Sulfated fucan from marine alga inhibits HeLa cells infection by HTLV-1 free particles: semi-quantitative analysis

A sulfated fucan from Laminaria abyssalis marine alga prevented the interaction of HTLV-1 particles, purified from the MT-2 cell line, with HeLa cells. The infection obtained using a concentrated virus suspension was detected only by amplification of the newly synthesized HTLV-1 proviral cDNA by the nested-polymerase chain reaction (PCR). The sulfated polysaccharide was not toxic to the cells at a concentration of 100 µg/mL and prevented infection by the viral particles when added to the cell monolayers. The proviral cDNA was only detected when the sulfated polysaccharide was added to the cells three hours post-infection, indicating that the inhibitory activity occurred in the initial stages of virus-cell interaction. Our results demonstrate, for the first time, the ability of a sulfated fucan from marine algae to inhibit virus transmission through free virus particles.

Human papillomavirus and penile cancers in Rio de Janeiro, Brazil: HPV typing and clinical features.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) DNA in penile cancers in Rio de Janeiro, Brazil. MATERIALS AND METHODS: We studied, prospectively, 80 consecutive cases of patients with penile cancers who underwent surgical treatment at three different Hospitals in Rio de Janeiro between March 1995 and June 2000. Of these patients, 72 were diagnosed with invasive squamous cell carcinoma and 8 patients with verrucous carcinoma. The following parameters were observed: presence or absence of HPV DNA viral type, histological subtypes, clinical stage and overall survival. RESULTS: HPV DNA was detected in 75% of patients with invasive carcinomas and in 50% of patients with verrucous carcinomas. High risk HPVs were detected in 15 of 54 (27.8%) patients with HPV positive invasive tumors and in 1 of 4 (25%) patients with HPV positive verrucous tumors. HPV 16 was the most frequent type observed. No correlation was observed between HPV status and histological subtype (p = 0.51) as well as HPV status and stage stratification (p = 0.88). HPV status was also not significantly associated with the presence of regional metastases (p = 0.89). The overall survival was related to the presence of lymph node metastases (p < 0.0001). CONCLUSIONS: HPV infection may have contributed to malignant transformation in a large proportion of our penile cancer cases but only inguinal metastasis was a prognostic factor for survival in these patients with penile carcinoma.

Human papillomavirus and penile cancers in Rio de Janeiro, Brazil: HPV typing and clinical features

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) DNA in penile cancers in Rio de Janeiro, Brazil. MATERIALS AND METHODS: We studied, prospectively, 80 consecutive cases of patients with penile cancers who underwent surgical treatment at three different Hospitals in Rio de Janeiro between March 1995 and June 2000. Of these patients, 72 were diagnosed with invasive squamous cell carcinoma and 8 patients with verrucous carcinoma. The following parameters were observed: presence or absence of HPV DNA viral type, histological subtypes, clinical stage and overall survival. RESULTS: HPV DNA was detected in 75 percent of patients with invasive carcinomas and in 50 percent of patients with verrucous carcinomas. High risk HPVs were detected in 15 of 54 (27.8 percent) patients with HPV positive invasive tumors and in 1 of 4 (25 percent) patients with HPV positive verrucous tumors. HPV 16 was the most frequent type observed. No correlation was observed between HPV status and histological subtype (p = 0.51) as well as HPV status and stage stratification (p = 0.88). HPV status was also not significantly associated with the presence of regional metastases (p = 0.89). The overall survival was related to the presence of lymph node metastases (p < 0.0001). CONCLUSIONS: HPV infection may have contributed to malignant transformation in a large proportion of our penile cancer cases but only inguinal metastasis was a prognostic factor for survival in these patients with penile carcinoma.

Subacute progression of human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.

Although human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is usually described as a chronic disabling disease, a rapid course over months or even weeks has been reported in some patients. The authors describe the clinical features of HAM/TSP in a Brazilian cohort and evaluate the prevalence of patients with a subacute progression of the disease. This was defined as the requirement of a wheelchair during the first 2 years after the onset of symptoms. Patients with this subacute course and patients with the chronic clinical course were compared in terms of their HTLV-I proviral loads (PLs) using real-time polymerase chain reaction (PCR). Seven out of 88 patients (7.9%) had a subacute progression. All patients were women and 5/7 acquired HTLV-I through sexual contact. There was no significant difference in the real-time PLs between the group with subacute evolution (mean 8.5 copies/100 cells, range 6.03 to 12.09) and those patients with a typical course of disease (mean 11.34 copies/100 cells, range 0.4 to 67.72) (P = .68), suggesting that factors other than the number of infected cells are implicated in the development of such an aggressive course of disease. Early recognition of this subgroup is important because immunosuppressive treatment might be beneficial if instituted promptly.

