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Biomedical subjects

F Yamamoto

Publications and source records attributed to F Yamamoto.

At least 37 records · Page 2Linked to original sources

[Evaluation of paclitaxel and carboplatin in patients with endometrial cancer].

The purpose of this study was to evaluate the combination of paclitaxel and carboplatin in patients with endometrial cancer who have high-risk histopathologic criteria with vessel permeation and low grade, advanced or recurrent disease. The combination of paclitaxel (180 mg/m2 over 3 hours) and carboplatin (dosed at an area under the curve of 5-6) was given intravenously every 3 weeks. Response and toxicity were evaluated according to the Japan Society of Clinical Oncology's response and adverse effect criteria. Eighteen patients were entered in this study and a total of 94 courses were administered. Eleven patients had evaluable lesions. Complete and partial responses were achieved in 5 (45.5%) and 3 (27.3%) patients, respectively. Grade 3 or 4 leukopenia and neutropenia occurred in 49.2% and 90.5% of the patients. G-CSF support was needed in 52.4% of the patients. Only one patient received a platelet transfusion. As a high response rate was obtained, this regimen is considered to be promising treatment for endometrial carcinoma. Prospective comparative study between this combination therapy and the conventional therapy for endometrial carcinoma is warranted.

Adenocarcinoma↗

Transgenic rats carrying copies of the human c-Ha-ras proto-oncogene exhibit enhanced susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine bladder carcinogenesis.

We have established a transgenic rat line carrying three copies of the human c-Ha-ras proto-oncogene with its own original promoter region, Jcl/SD-TgN(HrasGen)128Ncc (Hras128) rat. c-Ha-ras protein from expression of transduced and endogenous c-Ha-ras genes could be detected in the bladder epithelium of untreated transgenic rats. To examine their susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis, male transgenic and wild-type littermates were treated with 0.05% BBN in their drinking water for 10 weeks and then killed at week 20. The numbers and volumes of total macroscopic bladder tumors including both transitional cell papillomas and carcinomas (TCC) per rat were much greater in Hras128 rats than in their wild-type counterparts. The numbers of carcinomas per rat were also significantly greater in Hras128 rats. Two cases of TCC exhibiting invasion of the bladder muscle layer, which is extremely rare in the wild-type animals under the experimental conditions used, were also observed in Hras128 rats. The GGC-->GAC mutations at codon 12 of the transgene were observed in only two TCC out of 21 bladder tumors (9.5%), assessed by RFLP analysis and direct sequencing. SSCP analysis did not show any endogenous c-Ha-ras gene mutations. One of 25 tumors (4.0%) in wild-type rats had an endogenous c-Ha-ras gene mutation at codon 12 that was detected (GGA-->GAA) by single-strand conformation polymorphism and direct sequencing. These results indicate that the Hras128 rat is highly susceptible to BBN carcinogenesis and may be utilized as a rat model for analysis of bladder tumor development. The mutation findings indicate that the enhanced tumor development is not primarily due to mutations occurring in the transgene.

Animals↗

Molecular genetics of ABO.

This year commemorates the 100th anniversary of the discovery of the ABO blood group system by Karl Landsteiner. His findings of red cell agglutination by serum and recognition of blood groups laid the scientific basis for safe practice of blood transfusion. Even though dozens of blood systems have been identified, the ABO system still remains to be one of the most important systems in transfusion medicine. In 1990, we elucidated the molecular genetic basis of three major alleles at the ABO locus. Since then we have witnessed the progress in our understanding of ABO genes and A and B glycosyltransferases specified by a variety of functional alleles at this locus. Mutations affecting the activity and specificity of the enzymes have been identified. Not only has ABO genotyping become possible, but it has also become possible to genetically engineer the activity and specificity of the enzymes. We are now at a point of embarking upon the quest of understanding the functional significance of ABO polymorphism.

ABO Blood-Group System↗

Do we need hypothermia in myocardial protection?

