Another alternative for cardiac output measurement--pulse dye-densitometry.
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Blood Pressure Determination↗
Biomedical subjects
T Iijima
Publications and source records attributed to T Iijima.
Somatic mutation of the APC gene in thyroid carcinoma associated with familial adenomatous polyposis.
We report the existence of both germline and somatic mutations of the APC gene in thyroid carcinomas from familial adenomatous polyposis (FAP) patients. One papillary thyroid carcinoma from a 210-year-old woman, with germline mutation of the APC gene (TCA to TGA at codon 1110), showed a somatic mutation of AAAAC deletion between codons 1060 and 1063. Another somatic mutation of CAG to TAG at codon 886 was also found in one of multiple thyroid carcinomas from a 26-year-old woman with attenuated FAP and germline mutation at codon 175 (C deletion). This is the first evidence that total absence of the normal function of the APC gene is involved in development of thyroid carcinomas in FAP.
Adenomatous Polyposis Coli↗
A novel case of a sporadic desmoid tumour with mutation of the beta catenin gene.
A 42 year old man without familial adenomatous polyposis had recurrent desmoid tumours in the left subclavicular site. Histological examination showed a typical desmoid tumour. Molecular analysis was performed in genomic DNA from this tumour, using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing methods. No mutation could be detected in the entire coding sequence of the APC gene, nor in H-ras, K-ras, N-ras, or p53 genes. On seeking a mutation of the beta catenin gene (CTNNB1), an activating mutation from ACC (Thr) to GCC (Ala) at codon 41 was found. Immunohistochemical staining showed that accumulated beta catenin protein was predominantly localised in the nuclei of desmoid cells. This is the first example of a sporadic desmoid tumour in which a mutation of the beta catenin gene was revealed.
Adult↗
Mechanical stress-induced Ca2+ entry and Cl- current in cultured human aortic endothelial cells.
A fluid stream through a microtube was applied to cultured human aortic endothelial cells to investigate the endothelial responses of both the ionic currents and intracellular Ca2+ concentration ([Ca2+]i) to mechanical stimulation. The fluid stream induced an increase in [Ca2+]i that was dependent on both the flow rate and the extracellular Ca2+ concentration. Gd3+ and niflumic acid inhibited the fluid stream-induced increase in [Ca2+]i, whereas Ba2+ and tetraethylammonium ion exhibited no effect. The fluid stream-induced [Ca2+]i increase was accompanied by the activation of an inward current at -52.8 mV. The reversal potential of the fluid stream-induced current shifted to positive potentials when the external Cl- concentration was reduced but was not affected by variation of the external Na+ concentration. During the exposure to the fluid stream, [Ca2+]i was voltage dependent, i.e., depolarization decreased [Ca2+]i. We therefore conclude that the fluid stream-induced current is largely carried by Cl- and that the Cl- current may thus play a role in modulating the Ca2+ influx by altering the membrane potential of endothelial cells.
Aorta↗
Enhancement by arginine vasopressin of the L-type Ca2+ current in guinea pig ventricular myocytes.
Effects of arginine-vasopressin (AVP) on the cardiac L-type Ca2+ current (ICa,L) were investigated in single ventricular cells of guinea pig hearts by the conventional and nystatin-perforated patch clamp methods. Using the conventional whole-cell clamp method, AVP (0.01-1 micromol/l) appeared to have little effect on ICa,L, but the same concentrations of AVP consistently increased ICa,L using the nystatin-perforated patch clamp mode. The stimulatory effect was blocked by either OPC-21268 (8 micromol/l), a selective V1 receptor antagonist, or staurosporine (10 nmol/l), an inhibitor of protein kinases. AVP further increased the amplitude of ICa,L previously augmented maximally by isoprenaline (1 micromol/l). When myocytes were pretreated with ryanodine (2 micromol/l) or cyclopiazonic acid (3 micromol/l), the increase in ICa,L by AVP was partially reduced. The present results indicate that protein kinase C might be involved in the AVP-induced increase of ICa,L. The AVP-induced increase in ICa,L may require intracellular constituents, which might be washed out during the use of the conventional whole-cell patch clamp method.
