OATP1B3 is an organic anion transporting polypeptide (OATP) that functions as a multispecific transporter in the normal liver. We examined the expression and clinical significance of OATP1B3 in colon ...cancers in tissue microarrays.
Immunohistochemistry was used to assess OATP1B3 protein expression in paraffinized colon tumor tissue microarrays. OATP1B3 immunostaining was evaluated by location and intensity. Relationships between OATP1B3 expression, known prognostic variables and clinical outcomes were examined.
278 colon tumor samples of all stages were evaluated for OATP1B3 expression. OATP1B3 immunostaining was detectable in the majority (56%) of the tumor samples. Higher OATP1B3 expression was seen in lower stage tumors (p = 0.003) and lower grade (p = 0.004) tumors, but was not predictive of 5-year survival or tumor recurrence as an independent variable. Within individual tumor grades, OATP1B3 expression was associated with improved 5-year survival, but not recurrence in patients with poorly differentiated tumors.
OATP1B3 expression was seen in the majority of colon tumors and may be a marker of lower grade and lower stage tumors and may predict for improved outcome in certain tumors.
With the reintroduction of smallpox vaccination, detailed contemporary descriptions of adverse reactions to the vaccine are needed to adequately inform the public and clinicians. During a ...multicenter, randomized controlled trial investigating the efficacy of various dilutions of smallpox vaccine, we observed the appearance of a papulovesicular eruption (focal and generalized) in study volunteers.
To characterize the papulovesicular eruptions by clinical, virologic, and histopathological characteristics.
Prospective case series of papulovesicular eruptions following smallpox vaccination in healthy, vaccinia-naive adult participants compared with noncases conducted from October 2002 to March 2003. Variables potentially related to these eruptions were collected retrospectively through chart review. Eruptions were described based on viral culture, clinical examination, and histopathological evaluation (1 biopsy specimen from 1 case).
Cases of papulovesicular eruptions following vaccination.
During the trial, of 148 volunteers (56% women; mean age 23.6 years), 4 participants (2.7%) developed generalized eruptions and 11 (7.4%) noted focal eruptions. Viral cultures of sample lesions were negative for vaccinia. The result of a skin biopsy sample from 1 case of generalized rash revealed suppurative folliculitis without evidence of viral infection. All lesions resolved without scarring. In the cohort, cases and noncases did not show significant differences in terms of sex, in the use of nonsteroidal anti-inflammatory drugs or oral or depo contraceptives, in medication allergies, in the incidence of fever or lymphadenopathy after vaccination, or in the dilution of vaccine received.
Folliculitis is a common and benign eruption observed in vaccinia-naive adult volunteers following smallpox vaccination. This eruption may be seen in volunteers receiving the vaccine in the newly instituted vaccination programs and may be met with heightened anxiety, potentially being confused with generalized vaccinia. This description of folliculitis using clinical, virologic, and histopathological findings should allay these concerns and provide additional insight into this eruption.
Somatic hypermutation of antibody genes is mediated by activation-induced cytidine deaminase and targets primarily hotspot motifs. We tested the hypothesis that the antibody variable genes of ...virus-specific B cells from infants exhibit a decreased frequency of somatic mutations compared with adults. We also sought to determine whether virus-specific B cells exhibit predominantly hotspot or randomly directed processes. We analyzed somatic mutations in rotavirus (RV)-specific B cells from otherwise healthy but recently RV-infected infants or adults in comparison with B cells from healthy volunteers not recently infected. We compared these antibody variable gene sequences with those derived from RV-specific B cells from an adult patient with X-linked hyper-IgM syndrome (XHIM). We found that the overall mutational frequency within the antibody variable region was lowest in RV-specific B cells from RV-infected infants, followed by randomly selected B cells, followed by RV-specific B cells from the patient with XHIM. RV-specific memory B cells from healthy adults exhibited the highest frequency of mutations. Approximately half of mutations in random or RV-specific B cells from adults or infants occurred at the DGYW/WRCH or WA/TW hotspot motifs. These findings suggest that virus-specific antibodies require both hotspot and randomly-directed processes.
