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No previous records in the available literature about the cutaneous mast cell tumors in golden hamster. Two male golden hamsters with cutaneous lumps were brought to the Institute of Veterinary Pathology of Justus Leibig University of Giessen, Germany for diagnositic examination. Cutaneous lumps were taken and processed for histological, histochemical and immunohistochemical examination. Numerous oval and polygonal tumor cells with high mitotic count and basophilic metachromatic granules were observed; while the superjacent epidermis and adnexes were normal. Many unevenly proliferating cells showed positive proliferating cell nuclear antigen (PCNA) reaction and positive chymase activity. The reactions were negative to gene encoding KIT (c-Kit), Cyclooxygenase-2 (COX-2) and tryptase. These results indicated a well- differentiated grade I subcutaneous mast cell tumor. The results are discussed in relation to subcutaneous mast cell tumors in canines.

Highlights • ORF 3c is affected by deletions and stop codons more frequently than ORF 7b. • Deletions in ORF 3c are not a compelling feature of FIPV. • Sequences of different tissue specimens within one cat are mostly identical. • PCR amplification of ORF 7b is more efficiently than that of ORF 3c., Feline infectious peritonitis (FIP) is the most frequent lethal infectious disease in cats. However, understanding of FIP pathogenesis is still incomplete. Mutations in the ORF 3c/ORF 7b genes are proposed to play a role in the occurrence of the fatal FIPV biotype. Here, we investigated 282 tissue specimens from 28 cats that succumbed to FIP. Within one cat, viral sequences from different organs were similar or identical, whereas greater discrepancies were found comparing sequences from various cats. Eleven of the cats exhibited deletions in the 3c gene, resulting in truncated amino acid sequences. The 7b gene was affected by deletions only in one cat. In three of the FIP cats, coronavirus isolates with both intact 3c genes as well as 7b genes of full length could also be detected. Thus, deletions or stop codons in the 3c sequence seem to be a frequent but not compelling feature of FIPVs.

Zusammenfassung Gegenstand und Ziel: Die Treffsicherheit klinischer Verdachtsdiagnosen und die praktisch relevanten Differenzialdiagnosen häufiger maligner Tumoren bei Hund und Katze wurden untersucht. Material und Methoden: Anhand von 2109 unter Verdacht eines malignen Tumors an das Institut für Veterinär-Pathologie der Justus Liebig Universität Gießen eingesandter Bioptate der Jahre 1999–2004 wurden die Trefferquoten hinsichtlich der Verdachtsdiagnosen der Einsender und der histopathologischen Diagnosen errechnet. Chi-Quadrat-Test bzw. der verallgemeinerte Test nach Fisher dienten zur Überprüfung, ob sich diese an den verschiedenen Entnahmelokalisation der einzelnen spezifischen Tumoren signifikant unterscheiden. Zusätzlich erfolgte eine Zusammenstellung der häufigeren Differenzialdiagnosen an den verschiedenen Entnahmelokalisationen. Ergebnisse: Die Zusammenstellung der histopathologischen Diagnosen, in Abhängigkeit von den Entnahmelokalisationen, gibt in Verbindung mit den Trefferquoten bezüglich der Verdachtsdiagnosen der einsendenden Tierärzte einen Überblick über die Häufigkeit der untersuchten Tumorarten und deren makroskopische Ansprechbarkeit an den verschiedenen Lokalisationen. Die Treffsicherheit klinischer Verdachtsdiagnosen ist bei den einzelnen Tumorentitäten sehr variabel und oft tumor-und lokalisationsspezifisch. Sie liegt bei den häufigeren Tumoren zwischen 19% und 83%. Schlussfolgerung und klinische Relevanz: Die Ergebnisse zeigen, dass eine histopathologische Untersuchung resezierter Tumoren weiterhin unverzichtbar ist, da eine anhand des Erscheinungsbildes gestellte klinische Verdachtsdiagnose nur in einem kleinen Teil der Fälle mit der histopathologischen Diagnose übereinstimmt.

Tissues of mice that had had microchip transponders with surfaces made of bioglass, bioglass with a polypropylene cap, parylene C, titanium or aluminium oxide inserted were examined histologically, and the growth of two lines of feline fibroblastoid cells around these transponders was examined in vitro. The results for bioglass and aluminium oxide were similar. In vitro, there were almost no cells around or on the transponders; in vivo, there was often granulomatous inflammation in the surrounding tissue. In the case of the bioglass, this reaction seemed to be induced by petrolatum, which was added by the manufacturer for technical reasons, rather than by the bioglass itself. In some of the mice, polypropylene caused a proliferation of granulation tissue. In vitro, the cellularity around the transponders was high, but only a moderate number of cells were found on the material. In vivo, around the parylene C transponders, there were occasionally small fragments of foreign material, surrounded by a foreign body reaction; in vitro, the results for parylene C resembled those for polypropylene. In vivo, particles of titanium were sometimes visible in the connective tissue adjacent to the titanium transponders, and sometimes accompanied by a foreign body reaction; in vitro, a confluent layer of cells developed on the transponders, with a high cellularity around them.

