Biomedical subjects

H Hidaka

Publications and source records attributed to H Hidaka.

At least 91 records · Page 5Linked to original sources

PubMed1998

Neurocalcin-immunopositive nerve terminals in the muscle spindle, Golgi tendon organ and motor endplate.

The present study revealed the immunohistochemical distribution of neurocalcin, a three EF-hand calcium-binding protein, in the rat muscles and tendons. In the muscle spindles, annulospiral endings, which made spirals around the intrafusal muscles, showed intense neurocalcin-immunoreactivity. In the Golgi tendon organs, immunopositive thick nerve fibers entered the collagenous fibers resulting in the projection of many swelling terminals. In all examined muscles, nerve terminals in the motor endplates showed neurocalcin-immunoreactivity associated with the membranes of synaptic vesicles and mitochondria. These findings suggest that neurocalcin is distributed and regulates calcium signaling in both afferent and efferent nerve terminals in the muscles and tendons.

Animals↗

PubMed1998

Inter-isoformal regulation of nitric oxide synthase through heteromeric dimerization.

Biochemical characterization of neuronal nitric oxide synthase (nNOS) has demonstrated a unique complexity with the native protein being a homodimer. To cast light on its enzyme structure-activity relationship, inactive nNOS, generated by mutation of (Lys732-Lys-Leu) to (Asp732-Asp-Glu) (Watanabe et al., FEBS Lett., 403 (1997) 75-78), and active nNOS were co-expressed using the Sf9 and COS-7 cell expression system. Co-transfectants of active and inactive nNOS resulted in attenuation of Ca2+/calmodulin (CaM) dependent NOS enzyme activity to a level 46.4+/-4.30% as much as active homomeric enzyme. Dimerization between active and inactive nNOS was observed by low temperature SDS-PAGE in the co-transfectants. The dimerization and attenuation of Ca2+/CaM dependent activity were not observed when active and inactive nNOS were combined in vitro, indicating that nNOS dimerization occurs intracellularly to form an active enzyme. Furthermore, we co-expressed inactive nNOS with active inducible NOS (iNOS) to analyze inter-isoformal regulation of NOSs. Interestingly, inactive nNOS also showed similar effects on enzyme activity and heteromeric dimerization against iNOS, thus indicating that inter-isoformal regulation of the two isoforms might also be involved in control of neuron function.

Animals↗

PubMed1998

Neuronal nitric oxide synthase-membrane phospholipid interactions.

Most of the neuronal nitric oxide synthase (nNOS) is present in the particulate fraction of tissue extracts. Here, we show that the calmodulin (CaM)-binding domain of nNOS interacts with anionic phospholipid vesicles but not with neutral ones. Identification of residues in the CaM-binding domain of nNOS as the key domain for the interaction is also documented. Recombinant wild-type nNOS was found to associate with phosphatidylserine (PS) or phosphatidic acid (PA) but not with phosphatidylethanolamine (PE) or phosphatidylcholine (PC), indicating that nNOS-phospholipid binding requires an electrostatic interaction. A synthetic peptide corresponding to residues 732-754 blocked the interaction of nNOS with PS. Furthermore, a purified fusion protein containing residues 724-755 interacted with PS in a competitive fashion with CaM. Inactive nNOS lacking CaM-binding ability, generated by mutation of (Lys732LysLeu) to (Asp732AspGlu) (Watanabe, Y., Hu, Y., and Hidaka, H., FEBS Lett. 403, 75-78, 1997) did not interact with PS. Preincubation of nNOS with PS protected subsequent limited proteolysis of the synthase by Staphylococcus aureus V8 protease, probably as a result of conformational changes in the protein. Wild-type nNOS was found almost entirely in the membrane fraction of Sf9 cells, whereas inactive nNOS was also found in cytosolic fraction in Sf9 cells expressing the mutant enzyme. These results demonstrate that the mutated hydrophobic/basic amino acid cluster in nNOS sequence, Lys732LysLeu, is essential for nNOS-PS and nNOS-CaM interactions.

Amino Acid Sequence↗

PubMed1998

Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21.

