Biomedical subjects

M Hayakawa

Publications and source records attributed to M Hayakawa.

At least 91 records · Page 5Linked to original sources

PubMed2000

Is nitrotyrosine generated in human erythrocytes in circulation?

Nitrotyrosine is considered a stable biomarker of reactive nitrogen species, including nitrogen dioxide (NO2) and peroxynitrous acid (ONOOH) in biomaterials. There are inconsistent observations on the detection of free and protein-associated nitrotyrosine in normal human plasma. Human erythrocytes, differentiated from erythrocyte precursor cells in the bone marrow, circulating in the body for an average of 120 d, and finally removed by spleen macrophages, may be exposed to reactive nitrogen species. In the present study, membrane proteins and hemoglobin from the senescent erythrocyte population were compared with those from young erythrocytes separated from the same individuals in their nitrotyrosine presence using newly prepared rabbit polyclonal anti-nitrotyrosine-ribonuclease A and anti-nitro(N-butoxycarbonyl)tyrosine-bovine serum albumin antibodies. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the membranes and hemoglobin, and subsequent Western blot analysis, showed that these antibodies only slightly bind to the bands of the proteins from both young and senescent erythrocytes, whereas these antibodies definitely bind to the protein bands of membranes and hemoglobin nitrated by NO2 or ONOOH in vitro. This result indicates that nitrotyrosine is not detected in the membrane proteins and hemoglobin in human normal erythrocytes in circulation. However, this does not conclude that erythrocytes are not exposed to reactive nitrogen species in the circulation.

Aging↗

PubMed2000

[2-(O-Phenylalkyl)phenoxy]alkylamines III: Synthesis and selective serotonin-2 receptor binding (2).

A series of 12-(2-phenylethyl)phenoxy]ethylpyrrolidine derivatives were synthesized, and their affinity for serotonin-2 (5-HT2) and dopamine-2 (D2) receptors was examined. Among them, compound 17, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxylethyl] -1-methylpyrrolidine hydrochloride, showed high 5-HT2 receptor affinity in vitro. This compound was a more potent inhibitor of ex vivo 5-HT-induced platelet aggregation than compound 3, which was previously shown to be more potent than ketanserin (1) and sarpogrelate (2a). However, compound 17 produced gastric irritation in rats. Therefore, we carried out a further derivatization of 17, and compound 45 (R-102444), a lauryl ester prodrug of compound 17, was found to be a promising candidate as an antithrombotic agent. Oral administration of R-102444 produced a marked inhibition of 5-HT-induced ex vivo platelet aggregation, and R-102444 did not cause any gastric irritation. The antiaggregatory effects of R-102444 were more potent than those of sarpogrelate (2a) and its active metabolite, M-1 (2b). In addition, R-102444 exhibited more potent antithrombotic effects than sarpogrelate in a rat photochemically-induced thrombosis model.

Acylation↗

PubMed2000

[2-(omega-phenylalkyl)phenoxy]alkylamines.II: Synthesis and selective serotonin-2 receptor binding.

A series of [2-(omega-phenylalkyl)phenoxy]alkylamines was synthesized and their receptor binding affinity was examined in vitro. These compounds showed an affinity for serotonin-2 (5-HT2) and dopamine-2 (D2) receptors. [2-(2-phenylethyl)phenoxy]alkylamine derivatives with a pyrrolidine or piperidine moiety in the structure showed higher affinity for 5-HT2 receptors but lower affinity for D2 receptors. Among these compounds, (S)-2-[2- [2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methylpyrrolidine, (S)-27, exhibited the most potent and selective affinity for 5-HT2 receptors. Furthermore, (S)-27 was effective in inhibiting 5-HT-induced vasoconstriction in vitro and platelet aggregation both in vitro and ex vivo.

Animals↗

PubMed2000

Simultaneous intravascular two-dimensional plus Doppler ultrasound is useful for evaluation of postischemic vasodilatation: plasm NOx - levels determined by the Griess method may not reflect the extent of postischemic NO-induced vasodilatation.

