Search

Background: Biomarkers that facilitate the prediction of disease recurrence in head and neck squamous cell carcinoma (HNSCC) may enable physicians to personalize treatment. In the current study, DNA promoter methylation of programmed cell death 1 (PDCD1, PD-1) was evaluated as a prognostic biomarker in HNSCC patients., Results: High PDCD1 methylation (mPDCD1) was associated with a significantly shorter overall survival after surgical resection in both the discovery (HR = 2.24 [95%CI: 1.08-4.64], p = 0.029) and the validation cohort (HR = 1.54 [95%CI: 1.08-2.21], p = 0.017). In multivariate Cox proportional hazards analysis, PDCD1 methylation remained a significant prognostic factor for HNSCC (HR = 2.14 [95%CI: 1.19-3.84], p = 0.011). Further, mPDCD1 was strongly associated with the human papilloma virus (HPV) status., Materials and Methods: mPDCD1 was assessed retrospectively in a discovery cohort of 120 HNSCC patients treated at the University Hospital of Bonn and a validation cohort of 527 HNSCC cases analyzed by The Cancer Genome Atlas Research Network., Conclusions: PDCD1 methylation might aid the identification of HNSCC patients potentially benefitting from a radical or alternative treatment, particularly in the context of immunotherapies targeting PD-1/PD-L1.

Introduction: Diabetes mellitus is a well-defined risk factor for peripheral artery disease (PAD), but protects against the development and growth of abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial stiffening and peripheral arterial media sclerosis. Advanced glycation end-products (AGEs) are increased in diabetes mellitus and cardiovascular disease. AGEs are known to form cross-links between proteins and are associated with arterial stiffness. Whether AGEs contribute to the protective effects of diabetes mellitus in AAA is unknown. Therefore, the ARTERY ( A dvanced glycation end-p R oducts in patients with peripheral ar T ery dis E ase and abdominal ao R tic aneur Y sm) study is designed to evaluate the role of AGEs in the diverging effects of diabetes mellitus on AAA and PAD., Methods and Analysis: This cross-sectional multicentre study will compare the amount, type and location of AGEs in the arterial wall in a total of 120 patients with AAA or PAD with and without diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular parameters, including pulse wave velocity, will be measured to evaluate the association between arterial stiffness and AGEs. Finally, AGEs will be measured in serum, urine, and assessed in skin with skin autofluorescence using the AGE Reader., Ethics and Dissemination: This study is approved by the Medical Ethics committees of University Medical Center Groningen, Martini Hospital and Medisch Spectrum Twente, the Netherlands. Study results will be disseminated through peer-reviewed journals and scientific events., Trial Registration Number: trialregister.nl NTR 5363., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

NOMAD is a spectrometer suite on board the ESA/Roscosmos ExoMars Trace Gas Orbiter, which launched in March 2016. NOMAD consists of two infrared channels and one ultraviolet and visible channel, allowing the instrument to perform observations quasi-constantly, by taking nadir measurements at the day- and night-side, and during solar occultations. Here, in part 2 of a linked study, we describe the design, manufacturing, and testing of the ultraviolet and visible spectrometer channel called UVIS. We focus upon the optical design and working principle where two telescopes are coupled to a single grating spectrometer using a selector mechanism.

The population of patients with moderate and severe CKD is growing. Frail and older patients comprise an increasing proportion. Many studies still exclude this group, so the evidence base is limited. In 2013 the advisory board of ERBP initiated, in collaboration with European Union of Geriatric Medicine Societies (EUGMS), the development of a guideline on the management of older patients with CKD stage 3b or higher (eGFR >45 mL/min/1.73 m2). The full guideline has recently been published and is freely available online and on the website of ERBP (www.european-renal-best-practice.org). This paper summarises main recommendations of the guideline and their underlying rationales., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Squamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients., Results: PITX2 hypermethylation was associated with a better overall survival (hazard ratio, HR = 0.51, 95%CI: 0.35-0.74, p<0.001), while PANCR hypermethylation was significantly associated with an increased risk of death (HR = 1.64, 95%CI: 1.12-2.39, p=0.010)., Methods: Quantitative, methylation-specific real-time PCR assays for PITX2 and PANCR were employed to measure bisulfite-converted DNA from formalin-fixed, paraffin-embedded (FFPE) tissues in a cohort of 399 patients with localized or locally advanced HNSCC who received curative-intent treatment (surgery with optional adjuvant radiochemotherapy or definite radiochemotherapy)., Conclusions: PITX2 and PANCR methylation status were shown to be independent predictors for overall survival in HNSCC patients. Tissue-based methylation testing could therefore potentially be employed to identify patients with a high risk for death who might benefit from a more radical or alternative treatment.

