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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 469 records · Page 26Linked to original sources

Efficacy of slow-releasing anticancer drug delivery systems on transplantable osteosarcomas in rats.

New drug delivery systems for cis-diamminedichloroplatinum (CDDP) incorporated into vehicles, such as polymethylmethacrylate (PMMA), fibrin glue (F.G.), alpha-tricalciumphosphate (TCP) and ethylenevinyleacetate copolymer (Polymer) were examined using a rat osteosarcoma model. The materials containing CDDP were directly implanted into the tumors or subcutaneous tissue of rats, and the inhibitory effects on tumor growth and lung metastasis were evaluated. Data on in vitro kinetics of CDDP release revealed good results for both TCP and F.G., and the release pattern from TCP to be most appropriate for a slow-releasing drug delivery system. This was supported by the results of the implantation experiments, whereby the direct implantation of TCP containing CDDP (CDDP-TCP) into tumors, gave significantly better inhibitions of tumor growth and metastasis than either non-treatment (P < 0.01) or subcutaneous implantation (P < 0.05). In a second experiment, using different administration procedures, different inhibitory effects on tumor growth and lung metastatic potency were observed with intra-arterial and intravenous CDDP administration, as well as with CDDP-TCP implanted subcutaneously. Suppression effects of CDDP (10 mg/kg)-TCP directly implanted into tumors were equal to those of intra-arterial (2.5 mg/kg) and intravenous (5.0 mg/kg) administrations. The present results suggest CDDP-TCP implantation to be effective as a slow-release drug delivery system for inhibiting tumor growth and metastasis, and that it should be a useful adjuvant to conventional i.v. or i.a. chemotherapy.

Animals↗

Must theology remain silent in bioethics?

Bioethics tends to lack both breadth and depth; a theological perspective can provide the necessary lack. The essential role of a theologian has always been to direct attention to dimensions of human situations that may have escaped our notice, to account for the interpretive frameworks people bring to their experiences of health, medicine, suffering, and death within a vision of human nature and destiny.

Bioethics↗

Efficacy of the angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (AGM-1470) on osteosarcoma growth and lung metastasis in rats.

The efficacy of the anti-angiogenic agent, O-(chloroacetyl-carbamoyl)fumagillol (AGM-1470), against primary tumor growth and spontaneous lung metastasis was evaluated experimentally using a transplantable osteosarcoma line in rats previously established in our laboratory. Male Fischer 344 rats bearing the tumor with a high potential for metastasis received intermittent or continuous subcutaneous administrations of AGM-1470. Both treatment regimens resulted in significant inhibitions of spontaneous lung metastasis and primary tumor growth in a dose-dependent manner, with continuous administration of AGM-1470 exerting the most pronounced inhibitory effects on both parameters.

Animals↗

A rare case of disseminated intravascular coagulation caused by the nonionic contrast medium iohexol.

Nonionic contrast media are reported to cause serious adverse reactions less often than ionic contrast media. However, we treated an otherwise healthy woman with a left ureteral stone in whom disseminated intravascular coagulation developed due to intravenous administration of the nonionic contrast medium iohexol. We discuss the clinical course and possible causes of disseminated intravascular coagulation. Our case emphasizes that nonionic contrast media are not free from serious adverse reactions although the incidence seems extremely low.

Disseminated Intravascular Coagulation↗

Canine cadaveric study of flexor tendon repair using tendon splint: tensile strength and the work of flexion.

A total of 128 flexor tendon repairs in zone II were performed with various suture techniques using a canine cadaver model to determine the tensile strength, gap strength, and resistance to tendon gliding as measured by the work of flexion. The ultimate tensile strength in kilogram force (kgf) following tendon laceration and repair was the greatest after repair by the Savage technique (4.84 kgf) and the dorsal tendon splint technique (4.89 kgf), while the standard Kessler technique showed a strength of only 1.48 kgf. The greatest gap strength values were also obtained for the Savage and dorsal tendon splint techniques. The work of flexion increase was the greatest at 85.5% after repair using a mesh sleeve technique. While, the Savage and dorsal tendon splint techniques showed an increase of 24.3% and 25.1% with no significant difference compared to the other technique studied. Considering the values of these biomechanical parameters, we believe that the best flexor tendon repair techniques in the canine model are the Savage and dorsal tendon splint.

Animals↗

[Fontan procedure after pulmonary artery banding--surgical results and new anatomical repair for tricuspid atresia].

