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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 523 records · Page 29Linked to original sources

Detection of muscle layer invasion with submillimeter pixel MR images: staging of bladder carcinoma.

Conventional magnetic resonance (MR) images used for the pelvic organs generally have a pixel size of 1.3 mm x 1.3 mm. We obtained images with a higher resolution than conventional images, and evaluated the usefulness of this type of image in staging urinary bladder carcinoma. Twenty-six patients having either transurethral resection of bladder tumor (TUR-BT) or cystectomy were retrospectively studied. T2-weighted images of the bladder were acquired with a 20 cm field-of-view, a matrix size of 224 x 224 (pixel size: 0.9 mm x 0.9 mm), and a slice thickness of 7 mm using a 0.5 T system. MR appearances of the carcinoma were divided into the following five categories: no abnormality found on the inner surface of the bladder wall (0), high signal layer or protrusion without breakage of the wall (I), partial disruption of the wall (II), transmural disruption of the wall (III), and complete disruption with mass formations in the perivesicular region (IV). These findings were correlated with the TNM pathologic staging determined from each tissue specimen. A prediction for muscle layer invasion was calculated by selecting pathologic stage pT2 and MR category III as a boundary measure. The accuracy was 96.2%, the sensitivity 100.0%, and the specificity 91.7%. The results obtained indicate that submillimeter pixel MR imaging shows promise as a noninvasive method for the preoperative staging of bladder cancers.

Aged↗

Influence of molecular weight on passive tumour accumulation of a soluble macromolecular drug carrier.

The molecular weight-dependence of tumour capture of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers (fractions of mw 22,000-778,000) was studied in vivo using subcutaneous (s.c.) Sarcoma 180 or B16F10 melanoma models. At 10 min, all fractions were already detectable in the tumour (1.5-3% of dose administered per gram) and those of molecular weight greater than the renal threshold showed progressive tumour accumulation up to 20% of dose administered per gram after 72 h in the Sarcoma 180 model. Tumour-selective uptake was confirmed for all copolymer fractions in both tumour models and in the sarcoma 180 model, the ratio (accumulation index, AI) of the AUC in tumour to AUC in skeletal muscle (a typical normal tissue) increasing from six to 12 with increasing copolymer molecular weight. The tumour/blood AI was greater (1-3) in the Sarcoma 180 model than the B16F10 melanoma model (0.4-1.0).

Acrylamides↗

Are bacterial proteinases pathogenic factors?

Evidence is rapidly accumulating that suggests that the growth and proliferation of pathogenic bacteria depend on proteolytic enzymes of the invading organism and of the host. Proteinase inhibitors targeting bacterial proteinases may be useful antimicrobial agents.

Animals↗

Proton-cotransport of pravastatin across intestinal brush-border membrane.

PURPOSE: The purpose of the present study is to clarify the intestinal brush-border transport mechanism of a weak organic acid, pravastatin, an HMG-CoA reductase inhibitor. METHODS: The transport of pravastatin was studied by using intestinal brush-border membrane vesicles prepared from rabbit jejunum, and uptake by the membrane vesicles was measured using rapid filtration technique. RESULTS: The initial uptake of [14C]pravastatin was markedly increased with decreases in extravesicular pH and showed a clear overshoot phenomenon in the presence of a proton gradient (pHin/out = 7.5/5.5). A protonophore, carbonylcyanide p-trifluoromethoxyphenylhydrazone, significantly reduced the uptake of [14C]pravastatin. In addition, an ionophore for sodium, potassium and proton, nigericin, stimulated the uptake of [14C]pravastatin in the presence of a potassium gradient ([K+]in/[K+]out = 0/145 mM). On the other hand, neither the imposition of an inwardly directed sodium gradient nor an outwardly directed bicarbonate gradient stimulated the uptake of [14C]pravastatin. In the presence of a proton gradient (pHin/out = 7.5/5.5), the initial uptake of pravastatin was saturable with the apparent Kt of 15.2 +/- 3.2 mM and Jmax of 10.6 +/- 1.21 nmol/mg protein/10 sec. The uptake of pravastatin was significantly inhibited by monocarboxylic acid compounds such as acetic acid and nicotinic acid in a competitive manner but not by di- or tricarboxylic acids, or acidic amino acid. CONCLUSION: It was concluded that a pH-dependent transport of pravastatin across the brush-border membrane occurs by a proton-gradient dependent carrier-mediated mechanism rather than by simple diffusion of its unionized form.

