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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 127 records · Page 7Linked to original sources

A paucity of unusual trihydroxy bile acids in the urine of patients with severe liver diseases.

To clarify the relationship between the occurrence of unusual trihydroxy bile acids, namely hyocholic acid, ursocholic acid (UCA), and omega-muricholic acid (omega-MCA) in urine and liver disease severity, urinary bile acids were analyzed by gas-liquid chromatography in acute and late phases of acute hepatitis and before and after ursodeoxycholic acid (UDCA) loading in healthy adults and liver cirrhosis patients. In 11 patients with acute hepatitis, the occurrence rates and amounts of unusual trihydroxy bile acids were increased in the late (recovery) phase, as compared with those in the early phase. In 10 patients with severe acute hepatitis who had prothrombin times exceeding 16 seconds, these bile acids had completely disappeared from the urine in the early phase but reappeared in the late phase in those who had a good outcome, though never in a patient who died. After UDCA administration for a week, the amounts of unusual bile acids, especially UCA and omega-MCA, which are thought to be synthesized through 12 alpha- and 6 alpha-hydroxylations, respectively, from UDCA, were clearly increased in 10 healthy adults but only slightly changed in 10 patients with liver cirrhosis. In conclusion, hepatic hydroxylations of dihydroxy bile acids as a detoxification reaction were impaired in severe liver diseases, which may play a role in the intensification and perpetuation of hepatocellular injuries.

Acute Disease↗

Laparoscopic splenectomy for a giant splenic epidermoid cyst: report of a case.

The use of laparoscopic splenectomy has increased in recent years, primarily for patients with idiopathic thrombocytopenic purpura (ITP). We describe herein the first known case of a laparoscopic splenectomy to be performed in Japan for a patient with a giant splenic epidermoid cyst. A 26-year-old woman presented to our hospital with the major complaint of a feeling of abdominal fullness. Prior to surgery, an ultrasound-guided splenic cyst puncture was conducted for diagnostic purposes as well as to reduce the size of the cyst. The carbohydrate antigen 19-9 (CA 19-9) level was found to be elevated in the cystic contents and in the serum. Under laparoscopic guidance, the splenic vessels were ligated using a device for extracorporeal ligation, then divided. After the resected spleen had been placed in a retrieval bag, it was delivered out of the abdominal cavity without fragmentation. Following surgery, the patient's serum CA 19-9 level returned to normal. Splenic epidermoid cysts are most often encountered in young women, and laparoscopic surgery to remove cysts of this type is both minimally invasive and excellent from a cosmetic standpoint. Thus, laparoscopic surgery should be considered as the method of choice for the majority of patients diagnosed with a splenic epidermoid cyst.

Adult↗

The role of a staged approach for high-risk Fontan candidates.

The preoperative risk characteristics and surgical outcome were reviewed in 24 patients who underwent a one-stage Fontan procedure (One-stage Group) and in 16 patients who underwent bidirectional cavopulmonary shunt as an interim procedure prior to a subsequent Fontan procedure (Two-stage Group) to clarify the role of the staged approach for high-risk Fontan candidates. There were 2 hospital deaths after the one-stage Fontan, and another 2 after the takedown of the fenestrated Fontan to BCPS in patients considered to be less than ideal candidate because of the presence of 3 or more risk factors. In contrast, among the total of 16 patients in the Two-stage Group who had significantly more risk factors than those in One-stage Group (2.8 +/- 1.4, vs 1.1 +/- 1.2 p < 0.001), 14 patients survived after bidirectional cavopulmonary shunt, and a subsequent Fontan procedure was accomplished in 12 patients of these 14, with 2 operative deaths after the takedown to bidirectional cavopulmonary shunt. The rate of final Fontan completion in the Two-stage Group (10/16, 62.5%) was considered to be reasonable, considering the fact that this patient group essentially includes non-Fontan candidates. Additionally, in the category of high-risk with 3 or more risk factors, the rate of successful Fontan completion was higher in the Two-stage Group than in the One-stage Group (50% vs 25%). In the survivors of the Two-stage Group, the average number of risk factor decreased from 2.7 +/- 1.3 (range 0 to 5) to 1.0 +/- 1.0 (range 0 to 4) after bidirectional cavopulmonary shunt with concomitant procedures (i.e., extended pulmonary artery reconstruction in 8, and repair of atrioventricular valve regurgitation in 4), predominantly due to improved Fontan candidacy, relating to pulmonary and/or ventricular characteristics, and eliminated anatomical risks. In conclusion, the two-stage approach with bidirectional cavopulmonary shunt accompanied by concomitant repair of associated anomaly may be useful to lower the risk enough to allow subsequent Fontan completion in high-risk patients.

