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Biomedical subjects

T Suehiro

Publications and source records attributed to T Suehiro.

At least 55 records · Page 3Linked to original sources

A rare case of Cushing's syndrome due to bilateral adrenocortical adenomas.

We report a rare case of Cushing's syndrome due to bilateral adrenocortical adenomas in a 45-year-old female. She suffered from diabetes mellitus and hypertension for a decade, but her appearance was not Cushingoid. The plasma cortisol level in the morning was at the upper limit of the normal range, but did not show a diurnal rhythm or was suppressed by 1 mg of dexamethasone. The plasma level of ACTH was undetectable, and it failed to respond to human CRH (hCRH). Plasma cortisol responded well to synthetic ACTH. The urinary 17-OHCS level was high, and was not suppressed by 4 mg of dexamethasone. While these findings were consistent with a diagnosis of adrenocortical adenoma, computed tomography showed several nodules in both adrenal glands that suggested the presence of huge nodular adrenocortical hyperplasia or bilateral adrenocortical adenomas. Bilateral adrenalectomy demonstrated the presence of three adenomas, two in the right and one in the left adrenal. Analysis of the extract from each adenoma revealed that two of the three produced an excess amount of cortisol. Magnetic resonance imaging (MRI) of the brain suggested the presence of pituitary adenoma. Prior to adrenalectomy, TSH, GH or LH showed a low response to TRH, GHRH or LHRH, respectively. Since normal responses were restored after bilateral adrenalectomy, these abnormalities were attributed to hypercortisolemia.

Adrenal Cortex Neoplasms↗

Trp64Arg mutation of beta 3-adrenergic receptor and insulin sensitivity in subjects with glucose intolerance.

We investigated the relationship between the Trp64Arg mutation in the beta 3-adrenergic receptor gene and insulin sensitivity, which was evaluated by the euglycemic-hyperinsulinemic-clamp technique, in 54 patients with impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM) who were not receiving insulin therapy. The frequencies of Trp/Trp, Trp/Arg, and Arg/Arg genotypes in the patients were 63.0, 33.3, and 3.7%, respectively, which did not differ significantly from those of the 227 controls (67.0, 33.3, and 3.7%, respectively, which did not differ significantly from those of the 227 controls (67.0, 31.3, and 1.8%, respectively). The mean glucose infusion rate of the 34 patients with Trp/Trp did not differ from that of the 18 patients with Trp/Arg (4.3 +/- 2.2 and 5.3 +/- 2.4 mg/kg/min, respectively); while that of the 2 patients with Arg/Arg was 11.5 mg/kg/min. There were no differences in the BMI or fat distribution in the abdomen between each genotype of patients, although the frequency of the Arg64 allele tended to increase with body mass index (BMI) in the control subjects under 60 years of age, which suggests that the mutation is involved in weight gain.

Adipose Tissue↗

Audiological findings of sensorineural deafness associated with a mutation in the mitochondrial DNA.

OBJECTIVE: The aim of this study was to investigate audiologic features and the lesion site of sensorineural deafness with mitochondrial DNA mutation at position 3243. STUDY DESIGN: Case review. SETTING: The study was conducted at the Kochi Medical School. PATIENTS: A case of sensorineural deafness in a patient who had a mitochondrial DNA mutation was presented. The incidence of deafness and diabetes mellitus (DM) was very high in the patient's family, but she did not have DM. MAIN OUTCOME MEASURES: The patient's mitochondrial DNA was examined. Furthermore, the pure-tone audiogram, the Bekesy audiogram, an auditory brain stem response, and the electrocochleogram were analyzed. RESULTS: The patient's mitochondrial DNA had a point mutation at codon 3243 (A-->G). The pure-tone audiogram showed moderate sensorineural deafness. An auditory brain stem response showed normal latencies. The electrocochleogram showed an enhanced negative summating potential. CONCLUSIONS: It was speculated that the lesion site of the auditory system was the inner ear. The possible sites in the inner ear were hair cells, the stria vascularis, and the endolymphatic sac.

Adult↗

Differential contribution of graft and recipient to perioperative TNF-alpha, IL-1 beta, IL-6 and IL-8 levels and correlation with early graft function in clinical liver transplantation.

