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T Takao

Publications and source records attributed to T Takao.

At least 37 records · Page 2Linked to original sources
PubMed2001

Usefulness of thyrotropin (TSH)-releasing hormone test and nocturnal surge of TSH for diagnosis of isolated deficit of TSH secretion.

Six patients with idiopathic isolated deficit of TSH secretion were examined and reported on. Their clinical symptoms and routine biochemical data were unclear and were not specific for hypothyroidism. Serum triiodothyronine, free thyroxine and TSH levels were slightly low or low-normal. Basal metabolic rate and thyroidal (123)I-uptake were also slightly low or low-normal. The response of serum TSH to TRH stimulation was blunted in all patients. No nocturnal surge of serum TSH level could be seen in any of the patients. Empty sella was revealed in three patients, and pituitary microadenoma in one patient via magnetic resolution imaging. Antihuman pituitary cytosol antibody was seen in five patients. Autoimmunity may have played a role in the pathogenesis of idiopathic isolated TSH deficiency. Routine examination of thyroid function cannot easily detect this disease. TSH response to TRH stimulation and nocturnal surge of TSH should be examined when this disease is suspected.

Adult↗
PubMed2001

[A giant testicular tumor detected with dyspnea due to lung metastases: a case report].

A 19-year-old male presented with dyspnea. Clinical examination revealed the left infant-head-sized testicular tumor, multiple lung metastases and retroperitoneal bulky lymph node metastasis with marked elevation of serum lactic dehydrogenase (LDH) and alpha-fetoprotein. Left radical orchiectomy followed by the chemotherapy with etoposide and cisplatin (EP) for 4 cycles was performed. The tumor weighed 1,700 g, and was pathologically diagnosed as mixed germ cell tumor consisting of embryonal carcinoma and yolk sac tumor. After the treatment, the tumor markers were normalized with partial response (PR) of lung metastases and complete response (CR) of retroperitoneal lymph node metastasis. Thereafter, biopsy of lung metastases through video-assisted thoracoscopic surgery (VATS) was performed, and pathologically no viable cells were detected. Five months after the treatment, he was seized with convulsion due to brain metastasis with hemorrhage. Therefore, a surgical resection of brain metastasis and 2nd line chemotherapy with etoposide, ifosfamide and cisplatin (VIP) chemotherapy for 3 cycles was performed. The patient has been free of recurrence for 21 months after the 2nd line chemotherapy.

Adult↗
PubMed2001

[Usefulness of 99mTc-methoxy-isobutyl-isonitrile scintigraphy for preoperative localization of adenoma in primary hyperparathyroidism].

We evaluated the usefulness of 99mTc-methoxy-isobutyl-isonitrile (MIBI) dual phase scintigraphy for detecting hyperfunctioning parathyroid adenoma. We retrospectively reviewed 18 hyperparathyroid patients who received MIBI prior to neck exploration and compared the radiological findings of MIBI with ultrasonography (US) and magnetic resonance imaging (MRI). Fifteen patients were studied with MRI, and 17 patients were examined with US. All patients were found to have a solitary parathyroid adenoma histopathologically. MIBI correctly revealed the location of 17 adenomas among 18 confirmed tumors. In our series, there was one false-positive case that was found to have thyroid adenoma. The diagnostic sensitivity of MIBI MRI and US was 94.4%, 80% and 52.5%, respectively. The positive predictive value (PPV) was 94.4% for MIBI, 81.8% for MRI and 92.3% for US. We conclude that MIBI is useful and accurate for the preoperative localization of adenoma in primary hyperparathyroidism.

Adenoma↗
PubMed2001

[An autopsy case of dementia with motor neuron disease accompanying Alzheimer's disease lesion].

We report the case of a 60-year-old man with autopsy-proven dementia with motor neuron disease (D-MND) and Alzheimer's disease lesion. The patient presented with clumsiness of his right hand at the age of 55 years old and subsequently developed dysarthria, weakness and atrophy of his upper limbs. He was unaffectionate towards his family, repeated the same phrase, and showed severe disorientation of time and place. Neurological examination on admission showed not only diffuse lower motor neuron signs, such as weakness, atrophy, fasciculation and areflexia in both upper limbs, but also dementia (HDS-R 9/30). He died of respiratory insufficiency. Neuropathological examination showed mild atrophy of the frontal and temporal lobes and anterior spinal roots. Microscopic examination of cortical sections revealed degenerative changes with simple atrophy and gliosis, and these changes were predominant in layers 1 and 2 of the frontal and temporal cortices. Using immunohistochemical staining, ubiquitin-positive but tau-negative inclusions were frequently found in neurons of the hippocampal granular cell layers and temporal lobes. Many senile plaques and neurofibrillary tangles were present in all sections of the brain. Our final diagnosis was dementia with motor neuron disease accompanying Alzheimer's disease lesion, because of hypoperfusion in the parietal lobe as well as the frontal lobe demonstrated by SPECT, and the presence of many senile plaques and neurofibrillary tangles in the cerebral cortex. Overlapping of pathologically-proven D-MND and Alzheimer's disease lesion is extremely rare, and this case may improve our understanding of the process of neurodegeneration.