Adolescent↗

A 22-year course of the Kay-Shiley disc valve with muscle guard at the mitral position.

Almost 33 years have elapsed since the introduction of the Kay-Shiley disc valve in Japan. Following the development of pyrolite carbon, the Kay-Shiley valve is no longer in clinical use. We report the case of a female patient who had had an isolated mitral valve replacement with the Kay-Shiley disc valve with single muscle guard 22 years previously. After numerous thromboembolic episodes with the Kay-Shiley disc valve, a successful reoperation was done with the CarboMedics valve. The explanted valve revealed that the grooved occluder disc had a loosely adherent clot. The thromboembolism is a notorious complication associated with this valve. We recommend re-replacement of the Kay-Shiley valve whenever possible.

Adult↗

Contribution of the renal medulla to enhanced ketogenesis with Ringer's acetate administration during hepatic inflow occlusion.

We have reported that the administration of Ringer's acetate solution (AR) maintains plasma ketone body concentrations even during hepatic ischemia due to enhanced ketogenesis in the kidney. In this study we tried to clarify which part of the kidney, cortex or medulla, contributes to the enhanced ketogenesis. During 20 minutes of hepatic inflow occlusion, AR or Ringer's lactate solution (LR) was administered. Ketone body concentrations in arterial and renal venous blood and renal cortical and medullary tissue were measured enzymatically. Results are expressed as means +/- SEM. At 20 minutes of hepatic inflow occlusion, arterial ketone body concentrations decreased to 38% of preischemic values with the LR infusion but increased under AR administration and were four times higher than that with LR. The renal arteriovenous difference in ketone body concentration was 16 +/- 14 micromol/ml before hepatic inflow occlusion and -52 +/- 14 with AR administration, indicating that renal ketogenesis occurred during hepatic ischemia. Total ketone body concentrations in the renal cortex and medulla were 56 +/- 6 and 61 +/- 5 micromol/g, respectively with LR, but increased to 186 +/- 29 and 248 +/- 25 micromol/g, respectively during AR administration. The concentration in the medulla was higher (p = 0. 12) than that in the cortex but did not reach statistical difference. Renal ketogenesis increases during hepatic inflow occlusion with AR administration. It is likely that the enhancement of ketogenesis takes place predominantly in the medulla of the kidney.

Analysis of Variance↗

Study of p53 in elderly patients with myelodysplastic syndromes by immunohistochemistry and DNA analysis.

We analyzed the tumor suppressor gene product, p53, in elderly patients with myelodysplastic syndromes (MDS) and in overt leukemia patients after transformation from MDS using immunohistochemical techniques. We examined 52 MDS patients (mean age 79 years, range 68 to 96) from the time of initial diagnosis to death or development of overt leukemia. p53 protein was detected by immunohistochemistry (IHC) in 8/52 patients (15%) at initial diagnosis: 1/26 with refractory anemia (RA), 0/4 with RA with ringed sideroblasts, 3/11 with RA with an excess of blasts (RAEB), 3/8 with RAEB in transformation, and 1/3 with chronic myelomonocytic leukemia. We also analyzed gene mutations in patients with positive IHC. p53 mutations were detected in 3/8 (38%) patients. IHC-positive patients had a significantly higher incidence of leukemic transformation and the presence of a complex karyotype with monosomy 17. IHC-positive cells included blasts as well as mature myeloid cells, erythroblasts, and megakaryocytes. Scrutiny of our data in combination with previous data revealed that patients with positive IHC in multilineage cells were older than those in whom positivity was noted mostly in myeloblasts. This suggests that p53 IHC positivity with a multilineage pattern may be a characteristic of MDS in older patients.

