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Biomedical subjects

H Akimoto

Publications and source records attributed to H Akimoto.

At least 181 records · Page 10Linked to original sources

Possible processing of mitochondria-bindable hexokinase to the nonbindable form by a lysosomal protease in rat liver.

As a possible mechanism for the absence of mitochondria-bindable hexokinase in the liver, the presence of a protease similar in action to chymotrypsin, which specifically eliminates the binding ability of the bindable hexokinase without changing its catalytic properties, was investigated in rat liver. The lysosomal fraction prepared from the liver converted the bindable hexokinase prepared from rat brain to the nonbindable form with little change in catalytic activity. The activity of such a "processing protease" was much lower in rat brain, where the bindable form is predominant. The processing activity cosedimented with lysosomal marker enzyme activities in the subcellular fractionation of livers from normal and Triton WR-1339-injected rats. A fair portion of the activity was detected in the lysosomes without disruption. The activity was maximal at pH 6.0-7.0, inactivated almost completely by tosylphenylalanine chloromethyl ketone, tosyllysine chloromethyl ketone, leupeptin, antipain, and chymostatin, and dependent on dithiothreitol and mercaptoethanol. These results suggest that a protease, properties of which are fairly similar to those of cathepsin M, may be involved in the post-translational processing of original bindable hexokinase to the nonbindable form in rat liver.

Animals↗

Queuine analogues. Their synthesis and inhibition of growth of mouse L5178Y cells in vitro.

A variety of analogues of queuine (7-[(3S,4R,5S)-4,5-dihydroxycyclopent-1-en-3-ylaminomethyl]- 7 -deazaguanine), i.e., those with 7-N-substituted aminomethyl side chains and those in which the oxygen function at the 6 position of the 7-deazaguanine ring was replaced by sulfur, were synthesized and tested for ability to act as substrates for tRNA-guanine transglycosylase and for inhibitory effects on growth of mouse L5178Y leukemic cells in vitro. Of the compounds tested, analogues with sulfur at the 6 position of the 7-deazaguanine ring in place of oxygen or with an N-o-hydroxyphenyl, N-m-hydroxyphenyl, or iodoacetyl group in the 7-aminomethyl side chain in place of the naturally occurring cyclopentene diol moiety markedly inhibited the growth of cells at concentrations of 1-10 micrograms/mL, although queuine itself had practically no effect at a concentration of 100 micrograms/mL.

Animals↗

[Multidisciplinary therapy of hepatocellular carcinoma--TAI. TAE treatment by intra-arterial catheterization].

Two hundred sixty-six cases of hepatocellular carcinoma (HCC) were treated between June 1980 and October 1985 (4 years and 4 months) at our hospital. Hepatectomy was performed in 118 patients, 82 of which had received transcatheter arterial embolization with iodized oil (Lipiodol) 58 of then with an intraarterial catheter. HCC tumors were often multiple when they were combined with liver cirrhosis and smaller than 3 cm in diameter. For this reason treatment of HCC by surgery alone has limitations for prolongation of life. A multidisciplinary treatment is therefore necessary. We have found hepatectomy and transarterial embolization to be the most effective treatment for HCC. In order to perform repeated embolizations after hepatectomy, we developed a heparinized catheter with notches to permit safe fixation. This is suitable for long-term intraarterial use. While previous arterial catheters only permitted infusion of drugs due to their small diameters, our new catheter can be used for embolizations with Lipiodol and Gelfoam and for angiography. It is inserted through the right gastroepiploic artery into the gastroduodenal artery so that its tip lies at the level of the hepatic artery. It is brought out through the abdominal skin and flushed at two-week intervals with heparin-urokinase. The indications for the use of the catheter have been repeated embolizations 1) for prevention of tumor recurrence (surgical adjuvant therapy), and 2) after absolutely non-curative operations. For the first indication, we have found that multiple tumors and tumors larger than 5 cm frequently recur within 1 year after surgery. We have, since July 1983, used the catheter treatment to prevent recurrence in 30 such cases. Embolization with Lipiodol + Adriamycin followed by Gelfoam cubes is performed at three-month intervals for one year after surgery, starting one month after surgery, as a rule. The preliminary results indicate an improved survival rate after the treatment.

Aged↗

Selective portal branch occlusion by balloon catheter during liver resection.

An intraoperative ultrasonographically guided introduction of a balloon catheter into labor or smaller branches of the portal vein within the liver parenchyma made it possible to temporarily occlude them and perform regional staining during resection for tumors. The technique minimized blood loss without hilar dissection for vascular control, and the presence of the catheter facilitated intraparenchymal dissection of the portal stalk to the part of the liver to be resected.

Carcinoma, Hepatocellular↗

Effect of chemical sympathectomy with oxidopamine on systemic blood flow in rats with acute pancreatitis.

