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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 955 records · Page 53Linked to original sources

[Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibodies].

Aiming at radioimmunodetection of colorectal cancer, anti-CEA monoclonal antibodies (CEA102) were produced by immunization with purified CEA. CEA102 showed high specificity with colorectal cancer by mixed hemadsorption assay and immunoperoxidase technique. The antigen detected by CEA102 was confirmed to be carcinoembryonic antigen (CEA) and its molecular weight was estimated to be ca. 180,000 by biochemical analysis. The in vivo study using nude mice grafted a human colorectal cancer or a human malignant melanoma showed greater accumulation of 125I-labeled CEA102 in CEA-positive colorectal cancer than in nude mouse tissues and CEA-negative malignant melanoma. Moreover we successfully obtained scans with good localization of the grafted colorectal cancer on FCR (Fuji Computed Radiography). Using 131I-labeled CEA102 liver metastasis in the patient with colorectal cancer was successfully detected by external scanning with gamma-camera. These results suggest that radiolabeled CEA102 is useful for the detection of colorectal cancer.

Aged↗

Bone bonding behavior of bead-coated alumina ceramic under load-bearing conditions.

Alumina ceramic has good biocompatibility, high mechanical strength, and excellent lubrication properties. However, it is bioinert and does not bond with bone tissue. Therefore, to promote mechanical bonding, we have developed an alumina ceramic material coated with alumina ceramic beads using identical alumina ceramic binder. In this study, we evaluated the bone bonding capability of this material under load-bearing conditions along with its mechanical properties. The test pieces with or without bead-coating were implanted into the load-bearing portions of the medial and lateral femoral condyles of adult mongrel dogs. The dogs were euthanized 4, 8, and 24 weeks after implantation, and the pull-out test and histological examination were performed. The uncoated implants showed signs of loosening similar to those observed clinically. In contrast, the bonding strength of the bead-coated implants was significantly greater than that of the uncoated implants and increased with implantation time. This increase in strength differs from the results obtained in the non-load-bearing experiments, in which a plateau was seen relatively early after implantation. Results of histological examination suggested that this increase was caused by thickening of ingrown trabeculae, which could be observed as early as 4 weeks after implantation, at the bone-implant interface. In addition, the mechanical properties of the bead-coated alumina ceramic were comparable to those of grooved alumina ceramic which has been used clinically. These results indicate the possibility for clinical application of the bead-coated alumina ceramic.

Aluminum↗

[Preoperative localization of supernumerary and ectopic parathyroid glands in patients with secondary hyperparathyroidism].

The undetectable supernumerary and ectopic parathyroid glands have a high risk of persistent and recurrent hyperparathyroidism, especially in the patients with secondary hyperparathyroidism. Preoperative image diagnosis, CT scan, echogram and 201T1C1 scintigram were very useful for detecting supernumerary and ectopic parathyroid glands in our 132 patients who underwent parathyroidectomy for secondary hyperparathyroidism. Among these methods the scintigraphy showed the highest detection rate of the glands in the thymic tongue and in the upper mediastinum. CT scan showed the best detection rate of the glands located in the thyroid gland and those located between the thyroid gland and trachea. The echography was useful in detecting the glands in the thyroid gland, but could not offer easy visualization those located in the mediastinum. Even the ectopic parathyroid glands, weighing more than 500 mg were identifiable at about 90% when all the methods were applied routinely. In our experience, four patients had a supernumerary gland which was detected by the preoperative image diagnostic procedures at the initial surgery. One patient had a supernumerary gland in the mediastinum which was detected by image diagnosis after the initial operation and was removed at reoperation.

Adult↗

[Alteration of phenotype, morphology and drug sensitivity in colon cancer cell lines under various culture conditions].

Thirteen colorectal cancer cell lines were established from 120 fresh colon cancer specimens. Expression of colon cancer-related antigens and blood group-related antigens on these cell lines were evaluated by Mixed Hemadsorption test (MHA) and Immune Adherence test (IA). The results were compared with the results of immunohistological analysis of the antigen expression in sections of the original tissues, and deletions of several blood group-related antigens in cell lines were observed. Colon cancer cell line HT-29, cultured in different lots of FCS or in different types of serum-free medium showed various antigen expression, suggesting the effect of culture medium on phenotypic expression. In glucose-free medium, HT-29 cells showed the characteristic "dome formation" which is typical of enterocytic differentiation forming brush borders in such cells. HT-29 cells cultured on bovine corneal endothelial extracellular matrix (BCE-ECM) coated plates showed similar enterocytic changes under phase-contrast microscope. Also, irradiated HT-29 cells cultured under 8-Azaguanine containing medium retained their strong resistance to 8-Azaguanine. These results suggest that these cancer cell lines might alter their phenotype, morphology, differentiation, growth pattern and drug sensitivity depending on the culture environment.

