Characterization of methicillin-resistant Staphylococcus aureus isolated from tertiary care hospitals in Tokyo, Japan.

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) remains problematic in both hospital and community settings. Investigations of MRSA existing in the local area are necessary to understand the detailed epidemiology of healthcare-associated MRSA (HA-MRSA). In the present study, molecular epidemiological analysis was performed on 584 MRSA isolated from four hospitals in Tokyo, Japan. In the pulsed-field gel electrophoresis (PFGE) analysis, four epidemic pulsotypes (I to IV) were found. The isolates of the epidemic pulsotype I mainly consisted of the SCCmec type II, toxic shock syndrome toxin 1 gene (tst)-negative, spa type t002, and ST764 clones. The ST764 clone, which is a novel hybrid variant of the ST5 HA-MRSA lineage with the arginine catabolic mobile element (ACME), was first found in Niigata, Japan. However, no ACME genes were detected in the isolates of the epidemic pulsotype I. In contrast, the other isolates of the epidemic pulsotypes mainly consisted of the SCCmec type II, tst-positive, spa type t002, and ST5 clones, which are the most predominant clones of HA-MRSA in Japan. Resistance rates of non-ß-lactams for the isolates of the epidemic pulsotype I were higher than those of the other epidemic pulsotypes. Our data showed that the novel ACME-negative ST764 clones are being distributed throughout multiple hospitals in Tokyo. The ST764 clones in Tokyo have the potential to acquire ACME in the future, because the ACME-positive ST764 clones have already been found in both hospital and community settings in other areas of Japan.

Chronic eosinophilic pneumonia presenting with acute onset.

A 44-year-old woman was hospitalized with a 2-day history of cough, sputum, and fever. There was no history of atopic dermatitis or asthma. On admission, the chest X-ray revealed scattered infiltration in the left upper lung fields. Further examination revealed peripheral blood and bronchoalveolar lavage fluid eosinophilia. Transbronchial lung biopsy revealed eosinophilic pneumonia, with eosinophil infiltration of the alveoli, destroyed basal lumina, and connecting intraluminal fibrosis of the alveolar walls. Based on the findings, we made the diagnosis of chronic eosinophilic pneumonia. Treatment with prednisolone at 60 mg/day resulted in dramatic improvement of both the symptoms and the radiologic abnormalities.

Characterization of SCCmec type IV methicillin-resistant Staphylococcus aureus clones increased in Japanese hospitals.

Recently, the prevalence of staphylococcal cassette chromosome mec (SCCmec) type IV isolates, which are the major community-acquired methicillin-resistant Staphylococcus aureus (MRSA), have increased in Japanese hospitals. The aim of this study was to elucidate the detailed molecular epidemiological features of the SCCmec type IV clones in Japanese hospitals. When 2589 MRSA isolated from four hospitals in Tokyo, Japan between 2010 and 2014 were analysed, the proportion of SCCmec type IV overtook that of type II, which was the major type of hospital-acquired MRSA in 2014. Multilocus sequence typing showed that CC1 was the most predominant clone in the SCCmec type IV isolates. The clinical departments that the patients belonged to, pulsed-field gel electrophoresis analysis and antimicrobial susceptibility profiles suggested that the origin of the CC1-SCCmec type IV (CC1-IV) clone was a community setting. Our data show that the CC1-IV clone is becoming a predominant MRSA clone in Japanese hospitals.

Rembrandt's Maria Bockenolle has a butterfly rash and digital deformities: overlapping syndrome of rheumatoid arthritis and systemic lupus erythematosus.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are the most common autoimmune disorders, although they each have very different pathophysiology. In general, RA is considered to be a Th1-mediated disease, while SLE is a Th2-mediated disease. Thus, their overlapping, in so called "rhupus", is a rare condition. In Rembrandt van Rijn's (1606-1669) portrait of the middle-aged Maria Bockenolle, we have what may be the earliest depiction of a case of rhupus syndrome: the coexistence of a butterfly rash and digital deformities. This suggests the possible historical importance of an RA epidemic which took place in the early 17th century.

