Transnodal lymphangiography and post-CT for protein-losing enteropathy in Noonan syndrome

Noonan syndrome, which is a multiple congenital disorder, may be associated with lymphatic abnormalities. Protein-losing enteropathy (PLE) developing in Noonan syndrome is rare. We performed transnodal lymphangiography by directly accessing bilateral inguinal nodes under ultrasound guidance in a 17-year-old female with PLE developing in Noonan syndrome to assess detailed anatomical findings regarding lymphatic vessels. There have been no reports on transnodal lymphangiography for Noonan syndrome. Post-lymphangiographic CT images revealed multiple lymphatic abnormalities and lipiodol extravasation into the duodenum and the proximal jejunum. Transnodal lymphangiography was easy and safe for PLE developing in Noonan syndrome, and post-lymphangiographic CT provided invaluable information.     

A novel Doppler echocardiographic score reflecting cardiac functional status can predict adverse outcome in acute myocardial infarction

BACKGROUND: E/e' and s' are thought to reflect left ventricular diastolic and systolic function, respectively. However, there are no reports on the combined use of E/e' and s' in predicting the outcome in acute myocardial infarction (AMI). METHODS: For 20?months beginning in October 2006, we enrolled 65 AMI patients who had undergone Swan-Ganz (SG) catheterization and echocardiography just after reperfusion therapy. We measured the cardiac index (CI) and the pulmonary capillary wedge pressure (PCWP) via an SG catheter and determined routine echocardiographic indices, including transmitral flow velocity (E), mitral annulus velocities at systole (s') and early diastole (e'), and E/e'. In addition, we rounded off the values of s' (cm/s) and E/e' (ratio of cm/s to cm/s) to the nearest integer, and designated them the s'-score and E/e'-score, respectively. We also defined the cardiac status score as the s'-score subtracted from the E/e'-score. In Study 1, we investigated the relationships between hemodynamic parameters (CI and PCWP) and echocardiographic indices, including the cardiac status score. In Study 2, we excluded patients with Killip class ≥II, yielding a final study population of 55 patients in whom we investigated whether the cardiac status score could predict adverse cardiac events. RESULTS: Only the cardiac status score significantly correlated with both the PCWP and the CI. In the Cox proportional hazards model, significant predictors were the left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), and cardiac score ≥3.0. CONCLUSIONS: The novel score achieved in this study by subtracting the s'-score from the E/e'-score could be highly useful for predicting outcomes in AMI with Killip class I.     

Immunohistological evidence for renin in human endocrine tissues

The peroxidase-labeled antibody method and the avidin-biotin-complex method with antiserum to purified human kidney renin were used to identify renin in human endocrine tissues. Renin immunoreactivity was found in some large cells of the anterior pituitary, the zona glomerulosa and the zona reticularis of the adrenal, the Leydig cells of the testis, and the follicular epithelial cells of the thyroid and prostate glands. The specificity of the immunohistochemical reaction was confirmed by immunoabsorption tests. The specific localization of immunoreactive renin in each tissue suggests a possible role of renin in the function of these tissues.     

Serum decoy receptor 3 levels are associated with the disease activity of MPO-ANCA-associated renal vasculitis

Type 17 T-helper (Th17) cells have been suggested to be involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Th17 cell proliferation is promoted by tumor necrosis factor (TNF)-like ligand 1A (TL1A), which binds to death receptor 3 (DR3) expressed on Th17 cells. Decoy receptor 3 (DcR3) is known to block the TL1A-DR3 pathway by binding TL1A. To evaluate the Th17-TL1A systems as disease activity markers in AAV, we investigated the serum levels of TL1A and DcR3 in AAV patients. Serum IL-17, IL-23, TL1A, and DcR3 were measured by ELISA in 24 AAV patients with microscopic polyangiitis before the initial treatment, 24 AAV patients during remission, and 20 control subjects. There were no significant differences in serum IL-17, IL-23, and TL1A levels among the active-vasculitis patients, inactive-vasculitis patients, and controls. The mean serum DcR3 level was significantly higher in the active-vasculitis patients than in the inactive-vasculitis patients and controls (P?<?0.0001, respectively). There were significant positive correlations between the serum DcR3 levels and Birmingham Vasculitis Activity Score (BVAS), myeloperoxidase (MPO)-ANCA titers, white blood cell counts, serum creatinine levels, and serum C-reactive protein levels. In a multiple regression analysis, there was a significant positive correlation between the serum DcR3 level and BVAS (β?=?0.650, P?=?0.0462). The mean BVAS level was significantly higher in the active-vasculitis patients with high serum DcR3 levels than in those with the low serum DcR3 levels (P?=?0.0202). The serum level of DcR3 may be a useful marker for disease activity in AAV.     

