Reliability and validity of splenic volume measurement by 3‐D ultrasound

Aim: We prospectively evaluated the reliability and validity of splenic volume with 3‐D ultrasound measurement and clarified its clinical usefulness. Methods: Thirty healthy volunteers and 30 patients with cirrhosis were included in this study. All 3‐D ultrasound examinations of splenic volumes were performed twice by two experienced sonographers with transabdominal ultrasound using virtual organ computer‐aided analysis (VOCAL). Reliability was confirmed among all subjects by evaluating within‐observer repeatability and between‐observer reproducibility using intraclass correlation coefficients (ICC) and Bland–Altman plots. Overall between‐instrument agreement of the measurements and computed tomography (CT) volumetry among cirrhotic patients were performed to determine validity. Results: For all 240 examinations, 3‐D ultrasound visualization and measurement of the spleen volume was possible. Mean spleen volume was 104.0 mL for the volunteers and 283.5 mL for the cirrhotic patients. The repeatability was high, with ICC (95% confidence interval) of 0.996 (0.993–0.997) for observer A and 0.997 (0.994–0.998) for observer B. Moreover, the interobserver ICC was 0.996, indicating high reproducibility. Despite the difference in volume between the volunteers and cirrhotic patients, sensitivity analyses indicated consistent results for both groups. Regarding the validity of the 3‐D ultrasound measurement, it also showed moderate to high agreement with CT volumetry, with mean ICC of 0.922 and 0.924 for observers A and B, respectively. The reliability and validity results from the Bland–Altman plots were similar to those from the ICC, with limits of agreement consistently narrow from a clinically practical view. Conclusion: 3‐D ultrasound measurements using VOCAL are valid and reliable in spleen volume examinations.     

Factor for adipocyte differentiation 158 gene disruption prevents the body weight gain and insulin resistance induced by a high-fat diet

To clarify the molecular mechanism of adipocyte differentiation, we previously isolated a novel gene, factor for adipocyte differentiation (fad) 158, whose expression was induced during the earliest stages of adipogenesis, and its product was localized to the endoplasmic reticulum. We found that the knockdown of fad158 expression prevented the differentiation of 3T3-L1 cells into adipocytes. In addition, over-expression of fad158 promoted the differentiation of NIH-3T3 cells, which do not usually differentiate into adipocytes. Although these findings strongly suggest that fad158 has a crucial role in regulating adipocyte differentiation, the physiological role of the gene is still unclear. In this study, we generated mice in which fad158 expression was deleted. The fad158-deficient mice did not show remarkable changes in body weight or the weight of white adipose tissue on a chow diet, but had significantly lower body weights and fat mass than wild-type mice when fed a high-fat diet. Furthermore, although the disruption of fad158 did not influence insulin sensitivity on the chow diet, it improved insulin resistance induced by the high-fat diet. These results indicate that fad158 is a key factor in the development of obesity and insulin resistance caused by a high-fat diet.     

An infant case of macroprolactinemia with transient idiopathic central precocious puberty

Macroprolactinemia was recognized more than a decade ago as a cause of hyperprolactinemia and the prevalence of macroprolactinemia is thought to be 10%-26% of patients with hyperprolactinemia. However, there are few published reports about macroprolactinemia in childhood. We report a 7-year-and-1-month-old girl with hyperprolactinemia due to macroprolactinemia with the complication of transient idiopathic central precocious puberty (ICPP). At the age of 6 years and 9 months, she was diagnosed with ICPP at another clinic, on the basis of isolated mammary development and increased height velocity with slightly advanced bone age. At that time, the unexpected finding of high PRL level was also observed. Four months later, she was referred to our clinic for persistently high PRL level. At this time, other endocrinological data showed prepubertal stage and we demonstrated macroprolactinemia and the presence of anti-PRL autoantibody. After other causes of hyperprolactinemia such as prolactinoma and stress were ruled out, we finally diagnosed her with hyperprolactinemia due to macroprolactinemia. Because most patients with macroprolactinemia are symptom-free despite hyperprolactinemia and drug therapy would not be indicated, macroprolactinemia should be suspected even in children to avoid unnecessary examinations and treatments.     

Trifluoromethoxy-benzylated ligands improve amyloid detection in the brain using (19)F magnetic resonance imaging

The chemical properties of probes that improve amyloid detection by non-invasive (19)F magnetic resonance imaging (MRI) are of interest. We synthesized benzoxazole compounds with trifluoromethoxy groups, and found that these compounds displayed sharp (19)F nuclear magnetic resonance (NMR) signals in an assay buffer. However, the intensities of the (19)F NMR signals were dramatically reduced in mouse brain lysates. Our results indicate that the inhibitory effect of brain tissue on the (19)F NMR signals from these probes can be attributed to the hydrophobicity of the tissue. These results highlight the importance of using hydrophilic (19)F-MRI agents to avoid the inhibitory effects of brain tissues on (19)F NMR signals.     

