Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 163 records · Page 9Linked to original sources

PubMed2000

Collective multielectron tunneling ionization in strong fields

We investigate the quantum mechanical process of two-electron tunneling in strong external electric fields. Numerical solution of a two-electron s-wave model reveals the existence of collective tunneling ionization in a mode where both electrons stay at equal distance from the nucleus. Otherwise the lagging electron is immediately recaptured. The corresponding double ionization rate fails to explain nonsequential multiple ionization in strong-field laser experiments. However, an empirically modified version of the analytical one-electron tunneling rate of Ammosov, Delone, and Krainov agrees with the experiments to a surprising accuracy. The reason for this agreement is presently unknown.

Journal Article↗

PubMed2000

Saliva level of free 3-methoxy-4-hydroxyphenylglycol (MHPG) as a biological index of anxiety disorders.

To access the saliva level of free 3-methoxy-4-hydroxyphenylglycol (MHPG) as a biological index of anxiety disorders, gender- or age-dependent changes in saliva MHPG level in patients with anxiety disorders were investigated. Saliva MHPG levels in 196 normal volunteers (59 male, 137 female) and 42 outpatients with anxiety disorders (20 male, 22 female) at the initial consultation to the hospital were measured by gas chromatography-mass spectrometry. Saliva MHPG levels in patients were higher than those in normal subjects. The increase in saliva MHPG levels in male patients was greater than that in female patients. Age-associated increase in the saliva MHPG level was greater in patients than in normal subjects. Especially, a significant interaction of age vs. patient effect was found in female subjects (P=0.0005), but not in male subjects (P=0. 174). These data indicate that the measurement of saliva MHPG would be valuable for detecting pathological anxiety in male patients regardless of age and in older female patients, but not in younger female patients.

Adjustment Disorders↗

PubMed2000

Tumor necrosis factor-alpha augments contraction and cytosolic Ca(2+) sensitivity through phospholipase A(2) in bovine tracheal smooth muscle.

To elucidate the effects of tumor necrosis factor-alpha (TNF-alpha) on tracheal smooth muscle contraction, we simultaneously measured isometric tension and intracellular Ca(2+) ([Ca(2+)](i)) in fura 2-loaded muscle strips. Smooth muscle force generation was evaluated in a high potassium (K(+); 20.0-80.0 mM) solution and with acetylcholine (3 nM-10 microM ). TNF-alpha (1-100 ng/ml) did not directly contract muscle strips. The contractile response to acetylcholine was enhanced after application of 10 ng/ml of TNF-alpha for 30 min but not the response of [Ca(2+)](i). The contractile response and the response of [Ca(2+)](i) to a high K(+) solution were not altered after application of TNF-alpha. The [Ca(2+)](i)-tension curve indicated that TNF-alpha enhanced the responsiveness of tracheal smooth muscle through the acetylcholine-mediated Ca(2+) sensitivity of intracellular contractile elements. The augmentation of the acetylcholine concentration-response curves for muscle tension in the presence of TNF-alpha (10 ng/ml) was inhibited in part after application of manoalide, a phospholipase A(2) inhibitor. We conclude that a low concentration of TNF-alpha enhances smooth muscle responsiveness to acetylcholine by agonist-mediated Ca(2+) sensitivity facilitated by phospholipase A(2).

Acetylcholine↗

PubMed2000

Pulmonary surfactant-associated protein A levels in cadaveric sera with reference to the cause of death.

Pulmonary surfactant-associated protein A (SP-A) is an exclusively lung specific protein, and is considered to leak into the blood stream in alveolar septal damage. In this study we examined the serum SP-A level in forensic autopsy materials using an enzyme immunoassay with monoclonal antibodies to assess the postmortem level in relation to the cause and mode of death. Although a gradual postmortem degradation should be taken into consideration, topological relationship of serum level seemed to be fairly stable (arterial> or =venous blood in most cases), indicating no evident influence of postmortem diffusion. Significant elevation of serum SP-A (76.7-250 ng/ml in left heart blood) was observed in hyaline membrane diseases from various causes independent of the postmortem intervals (<30 h). However, mean SP-A levels in postmortem heart blood were usually low in asphyxia including hanging, strangulation and choking (left, 25.5 ng/ml; right, 22.3 ng/ml), polytrauma (left, 13.1 ng/ml; right, 9.0 ng/ml) and stab wound to the neck (left, 34.1 ng/ml; right, 29.4 ng/ml). Prominent elevation was noted in a case of fatal strangulation with complication of idiopathic interstitial pneumonia, and also in some deaths due to drowning, burns in fires, blunt and gunshot chest injuries. These findings indicated that postmortem elevation of serum SP-A levels was associated with alveolar septal damage due to inflammation, mechanical and physical stresses, which caused leakage of SP-A into the bloodstream.

