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Ocular melanoma is a rare type of malignant melanoma. Melanoma metastatic to the spine typically arises within the vertebral column, presents with back pain, and has a poor prognosis. We present a patient with a unique disease course: ocular melanoma metastasis occurred after an extended latency period of 14 years, attained a large size within the spinal intradural space, presented with severe neurological deficits without additional central nervous system disease, and the tumor was amenable to surgical intervention. We also review the literature on melanoma spine metastasis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

There are many autoimmune liver diseases in which diagnosis is difficult so that overlap is accepted, and this negatively affects treatment. The initial diagnosis is therefore important for later treatment and convalescence. We distinguished autoimmune cholangitis, autoimmune hepatitis and primary biliary cirrhosis by the Mahalanobis·Taguchi Adjoint (MTA) method in the Mahalanobis·Taguchi system and analyzed the pattern of factor effects by the MTA method. As a result, the characteristic factor effect pattern of each disease was classified, enabling the qualitative evaluation of cases including overlapping cases which were difficult to diagnose.

Objective: We examined the safety and efficacy of controlled-release basic fibroblast growth factor (b-FGF) for peripheral artery disease (PAD), compared with autologous bone marrow mononuclear cell implantation (BMCI)., Background: We recently developed a b-FGF-incorporated biodegradable hydrogel that enables slow-releasing drug delivery system., Methods: PAD patients were divided into a b-FGF group (n=10) and BMCI group (n=15). Injection of gelatin hydrogel containing 600 μg b-FGF or BMCI (0.4-5.1×10(10) cell) was performed. Visual analog pain scale (VAS), (99m)technetium-tetrofosmin (Tc-TF) scintigraphy, transcutaneous oxygen tension (TcPO(2)), and ankle-brachial index (ABI) were evaluated before and 4 weeks after each treatment, and 2-year prognosis was determined., Results: VAS (b-FGF 67±15 to 4±5, p<0.01, BMCI 67±42 to 5±9 mm, p<0.01) and TcPO(2) (b-FGF 16±14 to 47±17, p<0.01, BMCI 13±13 to 37±21 mmHg, p<0.01) were significantly improved in both groups. Tc-TF and ABI were not changed. Prognosis was similar between the groups (b-FGF 91%, BMCI 80%, NS)., Conclusion: Controlled-release b-FGF is as safe as BMCI, and its efficacy appears to be comparable. Thus, this therapy may be an alternative to BMCI.

Background: Endoscopic submucosal dissection (ESD) is more invasive than other common endoscopic procedures and may increase the risk for deep vein thrombosis (DVT)/pulmonary embolism. The incidence of DVT/pulmonary embolism after ESD has not been adequately studied., Objective: To evaluate DVT incidence and disease-specific features of D-dimer levels in ESD patients., Design: Prospective cohort study., Setting: Single academic center., Patients: This study involved 60 patients with superficial gastric neoplasms indicated for ESD., Intervention: For all patients who underwent ESD, ultrasonography of the lower limbs was performed to detect DVT the day after ESD. D-dimer levels were measured 3 times: before ESD, immediately after ESD, and the day after ESD., Main Outcome Measurements: DVT incidence after ESD., Results: The DVT incidence was 10.0% (6/60). At all 3 time points, D-dimer measurements were higher in patients with DVT than in patients without DVT. According to receiver operating characteristic curve analysis, the resulting cut-off value of the D-dimer level the day after ESD was 1.9 μg/mL (sensitivity 83.3%; specificity 79.6%) for ESD patients, with superior association to pre-ESD or immediately after ESD. In univariate analyses, high D-dimer levels the day after ESD and the presence of comorbidities were significantly associated with DVT development., Limitations: Single center and small number of patients., Conclusion: ESD procedures have a moderate risk for venous thromboembolism. In patients undergoing ESD, D-dimer levels, especially on the day after ESD, may have specific features associated with DVT development., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

The authors present the first case of spontaneous radiographic resolution and subsequent redemonstration of Gd enhancement of an untreated glioblastoma. They also review the literature on MR imaging enhancement patterns of high-grade gliomas and speculate that this phenomenon could be attributed to the dynamic biology of glioblastomas but could also represent pseudoregression following successful control of seizure activity. A 57-year-old woman presented with left-sided paresthesias and numbness. Initial Gd-enhanced MR images exhibited T2 and FLAIR signal changes in the right insular region without mass effect or contrast enhancement. Electroencephalography revealed intermittent sharp wave activity in this area. Antiepileptic medication was started, and the patient's symptoms resolved. Follow-up MR imaging 6 weeks later revealed enlargement of the lesion and contrast enhancement in the superior temporal gyrus. Consequently, the patient was scheduled for a brain biopsy. However, surgical planning MR images obtained on the day of surgery 4 weeks later showed that the enhancement had spontaneously resolved, and so the operation was cancelled. Repeat MR imaging performed 2 weeks later as a result of increased seizure frequency redemonstrated contrast enhancement. The patient then underwent a craniotomy, and final histopathology was consistent with glioblastoma.

Purpose: Despite advances in therapeutic angiogenesis by bone marrow cell implantation (BMCI), limb amputation remains a major unfavorable outcome in patients with critical limb ischemia (CLI). We sought to identify predictor(s) of limb salvage in CLI patients who received BMCI., Materials and Methods: Nineteen patients with CLI who treated by BMCI were divided into two groups; four patients with above-the-ankle amputation by 12 weeks after BMCI (amputation group) and the remaining 15 patients without (salvage group). We performed several blood-flow examinations before BMCI. Ankle-brachial index (ABI) was measured with the standard method. Transcutaneous oxygen tension (TcPO2) was measured at the dorsum of the foot, in the absence (baseline) and presence (maximum TcPO2) of oxygen inhalation. (99m)technetium-tetrofosmin ((99m)Tc-TF) perfusion index was determined at the foot and lower leg as the ratio of brain., Results: Maximum TcPO2 (p = 0.031) and (99m)Tc-TF perfusion index in the foot (p = 0.0068) was significantly higher in the salvage group than in the amputation group. Receiver operating characteristic (ROC) curve analysis identified maximum TcPO2 and (99m)Tc-TF perfusion index in the foot as having high predictive accuracy for limb salvage., Conclusion: Maximum TcPO2 and (99m)Tc-TF perfusion index in the foot are promising predictors of limb salvage after BMCI in CLI.

