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Biomedical subjects

T Suehiro

Publications and source records attributed to T Suehiro.

At least 37 records · Page 2Linked to original sources

The mechanism of hepatic graft protection against reperfusion injury by prostaglandin E1.

The purpose of this study was to evaluate the effect of prostaglandin E1 (PGE1) on protecting against hepatic endothelial cell damage and increasing graft viability after cold preservation and reperfusion, using an isolated perfused rat liver (IPRL) model. The grafts were divided into three groups, according to the cold preservation time and PGE1 administration, namely: 4h preservation (group 1, n = 9), 6h preservation (group 2, n = 9), and 6h preservation followed by PGE1 infusion (group 3, n = 9). After cold storage, the grafts were put on the recirculating IPRL system, then reperfused for 120 min at 37 degrees C with oxygenated Krebs-Henseleit buffer containing hyaluronic acid (HA). To examine the function of the sinusoidal endothelial cells and hepatocytes, serial measurements of HA, tumor necrosis factor-alpha (TNFalpha), thromboxane B2 (TXB2), acid phosphatase, and conventional parameters in the perfusate were made. After perfusion, the trypan blue exclusion test was performed to assess the presence of any microscopic sinusoidal lining cell damage. In group 3, the bile output and HA clearance were significantly greater, while glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, TNFalpha, TXB2, and acid phosphatase in the perfusate were significantly lower than in group 2. Histologically, less endothelial cell damage and hepatocyte damage than in group 2 was also confirmed. These results therefore suggest that the improvement of hepatic graft viability by PGE1 administration is mainly due to sinusoidal endothelial cell protection.

Acid Phosphatase↗

Screening for variants of the uncoupling protein 2 gene in Japanese patients with non-insulin-dependent diabetes mellitus.

We examined genetic mutations in the coding regions of the uncoupling protein 2 (UCP2) gene in 100 patients with non-insulin-dependent diabetes mellitus (NIDDM). The sequences of each exon-intron boundary were detected by polymerase chain reaction (PCR) using specific primer pairs designed in the cDNA sequence of UCP2 and a cycle-sequence method. Using the specific primer pairs in the intron 5'- or 3'-untranslated region, each exon with its exon-intron boundaries was amplified with the PCR method, and the PCR products were analyzed using a single-strand conformation polymorphism (SSCP) method. One nucleotide substitution in exon 4 was found, which exchanged Ala (gcc) at position 55 of the amino acid sequence for Val (gtc), previously reported in Denmark by Urhammer et al in 1997. The polymorphism was reanalyzed in all patients and 120 normal subjects using a PCR-restriction fragment length polymorphism method. There was no difference in the genotype distribution between patients and normal subjects, and our genotype distribution was similar to the Danish study. Furthermore, there were no clinical differences between genotype groups among the patients. No other mutation including the exon-intron boundary was found in these patients. Genetic mutations of UCP2 may not be commonly associated with obesity or diabetes in Japanese subjects.

Adult↗

Ferritin correlates with C-reactive protein and acute phase serum amyloid A in synovial fluid, but not in serum.

OBJECTIVE: To evaluate ferritin concentration in serum and synovial fluid (SF) as a marker of activity of arthritis in comparison with C-reactive protein (CRP) and acute-phase serum amyloid A protein (A-SAA). METHODS: We determined the concentrations of ferritin, CRP and A-SAA in paired serum and SF in 34 rheumatoid arthritis (RA) and 21 osteoarthritis (OA) patients. The erythrocyte sedimentation rate (ESR) was also measured. RESULTS: The serum concentrations of ferritin, CRP and A-SAA were 93 +/- 76 (mean +/- SD) ng/ml, 4 +/- 5 mg/ml, 8 +/- 4 mg/ml in OA and 140 +/- 227, 59 +/- 34, 289 +/- 223 in RA, respectively. There was no significant difference in serum ferritin levels between OA and RA, and serum ferritin did not correlate with ESR, CRP or A-SAA. Both serum CRP and A-SAA levels were significantly higher in RA than in OA (p < 0.0001, p < 0.0001), and correlated with ESR in all arthritis (r = 0.658, p < 0.0001, r = 0.404, p < 0.01), respectively. Serum CRP levels correlated with A-SAA levels in serum (r = 0.727, p < 0.0001). In SF, the concentrations of ferritin, CRP and A-SAA in RA (421 +/- 307, 25 +/- 20 and 39 +/- 41) were significantly higher (p < 0.01, p < 0.0001, p < 0.001) than those in OA (202 +/- 220, 2 +/- 2 and 2 +/- 2), respectively. There were significant correlations among SF ferritin, CRP and A-SAA. CONCLUSION: Ferritin levels in SF but not in serum are significantly elevated in RA more than in OA, and ferritin correlated with CRP or A-SAA in SF, but not in serum. Higher levels of SF ferritin, as well as SF CRP and SF A-SAA, seem to reflect greater degrees of joints inflammation in RA and OA.