NOMAD is a suite of three spectrometers that will be launched in 2016 as part of the joint ESA-Roscosmos ExoMars Trace Gas Orbiter mission. The instrument contains three channels that cover the IR and UV spectral ranges and can perform solar occultation, nadir and limb observations, to detect and map a wide variety of Martian atmospheric gases and trace species. Part I of this work described the models of the UVIS channel; in this second part, we present the optical models representing the two IR channels, SO (Solar Occultation) and LNO (Limb, Nadir and Occultation), and use them to determine signal to noise ratios (SNRs) for many expected observational cases. In solar occultation mode, both the SO and LNO channel exhibit very high SNRs >5000. SNRs of around 100 were found for the LNO channel in nadir mode, depending on the atmospheric conditions, Martian surface properties, and observation geometry.

The genomes of Ceratocystis eucalypticola, Chrysoporthe cubensis, Chrysoporthe deuterocubensis, Davidsoniella virescens, Fusarium temperatum, Graphilbum fragrans, Penicillium nordicum and Thielaviopsis musarum are presented in this genome announcement. These seven genomes are from plant pathogens and otherwise economically important fungal species. The genome sizes range from 28 Mb in the case of T. musarum to 45 Mb for Fusarium temperatum. These genomes include the first reports of genomes for the genera Davidsoniella, Graphilbum and Thielaviopsis. The availability of these genome data will provide opportunities to resolve longstanding questions regarding the taxonomy of species in these genera. In addition these genome sequences through comparative studies with closely related organisms will increase our understanding of how these pathogens cause disease.

NOMAD is a spectrometer suite on board ESA's ExoMars trace gas orbiter due for launch in January 2016. NOMAD consists of two infrared channels and one ultraviolet and visible channel allowing the instrument to perform observations quasi-constantly, by taking nadir measurements at dayside and nightside, and during solar occultations. In this paper, the design, manufacturing, and testing of the two infrared channels are described. We focus upon the optical working principle in these channels, where an echelle grating, used as a diffractive element, is combined with an acousto-optical tunable filter, used as a diffraction order sorter.

The genomes of Chrysoporthe austroafricana, Diplodia scrobiculata, Fusarium nygami, Leptographium lundbergii, Limonomyces culmigenus, Stagonosporopsis tanaceti, and Thielaviopsis punctulata are presented in this genome announcement. These seven genomes are from endophytes, plant pathogens and economically important fungal species. The genome sizes range from 26.6 Mb in the case of Leptographium lundbergii to 44 Mb for Chrysoporthe austroafricana. The availability of these genome data will provide opportunities to resolve longstanding questions regarding the taxonomy of species in these genera, and may contribute to our understanding of the lifestyles through comparative studies with closely related organisms.

