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Biomedical subjects

Y Tsuji

Publications and source records attributed to Y Tsuji.

At least 109 records · Page 6Linked to original sources

Quantitative EEG analyses and surgical outcome after corpus callosotomy.

PURPOSE: To clarify the relation between quantitative electroencephalogram (EEG) findings and outcome following corpus callosotomy (CC). METHODS: The degree of bilateral synchrony and morphologic similarity of spike-wave discharges was analyzed by using a cross-correlation analysis and the measurements of amplitude differences between bilateral homologous regions in 22 patients who underwent anterior CCs for intractable symptomatic generalized epilepsies (SGE; 17 patients) and frontal lobe epilepsy (five patients). RESULTS: Interictal generalized synchronous spike-wave (GSSW) bursts in the SGE patients were disrupted and changed to unilateral spike-waves (USWs) in 11 patients and to bilaterally independent spike-waves (BISWs) in six. The USW group had better surgical outcome than the BISW group. Preoperatively, the USW group had significantly lower interhemispheric synchrony (IS) and fewer regional changes in the side leading in time and the side dominant for amplitude, suggesting unilaterally predominant epileptogenesis that triggered the secondary bilateral synchrony. Postoperatively, the BISW group had a more marked reduction in IS because of independent discharges from bilateral epileptogenic areas, and the USW group had a greater amplitude difference because of unilateralized spike-waves. In addition, an excellent surgical outcome was related to (a) the preoperative degree of the morphologic similarity of the bilateral spike-waves (only a small variation during a burst of spike-waves) and the few instances of regional changes in the side leading in time and in the side dominant for amplitude; and (b) to large postoperative amplitude differences. CONCLUSION: Preoperative quantitative EEG analyses enabled us to predict the underlying conditions of epileptogenesis and the surgical outcomes in patients undergoing CC.

Adolescent↗

A substitutional mutation in the DNA binding domain of the androgen receptor causes complete androgen insensitivity syndrome.

DNA analysis of the androgen receptor gene in a patient with complete androgen insensitivity syndrome identified a substitutional mutation (tyrosine converted to cysteine at position 571) in the DNA binding domain. In vitro transfection experiments with the patients' androgen receptor gene, indicated normal expression of the androgen receptor in transfected COS-7 cells compared to the wild type gene. There was also no evidence of impaired thermal stability of the 5 alpha-dihydrotestosterone-androgen receptor complex. However, the capacity of the androgen receptor to activate target gene transcription was found to be completely disrupted in a luciferase assay. These results confirmed that only one substitutional mutation in the DNA binding domain was related to the pathogenesis of the complete androgen insensitivity syndrome.

Adult↗

[Assessment of adrenal function on steroid using renal diseases in children using the modified original ACTH tolerance test: comparing nephrotic syndrome with non-nephrotic syndrome].

Steroid therapy occupies a very important position in various types of kidney diseases in children. The period of steroid therapy in kidney disease tends to extend over a long time and the amount of medication tends to be high. Inhibition of the adrenal function because of steroid therapy is one of the major side effects requiring considerable care. In the present investigation, we examined the inhibition of adrenal function in various pediatric renal diseases using synthetic ACTH. In this study, we checked the serum 11-OHCS and cortisol levels and found that in nephrotic syndrome, the inhibition already existed at sideration. In other diseases we found inhibition of adrenal function using steroid and improvement of the function on reduction of the steroid dose. Patients who used steroid every other day showed better improvement. Therefore, we suggest that in nephrotic syndrome, the inhibition of adrenal function may participate in sideration in the syndrome. It was also found that reduction of the steroid given every other day inhibited the adrenal function to a lesser extent. We found that our challenge test using ACTH is safe and very useful for determining adrenal function.

Adolescent↗

Usefulness of cytofluorometric DNA ploidy analysis in distinguishing benign cartilaginous tumors from chondrosarcomas.

