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Biomedical subjects

K Yamauchi

Publications and source records attributed to K Yamauchi.

At least 91 records · Page 5Linked to original sources

A case of multiple endocrine neoplasia type 2B undiagnosed for many years despite its typical phenotype.

We report the case of a 24-yr-old man with a typical phenotype of multiple endocrine neoplasia type 2B (MEN 2B). The patient had previously undergone minor surgery to remove multiple tumors on the lip, but he had no further examinations. MEN 2B was suspected owing to characteristic multiple ganglioneuromatosis when the patient presented with a goiter associated with high levels of plasma calcitonin and CEA. Aspiration biopsy cytology revealed medullary thyroid carcinoma (MTC), and abdominal computed tomography and nuclear scanning with metaiodobenzylguanidine revealed bilateral adrenomedullary tumors. Adrenomedullary function tests showed high levels of serum and urinary fractionated catecholamines, and genetic analysis showed a point mutation in the codon 918 (M918T) of the RET gene. The patient was diagnosed with MEN 2B and underwent right adrenalectomy and total thyroidectomy. No distant metastasis of the MTC was noted although MEN 2B had remained undiagnosed since the ganglioneuromatosis was first noticed. MEN 2B is a rare hereditary disorder, but the occurrence of characteristic ganglioneuromatosis was quite helpful in making the diagnosis.

Adrenal Gland Neoplasms↗

Roles and mechanisms of action of pituitary adenylate cyclase-activating polypeptide (PACAP) in growth hormone and prolactin secretion.

It appears that PACAP has a direct action on somatotrophs to release GH. The intracellular signal transduction mechanisms for PACAP might be similar to but partly distinct from those for GRH. PACAP might play a role in GH secretion induced by serotoninergic mechanisms but not in ultradian rhythm of GH secretion in the rat. PACAP can stimulate PRL release from the pituitary in rats possibly through indirect paracrine effect. In addition, PACAP might participate in regulation of PRL secretion via hypothalamic VIP.

Adenoma↗

Glutamate is not a major conveyer of ATP-sensitive K+ channel-independent glucose action in pancreatic islet beta cell.

Insulinotropic action of glucose can be categorized as 1) triggering of release, 2) augmentation of exocytosis elicited by Ca2+, and 3) time-dependent potentiation (TDP) of the exocytotic machinery. Glucose-induced closure of ATP-sensitive K+ (K+ATP) channel is required for the first but not for the latter two. We examined the legitimacy of a novel hypothesis that glutamate is a conveyer of the K+ATP channel-independent glucose action, using intact rat pancreatic islets. To this end, we compared glucose and cell permeable glutamate donors such as dimethylglutamate and glutamine for their potency of augmentation and TDP in the presence of diazoxide (250 micromol/l), a K+ATP channel opener. One millimolar leucine was employed as an activator of glutamate dehydrogenase (GDH) as needed. A high concentration (16.7 mmol/l) of glucose applied simultaneously with a depolarizing concentration (50 mmol/l) of K+ augmented (5.80 fold) insulin release elicited by the latter. Pretreatment of the islets with 16.7 mmol/l glucose caused TDP so that insulin release subsequently elicited by 50 mmol/l K+ alone was enhanced (4.70 fold). The augmentation and TDP caused by dimethylglutamate and glutamine (10 mmol/l each), respectively, were very weak (12% of the glucose effect utmost), and dramatically enhanced upon activation of GDH by leucine. Insulinotropic effect of the glutamate donors, but not that of 50 mmol/l K+, was eliminated by 2 mmol/l NaN3, a mitochondrial poison. Glutamate per se serves as a weakly metabolizable mitochondrial fuel, but not a direct conveyer of the K+ATP channel-independent glucose action in the islet beta cell.

Adenosine Triphosphate↗

Norepinephrine inhibits glucose-stimulated, Ca2+-independent insulin release independently from its action on adenylyl cyclase.

