Biomedical subjects

T Nakajima

Publications and source records attributed to T Nakajima.

At least 73 records · Page 4Linked to original sources

PubMed2002

A patient homozygous for the SCA6 gene with retinitis pigmentosa.

The present authors studied a 55-year-old-patient homozygous for the SCA6 gene who experienced frequent attacks of positional vertigo at 37 years of age with subsequent staggering gait and night blindness. Retinitis pigmentosa (RP), as well as cerebellar ataxia and vertical antidirectional nystagmus, were detected. The subject's parents were first cousins, and two of his three male cousins, whose parents were also first cousins, had RP without ataxia or nystagmus. The numbers of CAG repeats in the expanded alleles of the SCA6 gene found by molecular analysis were 21 and 21. The genetic results were negative for SCA1, SCA2, SCA3, SCA7 and dentatorubral pallidoluysian atrophy. The retinal degeneration in this patient is most likely to be secondary to a genetic disorder of autosomal or X-linked recessive inheritance rather than SCA6. Other reported cases of patients homozygous for the SCA6 gene are also reviewed.

Calcium Channels↗

PubMed2002

Gastrin interferes with the differentiation of gastric pit cells and parietal cells.

BACKGROUND: Gastrin is known to have stimulatory effects on gastric mucosa; however, long-term effect of gastrin stimulation is not well known. AIM AND METHODS: To investigate the long-term effect of hypergastrinaemia, we established hypergastrinaemic transgenic mice by introducing a mutated human gastrin gene. Homozygously transgene-expressing mice showed serum gastrin levels of more than 600 pg/mL. RESULTS: Neither progastrin nor glycine-extended gastrin titre elevation were observed in hypergastrinaemic transgenic mice. Stomachs from the 30-35-week-old transgenic mice were 30-50% heavier and their mucosa were markedly thicker than those of the controls. The hypertrophic gastric mucosa of hypergastrinaemic transgenic mice consisted of elongated pits with widespread proliferative zones, and comprised depleted glandular regions. In situ hybridization study indicated that expression of H, K-ATPase mRNA in parietal cells of hypergastrinaemic transgenic mice was markedly decreased. By gastrin binding assay in vivo, specific gastrin binding sites were observed in the mid-glandular region of hypergastrinaemic transgenic mice that consisted mainly of prepit cells. CONCLUSIONS: These results suggest that long-term stimulation of gastrin increases the expression of CCK-B/gastrin receptors in the less-differentiated pit cells that are the main component of elongated gastric units, and lessens the well-differentiated characteristics of parietal cells.

Animals↗

PubMed2002

Finite element analysis of the stresses around endosseous implants in various reconstructed mandibular models.

PURPOSE: To calculate the location and intensity of the maximum stresses occurring around implants in the reconstructed mandible. MATERIAL AND METHODS: Human preserved mandibles and fibulae were used to design 3-D mandibular models on a Desktop Computer. Various 3-D simulation models representing mandibles were made. Implants (fixtures) and superstructures were then embedded in each model and occlusal pressure was applied to the cantilever portion of the superstructure. Von Mises stress, the maximum and minimum principal stress on each model were calculated using finite element structural analysis software. Finally, evaluation of the stresses around each fixture hole was performed. RESULTS: It appeared that for each fixture hole, the direction and the magnitude of the stresses were influenced by complex factors such as the thickness of the cortical bone where the fixtures were embedded, the degree of vertical displacement under load, and the relationship between adjacent fixtures. CONCLUSION: Location and intensity of the stresses occurring around fixtures differs significantly between various types of mandibular reconstruction. Published by Elsevier Science Ltd.

Bite Force↗

PubMed2002

Mesial temporal lobe epilepsy with lateral temporal lobe abnormalities in magnetoencephalography and glucose metabolism.

Magnetoencephalography (MEG) and positron emission tomography (PET) revealed abnormal findings in the lateral temporal lobe of a 22 year old female with mesial temporal lobe epilepsy. Electroencephalography identified the epileptogenic focus in the left mesial temporal lobe and standard anterior temporal lobectomy resulted in a good surgical outcome. These discrepancies can be explained by the presence of anatomical and functional pathways between the mesial and lateral temporal structures, or pathophysiological abnormalities in both the mesial and lateral temporal lobes. Careful evaluation is necessary for analysis of MEG and PET findings in patients with temporal lobe epilepsy.

