Inhibition of the replication of hepatitis B virus by the carbocyclic analogue of 2''-deoxyguanosine.

We report that treatment of 2.2.15, a human hepatoblastoma-derived cell line in which hepatitis B virus is actively replicating, with the carbocyclic analogue of 2'-deoxyguanosine [Shealy, Y. F., O'Dell, C. A., Shannon, W. M. & Arnett, G. (1984) J. Med. Chem. 27, 1416-1421] resulted in the nearly complete cessation of viral replication, as monitored by the absence of both intracellular episomal and secreted viral DNAs and by the absence of viral DNA polymerase activity. The drug was nontoxic in concentrations up to 200 times the minimum effective inhibitory concentration.     

Experience with the surgical management of childhood fractures and epiphyseal injuries]

Authors analyse 1792 fractures in children, treated during 10 years in their Department and distributed in age groups. They take the part of conservative treatment of the majority, about two third, of fractures in childhood. They consider as operative indication certain forms of epiphyseal injuries, the dislocated intraarticular fractures, the unstable fractures, certain cases of polytrauma and the open fractures.     

Hormone replacement therapy reduces mean 24-hour blood pressure and its variability in postmenopausal women with treated hypertension

BACKGROUND: The rate and severity of hypertension increase dramatically after menopause. Complications seem to be more frequent and marked in hypertensive patients with greater blood pressure (BP) variability, and antihypertensive treatment does not easily reduce this variability. The effect of hormone replacement therapy (HRT) on BP and its variability is not well understood in moderate to severe hypertension, but estrogen may have calcium channel-blocking properties. Cardiovascular events occur more frequently in the morning, likely in part because of a rise in BP. DESIGN: We prospectively studied 34 postmenopausal women with treated hypertension (mean age = 53 years) and receiving a cyclic combination of estradiol and norgestrel for 19 weeks with 24-h ambulatory BP monitoring. RESULTS: Mean daily BP and its variability decreased significantly with HRT (149.3 +/- 6.1 mm Hg vs. 140.3 +/- 8.5 mm Hg [p < 0.001]; diastolic: 95.4 +/- 4.7 mm Hg vs. 92.4 +/- 7.2 mm Hg [p < 0.05]). There was also a significant decrease in the early morning BP values after HRT (154.0 +/- 6.9 mm Hg vs. 145.6 +/- 11.0 mm Hg [p < 0.001]; diastolic: 98.0 +/- 4.8 mm Hg vs. 95.1 +/- 10.0 mm Hg [p < 0.05]). Subjects who were taking calcium channel blockers (n = 11) had only half the reduction in 24-h systolic BP compared with those who were not taking calcium channel blockers (5.3 mm Hg vs. 10.5 mm Hg), and the reduction in those who were taking calcium channel blockers failed to reach statistical significance. CONCLUSIONS: Our results demonstrate that HRT may have a role in decreasing the severity of hypertension, and the mechanism of its action might be through calcium channels.     

Cloning and genomic characterization of Felis domesticus papillomavirus type 1

A novel papillomavirus was cloned from hyperkeratotic cutaneous lesions of a Persian domestic cat. The Felis domesticus papillomavirus (FdPV-1) genome counts 8300 bp and has a typical genome structure with an early region (E1, E2, E4, E6, E7), a late region (L1, L2), and a noncoding upstream regulatory region (URR or NCR1) between the end of L1 and the beginning of E6. The FdPV-1 also shows an unusual second noncoding region (NCR2) of 1.3 kb, situated between the end of E2 and the beginning of L2. This NCR2 is uniquely related to a similar region in the canine oral papillomavirus (COPV). Phylogenetic analysis places FdPV-1 together with COPV, the cottontail rabbit papillomavirus, human papillomavirus type 1 (HPV-1), and HPV-63 in the group of the benign cutaneous papillomaviruses. The position of FdPV-1 in the phylogenetic tree allows us to hypothesize that already in an early phase of the papillomavirus molecular evolution, a split occurred into viruses with a dual tropism primarily for cutaneous epithelia but also secondarily for mucosal surfaces, and viruses with a specific monotropism for mucosal surfaces. The close relationship between FdPV-1 and COPV, and between their Canidae and Felidae hosts, supports the hypothesis that papillomaviruses have speciated and coevolved together with their hosts throughout vertebrate evolution. A papillomavirus mutation rate of 0.73 to 0.96 x 10(-8) nucleotide substitutions per base per year was calculated.     

Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications

We studied the pattern of E-cadherin expression in 183 invasive carcinomas (100 ductal, 42 lobular, 41 with mixed ductal and lobular features) and 198 in situ carcinomas (131 ductal, 53 lobular, 14 in situ with ductal and lobular features) by immunohistochemistry. We found a highly significant correlation of E-cadherin membrane expression with the histologic phenotype of the tumors. While moderate to strong membrane expression of E-cadherin was seen in all invasive and in situ ductal carcinomas, 41 of 42 invasive and 50 of 53 in situ lobular carcinomas showed complete loss of expression. All in situ carcinomas diagnosed histologically as showing mixed ductal and lobular features demonstrated complete loss of staining. Invasive carcinomas with ductal and lobular features showed 3 staining patterns: (1) complete or almost complete lack of membrane staining similar to that seen in lobular carcinomas, (2) uniform membrane expression throughout the tumor similar to ductal carcinomas, and (3) focal loss of E-cadherin staining, which correlated well with the histologic impression of focal lobular features. In tumors with histologically equivocal features, immunohistochemical detection of E-cadherin expression can be a useful diagnostic tool for the differentiation of ductal and lobular carcinomas of the breast.     

The innate immune response under the control of the LXR pathway

Macrophages play essential roles in infection and resolution of inflammation. This review summarizes recent findings that suggest a relevant role for the nuclear receptor liver X receptor (LXR) in the evolution of immune responses. By exerting both positive and negative regulation of specific macrophage gene expression networks, LXRs display anti-inflammatory activities and promote macrophage survival in bacterial infection settings. Agonists that activate the LXR pathway may be used to enhance innate immunity to highly virulent pathogens that otherwise induce macrophage apoptosis as a means to subvert host immune defense.     

Duodenal carcinoid tumor: report of a case diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy with immunocytochemical correlation

Fine-needle aspiration biopsy is a reliable and accurate method for the endoscopic diagnosis of gastrointestinal malignancies and it is particularly well suited for evaluation of submucosal lesions. We report the cytopathologic findings of a case of malignant carcinoid tumor of a 44-year-old male who presented with melena and a nonhealing duodenal ulcer. Endoscopic ultrasound examination revealed a submucosal lesion in the pyloric region. Fine-needle aspiration revealed abundant cellularity with tumor cells arranged in sheets and loose groups and dispersed single cells in a clean background. Papillary fragments, capillaries cuffed by tumor cells, and rosette formation were also noted. The cells were moderate in size, round to oval, with a small subpopulation of spindle-shaped cells. The nuclei were uniform, round to oval, with smooth nuclear borders. The chromatin pattern was finely granular with a salt-and-pepper appearance. The cytoplasm of the cells was small to moderate in amount, pale, and showed fine granularity. The differential diagnosis included a neuroendocrine neoplasm vs. an epithelioid gastrointestinal stromal tumor. The tumor cells were focally positive for chromogranin and negative for CD34, supporting the diagnosis of a neuroendocrine neoplasm. The differential diagnosis of primary gastrointestinal carcinoid tumors from gastrointestinal stromal tumors can be very difficult in cytologic material. In cases when diagnostic material is scant, or only present on one smear, the use of smear division and cell transfer in order to perform immunocytochemical stains may be of considerable value to confirm the neuroendocrine nature of the neoplasms.     

Loss of membrane expression of E-cadherin in leukemic erythroblasts

CONTEXT: The special societal relationships existing between various cell types in bone marrow suggests that there may be a link between the adhesive characteristics of hematopoietic cells and their maturation. Egress of the developing hematopoietic cells is also a highly regulated process governed by adhesive interactions. In leukemia, immature blasts are not retained within the marrow, suggesting a breakdown of adhesive mechanisms. Recent reports suggest that E-cadherin, an epithelial adhesion molecule, is expressed on erythroid precursors and megakaryocytes, but not on other hematopoietic marrow elements. OBJECTIVE: To characterize the expression pattern of E-cadherin in normal and leukemic erythroid precursors by immunohistochemistry in paraffin-embedded tissue and bone marrow aspirate smears. METHODS: Five normal bone marrow specimens from rib resections, 15 trephine bone marrow biopsy specimens, and 6 bone marrow aspirate smears from the iliac crest of patients with no known leukemia were selected. Fourteen bone marrow biopsy specimens from patients with erythroleukemia were also studied. Immunoperoxidase staining of paraffin-embedded tissue and air-dried aspirate smears for E-cadherin (1:200 dilution, HECD-1 clone) was performed using the avidin-biotin peroxidase technique. RESULTS: In paraffin-embedded bone marrow biopsy and rib specimens and in air-dried bone marrow aspirate smears, strong membrane expression of E-cadherin was seen in the normal erythroid precursors in all cases. In contrast, no membrane expression of E-cadherin was present in any of the bone marrow biopsy specimens from patients with erythroleukemia. CONCLUSIONS: Immunohistochemical detection of membrane expression of E-cadherin may be a useful tool for identification of erythroid precursors. Cells of erythroleukemia lack membrane expression of E-cadherin, in contrast to their normal counterparts. Further studies are needed to define the potential role of E-cadherin in the maturation of erythroid precursors and to ascertain the significance of loss of membrane expression of E-cadherin in erythroleukemia.