Adolescent↗

PubMed2000

S-nitrosylated human alpha(1)-protease inhibitor.

Alpha(1)-protease inhibitor (alpha(1)PI) is an acute phase plasma protein, and possesses a single cysteine residue at position 232. A single cysteinyl sulfhydryl of human alpha(1)PI is found to be readily S-nitrosylated by nitric oxide (NO) in vitro without affecting the inhibitory capacity against bovine trypsin or elastase, a major target protease of alpha(1)PI in vivo. S-nitroso-alpha(1)PI (S-NO-alpha(1)PI) was also formed by the reaction of alpha(1)PI with NO produced excessively by a murine macrophage cell line (RAW264 cells) upon infection with Salmonella typhimurium and in an ex vivo perfusion system of the liver obtained from lipopolysaccharide-treated rats. S-NO-alpha(1)PI (10(-9)-10(-6) M) induces a dose-dependent relaxation of the ring preparation of rabbit aorta. Also, S-NO-alpha(1)PI but not alpha(1)PI shows a potent inhibitory effect on platelet aggregation. Unprecedented observation is that S-NO-alpha(1)PI showed a potent bacteriostatic effect against a wide range of bacteria at the concentration of 1-10 microM, which was 10-1000-fold stronger than that of NO and other S-nitrosylated compounds including S-nitrosylated albumin and S-nitrosylated glutathione. These results suggest that S-NO-alpha(1)PI is produced as an NO sink under inflammatory conditions, where production of both alpha(1)PI and NO is highly up-regulated, and it may function as a soluble factor which consists of an innate defense system through not only the protease inhibitory activity but also its antibacterial activity and facilitating the peripheral blood flow. Therefore, S-nitrosylation of alpha(1)PI occurring under physiological conditions in vivo should diversify the biological functions contributing to cytoprotective effects of alpha(1)PI.

Animals↗

PubMed2000

DNA aptamers that bind to chitin.

We have succeeded in the acquisition of DNA aptamers that recognize chitin using in vitro selection. The obtained DNA aptamers have the stem-loop or bulge loop structures with guanine rich loop clusters and the clockwise B-form stems.

Base Sequence↗

PubMed2000

Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review.

Most solid tumors possess unique pathophysiological characteristics that are not observed in normal tissues or organs, such as extensive angiogenesis and hence hypervasculature, defective vascular architecture, impaired lymphatic drainage/recovery system, and greatly increased production of a number of permeability mediators. The phenomenon now known as the enhanced permeability and retention (EPR) effect for lipid and macromolecular agents has been observed to be universal in solid tumors. Primarily, enhanced vascular permeability will sustain an adequate supply of nutrients and oxygen for rapid tumor growth. The EPR effect also provides a great opportunity for more selective targeting of lipid- or polymer-conjugated anticancer drugs, such as SMANCS and PK-1, to the tumor. In the present review, the basic characteristics of the EPR effect, particularly the factors involved, are described, as well as its modulation for improving delivery of macromolecular drugs to the tumor. Tumor-specific vascular physiology is also described.

Animals↗

PubMed2000

Tumor-targeting chemotherapy by a xanthine oxidase-polymer conjugate that generates oxygen-free radicals in tumor tissue.

