Isolation of a rapidly labelled RNA fraction from calf thymus nuclei.
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Biomedical subjects
Publications and source records attributed to T Morimoto.
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Liver mitochondrial membrane potential was assessed during regeneration following partial hepatectomy in rabbits. Absorbance change of safranine O per milligram of mitochondrial protein was used to evaluate mitochondrial membrane potential. Absorbance change was calibrated to the membrane potential in millivolts produced by valinomycin-induced potassium diffusion potential. At 24 hr after hepatectomy, absorbance change of safranine O per milligram of mitochondrial protein increased from 15.0 +/- 2.2 X 10(-3) to 37.4 +/- 3.3 X 10(-3) per mg (p less than 0.005). This represents a mitochondrial membrane potential increase from 77.0 +/- 4.6 to 124.4 +/- 6.7 mV. Phosphorylative activity increased from 59.9 +/- 5.0 to 106.1 +/- 7.4 nmoles ATP synthesized per mg per min (p less than 0.005). The enhancement of phosphorylative activity was closely linked to the elevation in liver mitochondrial membrane potential (r = 0.77, p less than 0.005). We suggest that elevation of mitochondrial membrane potential, coupled with enhanced oxidative and phosphorylative activities, plays an important role in the regeneration process following hepatectomy.
Impaired glucose tolerance is a serious obstacle to major hepatic resection. To assess the predictability of surgical risk in major hepatectomy for patients with chronic liver diseases from the viewpoint of glucose metabolism, we evaluated the insulinogenic index (II) and redox tolerance index (RTI) in 48 patients who underwent major hepatectomy at our university hospital due to hepatocellular carcinoma. Patients with low II and low RTI fell into the high risk group. Based on this finding, the Z score was developed as an index of patient risk for major hepatectomy: Z = 3.11 x [II] + 1.43 x [RTI] - 2.27. When the Z score was negative, mortality reached 33.3%, but when it was positive the mortality was only 3.2%. Intraportal insulin supplementation after hepatectomy to patients with a negative Z score could reduce mortality. Preoperative evaluation of surgical risk by Z score seems to be useful for predicting patient prognosis after hepatectomy.
Since the tumor thrombus in the main portal vein appears in the terminal stage of hepatocellular carcinoma (HCC), any attempt to remove it surgically is thought to be impractical as the malignancy itself cannot be entirely removed. During the past 5 years, we have performed tumor thrombectomy combined with hepatectomy in 29 of 298 patients with HCC. This combined therapy was initially decided upon as an emergency measure to prevent impending rupture of esophageal varices, rather than to improve patient survival. Since portal flow was obtained after removal of thrombi, this condition enabled transcatheter arterial embolization (TAE) and/or percutaneous ethanol injection therapy (PEIT). Although improved patient survival was not the primary goal of the emergency operation and there was an operative mortality of 11%, half of the other patients in the present series had unexpectedly high survival rates of 1 year (52.2%), 2 years (23.2%), and 3 years (11.6%), which were significantly higher than in patients not undergoing operation (n = 22).
Of the 2790 patients with gastric carcinoma who underwent surgery between January 1978 and December 1993, there were 224 who underwent a D2 resection for cancer of the proximal third of the stomach. Survival in these patients was retrospectively analyzed with special reference to the survival benefit of pancreaticosplenectomy (PS). The D2 resection involved a splenectomy in 129 patients, a PS in 38 patients, and neither in 57 patients, with 5-year survivals of 74%, 59%, and 91%, respectively. Although these differences in survival were attributable to the apparent deviation in the incidence of prognostic variables, no significant survival benefit of PS was observed for patients with the same clinical stage disease (stages II and III) or the same modal status (n1 and n2). Because PS was associated with a significant increase in the incidence of anastomotic dehiscence and length of hospital stay, the dismal survival benefit implies that it should not be performed routinely with the D2 resection but should be employed only for lesions with direct invasion of the pancreas.
