Oncostatin M Maintains the Hematopoietic Microenvironment and Retains Hematopoietic Progenitors in the Bone Marrow

Bone marrow (BM) functions as the primary hematopoietic tissue throughout adult life by providing a microenvironment for the proliferation, differentiation, and retention of hematopoietic stem cells and progenitors. We describe novel roles for oncostatin M (OSM) in the BM hematopoietic microenvironment. Hematopoietic progenitor activity in OSM-deficient mice was reduced in BM but elevated in the spleen and peripheral blood. The level of circulating granulocyte colony-stimulating factor (G-CSF) was increased, whereas that of stromal cell-derived factor 1 (SDF-1) was decreased in OSM-deficient mice. Moreover, the ability of OSM-deficient BM stromal cells to support hematopoiesis in vitro was significantly reduced. These results indicate that OSM plays a unique role in hematopoiesis by maintaining the proper microenvironment for BM hematopoiesis; it also retains hematopoietic progenitors in BM by regulating G-CSF and SDF-1 levels.     

Increased type 3 iodothyronine deiodinase activity in a regrown hepatic hemangioma with consumptive hypothyroidism

Introduction

Infantile hepatic hemangioma with consumptive hypothyroidism is a rare condition.

Case report

A 4-month-old girl presented with diffuse hepatic hemangiomas during treatment of congenital hypothyroidism. Serum reverse triiodothyronine was elevated, and her hypothyroidism improved concomitant with involution of the hemangioma following prednisolone and interferon-α administration. At 20 months of age, 7 months after discontinuing prednisolone and interferon-α, a focal hemangioma regrew from one of the previous lesions and was surgically resected. The expression and activity of type 3 iodothyronine deiodinase (D3) were elevated in the resected tumor tissue compared with placenta.

Discussion

Here, we describe a patient with consumptive hypothyroidism and diffuse infantile hepatic hemangiomas, one of which regrew after involution following pharmacotherapy. The etiology of elevated D3 activity is also discussed.

Conclusion

It is important to identify infantile hepatic hemangioma in patients with hypothyroidism refractory to hormone replacement therapy, who have low free triiodothyronine despite high thyrotropin and normal free thyroxine levels, and long-term follow-up will be needed for these patients.     

Coincidental outbreak of methicillin-resistant Staphylococcus aureus in a hematopoietic stem cell transplantation unit

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common nosocomial pathogens among hospital-acquired infections, and immunocompromised patients are highly susceptive to infection. The molecular typing of isolated strains is a common method for tracing an outbreak of MRSA, but experience with this approach is still limited in the hematopoietic stem cell transplantation (HSCT) ward. METHODS: We experienced 6 cases of MRSA infection/colonization in our 26-bed HSCT ward during a 4-week period. This unusual outbreak strongly suggested that the same MRSA strain was involved despite strict isolation and aseptic patient care. Clarification of the transmission pattern was critical, and we applied pulsed-field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP) assays for evaluation. RESULTS AND CONCLUSION: In four of the six cases, the pattern of bands examined by PFGE and AFLP analyses supported the idea that direct person-to-person transmission was very unlikely and the outbreak was coincidental. This experience highlights the clinical value of molecular typing methods for the clinical epidemiological assessment of MRSA outbreak.     

In vitro activity of cefotiam against oxacillin-resistant Staphylococcus epidermidis strains--reevaluation of beta-lactam antibiotics efficiency on MRSE

We evaluated the efficacy of cefotiam (CTM) against Staphylococcus epidermidis (S. epidermidis) isolated from blood culture and central venous catheters. Of the S. epidermidis strains tested, 82.3% were methicillin (MPIPC)-resistant (MPIPC MIC > or = 0.5 microg/ml) and expressed the mecA gene, and 89.2% of these MPIPC-resistant S. epidermidis (MRSE) showed less than 8.0 microg/ml CTM MIC. In vitro killing kinetics of CTM against MRSE demonstrated that strains with high CTM MIC (> or = 4.0 microg/ml) showed high MPIPC MIC (> or = 4.0 microg/ml). All strains with low CTM MIC (< or = 2.0 microg/ml) showed MPIPC MIC lower than 2.0 microg/ml. In time-kill studies, CTM had high bactericidal activity against strains with low CTM MIC (< or = 2.0 microg/ml), regardless of whether they were mecA positive. These results demonstrated that MRSE isolates with low CTM MIC (< or = 2.0 microg/ml) are not easily induced CTM resistance by CTM treatment in vitro, and indicated the possibility that beta-lactams such as CTM could be an effective antibiotic agents against beta-lactam-sensitive MRSE infections.     