The molecular mechanisms regulating the amount of dietary cholesterol retained in the body as well as the body's ability to selectively exclude other dietary sterols are poorly understood. Studies of the rare autosomal recessively inherited disease sitosterolemia (OMIM 210250) may shed some light on these processes. Patients suffering from this disease appear to hyperabsorb both cholesterol and plant sterols from the intestine. Additionally, there is failure of the liver's ability to preferentially and rapidly excrete these non-cholesterol sterols into bile. Consequently, people who suffer from this disease have very elevated plasma plant sterol levels and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. Identification of this gene defect may therefore throw light on regulation of net dietary cholesterol absorption and lead to an advancement in the management of this important cardiovascular risk factor. By studying 10 well-characterized families with this disorder, we have localized the genetic defect to chromosome 2p21, between microsatellite markers D2S1788 and D2S1352 (maximum lodscore 4.49, theta = 0.0).

Cardiovascular Diseases↗

PubMed1998

Demonstration of a Ca2+/calmodulin dependent protein kinase cascade in the hog heart.

Members of the Ca2+/calmodulin dependent protein kinase (CaMK) family and a CaMK cascade have been identified and well characterized in the brain, but little is known about their equivalents in the heart. Thus only CaMKII and its function have been reported so far. Therefore, we purified and characterized CaMKI and CaMK kinase (CaMKK) as an associated activator from the hog heart for the first time. The heart CaMKI was revealed to be the alpha isoform of brain CaMKI with a molecular weight of 41 kDa to phosphorylate cardiac phospholamban peptide, and to exhibit autophosphorylation requiring CaMKK. Heart CaMKK was found as a 67 kDa band and proved to be a different kinase from that in brain. These data indicate the existence of a heart specific CaMK cascade, consisting of CaMKI and CaMKK, along with CaMKII, which should be taken into account in any consideration of Ca2+ signal transduction.

Amino Acid Sequence↗

PubMed1998

Unique inhibitory action of the synthetic compound 2-[N-(2-aminoethyl)-N-(5-isoquinolinesulfonyl)] amino-N-(4-chlorocinnamyl)-N-methylbenzylamine (CKA-1306) against calcium/calmodulin-dependent protein kinase I.

A newly synthesized compound, 2-[N-(2-aminoethyl)-N-(5-isoquinolinesulfonyl)]amino-N-(4-chlorocinnamyl )-N-methylbenzylamine (CKA-1306), was found to inhibit cyclic AMP-dependent protein kinase (PKA) and Ca2+/calmodulin-dependent protein kinase I (CaMK I) with IC50 values of 1.6+/-0.14 and 2.5+/-0.16 microM, respectively. In contrast, the established PKA inhibitors H-8 and H-89 inhibited CaMK I with relatively high IC50 values of >100 and 24.4+/-3.2 microM, respectively. An additional inhibitor, KN-62, against Ca2+/calmodulin-dependent protein kinase II (CaMK II) did not inhibit either PKA or CaMK I at the concentrations tested. In our library of many isoquinolinesulfonamide derivatives, only CKA-1306 inhibited CaMK I to a satisfactory degree, suggesting a unique mode of action. Indeed, the inhibition of CaMK I by CKA-1306 was competitive in every respect to Mg2+/ATP, peptide substrate (syntide-2), and Ca2+/calmodulin. This phenomenon may be understood from the context of the recently determined structure of the enzyme in its autoinhibited state. Such kinetic analysis was also extended to cases using a phosphorylated and activated enzyme at Thr177 or a constitutively active, COOH-terminal truncated mutant at Gln293. CKA-1306 still competed with Mg2+/ATP for the two enzymes, but it no longer achieved any competitive advantage over syntide-2. These results may reflect some differences in the active conformation of CaMK I. However, the compound should be constant in its recognition of an Mg2+/ATP-binding site of the enzyme. Though CKA-1306 is not specific to CaMK I, the compound will be useful in studying the enzyme further under limited conditions.

Animals↗

PubMed1998

Tumor cell resistance to topoisomerase II poisons: role for intracellular free calcium in the sensitization by inhibitors or calcium-calmodulin-dependent enzymes.