In this study, we undertook to prove the usefulness of cytofluorometric DNA ploidy analysis in distinguishing benign cartilaginous tumors from chondrosarcomas. We analyzed the DNA ploidy of 47 cartilaginous tumors using DNA cytofluorometry, which is more sensitive than flow cytometry. All of these tumors were classified into six groups on the basis of clinical, radiologic, and histologic criteria. The 25 tumors in the No. 1 group showed no histologic signs of malignancy regardless of their clinical signs. The four tumors in the No. 2 group showed histologic signs of malignancy, but had benign clinical signs like small bone origin or Ollier's disease. The No. 3 group (13 tumors), No. 4 group (four tumors), and No. 5 group (three tumors) were conventional grade I, II, and III chondrosarcomas, respectively, and the No. 6 group included three dedifferentiated chondrosarcomas. Tumor cells isolated from fresh tumor materials treated with papain and collagenase were smeared on a glass slide and their nuclear DNA was stained with propidium iodide. The DNA content of each cell was measured by a cytofluorometer as fluorescence intensity. The results of this study showed that all of the tumors in the No. 1 group had a diploid pattern with a significantly lower (P<.001) cell proliferative activity than the grade I chondrosarcomas in the No. 3 group, all of which had a diploid pattern. Cytofluorometric analysis also indicated that grade II and III chondrosarcomas in the No. 4 and 5 groups had a higher frequency of hyperdiploid cells (%HDC), including aneuploid and polyploid cells than grade I chondrosarcomas. Importantly, all of the grade I chondrosarcomas showed a %HDC >8%, whereas all of the tumors in the No. 1 and 2 groups showed a %HDC <8%. Therefore, we believe that a %HDC value of 8% is borderline between biologically benign and malignant states in cartilaginous tumors. Four of five patients with aneuploid chondrosarcoma had tumor recurrence and two of these patients died of metastatic disease, although all of the patients except for one with diploid chondrosarcoma were continuously disease free after surgery. Based on these results, we concluded that the data of DNA ploidy analysis, especially cell proliferative activity expressed as %HDC, is more reliable and clinically more useful than the histologic and clinical signs of malignancy in distinguishing benign cartilaginous tumors from chondrosarcomas and even from low grade chondrosarcomas.

Adult↗

[Cooperative study of intraarterial preventive chemotherapy after resection of hepatic metastasis from colorectal cancer].

This is a compilation of the results of preventive intraarterial infusion following resection of hepatic metastasis from colorectal cancer at four surgical centers. The cases studied included two groups: A) 76 patients who underwent normal liver resection only, and B) 78 patients who underwent resection with adjuvant chemotherapy. Methods included: 1) WHF, 50 cases; 2) other methods using 5-FU, 18 cases; and 3) intraarterial infusions other than 5-FU, 10 (2 cases, outcome unknown). Survival rates for groups A and B for 1 and 5 years were 71.2, 18.9% and 91.5, 56.2%, respectively, with the rates for the intraarterial infusion group showing far better results. The 1- and 5-year survival rates in terms of infusion methods were: 1) 90.7% and 64.6%; 2) 94.4% and 39.3%; and 3) 90% and 60%, respectively, showing no remarkable differences between methods. Total doses of 5-FU were (a) less than 5 g, 7 patients (b) 5-15 g, 16 patients (c) 15-30 g, 22 patients (d) greater than 30 g, 23 patients. A comparison of 1- and 5-year survival rates shows (a) 85.7% and 17.1%; (b) 66.5% and 44.3%; (c) 100% and 62.7%; (d) 100% and 66.5%, respectively, with doses (c) and (d) showing markedly better results than the (a) dosage. From this we conclude that the group undergoing intraarterial hepatic infusion had a markedly improved prognosis compared to the group not undergoing any type of adjuvant therapy. Also, groups receiving a dosage of 15 g or greater of 5-FU showed prolonged survival rates.

Antineoplastic Combined Chemotherapy Protocols↗

Pathological analysis of transmyocardial laser revascularization for acute myocardial ischemia.