The authors successfully assessed the lacrimal systems of two patients with dacryocystocele based on dacryocystographic observations using computed tomographic scanning. The results showed that both the lacrimal sac and the nasolacrimal duct were largely distended, and the duct terminated in a closed cyst in the nasal cavity.

The purpose of this study was to investigate differences between natural tooth color and that selected for artificial teeth in partial dentures at our department with a view to establishing criteria for obtaining greater harmonization between colors. The participants in this study comprised partial denture wearers visiting the Department of Prosthodontics, Tokyo Dental College Chiba Hospital, in whom both artificial teeth and natural teeth were present in the maxillary anterior tooth area. Natural tooth color was measured according to VITA classical shade guide number using a dental color measurement apparatus. Artificial tooth color in partial dentures produced at our department was investigated by referring to medical records. Color of 28 participants' natural teeth and 345 participants' artificial teeth was investigated. Differences in color distribution between the natural and artificial tooth were analyzed using the Fisher exact test. The most frequent color of natural tooth was C-type, accounting for 39%, followed by D- at 32%, A-at 22% and B-type at 7%. In terms of artificial tooth color, A-type was the most common (97%). The color distribution of natural teeth differed significantly from that of artificial teeth in partial dentures. These results suggest that artificial tooth color did not harmonize with the color of the natural teeth in partial denture wearers.

Churg-Strauss syndrome (CSS) causes necrotizing vasculitis affecting small- to medium-sized arteries, mainly in the lungs, gastrointestinal system, heart, kidneys, and skin. Skin lesions sometimes ulcerate because of severe ischemia and become intractable when complicated by bacterial infection. We report a rare case of CSS, characterized by a nonhealing ischemic skin ulcer of the right calf with bacterial infection resistant to antibiotics. After sterile maggot debridement therapy, 2 skin autografts failed. Subsequently, a slow-release formula of basic fibroblast growth factor incorporated in biodegradable gelatin hydrogel was administered into the calf muscles to induce vascular regeneration. The ulcer eventually healed with no recurrence. This report describes the use of controlled-release basic fibroblast growth factor for an ischemic leg ulcer in a patient with CSS, suggesting a possible therapeutic role of this novel neovascularization therapy in treating severe skin lesions complicating autoimmune vasculitis syndromes.

A 25-year-old man was admitted to our hospital because of abdominal fullness. Abdominal enhanced CT, ultrasonography, and MRI revealed massive ascites and obstruction of the hepatic veins and the inferior vena cava. Gastrointestinal endoscopy showed F(3) esophageal varices with the so-called "red color sign". A diagnosis of Budd-Chiari syndrome (BCS) was confirmed by angiography which detected membranous obstruction of the hepatic veins. The cause of BCS in this patient was unclear. After treatment with percutaneous transluminal angioplasty (PTA), his ascites and esophageal varices improved.

Background: This is a technical report describing a different technique for the insertion of epidural electrodes in the preoperative evaluation of epilepsy surgery. Our experience in 67 cases using this technique is analyzed., Methods: Cylinder electrodes with multiple recording nodes spaced 1 cm apart along a Silastic core are placed into the epidural space under general anesthesia through single or multiple burr holes. We reviewed the data on 67 cases of medically intractable epilepsy requiring intracranial monitoring that had epidural cylinder electrodes placed. The electrodes were placed bilaterally or contralateral to subdural grids in 64 of the 67 cases. Continuous monitoring was performed from 1 to 3 weeks., Results: This method was most useful when used bilaterally or contralateral to subdural grids. Definitive surgery was rendered in 48 of 67 cases. After monitoring, all electrodes were removed at bedside or upon return to the operating room for definitive surgery. There were no mortalities, infections, cerebrospinal fluid leaks, neurologic deficits, or electrode malfunctions. Two patients (2/67, 3%) did develop subdural hematomas early in our series after dural injury near the pterion; however, these patients did not sustain permanent deficit., Conclusions: Epidural cylinders are another option for preoperative monitoring, useful for determining lobe or laterality of seizure genesis. They offer an alternate method to EPEs in cases where epidural recording is desirable. The cylinder electrodes are easy to place and can be removed without a return to the operating theater. The electrodes' minimal mass effect allows them to be safely placed bilaterally or contralateral to subdural grids. The epidural cylinders can monitor cortex with a greater density of nodes and can access regions not amenable to EPEs.

The purpose of this study was to clarify which physiological and anatomical factors were involved in the formation of tongue indentations, which are believed to be a clinical sign of clenching. Twenty-four dentulous subjects were investigated. They were divided into two groups, depending on the presence or absence of tongue indentations: (i) a tongue indentation group and (ii) a no tongue indentation group. Intraoral appliances containing a small pressure sensor were placed at the lingual surfaces of the upper and lower right first molars. Lingual pressure on the lingual surfaces of the upper and lower right first molars was then recorded under different conditions. The tasks selected as physiological factors to be recorded were: (i) silent reading at rest for 10 min, (ii) maximum voluntary clenching (MVC) for 5 s, (iii) 10% of MVC for 1 min and (iv) swallowing. The results for all tasks were compared between groups. Tongue width and dental arch width were also measured as anatomical factors. No significant differences were found between groups during silent reading at rest, clenching, swallowing, or in tongue pressure integration during silent reading at rest. However, a significant difference was found in terms of tongue width (P < 0.05). These results indicate that neither volume of lingual pressure exerted on the lingual surface of the teeth during rest, clenching, nor swallowing are related to the formation of tongue indentations. The results do suggest; however, that tongue width at rest plays an important role in the formation of tongue indentations.

Aim: To make clear whether CD147 (EMMPRIN) expression in pathological tumor samples with a fine-needle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC)., Methods: Twenty-two patients (15 men and 7 women; median age 68 years, range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC. Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody, murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition, the degree of staining within tumor tissue was compared according to a number of clinicopathological variables., Results: The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues, even in tumors less than 15 mm in diameter. The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and gamma-GTP., Conclusion: CD147 serves potentially as a pathological target for cancer detection of early HCC.

