Search PubMed⌕ Search

Biomedical subjects

T Tsuda

Publications and source records attributed to T Tsuda.

At least 55 records · Page 3Linked to original sources

Skeletal aspects of the atlanto-occipital fusion in a Japanese brown calf.

Atlanto-occipital fusion in a Japanese Brown calf was examined morphologically, paying special attention to skeletal changes. At the craniovertebral junction, the basal occipital bone fused to the cranial extremity of the ventral arch of the atlas with the rudiment of the atlantal centrum. The dens was not formed at the axis. These changes suggest that a hypocentrum and a centrum of the atlas derived from the first cervical sclerotome had failed to separate the occipital base from the proatlantal sclerotome including the apical element of the dens. Although a developmental disturbance at the cervical and thoracic vertebrae was also associated, critical neurological signs such as ataxia and paralysis were absent.

Animals↗

[Causal inference in medicine--decision making].

In the field of occupational medicine, either when we consider some preventive plans or when we make decisions to compensate for occupational diseases, it has been necessary to discuss causality between work and disease. Furthermore, epidemiologic causality has recently been used in risk assessment in occupational and environmental settings. We have shown that the law of causality in medicine is recognized as probability and continuous variables. Such a law of causality has been recognized in the same way as probability in physics, too, and has been regarded as a model of science. Physicists and mathematicians had claimed the importance of probability in causal inference as well as the principle of uncertainty before it was discovered. We, then, explained Etiologic Fraction (EF), Attributable Proportion for the Exposed Population (APE), Probability of Causation (PC), and so on. The PC has been used to ascertain the conditional probability in an individual case of a disease having been caused by a particular prior exposure, by using the experience of exposed populations to determine the appropriate relative risk, and this has been used for compensation for exposed cases. Next the applicability of information from a population to individuals was presented. Third, we provided a brief historical aspect of epidemiology. The evolutions in Epidemiology have been very rapid, so we pointed out that, in Japan, we could observe many incommensurable phenomena in epidemiologists and physicians depending on the era which was studied by them. Fourth, we discussed judgement and political application based on epidemiologic evidence, using Yanagimoto's classification is also taken or not should be estimated and compared. We presented several examples of reasoning in judgements. Lastly, we discussed several tasks and assignments for the future of epidemiology.

Causality↗

Protection of mice from LPS-induced shock by CD14 antisense oligonucleotide.

CD14 is a pattern recognition receptor on myeloid cells and plays a pivotal role in an innate immune system that is responsible for Gram-negative and Gram-positive bacteria infection. Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, can induce production of a large quantity of proinflammatory cytokines into the circulation mediated by CD14-mediated macrophages and monocytes. These cytokines eventually cause septic shock. Several in vitro and in vivo studies have shown that suppression of a CD14 function by a CD14 antibody led to an inhibition of the production of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and IL-8. In the present study, we found that CD14 antisense oligonucleotide (ODN) can prevent lethal LPS shock in D-galactosamine-sensitized mice. This ODN inhibited CD14 expression in a mouse macrophage cell line, RAW264.7, and suppressed production of TNF-alpha in LPS-stimulated RAW264.7 cells. Furthermore, we designed a consensus antisense ODN that could hybridize human and mouse CD14 RNA, and we evaluated its efficacy. The consensus antisense ODN rescued mice primed with Mycobacterium bovis bacillus Calmette-Guerin (BCG) from the LPS-induced lethal shock. In this model, the CD14 antisense ODN down-regulated LPS-elicited CD14 expression in the liver, resulting in a decrease in LPS-induced TNF-alpha production. These findings suggest that the CD14 antisense ODN is distributed in the liver and efficiently suppresses LPS-induced TNF-alpha production by reducing CD14 expression on Kupffer cells. This CD14 antisense ODN may be useful for the development of a therapeutic agent against sepsis and septic shock.

Animals↗

Aortic aneurysm involving a right-sided arch complicating aortobronchopulmonary and aortoesophageal fistula.

A 66-year-old man with hemoptysis, chest pain, fever, and hoarseness was admitted to our department. A right-sided aortic arch and three aneurysms in the proximal arch, distal arch, and descending aorta were confirmed by aortography and surgery. Fistula formations were discovered between the proximal arch aneurysm and the right upper lobe (aortobronchopulmonary fistula: ABF), and between the descending aorta and the esophagus (aortoesophageal fistula: AEF). Concomitant ABF and AEF are very rare. Aortopulmonary and/or aortoesophageal fistula complicated by a right-sided aortic arch have not been previously reported.

