Behavior of a vigorous alpha- or beta-hemolysin-producing strain of Staphylococcus aureus in the cutaneous tissue of mice.

Two strains of Staphylococcus aureus were examined for behavior in the cutaneous tissue of mice by the fluorescent antibody technique, hematoxylin and eosin staining. When about 10(8) viable cells of an alpha-hemolysin-producing strain (Wood 46) were inoculated subcutaneously into a mouse, they multiplied in the subcutaneous tissue of the mouse and gradually entered the corium to produce alpha-hemolysin and nuclease. Edematous and necrotic lesions were observed in the cutaneous tissue where the organisms had multiplied. When 10(8) viable cells of a beta-hemolysin-producing strain (Kitami 3-9D) were inoculated into a mouse, they multiplied within a narrow extent surrounded mainly by infiltrating leukocytes and produced mainly beta-hemolysin. The changes of cutaneous tissue were weaker in mice inoculated with Kitami 3-9D strain than in mice inoculated with strain Wood 46. When 10(6) viable cells of both strains were inoculated into mice, they were phagocytized by leukocytes. Neither multiplication of organisms nor production of any active extracellular substance was observed in these mice. Edema, degeneration, and necrosis were also noticed in the cutaneous tissue of mice inoculated with alpha- and beta-hemolysin. In addition, the infiltration of leukocytes was inhibited mainly by alpha-hemolysin.     

Angiotensin II Reduces Lipoprotein Lipase Expression in Visceral Adipose Tissue via Phospholipase C β4 Depending on Feeding but Increases Lipoprotein Lipase Expression in Subcutaneous Adipose Tissue via c-Src

Metabolic syndrome is characterized by visceral adiposity, insulin resistance, high triglyceride (TG)- and low high-density lipoprotein cholesterol-levels, hypertension, and diabetes—all of which often cause cardiovascular and cerebrovascular diseases. It remains unclear, however, why visceral adiposity but not subcutaneous adiposity causes insulin resistance and other pathological situations. Lipoprotein lipase (LPL) catalyzes hydrolysis of TG in plasma lipoproteins. In the present study, we investigated whether the effects of angiotensin II (AngII) on TG metabolism are mediated through an effect on LPL expression. Adipose tissues were divided into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) for comparison. AngII accelerated LPL expression in SAT but, on the contrary, suppressed its expression in VAT. In both SAT and VAT, AngII signaled through the same type 1 receptor. In SAT, AngII increased LPL expression via c-Src and p38 MAPK signaling. In VAT, however, AngII reduced LPL expression via the G_q class of G proteins and the subsequent phospholipase C β4 (PLCβ4), protein kinase C β1, nuclear factor κB, and inducible nitric oxide synthase signaling pathways. PLCβ4 small interfering RNA experiments showed that PLCβ4 expression is important for the AngII-induced LPL reduction in VAT, in which PLCβ4 expression increases in the evening and falls at night. Interestingly, PLCβ4 expression in VAT decreased with fasting, while AngII did not decrease LPL expression in VAT in a fasting state. In conclusion, AngII reduces LPL expression through PLCβ4, the expression of which is regulated by feeding in VAT, whereas AngII increases LPL expression in SAT. The different effects of AngII on LPL expression and, hence, TG metabolism in VAT and SAT may partly explain their different contributions to the development of metabolic syndrome.     

Purified Human Synovium Mesenchymal Stem Cells as a Good Resource for Cartilage Regeneration

Mesenchymal stem cells (MSCs) have the ability to differentiate into a variety of lineages and to renew themselves without malignant changes, and thus hold potential for many clinical applications. However, it has not been well characterized how different the properties of MSCs are depending on the tissue source in which they resided. We previously reported a novel technique for the prospective MSC isolation from bone marrow, and revealed that a combination of cell surface markers (LNGFR and THY-1) allows the isolation of highly enriched MSC populations. In this study, we isolated LNGFR⁺ THY-1 ⁺ MSCs from synovium using flow cytometry. The results show that the synovium tissue contained a significantly larger percentage of LNGFR ⁺ THY-1 ⁺ MSCs. We examined the colony formation and differentiation abilities of bone marrow-derived MSCs (BM-MSCs) and synovium-derived MSCs (SYN-MSCs) isolated from the same patients. Both types of MSCs exhibited a marked propensity to differentiate into specific lineages. BM-MSCs were preferentially differentiated into bone, while in the SYN-MSC culture, enhanced adipogenic and chondrogenic differentiation was observed. These data suggest that the tissue from which MSCs are isolated should be tailored according to their intended clinical therapeutic application.     