Multibacterial sepsis in an alcohol abuser with hepatic cirrhosis.

An alcohol abuser with hepatitis C developed multibacterial sepsis. His mean 100% alcohol intake reached 400 ml/day. In January 2001, he suddenly experienced fever (39 degrees C) with no other symptoms. One week later, he was admitted to our hospital and was subsequently diagnosed with sepsis associated with four species of bacteria (Streptococcus constellatus, Fusobacterium mortiferum, Bacteroides thetaiotaomicron, and non-spore-forming anaerobic gram-positive bacillus). A drip infusion of imipenem/cilastatin was administrated, resulting in a successful therapeutic outcome. No underlying disorder was found except for gastric ulcers and hepatic cirrhosis. Damaged gastric mucosa was assumed to be the possible cause and route for the bacterial invasion.

[Anti-neutrophil cytoplasmic autoantibody-associated rapid progressive glomerulonephritis complicated with both limited and diffuse scleroderma].

We report two patients with scleroderma, 73-year-old female and 67-year-old female, who developed anti neutrophil cytoplasmic autoantibody (ANCA) associated rapid progressive glomerulonephritis (RPGN). Both patients have had a long history of scleroderma (23 and 14 years, respectively) when ANCA-associated glomerulonephritis occurred. In the first patient, scleroderma was localized in both fingers. She has been followed-up as CREST syndrome rather than systemic sclerosis. The complaints on admission were leg edema and left chest pain in the first patient, and a pyrexia and dyspnea in the second patient. Both patients showed pulmonary manifestation (pleural effusion in the first patient, interstitial pneumonia and alveolar hemorrhage in the second patient, respectively) and rapid progressive glomerulonephritis. Both patients died in spite of corticosteroid therapy. Autopsy findings in the second patient demonstrated crescentic glomerulonephritis and alveolar hemorrhage. Our cases demonstrated that MPO-ANCA associated glomerulonephritis could be associated with limited scleroderma as well as systemic scleroderma. In these condition, the prognosis will be poor if scleroderma seemed to be stable.

Wegener's granulomatosis complicated with intestinal ulceration.

Abstract We report the case of a 32-year-old man who developed Wegener's granulomatosis complicated with refractory intestinal ulceration. In August 2001, he presented with a high fever, nasal bleeding, and bilateral leg numbness. These symptoms worsened, which prompted him to consult his home doctor on February 18, 2002. In spite of treatment with antibiotics, his symptoms did not improve. Furthermore, abdominal pain and melena occurred as additional symptoms in March 2002. He was admitted to our hospital on April 5, 2002. A deformed nose condition (the so-called saddle nose) was observed at this time. Laboratory data showed a high erythrocyte sedimentation rate (103 mm/h) and a high level of serum C-reactive protein (14.98 mg/dl), and hematuria and proteinuria were also observed. The patient was positive for an antineutrophil cytoplasmic antibody specific for proteinase-3 (PR3-ANCA). A chest computed tomography (CT) scan revealed multiple pulmonary nodules in the lung field. A biopsied-specimen from the nasal mucosa showed necrotizing granulomatosis with giant cells. Together with his symptoms and the laboratory and pathological findings, the patient was diagnosed as having Wegener's granulomatosis. A colon fiberscopy showed multiple ulcerations with bleeding from the terminal ileum to the ascending colon, and nodular lesions at the terminal ileum. We started a combination therapy of prednisolone (60 mg/day) and cylophosphamide (100 mg/day) orally. The patient's gastrointestinal symptoms disappeared and abnormal serological indicators improved. Although Wegener's granulomatosis complicated with refractory intestinal ulceration is rare, this case indicates that the gastrointestinal region is also a target organ of Wegener's granulomatosis.

Early bone marrow hematopoietic defect in simian/human immunodeficiency virus C2/1-infected macaques and relevance to advance of disease.

