Toxoplasma gondii, Herpesviridae and long-term risk of transition to first-episode psychosis in an ultra high-risk sample.

BACKGROUND: Ultra high-risk (UHR) criteria were introduced to identify people at imminent risk of developing psychosis. To improve prognostic accuracy, additional clinical and biological risk factors have been researched. Associations between psychotic disorders and infections with Toxoplasma gondii and Herpesviridae have been found. It is unknown if exposure to those pathogens increases the risk of transition to psychosis in UHR cohorts. METHODS: We conducted a long-term follow-up of 96 people meeting UHR criteria, previously seen at the Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service in Melbourne, Australia. Transition to psychosis was assessed using the Comprehensive Assessment of the At-Risk Mental State (CAARMS) and state public mental health records. The relationship between IgG antibodies to Herpesviridae (HSV-1, HSV-2, CMV, EBV, VZV) and Toxoplasma gondii and risk for transition was examined with Cox regression models. RESULTS: Mean follow-up duration was 6.46 (±3.65) years. Participants who transitioned to psychosis (n = 14) had significantly higher antibody titers for Toxoplasma gondii compared to those who did not develop psychosis (p = 0.03). After adjusting for age, gender and year of baseline assessment, seropositivity for Toxoplasma gondii was associated with a 3.6-fold increase in transition hazard in multivariate Cox regression models (HR = 3.6; p = 0.036). No significant association was found between serostatus for Herpesviridae and risk of transition. CONCLUSIONS: Exposure to Toxoplasma gondii may contribute to the manifestation of positive psychotic symptoms and increase the risk of transitioning to psychosis in UHR individuals.

Fatal cowpox virus infection in captive banded mongooses (Mungos mungo).

Cowpox virus infections have been described in various domestic and exotic animal species. This report is the first on an outbreak of fatal generalized cowpox virus infection among captive banded mongooses (Mungos mungo, suborder Feliformia). All animals of a colony of 8 mongooses showed a fulminant course of disease. The whole population died (n=7) or was euthanized (n=1) within 11 days. Postmortem examinations were performed on 4 animals. All animals showed extensive necrotizing inflammation of retropharyngeal lymph nodes, typical poxviral skin lesions, and multiple necrotic foci in liver and spleen. Three animals exhibited an ulcerating stomatitis. Pulmonary lesions, a common feature of fatal cowpox virus infections in other feliform species, were not obvious. Histopathologically, characteristic cytoplasmic inclusion bodies were detected in all affected organs but the spleen. Based on transmission electron microscopy and cell culture, Orthopoxvirus was identified as the etiology. The virus was further characterized by polymerase chain reaction and sequence analysis, identifying it as cowpox virus. A survey in the habitat suggests wild brown rats (Rattus norvegicus) as the most likely source of infection.

Extraventricular neurocytoma of the spinal cord in a dog.

Central neurocytoma is a rare, prognostically favorable neuronal tumor of the human central nervous system, typically located intraventricularly near the foramen of Monro. Extraventricular cerebral neurocytomas and spinal tumors have also been reported. To date, however, neurocytomas have not been documented in domestic animal species. In this report, we describe a spinal cord tumor in a dog. The microscopic examination revealed tumor cells forming loosely packed clusters in some areas and palisades in other areas. In addition, they showed fine fibrillary neuropil-like areas of different sizes, sometimes resembling the "rosettes" of pineocytomas, as well as ependymoma-like perivascular pseudorosettes. The tumor cells had scant eosinophilic cytoplasm, with perinuclear halos, closely resembling the appearance of oligodendroglioma. Immunohistochemical staining showed expression of synaptophysin and neuron-specific enolase by tumor cells and pronounced in fibrillary areas. On the basis of histomorphology and immunohistochemical reactivity, the present tumor was diagnosed as extraventricular neurocytoma.

Gongylonema pulchrum infection and esophageal squamous cell carcinoma in a vari (Lemur macaco variegata; Kehr 1792).

This report describes the morphologic and histologic features of a case of esophageal Gongylonema pulchrum infection and esophageal squamous cell carcinoma in a 17-yr-old, female vari (Lemur macaco variegates). The lemur had lived in a German zoo and had a clinical history of dyspnea, vomiting, and anorexia. At necropsy, a whitish, soft, nodular, centrally necrotic mass was found in the caudal third of the esophagus. In addition, numerous intraepithelial nematodes (G. pulchrum) were observed in the entire esophagus. Results suggest a relation between infection with G. pulchrum and development of an esophageal squamous cell carcinoma.

