Comparison of the saccules and lagenae in six macrourid fishes from different deep-sea habitatsa).

There are substantial interspecific differences in the morphology of the ears of the more than 34 000 living fish species. However, almost nothing is known about the functional significance of these differences. One reason is that most comparative studies have been conducted on shallow-water species with far less focus on the numerous species that inhabit the depths of the oceans. Thus, to get a better sense of ear diversity in fishes and its potential role in hearing, this study focuses on the saccule and lagena, the primary auditory end organs, in six species of the family Macrouridae (rattails), a large group of fishes that typically inhabit depths from 1000 to 4000 m. The inner ears and, particularly, the saccules and lagenae in these species are large with the saccule resembling that of other Gadiformes. The lagenae of all macrourids studied here have serrated edge otoliths and highly diverse hair cell ciliary bundle shapes. The differences found in the inner ear anatomy of macrourids likely reflect the sensory advantages in different habitats that are related to the benefits and constraints at different depths, the fish's particular lifestyle, and the trade-off among different sensory systems.

Seroepidemiological analysis and literature review of the prevalence of Epstein-Barr virus and herpesvirus infections in pediatric cases with non-Hodgkin lymphoma in Central Europe.

BACKGROUND: Epstein-Barr virus (EBV) is linked to a variety of malignancies; most endemic Burkitt lymphoma (BL) harbor EBV, whereas only a subset of the cases of sporadic BL is EBV positive. PROCEDURE: We retrospectively determined the herpesvirus seroprevalence at the time of diagnosis in pediatric non-Hodgkin lymphoma (NHL) patients enrolled in NHL-BFM (Berlin-Frankfurt-Muenster) studies. We accessed the seroepidemiological data from 1147 patients that became available during 1990-2007. We included the records from patients 6 months to 18 years of age with BL, T-cell lymphoblastic lymphoma (T-LBL), lymphoblastic precursor B-cell lymphoma (pB-LBL), diffuse large B-cell lymphoma (DLBCL), or anaplastic large cell lymphoma (ALCL). RESULTS: EBV seropositivity was significantly more frequent in patients with BL than in those with T-LBL. EBV was more prevalent in patients younger than 6 years of age and in patients with BL than in those with non-BL or T-LBL. Event-free survival was significantly lower in varicella-zoster-seronegative patients, but there was no indication of an association to complications due to varicella zoster infection. We found no associations between herpes simplex virus, varicella zoster virus, or human cytomegalovirus seroprevalence and the pediatric Central European NHL cases. CONCLUSION: Early EBV exposure may increase the risk of BL in Central Europe. A higher involvement of EBV in European BL than originally reported appears at least probable. Our data support the thesis that the distinction between endemic and sporadic BL is artificial and should be replaced by the differentiation between EBV-positive and EBV-negative BL.

Light sensitivity in a vertebrate mechanoreceptor?

Using immunohistochemistry and western blot analysis, we demonstrate that melanopsin is localised in cells around the central pore of lateral line neuromasts in the African clawed frog, Xenopus laevis. Since melanopsin is a known photoreceptor pigment with diverse functions in vertebrates, we suggest that the lateral line of Xenopus laevis, which is primarily a mechanoreceptor, might also be light sensitive. Potential functions of such photosensitivity are discussed, including its role in mediating locomotor responses following dermal illumination.

Distribution of axon diameters in cortical white matter: an electron-microscopic study on three human brains and a macaque.