Zusammenfassung: Gegenstand: Darstellung von klinischer Symptomatik, Therapie und pathologischen Befunden eines endometrialen Adenokarzinoms bei einem Schwein. Material und Methode: Fallbericht eines 15-jährigen Hängebauchschweins. Ergebnisse: Das Tier zeigte blutigen Vaginalausfluss bei unauffälliger Allgemeinuntersuchung. Nach einer erfolglosen Endometritisbehandlung erfolgte eine Laparoskopie, bei der eine Zubildung im Uterus festgestellt werden konnte. Das Schwein wurde einer Ovariohysterektomie unterzogen. Die histologische und immunhistologische Untersuchung der Masse ergab die Diagnose eines endo - metrialen Adenokarzinoms. Die Neoplasie füllte das gesamte Uteruslumen aus und zeigte Lymphgefäßeinbrüche. Klinische Relevanz: Neoplasien des Uterus stellen bei Schweinen eine Rarität dar. So wurden in über 100 Jahren endometriale Adenokarzinome nur bei sechs Schweinen beschrieben. Vor allem bei nicht als Nutztiere gehaltenen Schweinen, die ein höheres durchschnittliches Lebensalter erreichen, sind diese Uterustumoren bei blutigem Vaginalausfluss differenzialdiagnostisch zu berücksichtigen.

Zusammenfassung: Gegenstand und Ziel: Darstellung der klinischen Symptomatik sowie der histopathologischen Veränderungen der zerebellären kortikalen Abiotrophie. Material und Methoden: Fallbericht zweier Labrador-Retriever-Welpen. Ergebnisse: Die Symptomatik in Form einer progredienten Gleichgewichtsstörung trat im dritten Lebensmonat nach einer bis dahin normalen Entwicklung der Tiere auf. Bei dem weniger stark betroffenen weiblichen Welpen fielen eine mittelgradige Ataxie der Hintergliedmaßen bei deutlicher Hypermetrie der Vorderbeine und unkoordinierte Bewegungen des Kopfes auf. Bei dem schwerer erkrankten Rüden war das Stehvermögen aufgehoben. Zeitweise verfiel das Tier in einen Opisthotonus mit Extensorspasmus aller Gliedmaßen und zeigte einen rotatorischen Nystagmus. Der Drohreflex ließ sich nicht auslösen. Die Befunde der neurologischen Untersuchung wiesen klar auf eine Erkrankung des Zerebellum hin. Aufgrund aussichtsloser Prognose wurden die beiden Wurfgeschwister euthanasiert und pathologisch untersucht. Die histopathologischen Veränderungen am Gehirn beschränkten sich auf den zerebellären Kortex und manifestierten sich in einem Verlust von Purkinje-Zellen. Die Größe der Kleinhirne war unverändert. Die histopathologischen Befunde führten zur Diagnose einer zerebellären Abiotrophie. Schlussfolgerung und klinische Relevanz: Die zerebelläre kortikale Abiotrophie stellt auch bei jungen Tieren eine Differenzialdiagnose für Ausfälle der Kleinhirnfunktion dar. Das erstmalige Auftreten und der Verlauf der Erkrankung sowie die zu erwartenden histopathologischen Befunde sind nicht bei allen Hunderassen einheitlich.

Zusammenfassung Gegenstand und Ziel: der vorliegenden Untersuchung war der Nachweis von MHC-II-Antigenen auf den verschiedenen Zellen der Haut bei Hunden mit Demodikose. MHC-IIProteine spielen eine zentrale Rolle bei der zellvermittelten Immunantwort. Sie präsentieren Fragmente von extrazellulär auftretendem Antigen, um eine Immunreaktion auszulösen. Material und Methoden: Als Material dienten 15 Hautbiopsien von Hunden, die in den Jahren 2003 und 2004 zur Routinediagnostik an das Institut für Veterinär-Pathologie der Justus-Liebig-Universität Gießen gesendet wurden. Die Kontrollgruppe stellten sieben Hautproben von Hunden aus dem Sektionsgut des Institutes dar. Die Expression der MHC-II-Antigene wurde immunhistologisch bestimmt. Ergebnisse: Die Untersuchung ergab eine MHC-II-Expression auf allen Zelltypen von infiltrierenden Entzündungszellen, wobei die Plasmazellen nur in 11 von 15 Fällen markiert waren. Daneben wurde in 12 Biopsien eine MHC-II-Expression auf follikulären Keratinozyten und in nicht immer identischen 12 Fällen eine Expression auf Endothelzellen beobachtet. Schlussfolgerungen und Relevanz: Die Untersuchung zeigt, dass die Demodikose zur Anwesenheit von MHC-II-Molekülen auf zahlreichen Zellen in der Haut führt. Als typisch für die mit der Demodikose einhergehenden Entzündungsformen kann die Expression von MHC II auf follikulären Keratinozyten angesehen werden.

