Search for clastogenic factors in the plasma of locally irradiated individuals.

In studies reported in the 1960s and in several investigations since, plasma from irradiated individuals was shown to induce chromosomal aberrations when transferred into normal blood cultures. In the present study, the aim was to investigate the occurrence of these clastogenic factors (CF) using markers representing DNA damage produced in reporter lymphocytes that are treated with plasma from locally exposed individuals. Blood plasma was obtained from clinical patients with benign conditions before and after they had received radiation to small treatment volumes. Three patient groups were studied: (I) marginal resected basal cell carcinoma, (II) painful osteoarthritis of the knee, and (III) painful tendinitis of the elbow or the heel. Patients in each treatment group obtained the same fractionated treatment regimen, ranging from a total dose of 40 Gy (8 × 5 Gy, 2 factions/week) to a very small volume (1-3.5 cm³) in group I to a total dose of 6 Gy (6 × 1 Gy, 2 fractions/week) for groups II and III (treatment volumes 800-1150 cm³ and 80-160 cm³, respectively). The presence of CF in the plasma was investigated through cytogenetic (chromosomal aberrations, micronuclei) assays and kinetics of early DNA damage (γ-H2AX foci) in reporter cells. With the experimental settings applied, local radiation exposure had no apparent effect on the induction of CF in patient plasma; no deviations in chromosomal aberrations or micronucleus or focus induction were observed in reporter cells treated with postexposure plasma with respect to pre-exposure samples when the mean values of the groups were compared. However, there was a large interindividual variation in the plasma-induced DNA-damaging effects. Steroid treatment of patients was demonstrated to be the most influential factor affecting the occurrence of plasma factors; plasma from patients treated with steroids led to significant reductions of γ-H2AX foci and reduced numbers of chromatid aberrations in reporter cells. In addition to the locally exposed patients, newly obtained plasma samples from three radiological accident victims exposed in 1994 were examined. In contrast to the patient data, a significant increase in chromosomal aberrations was induced with plasma from two accident victims.

Low-dose radiotherapy (LD-RT) and the modulation of iNOS expression in adjuvant-induced arthritis in rats.

PURPOSE: Low-dose radiotherapy (LD-RT) of arthritic joints applied during the peak of the acute inflammatory response improves the clinical and histomorphological development of adjuvant arthritis. The study was undertaken to investigate the cellular composition of the inflammatory infiltrate and the expression of the pro-inflammatory and anti-inflammatory enzymes, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX-2) and haem-oxygenase 1 (HO-1), in response to LD-RT. MATERIALS AND METHODS: Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat-inactivated mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham irradiated (group 1) or X-irradiated with either 5 x 1.0 Gy (group 2) or 5 x 0.5 Gy (group 3) from days 15 to 19 after induction (15 animals/group). On days 21 (n=12 joints/group) and 30 (n=18 joints/group), cryostat sections were analysed histologically and immunohistologically after specific staining for macrophages, iNOS, COX-2 and HO-1. RESULTS: A total of 5 x 1.0 Gy or 5 x 0.5 Gy led to a significant reduction of clinical symptoms from days 21 to 29, and a highly significant reduction of cartilage and bone destruction on day 30. Macrophage-positive areas could be detected continuously throughout the periarticular infiltrate, and were slightly reduced after LD-RT on days 21 and 30. This reduction was more pronounced after 5 x 1.0 Gy. Following LD-RT, the iNOS score was reduced by about 45-50% on days 21 (p<0.05) and 30 (p<0.001). In contrast, the HO-1 score was increased by about 50% on days 21 (p=0.08) and 30 (p=0.03). CONCLUSIONS: The clinically and histologically observed prevention of the progression of adjuvant arthritis after LD-RT given during the peak of the acute inflammatory response and the reduction of cartilage and bone destruction in the chronic phase appears to be related to the modulation of iNOS activity by low X-ray doses.

Practical realization of massively parallel fiber-free-space optical interconnects.

