Biomedical subjects

S Yamaguchi

Publications and source records attributed to S Yamaguchi.

At least 127 records · Page 7Linked to original sources

PubMed2001

Heme oxygenase (HO) isoforms in experimental C6 glioma: an immunocytochemical study.

Abstract Because of their potential to regulate tumoural blood flow and interactions with nitric oxide the expression of the type 1 and 2 isoforms of heme oxygenase (HO-1 and HO-2) were evaluated in implanted C6 striatal gliomas. Immunocytochemistry using antibodies specific for HO-1 and HO-2 were used in 20 C6 glioma tumours. The bulk of the tumour parenchyma and endothelium was negative for both HO isoforms. Isolated, but weak staining for HO-1 was seen in most tumours with focally increased expression in perinecrotic regions. Cells morphologically resembling macrophages stained with both HO-1 and HO-2, but were not numerous. These findings suggest that carbon monoxide, unlike nitric oxide, does not have a major role in regulating tumoural blood flow in this experimental glioma model. These findings once again demonstrate the differences between human malignant glioma and experimental implantation glioma models.

Animals↗

PubMed2001

Protection by quercetin and quercetin 3-O-beta-D-glucuronide of peroxynitrite-induced antioxidant consumption in human plasma low-density lipoprotein.

Effect of quercetin and its conjugated metabolite quercetin 3-O-beta-D-glucuronide (Q3GA), on peroxynitrite-induced consumption of lipophilic antioxidants in human plasma low-density lipoprotein (LDL) was measured to estimate the role of dietary flavonoids in the defense system against oxidative modification of LDL based on the reaction of nitric oxide and superoxide anion. Synthesized peroxynitrite-induced consumption of endogenous lycopene beta-carotene and alpha-tocopherol was effectively suppressed by adding quercetin aglycone into LDL solution. Q3GA also inhibited the consumption of these antioxidants effectively. These results indicate that dietary quercetin is capable of inhibiting peroxynitrite-induced oxidative modification of LDL in association with lipophilic antioxidants present within this lipoprotein particle.

Antioxidants↗

PubMed2001

Oxidative damage and direct adducts in calf thymus DNA induced by the pentachlorophenol metabolites, tetrachlorohydroquinone and tetrachloro-1,4-benzoquinone.

DNA damage induced by quinoid metabolites of pentachlorophenol (PCP), i.e. tetrachloro-1,4-benzoquinone (Cl(4)BQ) and tetrachlorohydroquinone (Cl(4)HQ), was investigated in calf thymus DNA. The (32)P-post-labeling assay revealed four major and several minor adducts (3.5 adducts per 10(5) total nucleotides) that were produced in calf thymus DNA treated with Cl(4)BQ (5 mM). These DNA adducts were chemically stable even after conditions that induce thermal depurination and are unlikely to undergo depurination/depyrimidination to form apurinic/apyrimidinic (AP) sites. In addition, increases in 8-hydroxy-deoxyguanosine (8-HO-dG) (5 8-HO-dG per 10(5) nucleotides) and AP sites (0.5 AP sites per 10(5) nucleotides) were observed in Cl(4)BQ-modified calf thymus DNA. Further investigation indicated that in the presence of Cu(II) and NADPH, low concentrations of Cl(4)BQ (1 microM) induced a doubling of 8-HO-dG (10 8-HO-dG per 10(5) nucleotides) and dramatic increases in AP sites (20 AP sites per 10(5) nucleotides) and DNA single-strand breaks. The types of DNA damage induced by Cl(4)HQ plus Cu(II) were similar to those by Cl(4)BQ plus Cu(II) and NADPH, whereas catalase inhibited the formation of DNA damage. These data suggest that oxidative damage is causally involved in the formation of AP sites. Concentration-dependent increases in 8-HO-dG induced by Cl(4)HQ plus Cu(II) and Cl(4)BQ plus Cu(II) and NADPH were correlated with the formation of AP sites (r(2) = 0.977) with a ratio of 8-HO-dG to AP sites at 1:1.6. The AP site-cleavage assay confirmed that approximately 85% of the AP sites induced by Cl(4)HQ and Cu(II) were detected as 5'-cleaved AP sites. Since hydrogen peroxide alone causes similar DNA damage, these results suggest the involvement of Cu(II) and hydrogen peroxide in the induction of oxidative DNA damage by Cl(4)HQ/Cl(4)BQ. The data demonstrate that PCP quinone and hydroquinone induce direct and oxidative base modifications as well as the formation of 5'-cleaved AP sites in genomic DNA. These lesions may have important implications for PCP clastogenicity and carcinogenicity.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