Induction of apoptosis by canine natural killer cells.

Besides a secretory pathway of canine natural killer (NK) cells, which results in necrosis of the target cell, a second pathway was demonstrated, which results in apoptosis of the target cell. Comparing the Chromium Release Assay (CRA) and the Rose Bengal Assay (RBA) for quantification of in vitro canine NK cell activity, a constant 10% higher NK cell activity was found in the RBA compared with the CRA. To find out the mechanism responsible for the different results of both tests, morphological studies of in vitro canine NK cell activity against epithelial and mesenchymal allogenic target cell lines were performed. Most target cells were undergoing necrosis as a result of NK cell killing, which was evidenced by transmission electron microscopy. However, besides necrotic target cells, shrunken target cells with dense cytoplasm, fragmented nuclei and disruption into membrane-bound bodies were detected, which are known as signs of apoptosis. Additionally, using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method, 13-23% of target cells presented a positive staining, indicative of apoptosis. These findings give evidence for the ability of canine NK cells to kill their target cells via two different pathways, which results either in apoptosis or necrosis.

Influence of different tumour types on natural cytotoxicity (NK cell activity) and mitogen-induced lymphocyte proliferation in isolated blood lymphocytes from 110 dogs with tumours.

The cell-mediated immune response of blood lymphocytes from 110 untreated dogs with different tumours was evaluated. The influence of different tumour types on the cellular immune system was examined by assessing the percentage of isolated large granular lymphocytes (LGL), in vitro natural cytotoxicity and mitogen-induced lymphocyte proliferation. Although the overall natural cytotoxicity of dogs with different tumours was decreased, the overall difference from control values was not statistically significant. However, mitogen-induced lymphocyte proliferation was significantly depressed in dogs with tumours in comparison with the controls. Dogs with mammary carcinomas showed significantly lower natural cytotoxicity than controls and dogs with myeloid neoplasms showed significantly lower mitogen-induced lymphocyte proliferation. Abnormalities exist not only in natural cytotoxicity but also in mitogen-induced lymphocyte proliferation. For the dog, this is the first study to assess the influence of different tumours using a combined evaluation of natural cytotoxicity and mitogen-induced lymphocyte proliferation in such a large number of animals.

Investigation of several selected adjuvants regarding their efficacy and side effects for the production of a vaccine for parakeets to prevent a disease caused by a paramyxovirus type 3.

The infection with paramyxovirus type 3 (PMV-3) of parakeets can lead to severe illness in small psittacines (Neophema spp. and other parakeets) as well as in passerines (finches). The disease is characterized by acute or chronical pancreatitis and central nervous symptoms, such as torticollis as well as walking in circles and by high mortality rates in the affected flocks. As there is no licensed vaccine for psittacines available to prevent this disease. The aim of the following study was to find a suitable vaccine formulation for parakeets with inactivated PMV-3 and a well-tolerated and effective adjuvant. Seven adjuvants have been examined in ovo and in vivo regarding their efficacy and side effects. In these investigations, the classical Freund's complete Adjuvant (FCA) and Freund's incomplete Adjuvant (FICA) and Alhydrogel, but also the more recent developments TiterMax Gold, Specol, Gerbu Adjuvant 100, and Diluvac Forte have been used. Regarding its efficacy and side effects, the vaccine formulation "PMV-3/Specol" has been evaluated positively and can be recommended for the production of a PMV-3 vaccine for parakeets.

Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B.

