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Byline: S. Chatterjee, J. Perignon, E. Van Marck, P. Druilhe Immunization against the pre-erythrocytic stages of malaria has attracted considerable efforts, since it induces a strong, sterile protection in humans [...]

Byline: Shyama. Chatterjee, E. Van Marck The human prion disease hypothesis is based on the authors' declaration that the large-scale import by UK of crushed/whole bones and carcass parts containing [...]

The article discusses the need for secondary school principals to adopt culturally proficient leadership to resolve the challenges brought by COVID-19 and improve academic achievement, particularly for African Americans and other minority students. Also cited are the high referral rate of African American male students to special education, and how principals can establish an engaging environment for African American male students like launching wellness calls, and online mentoring group.

Recently a new panel of monoclonal antibodies was developed against soluble egg antigens in the hatching fluid of Schistosoma mansoni. These antibodies have been used to develop an improved ELISA for the detection of circulating soluble egg antigens in serum and urine that would have a higher sensitivity in the immunodiagnosis of S. mansoniinfections. Although these antibodies showed no improvement in the immunodiagnosis of S. mansoniinfections compared with egg antigen-based ELISAs already described (Nourel Din et al.,1994a), they may have a potential role in the identification of S. haematobiuminfections. This study has looked into the immunolocalisation of S. haematobiumegg antigens in both the parasite and the host as recognised by four newly developed monoclonal antibodies (290-2D9-A, 290-2E6-A, 290-2H12-A and 290-4A8-A) and two already, described antibodies (114-5B1-A and 114-4D12-A). The antibodies 114-5B1-A and 114-4D12-A appeared to have in S. haematobiumeggs a similar staining pattern when compared to S. mansonieggs. The antibodies prepared against the hatching fluid showed a characteristic signal, especially 290-2E6-A. These antibodies recognised a component originating from the lateral glands of the miracidium. In the host a similar immunohistochemical tissue localisation pattern (mainly phagocytising reticulo-endothelial cells) was seen as previously described for S. imansoniinfected hamsters.

This paper presents the results of a study aimed at identifying the immunopathological and morphometrical characteristics of liver granulomas induced by the parasite Schistosoma haematobium. The OF1 mouse is a susceptible host for experimental infection with the Egyptian NAMRU-3 strain of S. haematobium. Formation of liver granulomas started after 13-14 weeks of infection. These hepatic granulomas reached a maximum volume after 20 weeks of infection (MGV: 1.82 +/- 0.15 x 107μm3) and regressed thereafter (1.55 +/- 0.16 x 107μm3after 24 weeks). Strong cellular upregulation of the adhesion molecules ICAM-1, LFA-1, syndecan-1, VLA-4, but not VLA-6 is seen, both in acute and chronic granulomas. Finally, pathological differences exist between hepatic S. mansoniand S. haematobiumgranulomas particularly at the level of extracellular matrix deposition. S. haematobiuminduced peri-ovular deposition of mainly fibronectin and to a lesser extent type I and IV collagen.

The aim of the study was to compare the angiogenic status, potential qualitative differences in microvessels and carbonic anhydrase IX expression in bone-marrow (BM) metastases and different haematological tumours at time of diagnosis. The microvessel density (MVD), endothelial-cell proliferation (ECP) and carbonic anhydrase IX (CA IX) immunoreactivity were determined on 210 trephine biopsies from 57 patients with multiple myeloma (MM), 13 with acute myeloid leukaemia (AML), 48 with chronic myeloproliferative syndrome (CMPS), 26 with chronic lymphocytic leukaemia (CLL), 25 with epithelial BM metastases, 18 with monoclonal gammopathy of undetermined significance (MGUS) and from a control group composed of 23 patients without haematological neoplasm. There was an increased MVD and ECP in epithelial BM metastases, MM, AML, CMPS and in a part of CLL. While an ECP greater than 0 was detected in 72% of MM, 75% of CMPS and 92% of AML, it was invariably observed (100%) in the BM metastases. The absence of ECP together with a MVD comparable with the control group in our MGUS cases supports the view that MGUS is a pre-angiogenic condition. Qualitative differences in microvessels were associated with growth patterns in MM and CLL and were observed between the different entities of CMPS. In one-third of the epithelial BM metastases, there was a focal CA IX immunoreactivity, which was never observed in the haematological diseases.

