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Biomedical subjects

M Akagi

Publications and source records attributed to M Akagi.

At least 91 records · Page 5Linked to original sources
PubMed1992

Application of L-DNA to the study of the specific DNA recognition mechanism of bleomycin.

The hexadeoxynucleotide analog, L-d(CGCGCG) composed of L-deoxyribose was synthesized and clearly shown to have the same conformation and dynamic properties with natural D-d(CGCGCG) except for chirality with CD spectra. This unnatural hexanucleotide was not cleaved by bleomycin, an antitumor DNA cleaving drug, but was able to bind to the DNA binding domain of bleomycin to a similar extent with the natural one. These results strongly suggest the importance of the other moiety than the DNA binding domain for the specific DNA recognition of bleomycin. Thus, L-oligonucleotides are useful for the study of DNA-drug interactions.

Binding Sites↗
PubMed1991

Photo-induced formation of the 2-deoxyribonolactone-containing nucleotide for d(ApCpA); effects of neighboring bases and modification of deoxycytidine.

Previously, we reported the formation of a 2-deoxyribonolactone-containing nucleotide by UV irradiation of d(ApCpA). In this paper, we report some mechanical feature of this novel photoreaction. From the results of photolysis of d(GpCpG), this reaction is independent of neighboring bases. On photolysis of deoxycytidine at acidic pH, 2-deoxyribonolactone was produced with 74.2% isolated yield. And effects of some modifications of deoxycytidine were investigated. The results suggest that hydrates are possible intermediates for this reaction and the protonation may be essential not for deoxycytidine, but for the intermediates.

Adenine↗
PubMed1991

Interstrand cross-linking of the hexadeoxynucleotide d(TACGTA) upon reaction with trans-diamminedichloroplatinum(II).

The reaction of trans-diamminedichloroplatinum(II), an inactive isomer of cisplatin, with d(TACGTA) was performed in aqueous solution, and the interstrand cross-linked adduct was isolated on a preparative scale. This adduct was characterized by 1 M thiourea treatment, atomic absorption spectroscopy, enzymatic digestion and 1H NMR as platinum coordinated to two molecules of d(TACGTA) at the N7 atom of the guanine residue. This interstrand cross-linked adduct did not form a duplex structure in the conditions where the free hexanucleotide adopts it.

Chromatography, High Pressure Liquid↗
PubMed1991

Role of the cytoskeleton in Ca2+ release from the intracellular Ca store of rat peritoneal mast cells.

In order to study the role of the cytoskeleton in histamine release from mast cells, the effects of cytochalasin D, cholchicine and vinblastine on Ca2+ release from the intracellular Ca store induced by compound 48/80 were investigated by means of a video-intensified microscopy system. When the quin 2-loaded mast cells were stimulated by 0.35 micrograms/ml of compound 48/80, a rapid increase in intracellular Ca2+ was observed. At concentrations higher than 10(-6) M, both colchicine and vinblastine pretreatments significantly inhibited the increase in intracellular Ca2+ concentrations caused by compound 48/80, although cytochalasin D had no effect. When permeabilized mast cells were exposed to potassium-antimonate solution, microtubules became attached to the endoplasmic reticulum, where many dots of Ca-antimonate were observed; in some areas, the microtubules interconnected the endoplasmic reticulum and granules in the mast cells. From the results of the present study, it was assumed that microtubules play some important role in the processes leading to Ca2+ release from the intracellular Ca store.

Aminoquinolines↗
PubMed1991

The existence of filaments connecting the granules and the cell membrane in rat peritoneal mast cells.

SEM images of rat peritoneal mast cells showed that microtubule-like filaments seemed to penetrate the granules and project several branches just beneath the granular surface. Each granule appeared to be a cluster of microgranules. TEM observations frequently revealed microtubules connecting the granule surface to the subplasmalemmal network or to the adjacent granule surface and on some occasions, microtubules also appeared to penetrate the granule membranes. Moreover, TEM revealed that individual granules seemed to consist of a mass of microgranules, each 10-15 nm in diameter; freeze-fracture images showed similar configurations. These findings suggest that the microtubule-like filamentous structures in mast cells play a role corresponding to that of the open canalicular system in platelets.

