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Biomedical subjects

T Aoki

Publications and source records attributed to T Aoki.

At least 199 records · Page 11Linked to original sources

Molecular evidence for the involvement of NR2B subunit containing N-methyl-D-aspartate receptors in the development of morphine-induced place preference.

The present study was designed to clarify the role of the NR1, NR2A and NR2B subunits of N-methyl-D-aspartate receptors in the development of morphine-induced place preference using specific antibodies to N-methyl-D-aspartate receptor subunits in the mouse. An i.c.v. injection with specific antibodies against the carboxyl-terminal region of either NR1, NR2A or NR2B subunits caused the attenuation of seizures induced by i.v. infusion of N-methyl-D-aspartate in the mouse. Using western blotting, NR1, NR2A and NR2B subunits were found to be highly expressed in the cerebral cortex and hippocampus of the mouse brain, which are key areas in producing seizures regulated by N-methyl-D-aspartate receptors. These findings indicate that all three subunits of the N-methyl-D-aspartate receptor in these areas are likely to be critical for the seizure induced by i.v. infusion of N-methyl-D-aspartate. Furthermore, present data provide evidence that these antibodies when given into the brain specifically act on the target sites, resulting in the blockade of the respective N-methyl-D-aspartate receptor subunit. Under these conditions, i.c.v. treatment with the antibody against NR2B subunits abolished the morphine-induced place preference, whereas antibodies against NR1 and NR2A subunits did not affect the rewarding effect of morphine. Furthermore, the NR2B subunit protein was specifically up-regulated in the limbic forebrain of morphine-conditioned mice, whereas the protein levels of either NR1 or NR2A subunits were not altered.From these results, we suggest that the stimulation of the carboxyl-terminal region of NR2B subunits in the limbic forebrain may contribute to the development of morphine-induced rewarding effect.

Animals↗

Pulmonary complications after surgical treatment of lung cancer in octogenarians.

OBJECTIVE: The purpose of this study was to analyze the risks associated with pulmonary resection for primary non-small cell lung cancer in octogenarians to help better management in these patients. METHODS: We reviewed the outcome in our 35 patients aged 80 years and older who underwent pulmonary resection between 1981 and 1998. RESULTS: The 5-year survival rate was 39.8%. The operative mortality rate was 0% and the morbidity 60%. There were ten major pulmonary complications, including respiratory insufficiency following bacterial pneumonia and sputum retention. Preoperative arterial pO(2) was significantly lower, A-aDO(2) was significantly higher, and operation time were significantly longer in patients with pulmonary complications after surgical treatment than in patients without complications (P<0.05). CONCLUSIONS: Surgical treatment was not contraindicated for octogenarians with lung cancer. However, a relatively preoperative low arterial pO(2), high A-aDO(2), and long operation time may be risk factors for postoperative pulmonary complications in such patients. Surgeons must assess the preoperative data prudently to determine appropriate surgical strategy.

Actuarial Analysis↗

Neoadjuvant chemotherapy by transcatheter arterial infusion method for uterine cervical cancer.

