Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 1,135 records · Page 63Linked to original sources

PubMedDate not supplied

Microdensity of solitary bone cyst after steroid injection.

The change of bone density in five patients with solitary bone cysts (SBC) was directly measured by microdensitometry (MD). Standard plain radiographs could not always predict the strength of the bone, but with MD, smaller changes in bone density could be found quantitatively. The density of the lesion temporarily decreased just after steroid injection and began to increase to maximum level in approximately 4 or 5 months. However, in two patients, the density decreased gradually to the first MD levels and refractured. In this article we stress the usefulness of direct MD in detecting the strength of the lesion.

Absorptiometry, Photon↗

PubMedDate not supplied

Recurrent dislocation of the patella in Turner's syndrome.

We report two patients with Turner's syndrome who presented with recurrent dislocation of the patella (RDP). Both had a positive family history of patellar instability. The association of RDP with Turner's syndrome has not been reported previously. A subsequent study in 14 patients with Turner's syndrome demonstrated radiographical patellofemoral incongruency in eight patients, but no clinical manifestation of patellar instability. Although the present study suggests a possible link between Turner's syndrome and patellofemoral incongruency, it could not ascertain whether or not Turner's syndrome predisposes a patient to RDP.

Adolescent↗

PubMedDate not supplied

Effects of vaso-active agents on hepatic function and blood gases in patients with cirrhosis: a study of vasopressin and nitroglycerin.

The effects of vaso-active agents on hepatic function and splanchnic oxygenation were studied in 17 patients with cirrhosis and portal hypertension. Eight patients received vasopressin (0.3 iu/min) and nine patients received nitroglycerin (50 micrograms/min). Both drugs caused a significant reduction in the portal venous pressure gradient. Vasopressin infusion significantly decreased intrinsic clearance of indocyanine green (-23%, P less than 0.01). This may be due to a decreased hepatic perfusion (-28%, P less than 0.01) and portal venous oxygenation (-15% in portal venous oxygen tension, P less than 0.05). In contrast, no changes in hepatic perfusion and portal venous oxygenation were observed after nitroglycerin infusion. Nitroglycerin did not decrease intrinsic clearance of indocyanine green. These results suggest that vasodilators, rather than vasoconstrictors, might be welcome in the treatment of patients with cirrhosis and portal hypertension.

Carbon Dioxide↗

PubMedDate not supplied

Quantitation of c-erbB-2 gene amplification in breast cancer tissue by competitive PCR.

Controversy exists regarding the relationship of the degree of c-erbB-2 amplification to other prognostic factors in breast cancer. To determine the degree of amplification of c-erbB-2 exactly, a sensitive and quantitative method is required. We have developed a competitive PCR method to quantitatively determine the amplification of the c-erbB-2 oncogene. Using this method, we evaluated DNA from 27 breast cancer tissue specimens and DNA from peripheral blood leukocytes from a normal individual. Regarding the relationship between the degree of c-erbB-2 amplification and clinicopathological factors, we found a greater degree of amplification of the c-erbB-2 oncogene in estrogen receptor- negative or progesterone receptor-negative specimens than in positive ones and in lymph node metastasis-positive specimens than in negative specimens, in stages II, III, and IV of disease compared with stage I disease, and in samples with positive lymphatic vessel invasion than with no lymphatic vessel invasion. Generally, these factors were seen in the group of patients who had a bad prognosis. By univariate analysis and multivariate analysis, reverse correlation was observed between amplification of c-erbB-2 and overall survival. Regarding disease-free survival, these relationships were observed only with univariate analysis in our group of patients.

Adult↗

PubMedDate not supplied

Effects of intravenous omega-3 and omega-6 fat emulsion on cytokine production and delayed type hypersensitivity in burned rats receiving total parenteral nutrition.

