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Biomedical subjects

Y Saitoh

Publications and source records attributed to Y Saitoh.

At least 289 records · Page 16Linked to original sources

Pharmacokinetics of intravenous adriamycin for anhepatic chemotherapy during liver transplantation.

Frequent recurrence of hepatocellular carcinoma after liver transplantation indicates the necessity to eliminate patients with advanced disease and combine transplantation with some form of perioperative adjuvant chemotherapy. This study was undertaken to elucidate adriamycin pharmacokinetics for anhepatic chemotherapy during liver transplantation. beagles of both sexes were allocated into two groups, controls (n = 4) and anhepatic animals with total hepatectomy under venovenous bypass (n = 5). In both groups, adriamycin was administered in 1 min at a dose of 1 mg/kg through the left antecubital vein and peripheral blood was obtained at intervals for up to 2 h to determine the plasma adriamycin levels. The animals were then sacrificed to determine tissue adriamycin levels in the liver, kidney, heart, lung, and skeletal muscle. Plasma adriamycin levels in anhepatic animals were significantly higher than those in controls at all measured time points after 10 min, resulting in a 50% reduction of the mean total body clearance of adriamycin compared with controls (P < 0.01). However, there was no statistically significant difference in adriamycin levels between the two groups for all measured tissues except for the liver. Despite the complete lack of hepatic function, anhepatic animals showed only a 50% reduction in total body clearance of adriamycin compared with normal controls, probably due to compensatory excretion from other organs such as the kidney. These results suggest that systemic chemotherapy with the standard dose of adriamycin may be tolerable during the anhepatic period of liver transplantation with enhanced tumoricidal effects on micrometastases.

Animals↗

A novel paper cuff for vascular reconstruction in canine liver transplantation.

A new, simple method of producing optimal cuffs using thin paper and then setting it in resin for vascular reconstruction in canine liver transplantation is herein described. Thin Paper was cut into a paper tape strip. By fixing both ends of this paper tape, a cylinder paper core of any desired size could thus be obtained. The paper core was immersed into a two-liquid mixture-type resin, removed, and left to harden. The paper cuffs (0.2 mm or less in thickness) were then used for anastomoses of the portal vein and the infrahepatic inferior vena cava in a series of 10 consecutive canine liver transplantations. Out of 10 animals, 8 survived for more than 5 days. The vascular patency in these 8 animals at the cuff anastomotic sites was 100% at postmortem. We therefore conclude that this paper cuff appears to be useful for various types of experimental liver transplantations in large animals.

Anastomosis, Surgical↗

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases.

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100-120 mg/m2, using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5-15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia < 2,000/mm3 in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intra-arterial chemotherapy in patients with unresectable hepatic tumors.

Adult↗

Resected acinar cell carcinoma of the pancreas with tumor thrombus extending into the main portal vein: report of a case.

The incidence of acinar cell carcinoma has been reported to be about 1% of all pancreatic neoplasms, and pancreatic cancer combined with tumor growth extending into the portal vein is a rare condition. We herein report a case of acinar cell carcinoma of the pancreas with a tumor thrombus extending into the main portal trunk. Preoperative imaging of the portal vein, consisting of computed tomography (CT), magnetic resonance imaging (MRI), and angiography, revealed an oval shadow defect in the main portal trunk along with an irregular mass in the pancreatic head. At operation, we confirmed a tumor thrombus extending from a tumor in the pancreatic head into the main portal trunk via the pancreatoduodenal veins. A pancreatoduodenectomy combined with partial resection of the portal vein was thus performed under a temporary portal vein shunt from the ileocecal vein to the umbilical vein. Immunohistochemical examination for alpha 1-antichimotrypsin and electron microscopic examination confirmed the diagnosis of acinar cell carcinoma of the pancreas with a tumor thrombus in the portal vein. Surgical excision combined with portal vein resection may therefore improve the prognosis of selected patients with portal tumor thrombus.

Carcinoma, Acinar Cell↗

Centrifugal pump-assisted venous bypass between the superior mesenteric vein and the umbilical vein during portal vein resection.