The aim of this study was to obtain information on the axonal diameters of cortico-cortical fibres in the human brain, connecting distant regions of the same hemisphere via the white matter. Samples for electron microscopy were taken from the region of the superior longitudinal fascicle and from the transitional white matter between temporal and frontal lobe where the uncinate and inferior occipitofrontal fascicle merge. We measured the inner diameter of cross sections of myelinated axons. For comparison with data from the literature on the human corpus callosum, we also took samples from that region. For comparison with well-fixed material, we also included samples from corresponding regions of a monkey brain (Macaca mulatta). Fibre diameters in human brains ranged from 0.16 to 9 µm. Distributions of diameters were similar in the three systems of cortico-cortical fibres investigated, both in humans and the monkey, with most of the average values below 1 µm diameter and a small population of much thicker fibres. Within individual human brains, the averages were larger in the superior longitudinal fascicle than in the transitional zone between temporal and frontal lobe. An asymmetry between left and right could be found in one of the human brains, as well as in the monkey brain. A correlation was also found between the thickness of the myelin sheath and the inner axon diameter for axons whose calibre was greater than about 0.6 µm. The results are compared to white matter data in other mammals and are discussed with respect to conduction velocity, brain size, cognition, as well as diffusion weighted imaging studies.

Generation of pluripotent stem cells from adult human testis.

Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

Epicardial halo phenomenon: a guide for pericardiocentesis?

The epicardial halo delineates the heart shadow in fluoroscopy. To establish whether the sign is applicable to pericardiocentesis guidance, three investigators evaluated its intensity as absent = grade 0, indistinct = 0.5, clear = 1, intensive = 2 in posterior-anterior (PA) and lateral fluoroscopies recorded before pericardiocentesis or cardiac catheterization (Philips Integris-II BH3000). Three populations were studied: (a) 32 patients with pericardial effusion (PE group), 53.1 % males, aged 53.9 ± 13.9 years; (b) 14 patients with perimyocarditis (PM group), 64.3 % males, aged 51.6 ± 14.4 years; and (c) 46 coronary patients (CAD group), no PE, 95.6 % males, aged 67.3 ± 11.8 years. The intensity of the halo phenomenon was highest in patients with PE, lowest in patients with CAD, and intermediate in patients with PM (median sum of grades in PA/lateral view: 4/5 vs. 2/2.5 vs. 3/3, respectively) (p < 0.01). The halo phenomenon correlated well with HR and echocardiographic PE size in both angiographic views. The correlation with body mass index (BMI) and age was significant only in the lateral view and with PE volume only in the PA view. The sensitivity of the halo sign for PE was 84.1 % in PA and 92.0 % in lateral views. In 10/32 PE patients, the evaluation of the sign was repeated after PE drainage, revealing lower grades both in PA and in lateral views (p < 0.01). In conclusion, the epicardial halo sign is highly sensitive for the detection of a PE; it correlates well in at least one angiographic projection with the PE volume, HR, age, BMI, and the PE size in echocardiography and could be therefore applied as a safety guide for pericardiocentesis.

[Chronic type B aortic dissection-what to do?] / Chronische Aortendissektion Typ B ­ was tun?

BACKGROUND: Chronic type B aortic dissection requires optimal medical therapy. However, secondary complications like organ or extremity malperfusion or development of aneurysmal dilatation require interventional therapy. OBJECTIVES: Presentation of different endovascular treatment options for complications of chronic type B aortic dissection. MATERIALS AND METHODS: Analysis of current literature with regard to indications, techniques, results, and differential indications of interventional techniques for the treatment of chronic type B aortic dissection complications. RESULTS: Endovascular implantation of an aortic stent graft is interventional standard therapy for treatment of aneurysmal dilatation of the aorta following type B dissection. Technical problems are the proximal and distal landing zones and the treatment of persistent flow in the false lumen. CONCLUSION: Endovascular treatment of chronic complicated type B aortic dissection is increasingly used compared to open surgical treatment because not only are more complex stent grafts (fenestrated and branched devices) available but also because of newly developed techniques for effective occlusion of flow in the false lumen (e.g., candy plug).

Percheron-like artery infarction after transsphenoidal surgery: illustrative case.

