Atypical pleomorphic epithelioid angiomyolipoma localized to the pelvis: a case report and review of the literature.

AIMS: Angiomyolipoma is the most common mesenchymal tumour of the kidney. It has been reported in several other sites outside the kidney, mainly in the liver. We report the first case of atypical pleomorphic angiomyolipoma in a man, arising from the pouch of Douglas and extending to the entire abdominal cavity. METHODS: A 17-year-old man underwent a complete resection of a giant abdominopelvic mass. The tissue was formalin fixed and paraffin embedded and 4 micro m thick histological sections were stained with haematoxylin-eosin. Immunohistochemical stains for HMB-45, smooth muscle actin, vimentin, calponin, S100 and desmin were performed. Sections for electron microscopy were also prepared. RESULTS: Microscopic examination revealed a neoplasm composed of pleomorphic epithelioid cells with atypical features, immunoreactive for HMB-45, MART-1, actin, vimentin and calponin, while S100 protein and desmin stains were negative. Ultrastructurally, the tumour cells showed prominent nucleoli, vacuolated cytoplasm, and some premelanosomes. A diagnosis of atypical pleomorphic epithelioid angiomyolipoma was then made. CONCLUSIONS: To date five patients with abdominal epithelioid angiomyolipoma have been described in the literature. All were women. Three of the five patients reported developed metastasis, while our patient is still free of disease at 16 months of follow-up. Clear prognostic pathological features have not been identified.

Immunomodulation of experimental colitis: the role of NK1.1 liver lymphocytes and surrogate antigens--bystander effect.

The imbalance between Th1 pro-inflammatory and Th2 anti-inflammatory cytokine-producing cells plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Induction of oral tolerance to colitis-extracted proteins was previously shown to down-regulate the anti-colon immune response, thereby alleviating experimental colitis. Immune bystander effect and liver-associated lymphocytes expressing the NK1.1 marker (NK1.1(+) LAL) have been suggested as being important in tolerance induction. The aims of the present study were to determine whether oral administration of inflammatory and non-inflammatory colon-extracted proteins of different species can induce peripheral immune tolerance and alleviate experimental colitis; and to examine the role of NK1.1(+) LAL in oral tolerance induction. Colitis was induced in C57/B6 mice by intracolonic instillation of trinitrobenzene sulphonic acid (TNBS). Mice received six oral doses of colonic proteins extracted from TNBS-colitis colonic wall, or normal colonic wall, from four different species. Standard clinical, macroscopic, and microscopic scores were used for colitis assessment. Serum interferon gamma (IFNgamma) and interleukin 10 (IL10) levels were measured by ELISA. To evaluate the role of NK1.1(+) LAL in maintaining the balance between immunogenic and tolerogenic subsets of cells, their cytotoxicity functions were tested in tolerized and non-tolerized-mice. The administration of mouse-derived colitis-extracted proteins, or of surrogate proteins extracted from normal mouse colon, or from rat or human inflammatory colons, was found to alleviate experimental colitis. Tolerized mice had less diarrhoea; showed a marked reduction of colonic ulceration, intestinal and peritoneal adhesions, wall thickness, and oedema; and demonstrated a significant improvement of all microscopic parameters for colitis. Induction of tolerance led to an increase in IL10 and a decrease in IFNgamma serum levels. NK1.1(+) LAL cytotoxicity function increased markedly in tolerized mice. In contrast, mice fed with proteins extracted from normal rat, rabbit, and human colon, or from rabbit inflammatory colon, developed severe colitis, with a marked increase in IFNgamma and a decrease in IL10 serum levels, and down-regulation of NK1.1(+) LAL function. This study has shown that oral tolerance can be induced in experimental colitis by means of the feeding of surrogate antigens; this alleviates experimental colitis. NK1.1(+) LAL cytotoxicity function is associated with peripheral tolerance induction and may help to maintain the Th1/Th2 immune balance.

Expression of EBV encoded nuclear small non-polyadenylated RNA (EBER) molecules in 32 cases of childhood Burkitt's lymphoma from Israel.