PURPOSE: The effects of transcatheter intraarterial infusion of anticancer drugs on the prognosis of cervical cancer were retrospectively studied. MATERIALS AND METHODS: Two or three sessions of transcatheter arterial infusion therapy were performed in 97 patients with primary uterine cervical cancer. The number of patients in stage I, II, III, or IV were 15, 37, 34, and 11, respectively. The drugs infused were cisplatin (60-70 mg/m2), doxorubicin hydrochloride (30-40 mg/m2), mitomycin (15 mg/m2), and 5-fluorouracil (500 mg/body). They were infused via the bilateral internal iliac arteries. Seventy-five patients of the 97 (78%) underwent radical hysterectomy after arterial infusion: stage I (14 of 15), stage II (31 of 37), stage III (25 of 34), and stage IV (5 of 11). Three stage II and nine stage III patients received radical radiation therapy. The other 10 patients (one with stage I, three with stage II, and six with stage IV) did not receive an operation and radiation therapy after arterial infusion because of their distant metastases at the time of operation. Thirty-eight patients of 75 (51%) received postoperative radiation therapy. RESULTS: The complete histologic response rates (no active cancer cells) after arterial infusion were four of 14, four of 31, six of 25, and one of five for stages I, II, III, and IV. The histologic response rates, which showed no parametrial invasion after arterial infusion, were 12 of 14, 24 of 31, and 15 of 25 for stages I, II, and III. The histologic response rates, which demonstrated no lymph node metastases after arterial infusion, were 12 of 14, 24 of 31, and 19 of 25 for stages I, II, and III. The overall 5-year survival rates of the patients with stages I, II, and III were 93.3%, 58.7%, and 69.7%, respectively. The 5-year survival rates of the operated patients with stages I, II, and III were 100%, 60.5%, and 63.6%, respectively. The 5-year survival rates of the irradiated patients with stage III was 87.5%. Leukocytopenia and thrombocytopenia occurred as an acute complication in 75% and 79% of the patients, respectively. As a late complication, ileus occurred in 7%. CONCLUSION: Arterial infusion may improve the prognosis of patients with cervical cancer without increasing the incidence of late complications.

Adenocarcinoma↗

Plasma catecholamine responses during laparoscopic gynecologic surgery with CO(2) insufflation.

STUDY OBJECTIVE: To compare adrenergic-sympathetic responses during pelvic laparoscopic surgery with CO(2) insufflation with those during laparotomy. DESIGN. Prospective study (Canadian Task Force classification II-1). SETTING: Tertiary care university hospital. PATIENTS: Twenty-one infertile women with a clinical diagnosis of endometriosis. INTERVENTION: Plasma norepinephrine (NE) and epinephrine (E) levels were measured in patients undergoing laparoscopic or open pelvic surgery. MEASUREMENTS AND MAIN RESULTS: During laparoscopic surgery, increases in NE and E levels were correlated with arterial tension of CO(2) (PaCO(2)) and were greater in patients with a larger increase in PaCO(2) than in those undergoing laparotomy. Hemodynamic changes were also more evident during laparoscopic surgery, with larger PaCO(2) increases. CONCLUSION: The PaCO(2) increases due to CO(2) insufflation are associated with adrenergic-sympathetic activation and hemodynamic changes during laparoscopic pelvic surgery.

Adult↗

Stress responses during laparoscopy with CO2 insufflation and with mechanical elevation of the abdominal wall.

STUDY OBJECTIVE: To compare the intensity of stress responses caused by laparoscopy combined with CO2 insufflation (CI) with those caused by mechanical elevation of the abdominal wall (MEA). DESIGN: Prospective study (Canadian Task Force classification I). SETTING: Tertiary care university hospital. PATIENTS: Thirty-one women. Intervention. Laparoscopy, 16 with CI and 15 with MEA. MEASUREMENTS AND MAIN RESULTS: Circulating levels of norepinephrine, epinephrine, cortisol, and interleukin (IL)-6 were compared in the two groups. Arterial partial pressure of CO2 (PaCO2) did not increase during laparoscopy by either method. Plasma norepinephrine and epinephrine levels increased after extubation in the MEA group but not in the CI group. Circulating cortisol levels in both groups increased during laparoscopy; mean intraoperative levels were higher in the CI group. Serum IL-6 levels increased after extubation in the MEA but not the CI group. Mean heart rate increased during laparoscopy in both groups, whereas blood pressure increased only in the CI group. More patients in the MEA group required postoperative analgesia. CONCLUSION: Laparoscopy with MEA caused more pronounced adrenosympathetic and cytokine responses than that with CI when PaCO2 was maintained within the range of normocapnia.

Carbon Dioxide↗

Descending necrotizing mediastinitis due to odontogenic infections.