The result of a Plasmodium sporozoite challenge is currently evaluated either by detecting the emergence or not of parasites in the blood, or by estimating the ‘prepatent period’, which is the time between sporozoite inoculation and the appearance of parasites in the blood. This type of measurement is relatively rough and has given way to another method of measuring sporozoite infectivity, which is to enumerate the exoerythrocytic forms (EEF) by microscopic examination of liver sections. Up until now, two different methods have been proposed to calculate and estimate the number of Plasmodium EEF forms in the livers of infected rodents, both of which are unfortunately biased to some extent. Here, we propose a different method of calculation, which more faithfully reflects the EEF number in the liver. This method is based on the calculated mean number of consecutive liver sections in which a schizont appears, and is host related.

In order to investigate whether the high bFGF serum levels encountered in cancer patients are derived from the tumour, we analysed serum bFGF levels in 18 untreated randomly selected patients with operable colorectal, cervical and ovarian cancer in the blood draining the tumour, i.e., in mesenteric and uterine veins, and compared these with arterial samples. No significantly elevated bFGF levels were found in the veins draining the tumours compared with arterial samples in our patient population. This suggests that, in contrast to what is generally presumed, serum bFGF levels might also be derived from other sources besides the tumour, e.g., platelets.

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Abstract.Between 1990 and 2000, 56 consecutive patients underwent lung resection for removal of metastatic disease. Mortality, disease-free interval, and overall survival were studied. Only patients with a complete follow-up were included and data were collected conform the protocol of the International Registry of Lung Metastases. The primary tumour in our series was an epithelial tumour in 25 patients (45%), sarcoma in 15 (27%), germ cell tumours in 11 (19%) and melanoma in 5. Operative mortality was 1.4% (1 out of 73 procedures). Germ cell tumours had the best survival (76% at 5 years), and melanoma the worst (0% at 5 years). Multivariate analysis showed that survival for patients who underwent 2 or more metastasectomies was surprisingly good with a 5-year survival rate of 46%. Survival was not related to disease-free interval, multiple lung metastases, or pneumonectomy. It is in accordance with some reports that a short disease-free interval, numerous lung metastases, or recurrence after the first metastasectomy should not preclude patients from operation.

The liver is a highly vascularized organ which frequently hosts metastases in patients with colorectal adenocarcinomas. The hypothesis of this study is that the hypoxic drive of angiogenesis might be minimal or absent in those growing liver metastases which are capable of preserving the stromal structure, including the numerous sinusoidal blood vessels. Representative paraffin sections of liver metastases from 26 patients with colorectal adenocarcinoma were investigated. Three different growth patterns were found. In the desmoplastic and in the pushing growth patterns (42% and 46% of all metastases, respectively), the architecture of the liver parenchyma was not preserved. In the replacement growth pattern (12% of all cases), the reticulin pattern of the liver parenchyma was conserved within the metastases at the tumour-liver parenchyma interface. The endothelial cells of the blood vessels near the interface in the metastases of the replacement type did not express CD34, nor were they surrounded by alpha-smooth muscle actin-positive mural cells. In the desmoplastic and in the pushing growth patterns, 23% and 52% of all blood vessels in this area were covered by pericytes. The fraction of proliferating endothelial cells was low in the metastases with a desmoplastic or a replacement growth pattern (about 3%), compared with metastases with a pushing growth pattern (11%). Tumour cell apoptosis was highest in the pushing-type metastases and was inversely correlated with microvessel density in liver metastases. The ratio of the proliferating tumour cell fraction and the proliferating endothelial cell fraction, roughly representing the degree of angiogenesis-dependent growth, was three- to four-fold higher in the replacement-type metastases compared with the other metastases. In summary, the present study has demonstrated that liver metastases are a heterogeneous group, with different growth patterns which predict the fraction of immature blood vessels, the fraction of proliferating endothelial cells, and the fraction of apoptotic tumour cells. The replacement growth pattern expands with minimal angiogenesis by co-opting the stroma with the sinusoidal blood vessels of the liver. Copyright © 2001 John Wiley & Sons, Ltd.