Our objective was 1) to assess postischemic vasodilatation using simultaneous intravascular two-dimensional and Doppler ultrasound, and 2) to clarify whether plasma nitrite and nitrate (NOx-) levels change during postischemic vasodilatation. The vascular cross-sectional area (CSA) was evaluated in 18 mongrel dogs, and the average instantaneous peak velocity (APV) in the iliac arteries after the 5-min occlusion of blood flow was determined. Plasma NOx- levels were measured at the baseline, during the occlusion of blood flow, and 1.5, 3, and 10 min after recanalization. The %CSA significantly increased from 30 s to 7 min after the recanalization, and maximal vasodilatation was observed at 1.5 min after the recanalization (14.1 +/- 0.9 to 15.8 +/- 1.0 mm2, p< 0.0001 vs. baseline). Plasma NOx- levels were significantly reduced during the occlusion of blood flow and remained reduced at 1.5, 3, and 10 min after recanalization compared with the baseline values. We concluded that simultaneous intravascular two-dimensional and Doppler ultrasound is useful for assessment during postischemic vasodilatation, and that plasma NOx- levels assayed with the Griess reagent do not significantly increase, even when maximal vasodilatation is observed.

Animals↗

PubMed2000

[Swallowing rehabilitation using balloon catheter treatment evaluated by videofluorography in an elderly patient with Wallenberg's syndrome].

A 65-year old man was admitted with severe dysphagia, ataxia and aspiration pneumonia. Dysphagia and ataxia were caused by lateral medullary infarction (Wallenberg's syndrome). The swallowing abnormality was assessed by videofluorography and we attempted the balloon dilatation method for cricopharyngeal dysphagia. Three months after initiation of swallowing training, videofluorography (VF) showed that the magnitude of aspiration to the trachea had decreased and the patient began taking food by mouth. The balloon dilatation method is successful for chronic stage cricopharyngeal dysphagia and the VF test is useful for quantitative assessment of dysphagia and for deciding when to start oral intake in elderly patients.

Aged↗

PubMed2000

Natural history of the neck remnant of a cerebral aneurysm treated with the Guglielmi detachable coil system.

OBJECT: The long-term durability of Guglielmi detachable coil (GDC) embolization of cerebral aneurysms is still unknown. The purpose of this study was to evaluate the anatomical evolution of neck remnants in aneurysms treated with GDCs. METHODS: Of 455 aneurysms treated with GDCs from 1990 to 1998 at the University of California at Los Angeles Medical Center, 178 aneurysms (39%) had residual necks postembolization. Long-term follow-up angiograms were obtained in 73 of these aneurysms in 71 patients. The mean duration of angiographic follow up was 17.3 months. Twenty-four of the aneurysms were small with small necks, 24 were small with wide necks, 15 were large, and 10 were giant aneurysms. In small aneurysms with small necks, postembolization angiography revealed 12 aneurysms (50%) with progressive thrombosis, eight (33%) unchanged, and four (17%) with recanalization. In small aneurysms with wide necks, six (25%) had progressive thrombosis, eight (33%) remained unchanged, and 10 (42%) had recanalization. In large aneurysms, two (13%) were unchanged and 13 (87%) had recanalization. Of the giant aneurysms only one (10%) remained unchanged and nine (90%) had recanalization. Overall, 18 aneurysms (25%) exhibited progressive thrombosis, 19 (26%) remained unchanged, and 36 (49%) displayed recanalization on follow-up angiography. During the last 2 years of the study, the recanalization rate decreased and a higher rate of progressive thrombosis was noted in aneurysms with small necks. These positive changes are related to important new technical developments. CONCLUSIONS: Treatment with GDCs appears to be effective and the results permanent in most small aneurysms with small necks. However, there are important technical limitations in the current GDC technology that prevent recanalization in wide-necked or large or giant aneurysms.

Adult↗

PubMed2000

[Comparison of combined operation and nasal CPAP treatments for sleep disorders].