OBJECTIVE: Acute purulent mediastinitis caused by oropharyngeal infection is termed descending necrotizing mediastinitis. Such infections usually have a fulminate course, leading to sepsis and frequently to death. The purpose of this study is to show the importance of early diagnosis, aggressive surgical intervention, and optimal antibiotics chemotherapy in controlling this fatal infectious disease. STUDY DESIGN: Two patients with descending necrotizing mediastinitis due to odontogenic infection who were treated at our institution are described. RESULTS: Both patients survived. CONCLUSIONS: From the patients, 23 different aerobic and anaerobic bacteria were isolated. All of the isolates were susceptible to carbapenem. Early evaluation by means of cervicothoracic computed tomography scanning was extremely useful for diagnosis and surgical planning. Knowledge of anatomic pathways from the mouth to the mediastinum is essential. We believe that tracheostomy is not always necessary. In both of the cases presented, mediastinal drainage was completed through use of a transcervical approach. However, a more aggressive drainage including tracheostomy might be necessary when the infection extends below the carina.

Acute Disease↗

Localization of gamma-tubulin to the basal foot associated with the basal body extending a cilium.

The human oviduct epithelium primarily consists of ciliated cells and secretory cells. Solitary cilia usually extend from the apical surface of the secretory cells. We investigated the localization of gamma-tubulin in the ciliary basal apparatus of both cell types by fluorescence immunohistochemistry and immunoelectron microscopy. In addition to basal bodies, gamma-tubulin was identified in the lateral basal foot, especially the basal foot cap. This observation is consistent with previous observations that microtubules radiate from the basal foot and the basal foot serves as the microtubule organizing centre.

Cilia↗

Long-term results of radiation therapy for pituitary adenoma.

PURPOSE: Local control for pituitary adenomas treated with external beam radiation therapy was retrospectively analyzed to evaluate the efficacy of radiation. MATERIALS AND METHODS: Thirty-eight patients treated with radiation therapy between 1979 and 1994 were analyzed. The median age was 46. Nineteen newly diagnosed tumors were treated with surgery and radiation therapy, while the others were recurrent cases. Twenty-two tumors were non-functioning, while 10 produced growth hormone (GH) and three each were prolactin-, and adrenocorticotropic hormone (ACTH)-producing tumors. The median-radiation dose was 50 Gy in 25 fractions. RESULTS: Non-functioning adenomas and prolactin-producing adenomas were completely controlled, judging from the absence of tumor progression on neuroimaging studies and clinical symptoms, and normalization of the serum prolactin level (< 25 ng/ml). On the other hand, local control was obtained in only one of the 3 patients with ACTH-producing adenomas, and the control rate at 10 years was only 46% for GH-producing adenomas. Panhypopituitarism developed in 35% of the patients after radiation therapy. No other serious complications were noted. CONCLUSION: Non-functioning pituitary adenomas and prolactin-producing adenomas were well controlled with external radiation therapy combined with surgery. However, dose escalation might be necessary to control GH-or ACTH-producing tumors. It is important to replace corticosteroid hormone and thyroid hormone in many patients.

Adolescent↗

One-step sandwich enzyme immunoassay using monoclonal antibodies for detection of human enamelysin (MMP-20).

A one-step sandwich enzyme immunoassay (EIA) system for human matrix metalloproteinase 20 (MMP-20, enamelysin) was established by use of a solid-phase monoclonal antibody and a separate peroxidase-labeled monoclonal antibody. The EIA system was shown to be sensitive and quantitative for the detection of MMP-20. As little as 1.0 ng/ml (50 pg/assay) of MMP-20 protein could be reliably detected. The EIA system was linear over a range of 2.5-160 ng/ml (125-8,000 pg/assay), and the EIA system was versatile in that it was capable of detecting with equal sensitivity proMMP-20, active MMP-20, and MMP-20 with COOH-terminal deletions. The EIA system was validated by the successful detection of MMP-20 in the culture medium of Chinese hamster ovary cells (CHO-K1) that were transfected with an MMP-20 expression vector. No MMP-20 was detected in normal human serum, normal saliva, or in selected tumors. However, when recombinant human MMP-20 was added to human saliva, the EIA system did detect quantifiable amounts of the MMP-20, indicating that the system will work within the framework of complex in biological fluids.