To clarify hematological abnormalities following infection with human immunodeficiency virus (HIV), we examined the hematopoietic capability of bone marrow by using cynomolgus monkeys infected with pathogenic simian/human immunodeficiency virus (SHIV) strain C2/1, an animal model of HIV infection. The relationship between the progress of the infection and the CD4/CD8 ratio of T lymphocytes or the amount of SHIV C2/1 viral load in the peripheral blood was also investigated. A colony assay was performed to assess the hematopoietic capability of bone marrow stem cells during the early and advanced phases of the infection. Colonies of granulocytes-macrophages (GM) were examined by PCR for the presence of the SIVmac239 gag region to reveal direct viral infection. There was a remarkable decrease in the CFU-GM growth on days 1 and 3 postinoculation, followed by recovery on day 56. During the more advanced stage, the CFU-GM growth decreased again. There was minimal evidence of direct viral infection of pooled cultured CFU-GM despite the continuously low CD4/CD8 ratios. These results indicate that the decrease in colony formation by bone marrow stem cells is reversible and fluctuates with the advance of the disease. This decrease was not due to direct viral infection of CFU-GM. Our data may support the concept that, in the early phase, production of inhibitory factors or deficiency of a stimulatory cytokine is responsible for some of the bone marrow defects described in the SHIV C2/1 model.

Granulocyte colony stimulation factor (G-CSF) suppresses interleukin (IL)-12 and/or IL-2 induced interferon (IFN)-gamma production and cytotoxicity of decidual mononuclear cells.

PROBLEM: The placenta is one of the few non-hematopoietic tissues to express granulocyte colony stimulation factor (G-CSF). Placental G-CSF production is considered to be one of the major causes of granulocytosis during pregnancy although its physiological role in pregnancy has not yet been examined. METHOD OF STUDY: The effects of G-CSF on interleukin (IL)-2 and/or IL-12 induced interferon (IFN)-gamma production of magnetic cell sorting (MACS) sorted decidual lymphocytes was examined by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT). The effect of G-CSF on cytotoxicity of decidual lymphocytes against the choriocarcinoma cell line JEG-3 was examined by lactate dehydrogenase (LDH) release assay. RESULTS: As previously reported by us, IL-2 and/or IL-12 activated decidual mononuclear cells were capable of killing choriocarcinoma cells. We observed that G-CSF abolished IFN-gamma production and cytotoxicity of decidual mononuclear cells and MACS sorted CD56+ cells. CONCLUSIONS: In addition to its well-known trophic effects on hematopoiesis, our results suggest about new roles of G-CSF in reproductive immunology.

Thrombophilic dysfibrinogen Tokyo V with the amino acid substitution of gammaAla327Thr: formation of fragile but fibrinolysis-resistant fibrin clots and its relevance to arterial thromboembolism.

Thrombophilic dysfibrinogen Tokyo V was identified in a 43-year-old man with recurrent thromboembolism. Based on analyses of the patient fibrinogen genes, the amino acid sequence of the aberrant fibrinogen peptide, and deglycosylation experiments, fibrinogen Tokyo V was shown to have an amino acid substitution of gamma Ala327Thr and possibly extra glycosylation at gamma Asn325 because the mutation confers the N-linked glycosylation consensus sequence Asn-X-Thr. The mutation resulted in impaired function and hypofibrinogenemia (hypodysfibrinogen). Polymerization of fibrin monomers derived from patient fibrinogen was severely impaired with a partial correction in the presence of calcium, resulting in very low clottability. Additionally, a large amount of soluble cross-linked fibrin was formed upon thrombin treatment in the presence of factor XIII and calcium. However, Tokyo V-derived fibrin was resistant to degradation by tissue plasminogen activator (tPA)-catalyzed plasmin digestion. The structure of Tokyo V fibrin appeared severely perturbed, since there are large pores inside the tangled fibrin networks and fiber ends at the boundaries. Taken together, these data suggest that Tokyo V fibrin clots are fragile, so that fibrinolysis-resistant insoluble fibrin and soluble fibrin polymers may be released to the circulation, partly accounting for the recurrent embolic episodes in the patient.