Adamantinoma of the long bones and Ewing's sarcoma are two malignant tumours between which, at first sight, there seems to be no morphological and clinical relationship. Both tumours, however, are known to express cytokeratins. Adamantinoma is a tumour of true epithelial nature, predominantly expressing cytokeratins 14 and 19. Ewing's sarcoma, believed to be from neuroectodermal origin, like other mesenchymal tumours, can aberrantly express cytokeratin 8 and 18. In the literature there are some reports of tumours showing clinical and/or morphological overlap between adamantinoma and Ewing's sarcoma, suggesting a possible relationship. These studies are mostly based on the epithelioid configuration of these lesions and their cytokeratin expression on immunohistochemistry. This raises the question of whether there is occasionally a morphological similarity between adamantinoma and Ewing's sarcoma, or whether there is a common genetic background. The Ewing's sarcoma/primitive peripheral neuroectodermal tumour (PNET) family is characterized in 90–95% of cases by a t(11; 22) and in 5–10% of cases by t(21; 22). In the few reports in the literature on cytogenetic investigations on adamantinoma, these translocations were never found using classical karyotyping. This study investigated the putative presence of t(11; 22) and t(21; 22) in 14 cases of adamantinoma by RT‐PCR. These translocations were not found in any of these cases. The results support the view that these tumours are genetically and clinically distinct, but may eventually show overlapping morphological and immunohistochemical features. Copyright © 2001 John Wiley & Sons, Ltd.

Oesophagostomiasis is an infrequently described and recognised parasitic infection in humans, caused byOesophagostomum bifurcum. Although the disease is most often found in the northern part of Togo and the neighbouring part of Ghana, sporadic cases have been described in other parts of Africa and in Asia and South America: Uganda, Ivory Coast, Sudan, Kenya, Ethiopia, Indonesia, Malaysia and Brazil. Infection probably occurs by way of the ingestion of L3 larvae. These larvae penetrate the intestinal wall, especially that of the colon. Some of these larvae develop into young adult worms and return to the bowel lumen. Other larvae, however, develop into immature worms, which fail to settle in the lumen, forming abscesses in the bowel wall and causing pathology. In the literature 105 human cases have been described, many originating in the northern regions of Ghana and Togo. The present study was performed to evaluate 13 new cases originating in the northern part of Ghana (7 female and 6 male patients, aged between 2 and 60 years). Histopathologically, the patients could be divided into two groups: the first group showed multinodular disease, while patients in the second group presented with a single, nodular mass. In the first group, abscesses were seen throughout the colonic wall. The mean size of the cavities was 4.3±0.7 mm. There was no relation between the size and the localisation in the colonic wall. Abscesses were significantly larger in male patients than in female patients. There was no correlation with age. In the second group, histopathological examination showed a cyst of variable wall thickness with very limited inflammation. These cysts represented older lesions, often encapsulated in the mesentery. In conclusion, in this study we present 13 new cases of human oesophagostomiasis. The abscess formation was found to be organ specific, independent of age, and gender-related, producing a more intense tissue reaction in male patients.

Background:This study investigates the effect of nephrectomy in young and aged mice on some biochemical, histological and behavioural aspects. Methods:Each age group, 2- and 12-months-old, comprised a sham-operated group, a unilaterally nephrectomized group and a subtotally nephrectomized group. Consequences of nephrectomy were examined 10 days postsurgery on urea and guanidino compound levels in body fluids and brain; the remaining kidney by light-microscopic examination; and learning and memory abilities using the Morris water maze task. Results:Effect of nephrectomy on urea and guanidino compound levels in plasma, urine and brain was significantly more pronounced in the young age group. Some guanidino compounds show a tendency to decrease with aging in the sham-operated group and the two nephrectomized groups. Higher compensatory kidney hypertrophy was found in younger nephrectomized mice whereas in older mice glomerular mesangial expansion was a common feature. Finally, young mice with subtotal nephrectomy displayed a slight but significant impairment in memory and learning; whilst old nephrectomized mice manifested no impairment. Conclusions:Nephrectomy induces more changes in younger mice than in older mice as observed in higher variation of urea and guanidino compound levels, glomerular volume and kidney hypertrophy and decline in spatial learning and memory.