We describe herein our method of performing centrifugal pump-assisted venous bypass between the superior mesenteric vein and the umbilical vein, developed with the aim of preventing congestion of the small intestine and promoting strong and constant hepatic blood flow during portal vein resection. By using this bypass method, portal vein resection and reconstruction was able to be carried out with ease and safety in six patients undergoing surgery for a pancreatic mass or cancer. No coagulation abnormalities, thrombocytopenia, leukocytopenia, severe liver dysfunction, or portal vein thrombosis developed in any of the patients postoperatively. Thus, we highly recommend this simple and reliable method of bypass when portal vein resection is being performed.

Carcinoma, Acinar Cell↗

The correlation of Ki-67 staining indices with tumour doubling times in regrowing non-functioning pituitary adenomas.

In order to improve our ability to predict the regrowth of nonfunctioning pituitary adenomas, we tried to assess the correlation between growth fractions with Ki-67 and PCNA (proliferating cell nuclear antigen) and tumour doubling times in regrowing tumours, and also to find out any difference of growth fractions between the regrowing and the cured cases. In 33 patients with non-functioning pituitary adenomas, 14 cases including 11 with cavernous sinus invasion showed residual tumour on MRI after the operation (regrowing group) and 19 cases had no tumour regrowth on MRI within 5 years after the operation (cured group). Immunocytochemical studies were done with monoclonal antibodies (anti-PCNA, anti-Ki-67: MIB-1). The growth fraction of each tumour was estimated by calculating the ratio of the positive nuclei to the total number of tumour cells with the aid of an image analyser (Mac SCOPE). The tumour doubling times were estimated from serial CT or MRI with the aid of the image analyser (NIH image). Ki-67 staining indices ranged from 0.2% to 1.5% (n = 14, 0.86 +/- 0.10%; mean +/- SEM) in the regrowing group, and from 0.1% to 0.5% (n = 19, 0.23 +/- 0.03%) in the cured group. PCNA staining indices of the regrowing group ranged from 0.6% to 24% (n = 14, 3.7 +/- 1.6%). In the regrowing group, the tumour doubling times ranged from 200 to 2550 days (930 +/- 180 days), and showed a significant inverse correlation with Ki-67 staining indices, but no correlation with PCNA staining indices. The regrowing group showed a significantly higher Ki-67 staining index (n = 14, 0.86 +/- 0.10%) than the cured group (n = 19, 0.23 +/- 0.03%) (p < 0.01). These results indicate that immunocytochemical studies using MIB-1 may be better than those with PCNA for the prediction of regrowth in non-functioning pituitary adenomas. Immunocytochemical study with MIB-1 could lead to the accurate prediction of the rapid regrowing lesions in non-functioning adenomas.

Adenoma↗

Possible involvement of Rab11 p24, a Ras-like small GTP-binding protein, in intracellular vesicular transport of isolated pancreatic acini.

Rab11 p24 is a Ras-like small guanosine triphosphate (GTP)-binding protein, and specific antibodies against it were newly developed to explore its function. Using the antibody, Rab11 p24 was shown to be abundant in rat pancreas as well as in most rat tissues. To explore the involvement of Rab11 p24 into the exocytotic process, the subcellular distribution of Rab11 p24 in rat pancreatic acini was evaluated also by use of the antibody. When the isolated acini were incubated with 1 x 10(-10) M cholecystokinin octapeptide (CCK-8) that induced the maximal stimulation, the amount of Rab11 p24 increased in the fractions of plasma membrane and zymogen granules, but decreased in the cytosol fraction. This redistribution was time-dependent and occurred within 1 min after the CCK-8 stimulation and reached a maximal level within 2 min after the stimulation. Moreover, a light microscopic immunolabeling technique on the isolated rat pancreatic acini also revealed that higher immunoreactivity with Rab11 p24 was observed over the zymogen granule membrane under CCK-8 stimulation. The present results indicate that Rab11 p24 is translocated from cytosol to the membrane fraction during stimulation with CCK-8 and suggest that Rab11 p24 is involved in the intracellular vesicular transport of isolated acini.

Animals↗

Characterization of DNA sequences constituting the terminal heterochromatin of the chicken Z chromosome.