Animals↗

In vivo angiogenesis induced by recombinant adenovirus vectors coding either for secreted or nonsecreted forms of acidic fibroblast growth factor.

In vivo gene transfer of angiogenic growth factors represents a potential approach to the treatment of ischemic diseases. The present study examined the in vitro and in vivo effects of two replication-deficient recombinant adenovirus (Ad) vectors coding for human acidic fibroblast growth factor (aFGF1-154). One vector codes for the nonsecreted form of the peptide (AdCMV.aFGF1-154), and the other vector codes for a recombinant, secreted form (AdCMV.sp+aFGF1-154). AdCMV.NLS beta gal, an adenovirus vector coding for beta-galactosidase (beta-Gal), was used as a control. Assessment of proliferation of starved human umbilical vein endothelial cells infected with AdCMV.aFGF1-154 and AdCMV.sp+aFGF1-154 (20 pfu/cell) showed approximately 6- and 10-fold increase in cell number over control, respectively. Infection with AdCMV.sp+aFGF1-154 and with AdCMV.aFGF1-154 enhanced endothelial cell differentiation into capillary-like structures in vitro. However, this effect was significantly more pronounced with AdCMV.sp+aFGF1-154 than with AdCMV.aFGF1-154. Angiogenesis in vivo was assessed by injecting subcutaneously into mice 750 microliters of reconstituted basement membrane proteins (Matrigel) and the Ad vectors (2 x 10(8) pfu). After 14 days, there was histologic evidence of neovascularization in the animal's tissue surrounding the Matrigel plugs with AdCMV.aFGF1-154 and AdCMV.sp+aFGF1-154. Further, the hemoglobin content of the Matrigel plugs with AdCMV.aFGF1-154 and with AdCMV.sp+aFGF1-154 was, respectively, 2.3- and 2.6-fold higher than with AdCMV.NLS beta gal. Together, these observations support the concept that adenovirus vectors coding for various forms of acidic FGF1-154 may be used to induce angiogenesis in vivo and may provide a new therapeutic approach to ischemic diseases.

Adenoviridae↗

Possible involvement of protein-tyrosine kinases such as p72syk in the disc-sphere change response of porcine platelets.

We previously reported that p72syk, a non-receptor tyrosine kinase, was activated maximally at 10 s after thrombin or thromboxane A2 stimulation, even in platelets that were not allowed to aggregate [Taniguchi et al. (1993) J. Biol. Chem. 268, 2277-2279; Maeda et al. (1993) Biochem. Biophys. Res. Commun. 197, 62-67]. Then, the change in the shape of porcine platelets induced by the thromboxane A2 analogue, STA2, and the role of protein-tyrosine kinases including p72syk in this response were evaluated, using the shape-change parameter. We show that p72syk activation is correlated with the disc-sphere change in a time- and dose-dependent manner following stimulation by STA2. Tyrphostin B44, a potent protein-tyrosine kinase inhibitor, reduced the thromboxane A2-evoked p72syk activation and the disc-sphere change in a dose-dependent manner. Furthermore, the translocation of p72syk to the cytoskeleton-rich fraction and an increase in the tyrosine phosphorylation of an about 120 kDa protein were observed during the disc-sphere change induced by STA2. These lines of evidence suggest that the activation of protein-tyrosine kinases such as p72syk may be involved in the disc-sphere change response in thromboxane A2-stimulated porcine platelets.

Animals↗

Effects of monoclonal anti-c-kit antibody (ACK2) on melanocytes in newborn mice.

Previous studies indicate that c-Kit is required for postnatal melanocyte development. To understand the precise mechanisms of c-Kit dependence, we studied melanocyte development in newborn C57BL/6 mice by means of peritoneal injection of a monoclonal anti-c-Kit antibody (ACK2), which blocks c-Kit functions. The mice were injected once or more with ACK2 at various intervals after birth. In experiment 1, skin samples were examined on day 10 post-partum and in experiment 2 they were examined daily until day 10 post-partum. We studied melanocytes in the hair follicles, epidermis, and dermis by light and electron microscopy with dopa reactions and immunohistochemistry. Epidermal melanocytes in untreated mice were dopa negative and c-Kit positive on day 0 post-partum but became dopa positive soon thereafter. In ACK2-treated mice, the earlier the mice received ACK2 injections after birth, the fewer melanocytes they had, not only in the epidermis, but also in follicles. In these mice, melanocytes that had undergone apoptosis in the dermis and the follicles were detected ultrastructurally. Some appeared to have produced tyrosinase, because they had dopa-positive melanosomes. These results suggest that melanocytes in newborn mice are c-Kit dependent and undergo apoptosis when c-Kit receptors are blocked by ACK2 in the early days after birth. During this c-Kit-dependent period, melanocytes differentiate from dopa negative to positive and migrate from the epidermis to hair follicles.

