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Biomedical subjects

T Iijima

Publications and source records attributed to T Iijima.

At least 199 records · Page 11Linked to original sources
PubMed1997

Transforming growth factor-alpha (TGF alpha)-producing gastric carcinoma with acanthosis nigricans: an endocrine effect of TGF alpha in the pathogenesis of cutaneous paraneoplastic syndrome and epithelial hyperplasia of the esophagus.

A case of well-differentiated adenocarcinoma (Borrmann type 3) of the stomach in a 76-year-old man associated with the typical skin manifestations of acanthosis nigricans and with multiple protruding lesions showing epithelial hyperplasia of the esophagus is reported. The advanced tumor was located in the cardiac region of the stomach, and measured approximately 8 cm in diameter, with partial invasion to the esophagus. The associated cutaneous lesions were characterized by hyperpigmentation and by protruding verrucous papules on the torso, head, face, neck, upper extremities, perineum, and inguinal region. Histologically, the protruding skin lesions showed keratinocytes proliferation throughout the epidermis, resulting in diffuse hyperkeratosis, papillomatosis, and acanthosis of the skin. Immunohistological analysis showed coexpression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptors in the tumor from the stomach. It is reasonable to conclude from this evidence that gastric carcinoma cells secrete TGF alpha in an autocrine for auto-stimulation. EGF receptor expression was also noted on the papillomatous hyperplasia of the cutaneous lesion. Serum level of TGF alpha, determined by an enzyme-linked immunosorbent assay, was high (144 pg/ml; normal, 22.0 +/- 16 pg/ml (Mean +/- SD)). Serum TGF alpha abruptly decreased to 49 pg/ml on day 7 after the total gastrectomy, and then gradually increased to 77 pg/ml within 28 days. Amelioration of the cutaneous lesions and the protruding lesions in the esophagus was observed after surgical resection of the gastric carcinoma. This suggests that the TGF alpha stimulates the proliferation of keratinocytes involved with EGF receptor. Large amounts of circulating TGF alpha in the blood over a long period released by the primary tumor seem to act as an endocrine-like mechanism causing epidermal and esophageal epithelial cells to proliferate. There is a possible link in the pathogenesis of the acanthosis nigricans as a cutaneous paraneoplastic syndrome, and epithelial hyperplasia of the esophagus.

Acanthosis Nigricans↗
PubMed1997

Effects of autoantibodies on the course of pregnancy and fetal growth.

OBJECTIVE: To assess the effects of autoantibodies on the course of pregnancy and fetal growth. METHODS: One thousand one hundred seventy-nine healthy women with singleton gestations were screened in early pregnancy for seven kinds of autoantibodies: antithyroid microsomal antibody, antithyroglobulin antibody, two kinds of rheumatoid factor, antinuclear antibody, anti-DNA antibody, and antimitochondrial antibody. RESULTS: In 228 cases (19.3%), at least one autoantibody was found; however, overlap of autoantibodies in the same individual was unexpectedly rare, and only two cases were positive for as many as four autoantibodies. A significantly higher rate of spontaneous abortion was observed in antibody-positive subjects, especially those with antithyroid microsomal (10.4%) or antinuclear antibodies (16.0%), compared with all antibody-negative subjects (5.5%). There were no significant differences in any outcome assessed among subjects positive for antithyroglobulin antibody, anti-DNA antibody, or antimitochondrial antibody compared with all antibody-negative subjects. None of the seven autoantibodies affected the rates of preterm delivery, stillbirth, pregnancy-induced hypertension, malformation, or gender ratio. CONCLUSION: Antithyroid microsomal antibody and antinuclear antibody are the only autoantibodies that increase the abortion rate.

Adult↗
PubMed1997

Electrophysiological evidence of an increase in cold tolerance of cardiac muscles in mice after energy restriction.

Life-prolonging energy restriction (ER) has been known to extend longevity. The heart was selected as the target organ of ER and the electrophysiological properties of ER on the heart were investigated. Action potential parameters were measured on ventricular papillary muscles of C57BL/6 mice (2-6 months of age). Resting membrane potential (Rm) did not change even when the temperature was lowered to 20 degrees C in ER mice (-67.5 +/- 0.8 mV), however, the membrane was depolarized in the control (-61.1 +/- 1.1 mV). Action potential duration measured at 30 and 50% repolarization was significantly prolonged in ER mice at 20-35 degrees C. Ouabain (10 microM) decreased Rm in ER mice at 20 degrees C (-68.6 +/- 1.0 to -63.6 +/- 0.8 mV), but failed to decrease Rm in the control (-60.6 +/- 1.8 to -62.1 +/- 1.2 mV). There were no significant differences in extracted Na, K-ATPase activity or affinity and binding capacity of ouabain between ER and control hearts. These results indicate that in ER mice the lack of effect of temperature on Rm was not due to a change in the physicochemical properties of Na, K-ATPase. The present study collectively suggests that ER increases cold tolerance in the heart of mice.