Aged↗

Distribution of nifedipine- and omega-conotoxin GVIA-sensitive Ca2+ channels in cultured rat neocortical neurons.

L- and N-type voltage-dependent calcium channels are widely distributed in neurons of the CNS. To investigate their subcellular distributions on CNS neurons, intracellular calcium concentration ([Ca2+]i) increase in response to high potassium ([K+]) solution was detected in primary cultured rat neocortical neurons using the calcium indicator dye Oregon Green with a confocal laser scanning microscope. Extracellular application of 90 mM [K+] solution induced fluorescence increase in a manner dependent on extracellular [Ca2+]. The increase was partially blocked by 10 microM nifedipine, and the reduction was higher in cell bodies compared to dendritic processes. In contrast, omega-conotoxin GVIA reduced the 90 mM [K+] induced fluorescence increase more in the dendritic processes. The results demonstrated the heterogeneous distribution of nifedipine- and omega-conotoxin GVIA-sensitive calcium channels, which may suggest a functional difference in nifedipine- and omega-conotoxin GVIA-sensitive channels in cultured neocortical neurons.

Algorithms↗

Catharanthine oxidation in flavin mononucleotide-mediated catharanthine-vindoline coupling reaction for synthesis of dimeric indole alkaloids under near-ultraviolet light.

A reaction model for the flavin mononucleotide-mediated coupling of catharanthine (C) and vindoline (V) under near-ultraviolet light was established based on the results of experiments on the effects of various physical and chemical factors on the disappearance of C and V, and the synthesis of the product, a dihydropyridinium intermediate (IM). The following events were deduced to occur. (i) C is oxidized in the presence of FMN and oxygen under near-ultraviolet light (C(OX1)). (ii) C(OX1) then couples with V to form IM. Degradation of C occurs simultaneously with its specific oxidation, as a result of which a part of the C is converted into the product (C*) which is incapable of coupling with V. When a reaction in which C(OX1) is further oxidized to another form (C(OX2)) is added and the counterpart for the coupling with V is changed to C(OX2) from C(OX1), the reaction model more appropriately describes the exponential increase in the product, IM, that occurs in the early stage of the coupling reaction. (iii) The degradation rate of IM is much greater after C has been consumed than before its disappearance. Using this reaction model, the coupling reactions under basal and optimized conditions were simulated and the results showed a good fit with the experimental values under both conditions. The kinetic study suggests that manganese ion (Mn2+) stimulates the binding of C(OX2) with V in addition to suppressing the degradation of C, resulting in an increased yield of IM. Mn2+ thus appears to be an important factor in the coupling reaction, in which it plays two different roles.

Journal Article↗

Rescue of liver grafts from hepatic artery occlusion in living-related liver transplantation.

BACKGROUND: Hepatic artery thrombosis after liver transplantation remains a significant cause of graft loss and death. Retransplantation is a difficult option after living-related liver transplantation in Japan. METHODS: Twenty-seven patients underwent living-related liver transplantation with left-sided liver grafts donated from their relatives. The hepatic artery was anastomosed end to end under a surgical microscope. Anticoagulant therapy was maintained for 2 weeks after operation. Routine post-transplant Doppler ultrasonography together with serum blood tests were performed twice a day during the first 2 weeks. RESULTS: Three patients developed hepatic artery occlusion, which was identified by routine Doppler ultrasonography before the serum transaminase values increased on days 7, 7 and 3 after surgery respectively. In two of the three patients, no apparent arterial thrombosis was recognized and vasospasm was therefore considered to be the cause of the occlusion. Arterial patency was restored by urgent revascularization with reanastomosis in all patients, but one patient with a functional graft died from a cerebral haemorrhage on day 47. CONCLUSION: Early diagnosis of hepatic artery occlusion by routine Doppler ultrasonography and revascularization of the graft is an indispensable strategy for preventing graft loss after living-related liver transplantation.