Induction of direct adducts, apurinic/apyrimidinic sites and oxidized bases in nuclear DNA of human HeLa S3 tumor cells by tetrachlorohydroquinone.

DNA damage induced by tetrachlorohydroquinone (Cl(4)HQ), the quinonoid metabolite of pentachlorophenol (PCP), was investigated in human HeLa S3 tumor cells. Formation of one major and two minor DNA adducts in cells treated with Cl(4)HQ (50-300 microM) was detected by (32)P-post-labeling assay and the adducts accumulated over the course of the experiment (0.5-2 h), with total adduct levels estimated to be 3-6 per 10(8) nucleotides. These adducts did not correspond to those derived from calf thymus DNA treated with tetrachloro-1,4-benzoquinone. Results from the apurinic/apyrimidinic (AP) sites assay indicated that the number of AP sites was 2-fold greater in cells exposed to Cl(4)HQ (300 microM) than the corresponding control. Further characterization of the AP sites confirmed that Cl(4)HQ induced predominantly (75%) putrescine-excisable AP sites in HeLa S3 cells. In parallel, the concentration of 8-hydroxy-2'-deoxyguanosine (8-HO-dG) in cells treated with Cl(4)HQ for 0.5 and 2 h was increased 2- and 5-fold, respectively, compared with the control. The extent of oxidative DNA damage induced by Cl(4)HQ was approximately two orders of magnitude greater than those of direct DNA adducts. Overall, it appears that reactive oxygen species mediate the parallel formation of AP sites and 8-HO-dG in HeLa S3 cells following treatment with Cl(4)HQ and that the contribution of depurination/depyrimidination of direct DNA adducts is relatively insignificant compared with the formation of oxidized AP sites. We conclude that putrescine-excisable AP sites represent a major type of ROS-mediated oxidative DNA damage in cellular DNA induced by Cl(4)HQ and may play a role in PCP-induced clastogenicity in mammalian cells.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

Taste-enhancing effects of glycine on the sweetness of glucose: a gustatory aspect of symbiosis between the ant, Camponotus japonicus, and the larvae of the lycaenid butterfly, Niphanda fusca.

The lycaenid butterfly, Niphanda fusca, has a parasitic relationship with its host ant, Camponotus japonicus: the caterpillars may use chemical mimicry to enter the ant nest where they are fed mouth-to-mouth by the adult ants until pupation. Nevertheless, larvae offer their host ants a nutritious secretion that contains 160 mM glucose and 43 mM glycine. Using glucose and glycine mixture as artificial secretions, we investigated the gustatory effect of glucose and/or glycine on the ants. Glycine induced neither feeding behavior nor gustatory response in the ants if its concentration was <500 mM. In the presence of glycine at the concentration in the secretion, however, the ants improved their preference to glucose, and the sugar receptor cell exhibited electrophysiological enhancement of response to glucose in a glycine-concentration-dependent manner. By adding glycine to glucose in their secretions, therefore, the butterfly larvae can manipulate the gustatory sense of the ants. The alluring taste of 'glycine-flavored glucose' could motivate the host ants to feed the larvae and thereby receive the secretions as a reward. The taste enhancement created by the combination of sugar and amino acid may play a role in the evolution of the parasitic relationships of these insects. The taste-enhancing effect appears to be analogous to taste enhancement by 'umami' substances in humans.