Acclimatization↗
PubMed1997

Lysophosphatidic acid sensitises Ca2+ influx through mechanosensitive ion channels in cultured lens epithelial cells.

We investigated the effect of lysophosphatidic acid (LPA), a bioactive phospholipid, on the response in cytosolic free Ca2+ concentration ([Ca2+]i) to mechanical stress in cultured bovine lens epithelial cells. Spritzing of bath solution onto cells as mechanical stress caused marked increase in [Ca2+]i in the presence of LPA and this increase was concentration-dependent (1-10 microM), whereas neither addition of LPA alone nor the mechanical stress in the absence of LPA affected [Ca2+]i. The mechanical stress-induced increase in [Ca2+]i in the presence of LPA was inhibited by removing extracellular Ca2+ or by addition of Gd3+, a blocker of mechanosensitive cation channels, but not by nicardipine, thapsigargin, an inhibitor of endoplasmic reticulum-ATPase pump, or U73122, a phospholipase C inhibitor. These results show that LPA sensitises Ca2+ influx through cation-selective mechanosensitive channels, but does not sensitise Ca2+ release from intracellular stores, triggered by changes in mechanical stress. On the other hand, phosphatidic acid had less of a sensitising effect than LPA, and neither lysophosphatidylcholine nor chlorpromazine had any effect. Also Ca2+ mobilising agonists, ATP, histamine and carbachol, did not sensitise Ca2+ response to the mechanical stress. These results show that LPA sensitises mechanoreceptor-linked response in lens epithelial cells, suggesting that it plays a role in the development of cataracts due to increases in [Ca2+]i induced by mechanical stress.

Animals↗
PubMed1997

Cardiac output and circulating blood volume analysis by pulse dye-densitometry.

OBJECTIVE: Pulse dye-densitometry (PDD) is a newly developed method for monitoring the indocyanine green (ICG) concentration in an artery with which cardiac output (CO) and circulating blood volume (CBV) can be determined. We evaluated its accuracy for clinical use. METHODS: In 7 patients under general anesthesia, ICG-sensitive optical probes (805 and 890 nm) were attached to a finger. Following injection of ICG, the arterial concentration of dye was recorded optically by the non-invasive test instrument and sampled arterial blood ICG concentration was also measured photometrically for comparison. In order to validate the PDD analysis, CO was also measured by both the dye dilution cuvette method and by thermodilution in 8 patients scheduled for coronary artery bypass grafting. In 30 other patients, CBV assessed by PDD was compared with its value estimated from body size. RESULTS: The blood dye concentration correlated well with the values obtained by PDD (r = 0.953, p < 0.01). Mean bias for the test PDD CO was +0.15 +/- 0.72 min l-1 (not significant (n.s.)) compared with the cuvette method while the mean bias of the thermodilution method vs the cuvette method was +0.79 +/- 0.84 min l-1 (p < 0.0001.). The average value of CBV obtained by PDD was 3.81 +/- 1.39 L compared with that estimated value, 3.72 +/- 0.77 L (n.s.). CONCLUSIONS: CO determined by PDD agrees well with cuvette densitometry, and somewhat less well with CO by thermodilution. The new method, by not requiring a pulmonary arterial catheter, is less invasive than either older method, and yields in addition a value of CBV.

Blood Volume↗
PubMed1997

Potentiation by nitric oxide of the ATP-sensitive K+ current induced by K+ channel openers in guinea-pig ventricular cells.