Inhibition of insulin release by norepinephrine has been attributed to activation of ATP-sensitive K+ channels, inactivation of voltage-dependent Ca2+ channels, and inhibition of adenylyl cyclase. However, direct inhibitory action of norepinephrine at a distal site of stimulus-secretion coupling has also been suggested. To obtain more direct evidence for norepinephrine inhibition of insulin release at a distal site, we performed experiments in intact, non-permeabilized beta cells. In rat pancreatic islets, a combination of glucose, phorbol ester and forskolin under stringent Ca2+-free conditions was used as a trigger of insulin exocytosis at a distal site. Norepinephrine inhibited this Ca2+-independent insulin release in a concentration-dependent manner, with an IC50 of 50 nM. The inhibition was complete, reversible, and pertussis toxin-sensitive, and not associated with any reduction of cAMP content in the islet cells. In conclusion, norepinephrine strongly, yet reversibly, inhibits insulin release in intact beta cells at a late step of exocytosis, through pertussis toxin-sensitive, G protein-mediated mechanism(s).

Adenylate Cyclase Toxin↗

Device for the removal of button batteries.

OBJECTIVE: There is an increasing number of accidents by erroneous ingestion of button batteries in recent years; the batteries arouse the interest of infants because of their attractive shape and luster. The batteries remaining in the gastrointestinal tract and discharging electric current over a long period of time may induce ulceration or perforation, thus must be carefully considered the selection of appropriate treatment. METHODS: We remove erroneously ingested button batteries with two tubes with ferrite magnets nearly the same size as the button batteries themselves. PATIENTS: Four cases of erroneous ingestion of button batteries. RESULTS: We easily removed button batteries from the stomach within 5 minutes in all cases with two magnet-attached tubes. CONCLUSION: We present this battery removal device together with a literature review, because it seems convenient and useful.

Equipment Design↗

Laparoscopic ovarian cystectomy using a single umbilical puncture method.

To establish a minimally invasive technique to perform ovarian cystectomy, the authors applied a single umbilical puncture method. A 2-month old female infant was admitted to the hospital because of an ovarian cyst that showed no spontaneous shrinkage after her birth. An umbilical semicircular incision was made to insert a 10-mm trocar, into which a 3-mm laparoscope was inserted. The ovarian cyst was grasped using forceps inserted through an operating channel of the scope, and the cyst was removed through the incision. After aspiration of the cyst, the free cyst wall was resected, leaving the intact ovarian tissue. The operation was performed without difficulty or complication. The postoperative course was uneventful. The wound was inconspicuous, and the result was cosmetically excellent. The case demonstrated the feasibility of the minimally invasive technique using a single umbilical puncture for ovarian cystectomy in an infant.

Female↗

Characterization of an apolipoprotein E3 variant (Arg 145-->His) associated with mild hypertriglyceridemia.

In a proband (21-yr-old female), we previously identified an apolipoprotein (apo) E variant, apoE3 (Arg 145-->His), with an isoelectric point midway between apoE3 and apoE2. ApoE gene analysis of 4 of the proband's kin indicated that 3 possess the same variant. All 4 had a high concentration of apoE in plasma, while 3 of 4 had hypertriglyceridemia. In the proband (who had no hypertriglyceridemia), most apoE was distributed in slow-alpha lipoproteins (predominantly in the form of apoE-AII heterodimer) and in larger molecules with apparent molecular weights of 80 and 100 kDa. In the proband's brother (with hypertriglyceridemia), however, most apoE was distributed in slow pre-beta lipoproteins, predominantly in the form of monomeric apoE. In each subject, the concentration of apoE3 variant was significantly higher than that of normal apoE3 in the predominant apoE-rich lipoprotein. The apoE3 variant, which displayed a slightly reduced binding ability to LDL-receptor and heparin, may induce an accumulation of apoE-rich lipoproteins. These observations suggest that the difference in distribution of apoE3 variant in plasma lipoproteins between the proband and her brother (combined with its reduced affinity for the LDL receptor) may provide key insights into the pathogenesis of hypertriglyceridemia.