UNLABELLED: Uvulopalatopharyngoplasty (UPPP) and nasal CPAP are used for the treatment of obstructive sleep apnea syndrome (OSAS) in different institutions. Although OSAS results from an abnormality in the soft-palate, almost no reports have been made on the selection of UPPP or nasal CPAP procedures according to the type of abnormality. The most probable reason for this is that a comparison of treatment methods in individuals cases is difficult. We performed CPAP titration before and after operations, and compared the treatment methods, and evaluated the medical therapy. METHOD: A sleep polygraph was performed on the first night, and cases diagnosed as OSAS received CPAP titration on the second night. The blocked region was identified by endoscopic examination. The results of the operation were evaluated after 1-2 months, and apnea hypopnea index (AHI) improvements of less than 50% received a second CPAP titration. RESULTS: The operation results were poor for cases where endoscopic examination showed full-circumference palatal type, and good for soft palate and tonsillar type abnormalities. When endoscopic examinations were performed in conjunction with nasal CPAP, the treatment was observed to act on the soft palate and expand the air way in all cases. Nasal CPAP was effective in cases with full-circumference palatal abnormalities because in these cases, the pressure was caused by inflamma. Combined medical treatments were effective in cases where CPAP alone was ineffective because the pressure was too high.

Adult↗

PubMed2000

[A case of biloma caused by early complications of hepatic artery infusion chemotherapy].

We report a 70-year-old male who had biloma as an early complication of hepatic artery infusion chemotherapy. The patient had a history of subtotal gastrectomy for a advanced gastric cancer. Two years after the primary operation on the stomach, a solitary metastatic liver tumor was indicated by follow-up abdominal CT, and a segmental hepatectomy was performed. Soon after the hepatectomy, intraarterial catheter placement was performed via the left subclavian artery for preventive chemotherapy. Infusion chemotherapy of 10.5 g 5-FU and 75 mg CDDP was administered for a month, during which time the patient had liver dysfunction, fever, tenderness, and abdominal fullness. Abdominal CT revealed a large low density mass at a lateral segment of the liver which could not be seen on the previous CT image. Also, extravasation of contrast media was identified by angiography via the reservoir catheter. Using an interventional technique, percutaneous transhepatic drainage for biloma and extubation of the reservoir catheter were performed. The present case is thought to be of an early and rare complication of hepatic artery infusion chemotherapy. The etiology is discussed herein.

Aged↗

PubMed2000

[Patent blue-induced false-methemoglobinemia].

We experienced an anesthetic case, in which interference in oxygen saturation values by patent blue was mistaken for nitroglycerin-induced methemoglobinemia. A 40-year-old woman underwent mastectomy for breast cancer under general anesthesia. Nitroglycerin was infused to produce hypotensive anesthesia. Patent blue was locally injected around the cancer by a surgeon and surgery was started. A few minutes later, oxygen saturation by finger pulse oximeter suddenly decreased from 100% to 90%. And then, blood gas analysis was performed to confirm this change. The decrease of oxygen saturation and the increase of methemoglobin were also observed in the finding of blood gas analysis. At first, we judged these changes as methemoglobinemia by nitroglycerin infusion. Finally, however, we concluded that all these changes were attributable to the interference by patent blue on oxygen saturation value because we found that there had been some inconsistent findings as methemoglobinemia. The fact seems that nothing happened to the patient during the episode. This case showed us that anesthesiologists should understand the principle of hematological monitors and the meaning of the data obtained by monitors.

Adult↗

PubMed2000

[Perioperative management for emergency cesarean section of a patient with reexpansion pulmonary edema].

A 27-year-old woman with 39 week gestation was admitted because of cough and dyspnea accompanied by massive right-sided pleural effusion. Following the right thoracocentesis, about 2000 ml of bloody pleural effusion was drained. Just after the thoracocentesis, the fetal heart rate (FHR) temporarily showed a variable deceleration pattern but the rate was restored spontaneously. One hour later, cough and dyspnea became worse. Changes in FHR pattern indicated the premature separation of the normally implanted placenta. Accordingly, an emergency cesarean section was performed under general anesthesia. Massive foamy tracheal secretion was drained from the tracheal tube during surgery. As her chest X-ray showed signs of pulmonary edema in the right lung, her status was diagnosed as reexpansion pulmonary edema (RPE). She was transferred to the intensive care unit and treated with mechanical ventilation, prednisolone and diuretics. Extubation was performed on the 2nd day after the surgery. On reexpansion of the collapsed lung, it is always necessary to consider not only the hemodynamic changes just after reexpansion but also RPE following reexpansion.

