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Aim: To assess the histopathological background of enhancement mechanisms in dynamic MR mammography studies., Methods: The dynamic MR mammography (MRM) examinations were done with a 1.5 T MR imager (Magnetom Vision, Siemens) using a double breast coil and a coronal FLASH-3D sequence. Enhancement data were acquired during 9 minutes post contrast medium injection (Gd-DTPA 0.2 mmol/kg). Acquisition time was 87 sec/slab. Early enhancement at the first post contrast measurement (E1) and slope of wash-out (SE2-L) were calculated. In immunohistology, proliferation was assessed by the monoclonal antibody Ki 67, capillaries were stained by a CD 31 antibody. Of a total of 48 operated patients, 58 lesions and 46 surrounding tissues were evaluated., Results: Cellularity, capillary density and proliferation showed statistically significant correlations with E1 (p < 0.01). In multiple regression analysis, E1 was significantly associated only with high cellularity (p = 0.002) and the combination of high cellularity and high microvessel density (p = 0.002); a negative slope of wash out was significantly associated only with malignant histology (p = 0.027)., Conclusions: Our findings indicate a direct influence of cellularity and microvessel density on early enhancement. The expression of the proliferation marker Ki 67 was not an independent predictor for contrast enhancement.

The serine protease urokinase-type plasminogen activator (uPA), its inhibitor (PAI-1), and its receptor (uPAR; CD87) facilitate cancer cell invasion and metastasis. Whereas uPA and PAI-1 antigen levels determined in tumor tissue extracts of breast cancer patients correlate with disease recurrence and overall survival, the prognostic relevance of uPAR is still a matter of debate. We established two new sandwich-type enzyme-linked immunosorbent assay (ELISA) formats (HU/IIIF10-ELISA and HU/HD13-ELISA) using the epitope-defined monoclonal antibody (mAb) IIIF10 or the conformation-dependent mAb HD13.1, a polyclonal chicken antibody (HU277), and recombinant soluble uPAR (CHO-suPAR) as the standard. The lower detection limit of the assays was at 0.16 ng/ml, with a linear dose-response up to 5 ng/ml of uPAR antigen. Both ELISA formats showed good reproducibility and recovery. The intra-assay and the inter-assay variation coefficients were respectively 4.3% and 11.7% (HU/IIIF10-ELISA) and 4.0% and 10.7% (HU/HD13-ELISA). The recovery rate of uPAR in cell lysates spiked with CHO-suPAR was above 82% and 88%, respectively. With these new ELISA formats, uPAR antigen content in breast cancer tissue extracts and tumor cell lysates was determined and compared to a commercially available ELISA (ADI-ELISA). By all of the three uPAR ELISA formats CHO-suPAR and uPAR present in lysates of non-malignant epithelial cells and stimulated monocytes were quantified with similar sensitivity. Interestingly, in breast cancer cell lines of epitheloid origin a higher uPAR antigen content was determined by the HU/IIIF10-ELISA than the HU/HD13- or ADI-ELISA formats. In lysates of fibroblastic breast cancer cell lines similar uPAR values were obtained with the HU/IIIF10- and ADI-ELISA formats, whereas with the HU/HD13-ELISA significantly lower uPAR concentrations were determined. The prognostic relevance of tumor uPAR antigen was evaluated in 199 primary breast cancer patients with a median follow-up of 24 months. uPAR antigen values above the cut-off of 3.33 ng/mg protein as determined by the HU/IIIF10-ELISA were significantly correlated with short disease-free survival (p=0.025). Results obtained by the other two ELISA formats (HU/HD13-ELISA and ADI-ELISA) were not associated with prognosis. Our findings stress the need of well-characterized antibodies, which detect both uPAR of non-malignant and tumor cells, in setting up a uPAR-ELISA useful for assessing breast cancer patient prognosis.

Using a 150-mum-thick CsLiB(6)O(10) crystal, we produced 100-fs, >200-nJ light pulses tunable between 175 and 180 nm by sum-frequency generation at a 1-kHz repetition rate with an all-solid-state laser system mixing the fourth harmonic of a femtosecond Ti:sapphire regenerative amplifier and the idler pulse from a traveling-wave optical parametric amplifier.

