Biomedical subjects

T Ikeda

Publications and source records attributed to T Ikeda.

At least 235 records · Page 13Linked to original sources

PubMed2000

Regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) by bone resorptive factors in osteoblastic cells.

In addition to their stimulating function on osteoclastic bone resorption, bone resorptive factors may regulate proteinases and related factors in osteoblastic cells to degrade bone matrix proteins. This study investigated the regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) by bone resorptive factors in the cultures of mouse osteoblastic MC3T3-E1 cells, mouse primary osteoblastic (POB) cells, and neonatal mouse calvariae. Expression of either MMP-2, -3, -9, -11, -13, and -14 or TIMP-1, -2, and -3 was detected in MC3T3-E1 cells and POB cells. When the bone resorptive factors parathyroid hormone, 1,25-dihydroxyvitamin D(3), prostaglandin E(2), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) were added to the cell cultures, MMP-13 mRNA levels were found predominantly to increase by all resorptive factors in the three cultures. mRNA levels of either MMP-3 and -9 or TIMP-1 and -3 were found to increase mainly by the cytokines IL-1beta and TNF-alpha. BB94, a nonselective MMP inhibitor, neutralized the (45)Ca release stimulated by these resorptive factors to an extent similar to that of calcitonin, strongly suggesting that bone resorptive factors function at least partly through MMP formation. We propose that MMP-13 mRNA expression in osteoblastic cells may play an important role in stimulating matrix degradation by both systemic and local resorptive factors, whereas either MMP-3 and -9 or TIMP-1 and -3 might modulate matrix degradation by local cytokines only.

Animals↗

PubMed2000

Sentinel lymph node biopsy using tin colloid RI and blue dye method.

Axillary dissection has been considered essential for breast cancer staging because nodal metastasis is the most powerful predictive factor for recurrence. On the other hand, morbidity, such as lymphedema and shoulder dysfunction, may occur. Sentinel node biopsy is a good way to avoid unnecessary axillary dissection. We used tin colloid as a carrier of Tc99m tracer together with the blue dye method. The detection rate of the sentinel node was 27 cases out of 29 (90%) for the blue dye method, 10 cases out of 19 (53%) for the RI method, and 27 out of 33 (82%) for the combined method. The detection rate of the RI method was improved after adding the subcutaneous injection over the tumor from 45% before adding the subcutaneous injection to 82% after adding it. The false negative rate was 11% for the blue dye method, 0% for the RI method, and 10% for the combined method. This yields a sensitivity of 89% for the blue dye method, 100% for the RI method, and 90% for the combined method. Specificity was 100% for all three methods. Accuracy was 96% for the blue dye method, 100% for the RI method, and 96% for the combined method. There were two false negative cases. The average number of sentinel lymph nodes was 2.12 for the dye method, 1.66 for the RI method, and 1.95 for the combined method. There were three of 49 cases with identified parasternal lymph nodes by RI imaging. Lymphatic mapping using tin colloid may be useful for detecting sentinel nodes.

Adult↗

PubMed2000

Lymph node metastasis from breast cancer diagnosed by F-18 FDG whole-body PET (case report).

We report a 48-year-old woman with lymph node (LN) metastases from breast cancer in whom diagnosis was difficult by conventional imaging methods but easy by F-18 fluorodeoxyglucose (FDG) PET. She was given a diagnosis of right breast cancer and then underwent modified radical mastectomy in December 1997. During routine CT and US studies in September 1998, a questionable LN measuring 1 cm in diameter was detected in the right supraclavicular region, but a definitive diagnosis of this LN was difficult by these tests. The patient underwent FDG PET test, which showed strong nodular activity (SUV= 7.1) in the right supraclavicular region, indicating a metastatic lesion. Moreover, an unexpected second metastatic LN lesion (SUV= 5.5) in the medial aspect of the right axillary was diagnosed by PET. The PET results were confirmed by pathological examination of the surgical specimens. FDG PET is a useful tool to detect small malignant lesions that are not easily diagnosed by conventional imaging techniques such as CT and US. It is expected that PET test will be feasible at many institutions.