Tumor cell resistance to inhibitors of topoisomerase II (topo II) is associated frequently with the overexpression of P-glycoprotein (PGP), and strategies to overcome resistance are focused on restoring defects in drug accumulation. Inhibitors of calcium-calmodulin-dependent enzymes sensitize resistant tumor cells to the topo II poison etoposide (VP-16) by enhancing DNA damage and an apoptotic response. In the present study, we have investigated the consequences of buffering intracellular calcium with 1,2-bis(o-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid tetra(acetoxy-methyl) ester (BAPTA-AM) on the sensitizing effects of the calmodulin-dependent protein kinase II inhibitor 1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-piperazine (KN-62) in etoposide-resistant human leukemia HL-60 (HL-60/ADR0.05) cells. In cells pretreated with 20 microM BAPTA-AM for 2 hr, extracellular ATP failed to trigger intracellular calcium transients, and no effects on the accumulation of VP-16 were apparent. Also, the effect of KN-62 in significantly (P=0.002 to 0.042) enhancing the accumulation of VP-16 in HL-60/ADR0.05 cells was unaffected due to pretreatment with BAPTA-AM. In contrast, pretreatment with BAPTA-AM reduced the DNA damage induced by VP-16, and significantly (P=0.038) reversed the enhancement by KN-62 of VP-16-stabilized topo II-mediated DNA cleavable complex formation. The pretreatment of HL-60/ADR0.05 cells with BAPTA-AM was also associated with the hypophosphorylation of topo IIalpha. Consistent with the ability of BAPTA-AM to circumvent the potentiation by KN-62 of VP-16-induced DNA damage, survival of cells treated with 40 microM VP-16 in the absence of KN-62 and 10 microM VP-16 in the presence of KN-62 was significantly (P=0.026 to 0.031) higher due to BAPTA-AM pretreatment. Results demonstrate that intracellular calcium transients could play a key role in the sensitization of etoposide-resistant tumor cells by inhibitors of calcium-calmodulin-dependent enzymes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

Mechanism of antitumor action of PKC activator, gnidimacrin.

Daphnane-type diterpene gnidimacrin isolated from the Chinese plant Stellera chamaejasme L. is an antitumor agent that activates protein kinase C (PKC). The mechanism of antitumor action of gnidimacrin and the possible involvement of PKC were examined using sensitive K562 and refractory HLE cells. Gnidimacrin did bind to K562 cells 3 times more than to HLE cells. Immunoblot analyses revealed pronounced PKC betaII expression in gnidimacrin sensitive cell lines including K562 cells, while refractory HLE cells strongly expressed PKC alpha, but not PKC betaII. In a 24-hr exposure of K562 cells to gnidimacrin, G1 phase arrest and inhibition of cdk2 kinase activity was found at growth-inhibitory concentration (0.0005 microg/ml). Complete inhibition of cdk2 activity and maximum G1 phase arrest were observed at 0.005 microg/ml, however, these biological effects were reduced at 0.05 microg/ml (260 times the 50% inhibitory concentration). Cellular PKC after a 24-hr exposure was examined by immunoblot analysis and specific binding of [3H]phorbol-12,13-dibutyrate as a ligand of PKC. Expression and the amount of functional PKC of K562 cells were not changed at 0.002 microg/ml, but down-regulated to less than 1/10th of the control at 0.05 microg/ml. The reduction of biological effects at 0.05 microg/ml is most likely due to PKC down-regulation. Our results suggest that PKC (particularly betaII) is one of the major determinants of the ability of cells to respond to gnidimacrin and that the antitumor action might be associated with cell-cycle regulation through suppression of cdk2 activity.

Antineoplastic Agents, Phytogenic↗

PubMed1998

2(1H)-quinolinone derivatives as novel anti-arteriostenotic agents showing anti-thrombotic and anti-hyperplastic activities.

In order to search for anti-arteriostenotic agents, a series of 2(1H)-quinolinone derivatives was synthesized and evaluated for anti-thrombotic activity and for anti-hyperplastic activity. From this series, (-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]propoxy]-2 (1H)-quinolinone (1p, OPC-33509) was selected as the best candidate by balancing the efficacy on anti-thrombosis and anti-hyperplasia.

Animals↗

PubMed1998

Neurocalcin immunoreactivity in the rat main olfactory bulb.