Glycated high-density lipoprotein regulates reactive oxygen species and reactive nitrogen species in endothelial cells

Nonenzymatic glycosylation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Although it is believed that high-density lipoprotein (HDL) is glycosylated at an increased level in diabetic individuals, little is known about a possible linkage between glycated HDL and endothelial dysfunction in diabetes. To clarify whether glucose-modified HDL affects the function of endothelial cells, we first examined herein the level of H(2)O(2) generation from cultured human aortic endothelial cells (HAECs) exposed to a glycated oxidized HDL (gly-ox-HDL) prepared in vitro. Incubation for 48 hours with 100 microg/mL of gly-ox-HDL induced significant release of H(2)O(2) from cells and gly-ox-HDL-induced H(2)O(2) formation was inhibited in the presence of diphenyleneiodonium, an inhibitor of NADPH oxidase. In addition, stimulation of HAECs with gly-ox-HDL for 48 hours elicited a marked downregulation of catalase and Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD), suggesting H(2)O(2) formation by gly-ox-HDL to be due to a disturbance involving oxidant and antioxidant enzymes in the cells. Treatment of HAECs with gly-ox-HDL attenuated the expression of endothelial nitric oxide synthase (eNOS), but not inducible nitric oxide synthase (iNOS), and this was followed by decreased production of nitric oxide (NO) by the cells. Furthermore, in vitro experiments with glycated HDL (gly-HDL) in the presence of 2 mmol/L EDTA and Cu(2+)-oxidized HDL suggested the effect of gly-HDL on endothelial function to be possibly potentiated by additional oxidative modification. Taking all of the above findings together, gly-ox-HDL may lead to the deterioration of vascular function through altered production of reactive oxygen species and reactive nitrogen species in endothelial cells.     

Post-stroke treatment with imidapril reduces learning deficits with less formation of brain oedema in a stroke-prone substrain of spontaneously hypertensive rats

The present study was undertaken to examine the effects of the ACE (angiotensin converting enzyme) inhibitor imidapril, on the brain, when administered after the onset of stroke in a stroke-prone substrain of spontaneously hypertensive rats (SHRSP). Learning deficits and induced lesions in the brain as well as in the kidneys and heart were investigated in detail. SHRSP were divided into two groups with or without salt loading at the age of 4 weeks. The salt loading was performed for 7-9 weeks to increase the incidence of stroke. Within 24 h after the first observation of stroke, animals were subsequently treated with 5 mg/kg imidapril orally once a day or the vehicle for up to the age of 27 weeks. Imidapril attenuated progression of neurological abnormalities such as irritability, hyperkinesia and motor dysfunction, and increased survival rate. In three-panel runway testing, learning deficits did not develop significantly in the imidapril-treated group, and was comparable to that in the non-salt-loaded/non-stroke group. Imidapril reduced oedema formation in the cortex, hippocampus and striatum, and also suppressed lesion formation in the kidneys and heart. Imidapril thus suppressed progression of neurological deficits with loss of learning ability following onset of stroke, and also suppressed formation of oedema in the brain and decreased the number of lesions in other organs. Imidapril-induced reduction of cerebrovascular damage, which presumably occurs in the brain after stroke, may account for the inhibitory effects of imidapril on lesion formation and learning impairment.     

Examination of soluble Fas (sFas) and soluble Fas ligand (sFasL) in patients with burns

The FasL–Fas system is one of the recognized apoptosis-inducing systems, and has been determined to have important functions in relation to homeostasis and biological defense mechanisms. In this study, we investigated the serum levels of soluble Fas (sFas), soluble FasL (sFasL) and tumor necrosis factor (TNF-) in patients with burns. The sFas levels were found to be significantly higher in the patients who eventually died as compared to those in the patients who survived (3.9±1.8 ng/ml versus 2.6±1.0 ng/ml). On the other hand, the sFasL levels were significantly higher in the patients who survived (61.5±29.9 ng/ml versus 37.2±14.4 ng/ml) than in those who eventually died. A positive correlation was noted between the TNF- level and the sFas level, and a negative correlation was observed between the TNF- level and the sFasL level. These findings suggest that worsening of the condition of a burns patient may be related to changes in the Fas–FasL system.     

Pulmonary artery obstruction caused by thoracic aortic dissection: a case with unique pathological findings.

Pulmonary artery obstruction is a rare complication of acute thoracic aortic dissection. A 74-year-old woman was admitted to hospital with respiratory distress. Computed tomography scan showed right pulmonary artery occlusion and a thoracic aortic dissection of the Stanford A type. Lung perfusion scan revealed a defect in the entire right lung field. These findings mimicked acute pulmonary thromboembolism accompanying aortic dissection. On the other hand, pulmonary angiography revealed a round smooth defect of the right pulmonary artery, indicating an extrinsic compression. The patient finally died of cardiac tamponade. Autopsy disclosed that the right pulmonary artery was compressed by a hematoma in the adventitial space around the pulmonary artery. Such a mechanism of pulmonary artery obstruction caused by acute aortic dissection is unique, and is distinct from that caused by chronic non-dissecting aortic aneurysms, which themselves compress the pulmonary arteries. This complication inevitably follows aortic rupture; therefore, emergency operation to repair the dissected aorta must be performed to avoid the following catastrophic event.     

Osteoporosis and intake of carbohydrates

Adequate energy intake including carbohydrates is essential to maintain bone mass. Emaciation along with deficiency in nutrients, such as calcium, vitamin D, and protein is a significant risk factor for bone loss, and should be avoided. However, there is no clinical evidence that shows the direct effects of carbohydrate on bone mass. On the other hand, excessive intake of carbohydrates results in obesity, which causes other metabolic diseases such as diabetes mellitus (DM). Therefore, dietary regimen must be balanced in general, and complications and conditions of individual patients should be taken well into account. In addition, energy intake is a basis for adequate exercise in order to maintain physical activity and ideal body weight, which will further decrease the risk of bone fracture. Some indigestible carbohydrates, such as inulin and oligofructose, are shown to increase the availability of minerals from foods, and thus can be beneficial to bone mass.