Abstract: A case of a man with biphasic sarcomatoid carcinoma of the right kidney with chondrosarcomatous foci and with invasion of the pelvic mucosa and submucosa into the peripelvic adipose tissue is presented. In situ carcinoma of the urothelium of the right renal pelvis and proximal ureter was also noted. Comments on the nomenclature of malignant tumours with apparently mixed carcinomatous and sarcomatous phenotypes and a hypothesis on the histogenesis of these tumours are presented. Cytokeratin and p53 protein expression patterns, and the results of angiogenesis quantification are consistent with an epithelial-to-mesenchymal conversion induced by the stroma.

Abstract: In the mid 1990s, the hypothesis emerged that the upregulation or re-expression of a telomere- synthesising ribonucleoprotein, called telomerase, is a critical event responsible for continuous tumour cell growth. In contrast to normal cells, in which gradual mitosis-related erosion of telomeres eventually limits replicative life span, tumour cells have telomerase and show no loss of these chromosomal ends. These data suggest that telomere stabilisation may be required for cells to escape replicative senescence and to proliferate indefinitely. Because of the close association between telomerase and malignancy, both pathologists and clinicians expect this molecule to be a useful malignancy-marker and a new therapeutic target. This review focuses on the components of the human telomere and of the human telomerase enzyme. A synopsis of reports studying the clinical–diagnostic value of telomere length measurements, of telomerase activity analyses and of the in situ telomerase detection is given. Finally, a summary of recent experimental work that sheds new light on the biological role of this fascinating molecule is presented.

Abstract: Objective. To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts). Design and patients. MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study. Results. On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody. Conclusions. Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images.

Objective:Inflammation is a frequent histological finding in prostate biopsies, performed on men without prostatic malignancy or clinical prostatitis. We investigated the relationship between morphological parameters of inflammation in prostatic tissue and total serum prostate–specific antigen (PSA) and prostate–specific antigen density (PSAD) levels to determine if subclinical inflammation can cause elevation of PSA and PSAD.Methods:We reviewed 268 prostate biopsies, performed on 238 men with elevated PSA and/or abnormal digital rectal examination of the prostate. All premalignant and malignant biopsies and cases of clinical prostatitis were excluded. The inflammation in the remaining 145 prostate biopsies was scored for extent of inflammation and aggressiveness of inflammation, using the four–point scale designed by Irani and co–workers. In this prostatic inflammation scoring system, extent of inflammation is graded from 0 up to 3 according to the degree of invasion of inflammatory cells in prostatic tissue. Aggressiveness of inflammation is graded from 0 up to 3 according to the degree of contact or disruption of prostatic glandular epithelium by inflammatory cells.Results:Each of the studied biopsies showed inflammatory cells. Median PSA levels in grades 1, 2 and 3 of extent of inflammation were, respectively, 5.7, 6.8 and 13.0. Median PSAD levels in these groups were 0.13, 0.16 and 0.33. There was no significant difference between these grades for PSA nor for PSAD. Median PSA levels in grades 0, 1 and 2 of aggressiveness of inflammation were, respectively, 3.9, 5.9 and 8.9. Median PSAD levels in these groups were 0.12, 0.18 and 0.17. For both parameters, there was a significant difference between grades (respectively, p = 0.0028 and p = 0.0330).Conclusion:Inflammation of the prostate is a histological finding in almost every set of prostate biopsies, even when there are no signs of clinical prostatitis. This subclinical inflammation can cause PSA elevation. Not the extent of inflammation is of importance, but the disruption of epithelial integrity caused by the inflammatory infiltrate. When confronted with a patient with an elevated PSA level whose prostate biopsies reveal no malignancy but only inflammation, this concept can help in determining the need for quick repeat biopsies.

Abstract: Desmoplastic fibroma of bone is a very rare benign tumor, which may be locally aggressive. In contrast to the well-documented radiological appearance, the literature on MR imaging features of this tumor is scarce. The MR imaging characteristics in our case are compared to those previously reported. Although there is a considerable overlap in the MR imaging features with other bone tumors, an interesting MR feature of desmoplastic fibroma is the presence of low to intermediate signal intensity foci on T2-weighted images, which radiographically does not correspond to calcifications. This feature may help narrow the differential diagnosis.