Adenocarcinoma↗

PubMed2000

Outlining the body contours with scattered photons in lymphoscintigraphy for sentinel nodes.

Although lymphoscintigraphy is a useful method of detecting the sentinel nodes of malignancy, conventional lymphoscintigraphy images only the sentinel nodes without revealing their anatomical location. We, therefore, used scattered photons to attempt to outline the body contours of patients with either breast or esophageal cancer. Lymphoscintigraphy was performed 3 to 4 hours after the injection of 111 MBq of 99mTc tin colloid into the peritumoral region. Images were obtained with dual-energy windows of 130 to 150 keV for the primary photons and 70 to 110 keV for the scattered photons. The images constructed from the scattered photons clearly showed the contours of the body, and the fusion images constructed from the primary and scattered photons allowed for easy identification of the location of the sentinel nodes. The results of this study confirm that images obtained from scattered photons on lymphoscintigraphy are helpful in identifying the anatomical location of sentinel nodes.

Adult↗

PubMed2000

Clinical assessment of unilateral pulmonary artery occlusion test with dobutamine infusion. Expansion of surgical indications in patients with primary lung cancer and impaired cardiopulmonary functions.

OBJECTIVES: We evaluated the possibility of expanding indications for pulmonary resection based on an assessment of the pressure-flow relationship in pulmonary circulation. METHODS: In 6 of 28 lung cancer patients whose total pulmonary vascular resistance index exceeded the threshold during unilateral pulmonary artery occlusion testing, we conducted unilateral pulmonary artery occlusion testing with dobutamine administration, followed by lung resection. We studied hemodynamics during testing and derived a new indication for pulmonary resection from the postoperative course. RESULTS: Cardiac output was 3.82 +/- 0.74 l/min before testing, 3.66 +/- 0.76 l/min during pulmonary artery occlusion testing, and 5.92 +/- 1.78 l/min during unilateral pulmonary artery occlusion testing with dobutamine infusion. The total pulmonary vascular resistance index was 890 +/- 350 dyne.sec.cm-5.m2 before testing, 1170 +/- 320 dyne.sec.cm-5.m2 during testing, and 800 +/- 160 dyne.sec.cm-5.m2 during testing with dobutamine infusion. Cardiac output increased (p = 0.014) during unilateral pulmonary artery occlusion testing with dobutamine infusion, and the total pulmonary vascular resistance index significantly decreased (p = 0.034). Of the 4 patients eligible for lobectomy, 2 underwent the procedure--one undergoing segmentectomy in which pulmonary metastasis was found during surgery and the other undergoing radiotherapy for cN2 disease with chest wall invasion. Of the 2 initially ineligible for lobectomy, one underwent partial pulmonary resection and the other underwent lobectomy because the total pulmonary vascular resistance index was less than 800 dyne.sec.cm-5.m2 during selective pulmonary artery occlusion testing with dobutamine infusion, indicating eligibility for lobectomy. No severe complications of cardiopulmonary function failure after surgery occurred in any of the 5 cases. CONCLUSIONS: Unilateral pulmonary artery occlusion testing with dobutamine infusion is useful in determining patient eligibility for pulmonary resection.

Aged↗

PubMed2000

HNK-1 expression patterns in the embryonic rat heart distinguish between sinuatrial tissues and atrial myocardium.

