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Biomedical subjects

K Suga

Publications and source records attributed to K Suga.

At least 19 recordsLinked to original sources
PubMed2004

Study on optimization for current distribution in magnetic stimulation therapy for urinary incontinence.

It has been reported that magnetic stimulation effectively eliminates urinary incontinence. However, this type of therapy has not been established as a practical treatment for urinary incontinence because of its poor power conversion efficiency and the leakage of current to regions other than that of the target of stimulation. It is therefore necessary to develop magnetic stimulators that are more efficient in stimulating the sphincter muscles and the peripheral nerves, and are more convenient than those presently available. By using a large-diameter coil, the magnetic stimulation method offers a larger current distribution over a wider area of the target region than electrical stimulation method, and the placement of the coil can be relatively easily changed to obtain better therapeutic results. We attempted, with a computer simulation model of the female abdomen, to simulate the distribution of the induced current density on the basis of biological tissue conductivity. We determined which method of stimulation is the most efficient by varying the stimulator coil location and size. A genetic algorithm (GA) was used for optimization.

Computer Simulation↗
PubMed2003

Localization of breast sentinel lymph nodes by MR lymphography with a conventional gadolinium contrast agent. Preliminary observations in dogs and humans.

PURPOSE: To test the capability of an indirect MR lymphography (MRLG) using a conventional extracellular gadolinium (Gd)-based contrast agent for localizing breast sentinel lymph node (SLN). METHODS: A total of 1 and 0.5 ml of undiluted gadopentetate dimeglumine were injected subcutaneously into the two periareolar areas overlying each caudal mammary gland in 10 female dogs. Contiguous 2-mm-thick fast gradient echo MR images were acquired through the upper breast and axilla before and for 60 min after gentle massage at the injection sites, yielding 3D displays. The localized SLN was resected from the living animals, followed by post mortem examinations. MRLG (1 ml contrast agent injected) was also attempted in 5 female volunteers. RESULTS: Even with 0.5-ml contrast agent, the MRLG clearly visualized the connection of SLN and lymphatic vessels directly draining from the injection sites, and the remaining distant nodes, with the maximal enhancement peaks within 10 min after massage. The 3D images provided comprehensive anatomy of these lymphatic pathways in each axilla. Of the 20 SLN and 128 distant nodes visualized on the MRLG, all the SLN (100%) and 107 (83.5%) distant nodes could be resected pre- and post mortem, in good correlation with the locations and sizes on the MR images. MRLG also effectively localized SLN in the volunteers, without significant adverse effects. CONCLUSION: An indirect MRLG using small volumes of conventional Gd-based contrast agent may have potential for accurate identification and surgical biopsy of breast SLN.

Animals↗
PubMed2003

Detection of genetically modified maize DNA fragments in the intestinal contents of pigs fed StarLink CBH351.

We tried to detect DNA fragments derived from maize in the intestinal contents of pigs fed genetically modified (GM) StarLink CBH351 maize (SL) or non-GM maize. Intestinal contents of 8 SL and 8 non-GM maize-fed pigs were collected at slaughter, and the genes of the recombinant cry9C and the maize intrinsic zein (Zel) were assayed by polymerase chain reaction (PCR) 3 times with a total of 4 primer pairs of different expected lengths. The cry9C gene (either 103 or 170 bp) was detected in the rectal contents (with a frequency of 25-37.5%) and in the cecal contents (25-50%) of the pigs fed SL. In a similar fashion, the zein (Zel) gene (either 242 or 329 bp) was detected in the rectal contents (with a frequency of 31.3%) and in the cecal contents (25-37.5%) of pigs fed on SL non-GM maize. These results suggested that ingested DNA was not totally degraded, but is present in a form detectable by PCR.

Animal Feed↗
PubMed2002

Assessment of regional lung ventilation in dog lungs with Gd-DTPA aerosol ventilation MR imaging.

