Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) comprises molecularly distinct subgroups such as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCLs. We previously reported that CD5(+) and CD5(-)CD10(+) DLBCL constitute clinically relevant subgroups. To determine whether these 2 subgroups are related to ABC and GCB DLBCLs, we analyzed the genomic imbalance of 99 cases (36 CD5(+), 19 CD5(-)CD10(+), and 44 CD5(-)CD10(-)) using array-based comparative genomic hybridization (CGH). Forty-six of these cases (22 CD5(+), 7 CD5(-)CD10(+), and 17 CD5(-)CD10(-)) were subsequently subjected to gene-expression profiling, resulting in their division into 28 ABC (19 CD5(+) and 9 CD5(-)CD10(-)) and 18 GCB (3 CD5(+), 7 CD5(-)CD10(+), and 8 CD5(-)CD10(-)) types. A comparison of genome profiles of distinct subgroups of DLBCL demonstrated that (1) ABC DLBCL is characterized by gain of 3q, 18q, and 19q and loss of 6q and 9p21, and GCB DLBCL is characterized by gain of 1q, 2p, 7q, and 12q; (2) the genomic imbalances characteristic of the CD5(+) and CD5(-)CD10(+) groups were similar to those of the ABC and GCB types, respectively. These findings suggest that CD5(+) and CD5(-)CD10(+) subgroups are included, respectively, in the ABC and GCB types. Finally, when searching for genomic imbalances that affect patients' prognosis, we found that 9p21 loss (p16(INK4a) locus) marks the most aggressive type of DLBCL.     

Incidence and risk factors for sepsis in surgical patients: a cohort study

Purpose

The aim of the study was to evaluate risk factors for infection and sepsis in surgical patients admitted to the intensive care unit (ICU).

Materials and Methods

Data were prospectively collected from a cohort of surgical patients from January 2005 to December 2007. We analyzed the incidence of infection and sepsis and certain other variables from the pre-, intra-, and postoperative periods as risk factors for infection and sepsis.

Results

We studied 625 surgical patients. The mortality rate was 18.2%, and the mean age of the subjects was 53.1 ± 18.8 years. The incidences of severe sepsis and septic shock were 5% and 11.5%, respectively. A multivariate analysis showed that the following variables were associated with sepsis in the postoperative period: urgent surgery (odds ratio, 2.63; 95% confidence interval [CI], 1.50-4.63), fluid resuscitation (odds ratio, 1.90; 95% CI, 1.18-3.05), vasoactive drugs (odds ratio, 2.58; 95% CI, 1.61-4.14), and mechanical ventilation (odds ratio, 5.51; 95% CI, 3.07-9.89). A Sequential Organ Failure Assessment was associated with infection or sepsis upon ICU admission (area under the curve, 0.737 ± 0.019; 95% CI, 0.748-0.825).

Conclusions

This study showed that sepsis has high incidence and mortality in surgical patients admitted to the ICU. Urgent surgeries, mechanical ventilation, fluid resuscitation, and vasoactive drugs in the postoperative period and Sequential Organ Failure Assessment at ICU admission were risk factors for sepsis.     

PSEUDOMEMBRANOUS COLITIS COMPLICATING ULCERATIVE COLITIS

Clostridium difficile toxin (CD toxin) causes antibiotic‐associated colitis, or pseudomembranous colitis (PMC). Although CD toxin is sometimes found in the stools of patients with ulcerative colitis (UC), UC is rarely complicated by PMC. We report herein a case of PMC complicating UC, and present a review of the literature. A 71‐year‐old woman was diagnosed as having UC of the left colon, and treated with prednisolone and mesalazine. Later, however, lumbar spinal stenosis was also detected. After surgery for lumbar spinal stenosis, she suffered postoperative infection of the lumbar region. After 3‐week treatment with antibiotics, she developed diarrhea, bloody stools, and abdominal pain. Colonoscopy revealed PMC of the cecum, ascending colon, sigmoid colon, and rectum. Stools were positive for CD toxin. As cefotiam hydrochloride, levofloxacin hydrate (LVFX), and prednisolone were suspected as the causative agents, she was treated with 1.5 g vancomycin (VCM) daily for 2 weeks without ceasing LVFX. Her symptoms improved, and colonoscopy confirmed resolution of PMC. The possibility of PMC should be considered in UC patients treated with antibiotics, immunosuppressive agents or corticosteroids who complain of gastrointestinal symptoms. These patients should be thoroughly investigated by several modalities, including colonoscopy and CD toxin testing.     

Winter morning surge in blood pressure after the Great East Japan Earthquake

This study investigated the association between winter morning surge in systolic blood pressure (SBP) as measured by ambulatory BP monitoring and the housing conditions of subjects in an area damaged by the Great East Japan Earthquake. In 2013, 2 years after disaster, hypertensives who lived in homes that they had purchased before the disaster (n = 299, 74.6 ± 8.1 years) showed significant winter morning surge in SBP (+5.0 ± 20.8 mmHg, P < 0.001), while those who lived in temporary housing (n = 113, 76.2 ± 7.6 years) did not. When we divided the winter morning surge in SBP into quintiles, the factors of age ≥75 years and occupant‐owned housing were significant determinants for the highest quintile (≥20 mmHg) after adjustment for covariates. The hypertensives aged ≥75 years who lived in their own homes showed a significant risk for the highest quintile (odds ratio 5.21, 95% confidence interval 1.49‐18.22, P = 0.010). It is thus crucial to prepare suitable housing conditions for elderly hypertensives following a disaster.     

