Mantle cell lymphoma with EBV-positive Hodgkin and Reed–Sternberg-like cells in a patient after autologous PBSCT: Phenotypically distinct but genetically related tumors

The case of 70-year-old man with mantle cell lymphoma (MCL) carrying t(11;14) translocation that relapsed as nodal lymphoma combining MCL and classic Hodgkin lymphoma (cHL) 9 years after autologous peripheral blood stem cell transplant (auto-PBSCT) is reported. Lymph nodes contained two separate areas of MCL and cHL-like components. Hodgkin and Reed–Sternberg (HRS)-like cells were accompanied by a prominent histiocyte background. HRS-like cells were CD5⁻, CD15⁺, CD20⁻, CD30⁺, PAX5⁺, Bob.1⁻, Oct2⁻ and EBER⁺. The MCL component expressed cyclin D1 and SOX11, whereas cyclin D1 and SOX11 expressions were reduced and lost, respectively, in HRS-like cells. Polymerase chain reaction results showed a single clonal rearrangement of the IGH gene in MCL and cHL-like components. CCND1 break apart fluorescence in situ hybridization showed split signals in both MCL and HRS-like cells, suggesting that MCL and cHL-like components were clonally related. Acquisition of p53 expression and Epstein–Barr virus (EBV)-positivity was seen in HRS-like cells. The patient died of disease progression with elevated hepatobiliary enzymes. The autopsy showed both MCL and cHL-like components around the bile ducts, splenic white pulp and bone marrow. The two components were phenotypically distinct, but genetically related, suggesting that transformation of MCL to HRS-like cells during the course of MCL in association with EBV infection.     

Skin application of urea‐containing cream affected cutaneous arterial sympathetic nerve activity,blood flow,and water evaporation

Background/purpose: We observed that olfactory stimulation with scent of grapefruit oil elevated the activities of sympathetic nerves, and increased the plasma glycerol concentration and blood pressure. In contrast, olfactory stimulation with scent of lavender oil had opposite effects in rats. These suggest that changes in autonomic activities cause physiological functions via histaminergic H1 and H3 receptor. Moreover, it has been reported that somatic sensory stimulation affected autonomic neurotransmission. To examine effects of skin application of urea‐containing cream on cutaneous arterial sympathetic nerve activity (CASNA), blood flow, and transepidermal water loss (TEWL). Method: The activity of CASNA was determined by electrophysiological method, and cutaneous blood flow was determined using laser flowmeter in urethane‐anesthetized rats, TEWL was measured using VapoMeter in the back skin of HWY hairless rats. Results: CASNA was markedly and significantly inhibited by skin application of 10% urea‐containing cream, whereas cutaneous blood flow was significantly elevated via histaminergic H3‐receptor. In conscious hairless rats, TEWL was significantly decreased 24 h after application of 10% urea‐containing cream to the back skin. Conclusion: These findings suggest that skin application of 10% urea‐containing cream increases the cutaneous blood flow and water retaining ability, and that histaminergic H3‐receptors may mediate these effects.     

Two patients treated with pegylated interferon/ribavirin/telaprevir triple therapy for recurrent hepatitis C after living donor liver transplantation

It is difficult to use protease inhibitors in patients with recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) due to interaction with immunosuppressive drugs. We report our experience with two patients treated with telaprevir (TVR) combined with pegylated interferon/ribavirin (PEG IFN/RBV) for recurrent HCV genotype 1 infection after LT. The first was a 63‐year‐old man with HCV‐related liver cirrhosis, who failed to respond to IFN‐β plus RBV after LT. Treatment was switched to PEG IFN‐α‐2b plus RBV and TVR was started. The donor had TT genotype of interleukin (IL)‐28 single nucleotide polymorphisms (SNP) (rs8099917). The recipient had TT genotype of IL‐28 SNP (rs8099917). Completion of 12‐week triple therapy was followed by PEG IFN‐α‐2b plus RBV for 36 weeks. Finally, he had sustained viral response. The second was a 70‐year‐old woman with HCV‐related liver cirrhosis and hepatocellular carcinoma. She failed to respond to PEG IFN‐α‐2b plus RBV after LT, and was subsequently switched to PEG IFN‐α‐2b/RBV/TVR. Genotype analysis showed TG genotype of IL‐28 SNP for the donor, and TT genotype of IL‐28 SNP for the recipient. Serum HCV RNA titer decreased below the detection limit at 5 weeks. However, triple therapy was withdrawn at 11 weeks due to general fatigue, which resulted in HCV RNA rebound 4 weeks later. Both patients were treated with cyclosporin, starting with a small dose to avoid interactions with TVR. TVR is a potentially suitable agent for LT recipients who do not respond to PEG IFN‐α‐2b plus RBV after LT.     

Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway

The ATM protein kinase is activated by intermolecular autophosphorylation in response to DNA damage and initiates cellular signaling pathways that facilitate cell survival and reduce chromosomal breakage. Here, we show that NBS1 and BRCA1 are required for the recruitment of previously activated ATM to the sites of DNA breaks after ionizing irradiation, and that this recruitment is required for the phosphorylation of SMC1 by ATM. To explore the functional importance of SMC1 phosphorylation, murine cells were generated, in which the two damage-induced phosphorylation sites in SMC1 are mutated. Although these cells demonstrate normal phosphorylation and focus formation of ATM, NBS1, and BRCA1 proteins after IR, they exhibit a defective S-phase checkpoint, decreased survival, and increased chromosomal aberrations after DNA damage. These observations suggest that many of the abnormal stress responses seen in cells lacking ATM, NBS1, or BRCA1 result from a failure of ATM migration to sites of DNA breaks and a resultant lack of SMC1 phosphorylation.     

Antidepressant-like effect of centrally acting non-narcotic antitussive caramiphen in a forced swimming test

Recently, we reported that a centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test in rats. Because pharmacological properties of tipepidine apparently differ from those of typical antidepressants developed to date, we speculated that caramiphen, another centrally acting antitussive, has an antidepressant-like effect. That effect of caramiphen was studied in rats using the forced swimming test. Caramiphen at 20 and 40 mg/kg i.p. significantly reduced immobility. At 40 mg/kg i.p., it increased climbing behavior. Even at 40 mg/kg, this drug had no effect on locomotor activity. Results suggest that a centrally acting antitussive possessing inhibition of GIRK channels has an antidepressant-like effect.     

The work hours of GPs: survey of English GPs

BACKGROUND: There is no current information about the hours worked by English GPs. AIM: To compare the reported hours worked by GPs with that of other professions and to explain the variation in GP hours worked and on call. Design of study: National postal survey of 1871 GPs in February 2004. SETTING: English general practice. METHOD: Multiple regression analyses of part-time versus full-time status, hours worked, and hours on call. RESULTS: Full-time male GPs report more hours worked (49.6; 95% CI [confidence interval] = 48.9 to 50.2) than males in other professional occupations (47.9; 95% CI = 47.6 to 48.1) and male managers (49.1; 95% CI = 48.8 to 49.5). Full-time female GPs report fewer hours (43.2; 95% CI = 42.0 to 44.3) than females in other professional occupations (44.7; 95% CI = 44.4 to 45.0) and female managers (44.1; 95% CI = 43.7 to 44.5). The number of hours worked decreased with practice list size, and increased with the number of patients per GP. GPs work longer hours in practices with older patients and with a higher proportion of patients in nursing homes. Fewer hours are worked in practices with higher 'additional needs' payments. Having children under 18 years of age increased the probability that female GPs work part-time but has no effect on the probability of male GPs working part-time. Given full-time/part-time status, having children under 18 years of age reduces the hours of male and female GPs. CONCLUSION: Male English GPs report longer hours worked than other professional groups and managers. The sex differences between GPs in hours worked are mostly attributable to the differential impact of family circumstances, particularly the number of children they have. Perversely, 'additional needs' payments are higher in practices where GPs work fewer hours.     

Predicted Tracheobronchial and Pulmonary Deposition in a Murine Asthma Model

Particulate matter dosimetry provides the critical link between exposures and initial doses reaching various sites in the respiratory tract. To extrapolate findings from animal models to humans, quantitative respiratory‐tract anatomical data dosimetry in these animal models is required. The goal of this study was to provide anatomical information for the tracheobronchial and pulmonary region so predictions of particle deposition could be performed for a widely used model of asthma; the sensitized Balb/c mouse. Tracheobronchial airway morphometry of sensitized male Balb/c mice was generated from three in situ prepared lung casts. Distribution of the number of generations to terminal bronchiole for each lung lobe was determined by assigning a unique binary number to each airway. This strategy enabled the median path length to terminal bronchiole to be determined. A total of 25 median length paths to terminal bronchiole were measured (airway length, diameter, and branch angle) in each lung cast. These 25 paths were proportionately distributed among the six lobes based upon the number of median length pathways in each cast. Airway length, diameter, and branch angle were measured for each airway in the 25 median length pathways. Measurements of airway length, diameter, and branch angle for each generation were averaged to create a typical path tracheobronchial anatomy model. A pulmonary airway model was also developed so that particle deposition predictions could be performed for particle diameters of 0.2–10 micrometers. Particle deposition efficiency predictions were consistent with in vivo measured deposition. Anat Rec, 290:1309–1314, 2007. © 2007 Wiley‐Liss, Inc.