Epidemiologic and virologic characteristics of hepatitis B virus genotype B having the recombination with genotype C

BACKGROUND & AIMS: Hepatitis B virus (HBV) isolates of genotype B (HBV/B) with or without the recombination with genotype C over the precore region plus core gene have been reported. METHODS: All the 41 HBV/B isolates having the recombination with genotype C (HBV/Ba) possessed the nucleotide 1838 of A in contrast to that of G in all 29 of those without the recombination (HBV/Bj). Taking advantage of this single nucleotide polymorphism, a restriction fragment length polymorphism method was developed that distinguished HBV/Ba from HBV/Bj. RESULTS: HBV/Bj was detected in 90 of the 97 (93%) carriers of HBV/B from Japan, whereas HBV/Ba occurred in all 177 carriers of HBV/B from other countries (China, 20; Hong Kong, 45; Taiwan, 32; Thailand, 30; Vietnam, 30; and the United States, 20 [all of an Asian ethnicity]). In a case-control study, hepatitis B e antigen (HBeAg) and the double mutation in the core promoter (T1762/A1764) were significantly more frequent in 80 carriers each of HBV/Ba than HBV/Bj (35% vs. 18%, P < 0.05 and 33% vs. 15%, P < 0.05, respectively). Differences in the prevalence of HBeAg were more conspicuous between the carriers of HBV/Bj and HBV/Ba older than 30 years (5 of 66 or 8% vs. 16 of 62 or 26%, P < 0.01). CONCLUSIONS: HBV/B having the recombination with genotype C is frequent in Asia, except in Japan, and HBeAg is more prevalent in carriers of HBV/Ba than HBV/Bj.     

Cyclic strain delays the expression of tissue factor induced by thrombin in human umbilical vein endothelial cells

Most studies of tissue factor (TF) expression in endothelial cells (EC) are performed under stationary culture conditions. The purpose of this study was to determine the influence of mechanical stimuli such as cyclic strain (CS) on the expression of TF in EC exposed to thrombin (Thr). Human umbilical vein endothelial cells (HUVEC) were exposed to 4 U·mL⁻¹ Thr in the presence or absence of 10% average CS at 60 cycles·min⁻¹ and then TF expression was measured. TF messenger RNA (mRNA) expression peaked at 2 hours in HUVEC exposed to Thr, but at 4 hours in HUVEC exposed to both Thr + CS. TF expression was inhibited by p38 and extracellular signal-regulated protein kinase (ERK) inhibitors. For both Thr or Thr + CS stimuli, p38 and ERK activity peaked at 5 minutes (p < 0.05). Nuclear factor-kappa B levels remained high in the Thr group but not in the Thr + CS group, while Egr-1 levels were elevated in the Thr + CS group. We demonstrated CS-delayed, Thr-induced TF mRNA expression in HUVEC, which may be modulated by p38 and ERK inhibitors.     

CBCT of skeletal changes following rapid maxillary expansion to increase arch-length with a development-dependent bonded or banded appliance

Objective:To assess the three-dimensional (3D) skeletal response to a standardized 5 mm of rapid maxillary expansion (RME) in growing children (6–15 years) with maxillary width deficiency and crowding.Materials and Methods:A bonded appliance was used prior to the eruption of the maxillary first premolars (Mx4s), and a banded appliance was used thereafter. A consecutive sample of 89 patients (29 boys and 60 girls) from a large pediatric dentistry and orthodontics practice was divided into four groups: 1) 6–8 years old (n  =  26), 2) 9–11 years old with unerupted Mx4s (n  =  21), 3) 9–11 years with erupted Mx4s (n  =  23), and 4) 12–15 years (n  =  19). For all patients, the 3D evaluation of dental and skeletal effects was performed with cone-beam computed tomography (CBCT).Results:For both appliances in all patients, CBCT confirmed a triangular pattern of expansion in both the frontal and sagittal planes. Overall, both appliances produced significant maxillary expansion (>80% of the 5-mm activation), but older children showed a progressively more dental (less skeletal) response. Comparison of the two types of expanders in the crossover sample, children aged 9–11 years, showed that the bonded RME produced the most efficient skeletal expansion in the preadolescent sample. Increased maxillary width at the level of the zygomaticomaxillary suture was the best indicator for development of maxillary arch circumference.Conclusion:Development-dependent appliances (bonded RPE before Mx4s erupt, and a banded device thereafter) provided optimal RME treatment for all children from age 6–15 years.     