Amino Acids↗

PubMed2001

Temporal and spatial mRNA expression of bone sialoprotein and type I collagen during rodent tooth movement.

To investigate the mechanism of bone formation during tooth movement, in situ hybridization was performed with digoxigenin-labelled RNA probes to detect bone sialoprotein (BSP) and type I collagen mRNAs in the dentoalveolar tissue of 72 Sprague-Dawley rats. An elastic band was inserted between the first and second right maxillary molars, and the teeth experimentally moved for 1, 3, and 7 days. The left first maxillary molar was used as the control. For the untreated molars, osteoblasts and osteocytes near the distal surface of the interradicular septum (IRS) expressed a high level of both BSP and type I collagen mRNAs, while cells on the mesial side of the IRS showed a low level of these mRNAs. For the first molars subjected to experimental tooth movement, a high level of type I collagen mRNA expression was found in the osteoblasts on the tension side of the IRS after 1 day of experimental tooth movement. A high level of BSP mRNA was detected after 3 days of experimental tooth movement. However, a negligible amount of both mRNAs was found in cells on the compression side. These results support the hypothesis that BSP may be involved in mineralization during physiological bone remodelling. On application of orthodontic force, osteoblasts were activated and induced to express BSP mRNA, which is involved in bone remodelling due to orthodontic force. In addition, response to the orthodontic force was observed in osteocytes.

Alveolar Process↗

PubMed2001

A 5-year retrospective examination of cognitive screening test stages in normal older adults and patients with Alzheimer's disease: the Tajiri project.

One conception of aging and cognitive deterioration is that cognitive decline becomes common with age, and dementia may be regarded as one extreme of the continuum. An alternative conception is that the cognitive process is spared by the aging process itself and that cognitive functioning of normal older adults and those with slight cognitive impairment, a CDR (Clinical Dementia Rating) score of 0.5 (suspected dementia), should be different. We examined changes in the screening test performances of 170 older adults over a 5-year period and found the following: (a) The CDR 0 (normal) participants did not show remarkable changes even in the older groups and (b) the subitems of orientation, memory, and so forth were useful for distinguishing normal older adults from early Alzheimer's disease patients. The results support the idea that dementia is better conceptualized as an age-related than as an "aging-related" disorder and that a CDR score of 0.5 should be considered very mild Alzheimer's disease.

Aged↗

PubMed2001

Monitoring of the refolding process for immobilized firefly luciferase with a biosensor based on surface plasmon resonance.

In order to examine the possibility of the use of a surface plasmon resonance (SPR) sensor for real-time monitoring of the process of refolding of immobilized proteins, the refolding of firefly luciferase immobilized on a carboxymethyldextran matrix layer was analyzed. The SPR signal of the immobilized luciferase decreased after unfolding induced by GdnCl and increased gradually in the refolding buffer, while there was no signal change in the reference surface lacking the immobilized protein. The decrease in the SPR signal on unfolding was consistent with the difference between the refractive indices of the native and unfolded protein solutions. The effects of blocking of the excess NHS-groups of the matrix layer on the refolding yield were examined by means of an SPR sensor. The results were consistent with those obtained with the enzymatic activity assay, indicating that the changes in the SPR signal reflected the real-time conformational changes of the immobilized protein. Hence, an SPR biosensor might be used for monitoring of the process of refolding of immobilized proteins and as a novel tool for optimization of the refolding conditions. This is the first demonstration that SPR signal changes reflect the conformational changes of an immobilized protein upon unfolding and refolding.

Animals↗

PubMed2001

Surface dynamics of bacteriorhodopsin as revealed by (13)C NMR studies on [(13)C]Ala-labeled proteins: detection of millisecond or microsecond motions in interhelical loops and C-terminal alpha-helix.