The morphological characteristics and distribution of neurocalcin (NC)-immunoreactive elements were studied in the rat main olfactory bulb (OB) using a polyclonal antibody and the avidin-biotin immunoperoxidase method. NC-positive elements were abundant in the glomerular layer (GL), where numerous immunostained external tufted cells and periglomerular cells were detected. Other less abundant NC-immunolabeled populations included middle and internal tufted cells, Van Gehuchten cells, horizontal cells, vertical cells of Cajal, deep short-axon cells and granule cells. This study demonstrates the presence of NC immunoreactivity in subsets of different neuronal types in the rat main OB. This calcium-binding protein has been found in interneurons, and no evidence of immunoreactivity to NC is detected in projecting neurons. Despite the large population of labeled external tufted cells, most of them belong according to morphological criteria to the local circuit group and some others to those with interbulbar and/or intrabulbar connections. The identification of neuronal subpopulations expressing NC provides a further characterization and shows the existence of biochemical differences within morphologically identical neurons. Thus, this marker may be a useful tool in unravelling the circuitries of the rodent OB in both normal and experimental conditions. The exact physiological function of NC in the olfactory system remains unknown. On the basis of similarities to recoverin, it could be involved in mechanisms responsible for sensory adaptation. Additionally, its calcium-binding abilities may contribute to improve the temporal precision of stimuli transmission, or be concerned with general calcium-related events occurring in specific interneuronal groups.

Animals↗

PubMed1998

Cloning and expression of a cDNA encoding a new neurocalcin isoform (neurocalcin alpha) from bovine brain.

Neurocalcin (NC), a neuron-specific EF-hand Ca2+-binding protein, purified from bovine brain [Terasawa, Nakano, Kobayashi and Hidaka (1992) J. Biol. Chem. 267, 19596-19599] contains multiple isoforms. We previously cloned NCdelta from bovine brain and showed high expression in neuronal tissues [Okazaki, Watanabe, Ando, Hagiwara, Terasawa and Hidaka (1992) Biochem. Biophys. Res. Commun. 185, 147-153]. We report here the molecular cloning and expression of a cDNA encoding bovine brain NCalpha. The translated bovine protein is 191 amino acids long and shares 69.1% of its amino acid sequence with NCdelta. Recombinant NCalpha migrates as a single 23 kDa band and exhibits a Ca2+-dependent mobility shift on SDS/PAGE. Analysis of fluorescence emission spectra showed the Ca2+-induced peak at 337 nm. Interestingly, the mobility shift and the fluorescence intensity at 337 nm were larger for NCalpha than for NCdelta. In Ca2+-overlay experiments, however, the apparent affinity of NCalpha for 45Ca2+ was similar to that of NCdelta. Immunohistochemical analysis revealed NCalpha expression in the granular layer of the rat cerebellar cortex whereas NCdelta was found in the Purkinje cell layer. In the rat olfactory bulb, NCalpha was located in external tufted cells, and NCdelta was found in the periglomerular cells. These data demonstrate that NC isoforms differ in their tissue distribution and conformational changes induced by Ca2+ binding. Thus differential regulation of the two NC isoforms may be involved in control of neuron function.

Amino Acid Sequence↗

PubMed1998

Regulation of calcyclin (S100A6) binding by alternative splicing in the N-terminal regulatory domain of annexin XI isoforms.

Annexin XI is a Ca2+/phospholipid-binding protein that interacts with a member of S100 protein family, calcyclin (S100A6), in a Ca2+-dependent manner. There are two isoforms of annexin XI, annexin XI-A and -B, generated by alternative splicing in the N-terminal regulatory domain. To determine the role of the alternative splicing region in the calcyclin-binding, we identified and characterized its calcyclin binding site. Experiments with glutathione S-transferase fusion proteins with N-terminal sites of annexin XI-A showed the calcyclin binding site to be in residues Gln49-Thr62 of rabbit annexin XI-A, which contains part of the splicing region. A synthesized peptide corresponding to Tyr43-Thr62 of annexin XI-A inhibited the interaction of annexin XI with calcyclin in liposome co-pelleting assay. The calcyclin binding site possesses a hydrophobic residue cluster conserved among S100 binding sites of annexin I and II. Recombinant annexin XI isoforms were expressed in Sf9 cells using a baculovirus expression system. In contrast to annexin XI-A, it was found that annexin XI-B protein could not bind to calcyclin by the liposome co-pelleting assay. In Sf9 cells coexpressing calcyclin with annexin XI isoforms, the calcyclin binding was observed only for annexin XI-A isoform. These results indicate that the calcyclin binding ability of annexin XI is an annexin XI-A isoform-specific character, suggesting that annexin XI isoforms might play distinct roles in cells through each alternative splicing regions.

Alternative Splicing↗

PubMed1998

The three-dimensional structure of Ca(2+)-bound calcyclin: implications for Ca(2+)-signal transduction by S100 proteins.