Defucosylated anti CC chemokine receptor 4 monoclonal antibody combined with immunomodulatory cytokines: a novel immunotherapy for aggressive/refractory Mycosis fungoides and Sezary syndrome.

PURPOSE: Sézary syndrome (SS) and Mycosis fungoides (MF) in the advanced stage have dismal prognoses. Because CC chemokine receptor 4 (CCR4) has an important role in the skin-homing capacity of MF/SS cells, we postulated that anti-CCR4 monoclonal antibody (mAb) could represent a novel therapeutic agent against aggressive/refractory MF/SS. EXPERIMENTAL DESIGN: The defucosylated next-generation therapeutic mAb KM2760 induces enhanced antibody-dependent cellular cytotoxicity (ADCC). Here, we assessed the therapeutic potential of this antibody against aggressive MF/SS tumor cells in vitro and in animal models in vivo. RESULTS: KM2760 induced robust ADCC by peripheral blood mononuclear cell (PBMC) from healthy controls against a MF/SS cell line as well as against primary tumor cells from patients with aggressive MF/SS. KM2760 also showed significant antitumor activity in disseminated and nondisseminated MF/SS mouse models. In addition, approximately 30% of autologous MF/SS tumor cells were killed in in vitro assays of KM2760-induced ADCC mediated by patients' PBMC after only 4 h, despite the low numbers of natural killer cells present in these PBMCs. It is also shown that ADCC induced by defucosylated therapeutic mAb can be greatly augmented by the immunomodulatory cytokines interleukin-12, IFN-alpha-2b, and IFN-gamma. CONCLUSIONS: The present study has encouraged us in the conducting of a phase I clinical trial of a completely defucosylated anti-CCR4 mAb in patients with CCR4-positive T-cell lymphomas, including aggressive MF/SS (ClinicalTrials.gov identifier: NCT00355472). In the near future, the efficacy not only of defucosylated anti-CCR4 mAb single-agent treatment but also of combination therapy with immunomodulatory cytokines will be clinically established to target aggressive/refractory MF/SS.     

Surgical Treatment of Malignant Fibrous Histiocytoma in the Left Atrium and Pulmonary Veins: Report of a Case

This report describes the case of a 16-year-old boy who underwent surgical treatment of a cardiac malignant fibrous histiocytoma (MFH). He was admitted to our hospital for exertional dyspnea. An ultracardiogram (UCG) revealed a tumor about 10 cm in diameter, in the left atrium. Extirpation of the left atrial tumor, including the part extending into the pulmonary veins, was performed under cardiopulmonary bypass. Histological examination confirmed a diagnosis of MFH. No adjuvant chemotherapy or radiotherapy was given. While there has been no evidence of local recurrence or metastasis in the 9 months since his operation, strict follow-up is being done by UCG and computed tomography. A few reviews of this entity have been reported; however, they have confused autopsy cases with surgical cases. Therefore, we reviewed only the surgical cases of this type of cardiac tumor documented in the literature. According to our review of the literature, this patient is the youngest among the 42 cases of surgically treated cardiac MFH reported to date. Received: December 28, 2000 / Accepted: September 11, 2001     

Endothelial and neuronal functions in cerebral and temporal arteries from monkeys fed a high-cholesterol diet