We propose a novel approach to realizing massively parallel optical interconnects based on commercially available multifiber ribbons with MT-type connectors and custom-designed planar-integrated free-space components. It combines the advantages of fiber optics, that is, a long range and convenient and flexible installation, with those of (planar-integrated) free-space optics, that is, a wide range of implementable functions and a high potential for integration and parallelization. For the interface between fibers and free-space optical systems a low-cost practical solution is presented. It consists of using a metal connector plate that was manufactured on a computer-controlled milling machine. Channel densities are of the order of 100/mm(2) between optoelectronic VLSI chips and the free-space optical systems and 1/mm(2) between the free-space optical systems and MT-type fiber connectors. Experiments in combination with specially designed planar-integrated test systems prove that multiple one-to-one and one-to-many interconnects can be established with not more than 10% uniformity error.

Effects of low dose radiation therapy on adjuvant induced arthritis in rats.

PURPOSE: Substantial clinical evidence shows the efficacy of low dose radiotherapy (RT) in the treatment of painful osteoarthritis. Experimental investigations into these empirically clinical observations remain scarce. This study investigated in vivo the effects of daily 5 x 1.0 Gy versus 5 x 0.5 Gy on adjuvant induced arthritis in rats in order to explore whether there is a dose dependence of anti-inflammatory efficacy. MATERIALS AND METHODS: Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat inactivated Mycobacterium tuberculosis on day 0. Both hind paws were X-irradiated daily from days 15 to 19 after induction according to four protocols (15 animals/group): group 1, 5 x 1.0 Gy (non-arthritic animals); group 2, sham-irradiated control; group 3, 5 x 1.0 Gy; group 4, 5 x 0.5 Gy. The clinical parameters arthritis score (AS), hind paw volume (HPV), body weight, and erythrocyte sedimentation rate (ESR) were determined. On days 21 and 30 histological sections of at least 12 ankle joints per group were analysed semi-quantitatively. RESULTS: Local irradiation of non-arthritic rats (group 1) with 5 x 1 Gy did not induce any arthritic signs. Sham-irradiated arthritic rats (group 2) showed a full-blown arthritic syndrome. Treatment of arthritic rats with 5 x 1 Gy (group 3) or 5 x 0.5 Gy (group 4) led to a reduction of mean AS from day 21 to 29 compared with group 2 (days 27-29--group 3: p=0.037; group 4: p=0.034), with no differences in efficacy between groups 3 and 4. Concurrently, following radiation treatment there was no further increase in HPV. At the end of the observation period, this effect demonstrated a dose-dependent level of significance (days 27-29--group 3: p=0.0036; group 4: p=0.039). A significant decrease in the ESR was noted in both irradiated arthritic groups on day 21 (group 3: p=0.015; group 4: p=0.006). The histopathological analysis revealed a highly significant reduction of cartilage and bone destruction on day 30 in both irradiated groups. CONCLUSIONS: This study confirms by objective criteria the anti-inflammatory efficacy of low dose RT and gives some indication for a dose dependence of its efficacy.

Iterative optimization of phase-only diffractive optical elements based on a lenslet array.

We describe the design of Fourier-type phase-only array generators. The numerical optimization employs the Fienup algorithm, where the parageometric design of the phase retardation profile, with the form of a lenslet array, is used as the initial guess of the optimization process. This approach provides designs with high performance that can be obtained with comparatively low computing effort. This is particularly true for elements generating large spot arrays. For symmetric reconstruction fields, the optimized phase profile typically has the same symmetry as that for the reconstruction field and can be easily unwrapped.

Compact planar-integrated optical correlator for spatially incoherent signals.

A new, to our knowledge, approach for the planar integration of optical correlators is demonstrated. A VanderLugt-type architecture was used to allow the processing of the spatially incoherent signals of active optoelectronic smart-pixel-device arrays. In a folded optical system all passive components were implemented as a single multiple-phase-level element. The relations among the spatial resolution, the light efficiency, and the system design parameters are derived. High signal quality and low noise levels were achieved experimentally.

Planar-integrated optical vector-matrix multiplier.