AbstractSevere eosinophilia may be complicated by acute or chronic visceral damage. The underlying origin of the hypereosinophilia may be infectious, allergic, toxic, malignant or systemic (the secondary or reactive hypereosinophilie syndrome), but in a number of cases no cause can be found (the idiopathic hypereosinophilie syndrome).We describe 4 cases with hypereosinophilia and sec-ondary visceral damage after residence in a tropical region. In three cases a helminthic infection was the obvious cause, the brain and the heart were the target organs. After treatment of the infection both the hypereosinophilia and the neurological and cardiac lesions disappeared. The fourth patient died of multiorgan disease. No definite trigger of the hypereosinophilia could be found.We discuss clinical findings, necessary investigations and therapeutic strategies.

Bladder wall wrapping and invagination have been used for the surgical treatment of the underactive detrusor and improvement of bladder emptying has been described. In a rat model we investigated the evolution in time of urodynamic parameters after 3 techniques of surgical bladder reduction.

AbstractA Belgian patient developed Q fever after a journey in Syria. Coxiella burnetiiinfection was diagnosed because of the presence of granulomas with a central vacuole in a bone marrow biopsy. During doxycycline treatment all his symptoms disappeared.

AbstractTwo HIV infected patients with multicentric Castleman's disease (MCD) and Kaposi's sarcoma are reported. Both died despite combination antiretroviral therapy including protease inhibitors.

Abstract: Adult Schistosoma mansoni worms can positively modulate soluble egg antigen (SEA)-induced granulomas formed around SEA-coupled beads implanted in the liver. In this study, our aim was to further unravel the immunopathological characteristics of S. mansoni-worm-derived antigens in vivo. (a) Adult worm antigen (AWA)-coupled Sepharose beads, implanted into the liver, induced granulomas, containing numerous eosinophilic granulocytes and elicited marked periparticular fibrosis (composed of interstitial matrix proteins and basement membrane components). (b) Quantitative morphological analysis demonstrated that in naive mice, AWA-induced hepatic granuloma formation peaked in volume 16 days after injection of the beads. An accelerated response against AWA-coupled particles (peak volume at 8 days) was observed in mice carrying a single-sex, male S. mansoni infection. (c) When the granuloma volume induced by SEA-coupled beads in unisexually S. mansoni infected mice was compared to granulomas induced by beads laden with both SEA and AWA in unsensitized mice, no significant differences in granuloma volume were seen, indicating the existence of in vivo egg/worm antigen cross-sensitization. (d) Naive mice, sensitized with the worm antigens circulating anodic antigen (CAA) or circulating cathodic antigen (CCA), mounted a strongly accelerated response towards SEA-coupled beads implanted in the liver. We infer that, in vivo, worm antigens cross-sensitize with egg antigens and have both granulomogenic and fibrogenic characteristics. The S. mansoni soluble worm antigens CCA and CAA prime hepatic egg-antigen-induced granuloma formation possibly through the presence of immunogenic carbohydrates. These mechanisms lead to an accelerated response against SEA.

Abstract: To further investigate the factors involved in the modulation of the schistosomal granuloma, mice were primed with immunogenic carbohydrates which were common to soluble egg antigen (SEA) and adult worm antigen. Mice sensitized with LewisX trisaccharide or lacto-N-fucopentaose-III (LNFP-III) displayed an increased cellular response towards SEA-coupled beads implanted in the liver by mesenteric injection, resulting in the formation of larger periparticular granulomas. When animals were sensitized with bovine serum albumin or a structurally related carbohydrate, an accelerated response was not seen. Since LNFP-III is built up of LewisX molecules, and LewisX carbohydrates are common to SEA and worm antigens such as the gut-secreted antigens CCA and CAA (two antigens that could prime egg-antigen-induced granuloma formation), this may explain why adult, live Schistosoma mansoni worms positively modulate egg-antigen-induced hepatic granuloma formation in the murine host. These observations provide new insights into the role of carbohydrates in parasite-host immunity and may yield important implications for choosing worm-derived antigens for the development of anti-schistosome vaccines.