Modifications by hyperlipidemia of endothelium-dependent and -independent relaxations were evaluated in cerebral and temporal arteries from control and hyperlipidemic (high cholesterol-fed) monkeys. Histologically atherosclerotic lesions were not observed in either group. Relaxations induced by histamine, abolished by N(G)-nitro->L-arginine (>L-NA), were significantly potentiated in the hyperlipidemic monkey cerebral arteries, compared with those in the arteries from control monkeys. Treatment with superoxide dismutase did not affect the histamine-induced relaxation. Conversely, endothelium-dependent relaxations induced by A23187, Ca2+ ionophore, in cerebral arteries did not differ between control and hyperlipidemic monkeys. In temporal arteries, relaxations by acetylcholine and A23187 did not differ between control and hyperlipidemic monkeys. Endothelium-dependent and -independent relaxations by adenosine diphosphate in cerebral and temporal arteries were not affected by hyperlipidemia. Endothelium-independent relaxations by exogenously applied nitric oxide did not differ in the arteries from control and hyperlipidemic monkeys. Nicotine-induced relaxations in cerebral arteries, which were mediated with nitric oxide released from nitroxidergic (nitrergic) nerves, and the contractions caused by nicotine in temporal and mesenteric arteries treated with >L-NA did not differ between control and hyperlipidemic monkeys. It is concluded that long exposure to hyperlipidemia did not affect endothelial functions of monkey middle cerebral and temporal arteries but enhanced nitric oxide-mediated relaxations caused by histamine, possibly due to upregulation of endothelial histamine receptor-mediated functions in the cerebral arteries. The nitroxidergic (nitrergic) and adrenergic nerve functions do not seem to be affected by hyperlipidemia.     

Proximal dome-shaped osteotomy for symptomatic bunionette

The results of a dome-shaped osteotomy of the proximal third of the fifth metatarsal in patients with symptomatic bunionette deformity were reviewed. The series was comprised of eight patients (10 feet; mean age of patients, 21 years). The average followup was 30 months. All patients were free from pain at the fifth metatarsophalangeal joint and were satisfied with the results of this procedure. The mean angle between the longitudinal axes of the fifth metatarsal and the proximal phalanx was 18.9 degrees before surgery and 2.6 degrees after surgery. The mean angle between the longitudinal axes of the fourth and fifth metatarsals was 12.2 degrees before surgery and 4.8 degrees after surgery. The overall results were good in all 10 feet. Three feet had delayed union at the osteotomy site, but union was obtained in all feet. The osteotomy site of the fifth metatarsal in feet with delayed union was more proximal than that of the other feet. Therefore, proximal osteotomy of the fifth metatarsal should be done not at the base, but at the proximal site of the diaphysis to prevent delayed union. A proximal dome-shaped osteotomy corrects the deformity and relieves the symptoms, but careful attention should be paid to the osteotomy site.     

Expression of peanut agglutinin-binding carbohydrates correlates with nodal involvement in human lung adenocarcinoma

The expression of 15 kinds of lectin-binding carbohydrates was examined histochemically in lung adenocarcinoma. The relation between expression of lectin binding carbohydrates and clinicopathologic factors was studied. The expression of peanut agglutinin (PNA) binding carbohydrates showed a high lymph node metastatic rate. Relation between PNA-binding carbohydrate expression and lymphatic vessel invasion was also recognized. Multivariate analysis showed that PNA-binding carbohydrate expression was an independent predictive factor of lymph node metastasis (odds ratio: 2.8) and of lymphatic vessel invasion (odds ratio: 5.2). The expression of PNA-binding carbohydrates would be a significant predictive factor for lymph node metastasis of lung adenocarcinomas.     

Erythropoietin receptor in myelodysplastic syndrome and leukemia

Erythropoietin (Epo) is one of the main regulators of growth and differentiation of hematopoietic cells. In normal bone marrow cells, the amount of erythropoietin receptor (EpoR) was highest in the CD34+ CD38- subset, and decreased on lineage committed progenitor cells expressing CD38 antigens. Among the erythroid cells expressing GpA antigens, CD34-positive fractions expressed more EpoR than CD34-negative fractions. Although the amounts of EpoR of bone marrow cells from patients with refractory anemia (RA) were less than those of normal bone marrow cells in all phenotypes examined, there was no statistical significant difference. EpoR was detected on leukemia cells from 60% of acute myeloblastic leukemia (AML) cases and 29% of acute lymphoblastic leukemia (ALL) cases, and distributed widely among all FAB-subtypes. In spite of the presence of EpoR, in vitro proliferative response to Epo was not observed in a large proportion of AML. And there was no correlation between the amount of EpoR and the in vitro response to EPO. Patients with both EpoR expression and in vitro response to Epo had shorter remission duration than those without EpoR.