Using optically and electrically detected magnetic resonance (ODMR and EDMR, respectively), recombination in a ${\mathrm{G}\mathrm{a}\mathrm{A}\mathrm{s}/\mathrm{A}\mathrm{l}}_{0.4}{\mathrm{Ga}}_{0.6}\mathrm{As}$ heterostructure is studied. ODMR performed at 35 GHz shows the presence of Ga interstitials in a GaAs quantum well codoped with Si and Be. Depending on the contacts used, EDMR (performed both at 9 and 34 GHz) is able to detect surface defects, intrinsic defects (Ga interstitial and ${\mathrm{As}}_{\mathrm{Ga}}$ antisite) as well as the ${\mathrm{Cr}}^{4+}$ transition-metal impurity. The location of the paramagnetic states in the heterostructure was determined with EDMR using light of different absorption length for the selective excitation of photoconductivity, combined with a phase shift analysis of the different EDMR signals with respect to the modulation reference. The temperature and microwave power dependence of the EDMR signal amplitude is discussed, providing guidelines for the experimental conditions needed to perform EDMR on GaAs. Finally, using $X$-band and $Q$-band detection, the defect parameters ($g$-factor and hyperfine constants) for the Ga interstitial are determined to $g=2.006,$ ${A}_{69}=0.048{\mathrm{cm}}^{\mathrm{\ensuremath{-}}1},$ and ${A}_{71}=0.061{\mathrm{cm}}^{\mathrm{\ensuremath{-}}1}.$ These results are compared to previous observations.

Two cases of clear cell trichoblastomas were diagnosed in young dogs. The tumour had ribbons of basaloid cells as seen in ribbon trichoblastomas, as well as differentiation to external root sheath of the hair follicle and few cells with sebaceous differentiation. This is the first report of clear cell trichoblastoma in dogs.

AlGaN epitaxial films have been grown on sapphire by plasma-induced molecular beam epitaxy (MBE) over the entire composition range from GaN to AlN. Structural and optical properties of the alloys have been investigated by X-ray diffraction (XRD), transmission electron and atomic force microscopy, Raman scattering, ellipsometry, optical transmission, and subgap absorption spectroscopy. Electron spin resonance has been used to study the dependence of intrinsic paramagnetic defects on Al mole fraction. N- and p-type doping with Si and Mg, respectively is found to become increasingly difficult with increasing Al content because of a continuous shift of the donor and acceptor levels deeper into the bandgap. Apart from the use of AlGaN as cladding layers in light emitting diodes, applications in MODFET transistors, solar blind photodetectors, surface acoustic wave devices and Bragg reflectors appear interesting and will be discussed briefly.

Transport processes and degradation of GaP:N green light‐emitting diodes have been investigated using electrically detected magnetic resonance (EDMR). An isotropic EDMR signal with a g value of g=1.996 and a linewidth of ΔHpp=68 G can be observed at low temperatures after current degradation. The signal exhibits a T−2 temperature dependence indicating a spin relaxation process faster than the relevant transport step. The microscopic origin of the EDMR signal—most probably recombination at a n‐type dopant‐related defect near the p–n interface—is analyzed with respect to possible degradation mechanisms.

Feline infectious peritonitis (FIP) virus antigen was demonstrated after methanol, ethanol or formalin fixation in paraffin-embedded tissues by means of monoclonal and polyclonal antibodies. The monoclonal antibody was induced by immunization with transmissible gastroenteritis virus. Polyclonal antibodies were obtained by purification on protein A-Sepharose of ascites fluid from a cat with FIP. Almost all cats diagnosed as suffering from FIP by postmortem and histological examination exhibited FIP virus (FIPV) antigen in macrophages in granulomas whereas FIPV antigen was only once demonstrable in another location.

The case of a 5-month-old male Weimaraner dog with severe osteodystrophia fibrosa (rubber jaw) and renal insufficiency is presented. Kidneys were smaller than normal with a granular cortical surface and a histopathological end-stage diagnosis consistent with juvenile nephropathy. Analysis of four described genetic mutations associated with Alport syndrome in dogs revealed no evidence for familiar inheritance in this dog.

