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Biomedical subjects

K Manabe

Publications and source records attributed to K Manabe.

At least 19 recordsLinked to original sources

Roles of aquaporin-3 water channels in volume-regulatory water flow in a human epithelial cell line.

Membrane water transport is an essential event not only in the osmotic cell volume change but also in the subsequent cell volume regulation. Here we investigated the route of water transport involved in the regulatory volume decrease (RVD) that occurs after osmotic swelling in human epithelial Intestine 407 cells. The diffusion water permeability coefficient (Pd) measured by NMR under isotonic conditions was much smaller than the osmotic water permeability coefficient (Pf) measured under an osmotic gradient. Temperature dependence of Pf showed the Arrhenius activation energy (Ea) of a low value (1.6 kcal/mol). These results indicate an involvement of a facilitated diffusion mechanism in osmotic water transport. A mercurial water channel blocker (HgCl(2)) diminished the Pf value. A non-mercurial sulfhydryl reagent (MMTS) was also effective. These blockers of water channels suppressed the RVD. RT-PCR and immunocytochemistry demonstrated predominant expression of AQP3 water channel in this cell line. Downregulation of AQP3 expression induced by treatment with antisense oligodeoxynucleotides was found to suppress the RVD response. Thus, it is concluded that AQP3 water channels serve as an essential pathway for volume-regulatory water transport in, human epithelial cells.

Aquaporin 3↗

Primary lung cancer occurring concomitantly with the cicatrized and calcified ova of a parasite: report of a case.

We report herein a rare case of primary lung cancer that occurred concomitantly with the calcified ova of a parasite. A 58-year-old man was referred to our department after a pulmonary abnormal shadow had been seen on a chest X-ray done at mass screening. A transbronchial lung biopsy (TBLB) revealed the calcified ova of a parasite. Because the possibility of concomitant lung cancer could not be ruled out, a lung biopsy was taken via video-assisted thoracic surgery (VATS). The pathological diagnosis was squamous cell carcinoma, and a left upper lobectomy was serially performed through a posterolateral thoracotomy. The patient recovered uneventfully and has remained in good health without any sign of recurrence for over 9 months. Following this case report, we review three other cases of this unusual disease combination documented in the literature.

Calcinosis↗

Arabidopsis transcriptional regulation by light stress via hydrogen peroxide-dependent and -independent pathways.

BACKGROUND: High (intense) light stress causes the formation of oxygen radicals in chloroplasts and has the potential to damage them. However, plants are able to respond to this stress and protect the chloroplasts by various means, including transcriptional regulation in the nucleus. Although the corresponding signalling pathway is largely unknown, the high light response in the expression of the Arabidopsis APX2 gene is reported to be mediated by hydrogen peroxide. RESULTS: We characterized light stress signalling by analysing expression profiles of another high light-inducible gene of Arabidopsis, ELIP2, with the aid of an ELIP2 promoter-luciferase gene fusion. The established ELIP2:LUC transgenic Arabidopsis showed activation by high light, but not by hydrogen peroxide. On the other hand, the native ELIP2 gene as well as the APX2 gene was activated by the hydrogen peroxide. The activation of ELIP2:LUC by intense light was not inhibited by K252a but by okadaic acid. CONCLUSION: The light stress signalling from the chloroplast to the nucleus is revealed to be mediated through at least two pathways: both hydrogen peroxide-dependent and -independent. The latter pathway is thought to be mediated by the protein phosphatase 2A/1 activity that is suppressed by okadaic acid.

Arabidopsis↗

Suppression of fatty acid metabolism after exercise stress in patients with no electrocardiographic ST segment shift during balloon angioplasty.