BACKGROUND: Since the concept of "elective cardiac arrest" has been introduced by Melrose et al., rapid arrest, hypothermia and additional protection has been employed in surgical myocardial protection in clinical and experimental settings. And cardioplegia technique employed these components improved clinical results of open heart surgery except special cases which require longer cardiac arrest. In 1991, Salemo et al. offered striking impact on most of cardiac surgeon with the report of retrograde continuous warm blood cardioplegia. Since then several reports pointed out the benefit of warm blood cardioplegia although inherent disadvantage of continuous cardioplegia were the inadequate visualization of the operative field. These reports recently lead some cardiac surgeon to intermittent warm blood cardioplegia. METHODS: This review introduced and examined our experimental and clinical data with reference to establish new surgical myocardial protection. CONCLUSIONS: Experimental and clinical data might encourage us to employ intermittent tepid (29 ) blood cardioplegia as a practical cardioplegia in open heart surgery.

Animals↗

Expression of human histo-blood group ABO genes is dependent upon DNA methylation of the promoter region.

We have investigated the regulatory role of DNA methylation in the expression of the human histo-blood group ABO genes. The ABO gene promoter region contains a CpG island whose methylation status correlates well with gene expression in the cell lines tested. The CpG island was found hypomethylated in some cell lines that expressed ABO genes, whereas the other cell lines that did not express ABO genes were hypermethylated. Whereas constitutive transcriptional activity of the ABO gene promoter was demonstrated in both expressor and nonexpressor cell lines by transient transfection of reporter constructs containing the ABO gene promoter sequence, HhaI methylase-catalyzed in vitro methylation of the promoter region prior to DNA transfection suppressed the promoter activity when introduced into the expressor gastric cancer cell line KATOIII cells. On the other hand, in the nonexpressor gastric cancer cell line MKN28 cells, treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine resulted in demethylation of the ABO gene promoter and appearance of A-transferase messages, as well as A-antigens synthesized by A-transferase. Taken together, these studies suggest that DNA methylation of the ABO gene promoter may play an important role in the regulation of ABO gene expression.

ABO Blood-Group System↗

Assessment of salivary gland dysfunction following chemoradiotherapy using quantitative salivary gland scintigraphy.

PURPOSE: To assess chemoradiotherapy-induced salivary gland dysfunction using quantitative salivary gland scintigraphy (QSGS), and whether QSGS is capable of predicting the grade of persistent salivary dysfunction after chemoradiotherapy. METHODS: From a time-activity curve using a stimulation test, the washout rate (WR) calculated was assessed. All glands (n = 155) were classified into four groups: a no-therapy group (n = 18), a chemotherapy alone group (n = 31), a radiotherapy alone group (n = 50), and a chemoradiotherapy group (n = 56). Subjective descriptions of xerostomia were recorded 1 year after the completion of the treatment period, and the 32 glands subjected to irradiation with or without chemotherapy were assessed. RESULTS: The WR values were significantly lower in glands that received chemoradiotherapy than in glands treated with radiotherapy alone (mean: 0.75 x 10(-3), n = 40 vs. 0.22, n = 36, p < 0.015), but there was no significant difference in the WR values between the no-therapy group and the chemotherapy alone group. The mean values of WR were lower in the chemoradiotherapy glands than in the radiotherapy alone glands in each of cumulative dose ranges of 1-20, 21-30, and 31-60 Gy. With regard to recovery from xerostomia, the WR values at a cumulative dose range of 20 to 40 Gy were significantly lower in the not improved group (-0.418, n = 16) than in the improved group (0.245, n = 16) (p < 0.0001). CONCLUSION: Chemotherapy per se has no or little adverse effect on salivary function, but combination chemotherapy can deteriorate radiation-induced injury of the salivary glands. QSGS appears useful in predicting the grade of persistent xerostomia following chemoradiotherapy.

Adolescent↗

Phage display cDNA cloning of protein with carbohydrate affinity.

Cell surface complex carbohydrate structures that are synthesized through the actions of glycosyltransferases play an important role in cell-to-cell and cell-to-extracellular matrix interactions. To examine the feasibility of phage display technique to clone cDNAs encoding glycosyltransferases, we performed biopanning experiments using human histo-blood group A transferase as a model enzyme and its substrate, blood group H-specific glycoproteins, as a bait ligand. Our attempts have been unsuccessful, possibly because of the enzyme's weak affinity with the target. However, we have selectively enriched several phage clones that expressed capsid proteins fused with galectin-3, a galactose/lactose-specific animal lectin of the galectin family. These results demonstrate that this novel approach of phage display is useful in cDNA cloning of proteins with carbohydrate-binding property.

Antigens, Differentiation↗

Is the use of catecholamine before ischemic arrest safe? Effect of catecholamine on rat heart ischemia/reperfusion injury.