Adolescent↗

Insulin-induced hypoglycemia activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system.

Recently, we found the presence of cytokine-induced neutrophil chemoattractant (CINC) neuronal pathway in the hypothalamo-pituitary system. This observation prompted us to investigate the effect of insulin-induced hypoglycemia on CINC neuronal pathway in the hypothalamo-pituitary system. An insulin injection decreased the plasma glucose level, which followed a prompt rise in plasma ACTH level and an increase in serum CINC level. Before the insulin injection, the signal for CINCmRNA was undetectable in the paraventricular hypothalamic nucleus (PVN). The hypoglycemic challenge induced strong hybridization signals of CINC mRNA in the parvocellular and magnocellular subdivision of the PVN within 30 min, and reached the peak within 3 h. No change was observed in the supraoptic nucleus after the hypoglycemic challenge. These studies demonstrate the presence of a hypoglycemia-sensitive chemokinergic neuronal pathway in the hypothalamo-neurohypophysial system and this newly described pathway will provide novel information for understanding pathophysiology of hypoglycemia.

Acute Disease↗

Impaired parathyroid hormone action on urinary phosphorus excretion in isolated perfused kidney of streptozotocin-induced diabetic rats.

To study the effects of diabetes on the renal actions of parathyroid hormone (PTH), we observed urinary excretion of cyclic adenosine monophosphate (cAMP) and phosphorus in isolated perfused rat kidney. Diabetic rats were kept for 7 days after an intraperitoneal injection of 70 mg/kg streptozotocin (STZ). STZ-induced diabetic rats were treated with a daily injection of 20 U/kg lente-type insulin for 7 days. Plasma albumin, calcium, phosphorus, and PTH levels were not different among normal control, diabetic and insulin-treated diabetic groups. In the control rat kidney, the addition of PTH increased urinary cAMP excretion from 8 +/- 3 to 190 +/- 49 pmol/5 min and urinary phosphorus excretion from 11.3 +/- 4.4 to 33.6 +/- 10.8 microg/5 min. In the STZ-diabetic rat kidney, basal urinary cAMP was impaired, and PTH altered neither urinary cAMP nor phosphorus excretion (from below 0.7 to below 0.7 pmol/5 min, and from 15.5 +/-4.5 to 13.6 +/- 8.1 microg/5 min, respectively). Insulin treatment completely recovered the PTH actions. These results show that insulinopenic diabetes induces PTH resistance in the kidney.

Animals↗

Increased T-helper-1-type immunity and decreased T-helper-2-type immunity in patients with preeclampsia.

PROBLEM: To examine whether preeclampsia involves type-1 T-helper (TH1) immune hyperactivity. METHOD OF STUDY: Expression of HLA-DR, a cell-surface marker of activation, was analyzed on CD3+, CD4+, and CD8+ T cells in 15 preeclamptic patients and 15 normal pregnant women using flow cytometry. Additionally, peripheral blood mononuclear cells from preeclamptic patients and normal pregnant women were cultured with or without phytohemagglutinin (PHA) stimulation, and interleukin (IL)-2, IL-4, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha concentrations were determined in the supernatant by immunoassays. RESULTS: HLA-DR antigen was expressed more strongly on CD3+ T cells in preeclamptic patients than in normal subjects. In preeclampsia, HLA-DR was expressed more strongly in CD8+ T cells than in CD4- T cells. More TNF-alpha, IL-2, and IFN-gamma were produced by unstimulated and stimulated cultured peripheral blood mononuclear cells from preeclampsia patients than by those from normal subjects. TNF-alpha/IL-4, IL-2/IL-4, and IFN-gamma/IL-4 ratios were higher in preeclamptic patients than in the normal group. Significant positive correlations were observed between mean blood pressure and concentrations of the Th-1 type cytokines IL-2, IFN-gamma, and TNF-alpha. CONCLUSION: Up-regulation of Th1 responses and down-regulation of Th2 responses occur in preeclampsia.