Purpose: To study the effect of candidate single nucleotide polymorphisms (SNPs) on chromosome 10q26, recently shown to be associated with wet age-related macular degeneration (AMD) in Chinese and Caucasian cohorts, in a Japanese cohort., Methods: Using genomic DNA isolated from peripheral blood of wet AMD cases and age-matched controls, we genotyped two SNPs, rs10490924, and rs11200638, on chromosome 10q26, 6.6 kb and 512 bp upstream of the HTRA1 gene, respectively, using temperature gradient capillary electrophoresis (TGCE) and direct sequencing. Association tests were performed for individual SNPs and jointly with SNP complement factor H (CFH) Y402H., Results: The two SNPs, rs10490924 and rs11200638, are in complete linkage disequilibrium (D'=1). Previous sequence comparisons among seventeen species revealed that the genomic region containing rs11200638 was highly conserved while the region surrounding rs10490924 was not. The allelic association test for rs11200638 yielded a p-value <10(-11). SNP rs11200638 conferred disease risk in an autosomal recessive fashion: Odds ratio was 10.1 (95% CI 4.36, 23.06), adjusted for SNP CFH 402, for those carrying two copies of the risk allele, whereas indistinguishable from unity if carrying only one risk allele., Conclusions: The HTRA1 promoter polymorphism, rs11200638, is a strong candidate with a functional consequence that predisposes Japanese to develop neovascular AMD.

An 81-year-old Japanese man with jaundice was strongly suspected clinically of having primary sclerosing cholangitis based on clinical examinations and later died of hepatic failure. The entire course of the disease lasted about 10 mo. The autopsy revealed extensive fibrinoid necrosis in the liver, kidney, spleen, pancreas, lung, lymph nodes, and pleura. Particularly extensive fibrinoid necrosis in the portal tracts of the liver induced severe stenoses of the intrahepatic bile ducts, resulting in cholestasis in association with prominent liver injury. There were no findings indicating primary sclerosing cholangitis. The hepatic lesions in this case did not coincide with any known disease including collagen diseases. To clarify the cause of irregular stenoses of the intrahepatic biliary trees on cholangiographic findings, we postulate that some form of immunological derangement might be involved in pathogenesis of fibrinoid necrosis. However, the true etiology remains unknown.

Chronic stimulation of beta-adrenergic receptors (betaARs) induces betaAR downregulation. However, it is not known whether continuous activation of adenylyl cyclase without direct stimulation of betaARs leads to receptor downregulation. This study investigated the effects of chronic stimulation of adenylyl cyclase with colforsin, on hemodynamic variables, and on myocardial betaAR density. In all, 55 rabbits received intravenous colforsin (1.6 microg/kg/min, n = 20), isoproterenol (ISO; 0.4 microg/kg/min, n = 16), or saline (n = 19) for two weeks. After chronic drug administration, responses of systolic (Delta% peak LV +dP/dt) and diastolic function (Delta% peak LV -dP/dt), and heart rate (Delta% heart rate), to acute administration of ISO (0.05 to 0.2 microg/kg/min) or colforsin (5 to 20 nmol/kg/min) were decreased compared to those before chronic administration. betaAR density in the colforsin group (69.8 +/- 13.8 fmol/ml protein) was less than that in the saline group (79.8 +/- 15.0 fmol/ml protein, P < 0.05), but was greater than that in the ISO group (56.3 +/- 8.4 fmol/ml protein, P < 0.05). Thus, chronic direct stimulation of adenylyl cyclase elicited systolic and diastolic functional desensitization to betaAR stimulation or adenylyl cyclase stimulation, and myocardial betaAR downregulation.

Patient: This is a clinical case report of esthetic and masticatory impairment due to a mandibular protrusion during occlusion. The patient was a complete edentulous subject who complained about esthetic and matiscatory disturbance. First of all, treatment dentures were done, in order to improve the mandible position and recover the facial aspect. Objective evaluations were carried out to compare the improvements achieved after the insertion of the new dentures., Discussion: The treatment dentures were used to improve patient's mandible position as well as vertical dimension. Once the facial appearance was recovered as a result of an appropriate mandible position, a reduction of the angle formed between the FH plane and the A-B plane from 87 to 83 was recognized after the insertion of the new dentures through the analysis of lateral cephalograms. It indicates that the mandible's position changed to backward position resulting in an improvement of the facial aspect., Conclusion: In the present clinical case report, not only subjective evaluation for appropriate mandible position and vertical dimension, but also including objective evaluation methods allowed us to evaluate and compare objectively the patient's pre and post operative condition.

Purpose: To study the frequency of five haplotypes previously reported in the complement factor H (CFH) gene for Japanese patients with age-related macular degeneration (AMD)., Methods: Genomic DNA was isolated from peripheral blood samples taken from 96 Japanese AMD patients and 89 age-matched controls. All patients were diagnosed as having exudative (wet-type) AMD. The amplified polymerase chain reaction (PCR) products of CFH exons 2, 9, and 13, and intron 6 were analyzed by temperature gradient capillary electrophoresis (TGCE) and by direct sequencing. The haplotypes were identified, and their frequencies were calculated and compared with reported results., Results: Five haplotypes were identified in the Japanese population including four already reported in the American population. The frequencies of these haplotypes were significantly different between Japanese and American in both control and case groups. The haplotype containing Y402H, which was previously reported to be associated with AMD, was only 4% in the control and case population, with a p value of 0.802. However, two other haplotypes were found as risk factors, which gave an increased likelihood of AMD of 1.9 and 2.5 fold (95% CI 1.12-3.69 and 1.42-6.38). One protective haplotype that decreased the likelihood of AMD by 1.6 fold (95% CI 0.26-0.67) was identified., Conclusions: The frequencies for five haplotypes previously identified were analyzed in a Japanese population with AMD. Four previously found haplotypes were identified and one additional haplotype was found. The frequencies of each haplotype were significantly different from that in found Americans affected with AMD. Two of the haplotypes were identified as risk factors and one was considered protective.