Alzheimer Disease↗
PubMed2000

A ubiquitin-like system mediates protein lipidation.

Autophagy is a dynamic membrane phenomenon for bulk protein degradation in the lysosome/vacuole. Apg8/Aut7 is an essential factor for autophagy in yeast. We previously found that the carboxy-terminal arginine of nascent Apg8 is removed by Apg4/Aut2 protease, leaving a glycine residue at the C terminus. Apg8 is then converted to a form (Apg8-X) that is tightly bound to the membrane. Here we report a new mode of protein lipidation. Apg8 is covalently conjugated to phosphatidylethanolamine through an amide bond between the C-terminal glycine and the amino group of phosphatidylethanolamine. This lipidation is mediated by a ubiquitination-like system. Apg8 is a ubiquitin-like protein that is activated by an E1 protein, Apg7 (refs 7, 8), and is transferred subsequently to the E2 enzymes Apg3/Aut1 (ref. 9). Apg7 activates two different ubiquitin-like proteins, Apg12 (ref. 10) and Apg8, and assigns them to specific E2 enzymes, Apg10 (ref. 11) and Apg3, respectively. These reactions are necessary for the formation of Apg8-phosphatidylethanolamine. This lipidation has an essential role in membrane dynamics during autophagy.

Amino Acid Sequence↗
PubMed2000

The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway.

Autophagy and the Cvt pathway are examples of nonclassical vesicular transport from the cytoplasm to the vacuole via double-membrane vesicles. Apg8/Aut7, which plays an important role in the formation of such vesicles, tends to bind to membranes in spite of its hydrophilic nature. We show here that the nature of the association of Apg8 with membranes changes depending on a series of modifications of the protein itself. First, the carboxy-terminal Arg residue of newly synthesized Apg8 is removed by Apg4/Aut2, a novel cysteine protease, and a Gly residue becomes the carboxy-terminal residue of the protein that is now designated Apg8FG. Subsequently, Apg8FG forms a conjugate with an unidentified molecule "X" and thereby binds tightly to membranes. This modification requires the carboxy-terminal Gly residue of Apg8FG and Apg7, a ubiquitin E1-like enzyme. Finally, the adduct Apg8FG-X is reversed to soluble or loosely membrane-bound Apg8FG by cleavage by Apg4. The mode of action of Apg4, which cleaves both newly synthesized Apg8 and modified Apg8FG, resembles that of deubiquitinating enzymes. A reaction similar to ubiquitination is probably involved in the second modification. The reversible modification of Apg8 appears to be coupled to the membrane dynamics of autophagy and the Cvt pathway.

Amino Acid Sequence↗
PubMed2000

Modulation of type I interleukin-1 receptor messenger RNA followed by one and repeated endotoxin treatment in the mouse.

The expression of transcripts for type 1 interleukin-1 receptors (IL-1R1) were investigated utilizing reverse transcription-polymerase chain reaction (RT-PCR) techniques in male C57BL/6 mice. First, we measured IL-1R1 mRNA 1, 2, 6, and 12 h after a single injection of endotoxin lipopolysaccharide (LPS; 30 microg/mouse). IL-1R1 mRNA was measured in relevant tissues utilizing semiquantitative RT-PCR. IL-1R1 mRNA levels were significantly increased 2 and 6 h after one LPS injection group in comparison with the saline injection group in the hippocampus and testis. Next, we investigated the effect of repeated injections of LPS on IL-1R1 expression. LPS or saline were injected at 24-h intervals for 4 consecutive days. The mice were divided into four groups: (1) LPS injections for 4 days and LPS injection on day 5 (LPS-LPS); (2) LPS injections for 4 days and saline injection on day 5 (LPS-saline); (3) saline injections for 4 days and LPS injection on day 5 (saline-LPS); (4) saline injections for 4 days and saline injection on day 5 (saline-saline). The mice were sacrificed by decapitation 2 h after the last injection. In the hippocampus and pituitary gland, significant increases of IL-1R1 mRNA levels were observed in the saline-LPS group, however, the increases were attenuated in LPS-LPS group. IL-1R1 mRNA levels in the hypothalamus were unchanged in all four groups. In the adrenal gland and testis, IL-1R1 mRNA levels were significantly increased in the LPS-LPS group as well as saline-LPS group. These data demonstrate differential regulation of IL-1R1 mRNA by one and repeated endotoxin treatment and suggest the importance of the cytokines in mediating the effects of infectious challenge on brain, endocrine and immune function during endotoxemia.