We present the design of a planar-integrated optoelectronic vector-matrix multiplier. The inherent parallel-processing potential is fully exploited by optical implementation of multiplications and summations. Planar integration makes the free-space optical system compatible with electronic VLSI technologies. It is composed of phase-only diffractive optical elements, which implement lens and multiple-beam-splitter functions. A demonstrator version of the optical system for a matrix of size 10 x 10 was fabricated on quartz glass by means of multimask lithography and reactive ion etching. It shows low cross talk and good uniformity of the signals.

Fabrication of microprisms for planar optical interconnections by use of analog gray-scale lithography with high-energy-beam-sensitive glass.

For an integrated free-space optical interconnection system we suggest the use of microprisms to achieve large coupling angles at low loss. Prisms were fabricated in photoresist and quartz glass by analog lithography. High-energy-beam-sensitive glass was used as the gray-tone mask. Optical testing of the prisms shows acceptable surface quality and high efficiency (95%).

Planar-integrated talbot array illuminators.

We demonstrate the planar integration of Talbot array illuminators designed to generate one-dimensional spot arrays. The array illuminator basically consists of a phase grating and a cylindrical diffractive lens integrated as a single diffractive optical element onto a transparent glass substrate. We discuss various design aspects, and we focus on problems typical for planar-integrated free-space optics like the tilted optical axis of the system. Experimental results and measurements, which were obtained from planar-integrated setups fabricated as surface-relief structures on a transparent glass substrate by use of standard photolithography, are included.

Diffractive optics and micro-optics: introduction to the feature issue.

This issue of Applied Optics features 19 articles related to the fabrication and the design of diffractive and micro-optics as well as their applications. A companion feature in the Journal of the Optical Society of America A includes papers on the modeling of diffractive elements.

Integrated micro-optical imaging system with a high interconnection capacity fabricated in planar optics.

An integrated free-space optical interconnection system with 2500 parallel data channels is demonstrated. The design is based on a combination of microchannel imaging and conventional imaging. A modification of the hybrid imaging configuration allows one to achieve optimized image quality over large image fields.

[Regression of Yoshida sarcoma during normoxia and hypoxia after fractionated irradiation]. / Regression des Yoshida-Sarkoms unter Normoxie und Hypoxie nach fraktionierter Bestrahlung.

PURPOSE: Tumor regression is one of the most important factors determinating the tumor control probability after radiotherapy. The changes in the regression of tumors during fractionated radiotherapy and the application of different radioprotectors or radiosensitizers make render to assess their effectivity. MATERIAL AND METHOD: The effect of hypoxic breathing (8.1% O2) on the tumor regression of Yoshida sarcoma was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. RESULTS: No significant changes in the tumor regression after radiotherapy in any group in any time independent from respiratoric hypoxia were recorded. The tumor regression rate was significantly influenced by treatment schedule (p < 0.0005). CONCLUSIONS: Our results support the hypothesis of hypoxy-radiotherapy: The acute hypoxic hypoxia, caused due the breathing of hypoxic gas mixture with 8 to 10% oxygen, did not influence the radiation induced tumor regression in animal experiment. For this criterium no protection can be shown. The influence of hypoxy-radiotherapy on the local tumor control is necessary to evaluate in further experiments.

[Reoxygenation in Yoshida sarcoma during different fractionated radiotherapy]. / Reoxygenierung im Yoshida-Sarkom unter unterschiedlich fraktionierter Bestrahlung.

PURPOSE: Tumor reoxygenation is one of the most important factors determining the tumor control probability after radiotherapy. In experimental studies reoxygenation has been measured preferably after single dose irradiation. Only few data exist about changes in the hypoxic tumor fraction during fractionated radiotherapy. MATERIAL AND METHODS: The changes in the pO2 during fractionated radiotherapy were studied in Yoshida sarcoma transplanted to Wistar rats. Tissue oxygenation was assessed using a polarographic electrode system at the beginning, in the middle and at the end of radiation therapy. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. RESULTS: In the statistical analysis significant changes emerged in the mean, median, 10%-percentile and 0 to 2.5 mm Hg and 0 to 5.0 mm Hg values dependent on time. The tumors were significantly more hypoxic at the end of therapy. This trend became more pronounced with decreasing dose per fraction. CONCLUSIONS: The Yoshida sarcoma has no effective reoxygenation during fractionated radiotherapy.