1. Modulation by nitric oxide (NO) of the ATP-sensitive K+ channel (KATP) current (IK(ATP)) was investigated in single ventricular cells dissociated from guinea-pig hearts. IK(ATP) was induced by 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine+ ++ (KRN4884) and cromakalim. 2. In the whole-cell patch clamp configuration, KRN4884 (0.1 3 microM) increased the outward current in a concentration-dependent manner with an EC50 value of 0.48 microM. This current was completely antagonized by glibenclamide (1 microM). 3. IK(ATP) induced by either KRN4884 (0.3 microM) or cromakalim (10 microM) was significantly enhanced by the additional application of a NO donor (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (NOR3, 0.1 and 1 mM). 4. The potentiating effect was observed only when NOR3 solution was prepared just before experiments, when release of NO was considered to be on-going. The effect was significantly eliminated in the presence of the NO scavenger oxyhaemoglobin (3 10 microM). Also, oxidative metabolites of NO, such as NO2 or NO3, were without effect. 5. 8-Bromo-guanosine-3':5'-cyclic monophosphate (8-Br-cyclic GMP, 0.1 0.5 mM) significantly decreased IK(ATP) induced by KRN4884. 6. In cell-attached patches, NOR3 (1 mM) potentiated the KRN4884-induced IK(ATP) in a way similar to that seen in whole-cell recordings. By contrast, NOR3 (1 mM) did not enhance the current in either inside-out or outside-out patches. 7. These results indicate that NO potentiates the action of K+ channel openers on the KATP through a mechanism which remains to be determined.

Adenosine Triphosphate↗
PubMed1997

Control of centrifugal blood pump based on the motor current.

In this study, centrifugal pump performance was examined in a mock circulatory loop to derive an automatic pump rotational speed (rpm) control method. The pivot bearing supported sealless centrifugal pump was placed in the left ventricular apex to aorta bypass mode. The pneumatic pulsatile ventricle was used to simulate the natural ventricle. To simulate the suction effect in the ventricle, a collapsible rubber tube was placed in the inflow port of the centrifugal pump in series with the apex of the simulated ventricle. Experimentally, the centrifugal pump speed (rpm) was gradually increased to simulate the suction effect. The pump flow through the centrifugal pump measured by an electromagnetic flowmeter, the aortic pressure, and the motor current were continuously digitized at 100 Hz and stored in a personal computer. The analysis of the cross-spectral density between the pump flow and motor current waveforms revealed that 2 waveforms were highly correlated at the frequency range between 0 and 4 Hz, with the coherence and phase angles being close to 1.0 and 0 degree, respectively. The fast Fourier transform analysis of the motor current indicated that the second harmonic component of the motor current power density increased with the occurrence of the suction effect in the circuit. The ratio of the fundamental to the second harmonic component decreased less than 1.3 as the suction effect developed in the circuit. It is possible to detect and prevent the suction effect of the centrifugal blood pump in the natural ventricle through analysis of the motor current waveform.

Algorithms↗
PubMed1997

Adequacy of pacing rate during exercise in rate responsive ventricular pacing.

Our objective was to determine the adequate pacing rate during exercise in ventricular pacing by measuring exercise capacity, cardiac output, and sinus node activity. Eighteen patients with complete AV block and an implanted pacemaker underwent cardiopulmonary exercise tests under three randomized pacing rates: fixed rate pacing (VVI) at 60 beats/min and ventricular rate-responsive pacing (VVIR) programmed to attain a heart rate of about 110 beats/min or 130 beats/min (VVIR 110 and VVIR 130, respectively) at the end of exercise. Compared with VVI and VVIR 130, VVIR 110 was associated with an increased peak oxygen uptake (VVIR 110: 20.3 +/- 4.5 VVI: 16.9 +/- 3.1; P < 0.01; and VVIR 130: 19.0 +/- 4.1 mL/min per kg, respectively; P < 0.05 and a higher oxygen uptake at anaerobic threshold (15.3 +/- 2.7, 12.7 +/- 1.9; P < 0.01, and 14.6 +/- 2.6 mL/min per kg; P < 0.05). The atrial rate during exercise expressed as a percentage of the expected maximal heart rate was lower in VVIR 110 than in VVI or VVIR 130 (VVIR 110: 75.9% +/- 14.6% vs VVI: 90.6% +/- 12.8%; P < 0.01; VVIR 110 vs 130: 89.1% +/- 23.1% P < 0.05). There was no significant in cardiac output at peak exercise between VVIR 110 and VVIR 130. We conclude that a pacing rate for submaximal exercise of 110 beats/min may be preferable to that of 130 beats/min in respect to exercise capacity and sympathetic nerve activity.

Cardiac Output↗
PubMed1997

Regulation of osteoclastogenesis by antisense oligodeoxynucleotides specific to zinc finger nuclear transcription factors Egr-1 and WT1 in rat bone marrow culture system.