BACKGROUND: The effects of fat emulsions containing omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) on fatty acid profile, cytokine production, and delayed type hypersensitivity (DTH) in burned rats receiving total parenteral nutrition (TPN) were investigated. METHODS: A fat emulsion containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was prepared (omega-3 fat emulsion). Sprague-Dawley rats were fed fat-free chow for 2 weeks and were divided into three groups according to the contents of TPN. Groups C (n = 11) and C' (n = 14) received fat-free TPN. Group omega6 received safflower oil emulsion containing linoleic acid (omega-6 PUFA) (n = 11). Group omega3 (n = 11) received safflower oil emulsion (19% of total caloric intake) and fat emulsion containing only EPA and DHA (1% of total calories). On day 5, all rats except for those in group C' were subjected to a 20% full-thickness burn. Group C' did not receive burns. After 48 hours, the rats were killed. RESULTS: The interleukin (IL)-8 concentration was significantly 45% lower in group omega3 than in group C (p < .05). The IL-10 concentration was significantly 15% lower in group omega3 than in group omega6 (p < .05). The IL-6 concentration was increased in group omega6 but not in group omega3 when compared with group C. The IL-6 and IL-8 were not detected in group C'. Prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) concentrations were increased by burn injury, but there were no significant differences among the burned groups. Cell-mediated immunity was thus significantly decreased in burned groups (groups C, omega6, and omega3; p < .01). However, the decrease of DTH was smaller in group omega3 and significantly greater when compared with groups C and omega6 (p < .05). CONCLUSIONS: omega-6 PUFAs increased serum inflammatory cytokine levels in a stressed state. omega-3 fat emulsion reduced IL-8 and IL-10 levels and prevented immunosuppression in burned rats that were receiving TPN.

Animals↗

PubMedDate not supplied

Effect of IGF-1 on protein metabolism in burned rats.

The effects of insulin-like growth factor-1 (IGF-1) on the catabolic and immune response induced by thermal injury were studied in burned rats fed by TPN. An increase of synthesis greater than the increase of breakdown resulted in improved nitrogen retention in the IGF-1 group. There was no effect on the mRNA in the structural proteins of the skeletal muscle and liver. However, the gene expression of albumin and the structural proteins of the diaphragm increased significantly in the rats receiving IGF-1. The proliferation of the gut mucosa and the fractional protein synthesis rate of the small intestine increased, and the endotoxin content of the liver and spleen were smaller in the burned rats that received IGF-1. Delayed type hypersensitivity increased significantly (p < .01) in the IGF-1 group. In conclusion, IGF-1 improved the whole-body protein metabolism, and albumin and respiratory muscle protein synthesis in the burned rats. It significantly promoted the proliferation of the intestinal mucosa, and reduced the intestinal translocation of endotoxin. Cellular immunity was also enhanced.

Analysis of Variance↗

PubMedDate not supplied

Hemoglobin A1 properties of diabetic and uremic patients.

Patients with diabetes mellitus as well as those with renal failure had high hemoglobin A1 (HbA1) levels. However, the portion of HbA1a+b fractions was larger in patients with renal failure than in diabetic patients. Thus, if renal disorder is advanced, caution should be exercised in evaluating HbA1 data. Furthermore, not only is the collective determination of Hb minor components such as HbA1 required, but also investigation of changes in HbA1a+b in patients with renal failure or diabetic nephropathy.

Diabetes Mellitus↗

PubMedDate not supplied

Analysis of the vestibulo-spinal system with a five-dimensional feedback model.

The role of the vestibulo-spinal system involved in the maintenance of upright standing posture was studied by a time series analysis with a 5-dimensional feedback model. The system was composed of sways of the head, shoulders, hips and activities of the nuchal and soleus muscles. The results were displayed as determinants of noise correlation matrix, power spectrum, correlogram, transfer function and relative power contribution. The five movements constitute a feedback system in normal subjects. Bilateral loss of labyrinthine function indicates a break in the feedback system. The power spectrum and relative noise contribution indicate that the vestibulo-spinal system regulates low-frequency body sway in upright standing. However, the contribution of the system was low in the overall control of standing posture.

Feedback↗

PubMedDate not supplied

Modulation by head and trunk positions of the vestibulo-spinal reflexes evoked by galvanic stimulation of the labyrinth. Observations by labyrinthine evoked EMG.

Modulation by head and trunk positions of the vestibulo-spinal reflexes was studied in the soleus muscle activities induced by galvanic stimulation of the labyrinth. The stimulation was applied using a bipolar-biaural method with the cathode on the right ear and the anode on the left ear. The intensity was 1 mA and duration 3 s. 1) When the labyrinth was stimulated with the head facing forward, soleus muscle activities increased on the right side and decreased on the left, with a latency of about 100 ms. In spite of the same stimulation, activities of the soleus muscle on both sides decreased with the head rotated to the right and increased with the head rotated to the left. 2) The responses in upper-body rotation were the same as in the case of head rotation. 3) In trunk rotation, some cases showed the same responses as with the trunk facing forward in rotation to the right and left, while others showed changes in muscular activities with the head rotation caused by rotating the trunk. 4) Changes in labyrinthine evoked EMG by head and trunk positions were considered to be due to interaction of vestibular and proprioceptive inputs on the interneurons of the spinal cord.