Adult↗

PubMed2002

Estimation of left ventricular systolic pressure by the left ventricular volume-time curve obtained from electrocardiograph gated 99m Tc-tetrofosmin single photon emission tomography using quantitative gated SPECT.

We report the estimation of left ventricular systolic pressure (LVSP) by a left ventricular (LV) volume-time curve obtained from electrocardiogram (ECG) gated 99mTc-tetrofosmin single photon emission computed tomography (SPECT) using quantitative gated SPECT (QGS). LVSP was calculated based on the following parameters: LV volumes, velocity and acceleration of LV contraction, aortic valve area and density of blood. The first three parameters can be derived from ECG gated SPECT. In 16 patients, the LV volume-time curve was obtained from ECG gated SPECT by using QGS. LVSP was estimated by the above-mentioned theory. The values of estimated peak LVSP were compared with those measured from a pressure transducer. There was a correlation between the values of peak LVSP estimated by the LV volume-time curve and those measured by pressure transducer (r=0.69, P<0.01). Using QGS, LVSP and the systolic LV pressure-volume relationship could be estimated by the LV volume-time curve.

Algorithms↗

PubMed2002

Regression of fundic gland polyps following acquisition of Helicobacter pylori.

The prevalence of Helicobacter pylori infection is very low in patients with fundic gland polyps (FGPs) of the stomach. We report here two cases with multiple FGPs that regressed following new H pylori acquisition. Patient Nos I and II had multiple FGPs in normal fundic mucosa without inflammatory changes or atrophy. Both were not infected with H pylori. Following acquisition of H pylori infection however, all FGPs in both patients completely disappeared except for one FGP in patient No I. Although the size of the remaining polyp in patient No I was greatly reduced after H pylori acquisition, it became enlarged again after eradication. Interestingly, in the remaining polyp, we found an activating beta-catenin gene mutation whereas no such mutations were detected in FGPs of patient No II. Thus H pylori infection may have an inhibitory effect on the development of FGPs.

Adult↗

PubMed2002

Apolipoprotein A-I concentration in tears in diabetic retinopathy.

BACKGROUND: Apolipoprotein concentrations in reflex tears from healthy and noninsulin-dependent diabetes mellitus (NIDDM) subjects were measured and correlated with the stage of diabetic retinopathy. METHODS AND RESULTS: The apolipoprotein A-I (apo A-I) concentrations in the tears from NIDDM patients with retinopathy were significantly higher than those from patients with no or negligible retinopathy (P<0.05), and apo A-I was not detected in healthy subjects by Western blotting. No reactive band was detected on apo A-I by Western blotting for nitrotyrosine, a marker for peroxynitrite oxidation of the tear proteins. Apo A-I concentration in tears was significantly correlated with the stage of retinopathy (r= 0.598, n = 59, P < 0.001). No apo A-I gene expression was detected in the conjunctiva by reverse transcription polymerase chain reaction. CONCLUSIONS: We conclude that there is increased secretion of native apo A-I from the main lacrimal gland in patients with advanced diabetic retinopathy.

Aged↗

PubMed2002

[Redo coronary artery bypass grafting using the patent left internal thoracic artery graft as an in flow with composite internal thoracic artery Y grafting; report of a case].

In redo coronary artery bypass grafting (CABG), graft selection and revascularization methods are major problems. We experienced a redo-CABG with occluded previous vein grafts. These grafts were to the circumflex artery and right coronary artery. We conducted operation using cardiopulmonary bypass. We at this operation, chose right internal thoracic artery (RITA) as a conduit and anastomosed it to the side of functioning left internal thoracic artery (LITA) graft, and then diogonal branch, posterolateral branch, and atrioventricular branch were revascularized with the RITA. Post operative course was uneventful. Internal thoracic artery (ITA) is superior to vein graft and other arterial graft as to long term patency. We believe composite Y graft with the use of bilateral ITA can be one of the revascularization strategy in redo CABG.

Coronary Artery Bypass↗

PubMed2002

Selection of surgical methods for infected infrarenal abdominal aortic aneurysms.