HNK-1 expression was studied by immunohistochemistry in serial sections of embryonic and fetal rat hearts from 11.5 to 16.5 embryonic days. Graphic reconstructions were made to obtain detailed 3D information on the localization of immunoreactive tissues. The antibody used appeared to stain most parts of the venous sinus and the sinuatrial transitional zone as well as the atrioventricular transitional zone, but the patterns varied through the different developmental stages. At 11.5 days, positive myocardium was found in the right atrium and on top of the ventricular septal primordium. At 13.5 days, the left venous valve and the posterior atrial wall containing the orifice of the pulmonary vein were immunoreactive, and so were the right venous valve, the septum spurium and the superior, right-lateral and inferior parts of the atrioventricular canal. From the latter, immunoreactivity continued onto the crest of the ventricular septum. At 15.5 days, HNK-1 positivity in the two venous valves had become continuous, whereas the right-lateral part of the atrioventricular canal had lost its positivity, thus making the positive areas in the superior and inferior parts of this canal discontinuous. From the venous valves immunoreaction continued into the venous sinus septum but this area remained discontinuous with the inferior part of the atrioventricular canal. It is concluded that the entirety of venous sinus and sinuatrial transitional zone expresses the HNK-1 antigen and that the orifice of the pulmonary vein belongs to this complex, rather than to the embryonic atrium proper, which is HNK-1 negative. Extrapolation of these data to the adult human atrium leads to the conclusion hat most "atrial septal structures" are of sinuatrial origin, leaving the flap valve of the oval fossa (atrial septum primum) as the only really atrial structure. It is suggested that the atrioventricular node is derived from the inferior portion of the atrioventricular canal, and that two expansions of sinuatrial tissue form the substrate for anterior and posterior atrionodal inputs which in the literature have been described as internodal tracts.

Animals↗

PubMed2000

Selective inhibition of monoamine neurotransmitter transporters by synthetic local anesthetics.

Synthetic local anesthetics (LAs) have been found to have cocaine-like characteristics with some psychotomimetic action, possibly through monoaminergic neurotransmission. To gain insight into the relation between LA action and monoamine transporters, we investigated the effect of synthetic LAs on neurotransmitter transporters, including monoamine transporters. We used cloned transporter cDNAs and examined transient functional expression in COS cells and stable expression in HeLa cells. Among the LAs tested, procaine and other ester-type LAs inhibited [3H]DA uptake and binding of [3H]2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT), a cocaine analogue, in COS cells expressing rat dopamine transporter (DAT). The inhibition was concentration-dependent. The inhibitory effect on [3H]DA uptake was reversible and not dependent on pH, as observed in HeLa cells stably expressing DAT. Procaine also inhibited uptake of norepinephrine (NE) and serotonin (5-HT) by the norepinephrine transporter (NET) or serotonin transporter (SERT) expressed in COS cells. On the other hand, procaine and other LAs had little or no effect on [3H]GABA and [3H]glutamate uptake in COS cells expressing mouse GABA or rat glutamate/aspartate transporter. IC50 values for [3H]DA uptake inhibition correlated well with those for [3H]CFT binding inhibition, but not with intrinsic anesthetic potency. Kinetic analysis of monoamine uptake inhibition by procaine in COS cells expressing rat DAT, NET or SERT revealed a competitive action similar to that of cocaine. These results demonstrate that certain LAs selectively inhibit monoamine transporters. This might contribute to the cocaine-like psychotomimetic action of certain LAs.

Anesthetics, Local↗

PubMed2000

Glial cell line-derived neurotrophic factor protects against ischemia/hypoxia-induced brain injury in neonatal rat.

Ischemic/hypoxic brain damage induced in 7-day-old rats was significantly attenuated in a dose-dependent manner by intracerebral injection of glial cell line-derived neurotrophic factor (GDNF; 2 or 4 microg) within 30 min after the insult. Whereas the great majority of the vehicle-treated animals showed massive infarction involving more than 75% of the affected cerebral hemisphere, GDNF injection resulted in a remarkable reduction in both the incidence and severity of the brain damage (incidence ranging from 76% to 93% in controls to 34% to 64% in the 2.0-microg group and 7% to 29% in 4.0-microg group). The induction of immunoreactive 70-kDa heat shock protein (HSP70) in cerebral cortical neurons was also significantly reduced in GDNF-treated animals as compared to controls. The mechanisms responsible for the neuroprotective effects of GDNF remain unknown, although it has been speculated that these may be endogeneous. The higher expression of GDNF and its mRNA in developing brains may be one of the factors responsible for the relative resistance to ischemia of fetal and neonatal as opposed to adult brains. GDNF may possibly act by protecting against oxidative stress or by scavenging free radicals generated during ischemia. The results of our study strongly suggest that GDNF may prove to be an effective and potent protective agent against perinatal ischemic/hypoxic encephalopathy.