Xanthine oxidase (XO) mediates anticancer activity because of its ability to generate cytotoxic reactive oxygen species (ROS), including superoxide anion radical and hydrogen peroxide. However, the high binding affinity of XO to blood vessels would cause systemic vascular damage and hence limits the use of native XO in clinical settings. We demonstrate here that chemical conjugation of XO with poly(ethylene glycol) (PEG; the conjugates hereafter referred to as PEG-XO) significantly enhanced the tumor-targeting efficacy and the antitumor activity of XO. By using a succinimide-activated PEG derivative, PEG was conjugated to epsilon-amino groups of lysine residues of XO, which play a crucial role in binding of XO to blood vessels. PEG-XO administered i.v. showed a 2.8-fold higher accumulation in solid tumor compared with that of native XO 24 h after injection, whereas a slight or negligible increase in accumulation of PEG-XO was observed in normal organs. The highest PEG-XO enzyme activity was detected in tumor compared with normal organs or tissues except blood; enzyme activity in tumor was 5.0, 3.9, and 9.4 times higher than that in liver, kidney, and spleen, respectively. Intratumor activity remained high for >48 h. Administration of hypoxanthine, a substrate of XO, at 33 mg/kg body weight i.p. 12 h after the administration of PEG-XO (0.6 unit/mouse, i.v.) resulted in significant suppression of tumor growth (P < 0.001), with no tumor growth even after 52 days. However, either PEG-XO or hypoxanthine alone, or native XO with hypoxanthine, showed no effect on the inhibition of tumor growth under present experimental conditions. These findings suggest that PEG-XO, which accumulates preferentially in tumor tissue, warrants further investigation as a novel anticancer agent.

Animals↗

PubMed2000

Novel functions of human alpha(1)-protease inhibitor after S-nitrosylation: inhibition of cysteine protease and antibacterial activity.

alpha(1)-Protease inhibitor (alpha(1)PI), the most abundant serine protease inhibitor found in human plasma (at 30-60 microM), is a glycoprotein (53 kDa) having a single cysteine residue at position 232 (Cys(232)). We have found that Cys(232) of human alpha(1)PI was readily S-nitrosylated by nitric oxide (NO) without affecting inhibitory activity to trypsin or elastase. S-nitrosylated alpha(1)PI (S-NO-alpha(1)PI) not only retained inhibitory activity against these serine proteases, but also gained thiol protease inhibitory activity against a Streptococcus pyogenes protease; the parental alpha(1)PI did not have this activity. Furthermore, S-NO-alpha(1)PI exhibited bacteriostatic activity against Salmonella typhimurium at concentrations of 0.1-10 microM, which were 20- to 3000-fold stronger than those of the other NO-generating compounds or S-nitroso compounds such as S-nitrosoalbumin and S-nitrosoglutathione. NO appears to be transferred into the bacterial cells from S-NO-alpha(1)PI via transnitrosylation, as evidenced by electron spin resonance spectroscopy with an NO spin trap. Thus, we conclude that S-NO-alpha(1)PI may be generated from the reaction between alpha(1)PI and NO under inflammatory conditions, in which production of both is known to increase. As a result, new functions, i.e., antibacterial and thiol protease inhibitory activities of alpha(1)PI, were generated.

Animals↗

PubMed2000

First synthesis of tetrapyrrolylporphyrin

[reaction: see text] N-alkyl-substituted meso-tetrapyrrolylporphyrin (TPyrP) and its derivatives were synthesized for the first time via an acid-catalyzed condensation between N-alkyl-2,4-diformylpyrrole and unsubstituted pyrrole and a subsequent deformylation reaction. X-ray structural analysis of formyl-substituted TPyrP shows the tilting of meso pyrrole rings ca. 60 degrees to the porphyrin plane. Formyl groups of meso pyrrole rings were removed by treatment with trifluoroacetic acid (TFA) in pyrrole.

Journal Article↗

PubMed2000

Generation of lipid peroxyl radicals from edible oils and their biological activities: a need for consideration for anti-radical components and purification processing.

Lipid hydroperoxides (LOOH or oxidized oils) are known as unfavorable food components. Molecular details of the fate and mechanisms of LOOH to exert adverse effects in vivo are, however, little understood. In the present study, we demonstrated that LOOH generated alkylperoxyl radical (LOO*) after reaction with various heme compounds such as myoglobin, cytochrome c, hemin, hematin, etc., but little formation of other radical species was noticed such as L* or LO*. It was also shown that LOO* thus formed exhibits cytotoxicity and caused DNA damages including strand breakage and abasic site formation. This highly toxic LOO* is effectively scavenged by hot water extracts of vegetable (soup), flavonoids, polyphenols as well as tocopherols. Another important finding is that crude vegetable oils are rich in potent-LOO* scavenging activity, which exhibits potent anti-oxidant activity as well; whereas highly purified oils are scanty in such components and LOO* scavenging activity. These findings imply that a considerate processing in the refining of oils should be needed to retain such potent endogenous anti-oxidative radical scavenging-components.

Anti-Bacterial Agents↗

PubMed2000

Progressive cross-section display of 3D medical images.