SummaryA case where a breast tumor was the initial manifestation of Wegener’s granulomatosis is presented. Breast biopsy revealed granulomatous mastitis, and treatment with tuberculostatic drugs was started. Following an initial improvement the patient finally died. Postmortem, the diagnosis of generalised Wegener’s granulomatosiswas made.Although Wegener’s granulomatosis is a very rare cause of granulomatous mastitis, it should be considered in the differential diagnosis. A brief outline of the literature is given.

SummaryCutaneous T-cell lymphomas represent a group of malignant lymphoproliferative disorders characterised by the occurrence of a monoclonal population of T-lymphocytes. Diagnosis of early stages of this disease is a difficult challenge for both the dermatologist and the dermatopathologist. With the aid of the polymerase chain reaction it is possible to amplify specific regions of the T-cell receptor gamma gene. The amplification products can then be separated by denaturing gradient gel electrophoresis in order to detect a monoclonal population of T-lymphocytes in the infiltrate. We studied 4 patients with the clinicopathologic diagnosis of mycosis fungoides and 2 patients diagnosed as large plaque parapsoriasis. A monoclonal population was detected in 3 of the 4 mycosis fungoides cases and in 1 of the patients with large plaque parapsoriasis. This indicates that our analysis can help us establishing a diagnosis, and it can also help us to identify patients with a possible early stage of the disease, which clinically or histologically is not yet recognised as such.

Abstract: DNA-like sequences of the p53 and pRB-inactivating simian virus 40 large T-antigen (SV40 LTag) have recently been found in mesotheliomas in the United States and several European countries. Nuclear expression of SV40 LTag, possibly in concert with detectable telomerase activity, could be responsible for immortalisation of (pre)malignant clones, as suggested by the mesothelioma-specific latency period. Depending on the antibody used, different results have been observed regarding the subcellular expression of SV40 LTag in mesotheliomas with SV40 LTag-like DNA sequences. In this study, we screened 28 Belgian mesothelioma tumour samples for the presence of SV40 LTag-like DNA and its gene product by polymerase chain reaction amplification, using the SV.for3/SV.rev primer set, and by tyramine-amplified immunohistochemistry, using the pAb419 and the pAb101 SV40 LTag antibodies. Amplicons were found in 13 of the 28 (46%) mesotheliomas. Cytoplasmic, but no nuclear, staining was found in 10 of these 13 cases. Although our study confirms the presence of SV40 LTag-like DNA sequences in Belgian mesotheliomas, we did not detect nuclear expression of the viral oncoprotein, which makes a pathogenic role of SV40 LTag in mesothelioma carcinogenesis questionable.

SummaryTwo imported cases of Penicillium marneffeiinfection in Belgium are reported. Both patients are Thai women co-infected with HIV. P. marneffeiinfection should be suspected in immunocompromised patients originating or travelling from South-East Asia with unexplained fever (>38°C), weight loss, a generalised lymphadenopathy, hepatomegaly, splenomegaly, skin lesions, cough and anaemia. Diagnosis is made by culture and/or histopathological examination. Mild to moderate infections are treated with itraconazole 400 mg/day as first choice. Amphotericin B parenteral therapy may be required for seriously ill patients. Maintenance therapy with itraconazole 200 mg/day is necessary to prevent relapses.

In this study the excretory system ofSchistosoma mansoni was ultrastructurally examined with a recently described monoclonal antibody (mAb) against a circulating antigen. In previous studies this mAb was found to have affinity for the excretory system. Strong immunoreactivity was found on the flagella of the flame cells and of the collecting ducts throughout the worm. The eggshell and the space between the miracidium and the eggshell showed strong reactivity with a declining gradient towards the exterior, suggesting a secretion process. In cercariae, immunoreactivity was restricted to the tegument, whereas in schistosomula the labeling pattern resembled that of the adult worm, demonstrating positive reactivity of the flame cells and no immunostaining of the tegument. This stage-dependent differential expression of different antigens in the excretory system and in the tegument could suggest a maturation process of the excretory system.