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PURPOSE: To investigate the effects of transjugular intrahepatic portosystemic shunt (TIPS) on hepatic metabolic function by measuring serial arterial ketone body ratio (acetoacetate/-hydroxybutyrate; AKBR). MATERIAL AND METHODS: The arterial blood of 30 TIPS patients was assayed before TIPS, 30 minutes after TIPS, and 24 hours after TIPS for acetoacetate, beta-hydroxybutyrate, and glucose. The authors compared the AKBR values to clinical outcome stratified by Child class, emergent versus elective TIPS, and before-TIPS AKBR value < or = 0.5 versus before-TIPS AKBR value > 0.5. RESULTS: A significant change was noted between the AKBR values obtained before TIPS and values 30 minutes after TIPS (0.76 +/- 0.09 vs 0.61 +/- 0.05, P < .05) and between 30 minutes and 24 hours after TIPS (0.81 +/- 0.10, P < .001), but not between the value obtained before TIPS and that obtained 24 hours after TIPS. The 30-day mortality rate in emergency TIPS patients was 50% compared to 7% in the elective TIPS patients (P < .01). The pre-TIPS AKBR values were significantly suppressed in the emergency TIPS patients compared to the elective TIPS patients (0.56 +/- 0.04 vs 0.99 +/- 0.17, P < .005). The 30-day mortality rate in patients with a pre-TIPS AKBR value < or = 0.5 was 75%, which was significantly higher than the 14% rate in patients with a pre-TIPS AKBR value > 0.5 (P < .01). CONCLUSION: A low pre-TIPS AKBR may be predictive of poor outcome after TIPS. Furthermore, AKBR may be of value in determining the timing for performing an elective TIPS.
Changes in the protein C-thrombomodulin (PC-TM) system in relation to other coagulofibrinolytic parameters were examined in 25 patients undergoing open heart surgery. Although all patients were given heparin, a decrease in antithrombin III (ATIII) and progressive increase in thrombin-ATIII complex (TAT) and fibrinopeptide A (FPA) levels were noted during cardiopulmonary bypass, which indicated that heparinization did not completely inhibit the formation of thrombin and its function. C1-inactivator (INA) resistant fibrinolytic activity increased markedly during CPB, in parallel with the change of tissue plasminogen activator antigen (t-PA;Ag), which indicates that fibrinolytic activity during CPB is mainly of extrinsic origin caused by t-PA. Protein C antigen (PC;Ag), protein S antigen (PS;Ag), and thrombomodulin antigen (TM;Ag) were all decreased significantly during CPB. This is considered to reflect the activation and consumption of the PC-TM system in response to generated thrombin. Furthermore, enhancement of the extrinsic fibrinolytic system is easily explained by the action of activated PC, which counteracts plasminogen activator inhibitor (PAI-1), to cause enhancement of t-PA activity.
Three noninvasive imaging methods, CT, scintigraphy with 201TlCl and 99mTcO4-, and ultrasonography, were performed on 36 patients with chronic renal failure and secondary hyperparathyroidism. The patients subsequently underwent total parathyroidectomy and parathyroid autograft. The detection rates of the three methods for the 143 excised parathyroid glands were compared according to gland weight and location. Computed tomography detected 53.8% of all glands and 77.6% of 76 glands weighing more than 500 mg. Scintigraphy detected 51.0% of all glands and 77.6% of glands heavier than 500 mg. Ultrasonography detected 42.7% of all glands and 65.8% of glands heavier than 500 mg. The detection rate of upper glands was best with CT (53.5 and 87.9%): that of lower glands was best with scintigraphy (62.0 and 78.6%). Although the combination of the three methods diagnosed 66.4% of all glands and 89.5% of glands heavier than 500 mg, CT and scintigraphy, the best two combinations, visualized 64.3 and 88.2%.
We describe a patient with epilepsy characterized by eyelid myoclonus, which often evolved into complex partial seizures, hemiconvulsions, or generalized convulsions. The outstanding feature was that seizures became markedly more frequent on exposure to light, movement in daily life, and hot water immersion. The patient was highly susceptible to seizures under constant light, but the dopamine level in the cerebrospinal fluid was quite low, and administration of levodopa transiently suppressed the seizures.