Transmyocardial laser revascularization (TMLR) is an alternative surgical procedure for the patients with intractable coronary artery disease. Efficacy of the treatment has been established, however, the mechanism of TMLR is still controversial. In this study, we investigated the effect of TMLR on acute myocardial ischemia with pathological analysis. Under general anesthesia, the hearts of mongrel dogs were exposed. Then, the anterior descending branch of the left coronary artery was ligated to make the ischemic area on the left ventricle. Laser punctures were made 30 minutes after coronary ligation in the TMLR group (n = 5), and no further procedure was performed after coronary ligation in the AMI group (n = 5). One month after these operations, the hearts were extirpated for pathological studies. The avascular area and the viable area in the infarcted area were macroscopically separated by Evans blue dye and triphenyltetrazolium chloride (TTC) staining. Thickness of the left ventricular wall in the infarcted area was also measured and compared. Furthermore, all of the infarcted area and the lased area were microscopically examined with Masson's trichrome stain. The size of the infarcted area in the TMLR group was smaller than that in the AMI group. It was significantly different (p < 0.05) in the basal and apical regions. As a result, the ratio of the viable area by the avascular area was larger in the TMLR group than in the AMI group. It was significantly different (p < 0.05) in the apical region. In the basal region, the thickness of the left ventricle in the AMI group was thinner than that of untreated dogs (normal group: n = 5), and there was no difference between the normal group and the TMLR group. Whereas in the apical region, significant difference of the thickness was found among AMI, TMLR, and normal groups (p < 0.05). In conclusion, our study supported; 1) TMLR reduced overall infarcted size, and increased the viable area in the infarcted area, 2) TMLR prevented the thinning of the left ventricular wall.

Animals↗

[Noninvasive screening for pheochromocytoma in patients with an incidentally discovered adrenal mass: usefulness of provocative test with metoclopramide and 131I-metaiodobenzylguanidine scintigraphy].

Pheochromocytoma accounts for approximately 25% of incidentally discovered adrenal masses. Certain diagnostic procedures (e.g., adrenal arteriography, needle biopsy of an adrenal mass), anesthesia and abdominal surgery may cause a sudden release of catecholamines from a pheochromocytoma and induce paroxysmal attacks of hypertension. In addition, pheochromocytoma is well known to cause unsuspected operating room deaths. Therefore, we must carefully separate this functioning neoplasm from other types of adrenal masses. In this study, we compared the results of noninvasive tests including (1) assay of urinary catecholamines and their metabolites, (2) a provocative pharmacologic test using metoclopramide (MCP test), and (3) 131I-metaiodobenzylguanidine (MIBG) scintigraphy to screen for pheochromocytoma in 10 consecutive patients with an incidentally discovered adrenal mass (6 pheochromocytomas and 4 non-functioning adrenocortical adenomas). We measured the 24-hour urinary excretion of catecholamines, metanephrines and vanillyl mandelic acid in all 10 patients; 5 were positive, 4 were negative and 1 was false-negative (sensitivity = 83%, specificity = 100%). The MCP test was performed in 7 patients; 3 were positive, 3 were negative and 1 was false-negative (sensitivity = 75%, specificity = 100%). MIBG scintigraphy was performed in 7 patients; 4 were positive, 1 was negative and 2 were false-negative (sensitivity = 67%, specificity = 100%). According to these results, all patients with an incidentally discovered adrenal mass should undergo a determination of the 24-hour urinary excretion of catecholamines and their metabolites, including metanephrines. If this urine assay is negative, other noninvasive tests including the MCP test and MIBG scintigraphy should be considered in selected patients with radiographic characteristics of pheochromocytoma.

3-Iodobenzylguanidine↗

[Outpatient chemotherapy with infusional 5-fluorouracil in advanced gastrointestinal cancer].

These studies were designed to evaluate the efficacy, toxicity, and resulting quality of life (QOL) of outpatient chemotherapy with infusional 5-FU for advanced gastrointestinal cancer. Schedule, sch. A: Treatment consisted of CI 5-FU 200 mg/m2/day, days 1-28, IVB Leucovorin 20 mg/m2 q week. Fifteen patients with advanced gastrointestinal cancer were treated to maintain the efficacy of prior inpatient chemotherapy. Twenty-one patients treated with adjuvant chemotherapy were added to evaluate toxicity and QOL. The mean time to progression (TTP) was 2.6 months. Grade 2 toxicities were seen, including mucositis (23%) and diarrhea (7%). Hand-foot syndrome was seen 60% of patients. The mean QOL score was 89.5 +/- 7.8. Sch.B: Treatment consisted of weekly 24 h infusion of 5-FU 2,600 mg/m2. 5-FU was administered using a Groshong catheter and Baxter infusor LV5 (5 ml/hr). Nine patients with advanced gastrointestinal cancer were treated. Twenty-one patients were treated with adjuvant chemotherapy. The mean TTP was 3.6 month. Grade 2 toxicities were seen, including leucocytopenia (7%), mucositis (3%), diarrhea (10%), and nausea and vomiting (10%). The mean QOL score was 82.6 +/- 10.7. In conclusion, both 5-FU schedules are feasible for outpatient chemotherapy for advanced gastrointestinal cancer.