PURPOSE: Gd-DTPA aerosol ventilation MR imaging was obtained using a modified aerosol delivery system with an aerosol reservoir to non-invasively assess regional lung ventilation in dogs. MATERIAL AND METHODS: Seven anesthetized, spontaneously breathing normal dogs inhaled 200 mmol Gd/l Gd-DTPA aerosol produced by an ultrasonic nebulizer, using an open-circuit aerosol delivery system with or without an aerosol reservoir. Fast gradient-echo MR images were sequentially acquired with an interval time of 1 min for 25 min before and after aerosol inhalation. The aerosol study was also performed using the aerosol delivery system with an aerosol reservoir in the same 7 dogs after airway obstruction with a balloon catheter, and in another 7 dogs after pulmonary arterial embolization with enbucrilate. An i.v. Gd-DTPA-enhanced dynamic MR study after i.v. bolus injection of a 0.1 mmol/kg dose of Gd-DTPA was combined to assess regional lung perfusion. Lung enhancement effect was evaluated by time-signal intensity curves and the subtracted ventilation- and perfusion-weighted images. RESULTS: With or without the aerosol reservoir, the normal dog lungs were gradually and gravity-dependently enhanced with time after aerosol inhalation. The use of the aerosol reservoir, however, showed significantly greater lung enhancement without a significant increase in breathing rate and with minimal reduction in PaO2 of less than 5 mm Hg in these animals. The enhancement effect of i.v. injection of Gd-DTPA at pulmonary arterial perfusion phase was significantly greater compared to that of Gd-DTPA aerosol throughout the normal lungs, and the subtracted ventilation-weighted and perfusion-weighted images showed homogeneous but gravity-dependent aerosol deposition and perfusion. These images clearly defined the regionally matched perfusion-ventilation deficits in the lung regions distal to bronchial obstruction in all the airway obstruction dogs, and the regionally mismatched perfusion-ventilation in the embolized regions of all the pulmonary arterial embolization animals. CONCLUSION: Gd-based aerosol can non-invasively image regional lung ventilation in spontaneously breathing animals, using an adequate aerosol delivery system. The combined use of Gd-DTPA perfusion MR imaging may be acceptable for defining regionally impaired lung function associated with acute airway obstruction and pulmonary arterial embolization.

Aerosols↗
PubMed2001

Kinetic analysis of megakaryopoiesis induced by recombinant human interleukin 11 in myelosuppressed mice.

Recombinant human interleukin 11 (rhIL-11) has previously been shown to ameliorate thrombocytopenia in several animal models. To elucidate the mechanisms involved in rhIL-11-induced hematopoiesis, a kinetic analysis of megakaryopoiesis was performed in mitomycin C (MMC)-induced myelosuppressive mice. Mice intravenously injected with MMC (2 mg/kg) for two consecutive days from day -1 developed severe thrombocytopenia with a nadir of platelet counts at 24x10(4)/microl on day 12 and neutropenia. Treatment with rhIL-11 (500 microg/kg/day) from day 1 to 21 significantly ameliorated the degree and duration of thrombocytopenia and enhanced the platelet recovery, and also enhanced the recovery from neutropenia. In MMC-treated mice, the decreases in bone marrow megakaryocyte progenitors and megakaryocyte counts preceded the decrease in platelet counts by MMC treatment. RhIL-11 induced an increase in the number of megakaryocyte progenitors from day 4 to 14, followed by an increase in the megakaryocytes by day 20. There was a ploidy shift in megakaryocytes towards lower ploidy cells by day 9 in myelosuppressed mice. RhIL-11 caused a shift towards a higher ploidy with 32 and 64N on day 4, and 32N on day 14. These results suggest that rhIL-11 ameliorates the thrombocytopenia via the stimulation of both the maturation and commitment followed by the proliferation of megakaryocytic cells.

Alkylating Agents↗
PubMed2001

CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of Rap1.