Aged↗

[Relationship between atopic factors and physical symptoms induced by gaseous formaldehyde exposure during an anatomy dissection course].

Formaldehyde (FA) is an occupational and general indoor hazard often affecting the respiratory airways. One of the main causes of multiple chemical sensitivity is gaseous FA, and it has become an important social problem in developed countries. FA concentrations in anatomy dissection classrooms are thought to be higher than under usual circumstances. The number of students developing physical symptoms during the anatomy dissection course in our university has been increasing over recent years. We planned to clarify the causes of such symptoms. Ninety-five medical students were interviewed using a questionnaire about allergic histories, physical symptoms developed during the anatomy dissection course, and symptoms related to chemical sensitivity up to three months after the course had finished. We measured total IgE, specific IgE to FA and specific IgE to house dust mites. Eighty-three percent of students had experienced symptoms, such as burning eyes, nasal discharge, sore throat, general fatigue or skin irritation during the course. Fifty percent of students had a past history of atopic disease. Fifty-eight percent of students tested positive to specific IgE to house dust mites; however, only one student, who did not complain of any symptoms during the course, tested positive to FA-IgE. Students with atopic factors (present histories of atopic diseases and higher total IgE) and/or chemical sensitivity demonstrated worse physical symptoms during the anatomy dissection course than students without such histories. In conclusion, it is suggested that gaseous FA exposure may exacerbate basic allergic symptoms, and moreover that people with chemical sensitivity demonstrated worse symptoms following gaseous FA exposure. Nevertheless, in our study we find no relationship between FA-IgE and the physical symptoms of gaseous FA exposure during or following an anatomy dissection course.

Air Pollutants↗

[A case of chronic hypersensitivity pneumonitis due to wild pigeons].

A 61-year-old woman was admitted to the Oita Medical University Hospital because of a nonproductive cough and exertional dyspnea. Interstitial changes had been seen on her chest radiograph 5 years previously, but no respiratory symptoms were identified at that time. On admission, chest radiography revealed linear and ground-glass opacities in the middle and lower lung fields. Computed tomography provided evidence of bronchiectasis and micro-honeycombing of the lungs, while lymphocyte and neutrophil counts in the bronchoalveolar lavage fluid were increased. Transbronchial lung biopsy demonstrated alveolitis and Masson's bodies. The patient was not a pigeon breeder, but she could have been exposed to pigeons at her workplace. Indeed, she had specific antibodies against pigeon serum and droppings, and her peripheral lymphocytes showed proliferation in response to pigeon serum. A positive provocation test involving inhalation of pigeon serum confirmed that she had chronic hypersensitivity pneumonitis caused by allergy to pigeons. This is a rare case of chronic hypersensitivity pneumonitis associated with wild pigeons, that progressed to pulmonary fibrosis. Antigen provocation testing proved to be of great value.

Alveolitis, Extrinsic Allergic↗

[A case of neuro-Behçet's disease presenting with chorea].

A 46-year-old man was admitted to our hospital because of emotional instability and involuntary movement of the right upper limb. Neurological examination revealed inability to concentrate, emotional incontinence, recent memory disturbance, chorea of bilateral upper limbs and neck, and bilateral pyramidal signs. Brain MRI showed atrophy of bilateral caudate nucleus and diffuse abnormal intensity area with low intensity on T1-weighted images and high intensity on T2-weighted images in cerebral white matter around the lateral ventricles. Huntington's disease was suspected at first, but it was ruled out by DNA analysis. After admission, oral and genital aphthae developed and the CSF examination showed pleocytosis (273 leukocytes/mm3; 39 polymorphonuclear leukocytes and 234 lymphocytes), so we diagnosed this case as neuro-Behçet's disease. Although basal ganglia is occasionally involved in neuro-Behçet's disease, chorea is rare. Neuro-Behçet's disease should be considered as a cause of chorea.

Behcet Syndrome↗

Mechanism for the peroxynitrite scavenging activity by anthocyanins.