The frequency of correct clinical presumptive diagnosis and the spectrum of important differential diagnoses were investigated in common canine and feline malignant tumours.Based on 2109 presumptive malignant tumour samples submitted to the Institute of Veterinary Pathology of the Justus-Liebig-University, Giessen, the hit rates of the presumed diagnoses of the submitting veterinarians and the actual histopathological diagnosis were calculated for the specific sampling sites. These hit rates were statistically evaluated for significant deviations between the different sampling sites using the chi-square test and Fisher's exact test. Additionally, the more common differential diagnoses with respect to the sampling site were established.This compilation of histopathological diagnoses, with respect to the varying sampling sites, combined with the hit rates of the presumed diagnoses of the submitting veterinarians, yields quantitative knowledge on the frequency of occurrence, correct clinical diagnosis and macroscopic appearance of the malignant tumours investigated. The correctness of the presumptive clinical diagnosis largely depends on tumour type and localization. For the more frequent tumours, it varies from 19% to 83%.The results show the importance of a histopathological evaluation of all tumour samples as the presumptive clinical diagnosis based on appearance only corresponds in a few cases with the histopathological diagnosis.

Congenital defects like myofibrillar dysplasia (splayleg), umbilical and inguinal hernias, cryptorchism, intersexes, and anal atresia occur relatively frequently in swine. On the other hand, some developmental anomalies like double monsters are very rare. The present paper reports a rare case of a congenital complex malformation including polymelia, duplicitas coli partialis et recti, atresia ani et fistula rectogenitalis, duplicitas corpori uteri, cervicis, vaginae et vulvae and duplicitas vesicae, urethrae et renalis. A plausible interpretation concerning the etiology is that the anomalies arose from unequal partial twinning. The pig has been healthy and inconspicuous. Although no anus was formed defecation took place via a fistula to one of the vaginas. Posture and behaviour of the pig were normal. Cytogenetic analysis of blood lymphocytes revealed no numerical or gross structural anomalies. There have been no further piglets with developmental disorders in the same litter, in a second litter of the same parents and in other twelve litters by the same boar.

The extravasation of erythrocytes into the lower respiratory tract occurs in numerous lung injuries and may lead to oxidative damages in lung tissues. Haptoglobin (Hp), the major haemoglobin-binding protein, is known to reduce lung injury associated with exposure to blood in mice. In pigs, Hp is a major acute phase protein and its serum concentrations are elevated in various infections of the respiratory tract. However, information on the porcine Hp response towards inflammatory stimuli is restricted to blood. We herein investigated the presence of Hp in lung tissues from pigs with acute and chronic bronchopneumonia via immunohistochemistry. Hp was localized in airway epithelial cells and immigrated leucocytes whereas in alveolar epithelial cells there was no distinct signal. Unaltered lungs showed less Hp-positive cells compared with lungs from pigs with acute or chronic bronchopneumonia.

Sera collected post mortem during a 6-month period from cats were tested for feline immunodeficiency virus (FIV)-specific antibodies by (1) an enzyme-linked immunosorbent assay (ELISA), (2) an indirect peroxidase-based immunocytological test (IP), (3) a Western immunoblotting (WB) method with FIV-infected cell lysates, and (4) a WB method with purified viral antigen. All four methods were capable of detecting FIV-specific antibodies in haemolysed sera. However, the ELISA showed the lowest "positive predictive value" (PVpos = 22%) followed by the IP (PVpos 50-60%). Serum was FIV antibody-positive in 6% (15/255) of all cats examined. The mean age of seropositive cats was 9 years (4 years among seronegative cases) and the male-to-female ratio in such cats was 1.8 to 1 (overall ratio 0.8 to 1). Forty per cent of the seropositive cats were in the final phase of acquired immune deficiency syndrome. Feline leukaemia virus (FeLV) predominated among viral co-infections. It was concluded that (1) a combination of the IP and WB reliably detected FIV-specific antibodies in sera collected post mortem, and (2) at post-mortem examination, cats from high-risk groups (male, > 5 years old, hypercellular bone marrow) were frequently infected with FIV.

Electrically detected magnetic resonance (EDMR) has been used to study carrier recombination in GaAs/AlGaAs quantum well structures grown by molecular beam epitaxy. The spin dependent photoconductivity signals depend strongly on the electrical contact properties. Using silver paste contacts a narrow (18 G) resonance located at g = 2.001 is observed. It has been previously attributed to surface defects on GaAs. Using alloyed In-contacts other signals are detected. The dominant resonance observed at 9 GHz has an isotropic g-value of g = 1.99 with a halfwidth of 200 G and is therefore assigned to Cr4+. Other signals of considerably lower intensity are explained by the well known electron paramagnetic resonance (EPR) properties of the Gai-interstitial and the AsGa-antisite defects. EDMR performed at 34 GHz allows the experimental separation of the two sets of hyperfine lines.