Animals↗

PubMed2000

A novel interstitial deletion of KAL1 in a Japanese family with Kallmann syndrome.

We identified a novel interstitial deletion that spanned from exons 5 to 10 of KAL1 in two Japanese brothers with X-linked Kallmann syndrome (KS; MIM no. 308700). Both brothers had hypogonadism, unilateral renal agenesis, and disturbance of the sense of smell, but they had no other neurological manifestations, including mental disturbance. Their mother was confirmed to be an asymptomatic carrier, by use of a comparative multiplex polymerase chain reaction (PCR) analysis. The present patients are further examples of patients with KS without mental disturbance caused by a mutation confined to KAL1.

Adult↗

PubMed2000

Important role of 72-kd heat shock protein expression in the endothelial cell in acquisition of hypoxic-ischemic tolerance in the immature rat.

OBJECTIVES: Hypoxic-ischemic tolerance can be induced in neonatal rats through hyperthermic preconditioning. The purposes of this study were to determine the interval between hyperthermic preconditioning and a subsequent hypoxic-ischemic insult that would provide optimal neuroprotection against the insult and to examine the relationship between tolerance induction and heat shock protein expression. STUDY DESIGN: On postnatal day 7 Wistar rat pups were separated into the following 2 groups: a heated group (those exposed to 15 minutes of hyperthermic pretreatment at a brain temperature of 41.5 degrees C-42.0 degrees C) and an unheated control group. At 6, 12, 24, 48, and 72 hours after the hyperthermic stress, rats from both groups were exposed to left carotid artery ligation followed by 2 hours of hypoxia (8% oxygen and 92% nitrogen) at 33 degrees C. Twenty animals from each group were used at each time point. All rats were killed at 1 week after hypoxia-ischemia, at which time the brains were processed and neuronal damage in the cortex and hippocampus was assessed histologically. Another set of 7-day-old rats (n = 30) was studied immunohistochemically at 6, 12, 24, 48, and 72 hours after the same hyperthermic treatment. Expression of 72-kd heat shock protein was measured in neuronal, glial, and vascular endothelial cells. RESULTS: Hyperthermia-induced hypoxic-ischemic tolerance was observed at 6, 12, and 24 hours but not at 48 and 72 hours after hyperthermic preconditioning. Heat shock protein 72 expression in the vascular endothelial cells, rather than in the glial or neuronal cells, was most strongly associated with hypoxic-ischemic tolerance. CONCLUSION: These findings suggest that heat shock protein 72 in endothelial cells plays an important role in the acquisition of hypoxic-ischemic tolerance at postnatal day 7, a time when maximal angiogenesis occurs and the blood-brain barrier is still immature.

Animals↗

PubMed2000

Histologic and biochemical study of the brain, heart, kidney, and liver in asphyxia caused by occlusion of the umbilical cord in near-term fetal lambs.