Development and validation of the Stimulant Relapse Risk Scale for drug abusers in Japan

OBJECTIVE: To develop and validate a multidimensional measure of relapse risk for stimulants in Japanese drug abusers. METHODS: A Stimulant Relapse Risk Scale (SRRS) was developed based on the Marijuana Craving Questionnaire and a discussion among three psychiatrists. We created 48 items after confirming the items including a variety of relapse risk, such as craving (expectancy, compulsivity, etc.) and emotionality problems. One hundred inpatients and outpatients with a history of stimulant abuse (71 males and 29 females) were recruited with informed consent, and were administered the SRRS. The Visual Analogue Scale for drug craving (VAS), Addiction Severity Index for Japanese (ASI-J), and data on relapse within 3 and 6 months after the rating were used for the validation. RESULTS: Exploratory factor analysis highlighted five factors: anxiety and intention to use drug (AI), emotionality problems (EP), compulsivity for drug use (CD), positive expectancies and lack of control over drug (PL), and lack of negative expectancy for drug use (NE). These accounted for 48.3% of the total variance. Thirty of the 43 items were classified into the five subscales. Cronbach's alpha coefficient for each subscale ranged from .55 to .82, and was .86 for the total SRRS, indicating their adequate internal consistency. AI, CD, PL, and total SRRS were significantly correlated with the drug-use composite score of the ASI-J, supporting their concurrent validity. AI, PL, NE, and total SRRS were significantly correlated with relapse, implying their predictive validity. CONCLUSIONS: The SRRS has multidimensional psychometric properties useful for assessing the various aspects of stimulant relapse risk.     

Measurement of catechol-O-methyltransferase activity in the brain of Dahl salt-sensitive rats

Metabolism by catechol-O-methyltransferase (COMT) is one of the inactivation pathways of catecholamines (CAs), which are important hormones in regulating blood pressure both in central and in peripheral sympathetic nerve endings. We have reported the rapid determination method of COMT activity using high-performance liquid chromatography (HPLC)-fluorescence detection. In the present study, we applied the method to brain tissues, cerebral cortex, cerebellum, hypophysis and hypothalamus. COMT activities were assessed by measuring normetanephrine with the use of norepinephrine as an endogenous substrate. We examined the COMT activities in the brains of Dahl salt-sensitive (DS) rats given normal-salt or high-salt diet for 13 weeks, and found that membrane-bound COMT activities in the cerebral cortex were significantly reduced in high-salt loaded DS rats compared with normal-salt loaded DS rats.     

Effect of histamine on muscimol-induced working memory deficits in radial maze performance

We investigated the participation of gamma-aminobutyric acid (GABA) neurons of the medial septal area in eight-arm radial maze performance in rats. The intra-septal injection of muscimol, a GABA(A) agonist, caused an increase in total error and working memory error. On the other hand, no significant effect was observed with reference memory error. Donepezil and tacrine (cholinesterase inhibitors) antagonized the muscimol-induced spatial memory deficits. Histidine (1500 mg/kg, i.p.) also improved the total error and working memory error induced by muscimol. At this dose, histidine caused a significant increase in the histamine content of the cortex, hippocampus, and hypothalamus in rats. In addition, the intra-hippocampal injection of histamine also antagonized muscimol-induced spatial memory deficits. The practical conclusion is that the GABA(A) receptor of the medial septal area plays an important role in working memory, and also, the disturbance of working memory induced by muscimol is mediated not only by cholinergic but also by histaminergic systems in the spatial memory of rats.