Animals↗
Dicarba-closo-dodecaboranes as a pharmacophore. Retinoidal antagonists and potential agonists.
Synthesis and biological evaluation of the first dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Their retinoidal activity were examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for retinoic acid receptor (RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. The 4-carboranyl-substituted compounds (7, 11) showed antagonistic activity but no agonistic activity even in the presence of the potent synergist HX630. On the other hand, the 3-carboranyl-substituted compounds (8, 12) showed potential agonistic activity, but no antagonistic activity. The results indicates that carboranes are applicable as the hydrophobic moiety of biologically active molecules.
Boron Compounds↗
Dicarba-closo-dodecaboranes as a pharmacophore. Novel potent retinoidal agonists.
The synthesis and biological evaluation of the dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Retinoidal activity was examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for the retinoid receptor RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. 4-[4-(1,2-Dicarba-closo-dodecaboran-1-yl)phenylamino]b enzoic acids and 4-[3-(1,2-dicarba-closo-dodecaboran-1-yl)phenylamino]b enzoic acids showed potent agonistic activity at concentrations of 10(-8)-10(-9) M. The results indicate that carboranes are applicable as the hydrophobic moiety of biologically active molecules.
Boron Compounds↗
On the inotropic actions of arginine vasopressin in ventricular muscle of the guinea pig heart.
Arginine vasopressin (AVP) (0.03-3 microM) produced transient negative responses that were followed by slowly developing positive inotropic responses in guinea pig papillary muscles. The inotropic responses were antagonized by OPC-21268 (10 microM), but not by OPC-31260, and suppressed by neomycin (3 mM). The negative inotropic response was hardly affected by staurosporine (10 nM) and H-7 (10 microM). AVP (1 microM) elicited a transient decrease followed by a slowly developing increase in I(Ca). The latter increase in I(Ca) was not elicited in the presence of staurosporine (1 nM). These results indicate that AVP stimulates V1 receptors that couple to phosphoinositide hydrolysis and thereby increases intracellular Ca2+ and activates protein kinase C.
Animals↗
Incidence of postpartum onset of disease among patients with rheumatoid arthritis.
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Abortion, Induced↗
[Mapping-guided focal cryoablation and endoaneurysmorrhaphy for a case of ischemic ventricular tachycardia with left ventricular aneurysm].
A 74-year-old woman admitted with exertional dyspnea. Echocardiography revealed the giant left ventricular aneurysm. In the hospital course, she fell into sustained monomorphic ventricular tachycardia. Coronary angiogram showed complete obstruction of the LAD. Left ventricular ejection fraction was 20%. The origin of tachycardia seems to be at infero-apicallateral area of LV by electrophysiology study. Because of the failure of RF energy ablation, we planned mapping-guided cryoablation, CABG and endoaneurysmorrhaphy. To prevent air embolism and myocardial ischemic damage for long aortic cross clamp, intraoperative endocardial mapping was carried out on beating heart due to continuous normothermic coronary blood perfusion (300 ml/min) from the aortic root cannula under aortic clamping. Cold crystalloid cardioplegia changed into the root cannula after EPS, focal cryoablation (-100 degrees C) was performed 3 times on cardiac arrest. Sustained VT was not inducible in the following study. CABG and endoaneurysmorrhaphy was performed on repeated cardiac arrest during single aortic clamp. Postoperative course was uneventful, and she discharged 8 weeks after the operation.
Aged↗
Intracellular nucleotide-mediated gating of SUR/Kir6.0 complex potassium channels expressed in a mammalian cell line and its modification by pinacidil.