[Hypoxyradiotherapy: changes in the oxygen partial pressure distribution in the tumor and in the healthy tissue under acute respiratory hypoxia]. / Hypoxie-Radiotherapie: Veränderungen in der Sauerstoffpartialdruckverteilung im Tumor und im gesunden Gewebe unter akuter respiratorischer Hypoxie.

PURPOSE: Based on the oxygen effect a new therapeutic modality has been developed to protect healthy tissues while breathing hypoxic gas mixture during irradiation. MATERIAL AND METHODS: The effect of breathing hypoxic gas mixture (8.1% O2) on pO2 in Yoshida sarcoma and muscle was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. Tissue oxygenation was assessed with a polarographic electrode system. RESULTS: The median pO2 in Yoshida sarcoma was 10 mm Hg. 21% of pO2-values were lower than 5 mm Hg. During breathing of hypoxic gas mixture no significant changes in median tumor pO2 or radiobiologic hypoxic values (< or = 5 mm Hg) were recorded. The median pO2 in muscle was 30 mm Hg. During breathing of gas hypoxic mixture a significant decrease of the median to the value 12 mm Hg and an increase of the radiobiologic hypoxic values (p < 0.00001) were observed. The changes of pO2-values were constant independent from fractionation. CONCLUSIONS: Between tumor and healthy tissue exists a significant difference regarding changes in the radiobiologic fraction during breathing of hypoxic gas mixture. This fact explains the experimental and clinical experience, that the breathing hypoxic gas mixture protects the healthy tissue without changes in the radiosensibility of chronic hypoxic tumor tissue.

Packaging considerations for planar optical interconnection systems.

We discuss various aspects of building an integrated optoelectronic system that is based on the concept of planar optics. A particular optical interconnection system has been fabricated and demonstrated. It provides parallel interconnections with 1024 optical channels that could be useful as an optical backplane in an optoelectronic multichip module. We consider the design and the fabrication of the optical system, schemes for the hybrid integration with optoelectronic device arrays, and the thermal management of an integrated system. The proposed hybrid integration scheme is based on mature technologies such as thermal anodic bonding and flip-chip bonding. Possibilities for efficient heat sinking are described.

Design and fabrication of high-efficiency beam splitters and beam deflectors for integrated planar micro-optic systems.

High-frequency gratings with rectangular-groove profiles are used to generate high-efficiency beam splitters and beam deflectors. The effects of the grating design parameters, i.e., period, groove depth, duty cycle, number of phase levels, and polarization state (TE and TM) of the incoming signal, are considered. The case of the binary beam splitter grating is analyzed by using rigorous electromagnetic grating analysis. Fabrication techniques are presented in which three different lithographic techniques are considered (optical contact, deep-UV stepper reduction, and electron-beam direct write). Experimental results of 97% efficiency for the beam splitter grating and up to 80% for the beam deflector grating are reported.

Precise alignment through thick wafers using an optical copying techniquev.

Submicrometer alignment of two mask patterns on the top and the bottom surface of a thick glass substrate is possible by using optical copying. The optical copying step transfers an alignment pattern from one surface to the other by shadow casting or Fresnel propagation. In a demonstration experiment, the alignment between the two surfaces of a 3-mm-thick quartz glass substrate was achieved with a precision of 0.5-0.7 microm.

Optical interconnects using top-surface-emitting microlasers and planar optics.

Optical interconnections made using two-dimensional arrays of top-surface-emitting microlasers and integrated free-space optics are discussed for use in chip-to-chip communications. A demonstration setup with a 2 x 2 array of lasers is presented. System parameters, such as light efficiency, the number of data channels, thermal effects, power requirements, and the issue of hybrid integration of laser chips with passive optics, are considered.

Array generation with lenslet arrays.

Lenslet arrays can be used as phase gratings, having many diffraction orders with equal intensity. Applications are multiple imaging and illumination of arrays of optical or optoelectronic devices in digital optics. The homogeneity of the intensities within the array can be improved by using field lenslets. The basic theory as well as experiments with diffractive and with graded index lenses are shown.