Adult↗

PubMed2000

[Tracheal tube damage by Harmonic Scalpel during tonsillectomy].

We experienced a case in which a tracheal tube was damaged by a Harmonic Scalpel during tonsillectomy. A 33-year-old man with chronic tonsillitis underwent tonsillectomy under general anesthesia. The trachea was intubated by Polar Preformed Tracheal Tube (Polar tube). About 45 minutes after the start of surgery, sudden massive air leakage in the trachea occurred. Surgery was accomplished under oral suctioning. After extubation, we found that an inflation cuff tube was cut off by the Harmonic Scalpel. The cause of damage was the position of an inflation cuff tube which had been in the dorsal side of the tracheal tube (near the surgical field) in the Polar tube. Anesthesiologists should be aware of the characteristics of the surgical equipment newly introduced.

Adult↗

PubMed2000

[Archives of environmental health digital maps and their delivery by the Internet].

Geographic Information System is becoming a very important tool for environmental health research. We have produced various digital maps for different scales for different purposes. The burst of E. Coli O-157, distribution of hazadarous chemicals in East Asia, and coastal resin pellets are some examples. It now becomes a problem how to archive these digital maps and how to retrieve these maps according to user's request. We have developed a computer system that can store various types of digital maps and can retrieve them from WWW client machines. The key concept of this archive system is to classify every digital maps according to their region of interest.

Environmental Health↗

PubMed1999

Differential temperature dependency of chemical stressors in HSF1-mediated stress response in mammalian cells.

Expression of stress proteins is generally induced by a variety of stressors. To gain a better understanding of the sensing and induction mechanisms of stress responses, we studied the effects of culture temperature on responses to various stressors, since the induction of hsp70 in mammalian cells by heat shock is somehow modulated by culture temperature. Hsp70 was not induced by treatment with sodium arsenite, azetidine-2-carboxylic acid, or zinc sulfate at the level of heat shock factor (HSF) 1 activation in cells incubated at low temperature, although these treatments induced hsp70 in cells incubated at 37 degrees C. The repression of sodium arsenite or zinc sulfate-induced HSF1 activation by low temperature was not simply due to the inhibition of protein synthesis. On the other hand, heat shock and iodoacetamide induced HSF 1 activation in cells incubated at either temperature. Thus, there seem to be two kinds of stressors that induce HSF1 activation independently of or dependent on culture temperature. Furthermore, the reduction of glutathione level seemed to be essential for HSF1 activation by chemical stressors.

Animals↗

PubMed1999

Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation.

IkappaB [inhibitor of nuclear factor kappaB (NF-kappaB)] kinase (IKK) phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses. IKK is composed of three subunits-IKKalpha and IKKbeta, which are highly similar protein kinases, and IKKgamma, a regulatory subunit. In mammalian cells, phosphorylation of two sites at the activation loop of IKKbeta was essential for activation of IKK by tumor necrosis factor and interleukin-1. Elimination of equivalent sites in IKKalpha, however, did not interfere with IKK activation. Thus, IKKbeta, not IKKalpha, is the target for proinflammatory stimuli. Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response.

Amino Acid Sequence↗

PubMed1999

Determination and characterization of the hemagglutinin-associated short motifs found in Porphyromonas gingivalis multiple gene products.

Porphyromonas gingivalis is a Gram-negative anaerobic bacterial species implicated as an important pathogen in the development of adult periodontitis. In our studies of P. gingivalis and ways to protect against periodontal disease, we have prepared the monoclonal antibody mAb-Pg-vc and its recombinant antibody, which are capable of inhibiting the hemagglutinating activity of P. gingivalis (Shibata, Y., Kurihara, K., Takiguchi, H., and Abiko, Y. (1998) Infect. Immun. 66, 2207-2212). To clarify the antigenically related hemagglutinating domains, we attempted to determine the minimum motifs responsible for P. gingivalis hemagglutinin. Initially, the 9-kilobase EcoRI fragment encoding the 130-kDa protein was cloned from the P. gingivalis chromosome using mAb-Pg-vc. Western blot analysis of nested deletion clones, the competition experiments using synthetic peptides, and the binding assay of the phage-displayed peptides using the mAb-Pg-vc allowed us to identify the minimum motifs, PVQNLT. Furthermore, the presence of multi-gene family coding for this epitope was confirmed via Southern blot analysis and PCR using the primers complementary to the domain corresponding to this epitope. It is suggested that the hemagglutinin-associated motif may be PVQNLT and that the gene families specifying this motif found in P. gingivalis chromosome encode many hemagglutinin and/or hemagglutinin-related proteases.