CD98 is a multifunctional heterodimeric membrane protein involved in the regulation of cell adhesion as well as amino acid transport. We show that CD98 cross-linking persistently activates Rap1 GTPase in a LFA-1-dependent manner and induces LFA-1/ICAM-1-mediated cell adhesion in lymphocytes. Specific phosphatidylinositol-3-kinase (PI3K) inhibitors suppressed both LFA-1 activation and Rap1GTP generation, and abrogation of Rap1GTP by retroviral over-expression of a specific Rap1 GTPase activating protein, SPA-1, totally inhibited the LFA-1/ICAM-1-mediated cell adhesion. These results suggest that CD98 cross-linking activates LFA-1 via the PI3K signaling pathway and induces accumulation of Rap1GTP in a LFA-1-dependent manner, which in turn mediates the cytoskeleton-dependent cell adhesion process.

Androstadienes↗
PubMed2001

Assessment of leg oedema by dynamic lymphoscintigraphy with intradermal injection of technetium-99m human serum albumin and load produced by standing.

This study was a preliminary evaluation of the utility of dynamic lymphoscintigraphy with technetium-99m human serum albumin (HSA) and a load produced by standing in the assessment of lymphatic dysfunction in patients with leg oedema. The 71 subjects investigated included 53 patients with lymphoedema, six with venous occlusion alone and five with lymphovenous occlusion, as well as seven normal subjects. After intradermal injection of 99mTc-HSA into an interdigital space in each foot, dynamic scintigrams were recorded with the patient supine for 15 min. The subjects then stood in place and images were recorded for an additional 15 min. Relative changes in lymphatic tracer transport before and after standing were analysed on time-activity curves (TACs). This test was compared with a conventional test in a supine position in six patients with lymphoedema, and was repeated in five other patients with lymphoedema. It was found that in the normal limbs, a standing load activated tracer transport to the draining lymphatic vessels, resulting in a rapid stepwise increase in tracer activity, large spiking waves and a decreasing phase following a peak in tracer activity on TACs. In 59 lymphoedematous limbs, including some with a mild form of oedema without morphological abnormalities on scintigrams, this load failed to induce a sufficient activation of tracer transport, and the frequencies of each of the three normally appearing changes described above significantly decreased compared with those in the 14 normal limbs (P < 0.0001, P < 0.01 and P < 0.0001, respectively). In addition, there were significant reductions in the relative increases in maximum activity and clearance times after standing (both P < 0.0001). These abnormalities significantly correlated with the grade of severity of oedema. Six limbs with lymphovenous occlusion showed significant reductions in tracer transport compared to six limbs with venous occlusion. Lymphatic dysfunction was accentuated more by this test than by the conventional test, and repeated tests showed consistent results in the same individuals. It is concluded that under a standardized load, this quick test seems of value in providing a sensitive and objective assessment of lymphatic dysfunction in the lower limbs, and is also advantageous for image interpretation since accelerated tracer transport clearly visualizes compromised lymphatics. This test may also be helpful in distinguishing purely venous oedema from mixed lymphovenous disease.

Adult↗
PubMed2001

Relationship between thallium-201 kinetics and proliferative activity assessed by monoclonal antibody MIB-1 in brain tumours.

To clarify the relationship between thallium-201 chloride kinetics and proliferative activity in brain tumours. a single-photon emission tomographic (SPET) study was performed and the results correlated with monoclonal antibody MIB-1 staining of the tumour tissue. 201T1 SPET was performed 10 min (early scan) and 2 h (delayed scan) after intravenous administration of 201TI (111 MBq) in 34 intra-axial tumours including 24 malignant tumours, and in 27 extra-axial tumours including one malignant tumour. Tumour 201T1 kinetic parameters [early and delayed uptake ratios (ER and DR, respectively), retention index (RI), and the ratio of tumour delayed activity to early activity (Td/Te)] were compared with tumour tissue MIB-1 labelling indices (MIB-1 LI) representative of tumour cell proliferative activity. In the intra-axial tumours, ER and DR and MIB-1 LI were significantly higher in the malignant tumours than in the benign tumours. ER and DR were significantly correlated with MIB-1 LI (P<0.01 and P<0.05, respectively), but RI and Td/Te were not. In the extra-axial benign tumours, ER was as high as that in the intra-axial malignant tumours, while MIB-1 LI was equal to that in the intra-axial benign tumours. There were no significant correlations between any 201T1 kinetic parameters and MIB-1 LI. This study indicates that 201T1 ER may be the most reliable parameter for predicting the proliferative activity of intra-axial tumours.