Animals↗
PubMed1991

Comparative study of the adverse effects of various radiographic contrast media, including ioversol, a new low-osmolarity medium. II. The complement system and endothelial cells.

The effects of ioversol, iohexol, iopamidol and meglumine sodium amidotrizoate (MSA) on the complement system and endothelial cells were investigated. The protein bindings of the radiographic contrast media (RCM), each tested with guinea pig plasma, were less than 1%. When guinea pig serum was incubated with any of the RCM, activation of the complement system, which leads to hemolysis, was not influenced by the nonionic agents, ioversol, iohexol or iopamidol. However, MSA, an ionic agent, significantly reduced hemolytic activity at 370 mgI/ml. Perfusion of the abdominal aorta with nonionic agents did not elicit significant endothelial damage; ioversol induced the least damage among the nonionic RCM, while MSA caused remarkable endothelial damage. Although MSA caused a marked release of endothelin-1 from cultured endothelial cells obtained from porcine aorta, nonionic RCM did not induce significant endothelin-1 release; no influence was elicited by ioversol and iohexol caused a weak suppression, while iopamidol had the opposite effect. These results indicate that ioversol could be used as a safe contrast medium in intravascular administration.

Animals↗
PubMed1991

Dislocation of the peroneal tendons in neonates and infants.

Twenty-three cases of dislocation of the peroneal tendons were found during routine orthopedic examinations of neonates and infants. All but one case was without foot deformity. One case was treated with a cast, and the others received no treatment. Follow-up observations revealed that the dislocations resolved spontaneously in almost all cases. This condition seems to be not as rare as had been previously considered. Dislocations of the peroneal tendons in neonates and infants without foot deformity should be untreated and allowed to resolve spontaneously.

Ankle Joint↗
PubMed1991

[A successful surgical treatment of cor triatriatum with VSD, PDA and CoA].

A successful repair of cor triatriatum with VSD, PDA and CoA is reported. A two-month-old boy was admitted for evaluation of growth failure and cyanosis. Physical examination on admission revealed systolic murmurs at left sternal border. Chest X-ray showed increased pulmonary vascularities without cardiomegaly. Echocardiography showed abnormal wall in left atrium with VSD, PDA and CoA. An emergency operation consisting of patch closure of VSD, ligation of PDA and resection of the anomalous left atrial membrane were performed. At postoperative course, an episode of pulmonary hypertension crisis happened. But the patient tolerated this episode and survived.

Aortic Coarctation↗
PubMed1991

[Successful surgical treatment of total anomalous pulmonary venous connection (supracardiac Ib type) showing an unusual shape of the pulmonary veins in an infant].

An experience of a 9-month-old infant with Darling's type Ib of total anomalous pulmonary venous connection is presented. In this case, the left pulmonary vein traveled horizontally behind the atrium, entered the right thoracic cavity and drained into the SVC together with the right lower, middle and upper pulmonary veins. The patient was treated with repair using Gersony-Malm's method and plasty of SVC because of the stenosis of the common pulmonary vein's entrance to the SVC. Her postoperative course was uneventful, and the result was satisfactory. To our knowledge, our case is the first successful correction not associated with other complex cardiac anomalies in the world.

Female↗
PubMed1990

Serum carcinoembryonic antigen level increases correlate with tumor progression in patients with differentiated gastric carcinoma following noncurative resection.

Serum carcinoembryonic antigen (CEA) levels were determined serially in 30 preoperative and postoperative patients with differentiated and 47 with undifferentiated gastric cancers. Macroscopic noncurative resection of the stomach was done for those patients. There was no difference between survival curves in the differentiated and undifferentiated cases, and the 50% survival was 13.1 months for the differentiated group and 12.5 months for the undifferentiated group. Preoperative serum CEA levels were 10.4 +/- 5.2 ng/ml for the differentiated and 4.0 +/- 1.6 ng/ml for the undifferentiated cases, and CEA-positive rates were 20.0% for the differentiated and 14.9% for the undifferentiated cases. There was no difference in preoperative CEA values with regard to tissue types. In the course of tumor progression, CEA levels increased during the first postoperative year in the differentiated cases and related reciprocally to decreases in survival rates. Little change was noted in the undifferentiated cases. Therefore, the serial postoperative assay of serum CEA levels has predictability with regard to tumor progression in patients with a differentiated gastric cancer.

