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Biomedical subjects

H Akimoto

Publications and source records attributed to H Akimoto.

At least 163 records · Page 9Linked to original sources

[Result of surgical treatment of true or dissected thoracic aneurysm: determinants analysis in operative mortality and morbidity].

Between 1986 and 1990, 69 patients underwent surgery either for thoracic aneurysm (27 patients) or aortic dissection (42 patients). Sixty one patients (88%) survived and 8 patients (12%) died after surgery. Main determinants of deaths in 4 patients with true arch aneurysm were bleeding from the sites of aortic clamping or anastomosis and intraoperative severe LOS. Three patients with acute type A dissection died from bleeding due to clamp injury or myocardial ischemia. The cause of death in the patient with chronic type B dissection was associated with brain damage due to hypoxia developed during left heart bypass. Postoperative cardiac, pulmonary, hepatic and renal functions were analyzed in the operative survivors. Cardiac functions were maintained well in all patients except two patients with chronic type A dissection. Four patients, one with true arch aneurysm, 2 with chronic type A and one with chronic type B dissection, required tracheostomy. The mean of maximum total serum bilirubin exceeded 4 mg/dl in the patients with true arch aneurysm, acute and chronic type A dissection. The level of serum creatinine showed slight increase in all patients but prophylactic peritoneal dialysis was performed in one patient with chronic type A dissection. In conclusion, the cause of deaths in most patients with thoracic aneurysm was due to inappropriate operative techniques and circulatory supports during surgery. Without the complication described above, the patients could tolerate surgery well.

Aged↗

[Postoperative respiratory dysfunction in patients with Stanford type A aortic dissection].

Between 1986 and 1990, 24 patients with Stanford type A dissection (acute; 14, chronic; 10) underwent surgery through median sternotomy. The patients were divided into two groups by a duration of postoperative ICU stay for respiratory care. Six patients in the long-period group stayed in ICU for more than 15 days and 18 patients in the short-period group stayed for less than 15 days after surgery. Acuity of disease, age, sex, operation time, pump time, aortic clamp time, lowest esophageal temperature, amount of blood transfusion, arch manipulation for cerebral perfusion with or without arch reconstruction, occurrence of phrenic nerve palsy and other postoperative complications, postoperative cardiac, hepatic and renal functions were compared between two groups. Conclusions are as follows: 1) Arch manipulation for cerebral perfusion with or without arch reconstruction, phrenic nerve palsy, other complications (pericardial and pleural fluid accumulation, recurrent nerve palsy, postoperative bleeding and coronary spasm) and high serum creatinine level were main factors for prolonged postoperative ICU stay for respiratory care and 2) arch manipulation in the patients with chronic type A aortic dissection induced high incidence of phrenic nerve palsy.

Adult↗

Induction of differentiation of human myeloid leukemia HL-60 cells by novel nonphosphorus alkyl ether lipids.

We synthesized a new series of nonphosphorus alkyl ether glycerolipids, in which the 2-acetyl group of platelet-activating factor was replaced by a pyrimidin-2-yl group and the 3-phosphocholine portion by an omega-(substituted ammonio)ethoxyethyl side-chain including omega-thiazolio-, imidazolio- and pyridinio groups with or without a carboxyl substituent, respectively (compound I-XI). Their effects on cell proliferation and differentiation of human myeloid leukemia HL-60 cells were examined. Incubation of HL-60 cells with these cationic and zwitterionic alkyl ether lipids inhibited proliferation of HL-60 cells with IC50 values ranging from 10 to 500 ng/mL. The cells were induced by the lipids to differentiate into morphologically and functionally mature granulocytes. Among the compounds we tested, 1-octadecyl-2-pyrimidinyl-3-[3-(5- carboxylatepentyl)imidazolioethoxyethyl]glycerol (compound I) was the most effective in inducing differentiation of HL-60 cells. Compound I showed on a molar basis, an inhibitory effect on the leukemic cells over 50 times greater than did 2-(2-dodecyloxyethoxy)ethyl 2-pyridinio-ethyl phosphate, the antileukemic alkyl ether phospholipid.

Antineoplastic Agents↗

Evaluation of mRNA levels by the polymerase chain reaction in small cardiac tissue samples.