Dissemination of single tumor cells to the bone marrow is a common event in cancer. The clinical significance of cytokeratin-positive cells detected in the bone marrow of cancer patients is still a matter of debate. In gastric cancer, overexpression of the receptor (uPAR or CD87) for the serine protease urokinase-type plasminogen activator (uPA) in disseminated cancer cells indicates shorter survival of cancer patients. A new immunofluorescence approach, applying confocal laser scanning microscopy, is introduced to locate CD87 antigen in cytokeratin-positive tumor cells and to quantify the CD87 antigen by consecutive scanning. At first, cytokeratin 8/18/19-positive carcinoma cells are identified at excitation wavelength 488 nm using monoclonal antibody A45B/B3 to the cytokeratins and goat anti-mouse IgG labeled with the fluorochrome Alexa488. Next, CD87 in tumor cells is identified by chicken antibody HU277 to the uPA-receptor and goat anti-chicken IgY labeled with fluorochrome Alexa568 (excitation wavelength 568 nm) and the fluorescence signal quantified on a single cell basis using fluorescently labeled latex beads as the fluorescence reference. From 16 patients with gastric or esophageal carcinoma, bone marrow aspirates were obtained, stained for cytokeratins and CD87 and then subjected to laser scanning fluorescence microscopy. Three of six gastric cancer patients had tumor cells present in the bone marrow of which 2 stained for CD87. Three of ten esophageal carcinoma patients had tumor cells in the bone marrow, all three samples stained for CD87. CD87-positive tumor cells were also dissected from stained bone marrow aspirates by laser microdissection microscope to allow analysis of single cells at the gene level.

We present a comprehensive study of the optimum operating regime in gain-switched Cr:forsterite lasers pumped at kilohertz repetition rates, comparing five crystals of similar quality but different dopant levels. The optimization of the cavity design includes selection of the proper pump fluence to account for excited-state absorption, optimum matching of the pump and laser modes, and consideration of thermal effects. As a result >1-W average output power is demonstrated at 2 kHz. The maximum conversion efficiencies achieved at 1 kHz are 24.2% (slope) and 20% (absolute). Narrow-band operation of this laser is possible with a birefringent filter, which is a prerequisite for efficient frequency doubling to cover the 585-660-nm part of the visible spectral range. Tunable second-harmonic generation in a temperature-tuned noncritical scheme that employs LiB(3)O(5) produces 60 mW of average power near 619 nm with 13.5% conversion efficiency.

We describe an oscillator-amplifier laser system for the generation of high-power femtosecond pulses near 1.25 microm based on chromium-doped forsterite. Chirped-pulse amplification at a 1-kHz repetition rate raises the pulse energy to >350 microJ. The nearly transform-limited 200-microJ, 135-fs-long recompressed pulses have a peak power of approximately 1.5 GW.

A mid-infrared femtosecond optical parametric amplifier tunable in the chemically important spectral region between 3.1 and 3.9 mum (at >10-muJ idler pulse energy) has been constructed on the basis of MgO:LiNbO(3) with 7% doping. With femtosecond pumping near 800 nm (Ti:sapphire regenerative amplifier) and narrow-band (long-pulse) seeding, this simple single-stage device provides maximum conversion efficiencies of 40% and exhibits extremely low seed threshold (<10-mW peak seed power for >1-muJ idler output). The generated idler pulses are almost transform limited with <200-fs pulse duration. The pulse-to-pulse fluctuations reproduce the stability of the pump source at 1-kHz repetition rate.

Femtosecond optical parametric amplification that results in microjoule mid-infrared pulses at wavelengths exceeding 3 mum is demonstrated. Narrow-band quasi-cw seeding at the signal wavelength is applied to ensure the generation of nearly transform-limited femtosecond pulses at the idler wavelength. The broad bandwidth of the parametric amplification provided by pumping with femtosecond pulses from a Ti:sapphire regenerative amplifier at high intensity results in idler pulse durations shorter than the pump pulse length. The potentials of three nonlinear optical crystals that belong to the potassium titanyl phosphate family are comparatively studied. At 1-kHz repetition rate our all-solid-state system produces highly synchronized ~100-fs pulses in the spectral range between 3 and 4 mum.

Since 1982 a total number of 1062 patients underwent surgical treatment of bronchogenic carcinoma. There were 972 men and 89 women, with a mean age of 62.5 years. In 484 cases a squamous cell carcinoma was diagnosed and in 416 patients an adenocarcinoma. An alveolar cell carcinoma was found in 54 and a polymorphocellular carcinoma in 68 patients respectively. 334 patients were found to be in stage I, 233 in stage II and 438 patients were in stage IIIa. The 5-year survival rate was 57.2% in stage I and 32.5% in stage II. The group of patients with N2 lymph node metastasis according stage IIIa showed a very poor 5-year-survival rate of 12.3%. A standard therapeutical procedure according to a multimodal concept is necessary to improve these patients' long-term survival. Systemic lymphadenectomy is essential for adequate therapy.