Although ST segment shift is a marker of myocardial ischemia, some patients have no ST segment shift during percutaneous transluminal coronary angioplasty (PTCA). The aim of this study is to investigate myocardial perfusion and metabolism in adaptation for ischemia using 201TI and 123I-BMIPP dual exercise stress myocardial single photon emission computed tomography (SPECT) (dual stress SPECT). In 28 patients with coronary artery disease, dual stress SPECT was performed 3 weeks before PTCA. Early and delayed images were obtained at 5 minutes and at 3 hours after termination of ergometer stress, respectively. During PTCA, 12-lead ECG was recorded, and a significant ST segment shift was defined as more than 1 mm elevation or a depression of the J-point at the first ballooning. No collateral circulation on the coronary angiogram or 201TI filling on the delayed images were observed on any of the target regions of PTCA. Patients were divided into 2 groups: with (Group A: n = 15) and without (Group B: n = 13) significant ST segment shift during PTCA. A redistribution of TI was observed in 14 (93%) of Group A and 10 (77%) of Group B patients. Incidence of BMIPP redistribution was significantly higher in Group B (11 [85%]) than in Group A (3 [20%]) (p < 0.05). Redistribution of BMIPP means suppression of fatty acid metabolism during exercise stress. Augmentation of glucose metabolism is speculated to be an energy source in ischemic preconditioning.

Angioplasty, Balloon, Coronary↗

[Development of catalytic reactions using water as a solvent].

In recent years, organic reactions in aqueous media have attracted much attention, not only because these reactions eliminate the necessity of vigorous drying of solvents and substrates, but also because unique reactivity and selectivity are often observed in the aqueous reactions. Furthermore, organic reactions in water may lead to the development of environmentally friendly chemical processes. We have now developed various types of catalytic organic reactions in aqueous media. Catalytic asymmetric aldol reactions in aqueous media have attained by using rare earth metal triflates and a chiral multi-dentate ligand. Lewis acid catalysis has become feasible in water by using combinations of water-compatible Lewis acidic cations and anionic surfactants. These new catalysts were found to form stable colloidal dispersions and catalyze various reactions in water. Moreover, Brønsted acid- and palladium-catalyzed reactions in water have also been performed with the aid of surfactants.

Acids↗

Effect of cilnidipine on left ventricular diastolic function in hypertensive patients as assessed by pulsed Doppler echocardiography and pulsed tissue Doppler imaging.

The purpose of the present study was to examine the mechanisms of improvement in left ventricular (LV) diastolic function in hypertensive patients treated with cilnidipine, a new and unique calcium antagonist that has both L-type and N-type voltage-dependent calcium channel blocking actions, using pulsed Doppler echocardiography and pulsed tissue Doppler imaging. The study comprised 35 untreated patients with essential hypertension (19 men and 16 women; mean age 65+/-10 years). The peak early diastolic and atrial systolic transmitral flow velocities (E and A, respectively) and their ratio (E/A), and the peak early diastolic and atrial systolic motion velocities (Ew and Aw, respectively) of the LV posterior wall and their ratio (Ew/Aw) were determined in all patients before and after 1, 3 and 6 months on cilnidipine (10 mg/day). One month: Systolic and diastolic blood pressures were significantly decreased. E and E/A were significantly increased, whereas there were no significant changes in Ew and Ew/Aw. Three months: Ew and Ew/Aw were significantly increased compared to those before and 1 month after cilnidipine. Six months: E and E/A were significantly increased compared with before and 3 months after cilnidipine, and Ew and Ew/Aw were significantly increased compared with before cilnidipine. Moreover, the LV mass index was significantly decreased compared to that before cilnidipine. In summary, changes in LV diastolic performance in patients with essential hypertension following cilnidipine treatment were biphasic with an initial increase in early diastolic transmitral flow velocity and a later increase in early diastolic LV wall motion velocity. The initial and later changes can be related to an acute change in afterload and a later improvement in LV relaxation.

Aged↗

Equal-quantum action spectra indicate fluence-rate-selective action of multiple photoreceptors for photomovement of the thermophilic cyanobacterium Synechococcus elongatus.