BACKGROUND: Calcyclin is a member of the S100 subfamily of EF-hand Ca(2+)-binding proteins. This protein has implied roles in the regulation of cell growth and division, exhibits deregulated expression in association with cell transformation, and is found in high abundance in certain breast cancer cell lines. The novel homodimeric structural motif first identified for apo calcyclin raised the possibility that S100 proteins recognize their targets in a manner that is distinctly different from that of the prototypical EF-hand Ca2+ sensor, calmodulin. The NMR solution structure of Ca(2+)-bound calcyclin has been determined in order to identify Ca(2+)-induced structural changes and to obtain insights into the mechanism of Ca(2+)-triggered target protein recognition. RESULTS: The three-dimensional structure of Ca(2+)-bound calcyclin was calculated with 1372 experimental constraints, and is represented by an ensemble of 20 structures that have a backbone root mean square deviation of 1.9 A for the eight helices. Ca(2+)-bound calcyclin has the same symmetric homodimeric fold as observed for the apo protein. The helical packing within the globular domains and the subunit interface also change little upon Ca2+ binding. A distinct homology was found between the Ca(2+)-bound states of the calcyclin subunit and the monomeric S100 protein calbindin D9k. CONCLUSIONS: Only very modest Ca(2+)-induced changes are observed in the structure of calcyclin, in sharp contrast to the domain-opening that occurs in calmodulin and related Ca(2+)-sensor proteins. Thus, calcyclin, and by inference other members of the S100 family, must have a different mode for transducing Ca2+ signals and recognizing target proteins. This proposal raises significant questions concerning the purported roles of S100 proteins as Ca2+ sensors.

Animals↗

PubMed1998

Neurocalcin-immunopositive neurons in the rat sensory ganglia.

Distribution of neurocalcin, a calcium-binding protein having three EF hand motifs, in the rat sensory ganglia was demonstrated immunochemically and immunohistochemically. Immunoblot analysis of trigeminal, nodose and dorsal root ganglia homogenates revealed an immunoreactive band at approximately 24 kDa. Neurons labeled by the neurocalcin-antiserum represent 54%, 41% and 46% cells in the trigeminal, nodose and dorsal root ganglia, respectively. Size distribution of immunopositive cells showed a varying range. Most large cells (more than 80%) showed immunoreactivity in the trigeminal and dorsal root ganglia. A double immunofluorescent study was performed to determine the colocalization with calbindin D28k or parvalbumin, which are both calcium-binding proteins. In the trigeminal and dorsal root ganglia, almost all calbindin- or parvalbumin-immunoreactive neurons showed neurocalcin-immunoreactivity, whereas approximately 30-40% neurocalcin-immunopositive cells had calbindin- or parvalbumin-immunoreactivity. In the nodose ganglia, parvalbumin showed localization similar to other ganglia, but about half the calbindin-immunoreactive neurons had neurocalcin-immunoreactivity. These studies show that neurocalcin-immunopositive neurons are widely distributed in the sensory ganglia and most calbindin- or parvalbumin-immunoreactive neurons also contain neurocalcin. In the sensory neurons, neurocalcin may have a significant role in calcium signaling.

Animals↗

PubMed1998

Neurocalcin-immunoreactive cells in the rat hippocampus are GABAergic interneurons.