Adrenal Glands↗
PubMed2000

Chemical structure of nuclear proteins which are phosphorylated during meiotic maturation of starfish oocytes.

Oocytes of the starfish, Asterina pectinifera, are arrested at the G2 phase of meiosis I and possess a prominent germinal vesicle in which maternal stores of nuclear proteins which are destined for use primarily by the early embryo are stored. Germinal vesicle breakdown and subsequent oocyte maturation is triggered by activation of the p34(cdc2)/cyclin B complex, which is present as the preform in the cytoplasm. The aim of the present study was to identify and biochemically characterize in vivo substrates of the kinase. Two nucleic acid binding nuclear proteins designated NAAP1 and NAAP2 were found, both of which contain 345 amino acid residues with pI 3. 6 and which serve as substrates. The only difference between the two proteins was in the primary amino acid sequence at position 51, which is Asn in NAAP1 but Thr in NAAP2. NAAPs are phosphorylated in vivo during oocyte maturation but not at the meiotic G(2) stage. NAAPs are phosphorylated in vitro by the cdc2 kinase on the same site as in vivo. Although there are other evolutionarily conserved consensus sequences for phosphorylation by mitotically active cdc2 kinase in NAAPs and NAAP-derived fragments containing the sequences were efficiently phosphorylated in vitro, these sites in the intact NAAPs were not phosphorylated either in vivo or in vitro. These results suggest that the tertiary structure of NAAPs affects the target specificity of the cdc2 kinase.

Amino Acid Sequence↗
PubMed2000

Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases.

The Src family of protein tyrosine kinases (Src-PTKs) is important in the regulation of growth and differentiation of eukaryotic cells. The activity of Src-PTKs in cells of different types is negatively controlled by Csk, which specifically phosphorylates a conserved regulatory tyrosine residue at the carboxy-terminal tail of the Src-PTKs. Csk is mainly cytoplasmic and Src-PTKs are predominantly membrane-associated. This raises a question about the mechanism of interaction between these enzymes. Here we present Cbp--a transmembrane phosphoprotein that is ubiquitously expressed and binds specifically to the SH2 domain of Csk. Cbp is involved in the membrane localization of Csk and in the Csk-mediated inhibition of c-Src. In the plasma membrane Cbp is exclusively localized in the GM1 ganglioside-enriched detergent-insoluble membrane domain, which is important in receptor-mediated signalling. These findings reveal Cbp as a new component of the regulatory mechanism controlling the activity of membrane-associated Src-PTKs.

Amino Acid Sequence↗
PubMed2000

Activation of rho through a cross-link with polyamines catalyzed by Bordetella dermonecrotizing toxin.

The small GTPase Rho, which regulates a variety of cell functions, also serves as a specific substrate for bacterial toxins. Here we demonstrate that Bordetella dermonecrotizing toxin (DNT) catalyzes cross-linking of Rho with ubiquitous polyamines such as putrescine, spermidine and spermine. Mass spectrometric analyses revealed that the cross-link occurred at Gln63, which had been reported to be deamidated by DNT in the absence of polyamines. Rac1 and Cdc42, other members of the Rho family GTPases, were also polyaminated by DNT. The polyamination, like the deamidation, markedly reduced the GTPase activity of Rho without affecting its GTP-binding activity, indicating that polyaminated Rho behaves as a constitutively active analog. Moreover, polyamine-linked Rho, even in the GDP-bound form, associated more effectively with its effector ROCK than deamidated Rho in the GTP-bound form and, when microinjected into cells, induced the anomalous formation of stress fibers indistinguishable from those seen in DNT-treated cells. The results imply that the polyamine-linked Rho, transducing signals to downstream ROCK in a novel GTP-independent manner, plays an important role in DNT cell toxicity.