The Gibberella fujikuroi complex includes many Fusarium species that cause significant losses in yield and quality of agricultural and forestry crops. Due to their economic importance, whole-genome sequence information has rapidly become available for species including Fusarium circinatum, Fusarium fujikuroi and Fusarium verticillioides, each of which represent one of the three main clades known in this complex. However, no previous studies have explored the genomic commonalities and differences among these fungi. In this study, a previously completed genetic linkage map for an interspecific cross between Fusarium temperatum and F. circinatum, together with genomic sequence data, was utilized to consider the level of synteny between the three Fusarium genomes. Regions that are homologous amongst the Fusarium genomes examined were identified using in silico and pyrosequenced amplified fragment length polymorphism (AFLP) fragment analyses. Homology was determined using BLAST analysis of the sequences, with 777 homologous regions aligned to F. fujikuroi and F. verticillioides. This also made it possible to assign the linkage groups from the interspecific cross to their corresponding chromosomes in F. verticillioides and F. fujikuroi, as well as to assign two previously unmapped supercontigs of F. verticillioides to probable chromosomal locations. We further found evidence of a reciprocal translocation between the distal ends of chromosome 8 and 11, which apparently originated before the divergence of F. circinatum and F. temperatum. Overall, a remarkable level of macrosynteny was observed among the three Fusarium genomes, when comparing AFLP fragments. This study not only demonstrates how in silico AFLPs can aid in the integration of a genetic linkage map to the physical genome, but it also highlights the benefits of using this tool to study genomic synteny and architecture.

The genomes of fungi provide an important resource to resolve issues pertaining to their taxonomy, biology, and evolution. The genomes of Amanita jacksonii, Ceratocystis albifundus, a Fusarium circinatum variant, Huntiella omanensis, Leptographium procerum, Sclerotinia echinophila, and Rutstroemia sydowiana are presented in this genome announcement. These seven genomes are from a number of fungal pathogens and economically important species. The genome sizes range from 27 Mb in the case of Ceratocystis albifundus to 51.9 Mb for Rutstroemia sydowiana. The latter also encodes for a predicted 17 350 genes, more than double that of Ceratocystis albifundus. These genomes will add to the growing body of knowledge of these fungi and provide a value resource to researchers studying these fungi.

The draft nuclear genomes of Diplodia sapinea, Ceratocystis moniliformis s. str., and C. manginecans are presented. Diplodia sapinea is an important shoot-blight and canker pathogen of Pinus spp., C. moniliformis is a saprobe associated with wounds on a wide range of woody angiosperms and C. manginecans is a serious wilt pathogen of mango and Acacia mangium. The genome size of D. sapinea is estimated at 36.97 Mb and contains 13 020 predicted genes. Ceratocystis moniliformis includes 25.43 Mb and is predicted to encode at least 6 832 genes. This is smaller than that reported for the mango wilt pathogen C. manginecans which is 31.71 Mb and is predicted to encode at least 7 494 genes. The latter is thus more similar to C. fimbriata s.str., the type species of the genus. The genome sequences presented here provide an important resource to resolve issues pertaining to the taxonomy, biology and evolution of these fungi.

We describe a new spectral imaging instrument using a TeO(2) acousto-optical tunable filter (AOTF) operating in the visible domain (450-900 nm). It allows for fast (~1 second), monochromatic (FWHM ranges from 0.6 nm at 450 nm to 3.5 nm at 800 nm) picture acquisition with good spatial resolution. This instrument was designed as a breadboard of the visible channel of a new satellite-borne atmospheric limb spectral imager, named the Atmospheric Limb Tracker for the Investigation of the Upcoming Stratosphere (ALTIUS), that is currently being developed. We tested its remote sensing capabilities by observing the dense, turbulent plume exhausted by a waste incinerator stack at two wavelengths sensitive to NO(2). An average value of 6.0±0.4×10(17) molecules cm(-2) has been obtained for the NO(2) slant column density within the plume, close to the stack outlet. Although this result was obtained with a rather low accuracy, it demonstrates the potential of spectral imaging by using AOTFs in remote sensing.

