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Biomedical subjects

Y Nakai

Publications and source records attributed to Y Nakai.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mitochondrial ATP-sensitive potassium channel plays a dominant role in ischemic preconditioning of rabbit heart.

BACKGROUND: The ATP-sensitive potassium (K(ATP)) channel has been shown to be important in the ischemic preconditioning (IPC) response. Recently, the mitochondrial rather than the sarcolemmal K(ATP) channel has been focused on due to its energy-modulating property. Hence, this study was undertaken to elucidate the role of the mitochondrial K(ATP) channel in IPC by modulating the mitochondrial K(ATP) channel in isolated perfused rabbit hearts. METHODS: Seven hearts served as a control with no interventions. Seven hearts underwent IPC consisting of two 5-min cycles of global ischemia followed by 5 min of reperfusion. Seven hearts received the selective mitochondrial K(ATP) channel blocker 5-dehydroxydecanoate (5-HD, 100 microM) for 5 min before IPC, and 7 hearts received the selective mitochondrial K(ATP) channel opener diazoxide (50 microM) for 5 min. Then, all hearts were subjected to 1 h of left anterior descending coronary artery ischemia and 1 h of reperfusion. Left ventricular pressures, monophasic action potentials and coronary flow were measured throughout the experiment and infarct size was detected at the end of experiment. RESULTS: (1) The mitochondria-selective K(ATP) channel opener diazoxide reduced infarct size as compared to control (p < 0.05); (2) IPC reduced infarct size and preserved postischemic diastolic function as compared to control (p < 0.05), and (3) the mitochondria-selective K(ATP) channel blocker 5-HD reversed these effects. CONCLUSION: The mitochondrial ATP-sensitive potassium channel may be a potential site of cardioprotection.

Action Potentials↗
PubMed2001

Clinical evaluation of the Q-tip test in normal pregnant women.

The crisis frequency of stress incontinence (SI) is known to be high among pregnant women. This preliminary study was performed to determine whether the diagnostic standard of the Q-tip test used in the diagnosis of SI in nonpregnant women is applicable to pregnant women. The Q-tip tests were performed regularly during pregnancy and after parturition on primipara (n = 71) and multipara (n = 55) who were not in SI crisis at any time during the pregnancy. The values measured in multipara were significantly higher than in primipara (p = 0.0001), and the tendency to be higher was more prominent at 2-5 months and 10 months of pregnancy. These findings show that different normal values of the Q-tip test are necessary for primipara and multipara.

Adult↗
PubMed2001

[The role of psychosomatic medicine in public health (hygieiology): an approach for lifestyle-related disease].

In the twenty-first century it has been hypothesized that lifestyle-related disease will account for more than 70% of all disease; thus, in the twenty-first the prevention and treatment of lifestyle-related disease will be of primary importance. Lifestyle differs from individual to individual. In the past preventive medicine has targeted groups while clinical medicine has dealt with disease. However, in the twenty-first century it will be necessary to integrate the two approaches to meet the needs of the individuals. Measures following the primary prevention of lifestyle-related disease will be the vital and they can only be delivered by primary care medicine. As a model that covers the prevention and treatment of lifestyle-related diseases, based on the conventional biomedical model, a systematic medical model that attaches importance to the relativity of all factors and individuality will be necessary. The medical model for psychosomatic medicine is the Bio-psycho-socio-ethical (ecological) model, and psychosomatic medicine has specific methods for implementing this model. We have used this perspective to explain the role of psychosomatic medicine in public health (hygieiology).

Behavioral Medicine↗
PubMed2001

[Serial angiographical changes of a ruptured dissecting vertebral aneurysm].

A 54-year-old woman presented a subarachnoid hemorrhage from a ruptured dissecting aneurysm on the right vertebral artery. A right vertebral angiogram revealed a fusiform dilatation distal to the right posterior inferior cerebellar artery and "pseudo lumen" was observed in a delayed arterial phase. Conservative treatment was carried out, and the patient condition gradually improved. An angiographical examination for planned endovascular treatment 46 days after the onset, revealed the normalization of the formerly dilated caliber of the right vertebral artery with only a minor luminal irregularity. However, 83 days after the onset, right vertebral angiogram showed reappearance of the fusiform dilatation. The right vertebral angiogram obtained 204 days after the onset showed that the dilated segment of the dissecting aneurysm had become normalized to a slight degree. The serial angiographical changes of the dissecting site might have been due to regression and organization following transient thrombosis of intramural hematoma. Such drastic changes within a short period have not been reported yet. In conclusion, careful repeated follow-up is recommended in monitoring aneurysmal formation during the early to chronic phase after rupture of a dissecting aneurysm. The repetition of angiography is important, because later, if angiography has been performed only once, aneurysmal dilatation may be overlooked. One has to be aware of such changes, because such changes may alter the clinician's decision about treatment, as they did in our case.