Persistent FeLV infection was demonstrated in more than 3000 necropsied cats by an immunohistological method. The findings were associated with the diagnoses established by means of post-mortem examination, histopathological, bacteriological, virological, and parasitological investigations. Statistically significant differences between FeLV-positive and FeLV-negative cats in the relative risk for certain lesions could be demonstrated for the first time. As a consequence, the importance of FeLV infection for the development of certain lesions in cats is to be seen under new aspects for some diagnoses. The relative risk for development of anemia, e.g., is only slightly increased in FeLV-positive animals whereas the relative risk for focal myocardial necrosis and coccidiosis is elevated tremendously in these cats. The relative risk for some lesions and diagnoses is much higher in FeLV-negative cats than in FeLV-positive animals. This is true, e.g., for myocardiopathy and hemorrhagic cystitis.

Electrically detected magnetic resonance (EDMR) is used to study recombination processes in two types of gallium nitride light emitting diodes: in m/i/n/n+- and InGaN/AlGaN double-heterostructure devices. In the MIS-diodes, two resonances at g=1.96 and 2.00, corresponding to the effective mass donor and a deep defect are observed at room temperature. At low temperatures, an acceptor-related resonance at g=2.06 is visible as well. After current degradation, the spectra are dominated by the defect resonance, indicating that the creation of this defect is responsible for the decreased electroluminescence efficiency. In the double-heterostrucrure devices, EDMR can only be observed below 60 K showing the g=2.00 defect resonance. The same defect resonance is also observed in conventional electron spin resonance experiments under illumination (light-induced ESR).

Summary A 13-year-old mixed breed dog was presented with difficulties to urinate, blood in the urine and a nodule at the root of the penis. The penis was completely resected, and an osteosarcoma of the penile bone was diagnosed. Radiographically, there was no evidence to suggest tumours in other bones or distant metastases. The dog was euthanized as a consequence of tumour recurrence after 2 months. This is believed to be the first reported case of a primary osteosarcoma of the penile bone.

As a common characteristic of tumor cells, as well as of normal proliferating cells in the G1-phase of cell cycle, one finds constitutive high levels of all the glycolytic metabolites arising between glucose 6-phosphate and phosphoenolpyruvate. Thus, it is that the phosphometabolites fructose 1,6-bisphosphate, ribose 5-P, P-ribose-PP, NAD, GTP, CTO, UTP, UDP-glucose, glycerol 3-P, glycerol phosphocholine and glycerol phosphoethanolamine are useful in the 31P-nuclear magnetic resonance (NMR) detection of solid tumors in animals and man. This expansion of phosphometabolites is achieved during tumor formation as a result of reductions in levels of enzymes degrading phosphometabolites, owing to the decline in the glycerol 3-P hydrogen shuttle, and as a consequence of alterations in the glycolytic isoenzyme equipment. Tumor cells typically express a particular isoenzyme of pyruvate kinase called type M2 (K) at high levels. This isoenzyme is subject to a complex regulation by amino acids, by fructose 1,6-bisphosphate, and by hormonal- and oncogene-dependent phosphorylation. Pyruvate kinase type M2 is a substrate for the oncogene encoded PP60v-src-tyrosine kinase. A drastic decrease in the affinity for its substrate phosphoenolpyruvate found after transformation by the src-oncogene can be explained as a consequence of the phosphorylation of pyruvate kinase in serine and tyrosine. These phosphorylations induce the breakdown of tetrameric pyruvate kinase to the trimeric and dimeric forms. Unlike the tetrameric form, the dimeric form as a low affinity for phosphoenolpyruvate. Partial inactivation of pyruvate kinase and enolase on the one hand, and a hyperactivation of hexokinase and phosphofructokinase on the other hand, lead to an expansion of all metabolites. Only when these metabolites attain high levels, thereby assuring a sufficient supply of metabolites for RNA, DNA, lipid, and complex carbohydrate synthesis, can cell proliferation proceed. This accumulation of metabolites in the G1-phase cells has been termed a "metabolic budget system" because it senses not only the actual nutrient levels, but also the supply over a period of time. Monoclonal antibodies specific for the dimeric form of pyruvate kinase type M2 can be used for the immunohistological detection of tumor cells. The amount of the dimeric form in tumor cells closely correlates with the degree of malignancy and can be used for a nonspecific detection of tumors based on assays performed with patient's plasma.

Immunohistology and special staining of plastic sections allow diagnosis and differentiation of subtypes of glomerulonephritis in dogs. Frequency and clinical importance of these forms of glomerulonephritis vary significantly. In cats, glomerulonephritis occurs frequently in FIV-positive cats but is rare in animals suffering from persistent FeLV infection or FIP.