Adolescent↗
PubMed2001

MRI appearance of a leiomyoma of the female urethra.

Leiomyomas are rare in the urinary tract, with the kidney capsule being the most common location [1]. Leiomyoma of the female urethra is very rare. In 1992, Cheng et al. reviewed a total of 29 cases. They concluded that urethral leiomyoma is a rare condition that is difficult to distinguish clinically from other urethral lesions and that a histological diagnosis is essential [2]. Although we agree that the histological diagnosis is essential, magnetic resonance imaging (MRI) provides useful pre-operative information in cases of leiomyoma of the female urethra, as our present case indicates. To our knowledge we report the second case of a primarily diagnostic approach with MRI for leiomyoma of the female urethra. Ikeda, R. (2001). Clinical Radiology56, 76-79.

Adult↗
PubMed2001

Interleukin-11 induces osteoblast differentiation and acts synergistically with bone morphogenetic protein-2 in C3H10T1/2 cells.

Interleukin-11 (IL-11) is a pleiotropic cytokine that supports various types of hematopoietic cell growth and is involved in bone resorption. We report here the involvement of recombinant human IL-11 (rHuIL-11) in osteoblast differentiation in mouse mesenchymal progenitor cells, C3H10T1/2. rHuIL-11 alone increased alkaline phosphatase (ALP) activity and upregulated expression levels of osteocalcin (OC), bone sialo protein (BSP), and parathyroid hormone receptor (PTHR) mRNA. rHuIL-11 had no effect on expression of type II collagen, peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), adipocyte fatty acid-binding protein P2 (aP2), and myogenic MyoD protein (MyoD). Recombinant human bone morphogenetic protein (rHuBMP)-2 increased ALP activity and mRNA expression of these genes except for MyoD. The expression patterns of ALP activity and osteoblast-specific or chondrocyte-specific genes suggest that rHuIL-11 may be involved in early differentiation of osteoblasts at a step earlier than that which is affected by rHuBMP-2. In support of this hypothesis, combined treatment with rHuIL-11 and rHuBMP-2 synergistically increased ALP activity and mRNA expression of OC and type II collagen, rHuIL-11 also abrogated the increased levels of PPAR-gamma2, aP2 mRNA caused by rHuBMP-2. Our results suggest that rHuIL-11 alone and in combination with rHuBMP-2 can induce osteoblastic differentiation of progenitor cells and plays an important role in osteogenesis.

Alkaline Phosphatase↗
PubMed2001

Potential of Gd-DTPA-mannan liposome particles as a pulmonary perfusion MRI contrast agent: an initial animal study.