Adult↗
PubMed1990

Histamine release induced by histone and related morphological changes in mast cells.

When isolated rat peritoneal mast cells were exposed to histone mixture, both histamine release and degranulation were evoked rapidly and dose-dependently at concentrations higher than 1 microgram/ml in a Ca-free medium. All of the histone subfractions (H1, H2A, H2B, H3 and H4) induced histamine release from mast cells in a Ca-free medium and, as in the case of histone mixture, the amount of histamine release was reduced by addition of Ca2+. By means of high-voltage electron microscopy, at least three types of degranulation were observed in mast cells exposed to histone mixture: (1) microfilament-associated degranulation, (2) extrusion of granules with the surrounding membrane, and (3) mass degranulation.

Animals↗
PubMed1990

Non-invasive assessment of the steal phenomenon following femoro-femoral bypass.

Clinical studies were performed on 42 patients who underwent femoro-femoral bypass and postoperative assessment of the ankle/brachial pressure index (API) and Doppler waveform for each limb was carried out. Patients who had poor runoff of the donor limb showed a significant decrease in API after ankle joint exercise (p less than 0.05), whereas no significant change was observed in patients who had poor runoff of the recipient limb. The response of pulsatility index was similar to that of API. Thirteen of the 42 patients underwent both pre- and postoperative assessments. Six of these patients underwent additional procedures such as thromboendarterectomy or profundaplasty on the anastomotic site of the donor limb, and the other 7 patients had no additional procedures performed. A decrease in API after exercise was prominent in the patients who had not undergone any additional procedures, in the postoperative stage (p less than 0.01). Thus, when performing femoro-femoral bypass, improving poor runoff in the donor limb by carrying out intraoperative additional procedures should be taken into consideration, as any imbalance of peripheral resistance must be kept to an absolute minimum.

Ankle↗
PubMed1990

Hemodynamic changes with arterial stenosis experimentally created using the sliding calipers method.

The relationship of blood pressure, blood flow and Doppler waveform to arterial stenosis was investigated in a canine model. The method of making a stenosis involved using slide calipers and the critical stenosis of the femoral artery was 75 per cent. Among the parameters from Doppler waveform; peak forward velocity, pulsatility index, acceleration and deceleration correlated well with arterial stenosis, having correlation coefficients of -0.729, -0.856, -0.824 and -0.739, respectively. The results of this method conform closely to clinical conditions with regard to progress of the occlusive process.

Animals↗
PubMed1990

Reduced bone marrow toxicity of neocarzinostatin by conjugation with divinyl ether-maleic acid copolymer.

Neocarzinostatin (NCS) was conjugated with divinyl ether-maleic acid anhydride copolymer (pyran copolymer), and its therapeutic effect was compared with that of NCS. The conjugated NCS (pyran-NCS) with a molecular weight of about 23,000, exhibited in vitro cytotoxic activity against eight cell lines and bone marrow cells that was similar to the cytotoxic activity of NCS on a molar basis. Furthermore, both drugs had similar effects against a multidrug-resistant Chinese hamster ovary cell line (CHR C5) and its parent cell line (AUXB1) in vitro. However, pharmacological analysis showed that pyran-NCS had reduced accumulation in the spleen, and most important was three times less hematotoxic in vivo compared with NCS. Also, pyran-NCS had a 1.7-fold higher 50% lethal dose (LD50). Antitumor activity of pyran-NCS and NCS was tested against two different forms of Meth A tumor. In a solid tumor model, pyran-NCS and NCS suppressed tumor growth at three-fourths of the LD50 to 12.8 and 19.0% of the control tumor as evaluated on day 28, respectively (P less than 0.025). In an ascitic tumor model, the percentage increase in the median life span caused by pyran-NCS and NCS was more than 400 and 150% on day 60, respectively. Pyran-NCS is more effective than NCS because the reduced acute toxicity permits an increased drug dosage.

