No abstract

Natural killer cells are important in innate defense against viral infections. The interplay between stimulatory and inhibitory natural killer cell receptors and their corresponding human leukocyte antigen ligands are known to influence the outcome of acute Hepatitis C virus infection. Frequencies of NK receptor genes (8 inhibitory, 6 activating and 2 pseudogenes) and HLA class II alleles (DRB1, DQB1) were analyzed in 160 Puerto-Rican American drug users with Hepatitis C virus infection; 121 had chronic viremia (CV) and 39 were spontaneous clearance (SC). We further ruled out genetic stratification using short tandem repeats. Interaction between KIR gene receptor 2DL3/2DL3 and its ligand, C1/C1 of HLA-Cw alleles and spontaneous clearance was confirmed (p=0.03, OR=3.05). We also found a new interaction between the KIR receptor gene 2DL3 with HLA-DRB1*1201 (p=0.0001, OR=22) associated with SC, and an association of HLA DQB1*0501 (p=0.05, OR=0.30) with CV. Our findings suggested a role for MHC class II alleles in Hepatitis C virus peptide presentation to T cells together with NK ligand interaction involving pathways that will be useful for the development of immunotherapeutic interventions.

The human T cell receptor (TcR) beta chain gene segment diversity has been studied using the anchored-polymerase chain reaction. Three hundred and fifty C beta-specific transcripts derived from peripheral lymphocytes were analyzed. Transcripts including V-D beta 1-J beta 2-C2 sequences were found with a high frequency (greater than 10%), suggesting that "illegitimate" joinings may constitute a cis-complementing rearrangement mechanism capable of substantially increasing the TcR beta chain combinatorial diversity. Twelve previously undescribed V beta gene segments have been identified. Five of them delineate four novel V beta subfamilies (V beta w21: two members, V beta w22, 23, 24: one member) which all have a murine homologue. The additional seven gene segments belong to the V beta 5, V beta 6, V beta 12 and V beta 13 subfamilies. In addition, the sequences of two known V beta 7 and V beta 9 gene segments have been extended. Together, the present data support the view that the contribution of the beta chain combinatorial diversity to the TcR alpha/beta variability has not yet been fully appreciated.

Since it has been postulated that liver hepatocytes may become infected by hepatitis B virus (HBV) in vivo through direct contact with infected macrophages, the possibility that a circulating cell of hematopoietic origin might be susceptible to infection with HBV was investigated. Cells positive for HBV surface antigen were identified in aspirates of bone marrow cells from people infected with HBV. These cells were used to prepare a lymphoblastoid suspension culture that contains HBV-infected cells.

The anchored-polymerase chain reaction has been used to study further the diversity of the human T cell receptor alpha chain. The analysis of 308 cDNA transcripts from human peripheral lymphocytes hybridizing with a C alpha probe led to the identification of a series of additional V alpha and J alpha gene segments. The sequences of seven V alpha gene segments which individually define a novel V alpha subfamily (termed V alpha w23 to V alpha w29) are reported. The sequences of some previously described V alpha 1, V alpha 2, V alpha 5, V alpha 7 and V alpha 22 gene segments are also extended. In addition, we report 14 novel J alpha gene segment sequences. Taken together, these data indicate that the contribution of the alpha chain combinatorial diversity to the human T cell receptor alpha/beta variability has not yet been fully appreciated.

No abstract

A total of 165 uterine cervix smears from Venezuelan women were examined by cytological techniques to identify malignant and pre-malignant cervical changes, as well as to identify Human Papilloma Virus (HPV) DNA types 6, 11, 16, 18, 31, 33 and 35. Of these smears, 119 were from nonmonogamous women who participated in a cervical carcinoma screening program. In this group, HPV-DNA was detected by hybridization in 42 samples (35%) and cervical intraepithelial neoplasia (CIN) in 13 (11%). Forty-six monogamous aboriginal women were similarly studied and no evidence of abnormal cytology or HPV-DNA of the types studied here was found in any of them. In the non-monogamous group, age at first sexual intercourse and index of parity were not associated with cervical HPV infection and/or CIN. The rates of HPV infection, however, were significantly different between the two populations, confirming that sexual behavior involving multiple partners is associated with HPV infection.

Chlorella supplementation was well tolerated in patients with chronic HCV and associated with a significant decrease in ALT liver enzyme levels.