Cytokines, produced by both the recipient and the newly vascularized allograft, are central mediators in the inflammatory response to allografted tissue. This study examines the relationship between pre- and intraoperative levels of TNF, IL-1, IL-6, and IL-8 and hepatic allograft function in the early postoperative period and also determines which cytokines are produced in a significant amount by the newly vascularized allograft. Baseline levels of IL-6 and IL-8 tended to be higher in patients with more advanced disease and showed an increase during the anhepatic period. TNF and IL-1 remained stable from baseline to anhepatic phase. IL-1 showed an increase from portal vein to effluent samples, suggesting that the graft has an important contribution to circulating IL-1 levels. Analysis of the data according to early graft performance revealed extremely high levels of effluent IL-1, IL-6 and IL-8, and the prolonged elevation of the latter two cytokines in patients with poor early graft function. Our findings demonstrate that sequential perioperative measurements of proinflammatory cytokines can be useful in monitoring graft function.

Adult↗

Paraoxonase gene polymorphism in Japanese subjects with coronary heart disease.

We investigated the association of paraoxonase (PON) gene polymorphism with both the occurrence of coronary heart disease (CHD) and the severity of coronary artery stenosis in Japanese subjects. PON is a protein associated with plasma HDL. It has been hypothesized an A/B (Gln 192-->Arg) polymorphism of PON may be involved in the pathogenesis of CHD, especially among subjects with non-insulin-dependent diabetes mellitus (NIDDM). The polymorphism was determined in 134 patients with myocardial infarction (MI) or angina pectoris, and in 252 healthy subjects as controls. The frequencies of the AA, AB, and BB genotypes in the patients were 15, 50 and 35%, respectively, and these frequencies did not differ from those in control subjects (14, 49, and 37%). The relative risk of CHD was not found to be associated with these genotypes. These data also were similar among selected subgroups (patients with MIs, those with a low-risk lipoprotein profile for CHD, and those with NIDDM). Neither the number of affected vessels nor Gensini's scores differed among the genotype groups. Our case-control study in Japanese subjects did not show that the PON A/B polymorphism is associated with a risk of CHD.

Aged↗

Assessment of damage and recovery of sinusoidal endothelial cell function by in vivo hyaluronic acid uptake in cold-preserved and transplanted rat livers.

We sought to evaluate the significance of endogenous hyaluronic acid levels and in vivo uptake of exogenous hyaluronic acid as markers of liver endothelial cell damage and correlate these findings to graft survival/function in a rat orthotopic liver transplant model. Endogenous hyaluronic acid levels were measured after orthotopic liver transplantation performed with freshly explanted livers, with livers preserved for 30 hr, and after sham operation. Exogenous hyaluronic acid uptake was evaluated in six study groups: fresh liver grafts, livers preserved for 12 hr, 24 hr, 30 hr and 48 hr, and sham-operated livers. Endogenous hyaluronic acid levels fell after orthotopic liver transplantation with freshly harvested livers and after sham operation, but rose in animals transplanted with livers preserved for 30 hr (P<0.01 vs. sham operation). In the preserved group, there was no difference in endogenous hyaluronic acid levels between survivors and nonsurvivors. Uptake of exogenous hyaluronic acid was significantly lower after orthotopic liver transplant with grafts preserved for 12 hr than after sham operation or orthotopic liver transplant with nonpreserved livers (P<0.05). Hyaluronic acid uptake further deteriorated in the 24-, 30-, and 48-hr groups. No significant difference in hyaluronic acid elimination rate was found when results obtained from livers preserved for extended periods (>12 hr) were compared in survivors and nonsurvivors. Hyaluronic acid uptake was reevaluated in surviving animals after 2 weeks. Completely restored function was observed in all survivors, indicating recovery of endothelial cells. We conclude that endogenous hyaluronic acid levels and exogenous hyaluronic acid uptake are reliable markers of liver sinusoidal endothelial cell function and that normal or moderately compromised hyaluronic acid uptake is associated with good graft function. On the other hand, endothelial cell dysfunction suggested by poor hyaluronic acid elimination is not a completely reliable predictor of subsequent deterioration of graft function in rat liver transplantation.

Animals↗

Significance of angiotensin I-converting enzyme and angiotensin II type 1 receptor gene polymorphisms as risk factors for coronary heart disease.