BACKGROUND: There is no standard treatment for patients with infected abdominal aortic aneurysm (AAA). To determine the basis for selection of a surgical method, we reviewed our experiences with all patients who underwent surgery for infected infrarenal AAA. METHODS: Between 1993 and 2000, 6 patients with infected infrarenal AAA underwent surgery. Extra-anatomic bypass grafting was performed in 2 of 3 patients with infection extending into the retroperitoneum. In situ grafting was performed in 3 patients with localized infection and in 1 patient with extended infection. RESULTS: Severe peritonitis occurred in 2 patients with extended infection in the early postoperative phase. One patient, who had undergone in situ grafting, died of sepsis. The other patient, who had undergone extra-anatomic bypass grafting, was treated by continuous irrigation with an electrolyzed strong acid aqueous solution (ESAAS). He recovered gradually and was discharged. After a follow-up period with a mean of 40 months (range: 17-102 months), all 5 patients who survived surgery are alive and asymptomatic. CONCLUSIONS: It was suggested that the method used for revascularization should be selected based on the degree of diffusion of infection. For a patient with extended infection, postoperative continuous irrigation with ESAAS appears to be effective in eradicating retroperitoneal infection.

Aged↗

PubMed2001

Anoplin, a novel antimicrobial peptide from the venom of the solitary wasp Anoplius samariensis.

A novel antimicrobial peptide, anoplin, was purified from the venom of the solitary wasp Anoplius samariensis. The sequence was mostly analyzed by mass spectrometry, which was corroborated by solid-phase synthesis. Anoplin, composed of 10 amino acid residues, Gly-Leu-Leu-Lys-Arg-Ile-Lys-Thr-Leu-Leu-NH2, has a high homology to crabrolin and mastoparan-X, the mast cell degranulating peptides from social wasp venoms, and, therefore, can be predicted to adopt an amphipathic alpha-helix secondary structure. In fact, the circular dichroism (CD) spectra of anoplin in the presence of trifluoroethanol or sodium dodecyl sulfate showed a high content, up to 55%, of the alpha-helical conformation. A modeling study of anoplin based on its homology to mastoparan-X supported the CD results. Biological evaluation using the synthetic peptide revealed that this peptide exhibited potent activity in stimulating degranulation from rat peritoneal mast cells and broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria. Therefore, this is the first antimicrobial component to be found in the solitary wasp venom and it may play a key role in preventing potential infection by microorganisms during prey consumption by their larvae. Moreover, this peptide is the smallest among the linear alpha-helical antimicrobial peptides hitherto found in nature, which is advantageous for chemical manipulation and medical application.

Amino Acid Sequence↗

PubMed2001

Genetic polymorphism in matrix metalloproteinase-9 and pulmonary emphysema.

Protease-antiprotease imbalance due to genetic variation may be responsible for the development of pulmonary emphysema induced by smoking. Since matrix metalloproteinases (MMPs) have recently been suggested to play important roles in the pathogenesis of pulmonary emphysema, the association between the functional polymorphism of MMP-9 (-1562C/T) and the development of pulmonary emphysema was examined in 110 smokers and 94 nonsmokers in Japan. The T allele frequency was higher in subjects with distinct emphysema on chest CT-scans (n = 45) than in those without it (n = 65) (0.244 vs 0.123, P = 0.02). Logistic regression analysis demonstrated that the T allele is a risk factor for smoking-induced emphysema (odds ratio = 2.69, P = 0.02). DL(CO)/VA was lower (P = 0.02) and emphysematous changes were more conspicuous (P = 0.03) in subjects with C/T or T/T (n = 35) than in those with C/C (n = 75). These results suggest that the polymorphism of MMP-9 acts as a genetic factor for the development of smoking-induced pulmonary emphysema.

Adult↗

PubMed2001

Solution structure of Ptu1, a toxin from the assassin bug Peirates turpis that blocks the voltage-sensitive calcium channel N-type.