Aneurysm, Ruptured↗
PubMed2001

Effects of umbilical arterial resistance on its arterial blood flow velocity waveforms.

BACKGROUND: We propose to clarify the effect of umbilical arterial resistance on umbilical arterial blood flow patterns in normal pregnant women. SUBJECTS: Pulsed Doppler examination was administered to 145 pregnant women of between 28 and 31 weeks of normal gestation without any prenatal complications. METHODS: The arterial flow velocity waveforms from two different arteries, one in the intra-abdominal portion and the other at the placental insertion, were sampled with the color flow mapping method, and the peak systolic velocity and the resistance index were calculated. RESULTS: The peak systolic velocity and resistance index on the placental side were significantly lower than those of the fetal side. CONCLUSION: A major difference exists between the umbilical arterial flow velocity waveforms on the fetal and placental sides, which might be caused by difference in the umbilical arterial resistance.

Blood Flow Velocity↗
PubMed2001

[A giant testicular tumor detected with dyspnea due to lung metastases: a case report].

A 19-year-old male presented with dyspnea. Clinical examination revealed the left infant-head-sized testicular tumor, multiple lung metastases and retroperitoneal bulky lymph node metastasis with marked elevation of serum lactic dehydrogenase (LDH) and alpha-fetoprotein. Left radical orchiectomy followed by the chemotherapy with etoposide and cisplatin (EP) for 4 cycles was performed. The tumor weighed 1,700 g, and was pathologically diagnosed as mixed germ cell tumor consisting of embryonal carcinoma and yolk sac tumor. After the treatment, the tumor markers were normalized with partial response (PR) of lung metastases and complete response (CR) of retroperitoneal lymph node metastasis. Thereafter, biopsy of lung metastases through video-assisted thoracoscopic surgery (VATS) was performed, and pathologically no viable cells were detected. Five months after the treatment, he was seized with convulsion due to brain metastasis with hemorrhage. Therefore, a surgical resection of brain metastasis and 2nd line chemotherapy with etoposide, ifosfamide and cisplatin (VIP) chemotherapy for 3 cycles was performed. The patient has been free of recurrence for 21 months after the 2nd line chemotherapy.

Adult↗
PubMed2000

Nuclear localization of yeast Nfs1p is required for cell survival.

Saccharomyces cerevisiae Nfs1p is mainly found in the mitochondrial matrix and has been shown to participate in iron-sulfur cluster assembly. We show here that Nfs1p contains a potential nuclear localization signal, RRRPR, in its mature part. When this sequence was mutated to RRGSR, the mutant protein could not restore cell growth under chromosomal NFS1-depleted conditions. However, this mutation did not affect the function of Nfs1p in biogenesis of mitochondrial iron-sulfur proteins. The growth defect of the mutant was complemented by simultaneous expression of the mature Nfs1p, which contains the intact nuclear localization signal but lacks its mitochondrial-targeting presequence. These results suggest that a fraction of Nfs1p is localized in the nucleus and is essential for cell viability.

Amino Acid Sequence↗
PubMed2000

Lysenin-sphingomyelin binding at the surface of oligodendrocyte lineage cells increases during differentiation in vitro.

We have investigated the relationship between the developmental expression of sphingomyelin, a major component of myelin, and oligodendrocyte lineage. Using lysenin as a cytochemical probe for membrane sphingomyelin, we have now determined the distribution pattern of sphingomyelin on the plasma membrane of rat cultured oligodendrocytes. Although lysenin does not bind to A2B5(+)/NG2(+) bipolar oligodendrocyte progenitors, lysenin recognizes sphingomyelin on the cell bodies of multipolar A2B5(+) cells, but not on their processes. O4(+) and O1(+) immature and MBP(+) mature oligodendrocytes are strongly labeled by lysenin from cell bodies to the tips of processes. The content of sphingomyelin in immature and mature oligodendrocytes is approximately 2-fold higher than that in oligodendrocyte progenitors. These findings show that sphingomyelin increases during differentiation of cells in the oligodendrocyte lineage. In multipolar oligodendrocyte progenitors exposed to Triton X-100 at 4 degrees C, lysenin labels cell processes in addition to cell bodies. In contrast, Triton X-100 extraction does not alter the distribution of lysenin binding on O4(+), O1(+) and MBP(+) cells, although the immunocytochemical intensities of the lysenin bindings increase. Our data suggest that the alteration in sphingomyelin content and distribution in the oligodendrocyte lineage cells could have important consequences for cell recognition and downstream signaling events through sphingomyelin-rich domains.