Antigens, Neoplasm↗

[Serum lipoprotein abnormalities in patients with nephrotic syndrome and effects of steroid therapy].

With polyacrylamide gel electrophoresis (PAGE), we studied serum lipoprotein (Lp) abnormalities in patients with nephrotic syndrome (NS) caused by primary glomerulonephritis. Nineteen untreated nephrotic patients were studied. Seven patients of them were followed up with PAGE in the remitting course. Serum total cholesterol, triglycerides and beta-Lp concentrations were higher in untreated patients than those in normal control. Serum HDL-cholesterol concentration was lower in untreated patients than those in normal control. PAGE showed broad midband-Lp and increased pre-beta-Lp in 16 of 19 untreated patients. Those findings suggested that untreated nephrotic patients had impaired catabolism of VLDL to LDL in peripheral tissue or impaired hepatic catabolism of IDL and LDL. Furthermore, PAGE showed decreased alpha-Lp in all patients with untreated NS. Correlation was not found between histological classification of glomerulonephritis and broad midband or hyperlipidemia. After administration of prednisolone, PAGE revealed the appearance of chylomicron, and increased pre-beta-LP and alpha-Lp. After remission, broad midband-Lp and pre-beta-Lp were markedly decreased or dis appeared in all 6 patients with broad midband-Lp in untreated phase, and serum total cholesterol and beta-Lp concentrations were markedly decreased, and HDL- cholestrol was markedly increased. In the course of remission, serum total cholesterol, triglycerides and beta-Lp concentrations had negative correlation with serum albumin concentration. Furthermore, serum total cholesterol and beta-Lp concentrations were decreased along with decrease of urinary protein excretion. The results of the present study suggest that the loss of serum albumin and/or some other substances to the urine cause broad midband.

Adolescent↗

[Autotransplantation of parathyroid glands in thyroid carcinoma surgery and their postoperative function].

Total removal and subsequent autotransplantation of parathyroid glands were carried out in operations for thyroid carcinoma in 25 cases. For the purpose of fine dissection of paratracheal lymph nodes, before thyroidectomy more than 2 parathyroid glands were found and transplanted into greater pectoralis muscle. The patients who underwent surgery were studied for more than one year following operation to determine the short term and long term outcomes of the procedure. None of the patients received prophylactic calcium supplement therapy except for hypocalcemic symptoms. In thirteen patients, the parathyroid function was almost completely restored within 3 weeks without any postoperative substitution therapy, with an obvious surge in the plasma PTH level on 5P.O.D. The serum Ca level started to elevate on 7P.O.D. and recovered to 97.4% of the preoperative value 3 weeks after transplantation. As for the 12 patients who exhibited hypocalcemic symptoms, Ca lactate and hydroxycholecalciferol were administered for only 24.7 and 17.0 days, respectively. Serum levels of Ca and P, as well as the index of bone mineral content, were all within the extremely excellent range even one year after operation. None of the patients was on a substitution regimen. These results suggest that autotransplantation is a valuable alternative for the preservation of the parathyroid function in operations for thyroid carcinoma.

Adult↗

A good outcome pregnancy in a patient with paroxysmal nocturnal hemoglobinuria.

In this report, the maternal and fetal risks in a patient with paroxysmal nocturnal hemoglobinuria (PNH) were evaluated. A patient with PNH carried a pregnancy to successful delivery, with a healthy male infant, and suffered from postpartum cerebral subcortical, but not hepatic, thrombosis followed by recovery. An elevation of serum levels of lactate dehydrogenase isoenzyme, alpha-hydroxybutyrate dehydrogenase, was observed during pregnancy. The level was ameliorated to the non-pregnant level by delivery. However, hemoglobin concentrations during pregnancy and post-partum were at least 8 g/dl. This is a first report that shows tight coupling between an onset of intravenous hemolysis and pregnancy. The management of pregnancies in such patients is also discussed.

Adult↗

[Report of 108 patients with valvular heart disease who underwent re-operations through repeated median sternotomy incision].