Animals↗

Reliability of the task-related component (P3b) of P3 event-related potentials.

Within session and between session reliabilities of the task-related component (P3b) of the P3 measures (amplitude, area and latency) and their habituation across eight sessions separated by 7-10 days, except for an interval of 1 month between the 6th and 7th sessions, were studied based on the difference waves, which were obtained by subtracting the ignored infrequent event-related potentials (ERP) from the target ERP elicited by a standard auditory oddball paradigm with eyes-open or eyes-closed conditions in 10 normal subjects. The within session reliabilities represented as Pearson correlation coefficients (r) were 0.57-0.66 for the three measures except for those for the latency and amplitude under the eyes-closed condition. The between session reliabilities expressed as intraclass correlation coefficients (R) ranged from 0.54 to 0.60 except for that for latency under eyes-closed conditions. Long-term habituation occurred within the first six sessions for the P3b amplitude and area, and dishabituation took place in the 7th session after an interval of 1 month, whereas no such phenomenon was observed for the P3b latency. Implications of the present results are discussed in terms of the clinical application of the P3 measures.

Adult↗

Effects of hCRH on sleep and body temperature rhythms.

We investigated the effects of human corticotropin-releasing hormone (hCRH) on the sleep structure and body temperature rhythms of seven healthy young men. Polysomnographic recordings were obtained and body temperatures were monitored continuously for 48 h in each subject following the intravenous administration of saline or of 100 micrograms hCRH. The administration of hCRH was associated with a significant phase-advancement in body temperature rhythm vs the saline control. The administration of hCRH affected non-rapid eye movement (NREM) sleep by reducing significantly slow wave sleep (SWS) and sleep efficiency, whereas the percentage of sleep stages 1 and 2 were increased significantly. These changes in body temperature rhythms and sleep structure induced by hCRH resembled those observed in patients with endogenous depression, except for the findings during rapid eye movement (REM) sleep. We hypothesize that a hypersecretion of hCRH in patients with endogenous depression may help to explain the changes in body temperature rhythms and sleep structure often reported in such patients.

Adrenocorticotropic Hormone↗

Prognosis of epilepsy withdrawn from antiepileptic drugs.

Antiepileptic drugs (AED) were discontinued in 55 epileptics who had been free from seizures treated with AED, in accordance with the following criteria and procedures. (i) A reduction in AED commences when patients have been free from seizures for at least 2 years and epileptic discharges have also disappeared in repeated electroencephalogram (EEG) recordings during that period. (ii) AED are gradually reduced if no relapse is seen in clinical seizures and epileptic discharges in EEG. (iii) As a rule at least 2 years are required as the interval from the onset of a reduction to the withdrawal of AED. Forty-three patients were followed up by a questionnaire and/or by telephone and the follow-up period from the withdrawal of AED to the survey ranged from 0.9 to 8.8 years; in 38 patients (88.4%) the period was longer than 2 years. No relapse of seizures was found in any of the 43 patients. The severity of epilepsy judged by the total number of frequency of seizures, the presence of neuropsychiatric complications, the combination of different types of seizures, and the duration of epilepsy from the seizure onset to the last seizure appeared not to be risk factors for the recurrence of seizure. Normal EEG was, however, considered to be an important prerequisite for a good prognosis.

Adolescent↗

Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus type 1 in vitro and in vivo.