Adult↗

Effect of nitrite and propolis preservative on volatile basic nitrogen changes in meat products.

Pig meat was treated with 0.3% ethanol extracted propolis (EEP), 0.3% water extracted propolis (WEP), 0.4% dried residue of ethanol extracted propolis (DREEP) and 0.2% potassium sorbate (PS). The samples were stored for 8 weeks at 4, 10 and 20 degrees C, respectively. Volatile basic nitrogen (VBN) tests were carried out to measure the influence of temperature after 0, 2, 4 and 8 weeks. The VBN value in 0.3% EEP pork sausages was the lowest for all treatments after 8 weeks of storage at 4 degrees C. The 0.3% EEP treatment was superior to the 0.2% PS treatment. This was due to the lower VBN of the former than that of the latter. Hence, EEP, WEP and DREEP can serve as good chemical preservatives of pork meat products and can contribute to promote human health because they are naturally produced.

Amino Acids↗

Application of resampling techniques to the statistical analysis of the Brier score.

We investigated the application of resampling techniques to the statistical analysis of the Brier score (B), and extended them to the statistical comparison of two Bs derived from the same set of patients. The resampling techniques are helpful in the statistical analysis of B, and there are almost no differences between the jackknife method and the bootstrap method in this analysis. Thus, we believe that B should be used more often as an index to evaluate probabilistic judgments in the case in which the data sets for the assessment are "degenerate" as the "receiver operating characteristic data sets."

Case-Control Studies↗

[Airway inflammatory marker].

Since asthma has been recognized as a chronic inflammatory airway disease, inflammatory markers are useful tools to show the degree of allergic airway inflammation. Asthmatic airway is characterized with infiltration of activated Th2 lymphocyte, eosinophils and mast cells/basophils. Eosinophil derived proteins such as ECP, MBP and EDN are important markers indicating eosinophilic inflammation. Histamine and tryptase are the products of mast cell/basophil activation. These markers are detected in sputum, BALF, serum and urine, and increased in asthmatics. In addition to these markers, NO concentration in exhaled air, cytokines such as IL-4, IL-5, chemokines such as RANTES, eotaxin, LTE4, MMP are inflammatory markers to indicate the quality and quantity of asthmatic airway inflammation. Assessment of these markers, therefore, contributes to better control of asthmatic symptoms with appropriate therapy.

Asthma↗

[Pulmonary complications following laparoscopic cholecystectomy in patients with abnormal spirometry].

The purpose of this study was to determine the incidence of postoperative pulmonary complications (PPC) and the value of preoperative spirometry to predict PPC after laparoscopic cholecystectomy. Sixty-four of 1372 patients (8%) showed abnormal spirometry data. One out of 1372 patients developed aspiration pneumonia. The patient had high risk factors for serious PPC such as ASA physical status 4.84 y/o, longer anesthesia duration (230 min), multiple brain infarction and low albuminemia. Thirty to 39% of patients with abnormal spirometry showed less severe PPC such as atelectasis, lung collapse and pleural effusion, and incidence was the similar with normal lung function patients. Postoperative blood gas analysis showed a slight increase in arterial carbon dioxide tension during oxygen therapy. However, none of the patients with abnormal spirometry and less severe PPC developed manifest PPC (pneumonia, respiratory failure). Less severe PPC disappeared within second to third postoperative days. We conclude that laparoscopic intervention significantly reduced the incidence of severe PPC and the preoperative spirometry was not recommended in patients with no pulmonary symptoms.

Aged↗

Cloning of 17beta-hydroxysteroid dehydrogenase-I cDNAs from Japanese eel ovary.