Two clones, pCZTH5-8 and pCZTH12-8, were isolated from a female chicken genomic library by screening with sequences obtained from genomic libraries which had been constructed from a terminal region of a single Z chromosome of chicken utilizing laser microbeam irradiation and PCR amplification. Fluorescence in situ hybridization to the mitotic Z chromosome and the lampbrush ZW bivalent of chicken demonstrated that both the cloned sequences are located in the heterochromatic region of the Z chromosome at the end opposite to the pairing region with the W chromosome. The sequences pCZTH-8 and pCZTH12-8 are distributed widely on both the telomeric bow-like loops (TBL) and the region I (short loops region) of the Z lampbrush chromosome. These clones, pCZTH12-8 particularly notably, hybridized also to the TBLs of lampbrush bivalents 1-4 of chicken. Both sequences are transcribed in the lampbrush stage oocytes on the Z chromosome and on other macrobivalents. The subfragment of pCZTH5-8 which hybridizes to the TBLs and the insert of pCZTH12-8 contain regions that are closely similar in sequence. The pCZTH-8 sequence has no internal repeats and may be part of the 24-kb macrosatellite repeating unit that is evident after Nhel digestion of the genomic DNA. A cloned 24-kb unit, pFN-1, does not show significant DNA curvature, but cytosines of its CpG dinucleotides may be highly methylated in vivo. This contrasts with the repeat sequences of the W heterochromatin which not only have highly methylated CpG but are also strongly curved. The 24-kb unit is repeated about 830 times in the diploid genome of a female chicken, suggesting that nearly the entire terminal heterochromatin on the Z chromosome consists of this macrosatellite family. Sequences of the greater part of the pCZTH-8 are restricted to the genus Gallus but the sequence of one subregion which hybridizes to TBLs is present in the genomes of the order Galliformes.

Animals↗

Recovery of post-tetanic and train-of-four responses at the first dorsal interosseous and adductor pollicis muscles in patients receiving vecuronium.

PURPOSE: To compare recovery of accelographical responses to post-tetanic twitch (PTT) and train-of-four (TOF) stimuli obtained at the first dorsal interosseous muscle (DI) with those at the adductor pollicis muscle (AP) after administration of vecuronium 70 micrograms.kg-1. METHODS: Sixty adult patients were randomly assigned to one of four groups: PTT-DI (n = 15), PTT-AP (n = 15), TOF-DI (n = 15), or TOF-AP (n = 15) group. In PTT-DI and PTT-AP groups, responses to PTT were measured accelographically at the DI and at the AP, respectively. In TOF-DI and TOF-AP groups, responses to TOF were measured at the DI and at the AP, respectively. RESULTS: The T1/T0 (T0 = control) was greater in the TOF-DI than in TOF-AP group throughout recovery (P < 0.05), and the T4/T1 was greater in the TOF-DI than in TOF-AP group during the 30-40 min after vecuronium injection (P < 0.05). Time to the return of the first response to PTT (post-tetanic count(1), PTC1) was less in the PTT-DI than in the PTT-AP group (17.7 +/- 4.2 vs 21.7 +/- 5.6 min, mean +/- SD, P = 0.0341). The post-tetanic count PTC (number of single twitch stimuli in response to PTT) was greater in the PTT-DI than in the PTT-AP group during the 10-30 min after vecuronium (P < 0.05). Time to the return of T1 was less in the TOF-DI than in the TOF-AP group (23.1 +/- 6.0 vs 27.6 +/- 4.9 min, P = 0.0334). CONCLUSION: Recovery of responses to PTT and TOF stimuli occurred earlier at the DI than at the AP.

Adult↗

Double burst stimulation2,3: a new stimulating pattern for residual neuromuscular block.

PURPOSE: We present a new stimulating pattern: double burst stimulation2,3 (DBS2,3) for evaluating residual neuromuscular block. METHODS: Forty adult patients were studied. For DBS2,3, two burst stimuli were applied every 750 msec. The first consisted of two tetanic stimuli of 0.2 msec duration and the second of three tetanic stimuli of 0.2 msec duration. At varying degrees of neuromuscular block induced by vecuronium, the presence or absence of fade, or the presence or absence of waxing (i.e., the feeling that the muscular contraction in response to the second burst was stronger than that to the first) was determined by an observer blinded to the depth of neuromuscular block. In addition, the relationship between the train-of-four (TOF) ratio and DBS2,3 ratio was established at varying depths of neuromuscular block (TOF ratio 0.04-1.00). RESULTS: The probabilities of tactile detection of fade in response to DBS2,3 were 100, 76, 15, 9, 3, 0, and 0% at a TOF ratio of 0-0.40, 0.41-0.50, 0.51-0.60, 0.61-0.70, 0.71-0.80, 0.81-0.90, and 0.91-1.00, respectively. Waxing in response to the DBS2,3 was identified in 0, 6, 32, 84, and 98% of cases when the TOF ratios were 0.00-0.60, 0.61-0.70, 0.71-0.80, 0.81-0.90, and 0.91-1.00, respectively. A close linear relationship existed between the TOF ratio and DBS2,3 ratio (r = 0.96, P < 0.000001). CONCLUSION: DBS2,3 is of clinical use because when residual neuromuscular block is clinically important, fade can be identified, but once neuromuscular function returns to a sufficient level, waxing can be detected.