Adenocarcinoma↗

Ultrasonographic diagnosis criteria using scoring for hypertrophic pyloric stenosis.

PURPOSE: For diagnosis of infantile hypertrophic pyloric stenosis (HPS), ultrasonography (US) is a useful and objective diagnostic method. In the current study, pyloric diameter, muscular thickness, and pyloric length were measured in normal infants (n = 26) and infants which is an adequate (n = 57). Each score was assigned to relevant measurements, and diagnostic criteria obtained with a scoring system were prepared using statistical skills by the probit analysis. METHODS: For scoring, points were given to relevant measurements in conformity with the probit analysis. Zero points were given to patients with no possibility of HPS, 1 point to those with less than 25% probability, 2 points to those with 25% or more but less than 50% probability, and 3 points to patients with 50% or more probability. Points were totaled, and analysis was performed. RESULTS: The composite score was evaluated by probit analysis, and cases with a composite score of 2 or less were all included in the normal group, whereas those with a composite score of 3 or more were all in the HPS group. Both groups could thereby be 100% identified. CONCLUSION: US was able to diagnose cases with overall score of 2 or less as normal and those with overall score of 3 or higher as having HPS. In addition, after the current diagnostic criteria were prepared, preoperative diagnoses were performed prospectively using them for vomiting neonates and infants, and all cases were correctly discriminated and diagnosed. These findings indicate our ultrasonographic diagnosis criteria are useful for diagnosing HPS.

Female↗

Lipid-lowering and antiatherosclerotic effect of NK-104, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in Watanabe heritable hyperlipidemic rabbits.

NK-104 ((+)-monocalcium bis(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy- 6-heptenoate), CAS 147526-32-7) an inhibitor of 3-hydroxy-3-metylglutaryl coenzyme A reductase, was administered in drinking water (0.5 mg/kg equivalent) to Watanabe heritable hyperlipidemic (WHHL) rabbits for 26 weeks. It lowered plasma total cholesterol (TC, 7-20%) and triglyceride (TG, 16-39%) levels throughout the experimental period due to a significant reduction of very low density lipoprotein cholesterol (VLDL-C, 61-62%, p < 0.05), intermediate density lipoprotein cholesterol (IDL-C, 49-60%, p < 0.05), VLDL-TG (40-53%, p = 0.06-0.08) and IDL-TG (29-59%, p = 0.06-0.14); low density lipoprotein cholesterol (LDL-C) was not affected. The pattern of the lipoprotein reduction along with a decrease in liver cholesteryl ester (CE, 33.1%, p < 0.01) suggests an intense reduction of VLDL secretion and a marginal induction of LDL-receptor. Enhanced expression of LDL receptor-related protein (LRP) in the liver was observed at mRNA levels (49.5% increase, P = 0.13), which might play a role in the lipoprotein reduction. Histological analyses of aorta revealed that aortic arch showed the most advanced lesions with larger lesion area (70.0 vs 41.3%) and much greater CE content (more than 2 fold) with less macrophages than thoracic aorta. NK-104 decreased the surface lesion area at the arch (23.1%, p = 0.054) and reduced the degeneration of media in the thoracic aorta (69.9% increase in medial smooth muscle cells, p < 0.01). Thus NK-104 preferentially reduced TG-rich lipoproteins (VLDL and IDL) without affecting LDL-C levels and prevented progression of atherosclerosis in WHHL rabbits.

Animals↗

Preparation and characterization of milk calcium salts by using casein phosphopeptide.