108 patients who underwent redo median sternotomy between January 1975 and April 1988 were studied to determine factors affecting risk of cardiac reoperations. (1) Seventeen of 108 patients died, yielding an overall mortality of 15.7%. (2) Preoperative diagnosis had a significant correlation with mortality, which was higher with prosthetic valve endocarditis (50.0%) than with all other indications for reoperation. (3) Operative mortality was related to pre-reoperation functional class: 8.7% for New York Heart Association (NYHA) class II, 9.8% for class III and 27.8% for class IV. (4) Based on the degree of urgency, elective reoperation had a mortality of 5.4%, while emergency procedures carried a mortality of 61.5%. (5) Cardiac catheterization information was available in 53 patients. The pulmonary artery pressure was higher in the died group. There were no significant differences in pulmonary capillary wedge pressure and cardiac index between the survived and died. (6) Operation time, aortic cross clamp time and pump run were significantly longer in the died than in the survived group. The died had more blood loss during operative procedure. To decrease operative mortality, technical improvement and increased experience were necessary for surgeons. We prefer to free entirely pericardial adhesion to facilitate mobilization and evacuate air, and to make intra-cardiac procedure more easier and safety. Furthermore early reoperation before irreversible deterioration occurs was necessary since myocardial function was found to be a major determinant of surgical results.

Adult↗

[Biological versus mechanical valves in the mitral position].

The long-term late results of isolated mitral valve replacement before April 1981 were retrospectively evaluated in 54 patients receiving a Hancock valve (HX) with a total follow-up of 424 patient-years (py) and 37 patients receiving a Björk-Shiley valve (BS) with a total follow-up of 366 py. There was no significant difference in regard to preoperative age, cardiothoracic ratio, electrocardiogram, or New York Heart Association functional class between the two groups. All of the BS group and 43 of the HX patients received long-term anticoagulant therapy. No significant difference was notable between the two groups in hospital mortality. Actuarial survival rate excluding hospital deaths was 75.5 +/- 6.7% for the HX group, and 80.8 +/- 7.1% for the BS group at ten years (not significant). There was no significant difference between the two groups in overall incidence of thromboembolism (HX 1.4% py, BS 1.9% py), anticoagulant related bleeding (HX 0.5% py, BS 0.8% py), or endocarditis (HX 0.5% py, BS 0.3% py). Actuarial freedom from reoperation at ten years was 69.6 +/- 8.1% for the HX group, and 93.5 +/- 4.4% for the BS group (p less than 0.01). Event free survival excluding hospital deaths at ten years was 49.2 +/- 8.1% for the HX group, 70.6 +/- 8.3% for the BS group (p less than 0.05). We prefer a mechanical prosthesis except in patients over 65 years old, who have a short life expectancy, in whom anticoagulation is thought to be difficult, and who hope a biological valve.

Adult↗

[A clinical experience of ofloxacin in patients with respiratory infection].

To a total of 31 patients (18 in- and 13 out-patients) having respiratory infections, we administered ofloxacin (OFLX) orally at a daily dose of 300 to 600 mg and examined its clinical effect. The clinical effect in the 31 cases was as good as 83.9%. Among these cases, 6 cases showed Pseudomonas aeruginosa, thereby indicating the effective rate of OFLX at 50%. In the present examination, we experienced cases in which OFLX-resistant P. aeruginosa appeared in the cases of long-term administration of OFLX. Therefore, our clinic carried out the sensitivity test of P. aeruginosa against OFLX, gentamicin (GM) and imipenem (IPM) in 1987, using clinically-segregated strains of P. aeruginosa obtained by sputum tests. The sensitive strains, which were 100% sensitive to OFLX, GM, IPM respectively in 1985, showed, in segregated strains in 1987, sensitivity of OFLX 57.1%, GM 85.7% and IPM 100%, thus indicating the high resistance-acquiring frequency of P. aeruginosa against OFLX.

Adult↗

[A case of coexistent adenocarcinoma and primary malignant lymphoma of the stomach].

A case of a simultaneous adenocarcinoma and a primary malignant lymphoma of the stomach is presented. A sixty-one-year-old male was referred to us with epigastralgia. Gastroscopy and a biopsy revealed a *** c-like lesion in the stomach and, on histological examination, was determined as being an adenocarcinoma. A proximal gastrectomy and an R2-resection of lymph nodes then was performed. A pathological examination of the resected stomach disclosed a malignant lymphoma neighboring the adenocarcinoma. The presence of a simultaneous carcinoma and a malignant lymphoma of the stomach is quite rare, with only twenty-eight documented patients reported in the Japanese literature. This entity is discussed.

Adenocarcinoma↗

Mutant subtilisin E with enhanced protease activity obtained by site-directed mutagenesis.