Adhesins, Bacterial↗

PubMed1999

Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IkappaBalpha overexpression.

We investigated whether the cell growth and apoptosis of multiple cytokine-producing bladder cancer cells can be regulated by nuclear factor kappaB (NF-kappaB). The bladder cancer cell line KU-19-19, obtained from a 76-year-old man who demonstrated marked leukocytosis, produces multiple cytokines and demonstrates autocrine growth by granulocyte colony-stimulating factor (G-CSF). Electrophoretic mobility shift assay (EMSA) revealed that NF-kappaB was activated in KU-19-19 but not in other bladder cancer cell lines (KU-1, KU-7, or T-24, respectively). The inhibition of NF-kappaB DNA-binding activity with adenovirus vectors expressing the stable form of the NF-kappaB inhibitor IkappaBalpha (multiplicity of infection [MOI] of 10) inhibited growth and induced apoptosis of KU-19-19, but not KU-1, KU-7, or T-24. The production of several cytokines was suppressed significantly in KU-19-19 by this gene delivery. Although dexamethasone (10 microM) could also suppress cytokine production, it did not induce dramatic cell death in KU-19-19 because it could not inhibit NF-kappaB activation stably and strongly. These results suggest that NF-kappaB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.

Adenoviridae↗

PubMed1999

REP-1 gene mutations in Japanese patients with choroideremia.

BACKGROUND: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. METHODS: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1-15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. RESULTS: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. CONCLUSIONS: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Low density lipoprotein particle diameter in young, nonobese, normolipidemic Japanese men.

BACKGROUND: prospective studies have demonstrated that a predominance of small, dense LDL particles (pattern B) precedes the clinical onset of coronary heart disease. Prevalence and characteristics of subjects with this LDL size abnormality were studied in young, nonobese, Japanese normolipidemic men. METHODS AND RESULTS: LDL peak particle diameter (PPD) was measured by continuous disc polyacrylamide gel electrophoresis in 223 nonobese normolipidemic men aged 18-20 years (mean+/-S.D. body mass index: 21.9+/-3.7 kg/m2, total cholesterol: 180+/-29 mg/dl, triglyceride: 62+/-34 mg/dl, HDL cholesterol: 58+/-12 mg/dl). Men with small LDL (PPD < 25.8 nm) were found in only 5.4% (n=12) whereas 197 men (88.3%) had a preponderance of large LDL (PPD 26.3 nm). As compared with men in a top tertile (PPD 27.5 nm) those in a low tertile (PPD < 26.9 nm) had higher serum levels of LDL cholesterol (120+/-31 vs 104+/-24 mg/dl), triglyceride (72+/-39 vs 49+/-16 mg/dl) and apolipoprotein (apo) B (84+/-21 vs 68+/-14 mg/dl), and lower HDL cholesterol (54+/-10 vs 60+/-12 mg/dl). They also had greater body mass index (23.2+/-4.6 vs 20.9+/-3.1 kg/m2) and percent body fat (21.5+/-7.7 vs 17.5+/-4.9%). LDL-PPD was positively correlated with HDL cholesterol (R=0.20, P=0.002) and was negatively correlated with apoB (R=0.34, P < 0.001), triglyceride (R=0.32, P < 0.001). percent body fat (R=0.26, P < 0.001), body mass index (R=0.24, P < 0.001), fat mass (R=0.23, P=0.001), total cholesterol (R=0.20, P=0.002). In multiple regression analysis, apoB, triglyceride, HDL cholesterol, apoAI and percent body fat explained 18% of LDLPPD variability. CONCLUSION: even in young, nonobese, normolipidemic men, LDL size appears to be associated with triglyceride-rich lipoprotein metabolism and body fat.

Adolescent↗