Oryzacystatin (OC) is the first-described cystatin originating from rice seed; it consists of two molecular species, OC-I and OC-II, which have antiviral action against poliovirus in vitro (H. Kondo, S. Ijiri, K. Abe, H. Maeda, and S. Arai, FEBS Lett. 299:48-50, 1992). In the experiments reported here, we investigated the effects of OC-I and OC-II on the replication of herpes simplex virus type 1 (HSV-1) in vitro and in vivo. HSV-1 was inoculated onto monolayers of monkey kidney epithelial cells (CV-1 cells) at a multiplicity of infection of 0.1 PFU per cell. After adsorption of the virus onto cells, the cultures were incubated in the presence of either OC-I or OC-II in the concentration range of 1.0 to 300 microM, and the supernatant virus yield was quantitated at 24 h. The effective concentration for 90% inhibition of HSV-1 was 14.8 microM, while a cytotoxic effect on CV-1 cells without infection of HSV-1 was not observed below 500 microM OC-I. Therefore, the apparent in vitro chemotherapeutic index was estimated to be more than 33. In the mouse model of HSV-1-induced keratitis and encephalopathy, topical administration of OC-I to the mouse cornea produced a significant decrease in virus production in the cornea (mean virus yields: 3.11 log10 PFU in the treated group and 4.37 log10 PFU in the control group) and significant improvement in survival rates (P = 0.01). The in vivo antiherpetic effect of OC-I was comparable to that of acyclovir, indicating that topical treatment of HSV-1 infection in humans with OC-I might be possible. Our data also suggest the importance of some thiol proteinases, which may be derived from either the host's cells or HSV-1, during the replication process of HSV-1.

Animals↗

Degradation of humoral host defense by Candida albicans proteinase.

The effect of an extracellular proteinase from the pathogenic yeast Candida albicans on the bactericidal and opsonizing activities of human serum was studied. The ability of human polymorphonuclear leukocytes to kill Staphylococcus aureus was greatly reduced when the bacteria were opsonized with human serum treated with the proteinase. The reduction in the opsonizing activity of human serum was attributed to degradation of the Fc portion of immunoglobulin G by the action of C. albicans proteinase as determined by immunoprecipitation reaction. However, the Fab portion of immunoglobulin G was resistant to proteolysis by the proteinase. A clear reduction in the bactericidal activity of human serum against Escherichia coli was observed when the serum was treated with C. albicans proteinase. The reduction of serum bactericidal activity was attributed to the degradation of complement C3 by proteolysis by the proteinase as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while C5 resisted the action of the proteinase. As determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the proteinase also degrades endogenous proteinase inhibitors, such as alpha 2 macroglobulin and alpha 1 proteinase inhibitor, which are involved in regulating inflammation. These results suggest that destruction of a host's defense-oriented or regulatory proteins facilitates debilitation of the infected host.

Aspartic Acid Endopeptidases↗

VEGF165 expressed by a replication-deficient recombinant adenovirus vector induces angiogenesis in vivo.

To evaluate the concept that localized delivery of angiogenic factors via virus-mediated gene transfer may be useful in the treatment of ischemic disorders, the replication-deficient adenovirus (Ad) vector AdCMV.VEGF165 (where CMV is cytomegalovirus and VEGF is vascular endothelial growth factor) containing the cDNA for human VEGF165, a secreted endothelial cell-specific angiogenic growth factor, was constructed. Human umbilical vein endothelial cells (HUVECs) and rat aorta smooth muscle cells (RASMCs) infected with AdCMV.VEGF165 (5 and 20 plaque-forming units [pfu] per cell) demonstrated VEGF mRNA expression and protein secretion into the supernatant. Furthermore, the conditioned medium from these cells enhanced vascular permeability in vivo. In contrast, neither VEGF mRNA nor secreted protein was found in uninfected HUVECs or RASMCs or in cells infected with the control vector AdCMV.beta gal (where beta gal is beta-galactosidase). Assessment of starved HUVECs at 14 days demonstrated sixfold more cells for AdCMV.VEGF165-infected HUVECs (20 pfu per cell) than for either infected or uninfected control cells. RASMC proliferation was unaffected by infection with AdCMV.VEGF165. When plated in 2% serum on dishes precoated with reconstituted basement membrane (Matrigel), HUVECs infected with AdCMV.VEGF165 (20 pfu per cell) differentiated into capillary-like structures. Under similar conditions, both uninfected HUVECs and HUVECs infected with AdCMV.beta gal did not differentiate. To evaluate the ability of AdCMV.VEGF165 to function in vivo, either AdCMV. VEGF165 or AdCMV.beta gal (2 x 10(10) pfu) was resuspended in 0.5 mL Matrigel and injected subcutaneously into mice. Immunohistochemical staining demonstrated VEGF in the tissues surrounding the Matrigel plugs containing AdCMV.VEGF165 up to 3 weeks after injection, whereas no VEGF was found in the control plugs with AdCMV.beta gal. Two weeks after injection, there was histological evidence of neovascularization in the tissues surrounding the Matrigel containing AdCMV.VEGF165, whereas no significant angiogenesis was observed in response to AdCMV.beta gal. Furthermore, the Matrigel plugs with AdCMV.VEGF165 demonstrated hemoglobin content fourfold higher than the plugs with AdCMV.beta gal. Together, these in vitro and in vivo studies are consistent with the concept that Ad vectors may provide a useful strategy for efficient local delivery of VEGF165 in the treatment of ischemic diseases.