Ear, Inner↗

PubMedDate not supplied

Pharmacokinetics of isolated hepatic perfusion with high dose tumor necrosis factor in rat model.

BACKGROUND: Although the application of an isolation procedure with tumor necrosis factor (TNF) to the liver is quite attractive, an animal model is not yet available to evaluate antitumor effects by TNF in isolated hepatic perfusion (IHP). To establish the rat model in IHP, the pharmacokinetics of TNF, both in a perfusate and in a systemic circuit should be examined. METHODS: All rats underwent IHP with TNF. After a 10 min perfusion, a washout procedure was performed for 5 min, after which isolation was terminated. Throughout the procedure and afterward, blood samples were obtained from the systemic blood and concentrations of TNF were assayed by L-929 cytotoxicity. RESULTS: After the administration of 240 micrograms of TNF in the circuit, TNF reached a plateau at about 12.7 micrograms/ml of perfusion fluid, lasting until the end of IHP. As a result of the washout procedure, regional TNF concentrations declined from 12.7 micrograms/ml to 1.5 micrograms/ml. At the beginning of the IHP, all rats exhibited no detectable level of TNF activity in the systemic circulation (< 100 pg/ml). With time, TNF plasma levels quickly increased to reach a plateau of about 0.2 microgram/ml at 15 min. Systemic leakage of TNF is calculated as less than 2% of the total TNF in perfusate during perfusion. CONCLUSION: Rat IHP models with TNF showed that systemic leakage of TNF was higher than that of pig models, although a large enough amount of TNF in perfusate was achieved without death. Rat models might be feasible to evaluate antitumor effect of IHP against liver metastatic tumors.

Animals↗

PubMedDate not supplied

Reduction of hepatotoxicity of tumor necrosis factor in isolated hepatic perfusion by administration of glucocorticoid as well as lipopolysaccharide.

BACKGROUND: The application of an isolation procedure with tumor necrosis factor (TNF) to the liver is quit attractive, however, one of problems to overcome is reducing the toxicity to the liver caused by high doses of TNF. MATERIALS AND METHODS: Rats underwent isolated hepatic perfusion (IHP) with TNF and pre-treatment of subcutaneous administration of dexamethasone (4 mg/kg) and/or intradermal administration of LPS (50 micrograms/rat). After a 10 min perfusion, a washout procedure was performed for 5 min, after which isolation was terminated. RESULTS: SD or Wister rats and F344 rats tolerated up to 120 mg/rat or 4 micrograms/rat, respectively. Dexamethasone and/or LPS was tolerated at 40 micrograms/rat of TNF in F344 rat and showed a significant reduction of hepatotoxicity, and indicated histologically the suppression of ballooning and of necrosis during and after perfusion by TNF. CONCLUSION: We propose new a protocol for IHP as follows: 1. the intradermal administration of LPS for protection against toxicity of TNF, 2. IHP with TNF-SAM2, a mutain of TNF-alpha, having less toxicity than conventional TNF-alpha, and 3. simultaneous perfusion with chemotherapeutic agents such as 5-fluorouracil (5-FU).

Adult↗

PubMedDate not supplied

Relationship between microvessel quantification and inducibility of endogenous tumor necrosis factor in colorectal adenocarcinoma.

BACKGROUND: Although we have reported that the inducibility of endogenous tumor necrosis factor (en-TNF) by tumor cells is an independent prognostic factor in Dukes stage C colorectal cancer patients, the mechanism by which the patients having high inducibility of en-TNF show better prognosis is still unclear. We hypothesize that the inducibility of en-TNF by colorectal tumor cells affects the prognosis of patients through the modulation of angiogenesis. Thus, the aim of this study is to clarify the relationship between inducibility of en-TNF and tumor vascularity in colorectal cancer. PATIENTS AND METHODS: Histological sections from 62 Dukes stage C colorectal cancer patients who received curative operation were immunostained for CD34 antigen. Microvessels were counted in the photograph of x200 fields (0.298 mm2). The average count of five most vascular areas was determined as a microvessel density of each case. RESULTS: Two of 62 cases were excluded from the analysis, because of insufficient staining. A total of 60 patients were dichotomized by a median vessel count of 34 into two groups: 30 patients with lower microvessel density (Low MVD group) and 30 patients with higher microvessel density (High MVD group). There was no significance in the distribution of all clinicopathological factors among these two groups. Regarding en-TNF inducibility, no difference was shown between the two groups. The five year survival rate of Low MVD group and High MVD group were 58.7% and 68.0%, respectively. And, the 5 year relapse-free survival rate of Low MVD group and High MVD group were 59.7% and 52.2%, respectively. No significant difference was demonstrated between Low MVD group and High MVD group. CONCLUSION: Intratumoral microvessel density did not influence on the prognosis of colorectal cancer patients in Dukes stage C after curative operation. The inducibility of en-TNF showed no correlation with intratumoral microvessel density in Dukes stage C patients after curative operation.