We have analyzed paraffin sections from 32 children with histologically confirmed Burkitt's Lymphoma (BL) for the presence of EBV using in situ hybridization to detect expression of the EBV-encoded early RNAs (EBERs). EBV was present in the tumors of 11 patients (34%). Sixty nine percent of the children presented with abdominal disease, 19% had bone marrow infiltration and only one child had jaw involvement. There was no statistically significant difference between EBV positive and EBV negative children with regard to age, gender, origin, primary site at presentation, or clinical stage of disease. However, there was a trend for younger age in the children with EBV positive BL with a median age of 4, compared to 7 years in children with EBV negative BL. None of the 7 children of Ashkenazi Jewish origin had EBER positive disease. There was no difference in the treatment outcome between the EBV positive patients (estimated survival at 24 months of 82%) and EBV negative children (estimated survival rate of 71% (p=0.58)). In conclusion, although this is only a small series it seems that childhood BL in Israel has the clinical characteristics of sporadic, non-African type with 34% EBV association and a low incidence of jaw tumors. Our data suggest that Ashkenazi Jewish children with BL are less likely to have EBV positive tumors than other ethnic groups. However, more patients will need to be studied in order to assess the validity of this observation.

Infantile hemangioendothelioma of the liver in an adult.

Hepatic infantile hemangioendothelioma (IHE) is a rare benign vascular tumor of the liver found mostly in infancy and early childhood. We describe herein a tumor of the liver, morphologically indistinguishable from IHE, that presented in an adult. The patient is a 56-year-old woman with a history of ductal carcinoma in situ of the left breast and a mass in the liver. The patient underwent resection of the tumor, and after 23 months of follow-up she is alive with no evidence of expansion of the liver tumor.

Enhancement of immune tolerance via induction of NK1.1 positive liver-associated-lymphocytes under immunosuppressive conditions.

BACKGROUND/AIMS: The liver was previously shown to play a critical role in oral tolerance induction. A subset of liver-associated-lymphocytes expressing NK1.1 marker (NK1.1+ LAL) have killing activities and it has been suggested that they play a role in immune modulation. FK506 is a powerful immunosuppressive agent affecting T-cell differentiation and function. The exact pathway involved in peripheral tolerance induction using this drug remains unknown. The aim of the present study was to determine the interaction between FK506 and NK1.1+ LAL in induction of peripheral immune tolerance in the experimental colitis model. METHODS: Colitis was induced in C57 mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall with and without FK506 treatment. The effect of FK506 treatment on NK1.1+ LAL was tested by cell-sorting and cytotoxicity assay. Colitis was assessed by standard clinical, macroscopic and histologic scores. RESULTS: Both FK506 treatment and oral tolerance induced a significant increase in NK1.1+ LAL number and cytotoxicity function. FK506 treatment enhanced the effect of oral tolerance on amelioration of disease activity. Orally tolerized mice treated with FK506 had no mortality nor increase in body weight, and manifested significant improvement in disease macroscopic and microscopic scores. CONCLUSIONS: This study shows for the first time that immune tolerance induced by both oral administration of an antigen and by FK506 treatment may be mediated via enhancement of NK1.1+ LAL. This subset of lymphocytes may play an immunoregulatory role in immune tolerance induction.

Treatment of experimental colitis by oral tolerance induction: a central role for suppressor lymphocytes.

OBJECTIVE: Inflammatory bowel diseases (IBD) are immune-mediated disorders wherein an imbalance between proinflammatory (Th1) and antiinflammatory (Th2) cytokines is thought to play a role in the pathogenesis. The aim of this study was to test whether induction of oral tolerance to proteins extracted from inflammatory colon alleviates experimental colitis, and whether oral tolerization mediated by suppressor cells can induce immune tolerance. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Rats received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Splenocytes harvested from tolerized and control rats were transplanted into irradiated naive rats. RESULTS: Feeding of colitis-extracted proteins ameliorated colonic inflammation, as shown by reduction of colonic ulcerations, as well as decreased diarrhea, intestine and peritoneal adhesions, wall thickness, and edema. A marked reduction of the fraction of injured colonic area and colon weight, and decrease in colon weight, were observed in tolerized rats versus controls. Histological parameters for colitis were markedly improved in tolerized animals that showed significant reduction in inflammatory response and mucosal ulcerations. Tolerized rats developed an increase in TGFbeta1 and a decrease in IFNgamma serum levels. TNBS-induced colitis was significantly attenuated in naive recipients of splenocytes from tolerized rats, compared with rats that received splenocytes from control donors. CONCLUSIONS: Induction of oral tolerance to colitis-extracted proteins downregulates the anticolon immune response, thereby ameliorating experimental colitis. Suppressor lymphocytes mediate the tolerance by induction of a shift from a proinflammatory to an antiinflammatory immune response.

Focal, steroid responsive myositis causing dropped head syndrome.