The clearance of schistosome-specific model immune complexes (IC) consisting of circulating anodic antigen (CAA), a gut-associated excretory-secretory antigen, and radiolabeled monoclonal antibody (IgG1) was investigated in mice with a light and heavy Schistosoma mansoni infection and in noninfected control animals. The size analysis of the in vitro prepared and injected IC, as determined by density gradient centrifugation, revealed a wide peak at 11S. In infected animals the injected IC were cleared at a significantly lower rate than in control mice. This was attributed to a decreased uptake of IC by the liver in infected mice. In heavily infected mice, 30 min after injection of 11S IC, 8S, 11S, and >11S IC were present in the serum, whereas only small 8S IC were detected in the serum of lightly infected animals and noninfected controls. Immune complexes were also present in the serum of heavily infected mice 30 min after injection of antibody and were detectable as 11S and >11S IC. The importance of this study is twofold. First, these results show that schistosome-specific monoclonal antibodies can be used in the production of model immune complexes applicable in clearance studies. Second, our findings might be of importance when the possible pathogenicity of circulating IC in schistosomiasis is considered.

Sera from rats with chronicTrypanosoma brucei gambiense infection were tested for autoantibodies by an indirect immunofluorescence assay. All the sera contained IgM autoantibodies which reacted with blood vessel walls. On cultured vascular smooth muscle cells positive sera reacted with cytoplasmic filaments which were rearranged into perinuclear coils of filaments in colcemid-pretreated smooth muscle cells. These observations strongly suggest that the cytoplasmic autoantigens are intermediate filaments (I.F.). It is probable that the anti-intermediate filament autoantibodies result from polyclonal lymphocyte activation, since in rats experimentally infected withT.b. gambiense the appearance of these autoantibodies occurs already 1 week post-infection.

Albino rats and white mice were infected with populations ofTrypanosoma brucei gambiense isolated from patients in four different areas in Central Africa. Differences in virulence as shown by the level of parasitaemia, number of relapses, and length of survival time, were observed amongst the stocks according to their geographical origin and secondarily to the degree of adaptation to the rodents. All the stocks are pathogenic for the laboratory rodents, and the presence of extravascular trypanosomes in the brain was confirmed in all infected animals. Spleen, liver, and kidneys were less constantly found to be positive. The morphology of the extravascular parasites was highly variable, ranging from long slender trypomastigotes to spheromastigotes and even amastigotes.

Histopathological findings on brain, heart, liver, and spleen of albino rats and white mice, infected with different stocks ofTrypanosoma brucei gambiense of human origin are presented. Classical brain lesions, including chronic inflammation of the choroid plexuses, were observed in all infected animals, the severity of which increased with the chronicity of the disease. Parasite stocks which gave rise to a less acute course of the disease more often induced myocarditis, while brain lesions were less pronounced, suggesting that virulence of the parasites is more closely related to the advent of myocarditis than to the appearance of brain lesions. Liver lesions were not obvious. In spleens, a variable and often very pronounced degree of lymphoid hyperplasia was observed.

Summary A 39-year-old Ugandan student is described presenting with general malaise, fever and a pulmonary infiltrate. Open lung biopsy showing infarction and positive ANCA lead to a diagnosis of Wegener's granulomatosis and a treatment with immunosuppressive drugs was instituted. Five weeks after admission, however, sputum cultures turned out to be positive for Mycobacterium tuberculosis. The importance of ANCAinterpretation and the possibility of false positive results is discussed.

Tumour stromal neovascularization was investigated in 114 invasive and 20 in situ carcinomas of the uterine cervix by staining representative sections with the specific endothelial marker anti CD31 (clone JC/70A, isotope IgG1). A digital image analyser was used to measure the immunoreactivity. The following parameters were determined in the 'hot spots': vessel counts, vessel perimeter and endothelial stained area (expressed per mm2). The results were correlated with clinical and histopathological data. There was no significant relationship between the histopathological findings (tumour histology, tumour differentiation, FIGO stage, presence of lymph node metastasis or lymphovascular space involvement) and the median vessel count. In a univariate analysis all angiogenesis parameters had prognostic value: a higher vascularity was associated with worse prognosis (P < 0.05). Multiple regression analysis showed that vascular permeation (P < 0.001) and the median vessel count (P = 0.005) were the most important prognostic indicators. In the future these criteria may be used for selection of patients for anti-angiogenesis therapy.