BACKGROUND: Activation of hepatic stellate cells is the earliest step in fibrogenesis. Alpha-smooth muscle actin (alpha-SMA), expressed by activated hepatic stellate cells, and C-terminal procollagen alpha1(III) propeptide (PIIICP) are early markers of fibrogenesis and should precede fibrosis. AIM: Determine if suppression of hepatitis B virus replication with lamivudine would decrease fibrogenesis as measured by immunohistochemical markers. METHODS: Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine (n=47) or placebo (n=33) were studied. alpha-SMA and PIIICP were detected in paraffin-embedded tissue by immunohistochemistry and quantified in a blinded manner by video imaging analysis. RESULTS: Liver biopsies from patients treated with lamivudine showed a significant decrease in alpha-SMA expression (1.06+/-0.23 vs. 0.58+/-0.11, pre vs. post, P<0.05). Placebo recipients had increased levels of alpha-SMA (0.82+/-0.14 vs. 1.32+/-0.21, P<0.05). PIIICP was similarly decreased after lamivudine. Among subjects whose Histologic Activity Index fibrosis score was unchanged or worsened, the mean change in alpha-SMA expression was significantly decreased in the lamivudine group compared with placebo. CONCLUSIONS: Lamivudine decreased markers of hepatic stellate cell activation and collagen synthesis. Immunohistochemical techniques are sensitive for assessing fibrogenesis and will be useful in trials of antiviral and antifibrotic agents.

An immunoassay for canine pancreatic elastase 1 as an indicator for exocrine pancreatic insufficiency in dogs.

The detection of pancreatic elastase 1 in stool samples has become the noninvasive gold standard for the diagnosis of pancreatic insufficiency in humans. Accordingly, the development of a sandwich-ELISA specific for canine pancreatic elastase 1, based on monoclonal antibodies, is presented here. The test has a detection range of 4-240 microg canine pancreatic elastase l/g feces. The intraassay coefficient of variation is 7.4%, and the interassay coefficient of variation is 7.7%. Spiking experiments show that canine elastase 1 is quantitatively detectable in fecal samples. Interestingly, the range of the elastase 1 concentration in canine feces within several days is higher as compared with humans. As the proposed cutoff of 10 microg/g is below this variation range in 96.1% of the tested samples, the effect on the test specificity is negligible. Because the test detects neither human nor bovine and porcine elastase 1, pancreatic function can be monitored without interrupting an enzyme replacement therapy.

Postoperative radiotherapy of NSCLC--outcome after 3-D treatment planning.

AIM: To evaluate the benefit of postoperative radiotherapy depending on lymph node involvement in non-small-cell lung cancer (NSCLC). PATIENTS AND METHOD: Retrospective analysis of patients with NSCLC, who have been treated at the University of Giessen between 1986 and 1996 by surgery (n = 437) or surgery and 3-D planned postoperative radiotherapy with 50-60 Gy (n = 115). Evaluation of survival rates and risk of death depending on postoperative radiotherapy taking into account N-category, tumor stage, completeness of resection and performance status. RESULTS: With individually 3-D planned postoperative radiotherapy there was a lower risk of death in all stages with lymph node metastases. The relative risks of death and the 95% CI were in pN1 0.64 (0.39-1.03), in pN2 0.31 (0.18-0.56) and in pN3 0.25 (0.10-0.64). CONCLUSION: Our results suggest that the risk of death in NSCLC with lymph node involvement can be reduced by individually 3-D planned postoperative radiotherapy.

Lymphocyte subpopulations in the caecum mucosa of rats after infections with Eimeria separata: early responses in naive and immune animals to primary and challenge infections.

This study aimed to characterise the local (intestinal) immune response of rats after primary and challenge infections with Eimeria separata. Naive rats and rats which had been immunised by two moderate infections were exposed to a heavy infection with 100000 oocysts per animal. Necropsies were performed 0, 24 and 48 h after infection and lymphocyte subpopulations were microscopically quantified in the caecum mucosa after marking by immunohistological techniques. There was no difference between naive and immune rats concerning the number of CD45R(+) (B) cells, whereas significantly more CD3(+) (T) cells were found in the caecum wall of the immune rats. CD4(+) T cells predominated in animals after primary infection, whereas CD8(+) T cells represented the major T-cell subset in challenged rats. The proportion of TCRgammadelta(+) T cells did not differ in the mucosa between the groups examined, whereas challenged rats showed significantly increased numbers of TCRalphabeta(+) T cells in the caecum wall when compared with animals after a primary infection. Thus, CD4(+) T cells may be particularly involved in the immune response to a primary infection of rats with E. separata whereas immunity to a challenge infection seems to be mediated predominantly by CD8(+) and TCRalphabeta(+) T cells.

Immunity in rats against Eimeria separata: oocyst excretion, effects on endogenous stages and local tissue response after primary and challenge infections.