Ambulatory Care↗

[Inverted papilloma of the renal pelvis: report of a case].

Inverted papilloma of the upper urinary tract is a rare lesion. To our knowledge, we report here the 32nd case of inverted papilloma of the renal pelvis. A 50-year-old man presented with asymptomatic gross hematria. Excretory urography showed a filling defect in the left upper calyx. Computerized tomography showed a poorly enhanced low-density area within the renal pelvis. Since radiographic findings suggested a renal pelvic tumor, the patient underwent total nephroureterectomy. Unexpectedly, a 3 x 2.5 cm polypoid tumor of the renal pelvis was consistent with inverted papilloma. Since this benign lesion is extremely rare within the upper tract and its radiographic characteristics closely resemble those of urothelial carcinoma, the preoperative diagnosis of inverted papilloma of the upper tract cannot be conclusively established even by modern imaging techniques. Therefore treatment consistent with that for urothelial carcinoma should be applied in this disease entity.

Humans↗

Reperfusion in acute ischemic myocardium by transmyocardial revascularization using CO2 laser.

Transmyocardial laser revascularization (TMLR) is currently applied to provide clinical benefits in the patients with end-stage coronary artery disease. However, this method is so far indicated only for chronic status of ischemic heart disease. In this study, we have investigated in the canine model whether acute ischemic myocardium could be reperfused by TMLR using CO2 laser. A CO2 laser was used to create transmural myocardial channels. The ischemic areas of 3 cm in diameter were created on the left ventricle with multiple coronary ligations. Laser procedure was carried out 30 minutes after coronary ligation in TMLR group (n = 6), while laser treatment was not performed after coronary ligation in acute myocardial infarction (AMI) group (n = 6). The level of MB isozyme of creatinine kinase (CK-MB) derived from coronary sinus was measured at 0, 3, 6, 12, 18, 24, and 48 hours after coronary ligations, and the pattern of serial CK-MB changing was analyzed. Animals were sacrificed 48 hours after treatment and histologically investigated. The time to peak level of CK-MB in TMLR group appeared significantly earlier (13.0 +/- 2.4 hours) than that in AMI group (22.0 +/- 3.1 hours). The value of CK-MB of 24 hours after ligation in TMLR group (1985 +/- 805 IU/L) was significantly lower than that in AMI group (4759 +/- 778 IU/L). The channels on the gross section after 48 hours of TMLR were patent with some of fibrin network. Red blood cells were scattered in the lumens. It was suggested that acute ischemic myocardium was directly reperfused through the open laser channels from the left ventricular chamber in the canine model.

Animals↗

Experimental investigations on relationships between myocardial damage and laser type used in transmyocardial laser revascularization (TMLR).