Unicellular thermophilic cyanobacterium Synechococcus elongatus displayed phototaxis on agar plate at 55 degrees C. Equal-quantum action spectra for phototactic migration were determined at various fluence rates using the Okazaki Large Spectrograph as the light source. The shapes of the action spectra drastically changed depending on the fluence rate of the unilateral monochromatic irradiation: at a low fluence rate (3 mumol/m2/s), only lights in the red region had significant effect; at a medium fluence rate (10 mumol/m2/s), four major action peaks were observed at 530 nm (green), 570 nm (yellow), 640 nm (red) and 680 nm (red). At high fluence rates (30-90 mumol/m2/s), the former two peaks remained, while red peaks at 640 nm and 680 nm disappeared and, interestingly, an action peak around 700-740 nm (far-red) newly appeared. These results indicate that two or more distinct photoreceptors are involved in the phototaxis and that suitable photoreceptors are selectively active in response to the stimulus of light fluence rates. Far-red or red background lights irradiated vertically from above drastically inhibited phototaxis toward red light or far-red light, respectively. These results indicate involvement of some phytochrome(s).

Cyanobacteria↗

Asymmetry in the nonmesonic weak decay of polarized (5)(Lambda)He hypernuclei

We have measured the asymmetric emission of protons from the nonmesonic decay of polarized (5)(Lambda)He produced by the (pi(+), K+) reaction. (5)(Lambda)He is an s-shell hypernucleus and its polarization is due to the Lambda. One expects to obtain direct information on the elementary weak Lambda-->p-->np process. The asymmetry parameter has been determined to be 0.24+/-0.22. The implication of the result is discussed.

Journal Article↗

Pre-penile arteries are dominant in the regulation of penile vascular resistance in the rat.

The amount of blood flow into the penis that will produce an erection is dependent on the sum of inflow resistance from the feeder arteries, arterioles and the intra-penile vasculature. In the present study, our objective was to determine quantitatively the contribution to inflow resistance of these different components of the rat penile vasculature. Using methods developed previously, we determined the resistance properties of the isolated perfused whole penis in situ, both in an intact system and after serial transactions of the vessels. These cuts eliminated progressively larger distal segments of the vascular bed. Perfusion pressures were recorded at different flow rates (0.5-3 ml/min/kg body weight) under conditions of maximal dilatation and maximal vasoconstriction induced by methoxamine (MXA, 40 microg/ml). Regardless of the level of vascular tone, the pudendal artery contributes approximately 70% of the total resistance of the penile vasculature. In contrast, the vasculature within the penis (tip, shaft, crus) contributes only about one quarter of the resistance. Penile arterial inflow resistance properties both at maximal vasodilation and maximal alpha1-adrenergic constriction are dominated by the extra-penile vasculature in the rat. The implications of these findings are that alterations in the pudendal-artery (eg vasodilation, vasoconstriction, stenosis) would have primary control of arterial inflow and suggest an important role for pharmacological agents which can promote a more generalized vasodilation (eg phosphodiesterase inhibitors) in contrast to selective corpus cavernosal agents.

Adrenergic alpha-Agonists↗

Prevention of doxorubicin (adriamycin)-induced cardiomyopathy by simultaneous administration of angiotensin-converting enzyme inhibitor assessed by acoustic densitometry.