OBJECTIVE: We sought to determine the relationship between the degree of histologic changes in the brain, heart, kidney, and liver in fetal lambs after severe asphyxia and to analyze the role of oxidative stress in the pathogenesis of fetal multiple organ failure. STUDY DESIGN: Eight chronically instrumented near-term fetal lambs were asphyxiated by partial umbilical cord occlusion for approximately 60 minutes until the fetal arterial pH reached <6.9 and the base excess reached <-20 mEq/L. An additional 6 fetuses were used as sham-asphyxiated controls. Fetal heart rates, blood pressure, fetal breathing movements, and arterial blood gases and acid-base states were serially monitored. The brain, heart, kidney, and liver were collected 72 hours after asphyxia, processed, and histologically examined after hematoxylin and eosin staining. Fetal brain histologic features were classified into 5 grades, with 5 being the most severe damage. The other organs were examined histologically by pathologists who were blinded to the treatment. Each organ was assayed for tissue concentrations of thiobarbituric acid-reactive substances, superoxide dismutase, glutathione, lactate, and glucose. RESULTS: Myocardial changes of necrosis, phagocytosis, and contraction bands occurred in only 2 of the most severely (grade 5) brain-damaged fetuses. The same 2 cases showed fatty changes and congestion in the liver. In the kidney all asphyxiated cases showed tubular necrosis, but glomeruli were generally spared. Of the measures of oxidative stress, only liver tissue levels of thiobarbituric acid-reactive substances and superoxide dismutase were significantly higher in the asphyxiated group than in the control group, but there was no correlation with the degree of damage. Lactate level was higher only in the heart in the asphyxiated fetuses. CONCLUSION: Renal tubular damage was seen with all degrees of asphyxia, despite variable brain damage. Histologic changes in the myocardium and liver were seen only with the most severe brain damage. Oxidative stress appears to play a role in the pathogenesis of liver damage.

Animals↗

PubMed2000

Tumors involving the tracheal carina: new technique of carinal reconstruction.

Carinal reconstruction is one of the most difficult operations, and postoperative complications occur frequently. Two patients were treated surgically using this new technique. With this technique, bronchial end to side anastomosis was added to the tracheobronchial end to end anastomotic site. No postoperative complications occurred. This new technique is technically easy and causes few complications. We think this technique is superior to other methods in suitable patients.

Aged↗

PubMed2000

The role of the sentinel lymph node in gastrointestinal cancer.

Evaluation of the clinical significance of the sentinel node concept in GI cancer has just begun. The authors' preliminary data, using intraoperative radiation techniques and the gamma probe, suggest that it is worthwhile to continue the evaluation of this procedure to determine its role in an accurate staging and a minimally invasive approach to GI cancers.

Feasibility Studies↗

PubMed2000

Expression of matrix metalloproteinase-2 (MMP-2) and of membrane-type-1-matrix metalloproteinase (MT1-MMP) in transitional cell carcinoma of the upper urinary tract.

Tumor cell invasion and metastasis are biologically dependent on the proteolytic destruction of surrounding matrix components. Matrix metalloproteinase-2 (MMP-2) is able to cleave type IV collagen, and membrane-type-1-matrix metalloproteinase (MT1-MMP) induces activation of proMMP-2. We investigated the expression of MMP-2 and MT1-MMP using in situ hybridization and immunohistochemistry in 102 cases of transitional cell carcinoma of the upper urinary tract (TCC-UUT). A positive expression of each metalloproteinase was recognized in all samples and was apparent within the cytoplasm of tumor epithelial cells and/or stromal cells situated at the interface between tumor and stroma. Our analysis of clinicopathologic findings showed a relationship between MMP-2 and MT1-MMP expression and stage. The correlation between the MMP-2 protein staining score for tumor epithelial cells and overall survival rate reached significance in the univariate analysis. However, only stage was associated with disease-free and overall survivals in the multivariate analysis. In conclusion, the detection of MMP-2 and MT1-MMP would appear to be of limited value in informing the prognosis of TCC-UUT.

Adult↗

PubMed2000

A combination of wrapping and clipping using a collagen-impregnated dacron fabric (Hemashield).