UNLABELLED: Suga K, Mikawa M, Ogasawara N, et al. Potential of Gd-DTPA-mannan liposome particles as a pulmonary perfusion MRI contrast agent: An initial animal study. Invest Radiol 2001;36:136-145. RATIONALE AND OBJECTIVES: A paramagnetic, particle-type MR contrast agent, (Gd-diethylenetriamine pentaacetic acid [DTPA]-mannan-cholesterol)-coated liposomes, was designed to localize in the lung by the mechanism of capillary blockade, and the potential of this agent for pulmonary perfusion MRI was experimentally investigated. METHODS: Before and up to 60 minutes after slow injection of this contrast agent, MR images were sequentially acquired at 10-second intervals along the same transaxial plane of the lung by using a gradient-echo pulse sequence with a short echo time of 1.2 ms on a 1.5-T MR scanner. After the minimal dose for obtaining a sufficient lung enhancement effect was determined in five rabbits, the time course of the enhancement effect was evaluated in six dogs by arterial blood gas analysis. The efficacy of MRI for detecting perfusion defects was evaluated in seven other dogs with pulmonary embolism. RESULTS: Normal lungs were dose-dependently enhanced by this agent, and with a 2.0 mL/kg dose, dependent lungs were enhanced by more than 201%, with an average half-life of the enhancement effect of 35.7 +/- 5.3 minutes. With less than this dose (1.0-1.5 mL/kg), all of the embolized lung portions were clearly identified as perfusion defects. The prolonged enhancement effect allowed the acquisition of subsequent multisectional lung images, thus facilitating the assessment of anatomic location and extent of the perfusion defects. The reduction of PaO2 in room air after injection was within 5 mm Hg in both normal and embolized animals. CONCLUSIONS: These initial, experimental results show that paramagnetically labeled liposome particles may be a successful MR contrast agent for pulmonary perfusion imaging.

Animals↗
PubMed2001

Perfusion characteristics of oleic acid--injured canine lung on Gd-DTPA--enhanced dynamic magnetic resonance imaging.

RATIONALE AND OBJECTIVES: We conducted an animal study to describe and interpret the perfusion characteristics of oleic acid (OA)-injured lungs on gadopentetate dimeglumine (Gd-DTPA)-enhanced dynamic perfusion magnetic resonance (MR) imaging. METHODS: Fourteen dogs received an intravenous OA infusion in the supine (n = 4), prone (n = 4), and right lateral decubitus (n = 6) positions, and 10 minutes later these animals in the same postures underwent the dynamic MR study. Regional Gd-DTPA kinetics was analyzed by the time-signal intensity (SI) curves and by qualitative functional map images of the mean transit time that was representative of the mean circulation time in the vascular bed and the average cumulative sum of the relative increases in SI representative of Gd-DTPA distribution volume during Gd-DTPA first pass. The results were compared with those in six control animals and in another six animals that underwent the MR study 3 minutes (n = 3) and 60 minutes (n = 3) after OA infusion. The MR findings were correlated with the distribution of lung damage and the infused OA particles as assessed by histology. RESULTS: The dynamic MR study showed postural shifts on the gravity-dependent perfusion map of normal lungs. Contrast enhancement during Gd-DTPA first pass in the lung was lower and more heterogeneous in the OA-injured lung models than in controls but was followed by conversely greater and persistent enhancement during the Gd-DTPA redistribution phase. Regardless of the postures for OA infusion, these abnormalities were predominant in the dependent lungs and became more pronounced with time after OA infusion, where more prominent capillary obstruction with OA droplets and alveolar/interstitial edema were histologically observed. On the functional map images, greater mean transit time and the average cumulative sum of the relative increases in SI values were also predominantly distributed in the dependent lungs. CONCLUSIONS: Low and heterogeneous enhancement was observed during Gd-DTPA first pass but was followed by persistent enhancement during the Gd-DTPA redistribution phase, and predominant abnormalities in the dependent lungs may be characteristic features of the perfusion of OA-injured lungs. The histological correlations indicate that these abnormalities may reflect OA-induced pathophysiologies associated with capillary OA obstruction, increased vascular resistance, and capillary permeability/extravascular spaces and that lung damage may be gravity dependent.

Animals↗
PubMed2001

Functional assessment of canine kidneys after acute vascular occlusion on Gd-DTPA-enhanced dynamic echo-planar MR imaging.