Transmyocardial laser revascularization (TMLR) using a CO2 laser is clinically attempted in end-stage ischemic heart disease that is not treated by conventional bypass grafting or transluminal angioplasty. Besides, clinical trials of TMLR using a Ho:YAG laser have started recently. In this study, we compared the degree of damage to normal myocardium using these 2 types of lasers. Hearts of adult mongrel dogs were exposed under general anesthesia. Dogs were divided into 2 groups; those with channels made in the left ventricle by CO2 laser (CO2 group, n = 5) and those with channels made by Ho:YAG laser (Ho:YAG group, n = 5). The chest was temporarily closed, then serum MB isozyme of creatinine kinase (CK-MB) and troponin T (TnT) were measured sequentially. Twenty-four hours after laser irradiation, hearts were isolated for pathological studies with hematoxylin-eosin and Masson's trichrome stains. The CO2 group produced CK-MB with a peak of 1162.2 +/- 462.2 IU/l and the Ho:YAG group 1804.0 +/- 992.4 IU/l after 12 hours, and there was a significant difference between two groups (p < 0.01). The CO2 group produced TnT with a peak of 1.2 +/- 0.4 ng/ml and the Ho:YAG group 11.6 +/- 4.1 ng/ml after 6 hours, and the peak value in Ho:YAG group was significantly higher than that in the CO2 group (p < 0.001). Thirty channels were confirmed histologically in the CO2 group, and the width of thermal damage layer around the channel lumen was 249 +/- 83 microns. Twenty-seven channels were confirmed histologically in the Ho:YAG group, and the width of thermal damage layer was 760 +/- 288 microns. Thermal damage in the Ho:YAG group was significant greater than that in the CO2 group (p < 0.01). We concluded that TMLR using a CO2 laser is more suitable for end-stage myocardial ischemia than a Ho:YAG laser in terms of myocardial damage.

Aluminum↗

Evaluation of local platelet deposition during laser thermal angioplasty.

Laser thermal angioplasty is one of the brand-new transluminal interventions for arterial occlusive disease. And one of the most important prognostic factors of this intervention is the degree of local platelet deposition which causes the acute platelet thrombus and increases the proliferation of smooth muscle cells. The purpose of this study is to assess the degree of platelet deposition on the laser ablated area and to investigate the optimal conditions of laser ablation from the point of thrombogenesis. First of all, the laser ablations of various delivered energy were carried out on canine femoral arteries, then thrombus formation after laser ablation was evaluated with angioscopy. No thrombus was recognized on all ablated areas in the cases with a laser energy of 16 Joule (J) and 20 J. On the other hand, small thrombus on the ablated area was observed in 1 of 4 cases (25%) with that of 24 J, and in 2 of 4 cases (50%) with that of 30 J. Then, the degree of platelet deposition on the laser ablated area was evaluated with platelet labeled radioimmunoassay. Laser ablations were employed in canine femoral arteries varying delivered laser energy. There were no differences in the numbers of platelet deposition when the laser energy for one shot was within 24 J. The numbers of platelet deposition with a laser energy of 30 J and 45 J were significantly (p < 0.05) higher than those with a laser energy within 24 J. The numbers of platelet deposition were gradually increased related to the frequency of laser ablations, and the numbers of platelet depositions in 10 repeated laser ablations of 16 J and 20 J were significantly (p < 0.05) higher than that in single laser ablation of 16 J and 20 J. From the aspect of local platelet deposition, the optimal laser energy for one shot should be restricted within 24 J and the repeated ablation was the most appropriate method of laser thermal ablation.

Aluminum↗

GATA-3 represses gp91phox gene expression in eosinophil-committed HL-60-C15 cells.

To study the regulatory mechanism of gp91phox gene expression in eosinophils, we transiently transfected eosinophil-committed HL-60-C15 cells with gp91phox promoter constructs, and identified a negative element from bp -267 to -246 of the gp91phox gene, the deletion of which caused an 83% increase in promoter activity. Electrophoresis mobility shift assays demonstrated GATA-3 binds to the GATA consensus site from bp -256 to -250. An 81% increment in promoter activity was obtained when a mutation was introduced in the GATA-3 binding site of the bp -267 to +12 construct, which is comparable to that of the bp -245 to +12 construct. We therefore conclude that GATA-3 specifically binding to the GATA site negatively regulates the expression of the gene in HL-60-C15 cells.

Base Sequence↗

Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinase.