Fusarium circinatum and Fusarium subglutinans are two distinct species in the Gibberella fujikuroi species complex. A genetic linkage map produced from an interspecific cross between these species was used to identify quantitative trait loci (QTLs) associated with variation in mycelial growth and morphology of colony margins (CMs) in the 94 F(1) progeny. Mycelial growth was assessed by measuring culture size at 25°C and 30°C, while CM morphology was characterized in the parents and assessed in their F(1) progeny. In order to test the pathogenicity of the progeny, Pinus patula seedlings were inoculated and lesion lengths were measured after 3weeks. Seven putative QTLs were associated with mycelial growth, three for growth at 25°C and four at 30°C. One highly significant QTL (P<0.001) was present at both growth temperatures. For CM morphology, a QTL was identified at the same position (P<0.001) as the QTL responsible for growth at the two temperatures. The putative QTLs accounted for 45 and 41% of the total mycelial growth variation at 25°C and 30°C, respectively, and for 21% of the variation in CM morphology. Only one of the 94 F(1) progeny was pathogenic on P. patula seedlings. This observation could be explained by the genetic constitution of this F(1) isolate, namely that ∼96% of its genome originated from the F. circinatum parent. This F(1) individual also grew significantly faster at 25°C than the F. circinatum parent (P<0.05), as well as more rapidly than the average growth for the remaining 93 F(1) progeny (P<0.05). However, no association was found between mycelial growth and pathogenicity at 25°C. The highly significant QTL associated with growth at two temperatures, suggests that this is a principal genomic region involved in mycelial growth at both temperatures, and that the same region is also responsible for CM morphology., (Copyright © 2011 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

The fungus Fusarium globosum was first isolated from maize in South Africa and subsequently from wheat in Japan. Here, multiple analyses revealed that, despite morphological similarities, South African maize and Japanese wheat isolates of the fungus exhibit multiple differences. An amplified fragment length polymorphism-based similarity index for the two groups of isolates was only 45%. Most maize isolates produced relatively high levels of fumonisins, whereas wheat isolates produced little or no fumonisins. The fumonisin biosynthetic gene FUM1 was detected in maize isolates by Southern blot analysis but not in the wheat isolates. In addition, most of the maize isolates produced sclerotia, and all of them produced large orange to dark purple sporodochia in carrot agar culture, whereas wheat isolates did not produce either structure. In contrast, individual isolates from both maize and wheat carried markers for both mating type idiomorphs, which indicates that the fungus may be homothallic. However, a sexual stage of F. globosum was not formed under standard self-fertilization conditions developed for other homothallic species of Fusarium. The inability to produce the sexual stage is consistent with the high similarity of 87-100% and G (ST) index of 1.72 for the maize isolates, which suggests that these isolates are undergoing asexual but not sexual reproduction. Together, the results suggest that the South African maize and Japanese wheat isolates of F. globosum are distinct populations and could be different species.

Proprotein convertases are serine endoproteases implicated in the proteolytic processing of a large variety of regulatory proteins. An important role of proprotein convertases in tumorigenic processes has been suggested by various studies. In this study, the role of the proprotein convertase furin in PLAG1 proto-oncogene-induced salivary gland tumorigenesis was investigated. PLAG1 overexpression in salivary glands has previously been shown to result in salivary gland tumors in 100% of mice within 5 weeks after birth. MMTV-cre-mediated inactivation of fur without over-expression of PLAG1 caused smaller but histologically normal salivary glands. Moreover, the lymph nodes close to the salivary glands were enlarged, and histology showed that they had activated follicles. When genetic ablation of 1 or 2 alleles of fur and overexpression of the PLAG1 transgene were simultaneously achieved, a significant delay in tumorigenesis was observed. Collectively, these results suggest an important role for furin in PLAG1-induced salivary gland tumorigenesis in mice.

A new compact spaceborne high-resolution spectrometer developed for the European Space Agency's Venus Express spacecraft is described. It operates in the IR wavelength range of 2.2 to 4.3 microm and measures absorption spectra of minor constituents in the Venusian atmosphere. It uses a novel echelle grating with a groove density of 4 lines/mm in a Littrow configuration in combination with an IR acousto-optic tunable filter for order sorting and an actively cooled HgCdTe focal plane array of 256 by 320 pixels. It is designed to obtain an instrument line profile of 0.2 cm(-1). First results on optical and spectral properties are reported.