RATIONALE AND OBJECTIVES: To assess the alteration in renal transit of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in dog kidneys after acute vascular occlusion on dynamic echo-planar imaging (EPI). METHODS: Dynamic 240-ms EPI series (repetition time/echo time/inversion time [TR/TE/TI] = 3000/42.1/100 ms) of the midcoronal plane of both kidneys of dogs anesthetized by intravenous administration of phenobarbital sodium and ketamine hydrochloride were obtained before and after ligation of the left renal vein (n = 6) or artery (n = 6) for 40 minutes after a 2-second-rate bolus injection of a 0.05 mmol/kg dose of Gd-DTPA. Renal Gd-DTPA transit was analyzed on the time-DeltaR2* curves in each layer of the outer cortex (OC), juxtamedullary cortex and outer zone of the medulla (JMC-OM), and the inner zone of the medulla (IM). The results were compared with those in six normal animals and those of a fast gradient-echo T1-weighted dynamic study performed in other vein- (n = 6) or artery- (n = 6) occluded animals and six normal animals. The histopathological basis of the altered Gd-DTPA transit was also evaluated. RESULTS: The dynamic EPI showed rapid Gd-DTPA transit through each of the five concentric layers, with three separate peaks on the time-DeltaR2* curves. The vein-occluded kidneys showed immediate swelling, with a significant increase in the cross-sectional area proportion of the JMC-OM layer compared with normals (32% +/- 2% vs 24% +/- 2%, P < 0.0001) and intensely congested capillaries, tubular, obliterated material, and gradual and persistent enhancement of the OC and JMC-OM layers but poor Gd-DTPA migration to the IM layer. The artery-occluded kidneys showed a significant reduction in the entire cross-sectional area compared with normals (1352 +/- 69 vs 1432 +/- 47 mm(2), P < 0.05) and poor enhancement, with significant decreases in the area under the time-DeltaR2* curve of the OC and JMC-OM layers compared with the vein-occluded kidneys (79 +/- 50 vs 324 +/- 108 and 82 +/- 42 vs 326 +/- 113, respectively; both P < 0.0001), despite minimal histological damage. In both models, the nonaffected kidneys showed significant increases in the area under the time-DeltaR2* curves compared with baseline. The time course of vascular and tubular Gd-DTPA transit was more detailed by the EPI study than by the T1-weighted imaging study. CONCLUSIONS: Echo-planar imaging has an excellent ability to follow the rapid, renal Gd-DTPA transit through the regional anatomy of the canine kidney. After venous occlusion, the JMC-OM layer may be the most affected site, primarily causing renal swelling and interruption of tubular Gd-DTPA transit and concentration. In contrast, an initial block of vascular Gd-DTPA inflow is the primary effect of arterial occlusion. Nonaffected kidneys seem to compensate by increasing excretion of Gd-DTPA.

Acute Disease↗
PubMed2001

Molecular significance of excess body weight in postmenopausal breast cancer patients, in relation to expression of insulin-like growth factor I receptor and insulin-like growth factor II genes.

A number of epidemiological and clinical studies have revealed that excess body weight increases the risk of postmenopausal breast cancer and also adversely affects subsequent malignant progression. To elucidate the molecular mechanisms underlying these observations, we examined mRNA expression of various genes in normal (non-cancerous) mammary gland and cancer tissue of Japanese patients with primary breast cancer, in association with their body mass index (BMI). On the basis of analysis of 106 breast cancer patients, we found that mRNA expression of insulin-like growth factor I receptor (IGF-IR) and insulin-like growth factor II (IGF-II) in the normal mammary gland showed a significant and positive association with increased BMI among postmenopausal patients. Furthermore, the positive association of increased BMI with IGF-IR mRNA expression was also found in postmenopausal breast cancer tissue, while this association was not observed among premenopausal patients. In addition, increased mRNA expression of cyclin D1 and bcl-2 was observed in association with increased mRNA levels of IGF-IR among the patients regardless of menopausal status. These findings suggest that the molecular consequence of the increased BMI is the increased expression of IGF-II and IGF-IR, resulting in development of postmenopausal breast cancer and its progression mediated through modulation of the cell cycle and apoptosis.

Adult↗