86 benign and malignant tumours were investigated histologically and immunohistologically. Staining intensity was measured by scanning-photometry. The computed optical density was digitalized and evaluated with an image analysis system. The results indicate a significantly higher amount of M2-PK in malignant tumours. In the adenocarcinomas of the mammary gland, the content of the M2-PK increased parallel with malignancy (p less than 0.01; r = 0.743). The M2-PK can serve as an indicator of the grade of malignancy in mammary tumours of the rat.

SIR, — We would like to report a case of lethal bluetongue virus infection in an alpaca in Germany. The affected animal was a five-year-old female alpaca, born and raised in a flock in a low mountain range area in central Germany. This area was affected by the bluetongue virus outbreak in Germany

SIR, – Feline infectious peritonitis (FIP) is caused by feline coronavirus (FCoV). It is a well known and widely distributed coronavirus- induced systemic disease in cats and non-domestic felids ([O’Reilly and others 1979][1], [Kennedy and others 2002][2]). The disease is characterised by

Influenza virus A/turkey/Ontario/7732/66 (H 5 N 9), which is highly pathogenic to chickens, is nonpathogenic to quails. After intratracheal or intramuscular inoculation of quails, virus replication was limited to the respiratory tract, genital organs, and pancreas. However, aggravation of the pathogenicity was achieved through adaptation only by several passages of lung homogenates in quails. The adapted virus caused a fatal generalized infection in quails as well as in chickens. The pathogenic change of the virus could not be explained by a change in the proteolytic cleavability of the hemagglutinin, because no difference was found in the cleavability between the original and the adapted viruses. The adapted virus formed larger plaques and grew a little faster than the original one in both chicken embryo and quail embryo cells. The faster multiplication of the adapted virus at the site of infection might be the reason for its change in pathogenicity. The original virus could circulate among quails by a direct contact transmission without causing disease. The shed virus, however, caused a fatal infection in chickens when they were kept in contact with the infected quails. The epidemiological significance of this observation is discussed.

Several strains of Staphylococcus aureus have been found to secrete proteases that activate infectivity of influenza virus by proteolytic cleavage of the hemagglutinin. The enzymes of the bacterial strains Wood 46 and M 86/86 have been characterized in some detail and were found to be serine proteases. In their substrate specificities and inhibitor sensitivities they proved to be similar to, but not identical with trypsin and plasmin. The hemagglutinin of an individual virus strain could be cleaved by the proteases of some but not all staphylococcal strains, and a given enzyme could cleave only some but not all hemagglutinins analyzed. When mice were coinfected intranasally with the appropriate strains of influenza virus and S. aureus, the hemagglutinin was readily activated allowing multiple cycles of virus replication in the lung. Under these conditions, the animals came down with a fatal disease exhibiting extended lesions in the lung tissue. In contrast, after infection with virus or bacteria alone, there were no significant pathological changes. When the staphylococcal strain did not contain a protease that was able to activate the hemagglutinin of the coinfecting virus strain, the animals did not exhibit disease. These observations demonstrate that coinfecting bacteria can play an essential role in the development of influenza pneumonia by providing a protease suitable for cleavage activation of the hemagglutinin.

Cellular uptake of fowl plague virus occurs 10–30 minutes after inoculation of chick embryo cells. The penetration of the virions is by pinocytosis (viropexis); fusion with the cellular membrane has not been observed. After pinocytosis the virions become gradually disintegrated. Budding of newly formed virions from the cellular membrane starts 3 hours post inoculation (p. i.) and reaches its maximum 8 hours p. i. At the same time budding takes place into electron microscopically empty and autophagic vacuoles. Eight hours p. i. about 3 per cent of the infected cells show budding of virions from the surface and into cytoplasmic vacuoles. Labelling of the cellular membrane with ruthenium red demonstrated that these cytoplasmic vacuoles are not simple cross-sections of invaginations of the cellular membrane. Cluster-like structures were found at 6 hours p. i. in the nuclei of infected cells; however, the suggestion that the clusters develop from nucleoli could not be confirmed.

Cats presented for post-mortem examination were examined by immune histological techniques for the presence of persistent FeLV infections. Persistent FeLV infection was found to be the most common fatal infectious disease currently occurring in cats. It was detected in 16 per cent of the cats referred for post-mortem examination, whereas a proportion of 3 per cent may be regarded as likely in the normal population.