The D allele of an insertion/deletion (I/D) polymorphism in the angiotensin I-converting enzyme (ACE) gene is associated with a risk of myocardial infarction, and the relative risk associated with the ACE D allele is increased by the C allele of an angiotensin II type 1 receptor (AT1R) gene polymorphism (an A-->C transversion at nucleotide position 1166) [28]. The relation of the ACE and AT1R gene polymorphisms to coronary heart disease and the severity of coronary artery stenosis has now been investigated in 133 patients with myocardial infarction (MI) or angina pectoris who underwent coronary angiography and in 258 control subjects. The frequency of the ACE DD genotype as compared with non-DD was significantly higher in the patients who experienced an MI and in the low-risk patients than that in the controls (P < 0.05). The DD genotype showed a significantly increased risk of MI (odds ratio 1.85). The frequency of the AT1R A/C genotypes did not differ between the patients and the controls. The severity of coronary stenosis in the patients was estimated by the number of affected vessels (> 75% stenosis) and the coronary score of Gensini. Neither the number of affected vessels nor the coronary score differed among the ACE I/D genotypes. However, the number of affected vessels was significantly greater in patients with the AT1R AC genotype than in those with the 4A genotype (1.93 +/- 0.27 vs. 1.27 +/- 0.99; P < 0.05) (CC genotype was not found in the patients). After excluding patients with diabetes mellitus, the coronary score of those with the AC genotype was also significantly higher than in those with the AA genotype (51.7 +/- 34.4 vs. 18.2 +/- 23.3; P < 0.01). These results suggest that the ACE D allele is associated with the occurrence of myocardial infarction, while the AT1R C allele is involved in the development of the coronary artery stenosis.

Adult↗

Thromboxane A2 in preservation-reperfusion injury: the effect of thromboxane A2 synthetase inhibitor.

It has been suggested that thromboxane A2 (TXA) plays important roles in preservation/reperfusion organ injury. In this report, we investigated the prostanoid release from the liver and the effect of a selective TXA synthetase inhibitor (E)-3-[p-(1H-imidazol-yl-methyl)-phenyl]-2-propenoic acid, OKY046) during cold preservation and after reperfusion. Rat livers were preserved in lactated Ringer's solution at 4 degrees C for 2, 4, and 6 hr and perfused with oxygenated Krebs-Henseleit buffer using recirculating perfusion system, and prostanoids were measured during cold preservation and after reperfusion. OKY046 and a novel TXA receptor antagonist [(9,11), (11,12)-Dideoxa-9a, 11a-dimethyl-methano-11,12-methano-13,14-dihydro-13-aza-14-oxo-15-cyclo pentyl-16,17,18,19,20-pentanor-15-epi-TXA, ONO3708] were added into the preservation solution and perfusate. Along with the preservation time, both the production and release of TXA was observed to increase; however, almost all the produced TXA was stored in the liver tissue. Afterwards, the stored TXA was released into perfusate in 15 min after reperfusion. OKY046 significantly decreased both the production and release of TXA. In addition, OKY046 improved the histological damage and trypan blue uptake of liver cells. Our results demonstrate that TXA, stored in the liver during preservation, might therefore be a potential trigger of reperfusion injury, and as a result, OKY046 reduces reperfusion injury by decreasing the production of TXA during preservation.

6-Ketoprostaglandin F1 alpha↗

Tolerance of the cirrhotic liver to cold ischemia: ex vivo analysis in rats.

We investigated the viability of rat cirrhotic livers preserved cold using an isolated rat liver perfusion model. Cirrhosis was induced by intravenous thioacetamide injection. Normal and cirrhotic livers were reperfused immediately or following 6 h of preservation through the portal vein with Krebs-Henseleit buffer and hyaluronic acid added. Cirrhotic livers with short cold ischemia showed higher portal venous resistance than their normal counterparts (p < 0.05), while cirrhotic livers preserved for 6 h exhibited marked elevation of the portal venous resistance as compared with their fresh counterparts or normal liver preserved cold for 6 h (p < 0.05). Similarly, the oxygen consumption of cirrhotic livers with short cold preservation was lower than that of normal livers (p < 0.05), which was further reduced by 6 h of cold preservation (p < 0.05). The bile output was not different between normal and cirrhotic livers. The sinusoidal endothelial cell function of cirrhotic livers as assessed by the clearance of hyaluronic acid was impaired even after a short period of cold ischemia. Histologically, cirrhotic livers showed severe sinusoidal endothelial cell damage, hepatocellular swelling, and marked septal edema which became more prominent by cold preservation. We conclude that the viability of the cirrhotic liver is impaired even by a short cold exposure, and that the prolongation of cold ischemia of the cirrhotic liver leads to further deterioration of the viability.

Animals↗

Simple obesity with cardiomyopathy of obesity.

