Relationship between the Immunohistochemical Expressions of Cathepsin B, Laminin and Tenascin and Clinicopathologic Features in Gallbladder Carcinomas

In the present study, the expression of protease indicated by cathepsin B (CB) and the expression of extracellular matrix indicated by laminin (LN) and tenascin (TN) was immunohistochemically examined in 25 gallbladder carcinomas. The incidence of expression of .CB and TN in normal epithelium was 1/25 (4%) and 0/25 (0%), respectively, and significantly increased in carcinomas (14/25 : 56% and 21/25 : 84%, respectively) (p<0.01). The LN expression was detected in the basement membrane of all normal epithelium, and the incidence of LN expression was significantly decreased in the carcinomas (7/25: 28%) (p<0.01). The incidence of CB expression in poorly differentiated adenocarcinomas (1/8: 13%) was significantly lower than that in papillary, welland moderately differentiated adenocarcinomas (11/15: 74%) (p<0.01). However, these responses were not significantly related with other histologic features or nuclear DNA ploidy pattern. The LN expression of the hepatic metastasis group (4/6 :67%) was significantly greater than that in the non-metastatic group (3/19 :16%) (p<0.05). The expressions of CB, LN and TN were not associated with the postoperative prognosis. In conclusion, the increased expressions of CB and TN, and the decreased expression of LN were cancerassociated alterations. The expression of CB was correlated with the histological grade of differentiation, and the expression of LN was correlated with the hepatic metastasis

Surgery for Gastric Cancer in Younger Patients

Twenty-five patients with gastric cancer were clinically evaluated in terms of a clinicopathological pattern in younger patients. 1) Female was more predominant than male. 2) The main tumor location was the cardia and the gross appearance was Borrmann IV of undifferentiated carcinoma in the majority. 3) Less hepatic metastases were seen in younger patients, whereas, the common extension in younger patients was peritoneal dissemination and serosal invasion. 4) The surgical outcome was satisfactory as far as a curative operation be performed. On the contrary, the result of non-curative operation was extremely pessimistic. Recently great strides in the surgical outcome of gastric cancer have been achieved in combination with adjuvant therapy of immunochemotherapy. Improvement of surgical outcome is attributable to the standarized operative procedure with reasonable node dissection. It is common that carcinomas in various organs affect older patients, not usually younger ones. The purpose of this study is to clarify the clinicopathologic features of gastric cancer in younger patients on the basis of our result of clinical experience

21-Hydroxylase gene mutant allele CYP21A2∗15 strongly linked to the resistant HLA haplotype B∗14:02-DRB1∗01:02 in chronic Chagas disease

We previously reported protective haplotype HLA-B*14:02-DRB1*01:02 against chronic Chagas disease in Bolivia. The V281L mutant allele of the 21-Hydroxylase gene, CYP21A2*15, is reported to be located in the Class III region of the Human leukocyte antigen region and linked to the haplotype HLA-B*14:02-DRB1*01:02. The mutant allele might play a primary role in the pathogenesis of chronic Chagas disease in the associated HLA region. We analyzed the frequency of this allele in the same subjects for the previous one. The statistical analysis showed a significant association of the CYP21A2*15 with resistance to severe chronic Chagas disease (OR=0.207273; Pv=0.0041). However, there is no significant tendency of the mutant gene contribution to the resistance after the elimination of the HLA-B*14:02-DRB1*01:02 linked mutants (OR=0.38; Pv=0.1533). Although the frequency of the CYP21A2*15 was small, we found no primary contribution of this mutation to the protection against chronic Chagas disease

Protective Human Leucocyte Antigen Haplotype, HLA-DRB1*01-B*14, against Chronic Chagas Disease in Bolivia