Animals↗
PubMed2000

Induction of apoptosis by the Vpr protein of human immunodeficiency virus type 1 occurs independently of G(2) arrest of the cell cycle.

The HIV-1 accessory gene product Vpr can inhibit cell proliferation via cell cycle arrest at the G(2) phase, and it can induce apoptosis after G(2) arrest. We found recently that C81, a carboxy-terminally truncated form of Vpr, induced apoptosis via G(1) arrest but did not induce G(2) arrest of the cell cycle. Thus, it seemed possible that expression of Vpr in cells might cause apoptosis independently of the ability of Vpr to induce G(2) arrest. We demonstrate here that Vpr-induced apoptosis occurs by a mechanism that does not necessarily require induction of G(2) arrest. First, it was found that the extent of apoptosis reached a maximum even when few cells were arrested at the G(2) phase of the cell cycle and was reduced in inverse proportion to the increased induction of G(2) arrest. Thus, the extent of induction of G(2) arrest was not correlated with the extent of Vpr-induced apoptosis. Furthermore, we replaced the Ile/Leu residues in the leucine zipper-like domain of Vpr with Ala or Pro and used cells that expressed the mutant protein to demonstrate that Vpr caused apoptosis in a manner that was independent of G(2) arrest. Finally, replacement of Ile/Leu by Pro at positions 60, 67, 74, and 81 within the leucine zipper-like domain of wild-type Vpr and C81 revealed that the Ile/Leu residues at positions 60, 67, and 74 in the leucine zipper-like domain were indispensable for induction of apoptosis induced by Vpr and by C81 and confirmed, in addition, that both processes might be regulated by the same pathway. C81 appears to be a useful tool for elucidation of the mechanism of apoptosis induced by expression of Vpr protein.

Amino Acid Sequence↗
PubMed2000

Study on selectin blocker. 8. Lead discovery of a non-sugar antagonist using a 3D-pharmacophore model.

We have developed a pharmacophore model of a ligand/E-selectin complex to screen drug candidates for selectin blockers. In a series of sugar mimetic studies of the E-selectin ligand, sialyl Lewis X (sLe(x)), we have already found a potent compound, a sulfated Le(x) analogue (1), and also have proposed how compound 1 binds to E-selectin (Tsujishita, H.; Hiramatsu, Y.; Kondo, N.; Ohmoto, H.; Kondo, H.; Kiso, M.; Hasegawa, A. J. Med. Chem. 1997, 40, 362-369). To find drug candidates that fit into the binding pocket of E-selectin, we constructed an original 3D-pharmacophore model from structural information of a compound 1/E-selectin complex model and screened lead compounds for selectin blockers using a commercially available database ACD-3D. As a result, we discovered a lead compound (2) containing good selectin inhibitory activity, and in addition, we succeeded to preliminarily optimize it to a more active lead compound (3) with micromolar IC(50) values, based on the 3D-pharmacophore model investigation. This methodology using the 3D-pharmacophore model could be applicable as a pre-screen system for selectin blockers.

Benzamides↗
PubMed2000

Pollen immunotherapy inhibits T helper 1 and 2 cell responses, but suppression of T helper 2 cell response is a more important mechanism related to the clinical efficacy.