The behavior and EEG of rat hyperthermic convulsions was studied. We found that a long run of high-voltage slow waves without convulsions, high-voltage irregular activity consisting of spikes and waves with intermittent myoclonus, and rapid spike and wave bursts accompanied by generalized clonic convulsions occurred sequentially. This behavioral and EEG activity is analogous to human febrile convulsions and supports the usefulness of this model for studies of human febrile convulsions. Rats frequently showed arrest of locomotion concurrently with paroxysmal EEG theta bursts before development of generalized convulsions. We speculate that this paroxysmal activity is a type of seizure discharge.
Hyperthermia induces seizures in both humans and rodents, but the underlying mechanism remains unknown. The present study showed that hyperthermia, causing rapid increase in body temperature, increases the concentration of glutamate (Glu) released into a cortical perfusate before onset of seizures in rats and that this increase in Glu concentration correlated with a decrease in seizure threshold temperature. These results indicate that increased cortical extracellular Glu induced by hyperthermia contributes to onset of seizures. The same mechanism may be involved in clinical seizures induced by fever in patients with febrile convulsions or epilepsy.
The authors report 11 cases who underwent reoperations upon for recurrent aneurysms. The initial operations were performed on average 10.1 years earlier for subarachnoid hemorrhage (SAH). The patients' mean age at the first surgery was 39.7 years. The locations were 9 internal carotid (IC)-posterior communicating artery (PC) and 2 anterior communicating artery (A-com) aneurysms. A residual aneurysmal neck after the first operation was observed in 3 of 10 cases confirmed by postoperative angiography. The primitive-type PC artery was seen in 8 of 9 recurrent IC-PC aneurysms. The recurrent manifestations were SAH in 9 cases. Clipping operations were conducted in 10 and ligation of the IC artery together with extracranial-intracranial bypass in 1 large IC-PC aneurysm. The present study demonstrated two risk factors for aneurysm recurrence, namely, young age and IC-PC aneurysms with a primitive-type PC. Furthermore, direct operation for recurrent aneurysm is often embarrassing due to adhesions to the surrounding tissue as a sequela of the previous operation, hence understanding of the anatomical correlation between the old clip and the recurrent portion is important.
Total parenteral nutrition (TPN) is known to induce mucosal atrophy and to increase macromolecular transmission of the small intestine. The potential participation of various proteases in that process was investigated. Male Wistar rats were randomly divided into two groups: the TPN group (n = 11) received a standard TPN (250 kcal/kg per day, 1.78 g nitrogen/kg per day) and the FED group (n = 10) received a standard rat food for 1 week. This was followed by an examination of gut macromolecular transmission of fluorescein isothiocyanate dextran 70,000 (FITC-dextran) after intragastric injection and of the activities of gut mucosal cathepsins B, H, and L and of proteasome. Mucosal wet weight and protein content decreased significantly by TPN for 1 week. In both groups, the activities of all proteases in the ileum were significantly greater than in the jejunum. In the TPN group, cathepsin L and H activities in the ileum, and cathepsin B activity in both the jejunum and the ileum, were greater than those in the FED group. The portal concentration of FITC-dextran was higher than arterial and venous concentrations in the both groups. In the TPN group, the portal FITC-dextran concentration increased significantly compared with the FED group. In conclusion, active proteolysis is not associated with TPN-induced mucosal atrophy. Cathepsins activities in the ileum increase as a result of TPN. Interrelationship is implicated between increase of lysosomal protease activity and the deterioration of the intestinal barrier function, which permits macromolecular transmission.
BACKGROUND: We have previously reported that the addition of nucleosides and a nucleotide mixture (OG-VI) to total parenteral nutrition (TPN) prevents TPN-induced intestinal mucosal atrophy and results in increased intestinal cathepsin activities under TPN. The aims of the present study are to examine the effects of OG-VI on mucosal barrier functions and to clarify whether the intestinal cathepsins can be used as a new marker of mucosal barrier function. METHODS: Male Wistar rats were divided into three groups: FED (food ad libitum), TPN (a standard TPN solution), and OG (OG-VI in addition to the TPN solution). Mucosal barrier functions were analyzed by the lactulose/mannitol (L/M) test, mucosal ZO-1 messenger RNA level, and electron micrographs in the gut. Intestinal cathepsin B, H, and L activities were also measured. RESULTS: The L/M ratio for TPN was much higher than that for FED. Only lactulose excretion was significantly reduced by OG-VI. The intercellular spaces of the mucosal cells for TPN were significantly wider than those for FED, but were reduced in size by the addition of OG-VI. All cathepsin activities of the ileum were higher for TPN than for FED, whereas OG showed no increase. CONCLUSION: OG-VI contributes to the improvement of gut mucosal barrier function. Intestinal cathepsin activities can be used as a new marker of mucosal barrier function.