The purpose of our study has to determine the myocardial protective effects of the angiotensin-converting enzyme (ACE) inhibitor temocapril (TEM, 7 mg/kg/day) simultaneously administered with doxorubicin (Adriamycin). Twenty male Sprague-Dawley rats were intraperitoneally administered a cumulative dose of 15 mg/kg of doxorubicin (each dose of 1.0 mg/kg x 15) for 3 weeks, and divided into TEM-untreated and -treated rats. Seven control rats were injected with saline intraperitoneally. Body weight, hemodynamics, and echocardiographic measurements including quantitative analysis of ultrasonic integrated backscatter (IB) were obtained for 12 weeks after treatment. Finally, rats were killed for histopathologic study. At 6 weeks, end-diastolic left ventricular diameter (LVD) and percentage fractional shortening (%FS) were similar in TEM-treated and TEM-untreated rats, but cyclic variation of IB (dB) significantly decreased in TEM-untreated rats (7.3 +/- 1.2; control rats, 9.7 +/- 0.9; p < 0.01). At 12 weeks, %FS decreased in TEM-untreated rats (26.1 +/- 6.1%: TEM-treated rats, 34.2 +/- 6.2; p < 0.05), and calibrated IB (dB) in TEM-untreated rats (15.5 +/- 0.5) increased as compared with that in TEM-treated rats (12.1 +/- 0.7; p < 0.01). Interstitial collagen accumulation increased in TEM-untreated rats and was inhibited in treated rats. Simultaneous administration of TEM with doxorubicin was beneficial in preventing doxorubicin-induced myocardial damage, and myocardial tissue characterization was useful for the early detection of myocardial damage and the assessment of therapy.

Angiotensin-Converting Enzyme Inhibitors↗

1alpha,25-dihydroxyvitamin D(3)-26,23-lactone analogs antagonize differentiation of human leukemia cells (HL-60 cells) but not of human acute promyelocytic leukemia cells (NB4 cells).

We examined the effects of two novel 1alpha,25-dihydroxyvitamin D(3)-26,23-lactone (1alpha,25-(OH)(2)D(3)-26,23-lactone) analogs on 1alpha,25(OH)(2)D(3)-induced differentiation of human leukemia HL-60 cells thought to be mediated by the genomic action of 1alpha, 25-dihydroxyvitamin D(3) (1alpha,25-(OH)(2)D(3)) and of acute promyelocytic leukemia NB4 cells thought to be mediated by non-genomic actions of 1alpha,25-(OH)(2)D(3). We found that the 1alpha,25-(OH)(2)D(3)-26,23-lactone analogs, (23S)-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactone (TEI-9647) and (23R)-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactone (TEI-9648), inhibited differentiation of HL-60 cells induced by 1alpha,25-(OH)(2)D(3). However, 1beta-hydroxyl diastereomers of these analogs, i.e. (23S)-25-dehydro-1beta-hydroxyvitamin D(3)-26, 23-lactone (1beta-TEI-9647) and (23R)-25-dehydro-1beta-hydroxyvitamin D(3)-26,23-lactone (1beta-TEI-9648), did not inhibit differentiation of HL-60 cells caused by 1alpha,25-(OH)(2)D(3). A separate study showed that the nuclear vitamin D receptor (VDR) binding affinities of the 1-hydroxyl diastereomers were about 200 and 90 times weaker than that of 1alpha-hydroxyl diastereomers, respectively. Moreover, none of these lactone analogs inhibited NB4 cell differentiation induced by 1alpha,25-(OH)(2)D(3). In contrast, 1beta,25-dihydroxyvitamin D(3) (1beta,25-(OH)(2)D(3)) and 1beta,24R-dihydroxyvitamin D(3) (1beta,24R-(OH)(2)D(3)) inhibited NB4 cell differentiation but not HL-60 cell differentiation. Collectively, the results suggested that 1-hydroxyl lactone analogs, i.e. TEI-9647 and TEI-9648, are antagonists of 1alpha,25-(OH)(2)D(3), specifically for the nuclear VDR-mediated genomic actions, but not for non-genomic actions.

Calcitriol↗

Antagonistic action of novel 1alpha,25-dihydroxyvitamin D3-26, 23-lactone analogs on differentiation of human leukemia cells (HL-60) induced by 1alpha,25-dihydroxyvitamin D3.

