Rectal endometrial stromal sarcoma arising in endometriosis

PURPOSE: Endometriosis of the rectovaginal septum can harbor different types of secondary tumors that may involve the rectal wall and protrude into its lumen, thus making diagnosis difficult. Extrauterine low-grade endometrial stromal sarcoma may rarely arise in endometriosis. The purpose of this article was to present the third case of this association. METHOD: This was a clinicopathologic study. RESULTS: A 42-year-old female presented with abdominal pain and fever. Laparotomy revealed a large pelvic mass involving the rectovaginal septum and the colonic wall and which protruded into the lumen forming endoluminal polypoid masses. Concomitant peritoneal nodules and a metastatic paracolic lymph node were also found. Histopathologically, primary endometriotic foci were found in close relationship with an endometrial stromal sarcoma which invaded the rectal wall. The female genital tract had no endometriotic lesions. The patient was treated by surgery and subsequent chemotherapy and was alive and well 20 months later. CONCLUSIONS: Endometriosis and its possible malignant changes should be taken into account in the differential endoscopic diagnosis of rectal masses in females.     

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Natural immunity against obligate and/or facultative intracellular pathogens is usually mediated by both humoral and cellular immunity. The identification of those antigens stimulating both arms of the immune system is instrumental for vaccine discovery. Although high-throughput technologies have been applied for the discovery of antibody-inducing antigens, few examples of their application for T-cell antigens have been reported. We describe how the compilation of the immunome, here defined as the pool of immunogenic antigens inducing T- and B-cell responses in vivo, can lead to vaccine candidates against Chlamydia trachomatis. We selected 120 C. trachomatis proteins and assessed their immunogenicity using two parallel high-throughput approaches. Protein arrays were generated and screened with sera from C. trachomatis-infected patients to identify antibody-inducing antigens. Splenocytes from C. trachomatis-infected mice were stimulated with 79 proteins, and the frequency of antigen-specific CD4(+)/IFN-γ(+) T cells was analyzed by flow cytometry. We identified 21 antibody-inducing antigens, 16 CD4(+)/IFN-γ(+)-inducing antigens, and five antigens eliciting both types of responses. Assessment of their protective activity in a mouse model of Chlamydia muridarum lung infection led to the identification of seven antigens conferring partial protection when administered with LTK63/CpG adjuvant. Protection was largely the result of cellular immunity as assessed by CD4(+) T-cell depletion. The seven antigens provided robust additive protection when combined in four-antigen combinations. This study paves the way for the development of an effective anti-Chlamydia vaccine and provides a general approach for the discovery of vaccines against other intracellular pathogens.     

Familial rates of affective illness in Sardinia with special reference to schizoaffective disorder

Summary Familial rates of psychiatric disorders were studied in southern Sardinia and showed an increase in relatives of probands with the following research diagnostic criteria (RDC) diagnoses: normal, unipolar depression, schizoaffective depressive, schizoaffective bipolar, bipolar with mania and bipolar with hypomania. A significantly higher risk for bipolar schizoaffective disorder was observed in relatives of bipolar schizoaffectives compared with relatives of normal probands.Supported by a grant from Regione Autonoma della Sardegna, Assessorato all'Igiene e Sanità     

Perivascular epithelioid cell (PEC) tumors of the uterus: a clinicopathologic study of two cases with aggressive features.

We report the clinicopathologic, immunohistochemical and ultrastructural features of two unusual tumors of the uterus composed of spindle and epithelioid cells strongly positive for HMB45. The two patients of 56 and 48 years of age had, respectively, hemoperitoneum and abnormal uterine bleeding. Morphologically, both tumors showed atypia and extensive necrosis. The neoplastic cells express immunohistochemically both melanogenesis (HMB45) and smooth muscle markers (actin). Ultrastructural analysis showed the presence of intracytoplasmic membrane-bound granules. We viewed these neoplasms as perivascular epithelioid cell (PEC) tumors with aggressive features. Follow-up has shown the death of one patient whereas the other is alive without disease 36 months after the surgery. The two patients were evaluated for signs of tuberous sclerosis complex, and findings were negative.     

Do acute lesions of Wernicke's encephalopathy show contrast enhancement? Report of three cases and review of the literature

Contrast medium was given intravenously to three nonalcoholic patients who underwent MRI or CT in the acute stage of Wernicke's encephalopathy. Pathological enhancement was not seen in one patient examined within 4 days of clinical onset, was mild in a another 3 days after clinical deterioration and marked in a patient examined 12 days after admission. Contrast enhancement of lesions was present in half of 12 cases of acute disease reported previously. There was a substantial overlap in the time interval between clinical onset and contrast-enhanced CT or MRI in the groups of enhancing and nonenhancing lesions. Since contrast enhancement may be absent in acute WE, proton-density and T 2-weighted images are more useful for diagnosis of this reversible but potentially fatal condition. Received: 18 December 1997 Accepted: 15 July 1998     

Blue nevus of the uterine cervix: description of a case and review of the literature

Blue nevus is a pigmented lesion of dermal melanocytes; the extracutaneous locations are uncommon. We report a case of a blue nevus of the uterine cervix in a 53 years old woman, with histochemical and immunohistochemical investigations.     

Female genital cancer incidence in the Province of Sassari from 1974 to 1983

The incidence of gynaecologic tumours in the Province of Sassari has been studied in order to estimate their value and to make a comparison with the ones industrialised countries. The global incidence of uterine cancer (corpus uteri plus cervix) is of 18.16/100,000 women; 11.99/100,000 for cancers of corpus uteri and 6.17/100,000 for cervical carcinoma including in situ forms. The incidence of gynaecologic tumors for the District of Sassari is equivalent to that reported in Western countries and it does confirm indeed a constant and progressive increase in tumours of the corpus uteri and a reduction in cervical carcinoma especially if in situ forms are excluded.     