3T3 Cells↗
PubMed2000

Increased adrenocorticotropin responses to acute stress in Otsuka Long-Evans Tokushima Fatty (type 2 diabetic) rats.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new diabetic strain of rats whose disease closely resembles human type 2 diabetes. We measured plasma adrenocorticotropic hormone (ACTH) and corticostrone levels, and iodine-125-labeled ovine corticotropin-releasing factor ([125I]oCRF) binding in the anterior pituitary after ether-laparotomy stress in OLETF rats to examine the alteration of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, we examined ACTH secretion following CRF administration in vivo and in vitro to characterize the mechanisms regulating the HPA axis in OLETF rats. Body weight, plasma glucose and insulin levels in OLETF rats were significantly higher than that in Long-Evans Tokushima Otsuka (LETO) rats. Basal plasma ACTH levels tended to be higher in OLETF rats than in LETO but it did not reach statistical significance. Ether-laparotomy stress dramatically increased plasma ACTH levels at 2 h after the stress both in either OLETF and LETO rats; the peak plasma ACTH level in OLETF rats following the stress was significantly greater than in LETO rats. Plasma ACTH levels following CRF (2 microg/kg, i.v.) in OLETF and LETO rats showed statistically significant increases at 10 and 30 min after CRF administration compared to ACTH levels at 0 min, however, the peak plasma ACTH level in OLETF rats at 10 min after CRF administration was significantly greater than in LETO rats. In contrast to ACTH levels, no significant differences in corticosterone levels between OLETF and LETO were observed at any of the time points. CRF (10 ng/ml) significantly increased ACTH secretion in pituitary cultures from OLETF compared to LETO rats. These data reveal a complex regulation of the endocrine system in this diabetic condition and suggest that HPA axis may be more stimulated during acute stress in diabetes mellitus than in unaffected subjects.

Acute Disease↗
PubMed2000

Automated interpretation of low-energy collision-induced dissociation spectra by SeqMS, a software aid for de novo sequencing by tandem mass spectrometry.

SeqMS, a software aid for de novo sequencing by tandem mass spectrometry (MS/MS), which was initially developed for the automated interpretation of high-energy collision-induced dissociation (CID) MS/MS spectra of peptides, has been applied to the interpretation of low-energy CID and post-source decay (PSD) spectra of peptides. Based on peptide backbone fragmented ions and their related ions, which are the dominant ions observed in the latter two techniques, the types of ions and their propensities to be observed have been optimized for efficient interpretation of the spectra. In a typical example, the modified SeqMS allowed the complete sequencing of a 31-amino acid synthetic peptide, except for the isobaric amino acids (Leu or Ile, and Lys or Gln), based on only the low-energy CID-MS/MS spectrum.

Amino Acid Sequence↗
PubMed2000

Differentiating alpha- and beta-aspartic acids by electrospray ionization and low-energy tandem mass spectrometry.

Spectra obtained by low-energy electrospray ionization tandem mass spectrometry (ESI-MS/MS) of 34 peptides containing aspartic acids at position n were studied and unambiguously differentiated. beta-Aspartic acid yields an internal rearrangement similar to that of the C-terminal rearrangements of protonated and cationized peptides. As a result of this rearrangement, two different ions containing the N- and the C-terminal ends of the original peptide are formed, namely, the bn-1 + H2O and y"l - n + 1 - 46 ions, respectively, where e is the number of amino acid residues in the peptide. The structure suggested for the y"l - n + 1 - 46 ion is identical to that proposed for the vn ions observed upon high-energy collision-induced dissociation (CID) experiments. The intensity of these ions in the low-energy MS/MS spectra is greatly influenced by the presence and position of basic amino acids within the sequences. Peptides with a basic amino acid residue at position n - 1 with respect to the beta-aspartic acid yield very intense bn-1 + H2O ions, while the y"l - n + 1 - 46 ion was observed mostly in tryptic peptides. Comparison between the high- and low-energy MS/MS spectra of several isopeptides suggests that a metastable fragmentation process is the main contributor to this rearrangement, whereas for long peptides (40 AA) CID plays a more important role. We also found that alpha-aspartic acid containing peptides yield the normal immonium ion at 88 Da, while peptides containing beta-aspartic acid yield an ion at m/z 70, and a mechanism to explain this phenomenon is proposed. Derivatizing isopeptides to form quaternary amines, and performing MS/MS on the sodium adducts of isopeptides, both improve the relative intensity of the bn + 1 + H2O ions. Based on the above findings, it was possible to determine the isomerization sites of two aged recombinant growth proteins.