BACKGROUND: The transsphenoidal approach to the skull base has enjoyed increasing popularity for surgery of the sellar region avoiding brain retraction and causing few severe complications. While vitally important vessels in this region show a high degree of variability, some anatomical variants might be involved in characteristic complications. OBSERVATIONS: We present the case of a 40-year-old female patient with acromegaly due to a pituitary adenoma that was transsphenoidally operated. Postoperatively, the patient presented with bilateral unresponsive mydriasis, loss of consciousness and tetraparesis. An MRI showed well-circumscribed bilateral paramedian thalamic infarctions which indicated a rare Percheron-like artery. At 2-year follow-up examination the patient was dramatically improved but with a profound impact on her ability to interact with the world. LESSONS: The basilar artery or perforators might be injured during dissection of suprasellar lesions. This vascular territory is essential to interaction of the brain with the outside world. We conclude that we will approach future suprasellar adenomas strictly intracapsularly.

The Inner Ear and its Coupling to the Swim Bladder in the Deep-Sea Fish Antimora rostrata (Teleostei: Moridae).

The inner ear structure of Antimora rostrata and its coupling to the swim bladder were analyzed and compared with the inner ears of several shallow-water species that also have similar coupling. The inner ear of Antimora has a long saccular otolith and sensory epithelium as compared to many other fishes. Some parts of the membranous labyrinth are thick and rigid, while other parts are thinner but attached tightly to the bony capsule. The partially rigid membranous labyrinth, along with its intimate connection to the swim bladder, may help the inner ear follow the sound oscillations from the swim bladder with better precision than would occur in a less rigid inner ear. In addition, the saccular sensory epithelium has an elaborate structure and an anterior enlargement that may be correlated with increased hearing sensitivity. Some of the features in the inner ear of Antimora may reflect the functional specialization of deep-water living and support the hypothesis that there is enhanced inner ear sensitivity in some deep-sea fishes.

Examining the origin of posttransplant lymphoproliferative disorder in a patient after a second allogeneic hematopoeitic stem cell transplantation for relapsed BCR-ABL positive acute lymphoblastic leukemia.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication because of the reactivation of the Epstein-Barr virus (EBV). Although after solid organ transplantation (SOT) EBV is typically of recipient origin, after hematopoietic stem cell transplantation (HSCT) donor-derived B cells are usually the source of the EBV-induced lymphoproliferation. OBSERVATION: We report a unique presentation of an EBV-associated PTLD in a 13-year-old boy who underwent 2 subsequent HSCTs from 2 different-sex donors for BCR-ABL-positive acute lymphoblastic leukemia (ALL) and relapses of leukemia, respectively. The PTLD tissue was analyzed for the origin of both B cells and T cells of the lesion. Chimerism analysis done with short tandem repeat systems (STR) showed no autologous signals; approximately 50% of the cells were from the first and second donors, respectively. XY-fluorescence in situ hybridization showed a B-cell PTLD originating from the first donor surrounded by T cells from the second donor. CONCLUSION: This case shows that EBV-infected B cells from a first donor can be the source of a PTLD after a second myeloablative HSCT from a different donor.

Ovarian tumor in a 12-year old female with severe hypothyroidism: A case of Van Wyk and Grumbach syndrome.

We report a 12-year-old female presenting with an abdominal tumor. Diagnostic workup revealed giant bilateral ovarian cysts, severe hypothyroidism as well as an elevation of CA 125. We refrained from ovariectomy, which would be necessary for a malignant tumor, in view of an evident Van Wyk and Grumbach syndrome. The patient promptly responded to L-thyroxine with complete regression of all symptoms. Hypothyroidism should be considered in the evaluation of ovarian cysts. Although the Van Wyk and Grumbach syndrome is rare, it is crucial to rule it out in order to avoid unnecessary ovarian surgery when thyroid replacement is completely sufficient.

Infection of T lymphocytes in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children of non-Asian origin.