The association between cancer and hemostasis has long been studied in cell culture, animal models, and cancer patients developing thrombosis. The variety of biologic mechanisms involved in malignancy and metastasis makes the understanding of the relative importance of each mechanism difficult. We have developed a novel in vitro perfusion model that allows for the isolated study of the interactions between tumor cells and components of the hemostatic system under normal physiologic conditions. Segments of denuded umbilical cord or saphenous vein are cut longitudinally and mounted in a perfusion chamber under sterile conditions. Human breast cancer cells are perfused for 24 h under venous flow conditions with either whole blood (WB), platelet-rich plasma (PRP), platelet-poor plasma (PPP), or serum. Tissue samples are fixed and stained with hematoxylin and eosin as well as with pan-cytokeratin. Morphometric analysis is performed to quantify cancer cell adhesion. With PRP, this model maintains normal human physiologic conditions for the duration of the experiment. It differentiates between previously characterized high and low metastatic breast cancer cell lines. In addition, different vein tissue types do not alter tumor cell attachment. This model appears to be an accurate representation of the pathophysiology of in vivo metastasis. This model may serve as a useful bridge between cell culture studies and animal models. It may be a useful tool to elucidate the role of selected hemostatic systems in blood-borne metastasis and may potentially serve as a screening tool for the development of antimetastatic pharmaceutical agents., (Copyright 2005 Wiley-Liss, Inc.)

To study whether chronic liver disease (CLD) and genetic polymorphism affect the hepatic activity of cytochrome P450 (CYP) isoforms, we compared in vivo CYP2C19 and CYP3A activities using 3-hour omeprazole hydroxylation index (plasma concentration ratio of omeprazole to its 5-hydroxylated metabolite; a higher index indicates lower CYP2C19 activity) and partial formation clearance of cortisol to 6beta-hydroxycortisol (CL(cortisol-->6beta-HC)) in 31 CLD patients (9 with chronic hepatitis; 22 with cirrhosis comprising 20 Child-Pugh type A, 1 type B, and 1 type C) and 30 healthy subjects with different CYP2C19 genotypes. The mean (+/-SEM) omeprazole hydroxylation index in CLD patients with homozygous extensive metabolizer (EM) genotype (*1/*1, n = 8), heterozyous EM (*1/*2, n = 11; *1/*3, n = 6) genotypes and poor metabolizer (PM) genotypes (*2/*2, n = 3; *3/*3, n = 3) were 17.15 +/- 2.12, 20.02 +/- 2.63, and 26.04 +/- 3.15, respectively, which were significantly higher compared with control subjects with the corresponding CYP2C19 genotypes (0.81 +/- 0.09, 1.55 +/- 0.20, and 15.5 +/- 1.52). CLD patients with PM genotype had significantly (P < .05) higher omeprazole hydroxylation indexes than did those with homozygous EM genotype, and those with heterozygous EM genotypes had intermediate values. The mean CL(cortisol-->6beta-HC) decreased significantly (P < .001) in CLD patients compared with control subjects (1.19 +/- 0.12 versus 2.26 +/- 0.24 mL/min). Multiple regression analysis showed that CLD, serum albumin level, and CYP2C19 genotype correlated significantly (P < .05) with the omeprazole hydroxylation index, whereas no significant correlation was observed between CL(cortisol-->6beta-HC) and other variables, except CLD. Because CLD and genetic polymorphism of CYP2C19 act additively to reduce CYP2C19 activity, genotyping these patients may be of value in averting adverse reactions of drugs that depend on CYP2C19 for elimination.

Background: The carcinogenic process can be modulated by exposure to endogenous or environmental substance(s) acting as carcinogens or protocarcinogens. Polymorphic enzymes of cytochrome P450 (CYP) that play a role in detoxication/toxication of such substances via metabolization may account for the interpatient variability of clinical course in cancers such as hepatocellular carcinoma (HCC). Many CYP genetic polymorphisms, which may change enzyme activity, are known to exist in Japanese. The aim of the present study was to compare the frequencies of CYP polymorphisms between hepatitis C virus (HCV)-related HCC patients and healthy subjects., Methods: Seven mutant alleles and related genotypes of CYP in 44 HCV-positive HCC patients were chosen as follows: *1C heterozygous, *1C homozygous and *1F homozygous for CYP1A2, *4A homozygous for CYP2A6, *2A or *3 heterozygous, *2A or *3 homozygous and *2A and *3 heterozygous for CYP2C19, and *10/*5 homozygous for CYP2D6. These mutant alleles have been reported to change the CYP enzyme activity in Japanese. The frequencies of the mutant alleles and genotypes were then compared with those reported in healthy Japanese., Results and Conclusion: There is no statistically significant difference in genetic mutant alleles between the two groups, except for the genotype of CYP2A6*4A homozygous. The frequency of this genotype in the HCC patients (0.144) is significantly higher than that in healthy Japanese (0.034; P < 0.05; odds ratio 3.36). The clinical significance related to HCC is unknown. Further evaluation of CYP2A6*4A (deletion type) in HCV-related HCC patients is required.

In a genetically engineered mouse line with disruption of type 5 adenylyl cyclase (AC5-/-), a major cardiac isoform, there was no compensatory increase in other isoforms of AC in the heart. Both basal and isoproterenol (ISO)-stimulated AC activities were decreased by 30% to 40% in cardiac membranes. The reduced AC activity did not affect cardiac function (left ventricular ejection fraction [LVEF]) at baseline. However, increases in LVEF after ISO were significantly attenuated in AC5-/- (P<0.05, n=11). Paradoxically, conscious AC5-/- mice had a higher heart rate compared with wild-type (WT) mice (613+/-8 versus 523+/-11 bpm, P<0.01, n=14 to 15). Muscarinic agonists decreased AC activity, LVEF, and heart rate more in WT than in AC5-/-. In addition, baroreflex-mediated, ie, neuronally regulated, bradycardia after phenylephrine was also attenuated in AC5-/-. The carbachol-activated outward potassium current (at -40 mV) normalized to cell capacitance in AC5-/- (2.6+/-0.4 pA/pF, n=16) was similar to WT (2.9+/-0.3 pA/pF, n=27), but calcium (Ca2+)-mediated inhibition of AC activity and Ca2+ channel function were diminished in AC5-/-. Thus, AC5-/- attenuates sympathetic responsiveness and also impairs parasympathetic and Ca2+-mediated regulation of the heart, indicating that those actions are not only regulated at the level of the receptor and G-protein but also at the level of type 5 AC.