Animals↗
PubMed1990

Histochemical determination of iodide peroxidase activity in various thyroid disorders.

We developed a histochemical method to demonstrate iodide peroxidase activity in various thyroid disorders and compared it with the biochemical and ultrastructural-cytochemical methods. All of the 26 adenomatous goiters and 43 follicular adenomas were peroxidase-positive. In the 74 cases of thyroid carcinomas examined, about half of the follicular carcinomas (17 of 33 patients), and a few papillary carcinomas (3 of 41 patients) were peroxidase-positive. Peroxidase-negative cases were seen in 70% (52 of 74 patients) of the follicular and papillary carcinomas. All the non-tumorous thyroid tissues adjacent to various disorders were peroxidase-positive. Since our histochemically demonstrated peroxidase activities almost parallel those determined biochemically and ultrastructural-cytochemically, we conclude that histochemical examination is a simple and useful method for the detection of peroxidase activity. As for the relationships between histochemically proved peroxidase activity and the histology of tumors, the histological differentiation of tumors was not consistent with their functional differentiation classified according to peroxidase activity.

Adenocarcinoma↗
PubMed1990

Role of Lugol dye endoscopy in the diagnosis of early esophageal cancer.

To evaluate the role of Lugol dye endoscopy in diagnosing early esophageal cancer, we reviewed findings of dye endoscopy and those of conventional endoscopy in 17 early esophageal cancers that were demonstrated as unstained areas on dyeing with Lugol solution. Histologically, all 17 lesions were squamous cell carcinomas; 10 lesions being mucosal carcinomas, the remaining 7 lesions mucosal carcinomas spreading beyond the epithelial layer. The lesions ranged from 0.7 to 4.0 cm in size. Abnormal findings were noted under conventional endoscopy in all but 3 lesions diagnosed only by postoperative pathohistology, regardless of the size and depth of the invasion. Under conventional endoscopy, the following types of morphological changes were noted in 8 (57.1%) of the 14 lesions: slight elevation (1 lesion), depression (6 lesions), and deformed arc (1 lesion). A color change was noted endoscopically in 12 of the 14 lesions (85.7%), this change being redness in all 12 lesions. The unstained area on the resected specimen was consistent with the size of the lesion that was determined by using serially sectioned blocks in all cases. Moreover, the former completely (100%) coincided with the histological area where PAS reaction was weak. In conclusion, under conventional endoscopy, a color change such as redness is an important indicator of minute or superficial esophageal cancer, as is such morphological change as depression, elevation or deformed arc. On the other hand, Lugol dye endoscopy is very helpful in detecting esophageal cancer unassociated with any morphological or color change. It also provides accurate information about the extent of the cancer.

Aged↗
PubMed1990

Detection of tumor associated antigen, PA8-15, in sera from pancreatic and gastrointestinal carcinoma patients.

A sandwich enzyme immunoassay was set up to measure tumor associated antigen (antigen PA8-15) detected by monoclonal antibody PA8-15. The cut-off value was set at 55 U/ml. Tests on 437 sera samples from patients with malignant or benign diseases yielded the following positive percentages: esophageal cancer, 9.1%; gastric cancer, 23.1%; colorectal cancer, 44.8%; hepatoma, 32.6%; biliary tract cancer, 47.5%; pancreatic cancer, 84%; lung cancer, 30.8%; breast cancer, 16%; benign diseases, 13.2%. Positive antigen PA8-15 levels in patients with gastric, colorectal and pancreatic cancers, increased with the progression of clinical stage. When antigen PA8-15 was monitored in 11 various cancer cases before and after surgery, a decrease in PA8-15 value was revealed in all resected patients postoperatively, whereas a more than 100% increase in PA8-15 values was noted in non-resected patients. Compared with CEA and CA19-9, the highest positive PA8-15 rate was seen in pancreatic cancer patients. By combining the rates of positive sera obtained with each tumor marker, the overall percentage increased. These results suggest that measuring serum PA8-15 levels will aid in serological cancer diagnoses, particularly pancreatic cancer.

Adolescent↗