Doxurubicin is an effective and widely used chemotherapeutic agent. However, use of this drug is often limited by its cardiotoxic side effects. We have observed that an early event accompanying doxorubicin cardiomyopathy is a selective decrease in levels of muscle gene transcripts in cardiac tissue (Ito et al., Proc. Natl. Acad. Sci. USA 87: 4275-4279). Since this decrease precedes ultrastructural evidence of cardiac damage, measurements of muscle transcripts might assist in the clinical evaluation of doxorubicin cardiotoxicity. We have therefore assessed the utility of the polymerase chain reaction in the measurement of mRNA in control and doxorubicin-treated animals. These measurements were performed on small tissue samples that simulate endomyocardial biopsies. We measured cardiac alpha-actin transcripts as a fraction of ferritin heavy chain transcripts using the method described by Chelly et al. (Nature 333: 858-860, 1988). 0.5 micrograms of total RNA, an amount equivalent to that obtainable from a typical endomyocardial biopsy, was efficiently co-amplified with cardiac alpha-actin and ferritin heavy chain specific primers. The cardiac alpha-actin/ferritin heavy chain ratio calculated from the PCR results correlated well (R = 0.981) with results obtained using Northern blot analysis of 10 micrograms RNA. The correlation was maintained over a wide range of cardiac alpha-actin transcript abundance. These results show that mRNA from cardiac tissue can be estimated by the polymerase chain reaction, even from a small, endomyocardial biopsy-sized sample.

Actins↗

Novel pyrrolo[2,3-d]pyrimidine antifolates: synthesis and antitumor activities.

New antifolates, characterized by a 6-5 fused ring system, a pyrrolo[2,3-d]pyrimidine ring, and a trimethylene bridge at position 5 (12a,b and 13a,b) were designed and efficiently synthesized. The synthetic method included (1) construction of the key intermediary acyclic skeleton, 5-[4-(tert-butoxycarbonyl)phenyl]- 2-(dicyanomethyl)pentanoates (6a,b), (2) cyclization with guanidine, followed by reduction to the pyrrolo[2,3-d]pyrimidine derivatives (8a,b and 9a,b), and (3) subsequent glutamate coupling and saponification. These antifolates were more growth-inhibitory by about 1 order of magnitude than methotrexate (MTX) against KB human epidermoid carcinoma cells and A549 human nonsmall cell lung carcinoma cells in in vitro culture. Growth inhibitory IC50 values for N-[4-[3-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5- yl)propyl]benzoyl]-L-glutamic acid (12a) against KB and A549 were 0.27 and 4.5 ng/mL, while those for MTX were 5.0 and 35 ng/mL, respectively. Other members of this class of antifolates, 12b and 13a,b, showed good activities nearly equal to that of 12a.

Antineoplastic Agents↗

Effects of pirmenol on electrical induction of sustained ventricular tachycardia in a seven-day-old canine myocardial infarction.

Effects of pirmenol on electrical induction of sustained ventricular tachycardia (VT) were examined in 14 dogs with 7-day-old myocardial infarctions. Before administration of the drug, sustained VT was induced in 8 of 14 dogs. After administration of 3 mg/kg pirmenol, induction of VT was suppressed in 2 dogs but remained inducible in 6 dogs. After cumulative administration of 5 mg/kg pirmenol, VT was no longer inducible in 3 dogs but in the other 3 dogs VTs were still inducible at increased cycle lengths. After 7 mg/kg pirmenol, VT was not inducible in the remaining three dogs. Arrhythmias could not be provoked in any postinfarction dogs after pirmenol administration. Plasma concentrations after sequential and cumulative administration of 3, 5, and 7 mg/kg pirmenol averaged 0.43, 0.65, and 1.15 micrograms/ml, respectively. Administration of pirmenol increased the effective refractory period (ERP) and paced QRS duration in both the normal and infarcted ventricular myocardium. In the infarcted myocardium, prolongation of the ERP for the second and third extrastimuli was greater than for the first one (p less than 0.05). Results indicate that pirmenol is effective for prevention of sustained VT owing to prolongation of both the ERP and conduction time in recent myocardial infarction.

Animals↗

[Analysis of hepatic and renal dysfunction after surgery of thoracic aneurysm].

To analyze causes of postoperative hepatic and renal dysfunction in patients with thoracic aneurysm, we examined 31 patients who survived surgeries and 2 patients died of MOF. The patients were separated into three groups as follows; Cardiopulmonary bypass (CPB) was used for circulatory support in group A (n = 7), CPB and low flow perfusion during open distal anastomosis in group B (n = 13) and temporary bypass or left atrial distal aorta arterial bypass was used in group C (n = 11). Operation time was significantly longer in group A (9.8 hrs) compared with group C (6.1 hrs). Amount of intraoperative blood transfusion was greater in groups A (4980 ml) and B (4860 ml) compared with group C (2320 ml). Postoperative highest total bilirubin level was significantly greater in group A (7.8 mg/dl) than group C (2.5 mg/dl). LDH was higher in groups A (1322 IU/l) and B (1336 IU/l) than group C (991 IU/l). GOT was higher in group B (200 IU/l) than group C (64 IU/l). There were no significant differences in GPT, creatinine and BUN among the three groups. Operation time and amount of intraoperative blood transfusion were positively correlated with postoperative hepatic function parameters. Two patients died of MOF showed severe hepato-renal dysfunction associated with LOS. The results indicate that hypothermic low flow perfusion during open distal anastomosis do not induce hepatic or renal dysfunction, and postoperative hyperbilirubinemia is resulted from bilirubin overload which patients can tolerate well if they are not complicated with MOF.