BACKGROUND: Epstein-Barr virus (EBV) is one of the most frequent triggers of hemophagocytic lymphohistiocytosis (HLH). EBV-associated HLH (EBV-HLH) and ectopic infection of T cells has been particularly described in patients from Far East Asia. PROCEDURE: In a cohort of 12 children with EBV-HLH treated in Germany, the EB viral load was detected by real-time polymerase chain reaction in plasma and peripheral blood mononuclear cells (PBMC). Virological and clinical data were analyzed retrospectively. RESULTS: Among the 12 mainly German patients, children with underlying immunodeficiencies as well as otherwise healthy individuals were affected. The clinical course ranged from a steroid-responding to a fatal disease despite intensive treatment. Increased EBV copy numbers in plasma and/or PBMC were found in all patients. Serial measurements reflected the course of the disease. Cell-type specific viral load was determined in seven patients and revealed EBV-infection of T cells in all of them. In contrast to the reported Asian patients a significant viral load was also found in B cells. CONCLUSIONS: T cell infection appears to be a typical feature of EBV-associated HLH irrespective of patients ethnic background and the clinical course. Evaluation of cell-type specific infection should be considered when targeted therapy is applied.

Selective internal radiotherapy with Yttrium-90 microspheres for hepatic metastatic neuroendocrine tumors: a prospective single center study.

BACKGROUND: To assess prospectively the safety and efficacy of Yttrium-90 microspheres in patients with unresectable liver metastases from neuroendocrine tumors. MATERIALS AND METHODS: Microspheres were administered via a temporarily placed hepatic catheter. Patients were monitored prospectively. All patients were followed with laboratory and imaging studies at regular intervals to determine response rates. Toxicity and quality of life scores were measured. RESULTS: Nine patients (7 female) with a mean age of 58.8 years were enrolled in this prospective trial. The mean tumor load was 58.8%. The estimated percentage shunting to the lungs on MAA scans was 5.04 +/- 2.4%. Visceral artery embolization of extrahepatic arteries before treatment was performed in 6 patients. The median dose of microspheres was 2.1 +/- 0.4 GBq. A total of 12 therapy sessions was performed. The mean follow-up was 21.7 months. Technical success was 100%. No major complications occurred. Survival rates were 100, 57 and 57% for 1, 2 and 3 years, respectively. Three months after SIRT therapy partial response (PR) was seen in 6 patients (66%). Calculated reduction of liver metastasis volume was 49%. In 3 patients (33%) stable disease was seen with a calculated tumor reduction of 13%. The estimated time to progression was 11.1 months. CONCLUSION: Radioembolization with (90)Y microspheres is safe and produces high response rates even with extensive tumor replacement for up to 1 year. Acute and late toxicity was very low. Further investigations compared with other local ablative techniques is warranted.

DNA double-strand breaks after percutaneous transluminal angioplasty.

PURPOSE: To determine exemplarily the amount of DNA damage and the repair kinetics after interventional radiologic procedures by using visualization of foci of the phosphorylated form of the H2AX histone variant (gammaH2AX) to quantify DNA double-strand breaks (DSBs) at percutaneous transluminal angioplasty (PTA) of the lower limb arteries. MATERIALS AND METHODS: After local ethics committee approval and written informed consent were obtained, five patients (two women, three men; mean age, 64.4 years; age range, 45-76 years) scheduled for computed tomography (CT) and 20 patients (six women, 14 men; mean age, 68.5 years; age range, 53-85 years) scheduled for PTA of lower limb arteries were prospectively entered into the study. Blood samples were taken before the first exposure to ionizing radiation and 5 minutes, 1 hour, 6 hours, and 24 hours after the last exposure. Additional samples were taken from the irradiated limb (femoral vein) of three patients who underwent PTA--before the first radiation exposure, 5 and 10 minutes after the first exposure, and 5 minutes after the last exposure. Lymphocytes were isolated, fixed, and stained with anti-gammaH2AX antibody, and gammaH2AX focus yields were determined with fluorescence microscopy. Data were analyzed with linear regression and two-sample F tests. RESULTS: Mean increase in number of gammaH2AX foci after CT (7.78 per 1 Gy x cm) depended linearly on dose-length product (r = 0.997). Number of foci reached background levels within 24 hours. Mean numbers of gammaH2AX foci per cell increased by factors of 4.08-20.67 in blood samples taken 5 minutes after PTA compared with mean numbers of foci before PTA. Mean radiation dose increase, 6.56/(10 Gy x cm(2)), depended linearly on dose-area product (r = 0.993). Maximal focus yield in cells taken directly from the irradiated limb was higher than that in cells from the systemic circulation (by mean factor of 1.46). Data showed compromised DSB repair capacity after PTA (P < .05). Mean number of foci at 24 hours (0.07 focus per cell) was significantly higher than mean number of foci in cell background (0.04 focus per cell, P < .05). CONCLUSION: GammaH2AX focus formation can be used to determine in vivo induction of DNA DSBs after PTA. DSB repair capacity is compromised in patients who undergo PTA of lower limb arteries.