Effects of cinnarizine on immune response in mice were investigated. Mice were orally administered with cinnarizine and were immunized with sheep red blood cells (SRBC) intravenously. Numbers of plaque forming cells (PFC) to SRBC in spleen of these mice were assayed and delayed-type hypersensitivity (DTH) response to SRBC was measured. 1) PFC response in immunization with 5 X 10(6) cells/mouse of SRBC was enhanced by administration of 25 mg/kg of cinnarizine, while the response in immunization with 5 X 10(8) cells/mouse was suppressed by 25 to 200 mg/kg of cinnarizine. 2) From study on timing of administration, suppression of PFC response by 6.25 to 200 mg/kg of cinnarizine was observed at 24 hr. after the immunization. 3) 12.5 to 200 mg/kg of cinnarizine suppressed polyclonal B cell activation induced by lipopolysaccharide (LPS). 4) Colchicine induced suppressor T cell inactivation was prevented by administration of 50 mg/kg of cinnarizine and it was suggested that cinnarizine may induce suppressor T cells from the study of adoptive cell transfer system. 5) 50 mg/kg of cinnarizine showed the suppression of DTH response in expression phase, but not in induction phase. It was concluded that immune responses in mice were modified by cinnarizine.
A new system of impedance measurement over a frequency range of 0 to 200 kHz was developed by a three-electrode method. In this study, the electrical impedances of various tumors were measured in vivo in 54 patients with breast disease (31 breast cancers, 13 fibroadenomas, and 10 fibrocystic diseases) and 57 patients with pulmonary disease (44 lung cancers, 5 metastatic pulmonary tumors, 4 pulmonary tuberculoses, and 4 organized pneumonias). On the basis of those impedance measurements and the equivalent circuits in vivo, we calculated the extracellular resistance (Re), intracellular fluid resistance (Ri), and cell membrane capacitance (Cm) in tissues, all of which were compared among the various diseases. It was found that Re and Ri were significantly higher in breast cancers than in benign tumors and normal breast tissues and that Cm was significantly lower in breast cancers than in other tissues. On the other hand, Re and Ri were significantly higher, and Cm was significantly lower, in normal lung tissues than in pulmonary masses. Re and Ri were significantly higher, and Cm was significantly lower, in malignant tumors than in organized pneumonias. The results showed that these parameters (Re, Ri, and Cm) exhibit significant differences among various tissues and tumors, suggesting possible applications in tumor diagnosis.
The relationship between human papillomavirus (HPV) infection and breast cancer is controversial. In this study, paraffin-embedded tissue blocks prepared from 72 patients with benign, premalignant or malignant mammary lesions were randomly collected from the Shanghai region of China and Tokushima in Japan. DNA specimens extracted from all tissues were amplified by the polymerase chain reaction (PCR) using HPV16, 18 and 33 primers. Southern blot hybridization showed 19 cases to be positive for HPV33 DNA: The positive rate for HPV33 DNA in Chinese (41.7%) was significantly higher than in Japanese (11.1%) (P < 0.01): The positive rate for HPV33 DNA in invasive ductal carcinoma (34.1%) was higher than in benign or borderline mammary lesions (5%) (P < 0.02). There were no statistically significant difference among the relationship of the nuclear grade of breast cancers with HPV33 DNA-positivity. This is the first report of a positive correlation between HPV33 DNA and breast lesions in Chinese and Japanese populations. These results suggest that the infection by HPV33, but not HPV 16 or HPV 18, may be involved in breast hyperplastic lesions, especially breast cancer, in humans.