17beta-hydroxysteroid dehydrogenase-I (17beta-HSD-I) is a key steroidogenic enzyme for estradiol-17beta (E(2)) production. cDNAs encoding 17beta-HSD-I were cloned for the first time in lower vertebrates from the ovary of a teleost, the Japanese eel. The deduced amino acid sequence from these cDNAs was approximately 50% identical to mammalian 17beta-HSD-Is. 17beta-HSD-I mRNA was not detected in previtellogenic ovaries by Northern blotting. However, transcript abundance increased in early vitellogenic ovaries obtained from fish artificially matured by gonadotropic treatment, but thereafter did not appear to change further. Recombinant 17beta-HSD-I expressed in human kidney 293 cells selectively converted estrone to E(2), but androstenedione, testosterone, or E(2) were not converted to any other steroids. Although it is widely accepted that E(2) is produced from testosterone in other species of teleosts, the substrate specificity of eel 17beta-HSD-I suggests that a steroidogenic pathway for production of E(2) from androstenedione via estrone exists in the Japanese eel ovary.

17-Hydroxysteroid Dehydrogenases↗

Ligand binding in the ferric and ferrous states of Paramecium hemoglobin.

The unicellular protozoan Paramecium caudatum contains a monomeric hemoglobin (Hb) that has only 116 amino acid residues. This Hb shares the simultaneous presence of a distal E7 glutamine and a B10 tyrosine with several invertebrate Hbs. In the study presented here, we have used ligand binding kinetics and resonance Raman spectroscopy to characterize the effect of the distal pocket residues of Paramecium Hb in stabilizing the heme-bound ligands. In the ferric state, the high-spin to low-spin (aquo-hydroxy) transition takes place with a pK(a) of approximately 9.0. The oxygen affinity (P(50) = 0.45 Torr) is similar to that of myoglobin. The oxygen on- and off-rates are also similar to those of sperm whale myoglobin. Resonance Raman data suggest hydrogen bonding stabilization of bound oxygen, evidenced by a relatively low frequency of Fe-OO stretching (563 cm(-1)). We propose that the oxy complex is an equilibrium mixture of a hydrogen-bonded closed structure and an open structure. Oxygen will dissociate preferentially from the open structure, and therefore, the fraction of open structure population controls the rate of oxygen dissociation. In the CO complex, the Fe-CO stretching frequency at 493 cm(-1) suggests an open heme pocket, which is consistent with the higher on- and off-rates for CO relative to those in myoglobin. A high rate of ligand binding is also consistent with the observation of an Fe-histidine stretching frequency at 220 cm(-1), indicating the absence of significant proximal strain. We postulate that the function of Paramecium Hb is to supply oxygen for cellular oxidative processes.

Amino Acid Sequence↗

Effect of apolipoprotein AII on the interaction of apolipoprotein E with beta-amyloid: some apo(E-AII) complexes inhibit the internalization of beta-amyloid in cultures of neuroblastoma cells.

Apolipoprotein (apo) E and its polymorphism are linked to the pathogenesis of late-onset and sporadic Alzheimer's disease (AD). ApoE facilitates the deposition and fibrillogenesis of beta-amyloid (Abeta), and may participate in Abeta clearance. We recently found that apo(E-AII) complex binds to Abeta much more strongly than does monomeric apoE. Here, we investigated the effect of apoAII on the interaction between apoE and Abeta. Addition of apoAII to apoE monomers increased the binding of apoE2 and apoE3 to Abeta(1-42), presumably following the formation of apo(E3-AII), apo(E2-AII), and apo(AII-E2-AII) complexes. This increased binding was not seen in the case of apoE4. When neuroblastoma cells were cultured in media containing Abeta(1-42) and a mixture of apoE3 and apoAII, intracellular Abeta was significantly reduced and cell viability was maintained at a higher level than in cells cultured without apoAII. ApoE2 itself seemed to act as an inhibitor of the endocytosis of Abeta, and we did not observe a significant effect of apoAII on the movement of Abeta in apoE2-containing medium. However, cell viability could be maintained at a higher level (as with apoE3) by adding apoAII to apoE2, despite the reduced viability of cells incubated without apoAII. In medium containing apoE4, both the amount of Abeta accumulated into cells and the cell viability were unchanged by the presence of apoAII in the medium. In addition, apoE4 itself was toxic, as previously suggested. These findings demonstrate that the type of apo(E-AII) complex present could underlie the isoform-specific role of apoE in the pathogenesis of AD.