Milk calcium salt solution was prepared by the following procedures using casein phosphopeptides (CPP). To CPP solution, 1 M citric acid, 1 M CaCl2 and 1 M K2HPO4 were added with stirring, while adjusting the pH to 6.7. The prepared solution was left for 12 hr at 25 degrees C and then used for subsequent experiments, or lyophilized. The concentrations of organic phosphate of CPP, calcium, inorganic phosphate, and citrate in the typical milk salt solution were 7, 30, 22, and 10 mM, respectively, which were close to those in bovine milk. The lyophilized sample was easily dissolved in water. No crystal structure of hydroxyapatite was shown in the lyophilized milk calcium salts by X-ray diffraction analysis, although the pattern of KCl crystal was observed. The X-ray diffraction pattern of commercial whey mineral, which was prepared by precipitation at alkaline pH from rennet whey, was similar to that of hydroxyapatite. It was confirmed by high-performance gel chromatographic analysis that the form of calcium phosphate in the milk calcium salts was similar to that of casein micelles.

Animals↗

Odor distinctiveness between enantiomers of linalool: difference in perception and responses elicited by sensory test and forehead surface potential wave measurement.

The effects on humans of inhalation of optically active linalools were examined in terms of sensory tests and portable forehead surface electroencephalographic (IBVA-EEG) measurements in order to assess their odor distinctiveness by chiral isomers. (R)-(-)-Linalools with specific rotation of [alpha](D) = -15.1 degrees were isolated by repeated flash column chromatography from lavender oil, while (S)-(+)-linalools with [alpha](D) = +17.4 degrees and (RS)-(+/-)-linalools with [alpha](D) = 0 degrees and content of (R)-form 50.9% and (S)-form 49.1% were obtained from coriander oil and commercial linalool, respectively, by using the same method. With the use of an inhalator, each was administered to subjects both before and after 10 min of work. It was found that administration after work evoked different subjective impressions when compared with that before work depending on the configuration of the isomers and the type of work employed. For instance, inhalation of (R)-(-)-linalool after hearing environmental sounds not only produced a much more favorable impression in the sensory test but was also accompanied by a greater decrease in beta waves after work in comparison with that before work. This is in contrast to the case of mental work, which resulted in a tendency for agitation accompanied by an increase in beta waves. These findings led us to conclude that enantiomeric stereospecificity of linalool evoked different odor perception and responses not only with chiral dependence but also with task dependence. In addition, in comparing these sensory profiling features and IBVA-EEG tendencies between hearing environmental sound and mental work, a tendency was observed for (R)-(-)-linalool to coincide with (RS)-(+/-)-linalool but not with (S)-(+)-linalool.

Acyclic Monoterpenes↗

A new approach to gene mutation analysis using "GFP-Display".

The unique behavior of green fluorescent protein (GFP) on SDS-PAGE was applied to the detection of a single amino acid substitution in GFP-tagged polypeptides. This simple detection method using SDS/urea gels was designated GFP-display. The N-terminal 18 or 37 amino acids of K-Ras was used as a model GFP-tagged polypeptide. K-ras exon 1 was fused to a gfp cDNA at each end and expressed in Escherichia coli. Amino acid number 12 of K-Ras (wild type; Gly) was changed to Ser, Arg, Cys, Asp, Ala, or Val, and the mobility shift of the greenish fluorescent bands in the SDS/urea gel was analyzed. These mutants were easily detected by GFP-display; however, detection depended strongly on the urea concentration and electrophoresis temperature. Subsequently, GFP-display was applied to the 36 amino acids encoding human p53 exon 7. Amino acid number 248 (wild type; Arg) was changed to Gly, Trp, Gln, Pro, or Leu, and similar mobility shifts were observed. GFP-display could be coupled with an in vitro translation system. Fluorescent active GFP and GFP-Ras fusion proteins were synthesized within a few hours. GFP-display shows potential as a modern approach to gene mutation analysis at the protein level, and is a useful method for protein engineering studies.