BACKGROUND: We describe techniques combining wrapping and clipping using a collagen-impregnated Dacron knitted fabric (Hemashield) for accidental arterial perforations and broad-based aneurysms. The results of these techniques in seven patients are presented. METHODS: Clip-reinforced wrapping was performed to obtain hemostasis in two patients with arterial perforations and in a patient with a ruptured broad-based aneurysm in the internal carotid artery. Clipping of the broad neck of the aneurysm and wrapping with Hemashield (wrap-clipping) was performed in four patients with unruptured aneurysms (one internal carotid artery, two middle cerebral artery, one basilar artery). RESULTS: In the three patients treated with clip-reinforced wrapping, complete hemostasis was obtained just after clip application. In the patient with a ruptured broad-based aneurysm, postoperative angiography demonstrated that the dome of the aneurysm was well compressed. In the four patients treated with wrap-clipping, postoperative angiography revealed successful clipping of the broad neck of the aneurysm. CONCLUSION: In this early experience, there were no problems in the use of Hemashield for clip-reinforced wrapping or wrap-clipping.

Aged↗

PubMed2000

Lack of carcinogenicity of gardenia blue colour given chronically in the diet to F344 rats.

The carcinogenicity of gardenia blue colour was examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given the material at dietary doses of 0 (control), 2.5 or 5% for 104 weeks and then sacrificed. The doses were selected on the basis of results from a 13-week subchronic toxicity study. A slight increase in relative organ weights of the left lung was observed in male rats of the 5% group. However, no significant differences between the control and treated groups were noted with regard to clinical signs, mortality and haematological findings. A variety of tumours developed in all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any type of neoplastic lesion was found for either sex in the treated groups. Thus, it was concluded that, under the present experimental conditions, gardenia blue colour is not carcinogenic in F344 rats.

Administration, Oral↗

PubMed2000

Rapid, real-time sampling of R-84760 in blood by in vivo microdialysis with tandem mass spectrometry.

A new technique involving rapid sampling of R-84760 in real-time was achieved using a combination of microdialysis (MD) and tandem mass spectrometry (MS/MS). After collecting the analyte in real-time by MD and separating it by MS/MS, the ion intensities are adapted to the data without any subsequent chromatographic separation or flow injection analysis. The R-84760 concentration was obtained from the plateau part of the ion intensities or the corrected values using an internal standard, after immersing the MD probe into the dialysis solution containing the drug for a definite time. Since contamination of the ion source was prevented by using an organic solvent for the perfused solution, it was possible to establish a stable analysis method. For an MD membrane of length 4 mm, the R-84760 concentration in saline was linear over the range 5-541.1 ng/ml (r2 = 0.9997). Moreover, the R-84760 concentration in rat whole blood was linear over the range 24.9-1868.9 ng/ml (r2 = 0.9993). As this method allowed the measurement of free drug concentration in rat blood, the analysis was also able to provide data needed for determining the protein-binding ratio. The protein-binding ratio obtained from the calibration curve in saline and rat whole blood was 87-90%, which was close to the result obtained by another analysis method. The concentration profile of R-84760 in blood as obtained by the MD-MS/MS method correlated well with the concentration profile in plasma, which was simultaneously monitored by LC-MS/MS.

Analgesics↗

PubMed2000

Purification and characterization of liver catalase in acatalasemic beagle dog: comparison with normal dog liver catalase.

Catalase from acatalasemic dog liver was purified to homogeneity and its properties were compared with those of normal dog liver catalase. The purified acatalasemic and normal dog liver catalases were found to have the same molecular weight (230,000 Da) and isoelectric point (pI: 6.0-6.2) and both enzymes contained four hematins per molecule. The catalytic activity of catalase from acatalasemic dog was normal. Furthermore, there was no difference between the acatalasemic and normal dog catalases in the binding affinity to NADPH (apparent Kd: 0.11-0.12 microM) and in the sensitivity to oxidative stress by hydrogen peroxide, the normal substrate of catalase. The acatalasemic dog enzyme was stable only in a narrow pH range (pH 6-9) although the normal enzyme was stable in a wide pH range (pH 4-10). Acatalasemic dog liver catalase also showed a slight low thermal stability at 37 degrees C and the heat-lability was remarkable at 45 degrees C, compared to the normal dog enzyme. These results indicated that the acatalasemic dog catalase is catalytically normal although it is associated with an unstable molecular structure.

Acatalasia↗