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Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 73 records · Page 4Linked to original sources
PubMed2001

Neural tube defects and neuroepithelial cell death in Tulp3 knockout mice.

The tubby-like protein 3 (Tulp3) gene has been identified as a member of a small novel gene family which is primarily neuronally expressed. Mutations in two of the family members, tub and tulp1, have been shown to cause neurosensory disorders. To determine the in vivo function of Tulp3, we have generated a germline mutation in the mouse Tulp3 gene by homologous recombination. Embryos homozygous for the Tulp3 mutant allele exhibit failure of neural tube closure, and die by embryonic day 14.5. Failure of cranial neural tube closure coincided with increased neuroepithelial apoptosis specifically in the hindbrain and the caudal neural tube. In addition, the number of betaIII-tubulin positive cells is significantly decreased in the hindbrain of Tulp3(-/-) embryos. These results suggest that disruption of the Tulp3 gene affects the development of a neuronal cell population. Interestingly, some Tulp3 heterozygotes also manifest embryonic lethality with neuroepithelial cell death. Our results demonstrate that the Tulp3 gene is essential for embryonic development in mice.

Animals↗
PubMed2001

Isolation and characterization of the Schizosaccharomyces pombe cDNA encoding the mitochondrial endonuclease(1).

We isolated the cDNA of the fission yeast mitochondrial endonuclease SpNUC1, which consists of 322 amino acids and has a significant homology with the budding yeast NUC1 and mammalian endonuclease G. Comparison of the cDNA sequence with the genomic sequence showed that the gene consists of three exons and two introns and spans 1.31 kb. The enzyme localization in mitochondria was demonstrated by expressing the SpNUC1-green fluorescent protein fusion in the yeast. The endonuclease was activated by truncation of the amino-terminal region of the protein, indicating that the enzyme is encoded as an inactive precursor. The active enzyme degraded single-stranded DNA and RNA, the activity being dependent on Mg(2+) (Mn(2+)).

Amino Acid Sequence↗
PubMed2001

Molecular orientation near the surface of a smectic liquid crystal cell showing V-shaped switching by means of attenuated total internal reflection ellipsometry.

Attenuated total internal reflection ellipsometry was used to probe the molecular orientation and switching near the surface of a smectic liquid crystal cell showing V-shaped switching. We find that the switching occurs collectively near the surface as in the bulk. The molecules form a twisted state, but the twist angle relative to the bulk layer normal is small because of compensating twist of the smectic layer normal. As a result, a rather uniform molecular orientation is produced, resulting in high extinction and a high contrast ratio in the absence of a field.

Journal Article↗
PubMed2001

Tumor necrosis factor alpha polymorphism associated with increased susceptibility to development of adult T-cell leukemia/lymphoma in human T-lymphotropic virus type 1 carriers.

Human T-lymphotropic virus type 1 (HTLV-1) is etiologically associated with adult T-cell leukemia/lymphoma (ATL). Nevertheless, most individuals infected with HTLV-1 do not develop ATL. To attempt to identify genetic factors promoting the progression to ATL, we investigated in HTLV-1 carriers the relationship between susceptibility to ATL and several polymorphisms: the three "decreased-detoxifying" polymorphisms in GSTM1, GSTT1, and CYP1A1, the "proapoptotic" polymorphism in BCL2, and the five "high-production" polymorphisms in tumor necrosis factor alpha (TNF-alpha) using PCR-based genotyping assays. ATL patients (n = 71) were younger than HTLV-1 carriers (n = 80; 57 +/- 12 versus 63 +/- 10 years; P = 0.0017). MALE:female ratio in ATL patients was higher than in carriers (52:19 versus 19:61, respectively; P < 0.0001), probably reflecting a higher incidence of HTLV-1 infection in females and a higher incidence of development of ATL in males. We found that the frequency of the TNF-alpha-857T allele, reported to be associated with high transcriptional activity of the promoter/enhancer region of the TNF-alpha gene, was enriched in individuals with ATL compared with healthy carriers (18.3% versus 8.8%, respectively; odds ratio, 2.34; 95% confidence interval, 1.2-4.7). None of the other four TNF-alpha polymorphisms was a significant indicator of risk of development of ATL, although odds ratios (ATL versus carrier) of all of the TNF-alpha polymorphisms were higher than 1.0. Furthermore, analysis of polymorphisms for GSTM1, GSTT1, CYP1A1, and BCL2 showed no significant difference between ATL patients and healthy carriers. Genetic polymorphism leading to increased TNF-alpha production may enhance susceptibility to ATL among HTLV-1 carriers. Alternatively, but less likely, the HLA loci might be an important factor because the TNF-alpha gene lies within the class III region of the MHC; however, the 857T allele is not in linkage disequilibrium with HLA alleles associated with ATL development.