Seventeen renal cell carcinomas (RCC) were classified histologically and investigated for their expression of L- and M2-pyruvate kinase (PK) immunohistochemically. Using monoclonal antibodies we were able to demonstrate L-PK within 15 RCC and two metastases (in thyroid gland and bone) after fixation with aceton and paraffin embedding. In normal renal tissue the enzyme was localized within proximal tubules selectively. No enzyme reaction of L-PK could be demonstrated in renal oncocytoma, thyroid carcinoma, and in carcinomas of renal pelvis and lung. In contrast to this the M2-PK was detectable in all tumors and metastases investigated in this study. The results presented in this paper are able to show that (1) RCC derive from the proximal renal tubules, but not the renal oncocytoma, (2) the detection of L-PK may be helpful for identification of metastases of RCC even if they are undifferentiated and (3) there is an enzyme shift from L-PK to M2-PK within tumor cells of RCC resulting in alteration of glucose utilization from energy supply to syntheses of substrates essential for tumor cells.

Summary Lectins of different specificities do not interfere with the maturation of myxoviruses; their inhibitory effect on virus replication is mainly due to prevention of the detachment of infectious virus particles from the host cell. In chick embryo fibroblasts infected with an influenza virus and treated with concanavalin A, budding occurs into intracytoplasmic vacuoles, but this phenomenon is not observed with a parainfluenza virus and with different cells.

Feline leukemia virus (FeLV) infection was diagnosed immunohistologically on paraffin-embedded tissues obtained from 1,095 necropsied cats. Significant association of FeLV infection was demonstrated by chi 2 and Fisher's tests with various conditions and diseases (ie, anemia, tumors of the leukemia/lymphoma complex, feline infectious peritonitis, bacterial infections, emaciation, FeLV-associated enteritis, lymphatic hyperplasia, and hemorrhage). Unexpected findings associated with FeLV infection were icterus, several types of hepatitis, and liver degeneration. A negative association with FeLV infection was found for most parasitic and viral infections, including feline panleukopenia. Neither positive nor negative associations were established for FeLV infection and most forms of nephritis, including severe glomerulonephritis. Feline leukemia virus-infected cats were significantly (Kruskal-Wallis test) older than were FeLV-negative cats with the same nonneoplastic FeLV-associated diseases.

A Japanese quail embryo cell line transformed by avian retrovirus, designated QERC-31F, was further characterized in virological and cytological aspects. Infectious virus produced by this cell line was found to belong to subgroup A. The virus failed to transform quail embryo cells, whereas it induced erythroblastosis by injection into neonatal quails. Injection of QERC-31F cells into neonatal quails resulted in the induction of solid tumors which morphologically diagnosed as undifferentiated sarcoma. Mitosis of pro-erythrocytic cells with also detected in the peripheral blood of the tumor bearing animals. Antiserum to chicken erythrocyte histone V fraction which was also shown to react specifically with the nucleus of quail erythrocytes stained the nucleus of QERC-31F cells. These results suggested that this cell line maintains characteristics of the erythroblast and possibly produces avian erythroblastosis virus as well as helper virus of subgroup A.

Pyruvatkinase (PK) ist eines der drei Schlusselenzyme der Glykolysekette. Von ihr sind drei Isoenzyme bekannt: Typ M1 findet sich in Muskulatur und Gehirn, Typ L in Leber und Nierenrinde und Typ M2 in fast allen ubrigen Geweben. Ein besonders hoher Gehalt an Pyruvatkinase Typ M2 tritt in der Lunge und in den meisten Tumoren auf.

The combined presence of WSN gene segments 6 (neuraminidase), 7 (M1 and M2), and 8 (NS1 and NS2) in reassortants of WSN with A/Aichi/2/68 (H3N2) has been found by others to be necessary for full expression of neurovirulence in mice. We are examining the expression of the analogous three gene segments in brains of mice after intracerebral infection with non-neuroadapted strains A/WS/33 (WS) (from which WSN was derived) and A/PR/8/34 (PR8). Our aim is to determine possible mechanisms by which one or more of the five gene products may restrict replication of these strains in mouse brain cells to a single cycle, yielding noninfectious hemagglutinating particles (incomplete growth cycle). We found that minority subsets of such particles did produce plaques, provided they were activated by trypsin (analogous to other abortive systems producing virions with uncleaved HA), a step obviated for some WSN virions by indirect promotion of hemagglutinin cleavage by the neuraminidase of that strain. The percentage of such potentially infectious virions, relative to total hemagglutinating particles, was significantly lower in WS- or PR8-infected than in WSN-infected brains, suggesting possible defects in synthesis or function of M1 protein in the former. Cells in immunostained sections and appropriate bands in Western blots (immunoblots) of viral proteins electrophoretically separated from lysates of PR8-infected brains reacted with antibody to nucleoprotein but not to M1 protein. Either method revealed the presence of both proteins in WSN-infected brains. In contrast, Western blot analyses of particles concentrated from PR8-, WS-, or WSN-infected brains by hemadsorption, elution, and pelleting did reveal NP and M1 bands with comparable relative peroxidase-antiperoxidase staining intensities. The findings suggest that availability of M1 protein is a factor influencing the extent or rate of assembly of potentially infectious (i.e., trypsin-activated) progeny virions in mouse brains and that in this respect the two non-neurovirulent strains differ from WSN quantitatively rather than qualitatively.