The paper presents a hierarchical coding algorithm for 3D medical images based upon hierarchical interpolation with radial basis function networks. By using the properties of the Kronecker product, the computation of the network parameters and the 3D image reconstruction are efficiently done in (L4) computation time and O(L3) storage space, when applied to 3D images of size (L x L x L). A further reduction in processing time is accomplished by using sparse matrix techniques. The salient features of the proposed coding method are that arbitrary cross-section images can be progressively displayed without reconstruction of the whole 3D image; the first image reconstruction starts as soon as the first data transmission has been completed; no expanding procedure is required in 3D image reconstruction, and the blocking effects are not apparent even in the lowest-resolution image. Experimental results using two 3D MRI images, of size (128 x 18 x 64) and with 8-bit grey levels, show that the coding performance is better than that of the 3D DCT coding by about 0.25 bits pixel-1 at higher bit rates, and that the new cross-section display method synthesises the coarsest (finest) section image about six (three) times faster than the standard method that requires the whole 3D image reconstruction.

Algorithms↗

PubMed2000

Early and delayed Tc-99m ECD brain SPECT in SLE patients with CNS involvement.

We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lobe in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients.

Adult↗

PubMed2000

Ipsilateral recurrence frequency after video-assisted thoracoscopic surgery for primary spontaneous pneumothorax.

OBJECTIVE: We retrospectively evaluated the results of video-assisted thoracoscopic surgery for primary spontaneous pneumothorax and recurrence. METHODS: A series of 424 patients with primary spontaneous pneumothorax were treated by video-assisted thoracoscopic surgery-289 with an ipsilateral recurrent episode, 88 with persistent air leakage for 7 days or longer, 34 with a contralateral episode, 9 with hemopneumothorax, and 4 with tension pneumothorax. The commonest management was stapling of an identified bleb, undertaken in 375 patients (88.4%). Pleural abrasion was conducted in 250 (59.0%), but the abraded area was one-third or less of the thoracic cavity in 187 (74.8%). RESULTS: No operative deaths occurred. Revisional thoracotomy was required in 1 patient with postoperative bleeding and another with incomplete postoperative lung reexpansion; 26 had prolonged air leakage, but none required revisional thoracotomy. During a mean follow-up of 31.4 months, ipsilateral pneumothorax recurred in 40 patients (9.4%), with 26 (65.0%) having recurrence within 1 year postoperatively. A video-assisted thoracoscopic surgery was conducted again in 8, and thoracotomy in 14. CONCLUSIONS: The ipsilateral recurrence of primary spontaneous pneumothorax after video-assisted thoracoscopic surgery was high at 9.4%. If video-assisted thoracoscopic surgery is to be considered as a treatment for spontaneous pneumothorax, we must therefore reduce postoperative ipsilateral recurrence by training practitioners not to overlook blebs during the procedure and/or consider widening the area of pleurodesis.

Adolescent↗

PubMed2000

Immunohistochemical investigation of a pulmonary surfactant in fatal mechanical asphyxia.

We evaluated the usefulness of pulmonary surfactant protein A (SP-A) as a practical diagnostic marker of fatal mechanical asphyxia in forensic autopsy cases. A total of 27 cases of asphyxia were examined histologically and immunohistochemically and compared with a control group consisting of 16 cases of poisoning (n = 9) and peracute death (n = 7). Both groups showed histological findings of local atelectasis and local emphysema, congestion, intra-alveolar and interstitial edema in most cases and pulmonary hemorrhages in some cases. The mechanical asphyxia group showed a significantly increased intensity of SP-A staining in the intra-alveolar space accompanied by many massive aggregates in approximately 60% of cases, which was not found in the control group. These structures may be interpreted as aggregates of pulmonary surfactant released from the alveolar wall due to enhanced secretion caused by strong forced breathing or over-excitement of the autonomic nervous system by mechanical asphyxia. The results of our investigation suggest the practical usefulness of the immunohistochemical detection of SP-A in distinguishing mechanical asphyxia from other types of hypoxia.

Adolescent↗

PubMed2000

Surgical results for small cell lung cancer based on the new TNM staging system. Thoracic Surgery Study Group of Osaka University, Osaka, Japan.