A 32-year-old obese female was hospitalized with dyspnea. Echocardiogram revealed left ventricular dilatation. Chest X-ray film showed enlarged heart size and prominent pulmonary congestion. Simple obesity with congestive heart failure (CHF) due to cardiomyopathy of obesity was diagnosed according to the absence of obvious disease that caused obesity or CHF. After diet therapy and medication, subjective symptoms disappeared and body weight was reduced from 137 kg to 85 kg. Although few reports of cardiomyopathy of obesity have been reported in Japan, we propose the possibility that similar cases will be on the increase because Japanese dietary habits are now becoming more similar to those of Caucasians.

Adult↗

A novel nonsense mutation in exon 1 and a transition in intron 3 of the lipoprotein lipase gene.

We examined the lipoprotein lipase (LPL) gene by single strand conformation polymorphism (SSCP) and by restriction fragment length polymorphism (RFLP) analysis in 106 patients with hypertriglyceridemia to screen for novel mutations and to study the contribution of LPL genetic defects in hypertriglyceridemia. We found a single incidence of a homozygous novel nonsense mutation (216G-->A; -14Tryptophan-->stop codon) in exon 1 and 6 cases heterozygous for a single transition (C-->T) at six bp upstream from splicing acceptor site of intron 3. These mutations were not found in 105 normolipidemic controls. The proband homozygous for the nonsense mutation in exon 1, a 74 year old woman, had mild hyperchylomicronemia and her post-heparin plasma showed no LPL protein. However, four heterozygous among family members did not demonstrate hypertriglyceridemia. The frequency of heterozygosity for the C-->T transition in intron 3 was significantly different from that in normolipidemic controls. Therefore, it was suggested that the mutation is involved in hypertriglyceridemia. All of the heterozygotes were men with 4 patients having impaired glucose tolerance or diabetes mellitus. These observations suggest that this polymorphism in intron 3 combined with other as yet undefined factors may be related to hypertriglyceridemia.

Adult↗

Clinicopathologic features and prognosis of resected hepatocellular carcinomas of varied sizes with special reference to proliferating cell nuclear antigen.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is an intranuclear protein that is linked closely to the cell cycle. An immunohistochemical study was performed on the expression of PCNA in various sized hepatocellular carcinomas (HCCs) to determine the relation between the proliferative activity of cancer cells and prognosis. METHODS: One hundred forty-one neoplasms resected from 141 patients who underwent hepatic surgery for HCC at Kyushu University hospital from April, 1991, to July, 1993, were studied immunohistochemically using monoclonal antibody for PCNA (PC10), and analyzed for a possible correlation between PCNA labeling index (PCNA-LI) and the prognosis of patients with HCC. RESULTS: Proliferating cell nuclear antigen reactive cancer cells were observed throughout the HCC. The PCNA-LI ranged from 1.2%-91.6%, with a mean of 37.7%. The high PCNA-LI (> 37.7) group showed a significantly higher incidence of tumor thrombus in the portal vein, higher Edmondson's Grade, and a higher recurrence rate than the low PCNA-LI (< 37.7) group. Hepatocellular Carcinomas were divided into three groups according to tumor size. Based on the clinicopathologic findings, in small (< 30 mm) HCCs, the high PCNA-LI (> 29.0) group showed a significant higher Edmondson's grade and a higher recurrence rate than the low PCNA-LI (< 29.0) group. In medium (30-60 mm) HCCs, the high PCNA-LI (> 36.1) group showed a significantly higher recurrence rate than the low PCNA-LI (< 36.1) group, although there was no difference in the pathologic findings between the high (> 59.4) and low (< 59.4) PCNA-LI groups. CONCLUSIONS: Proliferating cell nuclear antigen labeling index is closely related to cell differentiation and the prognosis of HCC. Furthermore, PCNA-LI was found to be useful in predicting the intrahepatic spread and prognosis of small (< 30 mm) and medium (30-60 mm) but not large (> 60 mm) HCCs.

Antigens, Neoplasm↗

Significance of hyaluronic acid for evaluation of hepatic endothelial cell damage after cold preservation/reperfusion.