Differentiation of osteoclasts is defined by the transcription factors expressed in response to bone microenvironments. In this work, we examined the effects of an expressional blockage of Egr-1 and/or WT1 on the differentiation of osteoclasts using specific antisense oligodeoxynucleotides (ODN). In a culture system forming preosteoclast-like cells (POC) from rat bone marrow cells depleted of marrow stromal cells, POC formation was markedly stimulated by the addition of Egr-1 antisense ODN compared to that in cultures in which sense ODN was added, whereas Egr-1 antisense ODN inhibited the formation of macrophage-like cells. The formation of multinucleated osteoclast-like cells was also stimulated by the addition of Egr-1 antisense ODN in whole bone marrow cultures. In contrast, WT1 antisense ODN did not affect POC formation induced by the treatment with Egr-1 antisense ODN; however, WT1 antisense ODN dramatically suppressed the formation of osteoclast-like multinucleated cells induced by the blockage of Egr-1 expression using Egr-1 antisense ODN. These data suggest that Egr-1 acts as the suppressor, not as the inducer, in osteoclastogenesis. The findings also suggested that WT1 could be involved in the multinucleation step of osteoclastogenesis, at least when Egr-1 expression was blocked.

Animals↗
PubMed1997

Efficient synthesis and gastric (H+/K+)-ATPase-inhibitory activity of 2-aryl-4,5-dihydro-1H-thieno[3,2-e]benzimidazoles.

A series of 2-aryl-4,5-dihydro-1H-thieno[3,2-e]benzimidazoles (1, 2) was prepared by condensation of 5-acylamino-4,5,6,7-tetrahydrobenzo[b]thiophen-4-ones (9, 10) with ammonium acetate under azeotropic reaction conditions. Various congeners, N-methyl and N-phenyl analogues (3-5), 4,5-dihydro-1H-thieno[2,3-e]benzimidazoles (6), 4,5-dihydro-1H-thieno[2,3-g]benzoxazoles (7), and 4,5-dihydro-1H-thieno[2,3-g]benzothiazoles (8), were also prepared. Several compounds in this series were shown to be K(+)-competitive inhibitors of the gastric (H+/K+)-ATPase and more potent inhibitors than SK&F-96067, 3-butyryl-8-methoxy-4-(2-tolylamino)quinoline, on pentagastrin-stimulated acid secretion in chronic gastric fistula rats after intraduodenal administration.

Animals↗
PubMed1997

Functional organization of chromaffin cells and cholinergic synaptic transmission in rat adrenal medulla.

Optical recordings of membrane depolarization and whole-cell patch-clamp recordings of membrane potentials and currents were obtained from chromaffin cells in slices of rat adrenal medulla. The stimulation of splanchnic nerve fibers caused a discontinuous spread of electrical activity across the slice. Cells in clusters with diameters of about 80 microns were excited simultaneously, suggesting that the adrenal medulla is organized into descrete cell complexes with common innervation. The electrical properties of chromaffin cells in situ were in agreement with previous reports on cultured cells. A fraction of the recorded cells displayed excitatory postsynaptic currents (EPSCs) of 0.2-1 nA upon the stimulation of presynaptic nerve fibers. The EPSC was blocked by hexamethonium, suggesting that nicotinic ACh receptors were involved. The decay phase of the EPSC was well fit by the sum of two exponentials with time constants of 6.3 and 57.3 ms. The relative amplitude of the fast component was 84.1%. These two exponentials may reflect activation of both fast and slow time-constant ACh receptor channels by presynaptic release of ACh. There were multiple peaks in the EPSC amplitude histograms in low-[Ca2+] saline, the first peak was at 37 pA. To resolve the quantal size, miniature EPSCs were recorded in a tetrodotoxin-containing high-[K+] solution. The miniature EPSC amplitude histograms were also multimodal with the first peak at 25 pA, which probably represents the quantal size of the synapse. The second and third peaks were at the integer multiples of the first one.

Action Potentials↗
PubMed1997

Significance of urinary type IV collagen in patients with diabetic nephropathy using a highly sensitive one-step sandwich enzyme immunoassay.

Urinary concentrations of type IV collagen in patients with diabetic nephropathy were measured by a highly sensitive, one-step sandwich enzyme immunoassay. Samples from 298 patients with noninsulin-dependent diabetes mellitus (NIDDM) and 80 healthy controls were examined. In diabetic patients with macroalbuminuria or renal insufficiency, the concentrations of urinary type IV collagen were significantly higher than those of diabetic patients with normoalbuminuria or healthy controls (P < 0.001). Urinary type IV collagen concentration in diabetic patients with microalbuminuria was significantly higher than that in diabetic patients with normoalbuminuria or that in healthy controls (P < 0.001). In contrast, there were no significant changes in the concentration of serum type IV collagen between microalbuminuric patients and normoalbuminuric patients. The area under the receiver operating characteristic (ROC) curve for the urinary type IV collagen concentration was equivalent to that of urinary albumin. It was concluded that urinary type IV collagen concentration determined using this method might be a useful marker for the early detection of diabetic nephropathy.