The second harmonic of a femtosecond Ti:sapphire regenerative amplifier system is used to pump parametric generator-amplifier producing visible light pulses of 160-fs duration near 570 nm and infrared pulses of < 100-fs duration between 1.23 and 1.45 µm.

The authors report about their first experiences concerning the treatment of gallbladder stones using a laparoscopic approach. 40 patients (33 female, 7 male) were treated with this new method. The age of the patients, who had undergone this procedure, varied from 24 to 76 years, the average age was 42 years. Our current indication is the symptomatical chronic gallbladder lithiasis. The average time of operation was 60 to 90 minutes. The mortality rate was zero. Slight operative bleeding from an accessory artery and vein occurred in two cases. This was controlled by electrocoagulation. We observed no complications in the postoperative phase. The patients were dismissed from the hospital on the 3. to 5. day. This method is very favourable with regard to the operative strain on the patients.

An allogenic transplantation of the total-pancreas with duodenum was carried out in the minipig model. The oral duodenum was closed blindly and the aboral part was led out as a stoma. The portal vein of the transplant was anastomosed end-to-side in the inferior vena cava and the celiac artery of the transplant in the distal aorta. Investigations for early diagnosis of rejection were carried out in this model parallelly respectively one by one. CT/MRT, selective angiography, laboratory chemical parameters were unsuitable for early detection. The pancreatic succus cytology and nuclear medical investigations show reproducible changes caused by rejection before the blood-sugar level was increased.

In order to show that for a possible application in medical diagnosis NMR-relaxation experiments at low Larmor frequencies (v0 less than or equal to 20 kHz) are more sensitive than the up to now done high field measurements in the MHz-range, we present dispersion curves (v0 = 50 Hz to 50 MHz) of the proton longitudinal relaxation time T1 and values of the transversal relaxation time T2 for the example of amniotic fluids. Only for Larmor frequencies below congruent to 100 kHz the relaxation times for healthy amniotic fluid and pathological meconium solutions are significantly different, whereas at high Larmor frequencies, i.e. in the conventional MHz-range, the observed changes are rather small.

Airtight protective clothing covering the skin of the human body, such as for example rubber gloves or rubber shoes, lead to heat accumulation and through transpiration to changes of the skin. Cutaneous diseases are encouraged by this. The herein presented aeration system functioning through air channels supplied by exterior lines, is improving the unhealthy skin conditions and is making it more agreeable to wear protective clothing.

The influence of pretransplant donor spleen cell infusions on murine skin graft survival was studied. In dependence on the time interval between transplantation and transfusion an accelerated or delayed rejection of the grafts was observed. If the donor spleen cells were treated with the photosensitizer 8-methoxypsoralen and UVA light (PUVA) a graft prolongation was achieved at all time intervals. Furthermore, the survival of antigenically unrelated grafts was also prolonged. An additional immunosuppressive treatment or the recipients with antilymphocyte serum, but not cyclophosphamide, led to a further prolongation of graft survival. The survival of PUVA treated skin grafts was not longer in recipients preinfused with PUVA treated donor cells compared with untreated hosts. The results presented in this work may have implications in clinical organ transplantation to prevent sensitizing reactions by sparing protective mechanisms for the graft.

Dispersion curves of the longitudinal relaxation T1 of protons in healthy amniotic fluid in a meconium solution are distinct at low Larmor frequencies (V0 less than 100 kHz). We are thus able to distinguish these fluids by T1 measurements in this range.

Treatment of human peripheral blood mononuclear cells with UVB light, the photosensitizing system 8-methoxypsoralen plus UVA light (PUVA), or hematoporphyrin derivative plus visible light leads to an inhibition of their stimulatory capacity in an allogeneic mixed leukocyte reaction despite unaltered expression of HLA-DR antigens when tested immediately after irradiation. However, HLA-DR positive cells disappear among mononuclear cells in the interval between 4 and 8 h after treatment with either UVB, PUVA, hematoporphyrin derivative and light, or heating to 45 degrees C. The expression of HLA-DQ, but not HLA-A,B,C, antigens, was similarly affected by these treatments. The significance of these results is discussed.