Human herpesvirus 8 (HHV8) sequence variations in HHV8 related tumours in Okinawa, a subtropical island in southern Japan

BACKGROUND: Although rare in mainland Japan, classic Kaposi's sarcoma (KS) is frequently reported in Okinawa, a subtropical island in southern Japan. Human herpesvirus 8 (HHV8) has been identified in the tumours and geographical differences occur. Aim: To sequence HHV8 in classic and AIDS associated KS in Okinawa. MATERIALS/METHODS: Eight classic KS cases, one AIDS associated KS, five granuloma pyogenicum cases, two inflammatory pseudotumours, two Castleman's disease cases, one angiosarcoma, and one primary effusion lymphoma (PEL) were studied. As a control, HHV8 positive cultured PEL cells (TY-1) were used. The presence of HHV8 sequences was evaluated by PCR and in situ hybridisation. PCR products were sequenced. RESULTS: There were no histological differences among KS resulting from the different virus genotypes. HHV8 was detected in all cases of KS, in one PEL, and one granuloma pyogenicum. Eight classic KS cases and one granuloma pyogenicum were infected with HHV8 genotype II/C (K1 region) or subtype C (ORF26 region), which had a five amino acid deletion at K1 VR2 region. An AIDS associated KS and a PEL were infected with type I/A virus. CONCLUSION: In Okinawa, classic KS cases and one granuloma pyogenicum case were infected with HHV8 genotype II/C, also classified as subtype C. AIDS associated KS and PEL were infected with a different HHV8 (genotype I/A), similar to that found in the USA. In Okinawa, HHV8 infection is more than four times higher than in mainland Japan, resulting in many cases of KS because of HHV8 genotype II/C infection.     

Proteasome inhibitor, bortezomib, potently inhibits the growth of adult T-cell leukemia cells both in vivo and in vitro.

Adult T-cell leukemia (ATL) is a fatal neoplasm derived from CD4-positive T-lymphocytes, and regardless of intensive chemotherapy, its mean survival time is less than 1 year. Nuclear factor-kappaB (NF-kappaB) activation was reported in HTLV-I associated cells, and has been implicated in oncogenesis and resistance to anticancer agents and apoptosis. We studied the effect of a proteasome inhibitor, bortezomib (formerly known as PS-341), on ATL cells in vitro and in vivo. Bortezomib could inhibit the degradation of IkappaBalpha in ATL cells, resulting in suppression of NF-kappaB and induction of cell death in ATL cells in vitro. Susceptibilities to bortezomib were well correlated with NF-kappaB activation, suggesting that suppression of the NF-kappaB pathway was implicated in the cell death induced by bortezomib. Although the majority of the cell death was apoptosis, necrotic cell death was observed in the presence of a caspase inhibitor, z-VAD-fmk. When bortezomib was administered into SCID mice bearing tumors, it suppressed tumor growth in vivo, showing that bortezomib was effective against ATL cells in vivo. These studies revealed that bortezomib is highly effective against ATL cells in vitro and in vivo by induction of apoptosis, and its clinical application might improve the prognosis of patients with this fatal disease.     

Prevalence and treatment of chronic idiopathic thrombocytopenic purpura of childhood in Sweden

The frequency and treatment of children with chronic idiopathic thrombocytopenic purpura in Sweden were characterized using a national enquiry based on a questionnaire. Seventy-five children diagnosed as having chronic idiopathic thrombocytopenic purpura on 1 September 1993 were identified. The prevalence in children between 0.5 and 15.5 years of age was calculated to be 4.6/100 000. The median age at the time of diagnosis was 5 years and the male/female ratio was 1:1.2. Almost half of the patients (43%) were not treated at all during the disease. Steroids (43%) and intravenous immunoglobulin (25%) were most commonly used. Only two children were splenectomized.     

Elevated erythrocyte sedimentation rate and thrombocytosis as possible indicators of active disease in Langerhans''cell histiocytosis

Langerhans' cell histiocytosis (LCH) is a disease with an unpredictable course and unpredictable reactivations. Since active disease may cause life-long sequelae, early detection of reactivation is important. The usefulness of erythrocyte sedimentation rate (ESR) and thrombocytosis as indicators of disease activity in patients with LCH were examined. The mean values for ESR and platelet count for each quarter of a year were compiled. The means of all the ESR estimates (n=76) during each quarter of a year with active disease was 21 mm h^-1, with intermediate disease activity 11 mm h^-1 and with resolution 7 mm h^-1. The corresponding platelet count estimates (n = 139) were 433 × 109 l^-1, 365 × 109 l^-1 and 304 × 109 l^-1, respectively. In conclusion, elevated ESR and platelet count may be clinically valuable indicators of disease activity in LCH.     