We show that anthocyanins can function as potent inhibitors of the formation of nitrated tyrosine in vitro, and clarified how pelargonidin (Pel), which has a mono-hydroxyl group on the B-ring, can scavenge peroxynitrite (ONOO(-)) by detection of the reaction products. Pel was reacted with ONOO(-), then the reaction mixture was analyzed using high-performance liquid chromatography (HPLC). The HPLC analyses showed two novel peaks assumed to be the reaction products. Based on the instrumental analyses, the reaction products were identified as p-hydroxybenzoic acid and 4-hydroxy-3-nitrobenzoic acid. Pel can protect tyrosine from undergoing nitration through the formation of p-hydroxybenzoic acid and 4-hydroxy-3-nitrobenzoic acid.

Anthocyanins↗

Increased production of beta-amyloid and vulnerability to endoplasmic reticulum stress by an aberrant spliced form of presenilin 2.

An alternative spliced form of the presinilin 2 (PS2) gene (PS2V) lacking exon 5 has previously been reported to be expressed in human brains in sporadic Alzheimer's disease (AD). PS2V encodes the amino-terminal portion of PS2, which contains residues Met1-Leu119 and 5 additional amino acid residues (SSMAG) at its carboxyl terminus. Here we report that PS2V protein impaired the signaling pathway of the unfolded protein response, similarly to familial AD-linked PS1 mutants and caused significant increases in the production of both amyloid beta40 and beta42. Interestingly, PS2V-encoding protein was expressed in neuropathologically affected neurons of the hippocampal CA1 region and temporal cortex in AD patients. These findings suggest that the aberrant splicing of the PS2 gene may be implicated in the neuropathology of sporadic AD.

Alternative Splicing↗

High prevalence of spinocerebellar ataxia type 1 (SCA1) in an isolated region of Japan.

Autosomal dominant cerebeller ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders that differ in both the clinical manifestations and modes of inheritance. At present, eight different genes causing ADCAs have been found: spinocerebeller ataxia type 1 (SCA1), SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA8, SCA12 and dentatorubropallidoluysian atrophy (DRPLA). The relative prevalence of each mutation varies according to race and native place. We studied 117 unrelated ADCA families that originated from the Tohoku District in the northernmost part of Honshu Island in Japan (mainly Miyagi Prefecture in the central part of Tohoku District). The SCA1 mutation was the most frequent among the known disorders (24.8% of all such families). The relative prevalence of SCA1 in the Tohoku District is very high compared with the values already reported from other regions in the world. Because the population of this area had seldom moved, the alleles with SCA1 mutations (including alleles with an intermediate CAG repeat number) are assumed to have been present in this area for a long time.

Ataxin-1↗

Determination of 4-nonylphenol, nonylphenol monoethoxylate, nonylphenol diethoxylate and other alkylphenols in fish and shellfish by high-performance liquid chromatography with fluorescence detection.

A simple and highly sensitive method is described for the HPLC determination of 4-nonylphenol (NP), 4-nonylphenol mono- (NP1EO) and diethoxylates (NP2EO) in fish and shellfish together with bisphenol A (BPA), 4-tert.-butylphenol (BP) and 4-tert.-octylphenol (OP). The NP, NP1EO, NP2EO and other alkylphenols in the samples are extracted with acetonitrile and the lipid in the sample extract is eliminated by partitioning between hexane and acetonitrile. After Florisil PR clean-up the sample extract is analyzed by HPLC with a fluorescence detection. Recoveries in Japanese smelt, carp and corbicura are 81.8-84.3% for NP, 83.5-84.3% for NP1EO, 90.5-96.2% for NP2EO, 70.7-72.9% for BPA, 71.0-73.4% for BP and 77.1-83.2% for OP spiked at 0.5 microg each chemical per 5 g of the fish and shellfish samples. The detection limits are 2 ng/g for NP, NP1EO and NP2EO, and 1ng/g for BPA, BP and OP.

Animals↗

Impaired chemosensitivity and perception of dyspnoea in Parkinson's disease.

Exacerbation of respiratory failure in Parkinson's disease could be the result of impaired perception of hypoxia. We assessed chemosensitivity to hypoxia and hypercapnia and perception of dyspnoea on the Borg scale in 25 patients (Hoehn and Yahr stage 2-3) and 11 controls. Chemosensitivity to hypoxia, but not that in response to hypercapnia, was lower in patients than in controls (0.196 [SE 0.030] vs 0.525 [0.360]; p=0.012); the mean Borg score was lower in patients than in controls under hypoxic conditions (2.9 [SD 1.4] vs 4.8 [2.1]; p=0.0015). Thus, even at an early stage of disease, patients with Parkinson's disease had a subnormal hypoxic response accompanied by blunted perception of dyspnoea.