Adult↗

Immunohistochemical detection of JC virus in nontumorous renal tissue of a patient with renal cancer but without progressive multifocal leukoencephalopathy.

We performed immunohistochemical staining on the nontumorous renal tissue of 45 patients with renal cancer but without progressive multifocal encephalopathy using JCV-specific antibody. For one patient we found positive staining of the nuclei of the renal collecting ducts. Immunoelectron microscopic examination of the positive cell nuclei revealed electron-dense polyomavirus-like particles.

Antibodies, Viral↗

An index for human lens transparency related to age and lens layer: comparison between normal volunteers and diabetic patients with still clear lenses.

OBJECTIVE: The light scattering intensity of normal, clear lenses varies with age and with the localization within the lens. Realizing the biometry of single lens areas together with their relevant light scattering intensity one should be able to calculate an index to express the lens transparency properties of normal human lenses in dependence on age. Performing the same procedure in cases of diabetic patients with still clear lenses it should become possible to obtain an index for the lens transparency properties of lenses under the 'risk factor' diabetes. METHODS: 748 eyes with transparent lenses in 383 healthy individuals and 134 eyes with clear lenses in 70 subjects with diabetes were examined. Scheimpflug slit images of the lens were documented by a Nidek EAS-1000 instrument. Biometry for measuring the distance of the single lens layers from the anterior capsule and densitometry for determining the light scattering intensity of six defined lens layers along the (theoretical) optical axis were performed. The index of the lens transparency properties was calculated using the light scattering intensity of a defined lens layer and its distance from the anterior capsule. RESULTS: Lens thickness and light scattering intensities increased linearly with increasing age in the normal population as well as in the diabetic patients. The densitogram pattern of the light scattering intensities in the defined representative six points was similar in both populations, but in the diabetic group the lens thickness was larger and the light scattering intensities were higher at all ages. CONCLUSION: The index of lens transparency properties calculated with the light scattering intensities of a certain lens area and its distance from the anterior capsule is a useful measure of lens clarity in dependence on age. 'Clear' lenses of the diabetic population show significantly higher indices for the lens transparency properties in all age groups.

Adult↗

Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) is generally a highly vascular tumor, but the mechanisms of neovascularization that permit rapid growth have not been defined. Angiopoietins (Ang) recently have been identified as ligands for vascular endothelial-specific Tie2 receptor tyrosine kinase and may be important growth factors in the generation of new blood vessels. We investigated Ang expression in 23 samples of HCC and paired adjacent uninvolved liver samples to determine if these genes have a potential role in the growth and spread of this disease. The full coding sequence of a variant angiopoietin-2 (Ang2) cDNA was obtained from HCC specimens, and the biologic consequences of overexpression on tumor formation and hemorrhage were determined in an animal model system. Angiopoietin-1 (Ang1) was equally expressed in HCC and adjacent noncarcinomatous liver tissue. Surprisingly, Ang2 was found to be highly expressed only in tumor tissue. In addition, Ang2 was expressed in 10 of 12 hypervascular HCC, but only in 2 of 11 hypovascular HCC. Ectopic expression of Ang2 in nonexpressing HCC cells promotes the rapid development of human hepatomas and produces hemorrhage within tumors in nude mice. These results suggest a role for Ang2 in the neovascularization of HCC. This enhanced gene expression may contribute to the clinical hypervascular phenotype, as well as tumor formation and progression.