Clinical and Genetic Studies of Familial Hemophagocytic Lymphohistiocytosis in Oman: Need for Early Treatment

Hemophagocytic lymphohistiocytosis (HLH) embraces the frequently indistinguishable conditions of familial hemophagocytic lymphohistiocytosis (FHL) and virus-associated hemophagocytic syndrome (VAHS). Without therapy FHL is invariably fatal, but successful therapy, including chemotherapy and immunotherapy followed by bone marrow transplantation (BMT), has been presented. To clarify the outcome of HLH in a developing country, with regard to clinical, laboratory, and genetic features, a nationwide study on all patients diagnosed with HLH in Oman during the 5-year period 1997-2001 was performed. In 5 patients and their families, mutational analysis was made. Thirteen patients with HLH were identified, 5 of whom had clinical manifestations of central nervous system involvement at presentation. In none of the patients could an infectious cause be identified. Ten children were referred late in the disease course, and the concern about starting chemotherapy before exclusion of an acute viral infection resulted in delayed treatment in some patients. Two children were started early on the HLH-94-therapy followed by successful BMT in one child. In the successfully transplanted child, the response to intrathecal hydrocortisone appeared to be better than standard therapy with intrathecal methotrexate. Finally, a novel missense mutation in the perforin gene was identified in 2 patients and their family members, causing a transition of proline to threonine at codon 89. Early diagnosis and treatment is important to improve outcome. Intrathecal corticosteroids may be considered, in addition to intrathecal methotrexate, in certain patients. Since the novel perforin mutation has been reported in only 2 patients from Oman, and since similar polymorphism in the sequencing data of the members of their families has been identified, a founder effect is possible in this population.     

Shiga-like toxin production and connective tissue protein binding of Escherichia coli isolated from a patient with ulcerative colitis

A 15-year-old girl with her first relapse of ulcerative colitis was treated with salicylazosulfapyridine, steroids, metronidazole and parenteral nutrition for 4 weeks without significant improvement. Her faecal specimens were negative for established intestinal pathogens, but strains of Escherichia coli producing Shiga-like toxin and expressing binding of fibronectin and collagen were repeatedly isolated. Neutralizing antibodies to Shiga-like toxin were detected in serum samples. Improvement was achieved during treatment with mecillinam to which the E. coli strains were sensitive.     

Clarithromycin suppresses the periodontal bacteria-accelerated abdominal aortic aneurysms in mice

Aoyama N, Suzuki J‐I, Ogawa M, Watanabe R, Kobayashi N, Hanatani T, Yoshida A, Ashigaki N, Izumi Y, Isobe M. Clarithromycin suppresses the periodontal bacteria‐accelerated abdominal aortic aneurysms in mice. J Periodont Res 2012; 47: 463–469. © 2011 John Wiley & Sons A/S Background and Objective: Although clarithromycin (CAM) has many biological functions, including regulation of MMPs, little is known about its effect on abdominal aortic aneurysms. Periodontopathic bacteria have been reported to be associated with several kinds of circulatory diseases. The purpose of this study was therefore to clarify the effect of CAM on periodontopathic bacteria‐accelerated abdominal aortic aneurysms. Material and Methods: Abdominal aortic aneurysm was produced in mice by the peri‐aortic application of 0.25 m CaCl₂. The mice were inoculated once per week with live Porphyromonas gingivalis, which is one of the major periodontopathic bacteria. Test mice (n = 8) were given a daily oral dose of CAM, while control mice (n = 13) were not. Results: Four weeks after the operation, the P. gingivalis‐injected and CAM‐treated mice showed a significant decrease in the aortic diameter in comparison with the mice only injected with P. gingivalis. Histopathologically, the samples obtained from the P. gingivalis‐injected and CAM‐treated mice showed less elastic degradation. Moreover, the plasma MMP‐2 concentration of the CAM‐treated mice decreased significantly. Conclusion: These findings suggest that CAM administration is useful to suppress periodontal bacteria‐accelerated abdominal aortic aneurysms via MMP regulation.     

Suicide Biomarkers to Predict Risk,Classify Diagnostic Subtypes,and Identify Novel Therapeutic Targets: 5 Years of Promising Research

BackgroundSuicide is a global health crisis. However, no objective biomarkers of suicide risk currently exist, and self-reported data can be unreliable, which limits prediction, diagnostic, and treatment efforts. Reliable biomarkers that can differentiate between diagnostic subgroups, predict worsening symptoms, or suggest novel therapeutic targets would be extremely valuable for patients, researchers, and clinicians.MethodsMEDLINE was searched for reports published between 2016 and 2021 using search terms (suicid*) AND (biomarker*) OR (indicat*). Reports that compared biomarkers between suicidal ideation, suicide attempt, death from suicide, or any suicide subgroup against other neuropsychiatric disorders were included. Studies exclusively comparing suicidal behavior or death from suicide with healthy controls were not included to ensure that biomarkers were specific to suicide and not other psychopathology.ResultsThis review summarizes the last 5 years of research into suicide-associated biomarkers and provides a comprehensive guide for promising and novel biomarkers that encompass varying presentations of suicidal ideation, suicide attempt, and death by suicide. The serotonergic system, inflammation, hypothalamic-pituitary-adrenal axis, lipids, and endocannabinoids emerged as the most promising diagnostic, predictive, and therapeutic indicators.ConclusionsThe utility of diagnostic and predictive biomarkers is evident, particularly for suicide prevention. While larger-scale studies and further in-depth research are required, the last 5 years of research has uncovered essential biomarkers that could ultimately improve predictive strategies, aid diagnostics, and help develop future therapeutic targets.