We examined the effects of two novel 1alpha,25-dihydroxyvitamin D3-26,23-lactone (1alpha,25-lactone) analogues on human promyelocytic leukemia cell (HL-60) differentiation using the evaluation system of the vitamin D nuclear receptor (VDR)/vitamin D-responsive element (DRE)-mediated genomic action stimulated by 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) and its analogues. We found that the 1alpha,25-lactone analogues (23S)-25-dehydro-1alpha-hydroxyvitamin-D3-26,23-lactone (TEI-9647), and (23R)-25-dehydro-1alpha-hydroxyvitamin-D3-26,23-lactone (TEI-9648) bound much more strongly to the VDR than the natural (23S, 25R)-1alpha,25(OH)2D3-26,23-lactone, but did not induce cell differentiation even at high concentrations (10(-6) M). Intriguingly, the differentiation of HL-60 cells induced by 1alpha,25(OH)2D3 was inhibited by either TEI-9647 or TEI-9648 but not by the natural lactone. In contrast, retinoic acid or 12-O-tetradecanoylphorbol-13-acetate-induced HL-60 cell differentiation was not blocked by TEI-9647 or TEI-9648. In separate studies, TEI-9647 (10(-7) M) was found to be an effective antagonist of both 1alpha,25(OH)2D3 (10(-8) M) mediated induction of p21(WAF1, CIP1) in HL-60 cells and activation of the luciferase reporter assay in COS-7 cells transfected with cDNA containing the DRE of the rat 25(OH)D3-24-hydroxylase gene and cDNA of the human VDR. Collectively the results strongly suggest that our novel 1alpha,25-lactone analogues, TEI-9647 and TEI-9648, are specific antagonists of 1alpha, 25(OH)2D3 action, specifically VDR/DRE-mediated genomic action. As such, they represent the first examples of antagonists, which act on the nuclear VDR.

Animals↗

Spontaneous regression of hepatocellular carcinoma.

A 62-year-old Japanese man with hepatitis B virus-related liver cirrhosis revealed alpha-fetoprotein (AFP) elevation. Dynamic computed tomography, taken at this time, showed a liver tumor in the anterior segment. As the patient refused any further medical treatment, he was observed in an outpatient clinic. The size of the tumor reduced and the serum level of AFP decreased gradually without any treatment. Twelve months after the initial diagnosis, the tumor could not be detected by computed tomography (CT) scan, and the level of AFP had declined to the normal range. Blood supply is essential for tumor growth and an arterioportal shunt near the tumor may change the dynamics of blood flow to the tumor. The shunt found in this patient was thought to be one of the causative factors leading to regression, but it could not be denied that immunological mechanisms may have played an important role in the spontaneous regression of hepatocellular carcinoma.

Biomarkers, Tumor↗

Idiopathic small-fiber sensory neuropathy in childhood: A diagnosis based on objective findings on punch skin biopsy specimens.

Idiopathic small-fiber sensory neuropathy (SFSN) has not previously been reported in children. Although affected patients complain of neuropathic pain, this condition is often difficult to diagnose because of the few objective physical signs and normal nerve conduction studies. We report a girl with idiopathic SFSN in whom the results of a sural nerve biopsy were normal, but punch skin biopsy revealed reduced intraepidermal nerve fiber density and established the diagnosis. Idiopathic SFSN should be considered in the differential diagnosis of children who have burning limb pain with no routine electrophysiologic or pathologic abnormalities.

Child↗

Subclinical portal-systemic encephalopathy in a child with congenital absence of the portal vein.

A 6-year-old girl with congenital absence of the portal vein (CAPV) who had persistent hyperammonemia due to a congenital portosystemic shunt is reported. The patient only exhibited mild intention tremor, without any apparent neurological manifestations of portal-systemic encephalopathy. However, magnetic resonance imaging of the head showed white matter atrophy with ventricular dilatation, which is thought to represent subclinical brain damage caused by chronic hyperammonemia. This is the first report of subclinical portal-systemic encephalopathy in a patient with CAPV. The present case suggests that the effect of a congenital portosystemic shunt on the central nervous system is serious, but can be clinically latent in children with CAPV.

Angiography↗