The purpose of the present study was to evaluate pigs as a large-animal model for female genital infection with two Chlamydia trachomatis human serovar E strains. Sixteen-week-old specific-pathogen-free female pigs (gilts) were intravaginally infected with the trachoma type E reference strain Bour or the urogenital serovar E strain 468. Several conclusions can be drawn from our findings on the pathogenicity of a primary C. trachomatis genital infection in gilts. First of all, we demonstrated that the serovar E strains Bour and 468 could ascend in the genital tract of gilts. The serovar E strains could replicate in the superficial columnar cervical epithelium and in the superficial epithelial layer of the uterus, which are known to be the specific target sites for a C. trachomatis genital infection in women. Second, inflammation and pathology occurred at the replication sites. Third, the organisms could trigger a humoral immune response, as demonstrated by the presence of immunoglobulin M (IgM), IgG, and IgA in both serum and genital secretion samples. Our findings imply that the pig model might be useful for studying the pathology, pathogenesis, and immune response to a C. trachomatis infection of the genital system.

The prevalence of Chlamydiaceae infections on 258 closed pig breeding farms in Belgium was examined. For this purpose, 258 farms were randomly selected in the provinces West-Vlaanderen (44%), Oost-Vlaanderen (20%), Antwerpen (10%) and Vlaams-Brabant (6%). Of all farms examined, 96.5% were positive for Chlamydia-specific antibodies in ELISA and most were moderately to strongly positive. ELISA results revealed only 9 (3.5%) sero-negative farms. None of the ELISA negative sera reacted in immunoblotting. Only 212 of 249 ELISA positive sera reacted positive in immunoblotting. Additionally, 23 autopsy samples were examined by isolation in Vero cells. The major outer membrane sequence of the one isolate obtained showed 98.6% amino acid homology to the one of Chlamydophila psittaci strain CP3, formerly isolated from a pigeon. Present observations indicate that chlamydial infections are nearly endemic in the Belgian pig population and that Belgian pigs can become infected with C. psittaci. Nevertheless, the role and significance of Chlamydiaceae as pathogens in pigs remain unsolved and require further investigation.

The submicroscopic anatomy of the eye in female Eupulvinaria is described. This scale insect has no compound eyes but simple pericerebral eyes composed of one pair of ocelli. The ocelli, located dorsolaterally to the brain, are of rhabdomeric type. They are situated in the subepidermal region underneath the basement membrane of the epidermis. Each ocellus consists of a cup made of a layer of numerous pigmented cells enclosing a few photoreceptive cells. The cuticular lens is facing the opening of the pigment-cup, while the optic nerve is emerging from the bottom of the cup. Pigmented cells show characteristic pigment granules. They are linked to each other by interdigitations or by desmosomes junctions. Both dendrites and cell body of the photoreceptor cell lie inside the eyecup, while the axon lies outside. The dendritic processes consist of large shaft-shaped rhabdomeres with microvilli extending perpendicular to the direction of the shaft. These microvilli are enveloped by digitiform cytoplasmic extensions of pigmented cells. These latter strands are free of pigment granules but contain microtubules orientated to the centre of the cup.

Four different chemical forms of the alpha-particle emitting radionuclide 211At were injected intraperitoneally in mice inoculated intraperitoneally 30 hr in advance with 10(6) cells of the K13 murine hybridoma cell line. The different 211At forms were (a) free 211At, (b) 211At-labeled TP-3 nonspecific monoclonal antibody (211At-TP-3), (c) 211At-labeled human IgG kappa (211At-hIgG kappa), and (d) 211At-labeled monodisperse polymer particles (211At-MDPP). A significantly prolonged survival (P < 0.05) was observed with injected doses down to 7 kBq for the 211At-MDPP, and down to 25 kBq for 211At-hIgG kappa. There were no significant differences in survival between 211At-MDPP, 211At-hIgG kappa, and 211At-TP-3 at the dose level of 200 kBq. The group receiving 250 kBq free 211At per animal had a shorter survival than the three other forms at 200 kBq. The groups treated with 500, 200, and 65 kBq 211At-MDPP had a similar survival. The group given the highest dose of 211At-hIgG kappa (275 kBq) had the highest fraction (50%) of long-term survivors of all groups. Biodistribution measurements and total body scintigrams in mice without tumor revealed that the free 211At was distributed all over the body within 10 min after injection while at 2 hr a high fraction of the 211At-TP-3 and 211At-hIgG kappa was still present intraperitoneally. In conclusion this study indicates that 211At-labeled MDPP and 211At-labeled IgG's may be efficient tools for treatment of intraperitoneal superficial tumor cells and malignant ascites.