Adenoviridae↗

Ischemic stroke events and carotid atherosclerosis. Results of the Osaka Follow-up Study for Ultrasonographic Assessment of Carotid Atherosclerosis (the OSACA Study).

BACKGROUND AND PURPOSE: To clarify the clinical significance of carotid atherosclerosis for ischemic stroke events, a follow-up study was performed in Japanese patients. METHODS: Two hundred fourteen patients were registered from nine hospitals in the Osaka community. All patients were checked for a prior history of stroke, and the risk factors for stroke and atherosclerosis were evaluated. Carotid atherosclerosis was assessed by 7.5-MHz duplex ultrasonography. We studied the relationship between the ischemic stroke event rate and the severity and appearance of the carotid atherosclerosis. We also studied the relationship between stroke events and various risk factors. RESULTS: The average duration of follow-up was 16 months. Ten patients suffered new ischemic stroke episodes during this follow-up period. At the initial ultrasonographic study, 16 patients had high-grade stenosis and 21 had ulcerated plaque. Proportional hazard regression analysis showed that grade of stenosis and plaque ulceration were positively related to the event rate. Patients with ulcerated plaque had a sevenfold higher hazard ratio for stroke in comparison to those without (P < .01). The ipsilateral stroke recurrence rate was 11 times higher in patients with ulcerated high-grade stenotic carotid lesions. CONCLUSIONS: The present findings demonstrate that the severity of carotid atherosclerosis as evaluated by ultrasonography is a useful indicator of the risk of ischemic stroke in symptomatic patients.

Aged↗

[Studies on structure of light degradation products of (-)-(S)-10-(1-aminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2,3-dihyd ro-7H- pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (T-3761) in aqueous solution and solid state].

The structures of light degradation products of (-)-(S)-10-(1-aminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2,3-dih ydr o-7H- pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (T-3761) in aqueous solution and in the solid state were investigated. In aqueous solution, ten products were detected using HPLC and in the solid state, one main product was detected. All these light degradation products were isolated and their structures were elucidated. It was revealed that in almost all light degradation products only the 1-aminocyclopropyl side chain at the 10-position of T-3761 is changed to various structures by light oxidation. Surprisingly we found a unique light degradation product, in which carboxylic acid at the 6-position of T-3761 is changed to the hydroxy moiety.

Anti-Infective Agents↗

Plasma free and sulfoconjugated dopamine before and after a half-marathon.

To elucidate whether increased plasma levels of free dopamine (F-DA) after exercise are due to deconjugation of sulfoconjugated (S-) DA in plasma, we compared the changes in plasma F- and S- DA, as well as changes in both the S- and F- forms of epinephrine (E) and norepinephrine (NE), after running a half-marathon. Free catecholamines (F-CAs) were measured by automated high-performance liquid chromatography (HPLC). Total (F+S) CAs were determined using an efficient deconjugation method as follows; 1200 microliters plasma was incubated with 152 mU arylsulfatase (AS) for 30 min at pH 7.6. The plasma levels of F-CA (pg/ml) (mean +/- SEM) all increased significantly (p < 0.01) after the half-marathon; i.e., F-DA increased from 13.3 +/- 5.7 to 176.3 +/- 32.2; F-E from 58.0 +/- 12.3 to 764.3 +/- 136.4; F-NE from 246.6 +/- 15.2 to 3082.0 +/- 690.3. OF S-CAs, S-E (from 127.8 +/- 26.0 to 1218.2 +/- 190.8) and S-NE (from 717.1 +/- 61.6 to 5586.9 +/- 761.9) also increased, but, in contrast, among the S-CAs, only the increase in S-DA (from 5324.9 +/- 1967.3 to 7359.6 +/- 1627.9) was not statistically significant. Sulfoconjugation may play an important role in inactivating F-DA as well as F-NE and -E, that are released into plasma in response to vigorous exercise. Thus, plasma F-DA is unlikely to be derived through deconjugation of plasma S-DA.

Adult↗