We examined the effects of gender and aging on cardiac and peripheral hemodynamic responses to beta-adrenergic receptor (beta-AR) stimulation in young (male = 5.9 +/- 0.4 yr old and female = 6.5 +/- 0.7 yr old) and old (male = 19.8 +/- 0.7 yr old and female = 21.2 +/- 0.2 yr old) conscious monkeys (Macaca fascicularis), chronically instrumented for measurements of left ventricular (LV) and arterial pressures as well as cardiac output. Baseline LV pressure, the first derivative of LV pressure (LV dP/dt), cardiac index, mean arterial pressure, total peripheral resistance (TPR), and heart rate in conscious monkeys were not different among the four groups. Increases in LV dP/dt in response to 0.1 microg/kg isoproterenol (Iso) were diminished (P < 0.05) in old males (+99 +/- 11%) compared with young males (+194 +/- 18%). In addition, the inotropic responses to norepinephrine (NE) and forskolin (FSK) were significantly depressed (P < 0.05) in old males. Iso-induced reductions of TPR were less (P < 0.05) in old males (-28 +/- 2%) than in young males (-49 +/- 2%). The changes of TPR in response to NE and FSK were also significantly attenuated (P < 0.05) in old males. However, the LV dP/dt responses to BAY y 5959 (15 microg. kg-1. min-1), a Ca2+ channel promotor independent of beta-AR signaling, were not significantly different between old and young males. In contrast to results in male monkeys, LV dP/dt and TPR responses to Iso, NE, and FSK in old females were similar to those observed in young females. Thus both cardiac contractile and peripheral vascular dynamic responses to beta-AR stimulation are preserved in old female but not old male monkeys. This may explain, in part, the reduced cardiovascular risk in the older female population.

The aim of this study was to clarify the factors related to the formation of the buccal mucosa ridging, which has been mentioned to be a clinical sign of clenching. Twenty-one individuals were investigated and divided into three groups: (i) those without buccal mucosa ridging, (ii) the buccal mucosa ridging located in all the posterior teeth region, and (iii) the buccal mucosa ridging corresponding only to the molar teeth region. A pressure sensor was used and placed at two points: first upper premolar and second upper molar. The recording tasks were: (i) silent reading at rest, (ii) light voluntary clenching, (iii) maximum voluntary clenching, (iv) holding the cheeks tightly against the teeth while light voluntary clenching, (v) holding the cheeks tightly against the teeth without tooth contact, (vi) pulling angle of mouth laterally while light voluntary clenching, (vii) pulling angle of mouth laterally without tooth contact and (viii) swallowing. No significant differences were found between groups in all the recording tasks except for the swallowing, at which significant difference (P < 0.05) was found between the groups of individuals having buccal mucosa ridging and without it. Based on these results it became clear that the buccal mucosa pressure exerted on the buccal aspect of teeth during swallowing plays an important role in the formation of buccal mucosa ridging.

Introduction: Intrarenal coagulation and fibrinolysis are thought to be involved in the pathogenesis of diabetic nephropathy. However, gene expression of fibrinolytic factors in diabetic nephropathy has not been clearly defined. Therefore we determined the gene expression of fibrinolytic factors in the kidneys of diabetic rats., Materials and Methods: As a model of type1 diabetes male Sprague-Dawley rats were used. They were divided into three groups: control, streptozotocin (STZ)-induced diabetic, and insulin-treated diabetic. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used as a model of type 2 diabetes; and Long-Evans Tokushima Otsuka (LETO) rats, as the control. Renal gene expressions of type-1 plasminogen activator inhibitor (PAI-1), tissue-type PA (tPA), and urokinase-type PA (uPA) were examined by real-time PCR. Localization of PAI-1 mRNA was investigated by in situ hybridization., Results: Renal PAI-1 mRNA levels (versus control) were increased by 60-80% in STZ-induced diabetic rats (10 days or 3 weeks post STZ injection); and insulin treatment reduced this increased expression to the control level. In OLETF rats (38 weeks old), the renal PAI-1 mRNA level was 2.5-fold higher than that in age-matched LETO rats. Both tPA and uPA mRNA levels were significantly lower than those in LETO rats. PAI-1 mRNA was observed in intraglomerular cells and tubular epithelial cells of both models., Conclusions: Renal PAI-1 gene expression is up-regulated in both type 1 and type 2 diabetic rats, and changes in gene expressions of fibrinolytic factors may play important roles in the development and pathogenesis of diabetic nephropathy.

Aim: This study describes the clinical profiles and outcomes of renal failure patients with late initiation of renal replacement therapies (RRT) based on uremic symptoms under intensive treatment prior to the start of RRT (IT)., Methods: Thirteen patients (male 10, female 3) with end-stage renal disease who preferred to wait for the initiation of RRT until uremic symptoms appeared regardless of serum creatinine (s-Cr) and 24-hour creatinine clearance (24-hour Ccr) were chosen. All patients received IT including a low-protein diet, antihypertensive drugs including enalapril, erythropoietin and others to prevent and manage uremic states until the initiation of RRT. Clinical findings at the initiation of RRT and the outcomes after the start of RRT were examined., Results: RRT was initiated 23.6 +/- 16.9 months after IT without any complication in all patients when mild uremic symptoms appeared. Uremic symptoms, blood pressure, serum albumin, potassium, calcium and urinary Cr excretion were well controlled except inorganic phosphate, hemoglobin and cardiac size. 24-hour Ccr and s-Cr were 3.4 +/- 0.7 ml/min and 17.4 +/- 3.8 mg/dl at initiation of RRT. The outcomes of all the patients were all well during chronic RRT., Conclusion: Intensive treatment prior to the start of RRT can diminish uremic symptoms and complications so that RRT might be initiated safely and with fewer problems, even in the face of lower 24-hour Ccr and markedly higher s-Cr., (Copyright 2002 S. Karger AG, Basel)