Adult↗

Resuscitation of ischemically damaged pancreas by the two-layer (University of Wisconsin solution/perfluorochemical) mild hypothermic storage method.

We have shown that 24-hour preservation by a two-layer [University of Wisconsin solution (UW)/perfluorochemical (PFC)] cold storage method at 4 degrees C allowed tissue ATP synthesis and resuscitated canine pancreases subjected to 90 minutes of warm ischemia. The purpose of this study was to examine whether the two-layer (UW/PFC) mild hypothermic storage method at 20 degrees C could shorten a preservation period for recovery of ischemically damaged pancreas and clarify changes of tissue adenine nucleotide metabolism and tissue perfusions. After 90 minutes of warm ischemia, canine pancreas grafts were preserved by the two-layer method and then autotransplanted. Tissue adenine nucleotide levels at the end of preservation and tissue perfusions after reperfusion were measured. Pancreas grafts subjected to 90 minutes of warm ischemia did not survive (0 of 5), without preservation. During a 5-hour preservation by the two-layer cold storage method the grafts did not synthesize enough ATP to repair damaged cell, although tissue perfusions were maintained after reperfusion. Consequently, ischemically damaged pancreases were not resuscitated (0 of 3). However, during 5-hour preservation by the two-layer mild hypothermic storage method, the grafts supplied enough ATP for processes that repair damaged cells, and tissue perfusions were maintained after reperfusion. As a result, ischemically damaged grafts were resuscitated (5 of 5). We conclude that 5-hour preservation by the two-layer mild hypothermic storage method accelerates ATP synthesis, which is essential for repairing damaged cells and protects the vascular microcirculation. This method can resuscitate ischemically damaged pancreas faster and holds promise for pancreas-kidney transplantation from cardiac arrest donors.

Adenine Nucleotides↗

Inhibition of platelet aggregation by endocardial endothelial cells.

We assessed the anti-platelet properties of endocardial endothelial cells (EECs) by measuring platelet aggregation after brief interaction with EECs isolated from the right ventricles of porcine hearts. Platelet aggregation in response to thrombin was significantly inhibited by brief incubation of platelet suspensions over EEC monolayers. Pretreatment of EECs with indomethacin restored platelet reaction but that with L-NAME and hemoglobin (Hb) did not. The PGI2 content of platelet suspensions after interaction with cultured EECs was significantly correlated with the inhibition of platelet aggregation. These results suggest that EECs inhibit platelet aggregation by releasing PGI2.

Animals↗

Immunocytochemical localization of heme oxygenase-2 in the rat cerebellum.

Carbon monoxide (CO) is a gas that can permeate biological membranes and it has been suggested that the gas plays a signaling role in the brain by activating soluble guanylyl cyclase (sGC). CO is generated by heme oxygenase during the conversion of heme to biliverdin. In this study, we raised an antiserum against the chemically synthesized amino-terminal fragment of heme oxygenase-2 (HO-2) and studied the distribution of this enzyme in the rat cerebellum by an immunocytochemical method. Immunoreactivity specific for HO-2 was observed only in neurons. In the Purkinje cells and the basket cells of the cerebellum, immunoreactivity was detected in the dendrites and the somata but not in the axon terminals, suggesting that CO might be liberated primarily from the dendrites and somata rather than from the axons in this region of the rat brain.

Amino Acid Sequence↗

Successful 14-day preservation of rat skin using a two-layer cold-storage method.