In response to previous demonstrations that either surgical or chemical sympathectomy can ameliorate the severity of acute experimental pancreatitis, and suggestions that the benefits of sympathectomy are related to alterations in the absolute blood flow or the pattern of blood flow within the pancreas or splanchnic organs, we studied blood flow in rats with acute deoxycholate pancreatitis. The animals had preliminary chemical sympathectomy with a false neurotransmitter (oxidopamine) prior to the experiment and were studied for 120 min after the onset of pancreatitis. All animals with pancreatitis had a fall in cardiac output by 120 min but maintained blood flow to the heart and brain by increasing the percent of cardiac output to these organs. Despite a 61% decrease in cardiac output, at 120 min the chemical sympathectomy group showed an increase in the percentage of flow within the pancreas. However, there was no change in the absolute organ blood flow in any group except at the 10 min measurement, when the pancreata showed an absolute increase in all groups. This study does not support the concept that chemical sympathectomy is beneficial in acute pancreatitis but does indicate a specific and possibly beneficial effect on the distribution of pancreatic blood flow. The decreased cardiac output after chemical sympathectomy is a clear disadvantage of this mode of treatment and probably disqualifies systemic chemical sympathectomy as a treatment consideration.

Acute Disease↗

Stimulated protein kinase activity during acute pancreatitis in rats. Possible mediation by proteolysis, lipolysis, and bile salts.

The rate of protein phosphorylation, as catalyzed by the protein kinase enzymes, was measured in the pancreas of rats with acute experimental pancreatitis. Two different methods were used to induce pancreatitis in rats: retrograde injection of deoxycholate (DOC) into the pancreatic duct, or daily intravenous administration of DL-ethionine. Basal protein kinase activity was elevated in rats with acute experimental pancreatitis. This increase in activity was not dependent on free Ca2+ and did not result from elevated cAMP levels. To assess the possible role of digestive enzymes in protein kinase activation, tissue extracts from healthy controls were subjected to mild treatment with digestive enzymes and DOC. Trypsin, chymotrypsin, phospholipase A, and DOC produced protein kinase activation of a similar magnitude as found in diseased tissue. Results indicate that stimulated protein kinase activity in tissue of animals with acute pancreatitis may arise from the action of digestive enzymes.

Acute Disease↗

Monoclonal antibodies to queuine.

Monoclonal antibodies specific for queuine have been prepared. Synthetic 9-(5-carboxypentyl)queuine (cp9Q) was conjugated with bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH), and the conjugate was used to immunize BALB/c mice by intraperitoneal and subcutaneous injection. Monoclonal antibodies were subsequently obtained by fusion of spleen cells and the mouse myeloma cell line X63Ag8U1. An enzyme-linked immunoabsorbent assay (ELISA) using o-phenylenediamine as peroxidase substrate was used for screening of clones and characterization of antibodies. Inhibition experiments with various homologous nucleosides revealed that the monoclonal antibody designated as 2D8E6 has no cross-reactivity with guanosine, adenosine or 7-methylguanosine.

Animals↗

Vasoactive drugs in acute pancreatitis.

Experimental evidence has shown that pancreatic blood flow is severely diminished during acute pancreatitis, but it is unclear whether a decrease in blood flow is a critical event in the evolution of complications of this disease. When an episode of edematous pancreatitis is complicated by necrosis of part of the gland, there is a risk of both acute and chronic complications, including sepsis, hemorrhage, and abscess. One of the questions that remains is whether the decreases in blood flow alluded to are primary or secondary causes. If primary, treatments that preserve pancreatic blood flow during pancreatitis might have a salutary effect on observed morbidity and mortality. This study determined whether two vasoactive drugs, oxidopamine (6-hydroxydopamine) and dihydroergotamine tartrate, given prior to experimentally induced pancreatitis in rats, affected observed mortality. After oxidopamine treatment, rats had a higher survival rate and greater pancreatic blood flow than untreated controls. The association of greater pancreatic blood flow and reduced mortality did not exclude other possible effects of oxidopamine treatment but was consistent with the hypothesis that vasoactive therapy may have a role in this disease.

Acute Disease↗

Perspective on extra-gastric vagal fibers: should they be preserved when possible?

A number of discoveries have forced both basic scientists and practitioners of medicine to reinterpret their view of the relation of the autonomic nervous system, the brain, and the gastrointestinal tract. There is growing support for the concept of an autonomous enteric nervous system, one which has many participant and regulatory peptide neurotransmitters, but which can apparently function independently of certain afferent or efferent (vagal) connections to the central nervous system. Recognizing the possibility that extra-gastric vagus nerves may serve an essential role in physiologic functions, it is logical to support the concept that these nerves be preserved when possible. Whether operations which spare extra-gastric vagal nerves will pass the test of time remains to be seen.

Autonomic Nervous System↗