Adenocarcinoma↗

PubMedDate not supplied

Inhibitory effect of erythromycin on P-glycoprotein-mediated biliary excretion of doxorubicin in rats.

The macrolide antibiotic erythromycin has recently been shown to overcome the resistance to anticancer drugs that results from overexpression of P-glycoprotein. The present study, using erythromycin lactobionic acid as a model drug, investigated the inhibitory effects of erythromycin on the efflux of doxorubicin from P388/ADR cells expressing P-glycoprotein and on the biliary excretion mechanism of doxorubicin in rats, which is primarily mediated by P-glycoprotein. Erythromycin lactobionic acid was found to inhibit the efflux of doxorubicin (5 microM) from P388/ADR cells in a concentration-dependent manner. In rats receiving constant-rate infusion of doxorubicin (30 micrograms/min), both the biliary and renal clearance of this drug dramatically decreased and its plasma concentrations increased after an intravenous injection of erythromycin lactobionic acid (100 mg/kg as erythromycin). These results suggest that erythromycin competitively inhibits P-glycoprotein-mediated biliary and renal excretion of doxorubicin. The effect of erythromycin on the biliary secretion of doxorubicin was also analyzed quantitatively by the competitive inhibition model. The computer-estimated values of Vmax/Km, Km and Ki were 8.79 ml/minute, 0.82 microgram/ml and 0.41 microgram/ml, respectively. The findings of these experiments suggest that the inhibitory effect of erythromycin on the P-glycoprotein-mediated biliary excretion of doxorubicin is competitive and that combination chemotherapy of doxorubicin with erythromycin may induce toxicity as a result of increased plasma concentrations of doxorubicin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Synergistic antitumour effect of TNF-SAM2 with melphalan and doxorubicin in isolated limb perfusion in rats.

An isolated limb perfusion model (ILP) using soft tissue sarcoma bearing rats (BN175) was used to study antitumour activity of a tumour necrosis factor alpha mutant (TNF-SAM2) in combination with melphalan and doxorubicin. Progressive disease was demonstrated after ILP without agents (sham) or with 50 micrograms TNF-SAM2. ILP with 40 micrograms melphalan or 400 micrograms doxorubicin resulted in no change of tumour volume or progressive disease five days after perfusion. Partial and complete response rates were demonstrated in 76% of rats when the combination of TNF-SAM2 and melphalan was used. TNF-SAM2 in combination with doxorubicin was synergistic as well with a 70% response rate. Histopathologically these responses consisted of hemorrhagic necrosis of the coagulative type. 2 In conclusion, TNF-SAM2 has similar antitumour activity in combination with melphalan or doxorubicin as rHuTNF in sarcoma-bearing rats and is eligible to be tested in clinical ILP or organ perfusion settings because of its potential decreased toxicity.

Animals↗

PubMedDate not supplied

A new method of antitumor therapy with a high dose of TNF perfusion for unresectable liver tumors.