Carrier State↗
PubMed2001

Expression of survivin in HTLV-I-infected T-cell lines and primary ATL cells.

Human T-cell leukemia virus type I (HTLV-I) is the etiological agent of adult T-cell leukemia (ATL), although the precise mechanisms involved in the transformation process have not yet been defined. Deregulated inhibition of apoptosis may facilitate the insurgence of leukemia. Survivin is an inhibitor of apoptosis and considered to play a role in oncogenesis. We investigated the expression of survivin in HTLV-I-infected T-cell lines and primary ATL cells. Northern blot analysis showed expression of survivin transcript in all 9 HTLV-I-positive T-cell lines. High survivin expression levels were detected in primary cells of patients with acute-type ATL, but no such expression was noted in the cells of chronic-type ATL or normal peripheral blood mononuclear cells. Treatment of an HTLV-I-infected T-cell line, MT-1, with survivin specific antisense oligonucleotide resulted in reduced cell growth. Our results suggest that expression of survivin may play an important role in the development and pathogenesis of ATL.

Acute Disease↗
PubMed2001

Solid-like mechanical behaviors of ovalbumin aqueous solutions.

Flow and dynamic mechanical properties of ovalbumin (OVA) aqueous solutions were investigated. OVA solutions exhibited relatively large zero-shear viscosity values under steady shear flow and solid-like mechanical responses against oscillating small shear strains, that is, the storage modulus was always larger than the loss modulus in the examined frequency range (0.1--100 rad s(-1)). These results suggest that dispersed OVA molecules arranged into a colloidal crystal like array stabilized by large interparticle repulsive forces. However, marked solid-like mechanical behaviors were detected even when electrostatic repulsive forces among protein molecules were virtually absent, which could not be explained solely on the basis of conventional Derjaguin--Landau--Verwey--Overbeek (DLVO) theory. Large non-DLVO repulsive forces seem to stabilize native OVA aqueous solutions.

Ovalbumin↗
PubMed2001

The effects of angiotensin IV analogs on long-term potentiation within the CA1 region of the hippocampus in vitro.

Within the brain-renin angiotensin system, it is generally assumed that angiotensin peptide fragments shorter than angiotensins II and III, including angiotensin IV (AngIV), are inactive. This belief has been challenged by the recent discovery that AngIV, and AngIV-like analogs, bind with high affinity and specificity to a putative angiotensin binding site termed AT4. In the brain these sites include the hippocampus, cerebellum, and cerebral cortex, and influence associative and spatial learning tasks. The present study investigated the effects of two AngIV analogs, Nle1-AngIV (an AT4 receptor agonist) and Nle1-Leual3-AngIV (an AT4 receptor antagonist), on long-term potentiation (LTP). Field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 stratum radiatum following stimulation of the Schaffer collateral pathway. Activation of AT4 receptors by Nle1-AngIV enhanced synaptic transmission during low-frequency test pulses (0.1 Hz), and increased the level of tetanus-induced LTP by 63% over that measured under control conditions. Paired stimulation before and during infusion of Nle1-AngIV indicated no change in paired-pulse facilitation (PPF) as a result of AT4 receptor activation suggesting that the underlying mechanism(s) responsible for Nle1-AngIV-induced increase in synaptic transmission and LTP is likely a postsynaptic event. Further, applications of Nle1-Leual3-AngIV prior to, but not 15 or 30 min after, tetanization prevented stabilization of LTP. These results extend previous findings from behavioral data in that AT4 receptor agonists and antagonists are capable of activating, and inhibiting, learning and memory pathways in the hippocampus, and suggest that the AT4 receptor subtype is involved in synaptic plasticity.

Angiotensin II↗
PubMed2001

Multiple sclerosis with secondary syringomyelia. An autopsy report.

We report an elderly woman with multiple sclerosis who showed an extensive cavity formation in the midthoracic cord in addition to multiple abnormal intensity signals in the central nervous system on magnetic resonance imaging (MRI). The cavity decreased in size in response to corticosteroid therapy with an improvement in neurological symptoms. The autopsy demonstrated a slit-like cavity lined with no ependymal cells on the luminal surface in the lower cervical to midthoracic cord, with circumferentially distributed demyelinative lesions, leading to the pathological diagnosis of secondary syringomyelia. In this patient a limited necrosis formed in the spinal cord might have developed into a cavity formation with edematous fluid leading to subsequent episodes of neurological exacerbation.

