(5′S)-8,5′-Cyclo-2′-deoxyguanosine Is a Strong Block to Replication, a Potent pol V-Dependent Mutagenic Lesion, and Is Inefficiently Repaired in Escherichia coli

8,5′-Cyclopurines, making up an important class of ionizing radiation-induced tandem DNA damage, are repaired only by nucleotide excision repair (NER). They accumulate in NER-impaired cells, as in Cockayne syndrome group B and certain Xeroderma Pigmentosum patients. A plasmid containing (5′S)-8,5′-cyclo-2′-deoxyguanosine (S-cdG) was replicated in Escherichia coli with specific DNA polymerase knockouts. Viability was \u3c1% in the wild-type strain, which increased to 5.5% with SOS. Viability decreased further in a pol II- strain, whereas it increased considerably in a pol IV- strain. Remarkably, no progeny was recovered from a pol V- strain, indicating that pol V is absolutely required for bypassing S-cdG. Progeny analyses indicated that S-cdG is significantly mutagenic, inducing ∼34% mutation with SOS. Most mutations were S-cdG → A mutations, though S-cdG → T mutation and deletion of 5′C also occurred. Incisions of purified UvrABC nuclease on S-cdG, S-cdA, and C8-dG-AP on a duplex 51-mer showed that the incision rates are C8-dG-AP \u3e S-cdA \u3e S-cdG. In summary, S-cdG is a major block to DNA replication, highly mutagenic, and repaired slowly in E. coli

Basic Taste Stimuli Elicit Unique Responses in Facial Skin Blood Flow

Facial expression changes characteristically with the emotions induced by basic tastes in humans. We tested the hypothesis that the five basic tastes also elicit unique responses in facial skin blood flow. Facial skin blood flow was measured using laser speckle flowgraphy in 16 healthy subjects before and during the application of basic taste stimuli in the oral cavity for 20 s. The skin blood flow in the eyelid increased in response to sweet and umami taste stimuli, while that in the nose decreased in response to a bitter stimulus. There was a significant correlation between the subjective hedonic scores accompanying these taste stimuli and the above changes in skin blood flow. These results demonstrate that sweet, umami, and bitter tastes induce unique changes in facial skin blood flow that reflect subjective hedonic scores

Activation-Induced Cytidine Deaminase Expression in CD4+ T Cells is Associated with a Unique IL-10-Producing Subset that Increases with Age

Activation-induced cytidine deaminase (AID), produced by the Aicda gene, is essential for the immunoglobulin gene (Ig) alterations that form immune memory. Using a Cre-mediated genetic system, we unexpectedly found CD4+ T cells that had expressed Aicda (exAID cells) as well as B cells. ExAID cells increased with age, reaching up to 25% of the CD4+ and B220+ cell populations. ExAID B cells remained IgM+, suggesting that class-switched memory B cells do not accumulate in the spleen. In T cells, AID was expressed in a subset that produced IFN-γ and IL-10 but little IL-4 or IL-17, and showed no evidence of genetic mutation. Interestingly, the endogenous Aicda expression in T cells was enhanced in the absence of B cells, indicating that the process is independent from the germinal center reaction. These results suggest that in addition to its roles in B cells, AID may have previously unappreciated roles in T-cell function or tumorigenesis

Resectable pancreatic small cell carcinoma

Primary pancreatic small cell carcinoma (SCC) is rare, with just over 30 cases reported in the literature. Only 7 of these patients underwent surgical resection with a median survival of 6 months. Prognosis of SCC is therefore considered to be poor, and the role of adjuvant therapy is uncertain. Here we report two institutions' experience with resectable pancreatic SCC. Six patients with pancreatic SCC treated at the Johns Hopkins Hospital (4 patients) and the Mayo Clinic (2 patients) were identified from prospectively collected pancreatic cancer databases and re-reviewed by pathology. All six patients underwent a pancreaticoduodenectomy. Clinicopathologic data were analyzed, and the literature on pancreatic SCC was reviewed. Median age at diagnosis was 50 years (range 27–60). All six tumors arose in the head of the pancreas. Median tumor size was 3 cm, and all cases had positive lymph nodes except for one patient who only had five nodes sampled. There were no perioperative deaths and three patients had at least one postoperative complication. All six patients received adjuvant therapy, five of whom were given combined modality treatment with radiation, cisplatin, and etoposide. Median survival was 20 months with a range of 9–173 months. The patient who lived for 9 months received chemotherapy only, while the patient who lived for 173 months was given chemoradiation with cisplatin and etoposide and represents the longest reported survival time from pancreatic SCC to date. Pancreatic SCC is an extremely rare form of cancer with a poor prognosis. Patients in this surgical series showed favorable survival rates when compared to prior reports of both resected and unresectable SCC. Cisplatin and etoposide appears to be the preferred chemotherapy regimen, although its efficacy remains uncertain, as does the role of combined modality treatment with radiation

Adenocarcinoma arising in a cystic duplication of the small bowel: case report and review of literature

Enteric duplications are rare, but can occur anywhere along the digestive tract. Most of the patients become symptomatic in early childhood and only a few cases of adult patients have been reported in literature. Here we report a unique case of an adenocarcinoma arising in a coincidentally found cystic duplication of the small bowel