Ultrastructural alterations in rats adrenal cortical cells produced by 4-aminopyrazolopyrimidine and ACTH administration

The correlation between adrenal cortical steroid metabolism and ultrastructural alterations was studied in rat adrenal glands stimulated by 4-aminopyrazolopyrimidine (4-APP) and ACTH. Ultrastructural alterations were focused on the outer fasciculata (Outer zone) and inner fasciculata-reticularis (Inner zone) of the rat adrenal cortical cells. In 4-APP administered rats, the most striking ultrastructural alteration was noted in the characteristic tubular profiles of smooth endoplasmic reticulum, mainly of the Inner zone. In ACTH administered rats, proliferation of fine tubulo-vesicular profiles of smooth endoplasmic reticulum was frequently seen in intermitochondrial space in both the Outer and the Inner zones. On the other hand, by 4-APP plus ACTH administration, the most striking ultrastructural changes were detected in mitochondria, mainly of the Inner zone. These mitochondria had a highly electron dense matrix and protrusions or blebs of mitochondrial outer membrane were frequently observed. In contrast, no remarkable changes were detected in the Outer zone of the cortex, except a slight enlargement of the mitochondria. On the bases of our findings, it is strongly suggested that the Inner zone of the cortex after 4-APP plus ACTH administration, at least in part, probably corresponds to highly activated steroid synthesis and it is further, speculated that steroidogenesis in the adrenal cortical cells after 4-APP administration is partially impaired in mitochondrial 11 beta-hydroxylase system.     

Pathology of the anomalous choledocho-pancreatic junction--action of pancreatic juice on the biliary tract

The mechanism of action of pancreatic juice on the biliary tract was investigated in a 5-year-old girl with choledochal cyst and animal models of the anomalous choledocho-pancreatic junction produced by pancreatico-cholecystostomy in 26 dogs. The results are as follows: Pancreatic enzymes are activated when bile and pancreatic juice are mixed in the biliary tract. Successively, lysolecithin and free fatty acids are produced by hydrolysis of lecithin in bile with phospholipase A2. These substances including phospholipase A2 destroy the mucosal barrier. The initial site receiving mucosal damage appears to be the epithelial apical cell membrane. The transfer of phospholipase A2 but not amylase from the biliary tract to the blood stream was suggested by comparing enzyme activity of portal and hepatic venous blood. The presence of some mutagenic substances in the contents of the choledochal cyst was confirmed by Ames assay and Rec-assay. This suggests that activated pancreatic enzymes and successively produced harmful substances in the anomalous choledocho-pancreatic junction are responsible for not only inflammatory but positively carcinogenic action on the biliary tract. In conclusion, the anomalous choledocho-pancreatic junction requires operative separation of the bile duct from the pancreatic duct despite the presence or absence of a choledochal cyst.     

Glomerular changes in the KK-Ay/Ta mouse: a possible model for human type 2 diabetic nephropathy

BACKGROUND: In type 2 diabetic nephropathy, there is no animal model which has been completely matched with humans. Advanced glycation end products (AGE) and transforming growth factor-beta (TGF-beta) are closely related to hyperglycaemia and their pathobiochemistry could explain diabetic nephropathy. The objective of the present study was to evaluate the KK-A(y)/Ta mouse as a suitable model for type 2 diabetic nephropathy including pathological changes and immunohistochemical analyses of AGE and TGF-beta, compared with the non-diabetic BALB/cA mouse. METHODS: The urinary albumin/creatinine ratio (ACR), body weight (BW), fasting and casual blood glucose, blood haemoglobin A(1c) (HbA(1c)), creatinine clearance (Ccr) and blood pressure were measured for phenotypic characterisation. The pathological changes of glomeruli were evaluated by light microscopy, immunofluorescence and electron microscopy. AGE and TGF-beta accumulation were evaluated by immunoperoxidase staining. RESULTS: The mean levels of ACR, casual blood glucose, blood HbA(1c) and Ccr in KK-A(y)/Ta mice were higher than those in age-matched non-diabetic BALB/cA mice after 12 weeks of age. There were no significant changes in the levels of systemic blood pressure among all groups. The pathological changes of glomeruli in KK-A(y)/Ta mice were consistent with those in the early stage of human diabetic nephropathy. AGE and TGF-beta protein appeared to be localised in the glomerular mesangial matrices. CONCLUSION: It appears that KK-A(y)/Ta mice, especially in terms of histopathological findings, are a suitable animal model for the early stage of type 2 diabetic nephropathy.     

Tumor suppressive effects of tocotrienol in vivo and in vitro

Tocotrienols have been reported to have higher biological activities than tocopherols. We investigated the antitumor effect of tocotrienols both in vivo and in vitro. Oral administration of tocotrienols resulted in significant suppression of liver and lung carcinogenesis in mice. In human hepatocellular carcinoma HepG2 cells, delta-tocotrienol exerted more significant antiproliferative effect than alpha-, beta-, and gamma-tocotrienols. delta-Tocotrienol induced apoptosis, and also tended to induce S phase arrest. On the other hand, gene expression analysis showed that delta-tocotrienol increased CYP1A1 gene, a phase I enzyme. Although further study will be necessary to investigate possible adverse effect, the data obtained in present study suggest that tocotrienols could be promising agents for cancer prevention.