Acute-Phase Reaction↗

Local expression of acute phase serum amyloid A mRNA in rheumatoid arthritis synovial tissue and cells.

OBJECTIVE: Serum amyloid A (SAA) protein, a bioactive protein produced during inflammation, is present in synovial fluid (SF) of patients with rheumatoid arthritis (RA). Based on our recent finding that SF SAA concentration exceeded the serum counterpart in some patients with RA, we examined the local steady state concentration of SAA mRNA isoforms in synovia and in synovial cells cultured from patients with RA and osteoarthritis (OA). METHODS: Total cellular RNA from synovial membranes of patients with RA or OA and from cultured synovial cells of patients with RA was analyzed by reverse transcription polymerase chain reaction and Northern blot. RESULTS: Acute phase SAA (A-SAA) mRNA isoforms were detected only in RA synovia, but not in OA synovia; however, the constitutive SAA (C-SAA) mRNA isoform was detected in similar abundance in both OA and RA synovia. There was evidence of C-SAA, but not A-SAA mRNA in cultured synovial cells at quiescence. After stimulation with both 1 mM dexamethasone and 10 ng/ml interleukin 1beta (IL-1beta), the quantity of steady state A-SAA muRNA in cultured synovial cells was markedly increased. CONCLUSION: Both A-SAA and C-SAA mRNA are detectable in RA synovia, while only C-SAA mRNA is detectable in OA and in quiescent cultured synovial cells. The steady state A-SAA mRNA isoform in cultured synovial cells was markedly increased in the presence of dexamethasone plus IL-1beta. The local synthesis of A-SAA may contribute, at least in part, to the concentration of A-SAA protein in SF and may contribute to the altered molecular and cellular physiology in RA joints.

Amino Acid Sequence↗

Neuropeptide Y Y1 receptor polymorphism as a prognostic predictor in Japanese patients with IgA nephropathy.

BACKGROUND: Neuropeptide Y exhibits a vasoconstricting action and regulates systemic blood pressure as well as noradrenalin. There are 5 types of NPY receptors, Y1 - Y5, which were introduced by pharmacological differences. Recently, a single point mutation in the first intron of the NPY Y1 receptor (NPYY1R) was reported. SUBJECTS AND METHODS: In this study, we investigated the relationship between NPYY1R gene polymorphism and clinical characteristics in patients with IgA nephropathy using polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Distribution of the NPYY1R genotypes which were defined as YY, Yy and yy genotypes, did not differ between 60 normal control subjects and 68 patients with IgA nephropathy (15 : 36 : 9 versus 21 : 40 : 7, respectively). In IgA nephropathy patients, the incidence of hypertension and the rate of urinary protein excretion were slightly higher in the non-YY genotype than in the YY genotype group (23% versus 5% and 1.1 +/- 1.2 versus 0.6 +/- 0.4 g/24 h, p = 0.09 and p = 0.05, respectively). The reciprocal of the serum creatinine level was estimated to determine the deterioration in renal function during follow-up after the renal biopsy. The level was lower in the non-YY genotype than in the YY genotype group (-0.002 +/- 0.064 vs 0.033 +/- 0.053/month, respectively, p < 0.01). Multiple regression analysis for the reciprocal of the serum creatinine level revealed that the NPYY1R genotype was an effective variable (p < 0.01). CONCLUSION: In conclusion, we propose that the NPYY1R gene polymorphism may be a novel prognostic predictor in patients with IgA nephropathy.

Adult↗

Effect of a polymorphism of endothelial nitric oxide synthase gene in Japanese patients with IgA nephropathy.