1. We have examined the properties of intracellular nucleotide-mediated gating of K+ channel constructs composed of the sulphonylurea receptor 2B and the inwardly rectifying K+ channel subunits Kir6.1 and Kir6.2 (SUR2B/Kir6.1 and SUR2B/Kir6.2 complex K+ channels) heterologously expressed in human embryonic kidney (HEK) 293T cells. In the cell-attached form, both types of K+ channel were activated by pinacidil. 2. In inside-out (IO) patches, the SUR2B/Kir6.2 channels opened spontaneously and were inhibited by intracellular ATP (ATPi). Pinacidil attenuated the ATPi-mediated channel inhibition in a concentration-dependent manner. In contrast, the SUR2B/Kir6.1 channels required intracellular nucleoside di- or tri-, but not mono-, phosphates for opening. The potency of adenine, guanine or uracil nucleotides to activate SUR2B/Kir6.1 channels was enhanced by pinacidil. 3. In the presence of pinacidil, adenine and guanine, but not uracil, nucleotides exhibited bell-shaped concentration-dependent activating effects on SUR2B/Kir6.1 channels. This was due to channel inhibition caused by adenine and guanine nucleotides, which was unaffected by pinacidil. 4. From power density spectrum analysis of SUR2B/Kir6.1 currents, channel activation could be described by the product of two gates, a nucleotide-independent fast channel gate and a nucleotide-dependent slow gate, which controlled the number of functional channels. Pinacidil specifically increased the potency of nucleotide action on the slow gate. 5. We conclude that Kir6.0 subunits play a crucial role in the nucleotide-mediated gating of SUR/Kir6.0 complex K+ channels and may determine the molecular mode of pinacidil action.
Adenosine Diphosphate↗
Chloride-sensitive nature of the histamine-induced Ca2+ entry in cultured human aortic endothelial cells.
1. Whole-cell currents and intracellular Ca2+ concentration ([Ca2+]i) were recorded in cultured human aortic endothelial cells (HAECs) to study the mechanisms underlying Cl--sensitive Ca2+ entry. 2. In the absence of histamine the membrane potential ranged between -90 and +5 mV and showed bimodal distribution with peaks at -17.8 and -67.5 mV. 3. Histamine (1-100 microM) activated an outward current, followed by a sustained inward current at -50 mV. The reversal potential (Vrev) was more negative than -60 mV for the initial outward current, and approximately -30 mV for the sustained inward current with normal Tyrode solution and internal solution containing 30 mM Cl-. 4. Vrev of the sustained inward current was hardly affected by varying the external concentrations of K+, Na+ and Ca2+, but was greatly changed by varying the external Cl- concentration ([Cl-]o). The relationship between Vrev and log[Cl-]o showed a slope of -44.8 mV per tenfold increase of [Cl-]o. 5. The Cl- channel blockers 9-anthracene carboxylic acid (1 mM), N-phenylanthranilic acid (0.1 mM) and niflumic acid (0.1 mM) all depressed the histamine-induced inward current. The non-selective cation channel blocker Gd3+ (10 microM) was without effect on the current. 6. In the absence of histamine, [Ca2+]i was not affected by varying the membrane potential. During the continuous presence of histamine, however, hyperpolarization increased and depolarization decreased [Ca2+]i, indicating that Ca2+ entry through the plasma membrane was activated by histamine. 7. Vrev of the histamine-induced Cl- current, measured by the gramicidin-perforated patch clamp method, was -28.4 +/- 6.6 mV (n = 8), which gave an intracellular Cl- concentration of approximately 34 mM. Under the current clamp condition, the membrane potential varied from cell to cell in the control, but application of histamine induced either depolarization or hyperpolarization, depending on the membrane potential before histamine application, and the membrane potential became stable near the equilibrium potential for Cl-. 8. We conclude that the histamine-induced inward current is carried mainly by Cl-. Although Ca2+ entry was also activated, we consider that its amplitude was too small to be resolved by the patch clamp method. The Cl- current may play a functional role in the sustained [Ca2+]i elevation by providing a constant driving force for Ca2+ entry in the presence of histamine.
Anthracenes↗
Scanning electron microscopy and immunohistochemical observations of the vascular nerve plexuses in the dental pulp of rat incisor.