DNA Mutational Analysis↗

Different effects of lung volume reduction surgery and lobectomy on pulmonary circulation.

OBJECTIVE: To clarify the effects of lung volume reduction surgery (LVRS) on cardiopulmonary circulation during exercise in comparison with pulmonary lobectomy for lung cancer. SUMMARY BACKGROUND DATA: LVRS improves pulmonary function and dyspnea symptoms acutely in selected patients with heterogeneous emphysema. However, there are few data concerning the effects of LVRS on the cardiopulmonary circulation, especially during exercise. METHODS: Pulmonary function tests and pulmonary hemodynamic study at rest and during exercise were performed before and 6 months after LVRS (seven patients) or pulmonary lobectomy (eight patients). In the workload test, an electrically braked bicycle ergometer (25 w) was used in the supine position for at least 2 minutes or until exhaustion or breathlessness developed. RESULTS: After lung lobectomy, the values of vital capacity, percentage of predicted vital capacity, forced expiratory volume in 1 second, percentage of predicted forced expiratory volume in 1 second, residual volume/total lung capacity, and maximal voluntary ventilation deteriorated significantly. Six months after LVRS, however, vital capacity, percentage vital capacity showed no significant change, and forced expiratory volume in 1 second, percentage of forced expiratory volume in 1 second, diffusing capacity for carbon monoxide, and maximal voluntary ventilation showed marked improvement. Cardiac index was changed neither at rest nor during exercise in either group by the operation. Although postoperative pulmonary arterial pressure in the lobectomy group was significantly increased by the exercise, LVRS did not affect postoperative pulmonary arterial pressure at rest or during exercise. Pulmonary capillary wedge pressure in the lobectomy group showed no significant change after the operation, whereas LVRS ameliorated the marked elevation of pulmonary capillary wedge pressure observed during exercise. After lobectomy, significant increases in the pulmonary vascular resistance index were observed at rest and during exercise. LVRS markedly increased the pulmonary vascular resistance index at rest but not during exercise. In the lobectomy group, the postoperative flow-pressure curve moved upward, and its gradient became steeper than the preoperative one. In the LVRS group, the curve moved upward in a parallel fashion. These results show that much more right-sided heart work is needed to achieve the same cardiac output against higher pulmonary arterial pressure, not only after lobectomy but also LVRS. CONCLUSION: The current study demonstrated that the effects of LVRS on the cardiopulmonary circulation were not negligible, especially during exercise, and successful LVRS may depend on improved respiratory function and also preserved cardiac function that can tolerate the damage to the pulmonary vascular bed induced by this operation.

Aged↗

E-cadherin expression in skin tumors using an AMeX immunohistostaining method.

The AMeX (acetone-methylbenzoate-xylene) method results in good preservation of tissue and morphological details, almost equivalent to that of routinely processed formalin-fixed and paraffin-embedded tissue specimens, and of antigenicity equivalent to that of fresh frozen tissue specimens. It has been reported that the expression of the cell-cell adhesion molecule E-cadherin is often decreased in some types of carcinomas. A decrease in E-cadherin expression is associated with the invasive or metastatic potential of tumor cells. We immunohistochemically examined the expression of E-cadherin with anti-E-cadherin monoclonal antibody in various skin tumors (25 basal cell carcinomas, 11 squamous cell carcinomas, 9 keratoacanthomas, and 11 Bowen's disease) using the AMeX method and found that this method preserved antigenicity well without pretreatment. E-cadherin expression was decreased in 18.2% of squamous cell carcinomas and 33.3% of keratoacanthomas. On the other hand, it was preserved in almost all Bowen's disease and basal cell carcinomas. From the results of our study, we suggest that Bowen's disease and basal cell carcinoma do not have much metastatic potential due to retention of high levels of E-cadherin expression. We hope to apply the AMeX method to other immunohistochemical examinations because this is a very useful staining method.

Acetone↗