There are primary and secondary malignant liver tumors for which principal treatment is surgical resection. There is no established treatment for unresectable malignant liver tumors, however, and the prognosis for these is quite poor. An effective treatment for malignant liver tumors is thus urgently needed. Recent advances in molecular biology have uncovered the structures and/or functions of many cytokines thought to have a strong relation with the mechanisms of the antitumor effect of biological therapies. Availability of those cytokines in large amounts and homogeneously owing to advances in recombinant technology makes it possible to use them clinically. Among cytokines demonstrating antitumor activities, tumor necrosis factor-alpha (TNF-alpha) is one of the strongest. However, severe toxicity such as hypotension, abnormalities in liver function, leukopenia, chill and thrombus formation makes TNF-alpha difficult to use systemically as an antitumor drug. To enhance cytotoxicity while decreasing the side effects, especially hypotension, we developed a mutein called TNF-SAM2 by protein-engineering. The biological activity of TNF-SAM2 was more beneficial than TNF-alpha for antitumor therapy, since its side effects were milder. In contrast, using the isolated limb perfusion (ILP) method against malignant melanoma and soft tissue sarcoma of the extremities in combination with TNF-alpha and melphalan, a high response rate of 70-100% was observed. These observations led to the re-evaluation of TNF as an antitumor drug. A preliminary clinical trial was done using TNF-alpha combined with the formation of a closed circuit (isolated hepatic perfusion method) targeting the liver and a response rate of over 75% was achieved against malignant liver tumors. To isolate the liver from the systemic circulation, however, required a laparotomy, so that patients were subjected to excessive surgical stress. Isolated hypoxic hepatic perfusion (IHHP) using balloon catheters is a treatment developed to overcome such stress and we are planning to do clinical trials of IHHP with TNF-SAM2 in combination with a chemotherapeutic agent against malignant liver tumor patients. IHHP combined with TNF-SAM2 and a chemotherapeutic agent might be more beneficial in antitumor effects as well as in maintaining good quality of life (QOL) for the patient.

Animals↗

PubMedDate not supplied

Agrimoniin, an antitumor tannin of Agrimonia pilosa Ledeb., induces interleukin-1.

The induction of interleukin-1 (IL-1) by agrimoniin, a tannin of Agrimonia pilosa Ledeb., in human peripheral blood mononuclear cells (PBMC) in vitro and in mouse adherent peritoneal exudate cells (PEC) in vivo was studied. A significant amount of IL-1 beta in the culture supernatant of the human PBMC stimulated with agrimoniin was detected with an enzyme-linked immunoadherent assay. Agrimoniin induced IL-1 beta secretion dose- and time-dependently. The adherent PEC from mice intraperitoneally injected with agrimoniin (10 mg/kg) also secreted IL-1 4 days later. These results suggest that agrimoniin, a plant tannin, is a novel cytokine inducer.

Adult↗

PubMedDate not supplied

Effects of sodium channel blockers on electrical field stimulation-induced guinea-pig tracheal smooth muscle contraction.

The effects of sodium channel blockers, a conventional one: tetrodotoxin, and clinically available ones: cibenzoline, flecainide and SUN 1165 [N-(2,6-dimethylphenyl)-8-pyrrolizidine-acetamide hydrochloride hemihydrate] on electrical field stimulation-induced and carbachol-induced guinea-pig tracheal smooth muscle contraction were investigated. Electrical field stimulation was performed at 50 V with 20 Hz and 0.8 msec square pulse duration. Carbachol (5 x 10(-8) M) was used for induction of tracheal contractions. All agents were administered before electrical field stimulation or carbachol administration. Electrical field stimulation-induced tracheal smooth muscle contraction was dose-dependently reduced by all sodium channel blockers used. The effects of sodium channel blockers on electrical field stimulation-induced contraction were greater than those on carbachol-induced contractions, except for SUN 1165 which reduced similarly both electrical field stimulation- and carbachol-induced contractions. These results indicate that the sodium influx is closely related to the acetylcholine release, resulting in smooth muscle contraction. Since the parasympathetic nervous system may be involved in the genesis of various pathological conditions, such as bronchial asthma, sodium channel blockers could contribute to the management of these conditions.

Animals↗

PubMedDate not supplied

The role of bone marrow in bone morphogenetic protein-induced repair of femoral massive diaphyseal defects.

The midshaft of the femur of one-year-old rats was resected and the reparative process completely blocked by distraction of the bone ends with an omega-shaped wire. Bone repair extended retrograde instead of across the diaphyseal defect and invariably culminated in nonunion. New bone was induced to grow across the defect by implantation of BMP, and regeneration was similarly enhanced by transplantation of autologous marrow, but union was produced only by composite transplants of marrow and implants of BMP. Union occurred more rapidly from the transplant-implant composite than from autologous cortical bone. These observations suggest that bone marrow stroma cell include both pre-existing osteogenic precursor cells and mesenchymal cells that respond to BMP by differentiating into osteoblast for the repair of large femoral bone defects.

Animals↗