BACKGROUND: The innervation of rat incisors, which are continuously erupting teeth, is quite unique. Although many reports have documented the neural control of the pulpal blood flow, only a few studies have examined the structure and distribution of vascular nerves in the rat incisors. This study examined the nerve plexuses and the spatial relationship of nerve terminals to smooth muscle cells of the pulp vessels of rat incisors. METHODS: The innervation of the pulp vessels of rat incisors was studied using immunohistochemical evaluations of calcitonin gene-related peptide (CGRP) and neuropeptide-Y (NPY). The three-dimensional ultrastructure of nerve meshworks and terminals on smooth muscle cells of pulp arterioles were examined by scanning electron microscopy (SEM) with a KOH digestion method. RESULTS: The blood vessels were associated with many nerve fibers immunoreactive for CGRP and NPY. Some NPY and frequent CGRP-immunoreactive nerve fibers were observed in the labial odontoblast layer. Three different morphologies of nerve fibers could be distinguished: fine nerve fibers with numerous terminal varicosities, medium-sized fibers associated with occasional or much scarcer varicosities, and thick fibers that had no varicosity and sometimes ran apart from blood vessels. The SEM observations identified five vascular segment types: terminal arterioles, precapillary arterioles, capillaries, postcapillary venules, and muscular venules. Nerve meshworks were observed around the large terminal arterioles; these meshworks were very comparable to those revealed by immunohistochemistry. The vascular smooth muscle cells were closely attached by one or more terminal varicosities. CONCLUSIONS: It has become evident that the large terminal arterioles in the rat incisors receive a dense nerve supply and provide well-developed wall architecture, suggesting an important role of neuronal regulation on the vessels.
Animals↗
Follow-up study on urinary type IV collagen in patients with early stage diabetic nephropathy.
Type IV collagen is a major component released from the glomerular and tubular basement membranes. To investigate the alteration of renal type IV collagen turnover in early stage diabetic nephropathy, urinary type IV collagen was measured by a highly sensitive one-step sandwich enzyme immunoassay (EIA). Urinary samples were obtained from 94 diabetic patients without overt proteinuria. Among those patients, 61 were normoalbuminuric and 33 patients were in the microalbuminuric group. Levels of urinary type IV collagen were serially examined at the start of this study and again one year later. The levels of urinary type IV collagen in patients in the microalbuminuric group were significantly higher than those in the normoalbuminuric group (P < 0.01). There was a significant correlation between the concentration of urinary albumin and urinary type IV collagen in both groups (P < 0.05). Twenty-eight patients (45.3%) in the normoalbuminuric group who showed an abnormal elevation of urinary type IV collagen in comparison to the reference range of normal healthy adults (normal range; less than 3.5 microg/g x Cr). Seven (25%) out of these 28 normoalbuminuric patients with increased urinary type IV collagen progressed to the microalbuminuric group one year later. The levels of urinary type IV collagen in such patients were significantly increased. In the 21 patients who stayed within the normoalbuminuric group, the urinary type IV collagen levels were significantly decreased one year later. It appears that the levels of urinary type IV collagen might reflect ongoing alteration of the extracellular matrix (ECM) turnover and might define more specifically the early stage diabetic nephropathy than the detection of microalbuminuria. It is concluded that the serial measurement of urinary type IV collagen can be a useful marker for detecting renal injury in diabetes.
Adult↗
Thermal analysis of cryoprotective solutions for red blood cells.
A differential scanning calorimeter was used to study the thermal behavior of glycerol-water solutions (binary system) and the more complex glycerol-based cryoprotective solutions that are used clinically in order to examine the cryoprotective role of glycerol in preserving frozen red blood cells. The melting and glass transition temperatures for the clinically used cryoprotective solutions were as expected, based on the nonequilibriumphase diagram for cryoprotective solutions incorporating isotonic phosphate-buffered saline. Two zones were identified in which solidification occurred without the formation of ice crystals: a glassy state that is crystallographically amorphous was found for glycerol concentrations between 40 and 55% in the binary system and between 45 and 60% in the complex system; a glassy state in the complete absence of ice was found at glycerol concentrations greater than 55% for the binary system or 60% for the complex system. In clinical practice, cryoprotectants are used at initial concentrations lower than those at which these two glassy states occur but there is an increase in the effective glycerol concentration inside and outside the cells as ice forms during the freezing process.