Ptu1 is a toxin from the assassin bug Peirates turpis which has been demonstrated to bind reversibly the N-type calcium channels and to have lower affinity than the omega-conotoxin MVIIA. We have determined the solution structure of Ptu1 by use of conventional two-dimensional NMR techniques followed by distance-geometry and molecular dynamics. The calculated structure of Ptu1 belongs to the inhibitory cystin knot structural family (ICK) that consists of a compact disulfide-bonded core from which four loops emerge. Analysis of the 25 converged solutions indicates that the molecular structure of Ptu1 contains a 2-stranded antiparallel beta-sheet (residues 24-27 and 31-34) as the only secondary structure. The loop 2 that has been described to be critical for the binding of the toxin on the channel is similar in Ptu1 and MVIIA. In this loop, the critical residue, Tyr13, in MVIIA is retrieved in Ptu1 as Phe13, but the presence of an acidic residue (Asp16) in Ptu1 could disturb the binding of Ptu1 on the channel and could explain the lower affinity of Ptu1 toward the N-type calcium channel compared to the one of MVIIA. Analysis of the electrostatic charge's repartition gives some insights about the importance of the basic residues, which could interact with acidic residues of the channel and then provide a stabilization of the toxin on the channel.

Amino Acid Sequence↗

PubMed2001

Age-related hypermethylation of the hMLH1 promoter in gastric cancers.

To determine whether methylation of the hMLH1 promoter is related to increasing age and gastric carcinogenesis, we examined hMLH1 methylation and expression in 100 gastric cancers. hMLH1 methylation and aberrant protein expression were observed in 9 and 13 cancers, respectively. Normal and intestinal metaplastic tissues adjacent to cancers with hypermethylation did not exhibit any hMLH1 methylation, indicating that it may be specific to gastric cancers. The frequency of hMLH1 methylation significantly increased with age. These results suggest that hMLH1 methylation plays an important role in gastric carcinogenesis in old people.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Characterization of unique amphipathic antimicrobial peptides from venom of the scorpion Pandinus imperator.

Two novel antimicrobial peptides have been identified and characterized from venom of the African scorpion Pandinus imperator. The peptides, designated pandinin 1 and 2, are alpha-helical polycationic peptides, with pandinin 1 belonging to the group of antibacterial peptides previously described from scorpions, frogs and insects, and pandinin 2 to the group of short magainin-type helical peptides from frogs. Both peptides demonstrated high antimicrobial activity against a range of Gram-positive bacteria (2.4-5.2 microM), but were less active against Gram-negative bacteria (2.4-38.2 microM), and only pandinin 2 affected the yeast Candida albicans. Pandinin 2 also demonstrated strong haemolytic activity (11.1-44.5 microM) against sheep erythrocytes, in contrast with pandinin 1, which was not haemolytic. CD studies and a high-resolution structure of pandinin 2 determined by NMR, showed that the two peptides are both essentially helical, but differ in their overall structure. Pandinin 2 is composed of a single alpha-helix with a predominantly hydrophobic N-terminal sequence, whereas pandinin 1 consists of two distinct alpha-helices separated by a coil region of higher flexibility. This is the first report of magainin-type polycationic antimicrobial peptides in scorpion venom. Their presence brings new insights into the mode of action of scorpion venom and also opens new avenues for the discovery of novel antibiotic molecules from arthropod venoms.

Amino Acid Sequence↗

PubMed2001

Glycated high-density lipoprotein induces apoptosis of endothelial cells via a mitochondrial dysfunction.

Glycation of plasma proteins may contribute to an excess risk of developing atherosclerosis in patients with diabetes mellitus. Although it is believed that high-density lipoprotein (HDL) is nonenzymatically glycosylated at an increased level in diabetic individuals, little is known about a possible linkage between glycated HDL and endothelium dysfunction in diabetes. This study set out to clarify whether glucose-modified HDL affects the function of endothelial cells by examining the apoptosis of cultured human aortic endothelial cells (HAECs) exposed to a glycated-oxidized HDL (gly-ox-HDL) prepared in vitro. Incubation of HAECs with 100 microg/ml of gly-ox-HDL for 48 h showed apoptotic features, such as cell shrinkage, membrane blebbing, and concentration and fragmentation of the nucleus, and the degree of apoptosis was dose-dependent on the glucose used in the preparation of gly-ox-HDL. Stimulation of HAECs with gly-ox-HDL elicited a marked increase in caspase 3 activity and the expressions of active caspase 3 and caspase 9, whereas concomitant treatment with a caspase 3 inhibitor significantly blocked gly-ox-HDL-induced apoptosis of HAECs. The release of cytochrome c into cytosols markedly increased in HAECs during the treatment with gly-ox-HDL. The increased expressions of Bax and Bad were detected in HAECs incubated for 24 h with gly-ox-HDL, but gly-ox-HDL failed to interfere with the expression of Bcl-2 and Bcl-x. Moreover, in vitro experiments with HDL (gly-HDL) glycated in the presence of 2 mM EDTA and Cu(2+)-oxidized HDL suggested that the apoptotic effect of gly-ox-HDL on endothelial cells might be due to an additional oxidative modification of gly-HDL. Taken altogether, additional oxidation of HDL under hyperglycemic conditions may induce endothelial apoptosis through a mitochondrial dysfunction, following the deterioration of vascular function.