The specific activity of subtilisin E, an alkaline serine protease of Bacillus subtilis, was substantially increased by optimizing the amino acid residue at position 31 (Ile in the wild-type enzyme) in the vicinity of the catalytic triad of the enzyme. Eight uncharged amino acids (Cys, Ser, Thr, Gly, Ala, Val, Leu, and Phe) were introduced at this site, which is next to catalytic Asp32, using site-directed mutagenesis. Mutant enzymes were expressed in Escherichia coli and were prepared from the periplasmic space. Only the Val and Leu substitutions gave active enzyme, and the Leu31 mutant was found to have a greatly increased activity compared to the wild-type enzyme. The other six mutant enzymes showed a marked decrease in activity. This result indicates that a branched-chain amino acid at position 31 is essential for the expression of subtilisin activity and that the level of the activity depends on side chain structure. The purified Leu31 mutant enzyme was analyzed with respect to substrate specificity, heat stability, and optimal temperature. It was found that the Leu31 replacement caused a prominent 2-6-fold increase in catalytic efficiency (kcat/Km) due to a larger kcat for peptide substrates.

Bacillus subtilis↗

The lateral vestibular nucleus is a site for the depressant action of benzodiazepines on the crossed extensor reflex.

The effects of diazepam microinjected into the subcerebellar nuclei, the lateral vestibular nucleus (LVN), the red nucleus and the substantia nigra were investigated using the crossed extensor reflex (CER) model in chloralose-anesthetized rats. Microinjections of diazepam at doses of 1 and 25 ng/animal into the left LVN, ipsilateral to the testing muscle, produced a dose-related CER depression, while injections of diazepam at a dose of up to 100 ng/animal into the right LVN and into other regions tested produced little effect. The CER depression produced by diazepam could be clearly reversed by a subsequent intravenous administration of Ro 15-1788, a benzodiazepine antagonist. Electrical lesions of the left LVN decreased the amplitude of CER in otherwise untreated rats. Intravenously administered diazepam at a dose of 0.01 or 0.05 mg/kg decreased spontaneous firing of LVN neurons. Iontophoretically applied GABA or flurazepam, a water-soluble benzodiazepine, decreased the spontaneous firing of LVN neurons. Depressant actions on neuronal activity in the LVN produced by both diazepam and flurazepam were clearly antagonized by intravenously administered Ro 15-1788, while it failed to reverse the depression produced by GABA. These findings indicate that the LVN is a major site of the CER depressant action of benzodiazepines and a possible mechanism of action is discussed.

Action Potentials↗

Ontogeny of calcitonin gene-related peptide-immunoreactive structures in the rat forebrain and diencephalon.

Ontogeny of the calcitonin gene-related peptide (CGRP)-containing structures was investigated in the forebrain and diencephalon of the rat by means of indirect immunofluorescence. CGRP-like immunoreactive (CGRP-IR) fibers first appeared at gestational day 18 (E18) in the primordia of the bed nucleus of the stria terminalis, central amygdaloid nucleus and posterolateral portion of the lateral hypothalamic nucleus. CGRP-IR fibers gradually increased in immunoreactivity and in number in these nuclei toward birth. A pronounced increase of CGRP-like immunoreactive fibers was found after birth in these nuclei and made very dense plexuses of fibers in adult animals. A few CGRP-IR fibers first appeared at the perinatal stage in the lateral septum, the most caudal portion of the caudate-putamen, and ventromedial and ventroposterior thalamic nuclei. Then the immunoreactive fibers increased and dense plexuses were present in these brain areas of the adult. A small number of immunoreactive fibers appeared at postnatal day 4-7 (P4-7) in the caudal insular cortex and ventromedial hypothalamic nucleus. A significant number of fibers was present in these areas of the adult. On the other hand, CGRP-like immunoreactivity in cell bodies was first detected with faint immunofluorescence at P4 in the anteromedial parts of the lateral hypothalamic area and ventromedial and ventroposterior thalamic nuclei. Thereafter CGRP-IR cells increased in immunoreactivity, and a significant number of cells was noted in these nuclei of the adult. In addition, CGRP-IR cells are identified in the medial amygdaloid nucleus, and medial preoptic area at P14. In conclusion, in the forebrain and diencephalon (1) CGRP-like immunoreactivity appears in fibers earlier than in cell bodies, suggesting that at least some of immunoreactive fibers originate from the lower brainstem, and (2) high density of CGRP-IR structures present in the brain at embryonic and early postnatal stages may indicate that CGRP could be an important factor involved in the developmental organization of the central nervous system.

Aging↗