Adult↗
PubMed1997

Macrophage inflammatory protein-1 alpha (LD78) expressed in human bone marrow: its role in regulation of hematopoiesis and osteoclast recruitment.

Human macrophage inflammatory protein-1 alpha (hMIP-1 alpha), also known as LD78, is a member of the chemokine/ intercrine family and an inhibitor of the proliferation of the hematopoietic stem cells in vitro. Using a specific monoclonal antibody, we observed significant localization of hMIP-1 alpha in eosinophilic myelocytes in human bone marrow. We further examined the expression of hMIP-1 alpha mRNA in human bone tissue by in situ hybridization. A high level of hMIP-1 alpha mRNA expression was detected in eosinophilic myelocytes in bone marrow, confirming these cells as the site of hMIP-1 alpha synthesis. hMIP-1 alpha mRNA expression was also detected in osteoblasts in the bone-remodeling sites, and osteoclasts were frequently observed in the vicinity of these osteoblasts. hMIP-1 alpha was also able to induce osteoclastogenesis on calcified matrices in the absence of any other osteotropic hormones. These results strongly suggest that hMIP-1 alpha is involved not only in the regulation of hematopoiesis but also in the modulation of bone remodeling.

Animals↗
PubMed1997

[Accumulation of 14C-cystine in inherited cataractous rat lens].

This study was designed to investigate the formation of mixed disulfides of protein and glutathione (GSH) in the cataractous lens. We compared the changes in accumulation of 14C-cystine in cultured inherited cataractous rat lens (ICR/f) during cataractogensis with those in Wistar strain rats. The accumulation of 14C-cystine in water insoluble protein (WIP) of the lens was increased, especially in lens recognized cataract. The radioactivity accumulated in the WIP was released by incubation with 2-mercaptoethanol (2-ME), dithiothereitol (DTT) and GSH. The accumulation of 14C-cystine in WIP was inhibited by pretreatment with DTT. The existence of some materials in the lens-which combined with S-S compounds became clear. A large part of the materials is present in WIP which is increased along with the lens opacification. We surmised that the accumulation of 14C-cystine was related to the reaction of protein-glutathione disulfide (PSSG).

Aging↗
PubMed1997

Activation of cardiac ATP-sensitive K+ channels by KRN4884, a novel K+ channel opener.

In the present study, we have investigated the mechanism underlying the activation by 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3- pyridinecarboxamidine (KRN4884), a new K+ channel opener, of ATP-sensitive K+ (KATP) channels in single ventricular cells of guinea pig hearts by the inside-out patch-clamp method. In the presence of intracellular ATP (1 mM), KRN4884 (0.1-3 microM) activated KATP channels in a concentration-dependent manner (EC50 = 0.55 microM) without affecting the unitary current conductance and the gating properties. KRN4884 (0.3 microM) shifted the concentration-response relationship for ATP-induced KATP channel inhibition to the right and slightly upward direction without altering the slope. After either the spontaneous or Ca++-induced channel rundown, KRN4884 (1 and 3 microM) partially restored the KATP channel activity. Furthermore, the effect of KRN4884 was augmented by the presence of uridine 5'-diphosphate (3 mM). The results indicate that KRN4884 activates cardiac KATP channels through not only decreasing the sensitivity of the channel to ATP but also directly stimulating the opening of the channel.

Adenosine Triphosphate↗
PubMed1997

Chloride- and voltage-dependent Ca2+ transient in cultured human aortic endothelial cells.

The Cl(-)-sensitive nature of histamine-induced Ca2+ entry was investigated in cultured human aortic endothelial cells by the patch-clamp method, combined with the fluorescence measurement of intracellular Ca2+ concentration ([Ca2+]i). The sustained increase in [Ca2+]i, caused by histamine, was decreased by lowering the external concentration of Cl-. The patch-clamp experiment revealed that [Ca2+]i was dependent on the membrane potential in the presence of histamine, but not in the absence of histamine. The sustained increase in [Ca2+]i was accompanied by activation of the Cl- current, of which the reversal potential was measured to be around -28 mV with physiological internal and external Cl- concentrations. The membrane potential of the endothelial cells varied from -90 to 0 mV in the resting condition and approached the equilibrium potential for Cl- during histamine application. The results indicate that the histamine-induced Cl- current plays a functional role in the sustained increase of intracellular Ca2+ during histamine application by providing a constant driving force for Ca2+ entry across the plasma membrane.

Aorta↗