The aim of the study was the characterization of the local immune response of Lewis rats to Eimeria separata, a caecum-dwelling coccidium. Rats infected twice at 10-day intervals with 5,000 oocysts developed a high degree of immunity to a heavy challenge with 100,000 oocysts, reducing the oocyst production by > 98% when compared with naive recipients. Histopathological investigations performed over a period of 0-72 h post-infection (pi) showed that 1st generation schizonts, developed within 24 h pi, represented the major target stages, although later stages were also affected. Preinfected animals showed significantly more lymphocytes in the caecum wall than naive animals. An increase in lymphocyte numbers after challenge observed in both groups was enhanced in challenged animals up to 36 h pi. The number of lamina propria lymphocytes predominantly was increased after primary infection whereas in repeatedly infected animals the increase also concerned intraepithelial lymphocytes. In addition, the numbers of plasma cells were enhanced in the caecum wall of immune animals. Macrophage infiltration in the caecum wall followed a similar time course in both groups up to 36 h pi. A subsequent further rise up to 48 h pi was enhanced in naive rats. Tissue infiltrations with eosinophils and mast cells were observed predominantly in the repeatedly infected rats. No obvious changes occurred with intestinal neutrophils and goblet cells. In conclusion, caecum tissue alterations suggest an early local immune response, which is related to development and maturation of the parasite.

A teratoma in a Muscovy duck ( Cairina moschata ).

Radiographic and ultrasonic examination of a sick, 5-month-old female domestic Muscovy duck revealed a large ill-defined mass in the abdominal cavity. Gross and histopathological examination characterized the mass as an intra-abdominal teratoma based on the presence of a variety of different epithelial and mesenchymal tissues, including squamous epithelium, tubular structures, feather follicles, cartilage and small amounts of osseous tissues.

Somatic isoform of angiotensin I-converting enzyme in the pathology of testicular germ cell tumors.

Retained fetal expression of angiotensin I-converting enzyme (ACE, CD143) has recently been shown in intratubular germ cell neoplasms (IGCN) and invasive germ cell tumors (GCT), suggesting the somatic isoform (sACE) as a characteristic component of neoplastic germ cells. We analyzed the distribution of sACE in 159 testicular GCT, including 87 IGCN. sACE protein was determined by immunohistochemistry (MAb CG2) on routinely formalin-fixed and paraffin-embedded tissue sections, supplemented by mRNA expression analysis using in situ hybridization. These data were compared with those obtained by germ cell/placental alkaline phosphatases (PIAP; MAbs PL8-F6 and 8A9) employing an uniform score system for the evaluation of immunoreactivity (IRS; possible values from 0 to 12). Expression of sACE and PIAP was found in all 87 analyzed IGCN (IRS > 4, median IRS of 12). Heterogeneous staining patterns were not related to the type of adjacent GCT but correlated with low expression in adjacent seminomas (P =.032 for sACE; P =.005 for PIAP). Both sACE and PIAP often showed a decreased and more heterogeneous but still moderate expression in 91 classic seminomas (median IRS of 8) and were completely absent in tumor cells of spermatocytic seminomas. Despite all similarities, we found sACE and PIAP differently regulated during GCT progression. This was documented by a well-preserved expression of either sACE or PIAP or both in all classic seminomas, low PIAP immunoreactivity in metastasis of seminomas, and completely diverging expression patterns in nonseminomatous GCT. Our findings underline the close molecular relationship between IGCN and seminoma, and suggest sACE as an appropriate marker for seminomatous differentiated tumors. HUM PATHOL 31:1466-1476.

[CD143 expression in testicular germ cell tumors]. / CD143-Expression in testikulären Keimzelltumoren.