UNLABELLED: Serum hyaluronic acid (HA) levels during or after liver transplantation can reflect graft viability in animal models. Decreased HA clearance in nonviable grafts seems to reflect hepatic endothelial cell damage induced by cold preservation/reperfusion. Therefore, we examined the relationship between HA clearance and endothelial cell damage, using an isolated perfused rat liver (IPRL) model. The grafts were separated into four groups, according to cold preservation time: minimal storage ( CONTROL: n = 9), 4-hr preservation (n = 9), 5-hr preservation (n = 8), 6-hr preservation (n = 9). After cold storage, grafts were put on the recirculating IPRL system and then reperfused for 120 min with 37 degrees C oxygenated Krebs-Henseleit buffer, containing HA and sodium taurocholate. To examine the function of sinusoidal endothelial cells and hepatocytes, serial measurements of HA, total bile acids, and conventional parameters in the perfusate were taken. After the perfusion, a trypan blue exclusion test was done to assess the microscopic sinusoidal lining cell (SLC) damage. HA clearance from the perfusate showed a preservation time-dependent decrease which clearly distinguished between 4- and 6-hr preserved grafts. Trypan blue uptake ratio of SLC increased in accordance with preservation time. HA clearance at 120 min after reperfusion showed a highly significant correlation with histologically assessed SLC damage. These results suggest that HA is useful to evaluate the extent of endothelial cell damage after cold storage and reperfusion. The significance of HA as a predictor of graft viability is also confirmed.

Animals↗

Partial hepatic grafting: porcine study on critical volume reduction.

BACKGROUND: The safe limit of volume reduction in partial hepatic transplantation, including extracorporeal hepatic resection, remains to be clarified. This study evaluated such a limit and pathologic features associated with transplantation of a less than critical volume. METHODS: Partial hepatic grafting was performed in a porcine orthotopic autotransplantation model. According to the remnant liver volume, animals were classified into three groups: group 1, 73.8% +/- 4.2% (SD); group 2, 52.6% +/- 6.7%; and group 3, 29.4% +/- 6.7% of the whole liver (n = 5 each). RESULTS: Three-day survival was achieved in five (100%), four (80%), and zero animals, respectively. All animals in group 3 died of graft nonfunction; their intraoperative clearance of the total bile acids was significantly worse than the other groups (p < 0.01). After operation the clearance of the total bile acids and hyaluronic acid, which is selectively cleared by hepatic endothelial cells, was significantly better in group 1 than group 2 (p < 0.01 and < 0.05, respectively). On histologic examination postperfusion biopsy specimens of group 3 exhibited severe ischemic changes and portosinusoidal hyperemia, whereas that of groups 1 and 2 exhibited only mild ischemic damages. CONCLUSIONS: Transplantation of less than 30% of expected full liver volume could lead to primary graft nonfunction after partial hepatic grafting.

Animals↗

Des-gamma-carboxy prothrombin and proliferative activity of hepatocellular carcinoma.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a useful marker for the prognosis of hepatocellular carcinoma (HCC). In this report we investigated the relationship between the positivity of DCP and proliferative activity of HCC and discuss the cause of poor prognosis of DCP-positive HCC. METHODS: Immunohistochemical and clinicopathologic study was done in 114 patients with resected HCC measuring less than 6 cm in diameter by using monoclonal antibody for proliferating cell nuclear antigen (PCNA). RESULTS: PCNA labeling index (PCNA-LI) was significantly higher in the patients with DCP-positive HCC than in those with DCP-negative HCC; also a positive correlation was noted between the PCNA-LI and the DCP level. We divided patients into two groups according to the PCNA-LI. In the high PCNA-LI group the patients with DCP-positive HCC exhibited a higher PCNA-LI than did the patients with DCP-negative HCC. As for pathologic prognostic factors, the DCP-positive high PCNA-LI group showed the highest incidence of tumor thrombus of the portal vein and intrahepatic metastasis while also exhibiting the lowest recurrence-freedom rate. From multivariate analysis we find that DCP, as well as PCNA-LI, is one of the risk factors for recurrence of HCC after hepatectomy. CONCLUSIONS: Our results thus suggest that DCP-positive HCC showed high PCNA-LI, and this might be the main cause for early intrahepatic spread and poor prognosis of DCP-positive HCC.

Adult↗

Hypothyroidism preceding hyperthyroidism in a patient with continuously positive thyroid stimulating antibody.

A 62-year-old woman was initially hypothyroid and then developed hyperthyroidism with continuously positive thyroid-stimulating antibody (TSAb). When she visited our hospital with the complaint of the feel of skipping beats, her serum free T4 level was initially low and thyrotropin (TSH) level was slightly elevated. One month after starting the supplement therapy with l-T4, she developed hyperthyroidism with increased 123I-thyroid uptake. TSH-binding inhibitor immunoglobulin (TBII) was slightly elevated only during the hypothyroid stage. Throughout the whole course, TSAb was continuously positive, while thyroid stimulation-blocking antibody (TSBAb) was not detectable. Primary hypothyroidism with TSAb may suggest the possibility of subsequent development of hyperthyroidism.

Female↗