROUND: More than 90% of house dust mite-allergic patients are sensitized to the major Dermatophagoides pteronyssinus allergen, Der p 2. The aim of this study was to develop and characterize an allergy vaccine based on carrier-bound Der p 2 peptides, which should allow reducing IgE- and T-cell-mediated side-effects during specific immunotherapy (SIT). METHODS: Five Der p 2 peptides (P1-P5) were synthesized and analyzed regarding IgE reactivity and allergenic activity. Lymphoproliferative and cytokine responses induced with Der p 2 and Der p 2 peptides were determined in peripheral blood mononuclear cells from mite-allergic patients. Der p 2-specific IgG antibodies induced with carrier-bound Der p 2 peptides in mice and rabbits were tested for their capacity to inhibit IgE binding and basophil activation in allergic patients. RESULTS: Of five overlapping peptides (P1-P5) covering the Der p 2 sequence, two peptides (P2 and P4) were identified, which showed no relevant IgE reactivity, allergenic activity, and induced lower Der p 2-specific T-cell activation than Der p 2. However, when coupled to a carrier, P2 and P4 induced Der p 2-specific IgG antibodies in animals, which inhibited allergic patients' IgE binding to the allergen and allergen-induced basophil activation similar as antibodies induced with Der p 2. CONCLUSIONS: Carrier-bound Der p 2 peptides should allow avoiding IgE-mediated side-effects, and because of their low potential to activate allergen-specific T cells, they may reduce late-phase side-effects during SIT. Further, these peptides may be also useful for prophylactic vaccination.

Anaesthetic management in a case of Huntington's chorea.

There are only a few case reports regarding the anaesthetic management of a patient with Huntington's chorea and the best anaesthetic technique is yet to be established for those patients which are at higher risk of perioperative complications. We describe the successful management of a 30-year-old patient suffering from Huntington's chorea admitted for urgent appendectomy. To minimize the risk of aspiration, the trachea was intubated using a fiberscope with the patient sedated and spontaneously breathing. Anaesthesia was maintained with isoflurane and fentanyl and the recovery was rapid and uneventful as the postoperative course.

Bagremycin A and B, novel antibiotics from streptomyces sp. Tü 4128.

Two novel secondary metabolites, bagremycin A (2) and B (3), were detected in the culture filtrate of Streptomyces sp. Tü 4128 by HPLC-diode-array screening. They are phenol esters of 3-amino-4-hydroxybenzoic acid with a derivative of p-coumaric acid and show a moderate activity against gram-positive bacteria and some fungi.

Conservative surgery and irradiation (QUART) in the treatment of 243 stage I-II breast cancer patients.

From 1980 to 1987, 243 evaluable patients with pT1, pT2 (less than 3 centimeters in diameter), N0, M0, invasive breast cancer were treated with "quadrantectomy" with axillary dissection followed by electron beam radiation therapy (QUART) at the St. Bortolo Hospital, Vicenza. Stage II patients received adjuvant chemotherapy (CMF) if preperimenopausal or hormonotherapy (tamoxifen) if postmenopausal. The median follow-up was 54 months (26 to 116 months). The 4.5-year overall survival (OS) and disease-free survival (DFS) were respectively 91% and 85%; the 10-year actuarially estimated OS and DFS was 77%. Thirty-three patients relapsed, 11 of whom had local recurrence, and 23 developed distant metastases. A significantly longer OS and DFS were observed in stage I versus stage II (p = 0.0008) and in pT1 versus pT2 (p = 0.001) tumors. No difference was found regarding menopausal status and histotype. The local control of disease was very high (95.5%), with a significantly higher local recurrence rate in premenopausal women compared to postmenopausal (10/117 versus 1/126; p = 0.009). Tumor size did not influence the frequency of local recurrence. No major complications occurred but a significantly higher rate of reversible radiation-pneumonitis occurred in patients treated with higher energies of electrons (17 to 20 MeV) compared with lower (6 to 13 MeV) (33/177 versus 7/66; p less than 0.05). Cosmetic results were judged as excellent in 20%, satisfactory in 68%, unsatisfactory in 6% and not evaluable in 6% of cases. We conclude first, that small pT2 breast carcinomas may also be safely treated with QUART, second, that the electron beam is a radiotherapeutic technique able to produce a good cosmetic result and to assure a satisfactory local control and, finally, that the use of tamoxifen in postmenopausal stage II breast carcinomas is safe and easy to combine with radiotherapy in the conservative management of early breast cancer due to the lower toxic effects, compared to those observed in premenopausal women treated with chemotherapy.