Blood Preservation↗
Laminin, a major basement membrane component of the blood vessel, as a negative regulator of osteoclastogenesis.
Laminin, the major basement membrane glycoprotein of the blood vessel, inducing many cellular responses, inhibited the differentiation of osteoclasts in a rat bone marrow culture system when immobilized on the surface of the culture wells, showing that laminin acts as a negative regulator of osteoclast differentiation in a nonsolubilized form. Laminin inhibited the process of preosteoclast formation from early progenitor cells in bone marrow. This laminin-mediated inhibition of osteoclastogenesis was blocked by the addition of laminin fragment YIGSR, indicating that the inhibitory effect of laminin was mediated via laminin receptors. This finding suggests a significant role of basement membrane laminin of the blood vessels as a negative regulator of osteoclastogenesis.
Acid Phosphatase↗
Successful detection of active osteoclasts in situ by systemic administration of an osteoclast-specific monoclonal antibody.
Cell-surface proteins preferentially expressed on osteoclasts are thought to play important roles in the functional modulation of the osteoclasts. Recently, we found a novel cell-surface antigen designated Kat1-antigen (Kat1-Ag) specifically expressed on rat osteoclasts. It would be useful to regulate the functional activity of the osteoclasts directly via an osteoclast-specific antigen expressed on the cell surface of the osteoclasts. In order to establish the basis of such an application, in the present study we established a method for the direct detection of osteoclasts in situ by a systemic administration of the anti-Kat1-Ag monoclonal antibody (mAb Kat1) to rats, and we successfully detected functional osteoclasts in situ. Prior to performing in vivo experiments, we examined the reactivity of the mAb Kat1 to the isolated rat osteoclasts. Approximately 40-80% of the osteoclasts were reactive with mAb Kat1, suggesting that this mAb recognizes osteoclasts in a specific differentiation or functional state. Calcitonin treatment of osteoclast-like cells formed in vitro from bone marrow cells resulted in a conversion of Kat1-positive osteoclast-like cells into Kat1-negative multinucleated cells, showing the positive correlation between the Kat1-Ag expression and the potential bone-resorbing activity of osteoclasts. Administration of this lineage-specific mAb to the peritoneal cavity of newborn rats resulted in a successful recruitment of mAb Kat1 to the newly formed osteoclasts and functional osteoclasts in a highly specific manner. Detailed analysis by immunoelectron microscopy revealed that this mAb specifically bound to the basolateral side of the active osteoclasts, which were identified by their typical ruffled border and clear zone, whereas the mAb did not react to postfunctional osteoclasts. These findings demonstrate a high potential utility of mAb Kat1 in osteoclast-targeted regulation of bone remodeling.
Animals↗
Concurrent enchondroma and periosteal chondroma of the humerus mimicking chondrosarcoma.
A case of concurrent enchondroma and periosteal chondroma of the right proximal humerus in a 19-year-old woman is reported. Radiographs and CT scans showed a periosteal lesion with saucerization and spicula-like mineralization of the lateral aspect of the right proximal humerus and an ill-defined irregular lucency with stippled calcifications of the medullary cavity adjacent to it. MRI showed a long intramedullary lesion in addition to the surface lesion. There was no cortical disruption by imaging and gross examination. Histologically, both lesions showed benign cartilaginous tumors; concurrent enchondroma and periosteal chondroma of the humerus was therefore diagnosed. This combination in the same bone in a patient without enchondromatosis is exceedingly rare. Radiographic features may be confused with chondrosarcoma.
Adult↗