Dim light vision--morphological and functional adaptations of the eye of the mormyrid fish, Gnathonemus petersii.

The African weakly electric fish Gnathonemus petersii is well known for its electrosensory capabilities. These animals can detect and distinguish objects through active electrolocation in complete darkness. Because of their nocturnal lifestyle, a low contribution of vision for orientation and object detection has been expected. However, as we show in this review, the retina of G. petersii is highly specialized with hundreds of rods and tens of cones grouped together in bundles in a complex way, ensheathed by a tapetum lucidum. The structure of the bundles goes beyond what would be expected if only photon catch was supposed to be increased. During daytime, the structure of these "macro-receptors" changes dramatically depending on retinomotor movements. During the day, the rods and cones are located in different compartments of the bundle, separated by a narrow canal in the form of a "bottle neck". Investigations on cell structure and neurochemistry in the retina indicate a general organization that is simpler in terms of bipolar and ganglion cell diversity than in tetrachromatic species such as goldfish, yet similar in terms of neurochemical differentiation of amacrine cells. In both respects, the inner retina of the elephantnose fish bears the greatest similarity to catfish and some deep-sea fish retinae. Neuronal circuits and bundle structure give hints of possible adaptations for contrast and/or movement detection. Behavioral experiments suggest that, in contrast to the vision specialists Lepomis gibbosus, pattern detection of G. petersii is not affected by higher spatial frequencies. A pattern of low spatial frequencies, however, was equally well detected by G. petersii and L. gibbosus. Optomotor response experiments indicate that motion vision is important for Gnathonemus, narrowing down the search for the functional specialization of the Gnathonemus retina and providing a starting point for work on multisensory integration in these fish.

Prospective evaluation of the diagnostic accuracy of secretin-enhanced magnetic resonance cholangiopancreaticography in suspected chronic pancreatitis.

The purpose of this study was to determine the improvement in sensitivity and specificity of magnetic resonance cholangiopancreaticography (MRCP) in the diagnosis of chronic pancreatitis due to the application of secretin. Sixty-two consecutive patients with suspected chronic pancreatitis were prospectively included in our study. All investigations were carried out in a clinical 1.0-T MR-scanner using heavily T2-weighted pre- and dynamic post secretin measurements. Dynamic images were acquired every 30 s for a total imaging time of 10 min. Two experienced radiologists blinded for all other results evaluated the images in random order in two sessions: one for the native images and one for the stimulated MRCP series. The gold standard for the final diagnosis was the summary of all clinical and radiological results. Sensitivity and specificity for the diagnosis of chronic pancreatitis and the kappa coefficient for the agreement between both observers were calculated. Prior to secretin application, investigators achieved sensitivities of 78% and 56%, respectively, and specificities of 89% and 96%, respectively. After secretin application, the sensitivity for the first observer remained at 78%; for the second observer it increased to 67%, whereas specificities improved to 94% and 98%, respectively. Following secretin application, agreement determined between the two investigators improved from 0.73 to 0.84. While MRCP already provides high sensitivity and specificity, application of secretin increases both values and the reliability of the diagnosis further.