BACKGROUND: Nitric oxide (NO) is synthesized by endothelial cell NO synthase (ecNOS) on vascular endothelium, and it plays a key role in the regulation of blood flow and pressure. A polymorphism of the ecNOS gene was recently shown to be associated with the development of cardiovascular disease. PATIENTS AND METHODS: We investigated the ecNOS gene polymorphism in 68 Japanese patients with IgA nephropathy (IgAN) and 134 normal controls. RESULTS: The genotype distributions were not different between the normal controls and the IgAN patients (ecNOS4b/b: ecNOS4b/a: ecNOS4a/a = 106:27:1 and 50:18:0, respectively). There was no significant difference in the renal histopathological grading between the patients with ecNOS4b/a and ecNOS4b/b. However, among the subgroup of patients whose duration of illness was two or more years, the advanced histopathological grading was more frequent in the patients with the ecNOS4b/a genotype (than in those with the ecNOS4b/b (p = 0.04)). The incidence of hypertension was also higher in the patients with the ecNOS4b/a genotype (50% in ecNOS4b/a versus 12% in ecNOS4b/b, p = 0.04). CONCLUSION: These results suggest that the ecNOS4b/a genotype (or ecNOS4a allele) of the ecNOS gene polymorphism may be involved in the progression of IgAN.

Adult↗

Donor des-gamma-carboxy prothrombin positivity is a risk factor for poor early graft function in liver transplantation.

Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin that lacks coagulating activity. The aim of this study was to determine if the presence of DCP in the donor could be used as a marker of post-transplant graft function. We collected data and serum samples on 90 organ donors. DCP level was correlated with donor-specific factors and with graft function intraoperatively and in the early post-transplant period. Twenty-seven donors (30.0%) had positive DCP levels before harvesting. Although recipients were similar in demographics, preoperative liver function, and primary disease distribution, patients transplanted with livers from DCP-positive donors needed significantly more intraoperative transfusion. Furthermore, donor DCP positivity was identified as a preoperative risk factor for poor early graft function based on multivariate analysis (odds ratio = 6.58, P = 0.0032). Our findings suggest that DCP is another valuable marker for evaluating the quality of donor livers.

Adolescent↗

Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus.

Paraoxonase (PON) is an esterase associated with high-density lipoprotein (HDL). Serum PON activity is affected by PON gene polymorphism (L/M, Leu-Met54, and Q/R, Gln-Arg191). We investigated PON activity and polymorphism in 108 patients (53 men and 55 women) with non-insulin-dependent diabetes mellitus (NIDDM) and 161 control subjects (82 men and 79 women) matched to the patients by age and gender. Serum PON activity was determined using paraoxon as a substrate. PON gene polymorphisms were detected by the restriction fragment length polymorphism method after a polymerase chain reaction. The mean PON activity in the patients was significantly lower than in the controls (116+/-55 and 162+/-57 U/L, respectively, P < .001). The distribution of each genotype showed no difference between the patient and control groups, and PON activity increased in the order of the QQ < OR < RR genotype and MM < LM < LL genotype in both groups. However, among each genotype subgroup, the activity was lower in patients than in controls. Forty-one patients with retinopathy had lower PON activity than those without the complication (94+/-36 and 129+/-61 U/L, respectively, P < .002). There was also a significant difference in PON activity between patients with and without overt proteinuria (93+/-38 and 122+/-58 U/L, respectively, P < .05). Logistic analysis showed that serum PON activity was one of the significant factors for retinopathy. These results suggest that decreased PON activity in patients with NIDDM is involved in diabetic vascular complications.

Adult↗

A longitudinal analysis of alteration in lecithin-cholesterol acyltransferase and paraoxonase activities following laparoscopic cholecystectomy relative to other parameters of HDL function and the acute phase response.

The composition of high-density lipoprotein (HDL) changes during inflammation; however, potential changes of HDL function during inflammation and the effects of acute phase proteins that are either on the HDL particles or in the serum have not been clarified. The concentrations of C-reactive protein (CRP), serum amyloid A protein (apoSAA) isoforms, lipids and apolipoproteins, and the activities of lecithin-cholesterol acyltransferase (LCAT) and paraoxonase (PON) were measured before and after laparoscopic cholecystectomy, in 12 patients with cholecystolithiasis to clarify the function of acute-phase HDL and the relationship between acute-phase proteins and HDL functions. Both acute-phase apoSAA (A-apoSAA) and CRP increased, reached their maximum levels 3-6 days after the operation, and then returned to preoperative levels after 2 weeks. In contrast, apolipoproteins and LCAT decreased reciprocally, reached their minimum levels 3-6 days after the operation, and returned to preoperative levels after 2 weeks. However, PON decreased 3-6 days after the operation, and remained low even after 2 weeks. At the nadir the mean activities of LCAT and PON were 56 and 76% of the preoperative levels, respectively. HDL-cholesterol or constitutive apoSAA did not change significantly. LCAT has been reported to be involved in reverse-cholesterol transport and PON to be preventive for lipid peroxidation of low-density lipoprotein in vitro. Thus, during the acute phase of inflammation, HDL may be altered to an atherogenic state due to a decrease in LCAT and PON activities. Therefore, this longitudinal analysis was carried out to determine whether HDL function is modified in a single episode of inflammation and thus may contribute to the occurrence of atherosclerotic disease in patients with chronic or recurrent acute inflammation.