Direct hemoperfusion (DHP) with an adsorbent column using polymyxin B-immobilized fiber (PMX-F) has been shown to improve the state of shock in patients with septic shock. However, no evidence has been presented for a direct link between endotoxin removal by DHP with PMX-F and improvement in septic shock. We retrospectively analyzed clinical profiles of 24 patients with septic shock (16 patients, gram-negative; 8 patients, non-gram-negative septic shock) who underwent DHP with PMX-F. Patients with gram-negative septic shock were characterized by hyperdynamic circulation. DHP with PMX-F reduced blood endotoxin concentrations and ameliorated shock, with an improvement in hyperdynamic circulation in patients with gram-negative septic shock. Mean arterial pressure also was elevated after therapy in patients with non-gram-negative septic shock, but systemic hemodynamics were unaffected. Regardless of the causative microorganism, patients with endotoxemia (blood endotoxin level > 10 pg/mL) showed hyperdynamic shock, and DHP with PMX-F reduced blood endotoxin levels and ameliorated hyperdynamic circulation, whereas patients without endotoxemia showed features of shock without hyperdynamic circulation, and DHP with PMX-F ameliorated shock without affecting cardiac performance. In patients with gram-negative septic shock, blood endotoxin concentration correlated positively with cardiac output and negatively with systemic vascular resistance before DHP therapy. Reduction in blood endotoxin concentration by DHP therapy positively correlated with the reduction in cardiac output. Our findings indicate that the improvement in hyperdynamic circulation was related directly to endotoxin removal by the PMX-F column, and endotoxin has an important role in the development of hyperdynamic circulation in patients with gram-negative septic shock., (Copyright 2002 by the National Kidney Foundation, Inc.)

A reaction of 13-hydroperoxide octadecadienoic acid (13-HPODE) with cytochrome c was analysed using ESR, HPLC-ESR and HPLC-ESR-MS by the combined use of the spin-trapping technique. The ESR, HPLC-ESR and HPLC-ESR-MS analyses showed that cytochrome c catalyses formation of pentyl and octanoic acid radicals from 13-HPODE. On the other hand, only the alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone/octanoic acid radical adduct was detected in the elution profile of HPLC-ESR for a mixture of 13-HPODE with haematin, indicating that haematin catalyses the formation of octanoic acid radical. In addition, the reaction of 13-HPODE with cytochrome c was inhibited by chlorogenic acid, caffeic acid and ferulic acid via two possible mechanisms, i.e. reducing cytochrome c (chlorogenic acid and caffeic acid) and scavenging the radical intermediates (chlorogenic acid, caffeic acid and ferulic acid).

Systemic inhibition of nitric oxide synthase (NOS) in streptozotocin-induced (STZ-induced) diabetic rats results in decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) and an increase in renal vascular resistance (RVR). However, the exact isoform of NOS involved in diabetic renal hyperfiltration has not been determined. This study was conducted to clarify whether NO derived from neuronal NOS is involved in diabetic renal hyperfiltration when using a selective inhibitor of neuronal NOS, 7-nitro indazole (7-NI). Continuous infusion of NG-nitro-L -arginine methyl ester (L-NAME) at 5 microg/kg/min ameliorated renal hyperfiltration, decreased RPF, and increased RVR in diabetic rats without affecting the mean arterial pressure (MAP). 7-NI administered intraperitoneally in diabetic rats significantly reduced GFR without affecting MAP, but the renal hyperfiltration was still observed after the administration of 7-NI. The combined administration of L-NAME after 7-NI caused a further decrease in GFR in diabetic rats and ultimately resulted in normalization of GFR. 7-NI did not change any parameters of renal hemodynamics in control rats. Urinary excretion of nitrite/nitrate and cyclic guanosine monophosphate was significantly increased in diabetic rats over values found in control rats. Our results suggested that a local inhibition of NO in the kidney was involved in the amelioration of diabetic renal hyperfiltration and that NO derived from neuronal NOS is involved, at least in part, in renal hyperfiltration in STZ-induced diabetic rats.

Background: Approximately 20 percent of all allogeneic blood transfusions are administered in connection with coronary artery bypass graft (CABG) operations. Transfusion practices vary across the country. The whole-body oxygen extraction ratio (O2 ER) reflects the adequacy of the patient's response to acute normovolemic anemia with an O2 ER of approximately 50 percent being shown to be an appropriate transfusion trigger. The present study monitored the O2 ER in patients undergoing CABG and determined if transfusion practices would have been different if an O2 ER > or = 45 percent were used as a transfusion trigger., Study Design and Methods: Seventy patients with a postoperative Hct < = 25 percent were the test subjects. Arterial and mixed venous contents were determined before the operation, in the intensive care unit after the operation, and 12 hours after the operation., Results: There were no deaths. Forty-one patients received allogeneic transfusion. These patients were older, weighed less, and had a preoperative Hct lower than the nontransfused patients. There were no significant differences between transfused and nontransfused patients with respect to postoperative Hct (21.0 +/- 0.4 vs. 22.2 +/- 0.4), cardiac index (2.5 +/- 0.1 vs. 2.7 +/- 0.1), O2 delivery (6.4 +/- 0.3 vs. 6.7 +/- 0.3), O2 consumption (2.5 +/- 0.1 vs. 2.5 +/- 0.1), and O2 ER (38.3 +/- 1.7 vs. 37.5 +/- 1.5). In the transfusion group, 7 of 21 patients had a postoperative O2 ER > or = 45 percent, while 3 of 35 in the nontransfused group had that result., Conclusion: The use of O2 ER as a transfusion trigger as part of a transfusion algorithm could lead to a reduction in allogeneic blood transfusion.

Our study was designed to clarify whether renal functional reserve (RFR) was impaired in rats chronically treated with oral low-dose cadmium (Cd). Rats (n = 15) were treated with 1 ppm of cadmium chloride added to drinking water. We measured RFR (representing the ability to increase glomerular filtration rate [GFR] and renal plasma flow [RPF] in response to infusion of glycine) at 2 and 10 months after initiation of exposure to Cd. Urinary excretion of Cd was significantly higher in 10-month Cd-treated rats than in age-matched control rats (provided with distilled water only). Weight gain was noted in Cd-treated rats, which was identical to that in age-matched control rats. Urinary volume and urinary excretions of sodium, protein, and glucose were similar in the two groups. There were no differences in the basal mean arterial pressure (MAP) and renal hemodynamics between 2-month Cd-treated and age-matched control rats. Infusion of glycine resulted in significant increases in GFR and RPF and a significant reduction in renal vascular resistance (RVR) in both 2-month Cd-treated and age-matched control rats (control, GFR: 133 +/- 10%, RPF: 148 +/- 8%; 2-month Cd-treated rats, GFR: 152 +/- 12% and RPF: 154 +/- 7%). The basal MAP and renal hemodynamics in 10-month Cd-treated rats were also identical to those in age-matched control rats. Infusion of glycine significantly increased GFR in 10-month control rats (132 +/- 15%), but not in 10-month Cd-treated rats (98 +/- 11%), but did not change MAP, RPF, and RVR in both groups. In addition to age-related pathological changes, mild renal interstitial edema and degenerative mitochondria with diminished matrix density and loss of the cristae in the proximal tubular cells were more frequent in 10-month Cd-treated rats. Our results suggest that long-term oral intake of low-dose Cd in rats exacerbate age-related impairment of renal functional reserve and degeneration of the proximal tubular epithelial cells., (Copyright 2000 Academic Press.)

