Detection of hepatitis C virus in thyroid tissue from patients with chronic HCV infection.

Thyroid dysfunctions are common in chronic hepatitis C virus (HCV) infection. HCV-RNA has been detected by reverse-transcription polymerase chain reaction (PCR) in thyroid from HCV infected patients with acquired immunodeficiency syndrome. However, morphological evidence of HCV replication in thyroid cells from immune competent patients has not been provided. In situ hybridization and real-time-PCR were used to analyze HCV-RNA replication in thyroid tissue from 11 patients (3 anti-HCV, serum HCV-RNA positive; 8 anti-HCV negative). Genomic and antigenomic HCV-RNA was detected in the thyroid of the 3 anti-HCV positive patients at concentrations of 2.6 x 10(4), 1.7 x 10(4), and 8.6 x 10(3) copies/microg of total RNA (genomic) and 3.2 x 10(2), 4.3 x 10(3) and 2.9 x 10(2) HCV-RNA copies/microg of total RNA (antigenomic). No HCV-RNA was detected in the thyroid tissue of the 8 anti-HCV negative patients. Presence of genomic/antigenomic HCV-RNA in the 3 anti-HCV positive cases was confirmed by in situ hybridization. Signals were observed in the cytoplasm of the thyroid cells. In conclusion, the data obtained indicate that HCV may infect cells of the thyroid in immune competent patients with chronic HCV infection. The pathogenic implications of this finding merit further research.

Herpesvirus saimiri transformation may help disclose inherent functional defects of mucosal T lymphocytes in patients with gastric adenocarcinoma.

To dissect the phenotypic and functional features of mucosal T lymphocytes in patients with gastric adenocarcinoma, we have used the Herpesvirus saimiri transformation procedure to achieve T-cell lines from gastric origin. Once achieved, cell function was assessed by in vitro stimulation with mitogens. CD2-specific monoclonal antibodies (alpha-CD2), alone or in combination with interleukin (IL)-2, rendered fewer counts in patients (34 408+/-3965 and 52 157+/-6473 c.p.m., respectively) than in controls (67 471+/-11 755 c.p.m., P<0.01 and 77 864+/-12 545 c.p.m., P<0.05, respectively). Likewise, CD3-based responses were defective in cancer cell lines: alpha-CD3 (54 794+/-9269 vs 86 104+/-10 341 c.p.m., P<0.01), alpha-CD3+IL-2 (57 789+/-8590 vs 88855+/-8516 c.p.m., P<0.01) and alpha-CD3+alpha-CD2 (52 130+/-7559 vs 120 852+/-16 552 c.p.m., P<0.01). Finally, IL-2 failed to adequately stimulate patient cell lines (39 310+/-4023 vs 60 945+/-9463 c.p.m., P<0.05). These results suggest that mucosal T lymphocytes in cancer patients are inherently impaired in their proliferative ability. This may be crucial in the control of tumour growth.

Expression of CD45 and proliferative response to CD3 as suitable classification markers of patients with gastric adenocarcinoma.

25 patients with resectable gastric adenocarcinoma, subdivided according to the absence or presence of residual neoplasic disease (RND- or RND+, respectively), were studied. Cytofluorometric analysis and proliferative responses to mitogens was performed in peripheral blood mononuclear cells of patients. When compared to healthy subjects, the percentage of CD3-expressing cells was significantly reduced in both groups of patients studied (p < 0.0001 in all instances). However, when CD45 is considered instead of (CD3, its expression is found to be significantly reduced only in the RND+ patients (72% +/- 11), when compared with the control group (96 +/- 1%, p < 0.0001). Likewise, cells from these patients significantly less proliferated when stimulated with monoclonal antibodies to CD3 than control cells (18,920 +/- 6,019 cpm vs. 42,697 +/- 1,798 cpm, p = 0.0036); a difference not found if RND- patients (33,619 +/- 11,733 cpm) were considered. We propose that the low expression of CD45 and the poor response to CD3 are markers that are able to identify the subgroup of patients in whom the disease will tend to progress more rapidly. We also suggest the use of such markers as additional criteria for the classification of patients with gastric adenocarcinoma or to identify patients who require more aggressive therapeutic strategies.

Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy.

BACKGROUND AND AIMS: Rectovaginal fistulas in patients with Crohn's disease are difficult to resolve, and surgical failure is very frequent. Recent studies have shown that adult stem cells extracted from certain tissues, such as adipose tissue, can develop into different tissues, such as muscle. PATIENT AND METHODS: We report here the case of a young patient with Crohn's disease who had a recurrent rectovaginal fistula that was treated by autologous stem-cell transplantation with a lipoaspirate as the source of stem cells. RESULTS: Although Crohn's disease is the worst condition for a surgical approach in cases of rectovaginal fistula, we observed good closure. Since the surgical procedure 3 month ago the patient has not experienced vaginal flatus or fecal incontinence through her vagina. Thus our treatment seems to be effective. CONCLUSION: Cell transplantation to overcome healing problems is a new surgical tool, and careful evaluation of this new modality may provide an opportunity to define a new era in the treatment of surgical challenges associated with healing disorders. Ethical and safety items do not seem to be critical problems using autologous stem cells.