Awareness↗

The Asn-420-linked sugar chain in human epidermal growth factor receptor suppresses ligand-independent spontaneous oligomerization. Possible role of a specific sugar chain in controllable receptor activation.

To elucidate a role(s) of Asn-linked sugar chain(s) in the function of epidermal growth factor receptor (EGFR), a series of the EGFR mutants were prepared in which potential glycosylation sites in the domain III were eliminated by site-directed mutagenesis. Although the wild-type and mutants of Asn-328, Asn-337, and Asn-389 underwent autophosphorylation in response to epidermal growth factor (EGF), the Asn-420 --> Gln mutant was found to be constitutively tyrosine-phosphorylated. This abnormal ligand-independent phosphorylation of the mutant appears to be due to a ligand-independent spontaneous oligomer formation, as shown by a cross-linking experiment using the purified soluble extracellular domain (sEGFR). As revealed by the dissociation of the Asn-420 --> Gln sEGFR oligomer by simple dilution, it seems likely that the equilibrium is shifted toward oligomer formation to an unusual degree. Furthermore, it was also found that the mutation caused a loss of the ability to bind EGF. These findings suggest that the sugar chain linked to Asn-420 plays a crucial role in EGF binding and prevents spontaneous oligomerization of the EGFR, which may otherwise lead to uncontrollable receptor activation, and support the view of a specific role of an Asn-linked sugar chain in the function of a glycoprotein.

Asparagine↗

Direct temperature-controlled trapping system and its use for the gas chromatographic determination of organic vapor released from human skin.

For controlling of trap temperature, the relationship between electric resistance of the trap tube and temperature is used. As the electric resistance of the trap tube (20 cm long stainless steel tubing) was very small, such as ca. 0.040 ohm for -70 degrees C and ca. 0.064 ohm for +90 degrees C, it was estimated by using the value of voltage output at both ends of the trap tube when a direct current (5 A) was applied for 6.5 ms at every 100 ms on the trap. By using this temperature measurement, a cycle of trapping is shortened, especially at the process of desorption, because it is possible to set a large increasing rate of temperature, such as 20 degrees C/s. The present trapping system has faster temperature response compared to that with a thermocouple. This system was applied for the study of the releasing of ethanol and water vapors from the human finger, which was treated as follows: dipping in 10% ethanol aqueous solution for 1 min, followed by washing with water and then drying in the air. In this case, a cycle of trapping took 53 s, and the period of total analysis was only 3 min. The present system is an efficient tool for the study of the exhalation of organic vapors from human skin.

Chromatography, Gas↗

A novel mutation of the McLeod syndrome gene in a Japanese family.

McLeod syndrome is a rare X-linked hematologic and neuromuscular disorder manifested by chorea, myopathy, cardiomyopathy, areflexia, hyperCKemia, and acanthocytosis. Only four mutations have been reported in the gene responsible for McLeod syndrome. We report a novel gene mutation in a Japanese family. Direct sequencing of the PCR-amplified genomic DNA revealed the mutation was a single C-nucleotide insertion at codon 151 in exon 2 of the XK gene, which resulted in a 3'-frameshift. Study of family members revealed that the patient's mother was a manifesting carrier heterozygous for this mutation.

DNA Mutational Analysis↗

Redefined substrate specificity of ST6GalNAc II: a second candidate sialyl-Tn synthase.

The acceptor substrate specificities of ST6GalNAc I and II, which act on the synthesis of O-linked oligosaccharides, were reexamined using ovine submaxillary mucin, [Ala-Thr(GalNAc)-Ala]n polymer (n = 7-11). It has been suggested that only ST6GalNAc I can synthesize carbohydrate structures of sialyl-Tn-antigen; i.e., NeuAc alpha2-6GalNAc-O-Thr/Ser [Kurosawa et al., J. Biol. Chem. 269, 19048-19053 (1994)] based on the result that ST6GalNAc I, not ST6GalNAc II, exhibited activity toward asialoagalacto-fetuin. In this study, we present evidence that both ST6GalNAc I and II exhibit activity toward asialo-OSM (ovine submaxillary mucin) and [Ala-Thr(GalNAc)-Ala]n polymer (n = 7-11) which have only the GalNAc-O-Thr/Ser-structures. These results strongly indicate that not only ST6GalNAc I but also II are candidates for sialyl-Tn synthases.

Animals↗