CD143 (angiotensin I-converting enzyme) occurs in two isoforms: a testicular form (tCD143) expressed during spermatogenesis, and a somatic form (sCD143) generally found in certain other cell types. To study these isoforms in normal and neoplastic germ cells of humans, we analyzed a broad collective of different testicular germ cell tumors (GCTs) of adults, adjacent intratubular germ cell neoplasms (IGCNs), and testicular tissues representing the regular germ cell development. Different techniques were employed on fresh frozen and formalin-fixed, paraffin-embedded tissues: CD143-mRNAs were analyzed by RT-PCR on selected cells after UV-laser-assisted cell picking and by in-situ hybridization using cRNA probes; the proteins were analyzed by semi-quantitative immunohistochemistry using monoclonal antibodies to CD143, and to PLAP/GCAP as controls. In contrast to normal germ cells bearing only tCD143 during spermiogenesis, both mRNA and protein of sCD143 were detected in neoplastic cells of all IGCNs and in the majority of seminomas. sCD143 expression also was found during testicular development, but was differently regulated in fetal germ cells and in GCTs compared with PLAP/GCAP. Thus, our findings (i) demonstrate profound changes in the expression of both CD143 isoforms during regular germ cell development and maturation, (ii) suspect sCD143 being involved in the regulation of germinal stem cell proliferation, (iii) are in agreement with the concept of an 'embryonic state' of neoplastic germ cells, (iv) indicate a close molecular relationship between IGCN and seminoma and, finally, (v) suggest sCD143 as an appropriate marker in the diagnosis of seminomas in addition to PIAP/GCAP.

Evaluation of canine lymphocyte proliferation: comparison of three different colorimetric methods with the 3H-thymidine incorporation assay.

To evaluate canine lymphocyte stimulation the radioactive thymidine incorporation assay is still the method of choice. In order to find a suitable non-radioactive alternative to the standard 3H-thymidine incorporation assay, proliferation of canine peripheral blood lymphocytes (PBL) was measured with three different colorimetric assays, using the two tetrazolium salts MTT and XTT and 5-bromo-deoxyuridine (BrdU). Isolated canine PBL were stimulated with two different mitogens, Concanavalin A (Con A) and Phytohemagglutinin (PHA), using different culture conditions. Applying statistical analysis we found that BrdU and MTT showed a high correlation to the 3H-thymidine incorporation assay, although the BrdU assay proved to be more sensitive than the MTT assay. No significant correlation between the XTT assay and the radioactive method was demonstrated. Consequently, the BrdU assay is the most suitable alternative to the radioactive method.

[Cystic testicular anomaly with subsequent stenosis of the small intestine in an emerald tree boa (Corallus caninus L., 1758)]. / Zystische Hodenmissbildung mit nachfolgender Dünndarmstenose bei einem Grünen Hundskopfschlinger (Corallus caninus L., 1758).

A case report with emphasis on diagnostic procedures and differential diagnoses is given. The etiology is discussed in comparison to similar malformations in mammals and other reptiles. The literature is reviewed with emphasis on differential diagnostic aspects.

Primary cancer of the fallopian tube. Treatment and results of 37 cases.

OBJECTIVE: A collective of 37 patients with primary cancer of the fallopian tube treated at the Gynecologic Clinic of the Justus Liebig University of Giessen, between 1976 and 1995 was retrospectively evaluated for stage, histo-pathology, treatment and results. PATIENTS: Median age was 61.5 years, FIGO stages: I 17 (45.9%), II 7 (18.9%,. III 12 (32.4%), and IV 1 (2.7%). Histopathology: adenocarcinoma 45.9%, papillary adenocarcinoma 27%, solid carcinoma 8.1%, undifferentiated carcinoma 5.4%, and others 13.6%. TREATMENT: 24 patients (64.9%) underwent complete bilateral salpingo-oophorectomy and hysterectomy (BSOH); 13 (35.1%) had incomplete surgery. POSTOPERATIVE TREATMENT: 31 patients (83.8%) had chemotherapy (since 1982 with platinum), 28 (75.7%) intraperitoneal radionuclides, 23 (62.2%) percutaneous irradiation, and 6 (16.2%) additional vaginal brachytherapy. RESULTS: The cumulative survival rates were 40% for the total of 37 patients, stage I 68%, stage II 29%, stage III 10%, stage IV 0%. From 1976 to 1985 the cumulative survival rate was 25%, from 1986 to 1995, 54%. Stage was a significant prognostic factor (p = 0.0001), surgery, age, chemotherapy and irradiation were not. Severe complications occurred in 7 patients (18.9%): 4 fistulas, 1 myelosuppression, 1 ileus, 1 peritonitis. CONCLUSION: Due to the long period of time and alterations in the mode of treatment the benefit of single treatment modalities could not be evaluated, but prognosis-dependent multimodality treatment (radical surgery, irradiation, platinum-containing chemotherapy) has resulted in higher 5-year survival rates for the last decade.