Impaired synthesis of retinol-binding protein and transthyretin in rat liver with bile duct obstruction

To gain further insight into the protein metabolism in bile duct-obstruction, we examined the synthesis of retinol-binding protein (RBP) and transthyretin (TTR) in rats with common bile duct-ligation. In these rats, liver and plasma levels of RBP and TTR decreased markedly, whereas liver retinoid contents remained unchanged. Although there appeared no decrease in the total amount of RBP or TTR mRNA expressed in the liver, the subcellular distribution of these mRNAs changed from the membrane-bound polysome fraction to the membrane-unbound polysome fraction. This abnormal distribution recovered rapidly after biliary drainage, resulting in the subsequent recovery of the plasma RBP and TTR levels. These observations suggest that cholestasis inhibits the synthesis and secretion of RBP and TTR by disrupting the binding of their mRNAs to membrane-bound polysomes. Plasma levels of RBP and TTR might be sensitive indicators of the recovery of protein synthesis after biliary drainage in patients with obstructive biliary disorders.Supported in part by Grant-in-Aids from the Ministry of Education, Science and Culture (05770350 to M.O.; 05670463 to H.M.; 07780553 to S.K.) and by a grant from the Ryoichi Naito Foundation for medical research (to S.K.).     

Chronic Kidney Disease Japan Cohort (CKD-JAC) study: design and methods

The prevalence and incidence of end-stage renal disease (ESRD) in Japan are the highest and the third highest, respectively, in the world, while the incidence of cardiac death in Japan is the lowest among developed countries. A recent study showed that the prevalence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m(2), is extremely high in Japan, about 20% of the adult population. However, the risk of ESRD and cardiovascular disease (CVD) in the CKD population has not been determined nationwide. For this observational study, we will establish a Chronic Kidney Disease Japan Cohort (CKD-JAC) by enrolling 3,000 patients with CKD in 17 clinical centers around Japan, which will be used to determine the incidence of ESRD and CVD in Japanese CKD patients. Risk factors associated with the development of CVD will also be examined. Comorbidity of diabetes in CKD patients will be analyzed to determine whether it is a risk for rapid progression of CKD and high incidence of CVD. In addition, we will study whether the burden of CKD decreases the QOL of patients, and increases hospitalization or health resource utilization. Insights from the CKD-JAC study will provide a basis for future interventional trials focused on reducing the burden of ESRD and CVD in patients with CKD in Japan.     

Unusual trihydroxy bile acids in the urine of patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and those with cirrhosis

Urinary bile acids from 20 patients treated with chenodeoxycholate, 18 treated with ursodeoxycholate, 15 treated with rifampicin and 8 patients with advanced cirrhosis were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry. Occurrence rates and amounts of three so-called unusual trihydroxy bile acids, hyocholate, ursocholate and omega-muricholate, were increased in patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and decreased in cirrhotic patients as compared with those in untreated healthy adults. These data suggest that chenodeoxycholate and ursodeoxycholate are hydroxylated to produce unusual trihydroxy bile acids in bile acid-loaded humans and that this metabolism may be related to the induction of hepatic microsomal enzymes by rifampicin. In contrast, the hydroxylation of chenodeoxycholate and ursodeoxycholate may be impaired by severe hepatic damage. Because the urine is a secretory pathway for internal bile acids, the occurrence of unusual trihydroxy bile acids in the urine may be used as an indicator of hepatic ability to metabolize "hydrophobic" dihydroxy bile acids to their secretory forms.     

A giant retention cyst of the pancreas (cystic dilatation of dorsal pancreatic duct) associated with pancreas divisum

We describe a rare case of pancreas divisum associated with a giant retention cyst (cystic dilatation of the dorsal pancreatic duct), presumably formed following obstruction of the minor papilla. The patient was treated by pancreatico(cysto)jejunostomy. A 50-year-old man was admitted with complaints of increasing upper abdominal distension and body weight loss. There was no previous history of pancreatitis, gallstones, drinking, or abdominal injury. An elastic-hard tumor-like resistance was palpable in the upper abdomen. Computed tomography and ultrasound (US) examinations revealed a giant cystic lesion expanding from the pancreas head to the tail. Endoscopic retrograde cholangiopancreatography findings showed a looping pancreatic duct which drained only the head and uncinate process of the pancreas to the main papilla. A US-guided puncture to the cystic lesion revealed that the lesion continued to the main pancreatic duct in the tail of pancreas. The lesion was connected to a small cystic lesion, which was located inside the minor papilla, and ended there. The amylase level in liquid aspirated from the cyst was 37 869 IU/l, and the result of cytological examination of the liquid showed class II. A pancreatico(cysto)jejunostomy was performed, with the diagnosis being pancreas divisum associated with a retention cyst following obstruction of the minor papilla. The histological findings of a specimen from the cyst wall revealed that the wall was a pancreatic duct covered with mildly inflammatory duct epithelium; there was no evidence of neoplasm. The patient is currently well, and a CT examination 2 years after the operation showed disappearance of the cyst and normal appearance of the whole pancreas. Received: April 24, 2001 / Accepted: September 14, 2001     

Renal osteodystrophy and vitamin D

Vitamin D deficiency is one of major pathogeneses of renal osteodystrophy (ROD). Vitamin D deficiency produces osteitis fibrosa via secondary hyperparathyroidism and osteomalacia via hypocalcemia. To prevent and treat ROD, vitamin D supplementation is an inevitable tool. Recent progresses of vitamin D therapy including development of new vitamin D analogues and direct injection to parathyroid gland will contribute to the successful treatment of ROD.     