Peripheral neuropathy in HTLV-I infected individuals without tropical spastic paraparesis/HTLV-I-associated myelopathy.

Tropical spastic paraparesis/ HTLV-I-associated myelopathy (TSP/HAM) is the classical neurological manifestation of HTLV-I. Only a few studies have described isolated peripheral neuropathy (PN) among HTLV-I infected individuals. 335 infected individuals without TSP/HAM were evaluated for the presence of PN and 45 of them showed evidences of peripheral nervous system involvement. Of these 21 patients had isolated PN, defined by clinical and/or electrophysiological criteria. Sural nerve biopsies revealed inflammatory infiltrates in 2, axonal degeneration in 2 and segmental demyelination in 1. Therefore, peripheral neuropathy can be found as an isolated manifestation of HTLV-I infection. We conclude that HTLV-I infection should be investigated in patients with PN of unknown origin.

Dermatological findings of human T lymphotropic virus type 1 (HTLV-I)-associated myelopathy/tropical spastic paraparesis.

Dermatological findings for patients with human T lymphotropic virus type 1(HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were investigated and were compared with dermatological findings for a control group. Only xerosis, cutaneous candidiasis, and palmar erythema were significantly associated with HAM/TSP. Histopathological patterns of cutaneous lymphoma were seen in 25% of 32 patients who underwent biopsy, and, thus, the cutaneous alterations in HAM/TSP can be classified into nonspecific lesions, infectious lesions, immune-inflammatory-mediated lesions, and premalignant or malignant lesions.

TP53 mutations in breast cancer tumors of patients from Rio de Janeiro, Brazil: association with risk factors and tumor characteristics.

Somatic mutations in the TP53 gene are the most frequently observed genetic alterations in human malignancies, including breast cancer, which is one of the leading causes of death among women in Brazil. In our study, we determined the frequency and the pattern of TP53 mutations in malignant breast tumors from 120 patients living in Rio de Janeiro, Brazil. TP53 mutations were found in 20% of the tumors, which contained a diversity of mutation types: missense (62.5%), nonsense (8.3%), silent (4.2%), intronic (12.5%), insertion (4.2%) and deletion (8.3%). Of a total of 15 missense mutations, 4 were observed at Arg248 and 2 at Cys242, which are directly involved in DNA binding and in zinc binding, respectively. A subgroup of 51 patients was analyzed with respect to the relation between the presence of TP53 mutations and classical risk factors and with tumor and patient characteristics. For this analysis, we used logistic regression and, in order to obtain more precise confidence intervals, they were recalculated using a bootstrap resampling technique. Our results demonstrate that these mutations are not statistically associated with the risk factors or the patients' characteristics. However, the presence of TP53 mutations is strongly associated with the aggressiveness of the tumors, measured by Elston classification (OR = 11.97 and 95% CI of 2.24-307.05). This finding is in agreement with previous studies, which report the presence of TP53 mutations in tumors with poor prognosis. This correlation between tumor aggressiveness and TP53 mutations could be a crucial variable for the treatment and prognosis of breast cancer.

Ultrastructural aspects of the human T-lymphotropic virus type I (HTLV-I) in Brazil

Nowadays, Brazil may be considered an endemic area for HTLV-I infection. Several studies showed a high incidence of HTLV-I infection among the general population and different groups such as blood donors, hemophiliacs, hematological and neurological patients. Cases of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-I associated myelopathy have been already described. Therefore the use of different technical approaches, to characterize Brazilian HTLV strains has become important. HTLV particles were characterized and recognized by the use of transmission electron microscopy in lymphocyte cocultures. The ultra-structural analysis revealed typical virus particles close to the lymphocyte membrane. The immunoelectron microscopy allowed the identification of the virus as HTLV, a type C oncovirus, group HTLV-BLV. The ethanol phosphotungstic acid technique showed structures similar to the virus budding process and the routine preparations have contributed to the analysis of the first virus-cell interaction events. Structures related to the endocytic route HTLV entrance are also pointed out.