Amino Acid Sequence↗
PubMed2000

Novel rearranged ions observed for protonated peptides via metastable decomposition in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

C-terminal rearrangement ions [b(n-1) + H2O] (where n refers to the total number of residues of peptides) are frequently observed for peptides which contain basic amino acid(s), especially arginine, at or near their N termini in low- and high-energy collision-induced dissociation or post-source decay (PSD) spectra. Here we report a novel rearrangement, associated with PSD for serine- or threonine-containing peptides that are susceptible to C-terminal rearrangement. Based on PSD analyses of serine- or threonine-containing bradykinin and its analogs, which have been ethyl-esterified or 18O labeled at their C termini, the [b(k) + H2O] (where k denotes the position adjacent to the left of the Ser/Thr residue) ion is generally thought to be formed by the transfer of the hydroxyl moiety of a serine or threonine residue to the carbonyl group of the residue to its left accompanied by the loss of the remaining C-terminal portion of the peptide. When the Ser/Thr is at or near the C terminus, the present [b(k) + H2O] ion could be formed via two pathways, i.e., the Ser/Thr-related rearrangement and the conventional C-terminal rearrangement, which has been clearly verified by 18O labeling at the C terminus. In addition, the ions which are formally designated as [y(m)b(l) + H2O], where y(m)b(l) denotes a b-type internal ion, are also briefly described.

Bradykinin↗
PubMed2000

Immunohistochemistry of chondromodulin-I in the human intervertebral discs with special reference to the degenerative changes.

The expression of the matrix protein chondromodulin-I has been studied in human intervertebral discs of 101 people using immunohistochemical analyses. The purpose of this report is to present data on the metabolic changes that were found to occur in the chondrocytes of intervertebral discs during development and aging. Chondromodulin-I was highly expressed during the gestational period and gradually decreased after maturation. It was detected in both the extracellular matrix and chondrocytes in the zone of hypertrophic cartilage, the zone of proliferative cartilage and the zone of resting cartilage in fetal discs. It was also present in the annulus fibrosus, nucleus pulposus and end-plate cartilage in mature discs. In degenerative discs, chondromodulin-1 immunoreactivity tended to be elevated in the remaining chondrocytes. Our findings suggest that the expression of the protein is developmentally regulated and upregulated through a defense mechanism against the degenerative processes of the aged intervertebral disc.

Adolescent↗
PubMed2000

Effect of orchidectomy on the age-related modulation of IL-1beta and IL-1 receptors following lipopolysaccharide treatment in the mouse.

OBJECTIVE: To compare the effect of orchidectomy (ODX) in 7- and 24-week-old C57BL/6 mice on the age-related responses of the cytokine interleukin (IL)-1beta and its receptor to intraperitoneal injection of the bacterial endotoxin, lipopolysaccharide (LPS). METHODS: We measured IL-1beta concentrations in the plasma, hippocampus, hypothalamus and adrenal gland using ELISA and iodine-125-labeled recombinant human IL-1alpha ([(125)I]IL-1alpha) binding in the hippocampus following the intraperitoneal administration of saline or LPS. RESULTS: There were no significant differences in the concentrations of IL-1beta and its receptors in the brain and peripheral tissues between sham-operated and ODX mice in both age groups injected with saline. LPS induced significantly higher IL-1beta production in the plasma and hippocampus in sham-operated 24-week-old mice than in 7-week-old mice. Coincident with the heightened IL-1beta response to LPS, hippocampal [(125)I]IL-1alpha binding was lower in 24-week-old mice than in 7-week-old mice after LPS injection in the sham-operated group. The age-related differences in the IL-1beta concentrations in the plasma and hippocampus and [(125)I]IL-1alpha binding in the hippocampus in response to LPS administration were abolished by ODX. Although LPS dramatically increased IL-1beta levels in the hypothalamus, no significant age-related differences in IL-1beta concentrations were seen, and ODX did not affect IL-1beta levels. In contrast, there were no significant differences between saline- and LPS-injected 7-week-old mice in relation to concentrations in the adrenal gland. Moreover, although the adrenal IL-1beta concentrations in 24-week-old mice were significantly higher than those in 7-week-old mice, ODX did not abolish these age-related differences in concentrations in the adrenal gland. CONCLUSIONS: Our data suggest the involvement of testosterone (or gonadal product) in plasma and hippocampal IL-1beta regulation in relation to age, and demonstrate the importance of the gonadal development in mediating the effects of infectious challenge on the brain and immune function.

Adrenal Glands↗