Clinical impact of selective spasm provocation tests: comparisons between acetylcholine and ergonovine in 1508 examinations

BACKGROUND: There are few reports regarding the concordance of coronary arterial response between acetylcholine (ACh) and ergonovine (ER) spasm provocation tests. OBJECTIVES: We attempted to perform selective spasm provocation tests to examine the incidence of provoked spasm in patients who had undergone first coronary angiography as much as possible and we compared the coronary arterial response and clinical usefulness between selective intracoronary injection of ACh and intracoronary administration of ER. METHODS: We performed 1508 selective spasm provocation tests, consisting of 873 ACh tests and 635 ER tests, from 1991 to 2002. We examined the frequency of provoked spasms of each agent retrospectively. ACh was injected in incremental doses of 20, 50 and 80 microg into the right coronary artery and 20, 50 and 100 microg into the left coronary artery. ER was administered as 10 microg/min over 4 min for a maximal dose of 40 microg in the right coronary artery and as 16 microg/min over 4 min for a total dose of 64 microg in the left coronary artery. Coronary spasm was defined as transient >99% luminal narrowing. RESULTS: Intracoronary ACh provoked spasms in 36.0% of patients and intracoronary ER induced spasms in 29.8% of patients. In patients with ischemic heart disease, the incidence of provoked spasms was not different between ACh tests (50.9%) and ER tests (43.8%). In contrast, the frequency of provoked spasms with ACh tests was significantly higher than that with ER tests (11.0% compared with 6.4%, P<0.05) in patients without ischemic heart disease. Moreover, ACh provoked more spasms in patients without fixed stenosis than ER (36.2% compared with 25.5%, P<0.01) and multiple spasms were frequently observed when performing ACh tests (40.0% compared with 27.0%, P<0.01). Major complications were observed in 1.4% of patients with ACh tests and in 0.2% of patients with ER tests. The need for intracoronary administration of isosorbide dinitrate to relieve coronary spasms during ER testing before performing another coronary artery test was more frequently observed in ACh tests (5.04% compared with 1.49%, P<0.01). However, no serious irreversible complications, such as death or acute myocardial infarction, were observed in this study. There was a significant difference in sex, history of smoking and hyperlipidemia between patients with and without spasms for both tests, whereas no difference in age or hypertension was observed in either test. CONCLUSION: Thus, both selective ACh and ER tests were useful as spasm provocation tests.     

Failure to find an association between CD14-159C/T polymorphism and asthma: a family-based association test and meta-analysis.

BACKGROUND: CD14 is an essential component of the receptor for lipopolysaccharide (LPS). LPS stimulates T-helper type 1 (Th1) cytokine expression, potentially suppressing Th2 immune responses involved in IgE-mediated allergic diseases. Previous studies have reported that -159C/T, a promoter polymorphism of CD14, is associated with total serum IgE levels and atopy, but other studies have shown conflicting results. METHODS: To examine possible associations of CD14 polymorphisms with asthma susceptibility, we performed transmission disequilibrium tests (TDTs) of 137 Japanese families identified through children with atopic asthma. RESULTS: We found no association between -159C/T polymorphism and asthma (p= 0.37). Quantitative TDT and ANOVA showed no association between the -159C/T genotype and total serum IgE levels. We also performed a meta-analysis of data from all available studies. Neither a fixed-effects model nor a random-effect model showed a significant odds ratio for the -159C/T polymorphism (p > 0.1). CONCLUSIONS: Our data indicate that CD14 does not contribute substantially to susceptibility to asthma. Further studies examining both genotypes and environmental factors will be necessary to elucidate the role of CD14 in the development of allergic diseases.     

Morphology and biochemistry of the lung from guinea pig after repeated injections of freund’s complete adjuvant

Guinea pigs received 5 daily injections of Freund’s complete adjuvant and the changes in the lung were investigated by light microscope and electron microscope. In the 20th week of experiment, fibrotic changes were found around the granulomata close to the surface of the lung. In addition the fraction of glycosaminoglycans was isolated from the lung and analyzed quantitatively. As a result, a decrease in quantity of hyaluronic acid and an increase in quantity of dermatan sulfate were observed.     

Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting

Purpose:To evaluate the feasibility for the detection of slight contrast effects after intravenous administration of single dose gadolinium-based contrast agent (IV-SD-GBCA), the time course of the GBCA distribution up to 24 h was examined in various fluid spaces and brain parenchyma using 3D-real IR imaging and MR fingerprinting (MRF).Methods:Twenty-four patients with a suspicion of endolymphatic hydrops were scanned at pre-administration and at 10 min, 4 and 24 h post-IV-SD-GBCA. 3D-real IR images and MRF at the level of the internal auditory canal were obtained. The signal intensity on the 3D-real IR image of the cerebrospinal fluid (CSF) in the cerebellopontine angle cistern (CPA), Sylvian fissure (Syl), lateral ventricle (LV), and cochlear perilymph (CPL) was measured. The T₁ and T₂ values of cerebellar gray (GM) and white matter (WM) were measured using MRF. Each averaged value at the various time points was compared using an analysis of variance.Results:The signal intensity on the 3D-real IR image in each CSF region peaked at 4 h, and was decreased significantly by 24 h (P < 0.05). All patients had a maximum signal intensity at 4 h in the CPA, and Syl. The mean CPL signal intensity peaked at 4 h and decreased significantly by 24 h (P < 0.05). All patients but two had a maximum signal intensity at 4 h. Regarding the T₁ value in the cerebellar WM and GM, the T₁ value at 10 min post-IV-GBCA was significantly decreased compared to the pre-contrast scan, but no significant difference was observed at the other time points. There was no significant change in T₂ in the gray or white matter at any of the time points.Conclusion:Time course of GBCA after IV-SD-GBCA could be evaluated by 3D-real IR imaging in CSF spaces and in the brain by MRF.