Amino Acid Sequence↗

An imbalance in plasma prostanoids in patients with Raynaud's phenomenon and pulmonary vasospasm.

Raynaud's phenomenon has been suggested as a predisposing factor for pulmonary vasospasm which may lead to pulmonary hypertension, but the occurrence of cold stimulus-induced pulmonary vasospasm has been inconsistent. Such inconsistent pulmonary vascular responses may be caused by differences in the production of endogenous vasodilators and vasoconstrictors among patients. Fourteen patients with Raynaud's phenomenon associated with mixed connective tissue disease (n=10) or systemic sclerosis (n=4) participated in the study. Right heart catheterization was performed before and after a cold pressor test, immersing a hand in cold water (15 degrees C) for 5 min. Plasma levels of 6-keto prostaglandin (PG)F1alpha, thromboxane (TX)B2 and endothelin (ET)-1 in the mixed venous blood were measured. Mean pulmonary artery pressure increased after the cold pressor test in five of 14 patients, and the patients were divided into those with pulmonary vasospasm (responders) and those without vasospasm (nonresponders). After the cold pressor test, levels of 6-keto PGF1alpha increased significantly in nonresponders (p<0.01) and decreased significantly in responders (p<0.05). The ratios of 6-keto PGF1alpha to TXB2 significantly increased in nonresponders (p<0.01) but not in responders and the difference between responders and nonresponders after the cold pressor test was also statistically significant (p<0.05). No significant change in plasma ET-1 levels occurred in either responders or nonresponders. The results suggest that an impaired production of prostaglandin I2 and an imbalance between prostaglandin I2 and thromboxane A2 are associated with the occurrence of pulmonary vasospasm induced by Raynaud's phenomenon.

6-Ketoprostaglandin F1 alpha↗

Natural antioxidant, chlorogenic acid, protects against DNA breakage caused by monochloramine.

Chlorogenic acid prevented a stepwise conversion of plasmid pUC18 DNA, from I-->form II-->form III, induced by 3 mM monochloramine with a half inhibition of 67.4 microM. Chlorogenic acid reacted with monochloramine in a time-dependent manner, and the reaction rate increased with decreasing pH. These results suggest that chlorogenic acid prevents genotoxicity of monochloramine in gastric mucosa.

Ammonium Chloride↗

Relaxing action of sodium nitroprusside independent of membrane potential in the CCh-induced contracture of the guinea pig stomach muscle.

Carbachol (CCh, 10(-6) M) induced biphasic contraction of longitudinal muscle of the guinea pig stomach, consisting of rapid phasic contraction and contracture. The contracture was almost completely inhibited by sodium nitroprusside (SNP, 10(-6) M) and S-nitroso-N-acetyl penicillamine (SNAP, 10(-6) M). A membrane permeable analogue of cyclic GMP, 8Br-cGMP (10(-4) M), also inhibited the CCh induced contracture. Although a heme site inhibitor of nitric oxide-sensitive guanylyl cyclase, 1-H-[1, 2, 4] oxadiazolo-[4, 3 a]quinoxalin-1-one (ODQ; 10(-6) M), reduced the inhibitory action of SNP, it did not affect the inhibitory action of 8Br-cGMP, indicating that the effect of SNP was developed via cyclic GMP production in the presence of D600. Charybdotoxin (10(-7) M), an inhibitor of Ca2+ activated K+ channel, did not influence on the CCh induced contracture. On the other hand, CCh induced a depolarization of the longitudinal muscle cell membrane (from -60 mV to -45 mV) in the presence of 10(-6) M D600, but SNP did not affect the depolarization. These results suggest that in the presence of D600 SNP induces relaxation of CCh induced contracture of the longitudinal muscle of the guinea pig stomach via cyclic GMP but not membrane potential dependent mechanism.

Animals↗