Aged↗

Doxorubicin selectively inhibits muscle gene expression in cardiac muscle cells in vivo and in vitro.

The anthracycline antibiotic doxorubicin produces a characteristic myopathy in cardiac muscle that limits its use in cancer therapy. We have shown in cultured neonatal rat cardiac muscle cells that doxorubicin treatment resulted in a rapid, selective decrease in the expression of muscle-specific genes, which preceded other changes characteristic of doxorubicin cardiomyopathy. Doxorubicin selectively and dramatically decreased the levels of mRNA for the sarcomeric genes, alpha-actin, troponin I, and myosin light chain 2, as well as the muscle-specific, but nonsarcomeric M isoform of creatine kinase. However, doxorubicin did not affect nonmuscle gene transcripts (pyruvate kinase, ferritin heavy chain, and beta-actin). Actinomycin D, an inhibitor of DNA-dependent RNA polymerase, did not show a similar selective decrease of muscle-specific mRNAs but, rather, produced a nonspecific, dose-dependent decrease of muscle and nonmuscle transcripts. The doxorubicin effect on muscle gene expression was limited to cardiac muscle; cultured skeletal myocytes were resistant to the effects of doxorubicin at 100-fold greater doses than those causing changes in mRNA levels in cardiac muscle cells. These effects of doxorubicin were reproduced in vivo; rats injected with doxorubicin showed a dose-dependent decrease in the levels of mRNAs for alpha-actin, troponin I, myosin light chain 2, and M isoform of creatine kinase in cardiac but not skeletal muscle. These selective changes in gene expression in cardiocyte cultures and cardiac muscle precede classical ultrastructural changes and may explain the myofibrillar loss that characterizes doxorubicin cardiac injury.

Actins↗

Review of pancreatic cancer.

In 83 cases of pancreatic cancer (25 resected and 58 non-resected cases) which underwent laparotomy in the Department of General and Gastroenterological Surgery, Osaka Medical College Hospital over the past 11 years, we analyzed symptoms at diagnosis, duration of illness, tumor markers, surgical procedures, and long-term results. In many cases, jaundice was the premonitory symptom of pancreatic cancer. There was no relationship between duration of illness and tumor resectability. In analysis of tumor markers, abnormal CA19-9 levels were noted in 71% of resected cases and 89% of non-resected cases, and abnormal CEA, elastase and amylase levels were found in 38, 46 and 47% of resected cases and 76, 58 and 27% of non-resected cases, respectively. Operative mortality was higher for non-resected cases (22%) than that for resected cases (8%). Long-term results were significantly better in resected cases than non-resected cases. However, 1-, 2- and 3-year survival rates after macroscopic curative resection were 45, 19 and 9%, respectively. Prognosis of patients after absolute non-curative resection was poor, indicating no efficacy of the resection. To improve these very poor surgical results for pancreatic cancer, the early cancer detection and multi-disciplinary therapy seem to be necessary.

Antigens, Tumor-Associated, Carbohydrate↗

Indications for surgery based on lung biopsy in cases of ventricular septal defect and/or patent ductus arteriosus with severe pulmonary hypertension.

Pathologic obstruction of the proximal lumen and secondary atrophy of the media of the peripheral small pulmonary arteries were absolute operative contraindications in cases of VSD and/or PDA with severe pulmonary hypertension. Such patients who were operated on died with no decrease in pulmonary arterial pressure. The index of pulmonary vascular disease (IPVD), a composite and quantitative evaluation of the severity of pulmonary vascular disease, was introduced to determine the operability of other patients. An IPVD rating of 2.2 in Down's syndrome and 2.1 without the syndrome were regarded as the upper permissible limits for surgical intervention based on results of 23 autopsies and 26 lung biopsies of patients operated on before 1981. Open lung biopsy was performed in 51 patients to determine applicability of our operative indications. Twenty-nine cases were considered operable by our criteria, and 28 underwent surgical correction without operative or late death. Twenty-two cases thought inoperable remain under observation. Comparative analysis of the pathology and preoperative hemodynamic data suggested that lung biopsy should be carried out to determine operability in cases with pulmonary vascular resistance greater than 8 units.m2.

Biopsy↗

[Refractory anemia with ringed sideroblasts complicated with delta beta-thalassemia-like hemoglobinopathy].