We examined our surgical experiences to determine the appropriate condition of pulmonary artery banding (PAB) for the Fontan procedure. From 1974 through 1992, thirteen patients underwent Fontan procedure following PAB at Tokyo Women's Medical College. Of these 6 had tricuspid atresia (TA), 5 had single ventricle, or 2 had other complex malformations. PAB was performed at the age of 1 to 14 months (mean 2.5 months). With monitoring pulmonary artery (PA) pressure and systemic arterial oxygen tension (PaO2), PA mean pressure decreased 43.6 to 18.8 mmHg and PA circumferences at the banding site decreased from 53.5 to 26.0 mm after PAB. This degree of PAB was tighter compared with the value estimated by Trusler's formula (27.9 mm) in most patients. After PAB, 5 patients required 8 additional palliative surgery including 3 systemic to pulmonary shunt, 3 rebanding, 1 palliative RVOTR to promote development of pulmonary vascular bed and 1 atrial septectomy to prevent pulmonary hypertension. Hemodynamic data before Fontan operation showed a tendency of higher PA pressure (17.5 vs 31.5 mmHg), and pulmonary vascular resistance (2.4 vs 5.5 Wood Unit) in non-survivors than in survivors. For patients with tricuspid atresia and high pulmonary vascular resistance, a new operation "Anatomical Repair" utilizing hypoplastic right ventricle with the translocation of pulmonary or aortic valve in tricuspid position was developed and successfully applied in three patients. In conclusion, initial tight PAB during early infancy and often repeated palliative surgery for development of adequate pulmonary vascular bed is the most important for maximizing the chance of subsequent successful Fontan procedure.

Age Factors↗

[Reoperation for coarctation of the aorta and interrupted aortic arch].

This report presented four patients who underwent surgery for restenosis after repair of coarctation of the aorta (CoA) or interrupted aortic arch (IAA) at our institution between January 1980 and October 1994. Case #1 underwent primary repair for IAA, VSD, and PDA consisting of aortic arch reconstruction using a EPTFE (expanded polytetrafluoroethylene) graft of 10 mm in diameter at the age of four years. After 17 years, pressure gradient of 58 mmHg between the ascending aorta and the descending aorta prompted the reoperation. Case #2 underwent primary repair for CoA, VSD, and PDA consisting of a bypass between the ascending aorta and the descending aorta with an EPTFE graft of 11 mm in diameter at the age of three years. After 13 years, he had reoperation because of pressure gradient of 64 mmHg. Case #3 had pressure gradient of 20 mmHg between the upper and lower limb at the hospital discharge following patch angioplasty for CoA at five years of age. He underwent unsuccessful percutaneous transluminal balloon angioplasty at age 12 and had reoperation at age 15. Case #4 underwent subclavian flap angioplasty as the first stage operation for CoA, VSD, and PDA at 1 month after birth. About 9 months after the initial operation, the pressure gradient between the upper and lower limb had reached 40 to 50 mmHg, and the patient had reoperation at the age of 1 year. The reoperation method for cases #1, #2 and #3 consisted of bypass grafting from the left subclavian artery to the descending aorta under a simple cross clamping of the thoracic aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[A case of chronic scrotal hematocele].

A 60-year-old man visited our hospital because of a painless swelling of the left scrotal content which enlarged gradually for these five years. He had no history of trauma at the perineum. Tumor markers such as HCG, AFP and CEA were within normal limits. Left high orchiectomy was carried out after the admission under the diagnosis of suspicious testicular cancer. The resected mass, 16.5 x 12.5 x 9.5 cm in diameter and 900 g in weight, was encapsulated within the tunica vaginalis by a fibrous membrane and contained about 300 ml of reddish black liquid. The normally-appearing left testis was located separately from the mass. Microscopic examination revealed depositions of cholesterine crista in the wall, which are characteristic for a chronic hematocele.

Chronic Disease↗

[Chorea with prominent spasticity associated with an expansion of the CAG trinucleotide repeat in the IT15 gene: a case report].