CT043, a Protective Antigen That Induces a CD4+ Th1 Response during Chlamydia trachomatis Infection in Mice and Humans

Despite several decades of intensive studies, no vaccines against Chlamydia trachomatis, an intracellular pathogen causing serious ocular and urogenital diseases, are available yet. Infection-induced immunity in both animal models and humans strongly supports the notion that for a vaccine to be effective a strong CD4⁺ Th1 immune response should be induced. In the course of our vaccine screening program based on the selection of chlamydial proteins eliciting cell-mediated immunity, we have found that CT043, a protein annotated as hypothetical, induces CD4⁺ Th1 cells both in chlamydia-infected mice and in human patients with diagnosed C. trachomatis genital infection. DNA priming/protein boost immunization with CT043 results in a 2.6-log inclusion-forming unit reduction in the murine lung infection model. Sequence analysis of CT043 from C. trachomatis human isolates belonging to the most representative genital serovars revealed a high degree of conservation, suggesting that this antigen could provide cross-serotype protection. Therefore, CT043 is a promising vaccine candidate against C. trachomatis infection.Chlamydia trachomatis is an obligate intracellular human pathogen which exists in two highly specialized morphological forms: the infectious elementary body (EB) and the replicative reticulate body (RB). The pathogen has been classified into 19 different serotypes (serovars), on the basis of which variant of the major outer membrane protein (MOMP) is expressed on its surface. Worldwide, C. trachomatis is responsible for more than 92 million sexually transmitted infections and 85 million ocular infections per year (45). These infections cause several types of diseases (35, 44), including trachoma-induced blindness (serovars A to C), pelvic inflammatory disease, ectopic pregnancy and infertility (serovars D to K), and lymphogranuloma venereum (serovars L1 to L3). Furthermore, recent studies indicate that chlamydia infections facilitate the transmission of both human immunodeficiency virus (28) and human papillomavirus (16).Although effective antibiotic treatments are available, they are often unsuccessful in halting the spread of the infection or inadequate to prevent the chlamydia-mediated long-term sequelae for a number of reasons. First, urogenital tract infections are frequently asymptomatic and therefore not properly treated in due time. Second, although C. trachomatis is generally sensitive to a panel of antibiotics, multiple-antibiotic-resistant strains of chlamydia have been reported (34). Third, there are indications from in vitro studies that antibiotic treatment could lead to the formation of aberrant chlamydia forms that remain dormant within inclusions and may eventually turn into EBs under favorable environmental conditions (9, 47). Finally, epidemiological data in industrialized countries indicate that the rate of chlamydia reinfection is rising, and this has been attributed to the interference of early antibiotic treatment with the acquisition of immunity against chlamydia (2).For these reasons, the development of an effective vaccine against C. trachomatis infection is urgently needed. Early trials with heat-killed preparations of whole EBs have been shown to elicit short-term protection, but a few cases of immunopathological reactions upon reexposure to chlamydia have also been reported (2). Based on these early findings, further efforts have been focused on the development of subunit vaccines (2, 13, 14). In particular, several studies have described the use of MOMP, the immunodominant chlamydial antigen accounting for 60% of the total mass of the chlamydia outer membrane (6). Immunization with MOMP purified from C. trachomatis elicited an immune response that fully protected mice against an intra-ovarian bursa chlamydia challenge (27). However, only correctly folded MOMP appears to provide protection, and no adequate, scalable processes for the production of soluble and properly folded recombinant MOMP have been developed yet. This has so far hampered the use of MOMP for vaccine development. Moreover, due to the sequence variability of MOMP, a broadly protective chlamydial vaccine will probably require the use of other immunogenic antigens in addition to, or in place of, MOMP.The search for other chlamydial antigens has been driven by the elucidation of the mechanisms of immune responses to chlamydia infection and the demonstration of the importance of CD4⁺ T cells in natural immunity. Animal models have shown that protective immunity to C. trachomatis depends on the elicitation of a Th1-polarized cell-mediated immune response, in particular, gamma interferon (IFN-γ)-secreting CD4⁺ lymphocytes. In mice, the depletion of CD4⁺ T cells results in the loss of protective immunity and adoptive transfer of chlamydia-specific CD4⁺ T cells confers protection against C. trachomatis challenge (36). Studies in primates have also emphasized the role of Th1 cells in immunity to chlamydia (42, 43).Here we report experimental evidence that CT043, a protein annotated as hypothetical, is a novel protective chlamydial antigen. This antigen appears to be associated with the bacterial cell surface and is expressed within the chlamydia inclusion in infected HeLa cells throughout the infection cycle. We show that CT043 is the target of CD4⁺ Th1 cells both in chlamydia-infected mice and in human patients with diagnosed C. trachomatis genital infection. Moreover, by using a DNA priming/protein boost immunization protocol, we show that the antigen significantly reduces the bacterial load in a mouse model of intranasal (i.n.) infection. Finally, sequence analysis of the CT043 gene in 22 C. trachomatis strains belonging to the most representative genital serovars revealed a high degree of conservation (99.4% amino acid identity), suggesting that the antigen could provide cross-serotype protection.Altogether, our study demonstrates that this antigen is a promising candidate to be included in a subunit-based vaccine against C. trachomatis.