Aged↗
PubMed2001

Li K-edge spectra of lithium halides.

We measured the Li K-edge spectra of lithium halides by means of total electron yield method (TEY), using the soft x-ray Beam Line 2 (BL2) of the compact synchrotron radiation facility at Ritsmeikan University in Japan. In lithium halides, the spectra have a sharp peak at about 60eV and a broad peak at the higher energy side. Various peak structures that appear in the absorption spectra are assigned to the corresponding Li-1s to valence band free orbitals transitions, which have been calculated by the Discrete Variational (DV)-Xalpha molecular orbital calculation method.

Journal Article↗
PubMed2001

Determination of double decker sandwich structured La-substituted chlorophyll a by EXAFS.

As a representative natural porphyrin derivative, it is interesting to know the chemical form of lanthanide in chlorophyll a. We select the natural fern dicranopteris dichotoma, the most lanthanide-concentrated plant known, to isolate the chlorophyll a for our study. It is found by EXAFS that lanthanum substitutes in the magnesium position in chlorophyll and coordinates with the porphyrin ring. The lanthanum is seen to have a similar coordination structure to a sandwich-type lanthanide complex, with the La surrounded by eight nitrogen atoms from two porphyrin rings with average La-N bond length of 2.65 A.

Chlorophyll↗
PubMed2001

Brain SPECT with 123I-IMP for the early diagnosis of Creutzfeldt-Jakob disease.

We performed brain CT and single-photon emission computed tomography (SPECT) using N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) as a tracer in the early stage of seven patients with Creutzfeldt-Jakob disease (CJD). In four of the patients, we determined absolute values of regional cerebral blood flow (rCBF) in the frontal, temporal, parietal and occipital lobes, thalamus and cerebellum using an autoradiographic method with a single blood sample. Brain CT demonstrated no abnormal findings other than a mild age-related atrophy in all patients except for one patient with a low-density area in the left cerebellar hemisphere due to an old hemorrhage, whereas SPECT revealed a decreased uptake of the tracer in various parts of the cerebral cortex of all patients, sometimes in an asymmetrical pattern. Absolute values of rCBF showed a significant decrease in all examined regions of the patients as against healthy controls (P<0.0001). In three patients, SPECT demonstrated a decreased uptake throughout the cerebral cortex on visual inspection, whereas absolute values of rCBF revealed an obvious decrease of the uptake also in the thalamus and cerebellum. These results suggest that SPECT with quantification of rCBF using 123I-IMP might be a sensitive and useful technique not only for detecting a focal metabolic dysfunction but also for diagnosis in the early stage of CJD.

Aged↗
PubMed2001

Dietary restriction impairs neutrophil exudation by reducing CD11b/CD18 expression and chemokine production.

HYPOTHESIS: Patients with malnutrition are susceptible to infection. Polymorphonuclear neutrophils (PMNs) are the major effector of the nonspecific immune response in host resistance to infection. Dietary restriction may impair PMN-mediated immunity in the peritoneal cavity by reducing PMN exudation, adhesion molecule expression on PMNs, and chemokine production. DESIGN: Randomized study of murine glycogen-induced peritonitis with dietary restriction. SETTING: University research laboratory. MATERIALS: Male C57BL/6J mice. INTERVENTIONS: Mice (N = 204) were assigned to ad libitum, moderate, and severe diet-restricted groups receiving mouse chow ad libitum (132 g/kg, 66 g/kg, and 33 g/kg daily for 7 days, respectively). After dietary restriction with or without 1 day of refeeding, mice were administered glycogen intraperitoneally to induce cell exudation. MAIN OUTCOME MEASURES: CD11b, CD18, and CD62L expressions on circulating PMNs, phagocytosis, and reactive oxygen intermediate production by exudative PMNs were measured after glycogen installation. The levels of PMN-specific chemokine, macrophage inflammatory protein 2 (MIP-2), in peritoneal lavage fluid were also measured. These parameters were measured after glycogen installation in the refeeding experiment. RESULTS: Seven days of dietary restriction decreased CD11b/CD18 expression on circulating PMNs, MIP-2 levels in peritoneal lavage fluid, and subsequent PMN exudation into the peritoneal cavity early in peritonitis. Both CD11b and CD18 expression on circulating PMNs and MIP-2 levels correlated significantly with numbers of exudative PMNs. Seven days of dietary restriction also impaired phagocytosis, while up-regulating reactive oxygen intermediate production by exudative PMNs. Only 1 day of ad libitum refeeding normalized CD11b/CD18 expression with PMN exudation into the peritoneal cavity. CONCLUSIONS: Short-term dietary restriction impairs PMN exudation into local inflammatory sites in murine peritonitis by reducing CD11b/CD18 expression and MIP-2 production. Even brief nutritional replenishment in diet-restricted patients may improve host defense via restoring these PMN functions and chemokine production at local inflammatory sites.