Alzheimer Disease↗

Effects of sigma(1) receptor ligand, MS-377 on apomorphine- or phencyclidine-induced disruption of prepulse inhibition of acoustic startle in rats.

To evaluate the antipsychotic property of a sigma(1) receptor ligand, (R)-(+)-1-(4-chlorophenyl)-3-¿4-(2-methoxyethyl)piperazin-1-yl¿ methyl-2-pyrrolidinone-L-tartrate (MS-377), an antagonistic effect of MS-377 on the disruption of prepulse inhibition (PPI) of the acoustic startle by apomorphine or phencyclidine (PCP) was investigated in rats. MS-377 antagonized the PCP-induced disruption of PPI. The ED(50) value of MS-377 for this effect was 0.66 mg/kg. In contrast, apomorphine-induced disruption of PPI was not attenuated by MS-377. These data indicate that the PCP-induced disruption of PPI in rats would be, at least partially, mediated by sigma receptors and MS-377 could be a novel anti-psychotic agent with clinical efficacy for the sensorimotor-gating deficit in schizophrenia.

5-Hydroxytryptophan↗

Selective attenuation of metabolic branch of insulin receptor down-signaling by high glucose in a hepatoma cell line, HepG2 cells.

The effects of a high concentration of glucose on the insulin receptor-down signaling were investigated in human hepatoma (HepG2) cells in vitro to delineate the molecular mechanism of insulin resistance under glucose toxicity. Treatment of the cells with high concentrations of glucose (15-33 mm) caused phosphorylation of serine residues of the insulin receptor substrate 1 (IRS-1), leading to reduced electrophoretic mobility of it. The phosphorylation of IRS-1 with high glucose treatment was blocked only by protein kinase C (PKC) inhibitors. The high glucose treatment attenuated insulin-induced association of IRS-1 and phosphatidylinositol 3-kinase and insulin-stimulated phosphorylation of Akt. A metabolic effect of insulin, stimulation of glycogen synthesis, was also inhibited by the treatment. In contrast, insulin-induced association of Shc and Grb2 was not inhibited. Treatment of the cells with high glucose promoted the translocation of PKCepsilon and PKCdelta from the cytosol to the plasma membrane but not that of other PKC isoforms. Finally, PKCepsilon and PKCdelta directly phosphorylated IRS-1 under cell-free conditions. We conclude that a high concentration of glucose causes phosphorylation of IRS-1, leading to selective attenuation of metabolic signaling of insulin. PKCepsilon and PKCdelta are involved in the down-regulation of insulin signaling, and they may lie in a pathway regulating the phosphorylation of IRS-1.

Adaptor Proteins, Signal Transducing↗

A novel two-over-two alpha-helical sandwich fold is characteristic of the truncated hemoglobin family.

Small hemoproteins displaying amino acid sequences 20-40 residues shorter than (non-)vertebrate hemoglobins (Hbs) have recently been identified in several pathogenic and non-pathogenic unicellular organisms, and named 'truncated hemoglobins' (trHbs). They have been proposed to be involved not only in oxygen transport but also in other biological functions, such as protection against reactive nitrogen species, photosynthesis or to act as terminal oxidases. Crystal structures of trHbs from the ciliated protozoan Paramecium caudatum and the green unicellular alga Chlamydomonas eugametos show that the tertiary structure of both proteins is based on a 'two-over-two' alpha-helical sandwich, reflecting an unprecedented editing of the classical 'three-over-three' alpha-helical globin fold. Based on specific Gly-Gly motifs the tertiary structure accommodates the deletion of the N-terminal A-helix and replacement of the crucial heme-binding F-helix with an extended polypeptide loop. Additionally, concerted structural modifications allow burying of the heme group and define the distal site, which hosts a TyrB10, GlnE7 residue pair. A set of structural and amino acid sequence consensus rules for stabilizing the fold and the bound heme in the trHbs homology subfamily is deduced.

Amino Acid Motifs↗