A 60-year-old female, who had been noted to have slowly progressive mental changes since the age of 40, subsequently developed irregular, abrupt, jerking movements of her limbs, and coordination and walking difficulty after 15 years. Her father, aunt and sister had also been suffering from similar involuntary movements and changes of personality. Neurological examination revealed slight dementia, choreic movements and the evidence of pyramidal tract signs; i.e., she showed general hyperreflexia of extremities, bilateral ankle clonus, and extensor plantar responses of lower extremities. laboratory data were all within normal ranges except iron deficiency anemia. Axial MRI showed moderate cortical atrophy, however, without dilatation of the frontal hours of lateral ventricles and the caudate head appeared normal. Our initial impression was dentatorubropallidoluysian atrophy (DRPLA). However, the genetic analysis of her peripheral leukocytes disclosed an expansion of the CAG repeats (43 copies) in the IT15 gene in chromosome 4p, indicating the diagnosis of Huntington's disease (HD). CAG repeats in chromosome 12, known to link with DRPLA, was not expanded. Thus, this case is unique in that the classical symptomatologies of HD was betrayed by the presence of prominent pyramidal tract signs. This patient may be of importance in demonstrating the diversity of neurological symptoms and neuropathologies caused by CAG trinucleotide repeats in HD.

Brain↗

[A modified Damus-Kaye-Stansel anastomosis for restrictive bulvoventricular foramen developed 5 years after Fontan procedure].

An one-year old girl, who had pulmonary artery (PA) banding and balloon atrioseptostomy done in the newborn period, underwent modified Fontan procedure on an emergency basis without cardiac catheterization, because of right heart failure. Echocardiogram showed no subaortic stenosis at Fontan procedure. Five years later, subaortic stenosis was documented with a 65 mmHg of ventricular-aortic pressure gradient at catheterization. A modified Damus-Kaye- Stansel (D-K-S) procedure was successfully performed using an end-to-end anastomosis of the distal aorta and a common stump, consisting of previously suture-closed main PA stump and the proximal aorta. At postoperative catheterization, the pulmonary valve was functioning well at LV outlet portion without regurgitation and stenosis. Significant subaortic stenosis may develop after Fontan procedure in patients with morphological narrowing without demonstrable pressure gradient. Such patients should have surgical intervention to the narrowing at the time of Fontan procedure. The modified D-K-S procedure can be an effective procedure to relieve subaortic stenosis after Fontan procedure.

Anastomosis, Surgical↗

Effect of angiotensinogen on blood pressure regulation in normotensive rats: application of a loss of function approach.

OBJECTIVE: To investigate the effect of plasma angiotensinogen on blood pressure regulation in normotensive rats, by a loss of function approach using antisense oligonucleotides. DESIGN AND METHODS: Eight-week-old male Wistar rats were transfected with antisense, sense or scrambled oligonucleotides using liposomes containing viral agglutinins, which are reported to be highly efficient in promoting fusion with target cells. The abdomen was opened with a median incision, and the liver and portal vein were exposed. Then 2.5 ml of hemagglutinating virus-liposome complex containing oligonucleotides was introduced into the liver by multiple direct injections or infusion via the portal vein. Blood pressure, plasma angiotensinogen and angiotensin II levels were measured after transfection. The hepatic angiotensinogen level was examined by Northern blotting and radioimmunoassay. RESULTS: The in vivo injection of antisense oligonucleotides against rat angiotensinogen by the hemagglutinating virus-liposome gene transfer method into normotensive rats resulted in a transient fall in blood pressure from day 1 to day 4 after injection. This was accompanied by a decrease in plasma angiotensinogen and hepatic angiotensinogen messenger RNA levels on day 2. No significant changes were noted in untreated rats or those treated with sense or scrambled oligonucleotides. Plasma angiotensin II concentration was also reduced by antisense treatment, but not sense or scrambled treatment. CONCLUSIONS: In vivo administration of antisense angiotensinogen oligonucleotides resulted in a transient decrease in blood pressure accompanied by a decrease in plasma angiotensinogen and angiotensin II levels, which suggests that angiotensinogen plays a pivotal role in the regulation of blood pressure in normotensive rats.

Angiotensin II↗

[Prognostic factors of radiation therapy for patients with non-operative stage III non-small cell lung cancer].