Impact of overweight on left ventricular function in type 2 diabetes mellitus

Background

Coexistence of left ventricular (LV) longitudinal myocardial systolic dysfunction with LV diastolic dysfunction could lead to heart failure with preserved ejection fraction (HFpEF). Diabetes mellitus (DM) is known as a significant factor associated with HFpEF. Although the mechanisms of DM-related LV myocardial injury are complex, it has been postulated that overweight contributes to the development of LV myocardial injury in type 2 diabetes mellitus (T2DM) patients. However, the precise impact of overweight on LV longitudinal myocardial systolic function in T2DM patients remains unclear.

Methods

We studied 145 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease. LV longitudinal myocardial systolic function was assessed by global longitudinal strain (GLS), which was defined as the average peak strain of 18-segments obtained from standard apical views. Overweight was defined as body mass index (BMI) ≥ 25 kg/m². Ninety age-, gender- and LVEF-matched healthy volunteers served as controls.

Results

GLS of overweight T2DM patients was significantly lower than that of non-overweight patients (17.9 ± 2.4% vs. 18.9 ± 2.6%, p < 0.05), whereas GLS of both overweight and non-overweight controls was similar (19.8 ± 1.3% vs. 20.4 ± 2.1%, p = 0.38). Furthermore, multiple regression analysis revealed that for T2DM patients, BMI was the independent determinant parameters for GLS as well as LV mass index.

Conclusions

Overweight has a greater effect on LV longitudinal myocardial systolic function in T2DM patients than on that in non-DM healthy subjects. Our finding further suggests that the strict control of overweight in T2DM patients may be associated with prevention of the development of HFpEF.

     

A Bayesian hierarchical method to account for random effects in cytogenetic dosimetry based on calibration curves

The dicentric chromosome assay (DCA) is one of the most sensitive and reliable methods of inferring doses of radiation exposure in patients. In DCA, one calibration curve is prepared in advance by in vitro irradiation to blood samples from one or sometimes multiple healthy donors in considering possible inter-individual variability. Although the standard method has been demonstrated to be quite accurate for actual dose estimates, it cannot account for random effects, which come from such as the blood donor used to prepare the calibration curve, the radiation-exposed patient, and the examiners. To date, it is unknown how these random effects impact on the standard method of dose estimation. We propose a novel Bayesian hierarchical method that incorporates random effects into the dose estimation. To demonstrate dose estimation by the proposed method and to assess the impact of inter-individual variability in samples from multiple donors on the estimation, peripheral blood samples from 13 occupationally non-exposed, non-smoking, healthy individuals were collected and irradiated with gamma rays. The results clearly showed significant inter-individual variability and the standard method using a sample from a single donor gave anti-conservative confidence interval of the irradiated dose. In contrast, the Bayesian credible interval for irradiated dose calculated by the proposed method using samples from multiple donors properly covered the actual doses. Although the classical confidence interval of calibration curve with accounting inter-individual variability in samples from multiple donors was roughly coincident with the Bayesian credible interval, the proposed method has better reasoning and potential for extensions.     

Responses of carbon and oxygen stable isotopes in rice grain (Oryza sativa L.) to an increase in air temperature during grain filling in the Japanese archipelago

Stable isotopic compositions of carbon (δ¹³C) and oxygen (δ¹⁸O) in plants reflect growth conditions. Therefore, these isotopes might be good indicators of changes in environmental factors, such as variations in air temperature caused by climate change. It is predicted that climate change will lead to a greater increase in minimum air temperatures (primarily during the night) than in maximum air temperatures (primarily during the day) in many parts of Japan. In the present study, we investigated whether the δ¹³C and δ¹⁸O of the rice grain Koshihikari (Oryza sativa L.) from the northern latitudes (30.49°–37.14°) of Japan reflect variations in air temperature during grain filling and are related to the yield and proportion of first-grade rice (<15 % transparency, roundness, and cracking) as an indicator of quality. We revealed that rice δ¹³C was not correlated with mean maximum or minimum air temperatures for each prefecture. By contrast, rice δ¹⁸O was positively correlated with mean minimum air temperature, suggesting that rice δ¹⁸O reflects changes in night air temperature. We further showed that an increase in the mean minimum air temperature during grain filling had a negative effect on rice yield and quality. Our findings indicate that the δ¹⁸O of rice grain may be a good indicator of physiological changes in response to minimum air temperatures during grain filling.