Using an isolated working heart model, we studied the effects of dopamine, adrenaline, or noradrenaline pretreatment on ischemia/reperfusion injury. Hearts from Wistar rats were perfused in the first 20-minute working mode, 15 minutes in Langendorff mode, and in the second 20-minute working mode. Hearts were treated with dopamine (0.52 and 2.60 mmol/L), adrenaline (16 and 80 nmol/L), or noradrenaline (16 and 80 nmol/L) during the second working perfusion, then arrested with St. Thomas' Hospital cardioplegic solution and subjected to global ischemia (37 degrees C or 20 degrees C). During reperfusion, recoveries of cardiac function and creatine kinase leakage were measured. At 37 degrees C, dopamine and adrenaline had a harmful effect at both doses; noradrenaline was harmful at a high dose but beneficial at a low dose. At 20 degrees C, adrenaline, dopamine, and noradrenaline had a harmful effect at high doses but no harmful effect at low doses. To determine the role of beta adrenergic stimulation before ischemia, a dose-response study was undertaken with isoprotelenol and milrinone at 37 degrees C. Combined pretreatment with isoprotelenol and milrinone accelerated ischemia/reperfusion injury dose-dependently. Preischemic beta adrenergic stimulation thus plays a significant role in the deleterious effect of catecholamine pretreatment at high doses. At low doses, however, the effect of the inotropic agent could be changed depending on ischemic temperature. Our results suggest that catecholamine should not be given at high doses before ischemia, regardless of temperature during ischemia.

Adrenergic beta-Agonists↗

As originally published in 1992: new surgical technique for total-defect aortopulmonary window. Updated in 1999.

A new technique is described to repair aortopulmonary window with total defect in an 8-day-old baby. Because we expected the future growth of aorta, we used the anterior wall of the pulmonary artery as a large flap to reconstruct the posterolateral aortic wall. An equine pericardial patch was used to repair the defect in the pulmonary artery. This is a logically effective method for aortic reconstruction in a neonate with a large aortopulmonary septal defect.

Aortopulmonary Septal Defect↗

Inhibitory effect of methylene blue-induced photooxidation on intimal thickening of vein graft.

BACKGROUND: We have previously speculated that methylene blue-induced photooxidation of adventitial surface for 5 minutes can completely inhibit the intimal and medial growth of surgically prepared saphenous vein in vitro. In this study, inhibitory effect of methylene blue-induced photooxidation on intimal thickening of vein graft in vivo was investigated. METHODS: Jugular vein grafts were photooxidized in 0.01% methylene blue solution for 5 minutes, and interposed into arterial circulation for 4 weeks in rabbits. Vein grafts were studied by morphometry and immunohistochemistry. RESULTS: The intimal thickening of photooxidized vein grafts were suppressed significantly compared with those in the nonphotooxidized group. Proliferated cell nuclear antigen (PCNA) index (total PCNA-positive cells/total cell count x 100%) of vein graft was significantly higher in the nonphotooxidized group than those in the photooxidized group. CONCLUSIONS: Methylene blue-induced photooxidation is effective in the inhibition of intimal thickening of vein graft interposed in the arterial circulation for 4 weeks in vivo.

Animals↗

Synthesis and characterization of lipophilic 1-[18F]fluoroalkyl-2-nitroimidazoles for imaging hypoxia.

In order to develop new imaging markers for brain hypoxia, two lipophilic nitroimidazoles, 1-(3-fluoropropyl)-2-nitroimidazole (FPN) and 1-(8-fluorooctyl)-2-nitroimidazole (FON) were synthesized and labeled with fluorine-18. The octanol/water partition coefficients were measured as an indication of lipophilicity, giving values of logP=0.28 for FPN and logP=2.72 for FON, respectively, which are in the range thought to be optimal for the diffusion of molecules across the blood-brain barrier. It was suggested from a comparative study of in vitro radiosensitization in V79 cells that these lipophilic analogs may have reduction potentials close to those of fluoromisonidazole (FMISO) and misonidazole (MISO), known hypoxic cell radiosensitizers. The preparation of 18F-labeled FON (18FON) and FPN (18FPN) was achieved via two-steps through [18F]fluoride ion displacement of tosylate precursors, in reasonable radiochemical yields. Tissue distribution of 18FPN and 18FON in normal rats and tumor-bearing mice after intravenous injection was investigated and compared to the behavior of 18F-labeled FMISO (18FMISO), a proven hypoxic imaging agent. The high lipophilicity of 18FON and 18FPN resulted in increased initial uptake into normal rat brain, relative to 18FMISO, followed by a rapid washout from brain. Both of these lipophilic analogs had significantly lower tumor uptake and lower tumor-to-blood ratios than 18FMISO, suggestive of a poor trapping mechanism within the tumor tissue. Neither 18FON or 18FPN offers improved biological properties over 18FMISO as a potential agent for use in brain hypoxic imaging.