Chronic Chagas disease consists of four different forms categorized on the basis of their clinical manifestations, namely; cardiac, digestive, cardiodigestive and indeterminate. In Latin America, there are 8–10 million seropositive persons who are at risk of, or have already developed serious clinical complications and who have limited access to effective treatment. The cardiac and digestive forms are characterized by tissue damage caused by persistent infection of Trypanosoma cruzi and are thought to be modulated by host immunity. In our large scale screening for chronic Chagas disease in Santa Cruz, Bolivia, hearts and colons of 229 seropositive patients were examined. We found 31.4% of patients had abnormal electrocardiograms (ECGs), 15.7% presented with megacolon, 5.2% had a combination of abnormal ECG and megacolon, and 58.1% were of indeterminate status. Previously, we attempted to ascertain whether parasite genetic polymorphism might account for the differences in clinical manefestations, by analyzing parasite DNA taken from the same study group (with the addition of a further 62 megacolon post-operational patients). We found no relationships between parasite lineages and clinical disease form. The present study reveals that host HLA polymorphisms associate with clinical manifestations of Chagas

Lineage Analysis of Circulating Trypanosoma cruzi Parasites and Their Association with Clinical Forms of Chagas Disease in Bolivia

Around 30–50% of Trypanosoma cruzi infections in Latin America cause chronic Chagas disease 10–30 years after the primary infection due to lack of effective treatment. The major clinical complications associated with chronic Chagas disease are cardiac myositis (leading to cardiac failure), and autonomous neuroplexus degeneration of the digestive tract that can cause megacolon or megaesophagus. Therefore, there are three major clinical forms of Chagas disease; cardiac, digestive and indeterminate (asymptomatic). The parasites, which can infect humans as well as other mammals, are transmitted by species of triatomines commonly found in the Americas. The parasite is divided in at least six discrete typing units: TcI, TcIIa–e. In humans, the TcI is mainly observed in Central America and northern parts of South America while the TcIIb/d/e is confined mainly to the southern cone of Latin America. We determined which DTU were prevalent in chronic patients in Bolivia, where the three clinical forms and several DTUs of the parasites are present, in order to determine whether there was a link between a particular parasite DTU and a particular clinical outcome. We found a vast majority of TcIId but its kDNA polymorphism showed no association with any of the clinical manifestations of chronic Chagas

Relationship between the Immunohistochemical Expressions of Cathepsin B, Laminin and Tenascin and Clinicopathologic Features in Gallbladder Carcinomas

In the present study, the expression of protease indicated by cathepsin B (CB) and the expression of extracellular matrix indicated by laminin (LN) and tenascin (TN) was immunohistochemically examined in 25 gallbladder carcinomas. The incidence of expression of .CB and TN in normal epithelium was 1/25 (4%) and 0/25 (0%), respectively, and significantly increased in carcinomas (14/25 : 56% and 21/25 : 84%, respectively) (p<0.01). The LN expression was detected in the basement membrane of all normal epithelium, and the incidence of LN expression was significantly decreased in the carcinomas (7/25: 28%) (p<0.01). The incidence of CB expression in poorly differentiated adenocarcinomas (1/8: 13%) was significantly lower than that in papillary, welland moderately differentiated adenocarcinomas (11/15: 74%) (p<0.01). However, these responses were not significantly related with other histologic features or nuclear DNA ploidy pattern. The LN expression of the hepatic metastasis group (4/6 :67%) was significantly greater than that in the non-metastatic group (3/19 :16%) (p<0.05). The expressions of CB, LN and TN were not associated with the postoperative prognosis. In conclusion, the increased expressions of CB and TN, and the decreased expression of LN were cancerassociated alterations. The expression of CB was correlated with the histological grade of differentiation, and the expression of LN was correlated with the hepatic metastasis

Two-digit and four-digit alleles association with Clinical Manifestations of Chagas disease.

<p>Footnote for <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001587#pntd-0001587-t002" target="_blank">Table 2</a>.</p>*<p>Comparison between Megacolon vs Indeterminate.</p>**<p>Comparison between ECG alteration vs Indeterminate.</p>ζ<p>Comparison between (ECG+ &/or Megacolon+) vs Indeterminate.</p>φ<p>Linkage Disequilibrium group of HLA-DRB1*03:01-MICB*008-B*08:01-A*01:01 as shown in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001587#pntd-0001587-t003" target="_blank">Table 3</a>.</p