Revision surgery for otosclerosis is analysed in 26 patients. Audiometric results are better in patients with recurrent rather than persistent transmission hearing loss. Total platinectomy with interposition may be a solution for patients with chronic tubal dysfunction.

Objectives: Our purpose was to identify prognostic factors in stage I epithelial invasive ovarian carcinoma., Study Design: The traditional clinical and pathologic prognostic variables and deoxyribonucleic acid ploidy were analyzed in a group of 290 patients., Results: A multivariate analysis identified degree of differentiation as the most powerful prognostic indicator of disease-free survival, followed by deoxyribonucleic acid ploidy and, finally, International Federation of Gynecology and Obstetrics (1986) stage. Tumors with clear cell carcinoma elements were not graded, and in this subgroup International Federation of Gynecology and Obstetrics (1986) stage was the most important prognostic characteristic. When the effects of the three most important factors were accounted for in graded tumors, then none of the following were prognostic: histologic type, dense adhesion, extracapsular growth, ascites, rupture during surgery, International Federation of Gynecology and Obstetrics (1973) stage, size of tumor, and age and type of adjuvant treatment. None of 77 patients with well differentiated deoxyribonucleic acid diploid tumors had relapses., Conclusion: Deoxyribonucleic acid ploidy is an important new independent prognostic factor in stage I ovarian carcinoma.

alpha-Emitting radionuclides such as 211At have a number of physical characteristics which make them attractive for the treatment of micrometastases. 211At was bound to polymer microspheres and its efficacy was compared with the beta-emitting 32P and 90Y colloids for the treatment of intraperitoneally growing K13 hybridoma tumors in mice. Single graded doses of 0.1-2.5 MBq 211At microspheres injected intraperitoneally 24 hr after inoculation of the hybridoma cells improved survival and produced higher cure rates than 32P colloid, 90Y colloid, or no treatment. One of the most striking contrasts between 211At microspheres and 90Y or 32P colloids was the ability of relatively low doses 211At to affect cures. When comparing the groups with the highest survival rate for each radionuclide (0.1-1 MBq 211At, 2.5 MBq 90Y, and 2.5 MBq 32P), 211At treatment resulted in an improved survival over that with 32P therapy, but the difference was not significant between 211At and 90Y. Toxicity studies with 211At microspheres showed that dosages up to 17 MBq per mouse were not lethal. In conclusion, the present study suggests that the high-energy transfer and the short-range cytotoxicity of the alpha-emitter 211At might be of benefit for intracavitary radiotherapy.

The alpha-emitter 211At was bound to polymer microspheres with a diameter of 1.8 microns. The distributions in mice of intraperitoneally injected 211At microspheres, 90Y silicate colloid, and 32P chromic phosphate colloid were compared. The microspheres with 211At spread rapidly in the peritoneal cavity and remained mainly on the intraperitoneal surfaces. Intraperitoneal injection of 90Y colloid resulted in high levels in intraperitoneal fat and the diaphragm, but 1 day after injection 8.5% of the injected dose per gram was found in blood and after 6 days 2.5% was observed in bone. The highest accumulation of 32P was found in liver and spleen. The injection of additional nonradioactive chromic phosphate colloid resulted in an even higher accumulation of 32P in spleen and liver. The same phenomenon was not observed with 211At microspheres. It is suggested that it is not only the particle size which is important in the distribution of intraperitoneally injected colloid, but the amount of colloid, the type of colloid, the addition or presence of other substances such as ascites, and the animal species might also influence the distribution. In conclusion, the intraperitoneal distribution of 211At-labeled microspheres in mice was favorable compared with 90Y and 32P colloid. These data must be viewed cautiously since the distribution might be different in other animal species or humans.

