A Wilms tumor cell line, HFWT, can greatly stimulate proliferation of CD56+ human natural killer cells and their novel precursors in blood mononuclear cells

OBJECTIVE: A Wilms tumor cell line, HFWT, selectively stimulates expansion of natural killer (NK) cells from human peripheral blood mononuclear cells (PBMC). In this study, we attempted to identify NK precursors in PBMC or in cord blood mononuclear cells (CBMC) that preferentially respond to feeder HFWT cells. MATERIALS AND METHODS: Human NK cells or candidate precursor cells were fractionated from PBMC or CBMC by magnetic antibody cell sorting or by flow cytometry and applied to limiting dilution analysis to determine the proportion of NK/NK precursor cells, which are able to proliferate on irradiated HFWT cells. NK and NK precursor cells were cultured in medium containing interleukin-2 (IL-2). Expansion of NK cells from both resting NK cells and NK precursor cells was examined using proliferation from single cells, expression of NK cell markers, and cytotoxic activity. RESULTS: In the limiting dilution analysis, NK cells expanded on irradiated HFWT cells not only from CD3-CD56bright and CD3-CD56dim NK cells, but also from CD16+/-CD122+ cells in the lineage-negative (Lin-, CD3-CD14-CD19-CD56-) cell fraction. The feeder HFWT cells stimulated Lin-CD122+ cell proliferation more strongly than feeder cells from the well-known human NK target cell line K562. CBMC contained significantly higher percentages of Lin-CD122+ cells than PBMC. CONCLUSION: CD3-CD14-CD19-CD56- cells expressing CD122+ (a subunit of the IL-2 receptor) preferentially respond to HFWT feeder cells and are novel precursors of CD3-CD56+ NK cells in human PBMC and CBMC.     

Quality of life improvements in dialysis patients receiving darbepoetin alfa

Short-acting hematopoietic agents can improve the quality of life (QOL) of hemodialysis patients, but questions remain regarding the domains of QOL affected, the relative importance of initial and final hemoglobin (Hb) concentrations, and the use of long-acting hematopoietic agents. We measured Hb concentrations and QOL in 487 hemodialysis patients who were switched from treatment with recombinant human erythropoietin to treatment with darbepoetin alfa. QOL was measured with the Japanese-language version of the SF-36, at the start of therapy with darbepoetin alfa and again 7-14 weeks later. We examined changes in QOL over time in the group as a whole, and in subgroups stratified by the change in Hb concentration. We also studied relationships between the final Hb concentration achieved and the magnitude of change in QOL. QOL scores increased significantly in all SF-36 domains except Social Functioning. The greatest increases were in vitality and in the two role-functioning domains. The magnitude of the increase in Hb concentration was related to the magnitude of the increase in QOL for only one subscale: Vitality. Patients with higher final Hb concentrations also had greater increases in Vitality scores. Hematopoiesis induced by darbepoetin alfa is associated with increased vitality and may also be associated with improved role functioning. Vitality increased significantly only in those patients with the greatest increases in Hb concentration and in those with higher final Hb concentrations.     

A new manometry device for evaluating the sphincter of Oddi using a fiber-optic pressure sensor

Introduction: Although measuring the pressure of the sphincter of Oddi and the bile duct is considered to be an important examination, called Sphincter of Oddi manometry (SOM), some complications related to the SOM device remain unsolved.

Material and methods: To decrease adverse complications, we developed a 0.46?mm manometry and we performed some in vitro studies.

Results: We successfully developed a 0.46?mm SOM. The diameter is the thinnest size used in endoscopic examinations. The results of in vitro studies show the suitability as SOM.

Conclusion: This device will decrease the risks related to SOM examination. To confirm the safety and feasibility, further studies including in vivo studies will be needed.     

Comparison of clinical, morphological, and prognostic features in hypertrophic cardiomyopathy between Japanese and western patients

Apical hypertrophic cardiomyopathy appears to be more common in Japan than in the West. Explanations for this difference include variable methods and criteria for the diagnosis. To assess morphological, clinical, and prognostic differences, 45 consecutive Japanese and 45 age- and gender-matched Western patients with hypertrophic cardiomyopathy were evaluated in two referral institutions by the same individuals. The diagnosis of hypertrophic cardiomyopathy was based on the echocardiographic demonstration of unexplained left ventricular hypertrophy. Patients were aged 8 to 64 years (mean 50); there were 66 males and 24 females. The pattern of left ventricular hypertrophy was similar in Japanese and Western patients: asymmetric septal 64 vs. 76%, concentric 22 vs. 13%, and apical 13 vs. 11% (p = NS). The incidence of an echocardiographic or Doppler calculated left ventricular gradient of > 30 mmHg was similar (11 vs. 18%; p = NS). The maximal left ventricular wall thickness was greater in Western patients (23 +/- 7 vs. 20 +/- 4 mm; p = 0.03), but was not different when adjusted for body surface area. Clinical features including incidence of family history and ventricular tachycardia during 24-h ambulatory electrocardiography were similar. During follow-up (4.9 +/- 4.0 years for Western vs. 4.4 +/- 2.0 years for Japanese), disease-related mortality was worse in Western patients (p < 0.05; 10 versus 2 patients). This evaluation, using the same diagnostic methods and criteria, reveals a worse prognosis in Western patients despite a similar clinical and morphological spectrum of hypertrophic cardiomyopathy.     

A pitfall in analyses of relevant factors concerning phenomena in the process of initiating dialysis: alterations in the characteristics of subjects diminish the significance of age

In our previous studies, relevant factors concerning the main phenomena related to the process of initiating dialysis were examined in elderly patients with chronic renal failure. Examined phenomena were as follows: (1) the acceptance of dialysis; (2) the urgency of initiating dialysis; (3) short-term outcome; (4) returning home. Multivariate logistic regression analysis was used to determine relevant factors. Although we speculated that age should be a relevant factor for each phenomenon, the phenomenon on which age had some impact was only the first. We suspected the existence of a pitfall, through which the relation of age was lost in the second, the third, or the fourth phenomenon. The fact that every phenomenon had its own relevant factors was thought to be an important clue to the discovery of pitfalls. Relevant factors were derived from both the number of dropout-patients and their demographic and clinical status. From the viewpoint of nondropout-patients, the progression of the process of initiating dialysis might alter the characteristics of subjects for successive phenomena In this study, we set out to investigate whether alterations in the characteristics of subjects were pitfalls. Alterations were regarded as a fall of the mean age, an increment of the rate of the patients with ability to walk, and an increment of the rate of the patients with normal cognitive function. In addition, the old-old patients tended to have limited numbers of those who had the ability to walk and normal cognitive function. In other words, aging changes in ambulatory and cognitive function were not brought to subjects. These alterations may cause the loss of the relation of age to each phenomenon. Thus, we presumed these alterations to be pitfalls. We must clarify whether aging changes are brought to subjects beforehand in analyses that include the old-old patients as subjects.     

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.     

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.