Records of patients with non-operative stage III non-small cell lung cancer registered at the Department of Radiotherapy, Cancer Institute Hospital, from January 1978 to June 1980 were examined in order to present prognostic information on survival. The data were derived from 100 carefully staged patients and include results from the patients' history, physical examination, pretreatment laboratory tests, radiological findings, nature of radiotherapy and response to treatment. Serum albumin, tumor site, performance status (PS), hemoglobin, TDF and response were identified as important prognostic factors in the univariate analyses. On the other hand, tumor site, PS and serum albumin were significantly related with survival in the multivariate analyses. However it was found that TDF and response significantly affected survival when posttreatment variables were taken into account. These patients were classified into low, intermediate and high risk groups according to those three pretreatment factors (tumor site, PS and serum albumin), and the median survival times for the groups were 10.3 months, 10.4 months and 2.5 months, respectively. These results suggest that high risk patients with stage III non-small cell cancer generally might be treated palliatively.

Adult↗

Crystallization and preliminary X-ray crystallographic studies of recombinant human leukotriene A4 hydrolase complexed with bestatin.

Recombinant human leukotriene A4 hydrolase complexed with bestatin, an inhibitor of metalloprotease, has been crystallized by the hanging drop vapor diffusion method using 0.1 M phosphate buffer (pH 6.5) and 50 to 54% saturated ammonium sulfate. The orthorhombic crystals belong to the space group I222 or I2(1)2(1)2(1) with unit cell dimensions of a = 273.6 A, b = 261.3 A and c = 52.9 A. They diffract beyond 2.5 A resolution and a native data set up to 3 A resolution has been collected on an imaging plate Weissenberg camera using synchrotron radiation.

Amino Acid Sequence↗

Hydrophobic interaction at the subunit interface contributes to the thermostability of 3-isopropylmalate dehydrogenase from an extreme thermophile, Thermus thermophilus.

We cloned and sequenced the leuB gene encoding 3-isopropylmalate dehydrogenase from Escherichia coli K-12 (JM103). Errors (33 residues) were found and corrected in the sequence previously reported for the leuB gene of Thermus thermophilus. The three-dimensional structure of the thermophile enzyme and the amino acid sequence comparison suggested that a part of the high stability of the T. thermophilus enzyme is conferred by increased hydrophobic interaction at the subunit-subunit interface. Two residues at the interface of the T. thermophilus enzyme, Leu246 and Val249, are substituted with less hydrophobic residues, Glu and Met, respectively, in the E. coli enzyme, whereas other residues in this region are highly conserved. The mutated T. thermophilus enzyme [L246E, V249M]IPMDH had reduced stability to heat. Two residues of the E. coli dehydrogenase, Glu256 and Met259, were replaced with the corresponding residues from the thermophile sequence. The resulted mutant enzyme was more resistant to heat than the wild-type enzyme.

3-Isopropylmalate Dehydrogenase↗

Substance P- and calcitonin gene-related peptide-immunofluorescent nerves in the repair of experimental bone defects.

Healing of an experimental bony defect in the rat's tibia was studied with an immunofluorescent technique to clarify when and where substance P (SP) and calcitonin gene-related peptide (CGRP) would develop. The normal tibia showed a few SP- and CGRP-immunofluorescent nerve fibres. In the experimental tibia, the number of these fibres increased on the 6th day after operation, reached a peak of proliferation on the 15th day and reverted to normal after the 24th day. The changes were associated with the development and decay of callus tissue suggesting that harmful stimuli from the injured site in a bone could be mediated by sensory nerves throughout the repair period. Most of the SP- and CGRP-immunofluorescence was seen near the vessels, frequently in the same nerve fibres. The SP- and CGRP-immunofluorescent nerves seemed to take part jointly in callus formation through the enhancement of local blood flow.

Animals↗

Electron microscopic evidence of a viral nature for osteoclast inclusions in Paget's disease of bone.

Circumstantial evidence from electron microscopic and immunological studies support the view that Paget's disease of bone represents a slow virus infection. However, there is only limited information available regarding its electron microscopic, enzyme and immunocytochemical characteristics. Two cases were studied using electron microscopy with particular emphasis on the inclusions in osteoclasts. Detailed ultrastructural and cytochemical studies including immuno-electron microscopy were performed. Some osteoclasts demonstrated specific virus-like structures composed of aggregations of microtubules in the nucleus and cytoplasm. The structures were easily digested by trypsin or protease, and were sensitive to RNase, which provided substantial evidence of a proteinaceous nature and inclusion of ribonucleic acid. Immunocytochemical examination identified binding of anti-respiratory syncytial virus and anti-measles virus antibodies in the tissue obtained from one of the two cases examined. The presence of viral antigens in structures in the cytoplasm of Pagetic osteoclasts supports the theory of paramyxovirus involvement in this disease.

Antigens, Viral↗