We have recorded (13)C NMR spectra of [2-(13)C]-, [1-(13)C]-, [3-(13)C],- and [1,2,3-(13)C(3)]Ala-labeled bacteriorhodopsin (bR), and its mutants, A196G, A160G, and A103C, by means of cross polarization-magic angle spinning (CP-MAS) and dipolar decoupled-magic angle spinning (DD-MAS) techniques, to reveal the conformation and dynamics of bR, with emphasis on the loop and C-terminus structures. The (13)C NMR signals of the loop (C-D, E-F, and F-G) regions were almost completely suppressed from [2-(13)C]-, [1-(13)C]Ala-, and [1-(13)C]Gly-labeled bR, due to the presence of conformational fluctuation with correlation times of 10(-4) s that interfered with the peak-narrowing by magic angle spinning. The observation of such suppressed peaks for specific residues provides a unique means of detecting intermediate frequency motions on the time scale of ms or micros in the surface loops of membrane proteins. Instead, the three well-resolved (13)C CP-MAS NMR signals of [2-(13)C]Ala-bR, at 50.38, 49.90, and 47.96 ppm, were ascribed to the C-terminal alpha-helix previously proposed from the data for [3-(13)C]Ala-bR: the former two peaks were assigned to Ala 232 and 238, in view of the results of successive proteolysis experiments, while the highest-field peak was ascribed to Ala 235 prior to Pro 236. Even such (13)C NMR signals were substantially broadened when (13)C NMR spectra of fully labeled [1,2,3-(13)C]Ala-bR were recorded, because the broadening and splitting of peaks due to the accelerated transverse relaxation rate caused by the increased number of relaxation pathways through a number of (13)C-(13)C homo-nuclear dipolar interactions and scalar J couplings, respectively, are dominant among (13)C-labeled nuclei. In addition, approximate correlation times for local conformational fluctuations of different domains, including the C-terminal tail, C-terminal alpha-helix, loops, and transmembrane alpha-helices, were estimated by measurement of the spin-lattice relaxation times in the laboratory frame and spin-spin relaxation times under the conditions of cross-polarization-magic angle spinning, and comparative study of suppressed specific peaks between the CP-MAS and DD-MAS experiments.

Alanine↗

PubMed2001

Identification of a component that induces flowering of Lemna among the reaction products of alpha-ketol linolenic acid (FIF) and norepinephrine.

A stress-induced fatty acid [FIF; 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid] incubated with (-)-norepinephrine (NE) strongly induces flower formation in Lemna paucicostata [Yokoyama et al. (2000), Plant Cell Physiol. 41: 110). The increase of flower-inducing activity was well correlated with the decrease in FIF in the incubation mixture, and the reaction proceeded rapidly at higher pH. We detected small amounts of many active components in the mixture after incubation by HPLC analysis. In this study, two major components, named FN1 and FN2, of the reaction mixture were isolated, and their absolute stereostructures were determined. FN1 showed a strong flower-inducing activity and was identified as a tricyclic alpha-ketol fatty acid, 9(R)-11-[(2'R,8'R,10'S,11'S)-2',8'-dihydroxy-7'-oxo-11'-[(Z)-2-pentenyl]-9'-oxa-4'-azatricyclo[6.3.1.0(1.5)]dodec- 5'en-10'-yl]-9-hydroxy-10-oxoundecanoic acid [corrected]. FN2, the C-9 epimer of FN1, showed no flower-inducing activity. The absolute stereostructure of FIF was also determined by a modification of Mosher's method. The 9-hydroxyl group was found to be predominantly 9R, with an enantiomeric excess of 40% (70% 9R and 30% 9S). FN1 was derived from 9R-type FIF and FN2 from 9S-type FIF. Various catecholamines and related substances were investigated for the ability to develop flower-inducing activity upon incubation with FIF. The essential structures were catechol and ethylamine groups (dopamine).

Catecholamines↗

PubMed2001

Correlation between messenger RNA expression of cytochrome P450 aromatase and its enzyme activity during oocyte development in the red seabream (Pagrus major).