The kinetic and immunological properties of purified, homogeneous pyruvate kinase type M2 from chicken lung and tumors, including that of Rous sarcoma virus transformed chicken fibroblasts, have been compared. The type M2 enzymes from both lung and tumors have immunologically distinct structures. The enzyme isolated from tumors is characterized by a low affinity for phosphoenol pyruvate, pronounced L-serine activation and a strong inhibition by L-alanine, L-proline and several other amino acids. The chicken lung enzyme is only slightly affected by serine. The cellular amino acid concentration is in such a range that the tumor enzyme is strongly inhibited whereas the lung enzyme is only partially inhibited. The characteristics of the tumor enzyme allow the optimal adaptation to lactic acid and production of energy from glucose or amino acids dependent on substrate and oxygen supply.

Coinfection of a cell culture with a human and avian influenza A virus had yielded a recombinant virus with high neurovirulence for mice. This study reports on the comparative pathogenesis of central nervous system infection in mice between the parental human and the recombinant virus using the immunohistologic peroxidase-antiperoxidase method and virus assay of tissue suspensions. The human virus replicated poorly in mice and did not replicate in the brain even after intracerebral inoculation. In contrast, the recombinant virus replicated to high titer in the lung and brain with resulting viremia after inoculation of young mice by the intracerebral, intraperitoneal, or intranasal routes. Different populations of cells in the brain became infected after inoculation by each of the three routes: choroid plexus, and ependymal and subependymal cells after intracerebral inoculation; cells in perivenous areas, neurons in the olfactory bulbs and trigeminal ganglia and nuclear groups in the brainstem and midbrain after intranasal inoculation. Intraperitoneal inoculation resulted almost exclusively in the perivenous spread of the virus. The intranasal inoculation suggested that virus entry into the brain both by spread along nerve cell processes from the nasal mucosa to the brain and trigeminal ganglia and subsequent perivenous spread after viremia developed following virus replication in the lung. To dissect these two mechanisms we inoculated neonatal mice that had acquired high levels of serum antibody by nursing from actively immunized mothers. Intraperitoneal inoculation of these mice failed to cause infection, whereas intranasal inoculation resulted in the same pattern of cellular spread through the olfactory and trigeminal pathways as noted previously. This proved that this recombinant influenza virus could invade the central nervous system after infection via a natural route of infection. This highly neuroinvasive agent provides one example of the extent of virulence which can be acquired by recombination of apathogenic influenza viruses and raises a note of caution for adequate control of those agents generated in the laboratory.

We have recently reported on the compatibility of opiates and local anaesthetics with cerebrospinal fluid (CSF) [3, 11]. These studies included in vitro as well as in vivo examinations, which were performed in order to evaluate the reliability and usefulness of drugs for spinal analgesia. The introduction of techniques for spinal treatment of spasticity requires additional investigations on CSF-compatibility of substances, which may be candidates for spinal antispastic therapy. Therefore we tested different drugs, which after systemic administration are effective against spasticity, such as baclofen, memantine-HCl, tizanidine and benzodiazepines. Additional examinations included commercially available preparations of calcium and magnesium and calcium blocking agents. It is well known that neuromuscular activity is related to an adequate balance of calcium and magnesium concentrations in CSF and that magnesium deficiency leads to hyperexcitability in several species including man.

Two preparations of L'/R-type pyruvate kinase from human erythrocytes characterized by SDS-PAGE were used for immunization of BALB/c mice. Their spleen cells were fused with mouse myeloma cells by polyethylene glycol according to standard techniques. Supernatants of hybridomas resulting from two separate experiments were assayed by ELISA and further characterized by immunoblotting. Using those monoclonal antibodies reacting with L'/R-PK in immunoblotting, a major band of 62 KDa MW was recognized in both preparations employed for immunization. Additionally, four smaller bands were detected. Furthermore, the monoclonal antibodies also detected a single band of 62 KDa MW in a highly purified L-PK prepared from human liver. In contrast, they showed no reaction with muscle and brain tissues containing M1-type PK. However, they reacted strongly with a single band of approximately 62 KDa in liver and kidney homogenates which is in line with immunocytochemical studies showing immunoreactive material in hepatocytes and proximal tubules of the kidney.