Skin-graft preservation for the purpose of delayed autografting to burn patients is a basic tool of plastic and burn surgery. This study was undertaken to evaluate the efficacy of the two-layer (physiological saline/perfluorochemical (PFC)) cold-storage method for skin preservation. In Wistar rats, a full-thickness skin graft, 3 cm in diameter, was harvested from the back, and separated from the dermis to obtain the epidermal sheet. This epidermal sheet was preserved at 4 degrees C using physiological saline (group 1, n = 15), physiological saline bubbled with a 95 per cent oxygen, 5 per cent carbon dioxide mixture (group 2, n = 15) or a two-layer method with bubbling with 95 per cent oxygen and 5 per cent carbon dioxide mixture (group 3, n = 15). The epidermal skin sheets were then autotransplanted to the backs of the original donor rats 7, 10 and 14 days after the start of preservation. The success rate of the skin autotransplantation was determined by measuring the ratio of viable area to total graft area 7 days after grafting. In group I, the success rates after 7, 10 and 14 days' perservation were 56.4, 47.4 and 0.09 per cent, respectively. In group 2, the corresponding success rates were 62.0, 48.4 and 0.8 per cent respectively, showing no improvement with oxygenated saline. In clear contrast, the success rates were significantly improved by the two-layer method, the values being 92.1, 87.9 and 77.6 per cent after 7, 10 and 14 days of perservation, respectively (P < 0.01 vs. groups 1 and 2 for all preservation durations). Based on these results, we concluded that the two-layer method is useful for not only improving the quality of the skin graft but also extending the preservation time of the skin graft up to 14 days.

Animals↗

In vivo effects of various therapies on complement-sensitive erythrocytes in paroxysmal nocturnal hemoglobinuria.

The percentage of complement-sensitive erythrocytes varies among patients with paroxysmal nocturnal hemoglobinuria (PNH) and is related to disease severity. We examined the changes of complement-sensitive erythrocytes following administration of androgens, prednisolone, dextran, and iron to 12 PNH patients using the complement lysis sensitivity test or flow cytometric analysis of decay accelerating factor and CD59/membrane attack complex-inhibitory factor expression for 11 years. Five untreated PNH patients were also studied as a control group. The complement-sensitive erythrocyte count remained almost constant in the control group, while it increased in four out of five patients receiving androgens. In addition, it decreased in two out of three patients receiving prednisolone, increased in both patients treated with dextran, and increased slightly in two of the three patients receiving iron therapy. Episodes of hemoglobinuria increased in three of the nine patients showing an increase of complement-sensitive erythrocytes, and decreased in four patients receiving prednisolone or dextran. A good response to treatment was clinically observed in four patients receiving androgens, in one patient treated with prednisolone, and in one patient receiving dextran according to the scoring system. These findings suggest that PNH remains stable when the number of complement-sensitive erythrocytes remains fairly constant, and that the PNH III erythrocyte count is especially related to the frequency of hemoglobinuria. Thus, it seems to be important to determine the long-term effect of drug therapy on complement-sensitive erythrocytes to select the most appropriate treatment.

Adolescent↗

Efficacy of high-frequency ultrasound probes for the preoperative staging of invasion depth in flat and depressed colorectal tumors.

BACKGROUND: Flat and depressed nonpolypoid types of colorectal tumors have drawn much attention. Since endoscopic mucosal resection technique is available, it is of great importance to distinguish intramucosal carcinoma from invasive carcinoma because determination of the invasion depth is essential for choosing this therapy. The usefulness of high-frequency (20 MHz) ultrasound probes for preoperative staging of invasion depth in this type of colorectal tumor was evaluated. METHODS: Forty-nine cases of flat and depressed tumors were examined with the ultrasound probe and diagnostic accuracy was confirmed by comparing ultrasonic images with the pathologic findings of the specimens resected either by endoscopic mucosal resection or surgical operation. RESULTS: The normal colonic wall was visualized as a nine-layered structure and the muscularis mucosae was depicted in 37 (76%) of 49 cases. Flat and depressed tumors were visualized as hypoechoic lesions and the invasion depth was accurately diagnosed in 43 (88%) of 49 lesions. CONCLUSIONS: High-frequency ultrasound probes proved to be useful in determining the invasion depth and therapeutic strategy in flat and depressed colorectal tumors.

Adenoma↗