Animals↗

[Maze procedure for a lone atrial fibrillation].

Between 1992. 2 and 1997. 12, the maze procedure for lone fibrillation or flutter (lone af) was performed in 8 patients including 2 patients with a sustained atrial fibrillation, 5 patients with a paroxysmal atrial fibrillation and 1 patient with a sustained atrial flutter. All patients had suffered from a drug resistance lone af which induced sever symptom that is the dyspnea, palpitation and fatigue. Therefore patients requested to receive the maze procedure, and they agreed with the informed concent. After the maze operation, the normal sinus rhythm was recovered in 7 of 8 patients (87.5%). In only 1 patient, a paroxysmal atrial fibrillation remained but his symptoms improved after surgery. So this operation is a good choice of a treatment for a drug resistance lone af.

Adult↗

Maze procedure for atrial fibrillation associated with atrial septal defect.

BACKGROUND: Atrial fibrillation (AF) is a relatively common complication in elderly patients with an atrial septal defect (ASD). However, use of the simultaneous maze procedure for AF associated with ASD remains controversial. We examined the efficacy and risk of the use of the maze procedure in these patients. METHODS AND RESULTS: Between March 1992 and April 1997, 26 patients underwent the maze procedure as a concomitant operation with ASD closure (maze group). Kosakai's modified maze procedure was performed in 17 patients, the modified Cox maze II or III procedure was performed in 6, and the restrictive right-sided maze procedure was performed in 3. The mean +/- SD age at surgery was 58.2 +/- 9.1 years. The mean +/- SD duration of AF was 7.8 +/- 8.5 years. The mean +/- SD left atrial dimension was 47 +/- 9 mm, and 24 patients (92%) had a larger-than-normal (> 35 mm) left atrium. The mean +/- SD follow-up period was 2.7 +/- 1.7 years. There were no hospital or late deaths. There was no thromboembolic episode in the late follow-up period. Sinus rhythm was regained in all patients who underwent conventional the right- and left-sided maze procedure except for 1 patient. However, 3 patients who underwent the restrictive right-sided maze procedure showed a return to AF rhythm. The atrial A wave was detected with the use of pulsed Doppler study in all patients who had a restored sinus rhythm. During the same period, 45 patients who were > 40 years old and without AF underwent only ASD closure (control group). The incidence of reopening the chest for bleeding was significantly (P = 0.046) higher in the maze group (12%) than in the control group (0%). Paroxysmal AF more frequently (P = 0.023) occurred in the control group (18%) than in the maze group (0%). CONCLUSIONS: These results suggest that the standard maze procedure should be considered in patients with AF associated with ASD. The restrictive right-sided maze procedure was not reliable, probably due to preoperative enlargement of the left atrium.

Aged↗

Focal, high dose, and fractionated modified stereotactic radiation therapy for lung carcinoma patients: a preliminary experience.

BACKGROUND: Stereotactic radiation therapy is highly effective in the treatment of small brain metastases, regardless of the histology. This suggests that small extracranial malignancies may be curable with similar radiation therapy. The authors developed a novel treatment unit for administering such therapy. METHODS: The unit consisted of a linear accelerator (linac), an X-ray simulator (X-S), computed tomography (CT), and a table. The gantry axes of the three machines were coaxial and could be matched by rotating the table. Patients were instructed to perform shallow respiration with oxygen. The motion of the tumor was monitored with the X-S. When the motion was slight enough, the table was rotated to the CT. To include all geometric movement on the CT images, each scan was made while the patient was performing shallow respiration. After the CT positioning, the table was rotated to the linac, and non-coplanar treatment was given. Beginning in October 1994, 45 patients with 23 primary or 43 metastatic lung carcinomas were treated. Radiation doses at the 80% isodose line were 30-75 gray in 5-15 fractions over 1-3 weeks with or without conventional radiation therapy. RESULTS: The treatment was performed with no or minimal adverse acute symptoms. The daily treatment time was short. During a median follow-up of 11 months, local progression occurred in 2 of 66 lesions. Interstitial changes in the lung were limited. CONCLUSIONS: With this unit and procedure, focal radiation therapy similar to stereotactic radiation therapy is possible for extracranial sites. The preliminary experience appeared safe and promising, and further exploration of this approach is warranted.