Reports of sex steroid receptor expression in chordoma suggest that these tumors may be responsive to hormone manipulation therapy. Immunohistochemical stains for estrogen receptor (ER)-alpha, ...ER-beta, progesterone receptor (PR), androgen receptor (AR), and cyclooxygenase 2 (COX-2), were performed on a tissue microarray containing 21 samples of chordoma. Most chordomas expressed COX-2, ER-beta, and AR, whereas ER-alpha and PR stains were negative in all cases. ER-beta expression did not correlate with AR expression (P = .4142; McNemar test). There were no statistically significant correlations between the expression of any of these markers and anatomic location of tumor, patient sex, patient age, or disease-free survival. Chordomas commonly express COX-2, AR, and ER-beta. These findings may have therapeutic implications concerning the use of agents that inhibit or modulate these signaling molecules.
Antiviral antibody responses in infants are limited in quality. One reason for this finding could be that the majority of B cells in infants are CD5
+ cells, a subset of B cells that is thought to ...contain cells expressing polyreactive, low-affinity B cell receptors. We analyzed the rotavirus (RV)-specific antibody heavy chain variable region (VH) repertoire in CD5
+ and CD5
− B cells of four RV-infected children between 10 and 19 months of age. We found that the RV-specific B cell repertoire in CD5
+ cells was VH3 family biased, in contrast to the VH1/VH4 dominance seen in CD5
− B cells. The immunodominant RV-specific gene segment in CD5
− B cells was VH1-46, which is the dominant segment used in RV-specific peripheral blood B cells from infants and adults. In contrast, the immunodominant gene segment was VH3-23 in RV-specific CD5
+ B cells, which is the dominant gene segment in randomly selected B cells. Both RV-specific CD5
+ and RV-specific CD5
− B cells from all children studied demonstrated very low frequencies of somatic mutations. In conclusion, CD5
+ B cells in infants responding to RV use an antibody gene repertoire that differs from the virus-specific repertoire of CD5
− B cells, and both CD5
+ and CD5
− RV-specific B cells exhibit a low frequency of somatic mutations.
The objectives of this study were to define the magnitude, time course, and virologic and immunologic correlates of HAART-associated reconstitution of cytomegalovirus (CMV)-specific cell-mediated ...immunity (CMI) in pediatric HAART recipients. Thirty-five HIV-infected CMV-seropositive subjects < or = 22 years on or about to receive HAART had CMV-CMI measured by responder cell frequency (RCF) and interferon-gamma (IFN-gamma) secretion over 3 years. RCF was detected in 33, 52, 38, and 28% before HAART and at years 1, 2, and > or = 3, respectively. Corresponding percentages for IFN-gamma were 100, 85, 100, and 38%. Neither RCF nor IFN-gamma was significantly associated with CD4% before or after HAART initiation. Lower HIV replication was associated with a higher proportion of subjects with positive RCF, but not IFN-gamma. There were no clinical CMV manifestations during the study. HIV-infected children did not demonstrate a significant increase in CMV-CMI with longer HAART duration, which suggests that CMV immunereconstitution involves more complex immunologic and virologic interactions than previously anticipated.
Somatic hypermutation (SHM) of immunoglobulin genes requires activation-induced cytidine deaminase (AID). The error-prone DNA polymerases, such as Pol η, Pol ζ, and Pol ι, also have been implicated ...in the process. Human adult antibodies directed to microbial pathogens are increased in affinity and function compared with those of infants. Adult antibodies achieve this increased affinity through somatic mutations, which are lacking in the B cells of infants. It is unknown if infant B cells are capable of upregulating the cell machinery needed to introduce mutations after stimulation through the antigen receptor. We show here that infant B cells exhibit similar kinetics and magnitude of transcription of
AID and
pol η genes and only marginally lower levels of
pol ι and
pol ζ genes after stimulation through the B cell receptor. These data suggest that the ability to upregulate gene transcription of enzymes mediating SHM is not a limiting determinant of the functional quality of infant antibody responses.
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