Previous immunohistochemical studies on malignant mesothelioma with antibodies recognizing both the wild and the mutant types of the p53 protein have shown immunoreactivity in 25–70% of cases. This study was designed to determine whether there is immunoreactivity for p53 and mdm2 protein in malignant mesothelioma and to correlate p53 expression with the detection of mutations in p53 at DNA level. In 10 of 15 cases there was immunoreactivity for p53. In 6 of these cases immunoreactivity for mdm2 was also detected. In one p53-immunonegative case, a mutation of the p53 gene resulting in a stop codon was found. These results suggest that mdm2 might be involved in the inhibition of p53 in malignant mesothelioma. Also, these data suggest the existence of other proteins than mdm2 that may associate with p53.

Immunohistochemical study of bcl-2 protein immunoreactivity in human non-neoplastic mesothelium (44 cases) and in malignant mesothelioma (62 cases) using a murine monoclonal antibody (clone 124) showed cytoplasmic immunoreactivity for bcl-2 protein in five cases of malignant mesothelioma. Non-neoplastic mesothelium was not immunoreactive. Immunoreactivity for bcl-2 protein does not add useful prognostic information in malignant mesothelioma since survival times of bcl-2 positive and bcl-2 negative cases did not differ. Nevertheless, the detection of bcl-2 protein in malignant mesothelioma might be useful for the differentiation from reactive mesothelium.

We developed a method for avoiding contamination by fibroblasts when cultures of peritoneal cells are initiated. Macrophages were identified by immunogold detection [light microscope, transmission (TEM) and scanning (SEM) electron microscopes] of membrane antigens (Mac-1+, Thy-1,2-), non-specific esterase activity and ultrastructural features (TEM). As compared with controls, the yield of peritoneal macrophages was 2- and 12-fold higher, respectively, in acutely and chronically infected mice. In all, 30 “chronic”, 18 “acute” and 18 control cultures were followed up. At a given cell-density seeding, the decline of control, “acute” and “chronic” cultures starts at about day 10, 15, and 27, respectively. In “chronic” cultures only, fibroblast-like cells appear from day 6 onwards; their number increases with time. Cells showing characters intermediary between macrophages and fibroblasts were observed. We suggest that fibroblast-like cells result from the in vitro transdifferentiation of a limited number of in vivo committed macrophages.

In the present study the kinetics of the uptake and deposition of the major circulating cathodic antigen (CCA) ofSchistosoma mansoni in liver, spleen, and kidney ofS. mansoni infected Swiss mice was investigated in relation to the duration of infection and infection dose (50, 100, 200 cercariae). The presence of antigen was studied with a direct immunofluorescence reaction on frozen sections of the mouse organs, using a fluorescein isothiocyanate (FITC)-labelled mouse IgM monoclonal antibody recognizing a repeating epitope of CCA.

In the present study the kinetics of the uptake and deposition ofSchistosoma mansoni antigens in liver, spleen and kidney ofS. mansoni infected Swiss mice have been investigated in relation to duration of infection and infection dose (50, 100, 200 cercariae). The presence of antigen was studied with a direct immunofluorescence reaction on frozen sections of the organs, using a number of fluorescein isothiocyanate (FITC)-labeled antisera produced against various antigen preparations isolated from different life-cycle stages of the parasite. The presence of antigen was demonstrable with two of the antisera, directed against the circulating anodic antigen (CAA) and against total soluble egg antigen (SEA).

The distribution of T-cell subsets, B cells, and class II MHC antigens was examined within the CNS of rats chronically infected withTrypanosoma brucei gambiense, using appropriate mouse monoclonal antibodies. The mononuclear infiltrates of the leptomeninges and the perivascular areas (Virchow-Robin spaces) were composed of IgM-producing plasma cells and Mott cells and T-helper/inducer cells. Cells defined phenotypically as suppressor/cytotoxic T cells were rare. Anti-Ia reactive cells were also abundant in these inflammatory lesions and in the white matter, representing Ia-expressing neuroglial cells, B cells, activated T cells, and macrophages. The Ia-positive neuroglial cells, possibly acting as accessory cells, associated with numerous T-helper/inducer cells and cells from the B-cell lineage, suggest that a T-dependent B-cell immune response can be initiated within the CNS of rats with a chronicT. b. gambiense infection.