Acute-Phase Reaction↗

Severe diabetic scleredema with extension to the extremities and effective treatment using prostaglandin E1.

We report a 49-year-old woman with severe diabetic scleredema (DS). The patient had non-insulin-dependent diabetes mellitus (NIDDM) for 9 years and noticed thickened skin on her back 3 years previously. Her DS rapidly extended to her back and extremities with pain and immobility. Her symptoms of DS improved dramatically after establishing strict glycemic control and intravenous administration of prostaglandin E1 (PGE1). However, the histological findings of her skin biopsy did not change even after the treatment for 12 weeks, and her symptoms worsened again after discontinuation of glycemic control and PGE1 treatment. The causes of DS have been considered to be metabolic abnormalities associated with hyperglycemia and hypoxia in the skin due to diabetic microangiopathy. PGE1 was an effective treatment for DS in our patient. Strict control of hyperglycemia and PGE1 treatment may be sufficient to manage DS, although a very long treatment period is necessary.

Acupuncture Analgesia↗

[Spontaneous regression of hepatocellular carcinoma: a case report].

A 65-year-old woman with hepatocellular carcinoma underwent right hepatic lobectomy. Her alpha-fetoprotein levels significantly dropped from 285,000 ng/ml to 3,100 ng/ml for one month without any preoperative treatment. The tumor thrombus in the portal vein showed complete necrosis, and lymphocytes infiltration around the main tumor were present microscopically. However, there was no necrotic area in the main tumor. This patient is living with no evidence of recurrence for 3 years and 6 months following hepatic resection.

Aged↗

[Necrosis of the hepatocellular carcinoma nodule can aggravate metastasis].

Since the stroma of hepatocellular carcinoma is composed of sinusoid-like structures, cancer cells are readily released from the primary tumor with possible injurious consequences. A 63-year-old woman with hepatocellular carcinoma underwent percutaneous ethanol injection therapy. During this treatment, tumor thrombus developed in the right hepatic vein. Partial hepatic resection was performed. Six months later, multiple nodules appeared in the lung fields. Partial necrosis may have allowed the release of cancer cells from the primary tumor. Perioperative therapy should have an effect on intrahepatic micrometastases, because removal of the main tumor can be done surgically.

Carcinoma, Hepatocellular↗

[Chronic liver disease prevents the development of atherosclerosis in spite the risk factor].

We investigated whether hypertension contributes to the development of atheloscrelosis in patients with chronic liver disease. There were no significant differences with respect to the ordinary biochemical data of serum concentrations of both protein and lipid metabolites between the hypertension group (n = 21) and the non-hypertension group (n = 31). In the hypertension group, serum creatinine level and serum concentration of lipoprotein (a) were significantly higher than those in non-hypertension group. However, there was no significant difference between the two groups with respect to the atherogenic index (apolipoproteins B versus A1 ratio). Serum glutamic oxaloacetic transaminase activity was positively correlated with serum apolipoprotein E concentration, and inversely correlated with serum lipoprotein (a) concentration, in 52 patients with chronic liver disease. Active hepatitis in patients with chronic liver disease might retard the development of atherosclerosis.

Aged↗

Assessment of liver allograft function by hyaluronic acid and endothelin levels.

BACKGROUND: Sinusoidal endothelial cells are considered the primary site of preservation-reperfusion injury occurring during cold storage and reperfusion. Hyaluronic acid (HA) and endothelin-1 (ET) are markers of endothelial cell integrity. The aim of this study was to evaluate the possible correlation between these markers and early graft function following liver transplantation. MATERIALS AND METHODS: Blood samples were collected from 85 adult orthotopic liver transplant recipients at the following time points: before surgery, just before reperfusion, first and last 20 cc of caval effluent, 30, 60, and 120 min after reperfusion, and on postoperative day (POD) 1. Levels of both HA and ET were measured by sandwich enzyme-binding assay. HA uptake was also defined for every sample as the ratio of the actual measurement to the value obtained just before reperfusion. RESULTS: Patients with severe liver disease displayed significantly higher pretransplant HA and ET levels compared with those of less advanced illness. Poor early graft function (PEGF) was defined as peak enzyme levels on the first three PODs higher than 2500 U/L and prothrombin time longer than 16 s on POD 2. Patients with PEGF (n = 9) showed significantly lower HA uptake than patients with good graft function (n = 76) at 60 and 120 min after reperfusion. There was also a significant difference in the average uptake values measured in the last 20 cc of caval effluent between the two groups. We could not find any difference in ET levels between these two groups. CONCLUSIONS: Perioperative HA uptake measurement may be an additional marker to evaluate early graft function.