BACKGROUND: Operation with combined chemotherapy has been recently recommended for very early stage of small cell lung cancer without lymph node metastasis. METHODS: A retrospective study was undertaken in 91 patients who had undergone pulmonary resection for small cell lung cancer according to the new international staging system. RESULTS: The 5-year overall probability of survival was 37.1%. The 5-year survival rate was 100% for p-stage 0, 56.1% for p-stage IA, 30.0% for p-stage IB, 57.1% for p-stage IIA, and 42.9% for p-stage IIB. In the p-stage IA-IIB patients who underwent a complete resection, the 5-year survival rate of the patients treated by operation with chemotherapy was better than that of patients treated by operation alone. In addition, the 5-year survival rate of the patients who had four or more courses of chemotherapy was 80.0%. CONCLUSIONS: These results suggest that operation should be considered for p-stage IA-IIB patients and more than four courses of combined chemotherapy might be desirable in these resectable cases.

Adult↗

PubMed2000

Tumor-targeted chemotherapy with SMANCS in lipiodol for renal cell carcinoma: longer survival with larger size tumors.

OBJECTIVES: To evaluate the anticancer effects of a lipophilic macromolecular anticancer agent, poly(styrene-co-maleic acid)-conjugated neocarzinostatin (SMANCS), dissolved in a lipid contrast medium (Lipiodol) given via the renal artery to patients with renal cell carcinoma. METHODS: Among 467 patients with renal cell carcinoma treated between April 1984 and March 1993, 191 were treated with SMANCS dissolved in a lipid contrast medium (a 3:2 mixture of Lipiodol F and Lipiodol Ultrafluid; Lpd). Selective arterial infusion of SMANCS/Lpd was performed at a dose of 1.0 or 1. 5 mg/mL. The infusion was repeated at intervals of about 2 weeks or longer, but the doses and the total number of infusions varied among patients, according to results of computed tomography analysis. RESULTS: Statistical analysis was performed for 415 patients who met the criteria of this study. Twenty-six surgical patients with metastases who underwent infusion therapy of SMANCS/Lpd for primary lesions showed 3 and 5-year survival rates of 23.0% and 12.8%, respectively; the rates were 19.3% and 9.7% in 31 patients who did not receive SMANCS infusion therapy. In 125 surgical patients without metastases who underwent SMANCS/Lpd infusion, the 5 and 10-year survival rates were 83.0% and 75.2%, respectively, whereas rates of 84.6% and 78.9% were observed in 199 surgical patients whose median tumor size was significantly smaller, however, than the SMANCS/Lpd infusion group. The maximal tumor diameter at the beginning of treatment was significantly larger (mean diameter 70.8 mm) in the SMANCS/Lpd infusion group than in the noninfusion group (59.1 mm). The survival rate was statistically better for patients with tumors of 100 mm diameter or larger in the SMANCS/Lpd infusion group (P <0.05): 5 and 10-year survival rates were 70.4% and 61.6%, respectively, for the infusion group and 64.6% and 50.9% for the group receiving no drug. In patients with larger tumor (greater than 110 mm), the survival rate at 13 years was 75% in the SMANCS/Lpd infusion group and 0% in the surgery group. CONCLUSIONS: Arterial infusion therapy with SMANCS/Lpd appears to be effective for large renal cell carcinoma without metastases in conjunction with surgery.

Adolescent↗

PubMed2000

Allelotype and loss of heterozygosity around the L-myc gene locus in primary lung cancers.

L-myc S-allele was reported to be associated with metastasis of lung cancer, indicating the existence of a putative tumor suppressor gene around the L-myc locus, in linkage disequilibrium. The relationship between the S-allele and inactivation of some tumor suppressor gene should be indicated by allelic loss. Therefore, we examined the association between the L-myc S-allele and loss of heterozygosity at 11 loci around the L-myc locus (1p34.3) in primary lesions or other biological characteristics in lung cancer. No associations between the S-allele and allelic loss around the L-myc locus or other characteristics were found. According to the deletion map, three shortest regions of overlap between D1S230 and D1S76 were identified. While loss of heterozygosity at SRO1, between D1S2797 and MYCL1, showed no relationship with the pathological stage, it was more frequently observed in squamous cell carcinoma than adenocarcinoma (P=0.019), and associated with high telomerase activity (P=0.046), an indicator of cellular immortality. In conclusion, we found three shortest regions of overlap (SROs) from D1S2797 to pter, and a tumor suppressor gene, which might be associated with suppression of lung cancer development but not with L-myc S-allele, may exist in SRO1.

Adult↗