Retinotectal ganglion cells in the zebrafish, Danio rerio.

The morphology of retinotectal ganglion cells was investigated by retrograde transport of dextran amines applied into the optic tectum in vitro. Based on criteria such as stratification pattern and size of the dendritic processes, as well as the shape and position of the soma within the dendritic field, three main groups of ganglion cell types with a total of nine different types were identified. The first group included monostratified cells, of which two types (Ma(2) and Mb(5)) may be ON- and OFF-variants, and the third (Mb(6)) had its dendritic field as a narrow band at the inner border of the inner plexiform layer. These three cells had the largest dendritic fields, with areas exceeding 40,000 microm(2). In two additional monostratified cells the dendrites were spread over the entire width of either sublamina a or sublamina b of the inner plexiform layer (Ma, Mb). They were of intermediate size with mean dendritic field areas between 10,000 and 20,000 microm(2). The second group contained two types of bistratified cells (Bb(4/5) and Bb(4,5/5,6)) with two distinct bands of dendritic stratifications in sublamina b. One of them had the smallest dendritic field (below 5,000,mm(2)) of all cell types in the sample. The diffuse cells of the third group had their dendrites across the entire width of the inner plexiform layer. The sample of retinotectal cells investigated in this study included types described previously (Mangrum et al. [2002] Vis Neurosci 19:767-779) but also new types not described previously.

Adaptive plasticity during the development of colour vision.

Colour vision greatly enhances the discriminatory and cognitive capabilities of visual systems and is found in a great majority of vertebrates and many invertebrates. However, colour coding visual systems are confronted with the fact that the external stimuli are ambiguous because they are subject to constant variations of luminance and spectral composition. Furthermore, the transmittance of the ocular media, the spectral sensitivity of visual pigments and the ratio of spectral cone types are also variable. This results in a situation where there is no fixed relationship between a stimulus and a colour percept. Colour constancy has been identified as a powerful mechanism to deal with this set of problems; however, it is active only in a short-term time range. Changes covering longer periods of time require additional tuning mechanisms at the photoreceptor level or at postreceptoral stages of chromatic processing. We have used the trichromatic blue acara (Aequidens pulcher, Cichlidae) as a model system and studied retinal morphology and physiology, and visually evoked behaviour after rearing fish for 1-2 years under various conditions including near monochromatic lights (spectral deprivation) and two intensities of white light (controls). In general, long-term exposure to long wavelengths light had lesser effects than light of middle and short wavelengths. Within the cone photoreceptors, spectral deprivation did not change the absorption characteristics of the visual pigments. By contrast, the outer segment length of middle and long-wave-sensitive cones was markedly increased in the blue rearing group. Furthermore, in the same group, we observed a loss of 65% short-wave-sensitive cones after 2 years. These changes may be interpreted as manifestations of compensatory mechanisms aimed at restoring the balance between the chromatic channels. At the horizontal cell level, the connectivity between short-wave-sensitive cones and the H2 cone horizontal cells, and the spinule dynamics were both affected in the blue light group. This observation rules out the role of spinules as sites of chromatic feedback synapses. The light-evoked responses of H2 horizontal cells were also sensitive to spectral deprivation showing a shift of the neutral point towards short wavelengths in the blue rearing group. Interestingly, we also found an intensity effect because in the group reared in bright white light the neutral point was more towards longer wavelength than in the dim light group. Like the changes in the cones, the reactions of horizontal cells to spectral deprivation in the long wave domain can be characterised as compensatory. We also tested the spectral sensitivity of the various experimental groups of blue acara in visually evoked behaviour using the optomotor response paradigm. In this case, the changes in the relative spectral sensitivity were more complex and could not be explained by a simple extrapolation of the adaptive and compensatory processes in the outer retina. We conclude that the inner retina, and/or the optic tectum are also involved and react to the changes of the spectral environment. In summary, we have shown a considerable developmental plasticity in the colour vision system of the blue acara, where epigenetic adaptive processes at various levels of the visual system respond to the specific spectral composition of the surroundings and provide a powerful mechanism to ensure functional colour vision in different visual environments. We suggest that processes involving an active fine-tuning of the photoreceptors and the postreceptoral processing of chromatic information during ontogenetic development are a general feature of all colour vision systems. Such mechanisms would establish a functional balance between the various chromatic channels. This appears to be an essential condition for the cognitive systems to extract the relevant and stable information from the unstable and changing stimulus situation.