Adult↗

Suppression of plasma cholesteryl ester transfer protein activity in acute hyperinsulinemia and effect of plasma nonesterified fatty acid.

Cholesteryl ester transfer protein (CETP) is a major determinant of the plasma high-density lipoprotein cholesterol (HDL-C) level and plays an important role in the reverse cholesterol transport system. The purpose of this study was to determine the effect of acute hyperinsulinemia on plasma CETP activity in normal subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Hyperinsulinemia was achieved using the hyperinsulinemic-euglycemic clamp. CETP activity was determined as the transfer of radiolabeled cholesterol in HDL3 to acceptor lipoprotein. Mean plasma CETP activity during an insulin infusion in both subject groups was significantly decreased compared with the mean basal activity. Suppression of plasma CETP activity in the NIDDM patients was significantly less than in the normal subjects (-4.2% +/- 7.9% v -9.6% +/- 6.4%, P < .02). Regression analysis showed that this suppression was correlated with plasma nonesterified fatty acid (NEFA) levels after the clamp and with the magnitude of the NEFA decrease (r = .318, P < .02 and r = .292, P < .05, respectively). The data suggest that acute hyperinsulinemia reduces plasma CETP activity through a decrease in plasma NEFA.

Adult↗

Effect of smoking on the prevalence of albuminuria in Japanese men with non-insulin-dependent diabetes mellitus.

Smoking is a risk factor for diabetic nephropathy in patients with IDDM and potentially those with NIDDM. We investigated the relationship between renal involvement and cigarette smoking in 148 men with NIDDM. The presence of renal involvement was assessed by determining the overnight urinary albumin/creatinine ratio (mg/g, ACR). The patients were divided into three groups, normo-, micro-, and macroalbuminuria, based on the ACR (< 30, 30-300, and 300 < or = mg/g, respectively). The incidence of micro-/macroalbuminuria in 81 smokers was significantly higher than that in 21 ex-smokers (stopped smoking at least 10 years prior to the study) or 40 non-smokers (53.1, 33.3, and 20.0%, respectively). The prevalence of smoking in the groups of patients with normo-, micro-, and macroalbuminuria were 45, 73, and 76%, respectively. The relative risk (odds ratio) for the prevalence of micro-/macroalbuminuria associated with smoking was 4.5 (95% CI, 1.9-11.6, P < 0.001) in smokers and was 2.0 (not significant) in ex-smokers. Our results indicate that stricter counselling about the importance of quitting smoking will be necessary in patients with NIDDM to protect against the development of diabetic nephropathy.

Aged↗

Effluent levels of thrombomodulin predict early graft function in clinical liver transplantation.

Thrombomodulin is a surface protein on vascular endothelial cells that serves as a binding site for thrombin and plays an important role as an anticoagulant factor. We correlated plasma thrombomodulin levels with early graft function after liver transplant in 58 recipients. Blood samples were collected at the following time points: before surgery, just before reperfusion, 30, 60, 120 min after reperfusion, and post-operative day 1. The first and last 20 cc of caval effluent were also collected. Plasma thrombomodulin levels were measured by a sandwich enzyme-binding assay in the blood samples; tissue expression was determined by immunohistochemistry. Poor early graft function was defined as peak aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2500 U/l during the first 3 post-operative days and prothrombin time >16 s on post-operative day 2. Thrombomodulin levels in the first 20 cc of caval effluent ranged from 1.33 to 91 FU/ml and showed a significant positive correlation with ischemic time, intra-operative blood transfusion requirement, and early graft function. In grafts with high effluent thrombomodulin (>20 FU/ml, n=12), the incidence of poor early graft function and primary nonfunction was 66.7% and 25.0%, respectively; in grafts with low effluent thrombomodulin (<20 FU/ml, n=46), graft function was not impaired. By immunohistochemistry, thrombomodulin was detected in large vessels of every donor liver. Sinusoidal cells, however, showed positive staining only in livers with poor early graft function. Effluent thrombomodulin levels reflect the extent of preservation injury and might be a useful marker for predicting graft function after liver transplantation.

Adult↗