In teleosts, estradiol-17beta (E2) is an important hormone responsible for oocyte development. To elucidate the molecular mechanisms underlying E2 biosynthesis, we characterized the structure of red seabream (Pagrus major) cytochrome P450 aromatase (P450(arom)) that is directly involved in E2 biosynthesis and found changes in mRNA levels of P450(arom) during oocyte development induced by implantation of gonadotropin-releasing hormone analogue. A cDNA clone encoding P450(arom) is 1779 base pairs in length and encodes a protein of 519 amino acids in length, with a calculated molecular weight of 58.9 kDa. Northern blot analysis showed that P450(arom) mRNA levels increased gradually from Day 8, when oocytes reached the secondary yolk globule stage, and were maintained at high levels at the day of spawning (Day 15). The P450(arom) mRNA levels increased in association with an increase of the gonadosomatic index (gonad weight/body weight x 100%), serum E2, and P450(arom) enzyme activity (in vitro conversion of testosterone to E2 in the ovarian fragments). Furthermore, an increase in mRNA levels of the LHbeta, but not FSHbeta, correlated with increased P450(arom) mRNA levels during the course of ovarian development. In addition, the levels of P450(arom) mRNA increased in isolated ovarian follicles during the course of vitellogenic oocyte growth and became undetectable in follicles at the migratory nucleus and the mature stages. These findings, together with those of the previous studies, suggest that LH, not FSH, may regulate E2 biosynthesis via increased levels of P450(arom) mRNA during oocyte development of red seabream.

Amino Acid Sequence↗

PubMed2001

Immunohistochemical expression of gastric mucin and p53 in minimal deviation adenocarcinoma of the uterine cervix.

Comparative immunostaining with antibodies against gastric mucin and p53 was performed on 6 cases of minimal deviation adenocarcinoma (MDA) of the uterine cervix. The MDAs consisted of predominant areas of glands lined by extremely well-differentiated tall columnar epithelial cells with little cytological atypia and minor foci of less well-differentiated glandular epithelium with a minor degree of nuclear atypia. Immunostaining for gastric mucin with a monoclonal antibody HIK1083 revealed that all the tumors areas of typical MDA were partly immunoreactive for HIK1083, but the coexisting less well-differentiated glands were essentially negative. Four MDAs focally contained cells with p53 positive nuclei that were located exclusively in the less well-differentiated cells that lacked gastric mucin. In the pelvic lymph nodes in 2 cases, most of the metastatic tumor was less differentiated and a positive reaction for HIK1083 was observed only in small foci of typical MDA. No significant overexpression of p53 was observed in the metastases. Immunohistochemical expression of gastric mucin and p53 may be related to the histological differentiation of MDA, and detection of p53 overexpression may help to identify critical steps in the local progression of MDA.

Adenocarcinoma↗

PubMed2001

Reverse redistribution of 99m Tc-sestamibi after direct percutaneous transluminal coronary angioplasty in acute myocardial infarction: relationship with wall motion and functional response to dobutamine stimulation.