Animals↗
PubMed2001

Structural changes during heat-induced gelation of globular protein dispersions.

Macroscopic and molecular structural changes during heat-induced gelation of beta-lactoglobulin, bovine serum albumin, ovalbumin, and alpha-lactalbumin aqueous dispersions were probed by the mechanical and CD spectroscopy, respectively. Aqueous solutions of the native globular proteins, except for alpha-lactalbumin, exhibited solid-like mechanical spectra-namely, the predominant storage modulus G' over the loss modulus G" in the entire frequency range examined (0.1-100 rad/s), suggesting that these protein solutions were highly structured even before gelation, possibly due to strong repulsions among protein molecules. Such solid-like structures were susceptible to nonlinearly large shear but recovered almost immediately at rest. During gelation by isothermal heating, major changes in the secondary structure of the globular proteins completed within a few minutes, while values of the modulus continued to develop for hours with maintaining values of tandelta (= G"/G') less than unity. As a result, a conventional criterion for mechanically defining the gelation point, such as a crossover between G' and G", was inapplicable to these globular protein systems. beta-Lactoglobulin gels that had passed the gelation point satisfied power laws (G' approximately G" approximately omega(n)) believed to be valid only at the gelation point, suggesting that fractal gel networks, similar to those of critical gels (i.e., gels at the gelation point), were formed.

Circular Dichroism↗
PubMed2001

Abnormal activity in the globus pallidus in off-period dystonia.

Pallidotomy was performed in a parkinsonian patient with off-period foot dystonia. Dystonia appeared at the beginning of surgery and disappeared after the first microelectrode penetration of the globus pallidus, perhaps a micropallidotomy effect. Neuronal recording during dystonia revealed that the mean firing rates were low in both the internal and external segments of the globus pallidus, and that firing was irregular in the internal segment of the globus pallidus, compared with firing patterns in offstate parkinsonian patients without dystonia. These firing patterns immediately changed into those of nondystonic, off-state parkinsonism after relief of dystonia These results suggest that off-period dystonia results from the same physiological change in the basal ganglia as that in primary dystonia.

Dystonia↗
PubMed2001

Neuronal activity in the globus pallidus in chorea caused by striatal lacunar infarction.

Pallidotomy was performed in a patient with hemichorea caused by lacunar infarction in the striatum. Chorea in the lower limb was reduced after a neurosurgical lesion in the medial portion of the sensorimotor territory of the internal segment of the globus pallidus, and chorea in the upper limb disappeared after an additional lesion in the lateral portion of that same area. Intraoperative neuronal recording revealed that mean firing rates were low, and that firing was irregular in the globus pallidus compared with off-state parkinsonian patients. These results suggest that chorea with striatal infarction is driven by phasic neuronal activity with a low firing rate in the globus pallidus and that the neural pathway of chorea has a functional somatotopical organization in the globus pallidus.

Action Potentials↗
PubMed2001

Drugs of abuse in a non-conventional sample; detection of methamphetamine and its main metabolite, amphetamine in abusers' clothes by HPLC with UV and fluorescence detection.

In this paper, we report the detection of methamphetamine and its major metabolite, amphetamine, in garments belong to known-abusers. These compounds were extracted from the textile using a mixture of chloroform:propan-2-ol (3:1, v/v), derivatized with 4-(4,5-diphenyl-1H-imidazol-2-yl) benzoyl chloride and separated using a reversed-phase high-performance liquid chromatography. The derivatives were detected by measuring either fluorescence at 440 nm or absorbance at 330 nm. By using 1-methyl-3-phenyl propylamine as an internal standard, calibration curves of spiked textile samples were linear over a wide range with correlation coefficients of 0.997 or better. Detection limits at a signal-to-noise ratio of 3 were less than or equal to 37.3 and 0.4 pg on column for the high-performance liquid chromatography-ultraviolet and -fluorescence detection methods, respectively. Intra- and inter-day variations at high and low concentrations (n > or = 3) were < or =12.7%. The developed methods were successfully applied to the determination of methamphetamine and amphetamine in clothes samples belong to abusers.

1-Propanol↗