Adenocarcinoma↗

[Decreasing sarcoplasmic reticular calcium gives rise to myocardial protection--the effect of thapsigargin for myocardial protection under conditions of normothermia].

Deceasing sarcoplasmic reticular (SR) calcium may contribute to the myocardiac protection against ischemia and reperfusion-induced injury. Therefore, using the isolated working rat heart model, we investigated the effect of Thapsigargin (TH)-induced SR calcium diminution on the myocardial protection when added either before onset of ischemia or at time of reperfusion under conditions of normothermic ischemia. Hearts (n = 6/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer. In the experimental protocol A, this was followed by a 3 min infusion of St. Thomas' Hospital cardioplegic solution No. 2 (STS) containing various concentrations of TH. Hearts were then subjected to 34 min of normothermic (37 degrees C) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). Reperfusion cardiac functions at 20 min of working perfusion was measured and compared with the preischemia values. STS added to 0.1 and 0.25 mumol/L TH improved recovery of aortic flow after 20 min reperfusion from 47 +/- 3% in the TH free controls to 62 +/- 3, 63 +/- 2% (n = 6) (p < 0.05). There was no difference in creatine kinase (CK) leakage during Langendorff reperfusion between the TH treated groups and the control group. In the experimental protocol B, 3 min of cardioplegia without TH and 34 min of ischemia (37 degrees C) were followed by a 10 min Langendorff reperfusion with various concentrations of TH, then 10 min Langendroff reperfusion for washing out, and 20 min working reperfusion. When TH was added to reperfusate the recovery of aortic flow did not change, 0.5 mumol/L TH group had the detelious effect. Thus, TH, when added to the cardioplegia, enhanced myocardial protection. We conclude that lessened uptake of Ca2+ into sarcoplasmic reticulum by inhibitors of the Ca(2+)-ATPase pump can decrease ischemia and reperfusion-induced injury.

Animals↗

[Surgical treatment for mitral regurgitation associated with secundum atrial septal defect].

We reviewed 25 patients who underwent a mitral valvuloplasty, from 1984 to 1996, for mitral regurgitation (MR) associated with atrial septal defect (ASD). Mean grade of MR was 2.3 +/- 0.7. The locations of mitral valve lesion were as follows; Postero-medial side of the anterior leaflet (AML) (11 patients: 44%), posteromedial side to center of the AML (7 patients: 28%), whole of the AML (5 patients: 20%), center of the AML (1 patient: 4%), posteromedial side of the posterior leaflet (PML) (1 patient: 4%). In summary, the mitral valve lesion was located in the AML in 96% patients and were seen in the postero-medial side of 96% patients. Mitral valve repair was performed as follows; chordae shortening only (3 patients: 12%), chordae shortening + Kay's annuloplasty (9 patients: 36%), Kay's anuloplasty (10 patients: 40%), using artificial chordae only (1 patient: 4%), using artificial chordae + Kay's annuloplasty (1 patient: 4%), using artificial chordae + ring annuloplasty (1 patient: 4%). In 24 patients, the grade of MR was less than 2/4 in the early postoperative period. In one patient, the grade of 3/4 MR was still remained. Reoperation were required in 2 patients, because of gradual increase of MR, 9 years and 10 years after the initial operation, respectively. In another patient, the grade 3/4 MR recurrently occurred at 6 months after the operation. He has been well maintained medically. In all 4 patients who had more than the grade 3/4 MR postoperatively, the annuloplasty was performed with Kay's method and the cause of MR was poor coaptation around the center of the AML. The mitral valve lesion associated with ASD seemed to be the dislocation of the AML which cause the discrepancy of the coaptation zone between both leaflets, without any prominent prolapse and chordae elongation. We put a particular emphasis on that the mitral valve repair should be performed with the recognition of the etiology of the mitral valve lesion. Especially, if the lesion extends around the center of the AML, sufficient coaptation area of both leaflets at the center of the AML should be obtained by anuloplasty.

Adult↗