Reverse redistribution (RR) of 99mTc-sestamibi is observed after direct percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI). The purpose of this study was to clarify the functional characteristics of myocardial segments with RR after direct PTCA in AMI. Thirty patients with AMI who had undergone direct PTCA were examined. Myocardial perfusion tomography with 99mTc-sestamibi and low dose dobutamine echocardiography were performed within 2 weeks of the onset. The 99mTc-sestamibi images were obtained 1 and 3 h after tracer administration. The left ventricle was divided into nine segments, and regional 99mTc-sestamibi uptake and clearance were quantitatively evaluated in each segment. RR was defined as a decrease in 99mTc-sestamibi uptake of >10% on 3 h delayed images compared with the 1 h early images. The left ventricle in the echocardiographic images was also divided into nine segments corresponding to the scintigraphic images, and regional wall motion was assessed in the resting condition as the baseline and during dobutamine administration (5-10 microg x kg(-1) x min(-1)). Out of a total of 270 myocardial segments, 111 segments were perfused by the culprit coronary artery and were defined as ischaemic segments. There were 25 segments with RR and 86 segments without RR in the ischaemic myocardium. Enhanced clearance of 99mTc-sestamibi was observed in ischaemic segments with RR (P<0.001). Echocardiography demonstrated that 24 out of 25 segments with RR and 61 out of 86 segments without RR had wall motion abnormalities. Dobutamine infusion improved wall motion in 20 (83%) of the 24 dysfunctional segments with RR and 33 (54%) of the 61 dysfunctional segments without RR (P<0.02). These findings suggest that RR indicates reversible functional abnormalities associated with preserved contractile reserve in response to dobutamine. The early and delayed imaging of 99mTc-sestamibi provides useful information regarding the residual viability of the dysfunctional myocardium in AMI patients.

Acute Disease↗

PubMed2001

Identification of a genetic determinant of pathogenicity in chicken anaemia virus.

The molecular basis of pathogenicity of the chicken anaemia virus (CAV) needs to be clarified in order to develop a safe, live virus vaccine. In this study, several high- and low-pathogenic infectious DNA clones were obtained from field virus samples after 12 or 38 passages in MDCC-MSB1 cells. The high-pathogenic clones induced a low haematocrit, low weight gain and high mortality. Nucleotide sequence analyses identified one amino acid, at residue 394 of the VP1 capsid protein, as a major determinant of pathogenicity. To determine the role of this amino acid in pathogenicity, chimeric infectious DNA clones and point-mutated clones were used for chicken pathogenicity tests. These analyses clearly demonstrated that residue 394 of VP1 was crucial for the pathogenicity of CAV; all of the cloned viruses with glutamine at this position were highly pathogenic, whereas those with histidine had low pathogenicity. Low-pathogenic CAV, based on an infectious DNA clone, is a candidate for a genetically homogeneous and stable CAV live vaccine.

Amino Acid Sequence↗

PubMed2001

Intergenic suppression between the flagellar MS ring protein FliF of Salmonella and FlhA, a membrane component of its export apparatus.

The MS ring of the flagellar basal body of Salmonella is an integral membrane structure consisting of about 26 subunits of a 61-kDa protein, FliF. Out of many nonflagellate fliF mutants tested, three gave rise to intergenic suppressors in flagellar region II. The pseudorevertants swarmed, though poorly; this partial recovery of motile function was shown to be due to partial recovery of export function and flagellar assembly. The three parental mutants were all found to carry the same mutation, a six-base deletion corresponding to loss of Ala-174 and Ser-175 in the predicted periplasmic domain of the FliF protein. The 19 intergenic suppressors identified all lay in flhA, and they consisted of 10 independent examples at the nucleotide level or 9 at the amino acid level. Since two of the nine corresponded to different substitutions at the same amino acid position, only eight positions in the FlhA protein have given rise to suppressors. Thus, FliF-FlhA intergenic suppression is a fairly rare event. FlhA is a component of the flagellar protein export apparatus, with an integral membrane domain encompassing the N-terminal half of the sequence and a cytoplasmic C-terminal domain. All of the suppressing mutations lay within the integral membrane domain. These mutations, when placed in a wild-type fliF background, had no mutant phenotype. In the fliF mutant background, mutant FlhA was dominant, yielding a pseudorevertant phenotype. Wild-type FlhA did not exert significant negative dominance in the pseudorevertant background, indicating that it does not compete effectively with mutant FlhA for interaction with mutant FliF. Mutant FliF was partially dominant over wild-type FliF in both the wild-type and second-site FlhA backgrounds. Membrane fractionation experiments indicated that the fliF mutation, though preventing export, was mild enough to permit assembly of the MS ring itself, and also assembly of the cytoplasmic C ring onto the MS ring. The data from this study provide genetic support for a model in which at least the FlhA component of the export apparatus physically interacts with the MS ring within which it is housed.