A 73 year-old man suffering from marked anemia for several years admitted in our hospital. Diagnosis was immediately made of refractory anemia with ringed sideroblasts by the existence of ringed sideroblasts. Hemoglobin analysis revealed a high fetal hemoglobin, a low hemoglobin A2, a decreased beta/alpha synthetic ratio, and a decreased G gamma/A gamma synthetic ratio. This acquired hemoglobinopathy resembled delta beta-thalassemia. His anemia was remarkably improved because of the responsiveness to anabolic steroid hormone, and this abnormal globin synthetic pattern was identical as those of the normal adult. We consider this hemoglobinopathy may due to an abnormal expression of globin mRNA.

Aged↗

[A case of congenital myotonic dystrophy with infantile autism].

An 11-year-old girl with congenital myotonic dystrophy and infantile autism was reported. Her mother also suffered from typical myotonic dystrophy. Since her birth, the patient had been floppy, and showed bilateral talipes equinus at 1 year of age. Her subsequent psychomotor and speech development has been retarded. She showed autistic behavior and persistence to the sameness before 2 years old. She was admitted to Sawarabien at the age of 10 years. She could not talk anything but could understand simple, oral messages. Although she had severe degree of mental retardation, her ability for matching figures was relatively well reserved. Her autism was so manifest that it could not be explained by the degree of mental retardation. Neurological examinations revealed that she had facial diplegia, inverted V-shaped mouth, high-arched palate, talipes equinus, percussion myotonia of the tongue, generalized muscular atrophy and weakness, lordosis, areflexia, and congenital cataracta. The serum CPK was slightly elevated. EMG showed a myopathic pattern but did not show any myotonic discharge yet. The brachioradial muscle was biopsied and examined by light- and electron-microscopy. It mainly showed mild varieties of muscle fiber diameter and internal nuclei. Ultrastructurally, irregularly indented central nuclei and perinuclear degeneration of myofibrils associated with secondary lysosomes, lipid droplets and glycogen granules were revealed. Ventricular dilatation and some dysfunction of the brain were also revealed by CT scan and EEG respectively. The present case suggests that congenital myotonic dystrophy can be added into the disease group associated with infantile autism.

Autistic Disorder↗

[Surgical management of stab wound of the chest].

During the past three and half years, we experienced eighteen patients with stab wound of the chest. Ten patients were homicidal victims and the remainders were suicides. According to our indications (Table 4), thoracotomy was done in eight patients (44%). The major reason for thoracotomy in this series was massive bleeding. Five pulmonary, four diaphragmatic, four intercostal-artery's and two pericardial injuries were repaired. In our series, six patients (33%) were accompanied with abdominal stab wound and laparotomy was done in five patients. Four liver's one stomach's, one spleen's, one intestine's and one omentum's injuries were repaired. There were three DOA's (dead on arrival). The causes of DOA's were massive bleedings from the heart in two patients and from the liver in one patients. Except for the DOA's, four patients (27%) were not operated on. In conclusion, three DOA's, could not be resuscitated, but all remainders (the thoracotomy's, the laparotomy's and the non-surgical patients) survived and had no complications.

Adolescent↗

Combined peripheral and central chemoembolization of liver tumors. Experience with lipiodol-doxorubicin and gelatin sponge (L-TAE).

Patients with primary and a few with secondary liver tumors were embolized through the hepatic artery. Lipiodol and doxorubicin occluded peripherally, which was immediately followed by central embolization with gelatin sponge cubes. Preoperative embolizations were made for diagnostic and possible surgical adjuvant purposes. Extensive postembolization necrosis was common in tumors less than 5 cm in diameter, and tumor markers usually decreased temporarily after treatment. There were moderate side effects of pain, fever and nausea, and an acceptable complication and mortality rate with no deaths after embolization alone. This warrants further research on the method, which also seemed to improve the detection rate for small hepatocellular carcinomas.

Carcinoma, Hepatocellular↗

Interactions between cations in modifying the binding of hexokinases I and II to mitochondria.

Interactions between cations in modifying the binding of hexokinases I and II to mitochondria was examined with reference to the intracellular condition. Mitochondria-binding of either of hexokinases I and II, both prepared from mouse ascites ELD cells, was markedly increased by Mg2+ as has been known well. However, even in the absence of Mg2+, marked binding was attained by 100 mM K+ alone especially for hexokinase I, which seemed generally more ready to bind to mitochondria. On the other hand, the effect of Mg2+ to increase the binding was reduced by the addition of K+, and the decreasing effect of K+ was much more marked for hexokinase II than I. These results indicate that, in addition to Mg2+, monovalent cations as represented by K+, also have marked effect on the binding, and the effect is different for each hexokinases I and II, which may be responsible for the difference in the intracellular distribution between these hexokinases.

Animals↗