Background: Hepatocellular carcinoma (HCC) occurs more frequently in patients with hepatitis C virus (HCV)-related chronic liver disease than those with hepatitis B virus-related disease. It is important to assess the factors affecting the development of HCC., Methods: A long term follow-up study involving patients with chronic HCV was performed retrospectively. A total of 153 patients diagnosed between June 1981 and November 1990 with chronic HCV with or without cirrhosis by liver biopsy were enrolled in a long term follow-up study (average, 99.4 months) and the cumulative incidence rate of HCC and factors affecting the appearance of HCC were examined., Results: The 5-year cumulative incidence rate was 9%, the 10-year cumulative incidence rate was 23%, and the 15-year cumulative incidence rate was 42%. The annual rate of incidence increased as the follow-up period progressed. The authors selected ten variables and investigated their effect on the incidence rate of HCC, including age, gender, habitual heavy drinking, positivity of antibody against hepatitis B virus surface antigen, treatment with interferon (IFN) during the follow-up period, maximum and minimum serum alanine aminotransferase levels during the follow-up period, histologic staging, grading, and irregular regeneration of hepatocytes. Of the 10 variables, age (> 50 years), habitual heavy drinking, and histologic staging were determined to be independent risk factors according to multivariate Cox proportional hazards regression analysis. IFN therapy by itself was not found to be an independent factor affecting the appearance of HCC., Conclusions: In patients with chronic HCV, the annual incidence rate of HCC appeared to increase as the follow-up period progressed. According to the results of the current study, the factors that independently affected the development of HCC were age, habitual heavy drinking, and histologic staging., (Copyright 2000 American Cancer Society.)

Unlabelled: The Mahalanobis-Taguchi System (MTS), an evaluative technique used in quality engineering, was utilized in a system analysis of medical examinations to determine practicability, to differentiate cost reduction benefits of specific components for increasing efficiency, and to determine possibility of utility on forecasting of future health condition of individuals., Methods: 1. Medical examination date over a two year period were utilized to differentiate subject into two groups: Group A--Healthy or normal; and Group C--Patient group requiring treatment or currently undergoing treatment. The Mahalanobis distance for Group C from the Mahalanobis space of Group A was calculated for each subject to determine differentiability. 2. Utilizing the MTS method specific components of the examination system were selected and analyzed for effectiveness in diagnosis and screening to enhance efficiency of the examination. 3. Group A subjects (determined from the two year data), were analyzed using the data at the end of 1 year to develop the Mahalanobis space and the Mahalanobis distance at the 2nd year point was calculated and analyzed., Results: 1. Subjects who were classified as group A at both 1st and 2nd year points numbered 159. With a cutoff point of 2.0 for Mahalanobis distance 98.1% of the healthy subjects (Group A) were classified as belonging to the healthy group, and 91.9% of C group as belonging to the patient group. 2. Blood pressure, GOT, GPT, gamma-GTP, T Chol, TG, UA, Cr, BS, HbA1c, Hb, and MCH were found to be effective components in the examination. Based on this result the items included in the examination can be reduced by approximately 60%. 3. With cutoff value of 1.5, the results of 90% of subjects 1 year later could be predicted. The prediction that 15% of Group C subjects would improve to join Group A could be made. Overall, the results 1 year later could be predicted at a level of 90% accuracy., Conclusion: These results suggest that the Mahalanobis-Taguchi System technique can accurately assess medical examination quality and can also be used, with reasonable accuracy, to predict the condition of individuals one year later. Therefore, the MTS can be used to help determine which patients should be receiving the examination 1 year later. In addition, components of the examination can be assessed using the MTS for benefits and costs to determine levels of essentiality of components. As a result, it can be used an effective tool for development and improvements in the examination system. With further development in the technique, it may become possible for use as a tool in disease diagnosis and treatment.

The possibility of producing calcium-induced alginate gel beads as a vehicle for liposomes was explored. The maximal loading of egg phosphatidylcholine liposomes (ca. 26 nm in diameter) in a fully-cured bead (1.2 mm in radius, initial alginate concn. of 4%) was 2.9 x 10(-6) mol/bead or ca. 18%, and the size of the bead slightly increased with an increase in liposome loading. The liposomes were well maintained within both fully-cured and washed beads. The liposome release from the fully-cured bead was much slower than that from the corresponding washed bead in a pH 7.4 releasing medium. The greater the liposome loading, the faster the release of the vesicles. The liposome release was investigated in terms of liposome loading, swelling of the gel body, calcium discharge and gel erosion, using washed beads. The liposome loading did not affect the bead erosion or calcium discharge but did the initial swelling ratio and liposome release. The results suggest that the loaded liposomes are not uniformly distributed in the bead but are rather gradually concentrated to the center. Such an inhomogeneous distribution of liposomes is possibly due to the fact that the gelation occurred instantly on the surface of the droplets, and the resulting gel network or layer acts as semipermeable membrane for liposomes and forces the vesicles to move into deeper concentric sections as gelation proceeds to the interior. As the liposomes loading increases, the forced migration might be very limited because of concentrically decreasing extra room to accommodate the vesicles in the bead.