The dropped head syndrome, which occurs in a variety of neuromuscular disorders, is usually not due to an inflammatory process and generally either self-limited or nonresponsive to therapy. We present an 80-year-old woman who developed progressive neck weakness over a few months due to a focal and restricted inflammatory process involving the neck extensor muscles. She responded dramatically to treatment with immunosuppressive therapy.

Liver-associated lymphocytes expressing NK1.1 are essential for oral immune tolerance induction in a murine model.

Oral tolerance is the induction of immunological hyporesponsiveness towards orally administered antigens. Tolerance initiation involves induction of anti-inflammatory (Th2) lymphocytes, with downregulation of pro-inflammatory (Th1) lymphocytes. The liver was previously shown to play a critical role in oral tolerance induction. The aim of the present study was to test whether liver-associated-lymphocytes expressing the NK1.1 marker (NK1.1+ LAL) are substantial for induction of oral tolerance in an experimental colitis model. Colitis was induced in C57 mice by intracolonic instillation of trinitrobenzensulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Anti-NK1.1 monoclonal antibodies were injected before tolerance induction. Colitis was assessed by standard clinical, macroscopic, and microscopic scores. Serum IFN-gamma, TGF-beta1, and IL4 levels were measured by enzyme-linked immunosorbent assay. To evaluate the role of NK1.1+ LAL in keeping the balance between immunogenic and tolerogenic subsets of cells, we tested whether peripheral lymphocytes harvested from tolerized and NK1.1-depleted nontolerized mice can adoptively transfer the tolerance into naive irradiated rats. Depletion of NK1.1+ LAL prevented immune tolerance induction in the experimental colitis model. NK1.1+ LAL-depleted nontolerized mice, disclosed severe clinical, macroscopic, and microscopic parameters of colitis. These mice had significantly lower TGF-beta1, IL4, and higher IFN-gamma serum levels, and their lymphocytes failed to transfer the tolerance into naive animals. In contrast, the feeding of colitis-extracted proteins, without NK1.1+ LAL depletion, markedly alleviated the disease. Tolerized mice had higher IL4 and TGF-beta1 and lower IFN-gamma serum levels, and adoptive transfer of their suppressor splenocytes markedly alleviated colitis in naive recipients. NK1.1+ LAL plays a critical role in oral tolerance induction. Depletion of this subset of LAL prevents a shift from Th1 to a Th2 type of immune response, hindering the ability to induce immune tolerance.

A novel assay for hepatitis B e markers.

The evaluation of a novel assay that allows simultaneous testing for hepatitis B e antigen and its antibody in a single well is described. The results of routine application and sequential studies on patients with acute hepatitis B and chronic hepatitis B treated with interferon are presented. The specificity and sensitivity of the assay and its ability to be used to follow the response of a patient during the whole seroconversion episode has been evaluated. The assay proved to give useful information about the reactivity of the sample, especially in those patients who were changing their "e" status.

[Hyponatremia due to prolonged excessive ingestion of water].

We report a 1.5-year-old boy admitted for restlessness and constipation. He was found to have hyponatremia caused by voluntary drinking of excessive amounts of water. Although unusual in children, intoxication by oral water is a recognized clinical syndrome in infants, 3-6 months old, fed with dilute formula. Water intoxication in older children is rare. The diagnosis was established by the water deprivation test.

Measurement of anti-HBc IgM levels using the Amerlite anti-HBc IgM assay.

The Amerlite anti-HBc IgM assay was evaluated as a tool for determination of antibody levels. With an assay time of 1 hour, the test showed a broad dose response range with high sensitivity and specificity. The software configuration of the analyser can be customized to suit specific research requirements.

Avian erythrocyte agglutination tests with the sera of bird fanciers.

The agglutination of avian red cells, particularly pigeon and budgerigar cells, by sera from patients who had been exposed to birds and had respiratory symptoms, as well as from healthy bird fanciers, has been used to detect the presence of avian specific antibody. Agglutination tests performed by standard techniques using bird erythrocytes can be read within 45 minutes. One hundred and sixty-five sera were tested, and the 44 which were precipitin positive gave a positive agglutination test with one exception. Of 61 sera which gave positive agglutination tests, 43 gave positive precipitin tests with unconcentrated serum and seven others after fourfold concentration of the serum. Avian antibodies were demonstrated in the remaining 11 sera by radioimmunoelectrophoretic tests. Absorption of the sera with pigeon IgG and IgM and the use of animal antisera directed against pigeon IgG showed that the agglutination reactions were mediated by antibodies directed against pigeon IgG and IgM, and against light chains derived from pigeon IgG.