Amino Acid Substitution↗

PubMed2001

Imported parakeets harbor H9N2 influenza A viruses that are genetically closely related to those transmitted to humans in Hong Kong.

In 1997 and 1998, H9N2 influenza A viruses were isolated from the respiratory organs of Indian ring-necked parakeets (Psittacula Krameri manillensis) that had been imported from Pakistan to Japan. The two isolates were closely related to each other (>99% as determined by nucleotide analysis of eight RNA segments), indicating that H9N2 viruses of the same lineage were maintained in these birds for at least 1 year. The hemagglutinins and neuraminidases of both isolates showed >97% nucleotide identity with those of H9N2 viruses isolated from humans in Hong Kong in 1999, while the six genes encoding internal proteins were >99% identical to the corresponding genes of H5N1 viruses recovered during the 1997 outbreak in Hong Kong. These results suggest that the H9N2 parakeet viruses originating in Pakistan share an immediate ancestor with the H9N2 human viruses. Thus, influenza A viruses with the potential to be transmitted directly to humans may be circulating in captive birds worldwide.

Amino Acid Sequence↗

PubMed2001

Impaired distensibility of the left ventricle after stiffening of the right ventricle.

Acute and chronic alterations of right ventricular (RV) wall properties can change left ventricular (LV) performance. We investigated whether and how stiffening of the RV free wall alters LV diastolic distensibility. We used cross-circulated isolated hearts, in which the LV and RV were independently controllable. Stiffness of the RV free wall was altered by intramuscular injections of glutaraldehyde into the RV free wall after right coronary artery ligation. We measured circumferential and longitudinal regional lengths in the septum and LV free wall. During data acquisition, RV volume was held constant. After the RV free wall was stiffened by glutaraldehyde, the LV diastolic pressure-volume relation shifted upward and became steeper. Importantly, stiffening of the RV free wall increased the diastolic regional area in the septum and LV free wall under constant LV volume. The augmented regional dimensions may result in enhanced regional tension under constant LV volume and may be related to the observed increase in LV diastolic intracavitary pressure. The impaired LV diastolic distensibility by stiffening of the RV free wall may be at least partly explained by myocardial stretch, probably due to LV deformation.

Animals↗

PubMed2001

Myopathic form of very-long chain acyl-coa dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.

In a 14-year-old Japanese girl, manifested recurrent myalgia with elevated serum creatine kinase after moderate exercise became evident, and she was diagnosed as having a myopathic form of very-long chain acyl-CoA dehydrogenase deficiency. Her first clinical symptom of the disease was evident when she was 6 y of age. She had never had hypoglycemic attacks, and hepatomegaly and cardiomyopathy were absent. The diagnosis was suspected on the basis of the urinary organic acid profile after a 36-h fast, long-chain fatty acid-loading test, and the blood acylcarnitine profile. Acyl-CoA dehydrogenase activity with palmitoyl-CoA as a substrate was severely decreased in her fibroblasts, and the amount of very-long chain acyl-CoA dehydrogenase protein was reduced. She was a compound heterozygote of A416T from her father and R450H from her mother. Transient expression of mutant A416T cDNA retained a significant residual acyl-CoA dehydrogenase activity of 10% and 20% normal at 37 degrees C and 30 degrees C, respectively. Specific activity of A416T mutant protein was calculated to be one fifth that of control. In the case of R450H mutant expression, a low residual acyl-CoA dehydrogenase activity of 5% normal was detected at 30 degrees C although significant activity was absent at 37 degrees C. The R450H protein was not detected at 37 degrees C but was clearly detected at one fourth the normal amount at 30 degrees C. These results indicate that both mutations were temperature-sensitive mild mutations, the result being the mildest phenotype of very-long chain acyl-CoA dehydrogenase deficiency.

Acyl-CoA Dehydrogenase, Long-Chain↗