[Block of the cervical plexus in surgery of the carotid artery. Our experience with 142 cases]. / Il blocco del plesso cervicale nella chirugia della carotide. Nostra esperienza su 142 casi.

The main anesthesiological problem in TEAC operations is the possibility of evaluating the degree of tolerance after carotid artery clamping. When facing this situation, some anesthesiologists prefer to administer general anesthesia, others prefer loco-regional anesthesia. On the basis of their background and experience, the Authors, from 1.1.1987 to 12.31.1988, have performed 142 nerve blocks of the superficial and the cervical plexus. The proposed technique is simple. No side effects are observed. Moreover it is gratifying for the surgeon and safe from risks for patients. Loco-regional anesthesia permits a close neurologic monitoring that is easily understandable and inexpensive. When performing this kind of surgery, this technique seems to be valid and effective.

[Evaluation of materials and technics in vascular surgery using 111-Indium]. / Valutazione dei materiali e delle tecniche in chirurgia vascolare mediante Indio 111.

The thrombogenicity of the graft materials is a significant factor incriminated in early failures. Some improvements have been achieved by modification of physical characteristics of the material as porosity, compliance, durability in order to improve patency rates. Platelets are major determinants of thrombus formation and may still be thrombogenic by activation of the coagulation enzymes. The purpose of this work is to study the platelets deposition on different material grafts, utilizing autologous platelets labelled with 111-Indium. The radioactivity pulses was recorder before and 4 days after surgery in aortoiliac and femoropopliteal districts. The graft material used in aortoiliac occlusions was: velour, double velour PTFE; in femoropopliteal: Double velour, PTFE, saphenous vein, umbilical vein, bovine carotid. In some patients the operation was TEA with patch in PTFE. The authors show the results of this study in 92 patients in relation of the material graft an location.

[Usefulness of morphoscillography for the prognosis of the duration of aorta-femoral bypass in complex ilio-femoral arteriopathies]. / Utilità della morfoscillografia per la prognosi di durata dei by-pass aorto-femorali nelle arteriopatie complesse ilio-femorali.

The work has the purpose to draw some prognostic indications and therapeutical directions in the aorto-iliac arteriosclerotic disease, with reference to the preoperative arteriographic and morphoscillographic reports. In the 94 patients, corresponding to 140 limbs operated on, it was possible to remark the progression in worsening of the sphygmic activity in the limbs segments goes along with a deterioration of the surgical results, and the prognosis is particularly severe when the minimum values of total vascular caliber are remarked at thighs.

[Surgical treatment of caval obstructions]. / Il trattamento chirurgico delle ostruzioni cavali.

The vena cava is the seat of obstructive disorders for which direct reparative surgery may sometimes become necessary. S.C.S. is mainly caused by neoplastic invasions or, in the case of the inferior vena cava, by progression of phlebothrombosis of the lower limbs. Prosthesis or autologous substitution and thrombointimectomy are specifically indicated in the two cases respectively. The two methods are described in detail and exemplified through the authors' personal cases consisting in an inferior caval thrombointimectomy and four superior caval by passes. It is concluded that surgical procedures are effective when the primitive disorder can be dominated and the thrombosis is not excessively extensive.

[Intestinal lymphagiectasis of surgical interest]. / Linfangectasia intestinale di interesse chirurgico

Surgical management of a case of intestinal lymphangectasis with unusual features is reported. The view that the picture was one of early segmentary enteritis was supported by some aspects of the course and various anatomopathological features.