Neurocalcin (NC) is a recently described calcium-binding protein isolated and characterized from bovine brain. NC belongs to the neural calcium-sensor proteins defined by the photoreceptor cell-specific protein recoverin that have been proposed to be involved in the regulation of calcium-dependent phosphorylation in signal transduction pathways. We analyzed the distribution and morphology of the NC-immunoreactive (IR) neurons in the rat dorsal hippocampus and the coexistence of NC with GABA and different neurochemical markers which label perisomatic inhibitory cells [parvalbumin (PV) and cholecystokinin (CCK)], mid-proximal dendritic inhibitory cells [calbindin D28k (CB)], distal dendritic inhibitory cells [somatostatin (SOM) and neuropeptide Y (NPY)], and interneurons specialized to innervate other interneurons [calretinin (CR) and vasoactive intestinal polypeptide (VIP)]. NC-IR cells were present in all layers of the dentate gyrus and hippocampal fields. In the dentate gyrus, NC-IR cells were concentrated in the granule cell layer, especially in the hilar border, whereas in the CA fields they were most frequently found in the stratum radiatum. NC-IR cells were morphologically heterogeneous and exhibited distinctive features of non-principal cells. In the dentate gyrus, pyramidal-like, multipolar and fusiform (horizontal and vertical) cells were found. In the CA3 region most NC-IR cells were multipolar, but vertical and horizontal fusiform cells also appeared. In the CA1 region, where NC-IR cells showed most frequently vertically arranged dendrites, multipolar, bitufted and fusiform (vertical and horizontal) cells could be distinguished. All the NC-IR cells were found to be GABA-IR in all hippocampal layers and regions, and they represented about 19% of the GABA-positive cells. NC/CB, NC/CR and NC/VIP double-labeled cells were found in all hippocampal regions, and represented 29%, 24% and 18% of the NC-IR cells, respectively. NC and CCK did not coexist in the dentate gyrus; however, 9% of the NC-IR cells in the CA fields also contained CCK. No coexistence of NC with PV, SOM or NPY was found in any hippocampal region. We conclude that NC is exclusively expressed by interneurons in the rat hippocampus. NC-IR cells are a morphologically and neurochemically heterogeneous subset of GABAergic non-principal cells, which, on the basis of the known termination pattern of the colocalizing markers, are also functionally heterogeneous and are mainly involved in feed-forward dendritic inhibition in the commissural-associational and Schaffer collateral termination zones (CB containing cells), in innervation of other interneurons (CR- and VIP-containing cells), and in perisomatic inhibition (CCK-containing cells). NC is never present in perisomatic inhibitory PV-containing cells, or in feed-back distal dendritic inhibitory SOM/NPY-containing cells.

Animals↗

PubMed1998

Intrapulmonary cystic lymphangioma: report of a case.

We describe herein the case of a 52-year-old man found to have a solitary pulmonary lymphangioma. Computed tomography (CT) scan demonstrated a nodule with homogeneous density and a well-defined border in the lower lobe of the right lung. T2-Weighted magnetic resonance imaging (MRI) revealed a nodule with homogeneously high signal intensity. The tumor was removed by partial resection, and pathologic examination confirmed a diagnosis of primary lymphangioma of the lung.

Humans↗

PubMed1998

Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty rats.

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are reported to be obese Type II (non-insulin-dependent) diabetic rats with insulin resistance and impaired insulin secretion. To investigate the contribution of intestinal glucose absorption to postprandial hyperglycaemia, we determined the plasma xylose concentrations after an 0.8 g/kg oral xylose load which was used as a test of small intestinal glucose absorption in 6-week-old OLETF rats and weight-matched Long-Evans Tokushima Otsuka (LETO) rats. An oral glucose tolerance test showed that OLETF rats developed hyperglycaemia at 60 and 90 min after the glucose load, though the fasting plasma glucose concentration, insulin concentration and insulin-induced in vivo glucose utilization rate were similar. Consistently, in an oral D-xylose loading test, the peak concentration of plasma xylose in OLETF rats was increased by 58.7% compared with that of LETO rats (p < 0.005). The disappearance rate of plasma xylose concentrations after intravenous xylose loading did not differ between the two strains. Co-treatment with 0.4 g/kg phlorizin, a specific inhibitor of sodium-dependent glucose transporter 1 (SGLT1), abolished both plasma glucose and xylose concentrations after the loads. Morphological studies showed that both the small intestinal wet weight and surface area were 30% larger in the OLETF rats than in the LETO rats. Furthermore, the SGLT1 mRNA content of OLETF rats also increased compared with LETO rats. These results suggest that an increased SGLT1 expression concomitant with intestinal hypertrophy in OLETF rats is partly associated with postprandial hyperglycaemia before the onset of insulin resistance and hyperinsulinaemia.

Animals↗

PubMed1998

Acoustic reflex threshold and loudness in patients with unilateral hearing losses.

The relationship between the acoustic reflex threshold (ART) and loudness was examined in patients with unilateral hearing losses and subjects with simulated hearing losses using a masking method. Significant differences in the ART between the two ears of patients with unilateral hearing losses were correlated with differences in loudness at the level of the ART with differences in loudness determined by the alternate binaural loudness balance test. A similar relationship of ART and the sensation of loudness was also observed in ears with simulated hearing losses. The results obtained in the present study suggest a positive relationship between the ART and loudness, and provide some support for the assumption that a common neuronal information pathway plays an important role both in producing the loudness and eliciting the acoustic reflex.

Adolescent↗