To explore the feasibility of alginate gel as a vehicle for liposomes, we investigated the effects of various factors associated with the loading of drug-containing liposomes into the gel beads. The loading process includes (I) mixing of liposomes and alginate solution, (2) calcium induced gelation of alginates, (3) the time-dependent contraction of a gel body squeezing out interior water, and (4) possible leakage or release of a drug entrapped in liposomes in a series of each of theses processes. These effects were examined in terms of the leakage of a marker 5(6)-carboxyfluorescein (CF) from liposomes of egg phosphatidylcholine (EPC) and EPC/cholesterol (EPC/Cho) and liposome (phosphorus) release from curing and fully-cured gel beads whose initial polymer concentrations were 4 and 2%. Major findings were: (1) Alginate induced the leakage of a water-soluble drug incorporated in the liposomes as a function of the polymer concentration and the mixing time. (2) Calcium ions also stimulated the leakage of the drug. EPC/Cho liposomes were several times more resistant to the leakage of CF than were EPC liposomes. (3) The liposomes were well loaded without any loss in the gel bead despite the squeezing outflow of water and the bead contraction during gel curing. (4) Such curing caused leakage of the drug from the EPC liposomes in the very early stage while no effect was observed in the EPC/Cho liposomes. (5) In the gel-eroding medium (pH 7.4 Tris-HCl, 37 degrees C), the total drug release was controlled by the erosion rate of the bead body. Immediately after the bead erosion, EPC liposomes retained about 60% of the drug in the 2% bead and only about 20% in the 4% bead, whereas EPC/Cho liposomes retained more than 85% regardless of the initial alginate concentration. The results provide valuable information for the design and applicability of the gel-loaded liposome delivery system.

Pollen of Chamaecyparis obtusa (Japanese cypress) is one of the causes of allergic pollinosis in Japan. A major allergen of the pollen designated Cha o 1, was purified by two-step ion exchange chromatography. Cha o 1 was separated into four components with molecular masses of 48.5 kDa and 52.0 kDa, each with pIs of 6.77 and 6.82. The 23-residue N-terminal sequence of Cha o 1 was determined and shown to have high identity with that of Cry j 1, a major allergen of Cryptomeria japonica pollen. cDNA coding for Cha o 1 was cloned by hybridization screening using Cry j 1 cDNA as a probe. One of the cDNA clones, pCHA-1 was sequenced and found to code for a putative 21-residue signal peptide and a 354-residue native protein with a derived molecular mass of 38.1 kDa. The deduced amino acid sequence of Cha o 1 showed 79-80% identity with those of Cry j 1. These findings were consistent with observations of a close crossreaction between the two allergens. Homology analyses revealed that Cha o 1 had 46-49% identity with Amb a 1 families and Amb a 2, the major allergens of short ragweed. Cry j 1 has pectate lyase enzyme activity, suggesting that Cha o 1 may have the same enzyme activity as Cry j 1.

Allergic rhinitis is conventionally treated with anti-histamine or immunotherapy, although in many cases the results are unsatisfactory. Using a contact type Nd:YAG laser we have succeeded in relieving the symptoms of rhinitis by thermocoagulating only the inferior turbinate, making this a quick and effective form of treatment. The subjects were 60 patients with severe house-dust induced allergic rhinitis presented to the out-patient clinic of the ENT department of Nagoya City University Hospital. There were 25 men and 35 women ranging in age from 17 to 53 years. Patients were irradiated at an output of 10 W for 0.5 s for a total of about 386 joules for both nasal cavities. Prior to the procedure, surface anesthesia was applied using 10% cocaine. The irradiation was completed in only one out-patients session. The effects of this therapy were evaluated using 4 points to express the degree of subjective symptoms and intranasal findings. From one week before surgery the patient was asked to record symptoms (sneezing, blowing, blockage) every day, and to continue this recording until 4 weeks after surgery. After surgery no drugs were used. The effects were evaluated by adding up the total scores for sneezing, blowing, and blockage at one week intervals, and comparing the total scores between one week pre-operatively and those 1, 2, 3, and 4 weeks post-operatively. Full effect, including disappearance of symptoms, was obtained in 80%, good effect in 10%, fair effect in 5%, and no effect in 5%.

In type I allergy such as allergic rhinitis, not only immunocytes but also interleukin 4 (IL-4) and other cytokines are significant factors. In the present study we explored the course of change in IL-4 in the sera of allergic rhinitis patients upon immunotherapy. Assays of serum IL-4 were performed by the chemiluminescence sandwich enzyme immunoassay using AMPPD(3-(2'-spirodamantane)-4-methoxy-4-(3'-phophoryloxy+ ++) phenyl-1,2-dioxetane). The results indicated that immunotherapy reduced the IL-4 level from the pre-treatment baseline but not significantly. However, as far as good responses to the therapy are concerned a significant decrease in IL-4 was seen, and s-CD23, assayed at the same time, was also significantly decreased by immunotherapy.

Identification of allergens is necessary for proper treatment of allergic diseases. We have so far mainly used two types of allergen identifying tests, one type based on the quantification of specific serum IgE (e.g. radioallergosorbent test (RAST)), the other on allergen challenging (e.g. prick test, provocation test) for an estimation of immediate allergic reaction. However, with the former test, a high level of serum specific IgE does not necessarily indicate evidence of allergy; the latter type causes itching on the challenged focus and may, in some cases, cause anaphylaxis. The histamine release test using the glass-fiber method (HRT) is based on the measurement of an immediate allergic reaction but can be performed safely in vitro. In this investigation, we measured the reaction of samples taken against 10 allergens simultaneously using HRT with a small amount of peripheral whole blood. HRT showed a high correlation and concordance with the CAP-RAST system. HRT also had a significant correlation with the nasal provocation test, and had good specificity and positive predictive value. With these advantages, HRT is considered to be clinically useful and especially suitable for screening of allergens because of its high specificity and positive predictive value, and also because of its safety and ease of performance.

In Japan, pollen of Cryptomeria japonica and Chamaecyparis obtusa are a yearly source of distress for many people suffering seasonally from allergic rhinitis. To study common epitopes shared by the two species, two monoclonal antibodies (moAbs) were raised against Cry j 1, which is the most predominant allergen in C. japonica. One of the moAbs was found to be reactive even to the major allergen of C. obtusa, demonstrating that the moAb (J1B01) can detect an epitope shared by both species J1B01 strongly inhibited the binding of the major allergens of C. japonica and C. obtusa to IgE of patients who are sensitive to C. japonica and C. obtusa. This finding signifies the importance of the epitope recognized by J1B01.