Growth hormone (GH) and prolactin (PRL) binding to their receptors, which belong to the cytokine receptor superfamily, activate Janus kinase (JAK) 2 tyrosine kinase, thereby leading to their biological actions. We recently showed that GH mainly stimulated tyrosine phosphorylation of epidermal growth factor receptor and its association with Grb2, and concomitantly stimulated mitogen-activated protein kinase activity in liver, a major target tissue. Using specific antibodies, we now show that GH was also able to induce tyrosine phosphorylation of insulin receptor substrate (IRS)-1/IRS-2 in liver. In addition, the major tyrosine-phosphorylated protein in anti-p85 phosphatidylinositol 3-kinase (PI3-kinase) immunoprecipitate from liver of wild-type mice was IRS-1, and IRS-2 in IRS-1 deficient mice, but not epidermal growth factor receptor. These data suggest that tyrosine phosphorylation of IRS-1 may be a major mechanism for GH-induced PI3-kinase activation in physiological target organ of GH, liver. We also show that PRL was able to induce tyrosine phosphorylation of both IRS-1 and IRS-2 in COS cells transiently transfected with PRLR and in CHO-PRLR cells. Moreover, we show that tyrosine phosphorylation of IRS-3 was induced by both GH and PRL in COS cells transiently transfected with IRS-3 and their cognate receptors. By using the JAK2-deficient cell lines or by expressing a dominant negative JAK2 mutant, we show that JAK2 is required for the GH- and PRL-dependent tyrosine phosphorylation of IRS-1, -2, and -3. Finally, a specific PI3-kinase inhibitor, wortmannin, completely blocked the anti-lipolytic effect of GH in 3T3 L1 adipocytes. Taken together, the role of IRS-1, -2, and -3 in GH and PRL signalings appears to be phosphorylated by JAK2, thereby providing docking sites for p85 PI3-kinase and activating PI3-kinase and its downstream biological effects.

Androstadienes↗

Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency.

To ascertain the molecular background of combined pituitary hormone deficiency, screening for mutations in the pituitary-specific transcription factor (Pit-1/GHF-1) gene (PIT1) was performed on a cohort of 15 children from Russia with combined growth hormone (GH)/prolactin (Prl)/thyroid-stimulating hormone (TSH) deficiency. The group of patients, suspected of PIT1 mutations, consisted of four familial cases (seven patients) and eight sporadic cases. All had complete GH deficiency and complete or partial Prl and TSH deficiency. Direct sequencing of all six exons of PIT1 and its promoter region showed a C to T transition mutation at codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in a proline to leucine substitution (P14L). The patient was heterozygous for mutant and normal alleles. The heterozygous P14L mutation was also present in her mother as well as in her maternal aunt and grandmother, all of whom were phenotypically normal. There was no mutation in the father's DNA, suggesting the need for reevaluation of genomic imprinting. In other children of our series, no mutation in PIT1 or in its promotor region was identified. This is the first report on the analysis of PIT1 and its promoter region in Russian children with GH/Prl/TSH deficiency. However, as the involvement of PIT1 mutation is rare in Russia, the other negative cases need to be analyzed for another candidate gene responsible for combined GH/Pr/TSH deficiency.

Adolescent↗

PU.1 as an essential activator for the expression of gp91(phox) gene in human peripheral neutrophils, monocytes, and B lymphocytes.

We have reported a deficiency of a 91-kDa glycoprotein component of the phagocyte NADPH oxidase (gp91(phox)) in neutrophils, monocytes, and B lymphocytes of a patient with X chromosome-linked chronic granulomatous disease. Sequence analysis of his gp91(phox) gene revealed a single-base mutation (C --> T) at position -53. Electrophoresis mobility-shift assays showed that both PU.1 and hematopoietic-associated factor 1 (HAF-1) bound to the inverted PU.1 consensus sequence centered at position -53 of the gp91(phox) promoter, and the mutation at position -53 strongly inhibited the binding of both factors. It was also indicated that a mutation at position -50 strongly inhibited PU.1 binding but hardly inhibited HAF-1 binding, and a mutation at position -56 had an opposite binding specificity for these factors. In transient expression assay using HEL cells, which express PU.1 and HAF-1, the mutations at positions -53 and -50 significantly reduced the gp91(phox) promoter activity; however, the mutation at position -56 did not affect the promoter activity. In transient cotransfection study, PU.1 dramatically activated the gp91(phox) promoter in Jurkat T cells, which originally contained HAF-1 but not PU.1. In addition, the single-base mutation (C --> T) at position -52 that was identified in a patient with chronic granulomatous disease inhibited the binding of PU.1 to the promoter. We therefore conclude that PU.1 is an essential activator for the expression of gp91(phox) gene in human neutrophils, monocytes, and B lymphocytes.

B-Lymphocytes↗