Contribution of nitrergic nerve in canine gingival reactive hyperemia

Reactive hyperemia reflects a compensatory vasodilation response of the local vasculature in ischemic tissue. The purpose of this study is to clarify the mechanism of regulation of this response in gingival circulation by using pharmacological analysis of reactive hyperemia and histochemical analysis of gingival tissue. Application of pressure to the gingiva was used to create temporary ischemia, and gingival blood flow was measured after pressure release. Reactive hyperemia increased in proportion to the duration of pressure. Systemic hemodynamics remained unaffected by the stimulus; therefore, the gingival reactive hyperemia reflected a local adjustment in circulation. Gingival reactive hyperemia was significantly suppressed by nitric oxide (NO) synthase inhibitors, especially the neural NO synthase-selective antagonist 7-nitroindazole, but not by anticholinergic drugs, β-blockers, or antihistaminergic drugs. Moreover, immunohistochemical staining for neural NO synthase and histochemical staining for NADPH diaphorase activity were both positive in the gingival perivascular region. These histochemical and pharmacological analyses show that reactive hyperemia following pressure release is mediated by NO-induced vasodilation. Furthermore, histochemical analysis strongly suggests that NO originates from nitrergic nerves. Therefore, NO may play an important role in the neural regulation of local circulation in gingival tissue ischemia.     

The growth factor midkine regulates the renin-angiotensin system in mice

The renin-angiotensin system plays a pivotal role in regulating blood pressure and is involved in the pathogenesis of kidney disorders and other diseases. Here, we report that the growth factor midkine is what we believe to be a novel regulator of the renin-angiotensin system. The hypertension induced in mice by 5/6 nephrectomy was accompanied by renal damage and elevated plasma angiotensin II levels and was ameliorated by an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin receptor blocker. Notably, ACE activity in the lung, midkine expression in the lung, and midkine levels in the plasma were all increased after 5/6 nephrectomy. Exposure to midkine protein enhanced ACE expression in primary cultured human lung microvascular endothelial cells. Furthermore, hypertension was not induced and renal damage was less severe in midkine-deficient mice. Supplemental administration of midkine protein to midkine-deficient mice restored ACE expression in the lung and hypertension after 5/6 nephrectomy. Oxidative stress might be involved in midkine expression, since expression of NADH/NADPH oxidase–1, –2, and –4 was induced in the lung after 5/6 nephrectomy. Indeed, the antioxidative reagent tempol reduced midkine expression and plasma angiotensin II levels and consequently ameliorated hypertension. These results suggest that midkine regulates the renin-angiotensin system and mediates the kidney-lung interaction after 5/6 nephrectomy.     

Selective adsorption of human CD4 T cells

The pathogenesis of most autoimmune diseases directly involves CD4(+) helper T cells. To remove CD4(+) T cells selectively from the circulation, we designed a new column in which an anti-CD4 monoclonal antibody was immobilized on the activated substance. Nearly 90% of CD4(+) T cells were selectively adsorbed from whole blood with a single passage through the column in vitro, resulting in depletion of the antigen-specific T cell responses. We conclude that this new column would be potentially useful for treatment of T cell-mediated autoimmune diseases.     

HLA class I distribution in Japanese patients with schizophrenia

Several Caucasian studies and one Japanese study have observed associations between human leukocyte antigen (HLA) class I specificities, including A24 (9) and A26 (10) and schizophrenia. Most of those studies were conducted in 1970s and early 1980s, when the typing technique of HLA was not adequately reliable. Also, an operational diagnostic system was not employed in many of the studies. The present study investigated frequencies of HLA-A specificities in schizophrenia patients (ICD-10 and DSM-III-R, n=98) and sex-matched healthy controls (n=392) from population in the southwestern part of Japan. HLA-B and -C specificities were studied in addition. Frequencies of subjects possessing A24 and A26 were not different between the patients and controls (54% and 24% in the patients and 62% and 24% in the controls, respectively). No significant difference was found in frequencies of other class I (A, B, and C) specificities between the patients and the controls. Thus, the present study provided no evidence for an association between the HLA class I specificities, including A24, A26, and others, and schizophrenia in the Japanese population.     

Crosstalk between high-molecular-weight adiponectin and T-cadherin during liver fibrosis development in rats

Adiponectin, a circulating adipocyte-derived secretory protein, reportedly plays an important role in liver fibrosis development, although the biological role of adiponectin in liver fibrogenesis is still controversial. Adiponectin is present in the serum as three oligometric complexes; namely, high-, middle-, and low-molecular weight (HMW, MMW, and LMW, respectively). Adiponectin exerts different biological activities in an oligomerization-dependent manner. The aim of our current study was to examine the alteration of each isoform of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) during the choline-deficient L-amino acid-defined (CDAA) diet-induced rat liver fibrosis development. We also elucidated the methylation status of all receptors. The serum level of total adiponectin significantly increased during the liver fibrosis development. Among the three isoforms, only HMW adiponectin was significantly up-regulated whereas MMW and LMW were not. The expression of T-cadherin, which exclusively binds with HMW adiponectin, was significantly augmented as well. The AdipoR2 expression was markedly decreased and showed no marked difference from that of AdipoR1. No obvious methylation change was observed in all three receptors, suggesting that another mechanism is involved in the alteration of receptor gene expression. Collectively, since the specific ligand and receptor were augmented together, crosstalk between HMW adiponectin and T-cadherin may play an important role during liver fibrosis development in rats.