OBJECTIVES: To investigate the allergen-induced IgE synthesis and cytokine production by peripheral blood mononuclear cells from patients with seasonal allergic rhinitis due to Japanese cedar (Cryptomeria japonica) pollens and to elucidate the immunological mechanisms related to the clinical efficacy of immunotherapy (IT) for seasonal allergic rhinitis. DESIGN: This study included 51 patients with seasonal allergic rhinitis due to the pollen and 8 nonatopic healthy volunteers (nonatopic group). Thirty-nine patients had been undergoing IT using the pollen extracts for various lengths of time (IT group). The remaining 12 patients had never been treated with IT (untreated group). Peripheral blood mononuclear cells (3.3 x 10(6) cells per milliliter) from each individual were cultured with Cry j 1, 4.17 microg/mL. After 96 hours, culture supernatants were harvested to determine the concentrations of IgE, interleukin (IL) 5, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha). RESULTS: The levels of IgE (P = .02), IL-5 (P<.01), and TNF-alpha (P = .05) were significantly higher in the untreated group than in the nonatopic group. The levels of IFN-gamma did not differ significantly between the untreated and the nonatopic groups (P = .19). The levels of IgE, IL-5, and IFN-gamma, but not of TNF-alpha, were inversely correlated with the duration (in years) of IT, and none of the levels of IgE (P = .74), IL-5 (P = .15), IFN-gamma (P = .61), and TNF-alpha (P = .55) differed significantly between the nonatopic group and those who had been treated with IT for 10 years or more. The levels of IL-5 were significantly lower in the good responders than in the poor responders to IT (P<.001), whereas the levels of total IgE (P = .20), IFN-gamma (P = .16), and TNF-alpha (P = .14) did not differ significantly between them. CONCLUSION: The mechanisms responsible for the clinical efficacy of pollen IT are principally related to the tolerance or anergy of T helper 2 cells.

Adult↗
PubMed2000

Allergen-induced mRNA expression of IL-5, but not of IL-4 and IFN-gamma, in peripheral blood mononuclear cells is a key feature of clinical manifestation of seasonal allergic rhinitis.

OBJECTIVES: To investigate the allergen-induced messenger RNA (mRNA) expression of interleukin (IL) 4, IL-5 and interferon gamma (IFN-gamma) in peripheral blood mononuclear cells from individuals sensitized by Japanese cedar (Cryptomeria japonica) pollens, and to elucidate the clinical role of IL-4, IL-5, and IFN-gamma in the allergen sensitization and clinical manifestation of allergic disorders. DESIGN: This study included 30 patients sensitized to the pollen and 14 nonatopic healthy volunteers. Peripheral blood mononuclear cells (1.0 x 10(6) cells/mL) of each individual were cultured at 37 degrees C for 24 hours in the presence of 10 microg/mL of Cry j 1, a major allergen of the pollens. Total cellular RNA was extracted from the peripheral blood mononuclear cells, and IL-4, IL-5, and IFN-gamma mRNA expression was determined with a reverse transcriptase polymerase chain reaction. RESULTS: From the results of a survey of symptom diary cards and interviews regarding nasal symptoms during the pollen season in 1998, we found that 20 patients (symptomatic group), but not 10 patients (asymptomatic group), had typical symptoms of seasonal allergic rhinitis. Interleukin 4 mRNA was not expressed in the nonatopic subjects but was expressed in 9 asymptomatic patients and in 17 symptomatic patients. Interleukin 5 mRNA was exclusively expressed in the symptomatic patients. Interferon gamma mRNA expression did not differ significantly among the nonatopic subjects, asymptomatic patients, and symptomatic patients. CONCLUSIONS: This study has clearly highlighted an interesting and new concept that IL-4 is implicated in allergen sensitization but not in clinical manifestation, and that IL-5 may not be a feature of atopy in itself but seems to be a hallmark of clinical manifestation of ongoing atopic diseases.

Adolescent↗
PubMed2000

Sites of expression of mRNA for lysenin, a protein isolated from the coelomic fluid of the earthworm Eisenia foetida.

Lysenin is a 33-kDa protein of 297 amino acids that was originally purified from the coelomic fluid of the earthworm Eisenia foetida. It binds specifically to sphingomyelin. In this study, we attempted to identify the site of synthesis of lysenin in the earthworm. We detected the expression of mRNA for lysenin and the presence of immunoreactive lysenin in the large coelomocytes and in the free large chloragocytes present in the lumen of the typhlosole, a depression in the dorsal wall of the intestine. These coelomocytes and chloragocytes seemed to be mature and separate from the chloragogen tissue that lined the typhlosole. The free large chloragocytes in the typhlosole contained numerous vacuoles. The nuclei were small and irregular in shape, and glycogen granules and mitochondria were occasionally found between vacuoles. The chloragocytes of the chloragogen tissue that surrounded the coelomic side of the intestine and the dorsal blood vessel did not react with the lysenin antiserum and no expression of lysenin mRNA was detected in these cells. Furthermore, no evidence of the protein or of the mRNA was found in the cells of the pharyngeal gland. Our findings suggest that lysenin is produced in the free large chloragocytes in the lumen of the typhlosole.

Animals↗