Aorta↗

PubMed2001

Simultaneous determination of ingredients in an ointment by hydrophobic interaction electrokinetic chromatography.

Hydrophobic interaction electrokinetic chromatography was used to simultaneously determine seven active ingredients (diphenhydramine hydrochloride, dibucaine hydrochloride, chlorhexidine hydrochloride, phenylephrine hydrochloride, hydrocortisone acetate, allantoin and tocopherol acetate) in an ointment. Not only hydrophobic but also ionic compounds were successfully separated by use of a separation solution composed of acetonitrile-water (80:20, v/v), tetradecylammonium salt and ammonium chloride. The migration behavior of the hydrophobic compound depended on tetradecylammonium concentration, while that of the ionic compounds depended on ammonium chloride concentration. An addition of triethylamine to the separation solution markedly improved the reproducibility of the peak areas of cations with a relative standard deviation (RSD) of less than 1.7% (n=6). The established method was validated and confirmed to be applicable to the determination of the active ingredients in a commercial ointment. Sample preparation was performed by liquid-liquid extraction and no interference from the formulation excipients was observed. Good linearities were obtained, with correlation coefficients above 0.999. Recoveries and precisions ranged from 98.0 to 100.8%, and from 0.4 to 2.9% RSD, respectively. These results suggest that hydrophobic interaction electrokinetic chromatography can be used for the determination of ionic compounds as well as hydrophobic compounds in ointment.

Chromatography, Micellar Electrokinetic Capillary↗

PubMed2001

IsCT, a novel cytotoxic linear peptide from scorpion Opisthacanthus madagascariensis.

A novel cytotoxic linear peptide, IsCT, was characterized from scorpion Opisthacanthus madagascariensis. It is a linear peptide with a molecular weight of 1501.9 Da composed of 13 amino acid residues without cysteines. MS/MS analysis showed that its C-terminal is amidated. The identity of IsCT is re-confirmed by comparing the chemical synthesized peptide with the natural one. IsCT demonstrated antimicrobial activity against both gram-positive and gram-negative bacteria and hemolytic activity to sheep red blood cells. Also, it can release histamine from rat peritoneal mast cells. The CD absorption suggested that IsCT had an alpha-helix configuration in aqueous TFE. IsCT is one of the shortest natural cytotoxic peptides described, and it will be a suitable model for studying peptide-lipid interactions.

Amino Acid Sequence↗

PubMed2001

Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11.

Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, a devastating condition with high morbidity and mortality. Angiographic and autopsy studies show that IA is a common disorder, with a prevalence of 3%-6%. Although IA has a substantial genetic component, little attention has been given to the genetic determinants. We report here a genomewide linkage study of IA in 104 Japanese affected sib pairs in which positive evidence of linkage on chromosomes 5q22-31 (maximum LOD score [MLS] 2.24), 7q11 (MLS 3.22), and 14q22 (MLS 2.31) were found. The best evidence of linkage is detected at D7S2472, in the vicinity of the elastin gene (ELN), a candidate gene for IA. Fourteen distinct single-nucleotide polymorphisms (SNPs) were identified in ELN, and no obvious allelic association between IA and each SNP was observed. The haplotype between the intron-20/intron-23 polymorphism of ELN is strongly associated with IA (P=3.81x10-6), and homozygous patients are at high risk (P=.002), with an odds ratio of 4.39. These findings suggest that a genetic locus for IA lies within or close to the ELN locus on chromosome 7.

3' Untranslated Regions↗