Murine B-cell hybridoma cells producing an immunoglobulin G1 (K13), specific for human immunoglobulin kappa chains were inoculated intraperitoneally in mice. After intraperitoneal injection of 10(6) K13 hybridoma cells, superficial intraperitoneal implants and ascites developed, resulting in death after 10 +/- 3 days (mean +/- SD). An immunoradiometric assay was developed to measure K13 in murine blood, ascites and culture supernatant. The assay utilized polymer beads coated with human immunoglobulin G. The amount K13 bound to the particles was measured with a 125I-labelled monoclonal rat antibody (LO-MG1-13) specific for mouse IgG1. The assay could be used over a wide working range (2-500 micrograms/l). Kinetic studies suggested that about 10(5) secreting cells were required for detection of K13 in blood. After injection of 10(6) cells, K13 was measurable in blood 1 day later in all animals. Nine of 33 mice injected with 10(5) or less cells survived, and initially showed rising K13 blood levels followed by decreasing blood levels. In conclusion, a close relationship was established between i.p. growth of the hybridoma K13 cell line and the MAb blood levels. The basic concepts of this assay can readily be adopted for other clones with the limitation that pure antigen is needed for solid phase extraction of the MAb from mouse blood.

The aquiferous system of representatives of the orders Dictyocer-atida, Dendroceratida, and Verongida has been studied to note its relevance to the systematics of the groups. The volume of the choanocyte chamber, the size and shape of the choanocytes, the number of choanocytes per chamber, the relative development of the mesohyl, and the features of endopinacocytes are estimated from scanning and transmission electron microscopic observations of representatives of most families of the three orders. Although the Dysideidae have a reticulate skeleton and were classified in the order Dictyoceratida, they are actually closer to the Aplysillidae (Dendroceratida) than to dictyoceratids. The anatomy and cytology of the Halisarcidae differ profoundly from those of these three orders and are clearly more closely related to nonkeratose sponges. Some changes in classification lead to a pattern with highly homogeneous orders that clearly differ in their anatomic and cytologic features, which does not support the hypothesis of a common origin of the "keratose" sponges., (Copyright © 1989 Wiley-Liss, Inc.)

We studied a patient with severe ulcerations on the lower limbs due to cutaneous periarteritis nodosa. Chronic relapsing course during more than 12 years with no systemic involvement was documented.

The choanoderm and pinacoderm of representatives of the two families of Homoscleromorpha sponges, the Oscarellidae and Plakinidae, have been examined by transmission and scanning electron microscopy. Different fixative procedures have shown the dramatic influence of fixation conditions on the morphology of choanocytes. These two families of sponges have the following morphological features in common: flagellated endopinacocytes with short apical microvilli and basal pseudopods; the presence of a very thin and dense sheet of matrix material which limits the mesohyl. There are, however, only minor differences in the flagellar morphology, granule content, and anchoring system of their choanocytes. Two findings are of particular interest: (1) the presence of glycocalyx bridges between the microvilli of the choanocyte collar; and (2) the discovery of a new cell type, the apopylar cell, which has a morphology intermediate between that of pinacocytes and choanocytes. The apopylar cells limit the apopylar opening of the choanocyte chamber and indicate the transition between choanoderm and pinacoderm., (Copyright © 1984 Wiley-Liss, Inc.)

Terminal fibroblasts differ from early ones by slowing down in replicative activity, increase in cell area, changes in the cytoskeleton and changes in the way of dying. Replication was inhibited in early fibroblasts either with aphidicolin or by serum deprivation. Both treatments induce cell flattening and increase in cell surface. Aphidicolin has no effect on actin-microfilaments whereas serum deprivation induces the terminal pattern of filaments in many early cells. After both treatments, fibroblasts keep dying as early cells do. We conclude that there is no direct relation between changes in the organization of cell filaments and slowing down of replication (inducing cell flattening); we suggest that they depend on changes in the cell membrane structure appearing during in vitro terminal differentiation.