Localisation and origin of the bacteriochlorophyll-derived photosensitizer in the retina of the deep-sea dragon fish Malacosteus niger.

Most deep-sea fish have a single visual pigment maximally sensitive at short wavelengths, approximately matching the spectrum of both downwelling sunlight and bioluminescence. However, Malcosteus niger produces far-red bioluminescence and its longwave retinal sensitivity is enhanced by red-shifted visual pigments, a longwave reflecting tapetum and, uniquely, a bacteriochlorophyll-derived photosensitizer. The origin of the photosensitizer, however, remains unclear. We investigated whether the bacteriochlorophyll was produced by endosymbiotic bacteria within unusual structures adjacent to the photoreceptors that had previously been described in this species. However, microscopy, elemental analysis and SYTOX green staining provided no evidence for such localised retinal bacteria, instead the photosensitizer was shown to be distributed throughout the retina. Furthermore, comparison of mRNA from the retina of Malacosteus to that of the closely related Pachystomias microdon (which does not contain a bacterichlorophyll-derived photosensitzer) revealed no genes of bacterial origin that were specifically up-regulated in Malacosteus. Instead up-regulated Malacosteus genes were associated with photosensitivity and may relate to its unique visual ecology and the chlorophyll-based visual system. We also suggest that the unusual longwave-reflecting, astaxanthin-based, tapetum of Malacosteus may protect the retina from the potential cytotoxicity of such a system.

A strategy for treatment of Epstein-Barr virus-positive Hodgkin's disease by targeting interleukin 12 to the tumor environment using tumor antigen-specific T cells.

Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T cells (CTL) is effective for the prophylaxis and treatment of EBV-induced lymphoma in hematopoietic stem cell recipients. However, in EBV-positive Hodgkin's disease (HD) the efficacy of adoptively transferred EBV-specific CTL may be limited by tumor-derived immunosuppressive factors, such as T-cell growth factor (TGF) beta, interleukin (IL)13 and the chemokine TARC. Local delivery of IL12 to tumor sites by tumor-specific CTL could provide direct antitumor effects and overcome the CTL-inhibitory effects of the Th2 tumor environment while avoiding the systemic toxicity of recombinant IL12. EBV-specific CTL transduced with a retrovirus vector expressing the p40 and p35 subunits of IL12 as a single molecule (Flexi-IL12), produced IL12 following antigenic stimulation. This resulted in an elevated production of Th1 cytokines, including interferon gamma and tumor necrosis factor alpha, and a reduction in the Th2 cytokines IL4 and IL5. Flexi-IL12-transduced CTL resisted the antiproliferative and anticytotoxic effects of exogenous TGFbeta, likely by antagonizing the TGFbeta-induced downregulation of the Th1 transcriptional factor T-bet. In addition, Flexi-IL12-transduced CTL demonstrated a proliferative advantage in the presence of inhibitory supernatants from HD-derived cell lines. Tumor-specific, Flexi-IL12-transduced EBV-specific CTL should have a functional advantage over unmodified CTL, particularly in the presence of the adverse Th2 cytokine environment produced by Hodgkin tumor cells.