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Biomedical subjects

I Tatsuno

Publications and source records attributed to I Tatsuno.

At least 37 records · Page 2Linked to original sources
PubMed2000

Glucocorticoid-dependency on GH secretion and tumor growth in a GH-producing pituitary adenoma with Cushing's syndrome.

We report a rare case of a 40-year-old woman with Cushing's syndrome and Acromegaly. At the age of 28 she was diagnosed with Cushing's syndrome due to a left adrenal tumor concomitant with a GH-producing pituitary tumor. Before adrenal surgery her basal GH levels were extremely high and CT scanning revealed a high-density mass in the sella turcica. A 28 g left adrenocortical adenoma was removed by adrenalectomy. During the four months after the adrenalectomy, basal GH levels dramatically decreased and the high-density mass detected by CT scanning had disappeared but the basal GH levels and IGF-1 had not been normalized. She gradually became acromegalic in the twelve years after the adrenalectomy. At the age of 40 CT scanning showed reappearance of the pituitary tumor. In order to examine the glucocorticoid dependency on GH secretion, we compared the GH secretion in a series of endocrinological tests before and after oral 8 mg dexamethasone administration for 7 days. There was no difference between before and after dexamethasone administration in the GH secreting pattern, but basal GH levels were apparently increased after dexamethasone treatment. Transsphenoidal surgery was done and pathological examination showed a GH-producing pituitary adenoma. In vitro, dexamethasone increased GH secretion from the cultured GH-producing adenoma cells in a dose-dependent manner. In this case, both GH secretion and pituitary tumor growth seemed to be dependent on glucocorticoid.

Acromegaly↗
PubMed2000

Octreotide improved ventricular arrhythmia in an acromegalic patient.

We saw a remarkable effect of octreotide, the long-acting somatostatin analogue, in reducing the number of ventricular premature complexes (VPCs) in a 59-year-old woman with acromegaly. Her basal GH and IGF-1 levels were up to 22.9 ng/ml and 934.9 ng/ml respectively. MRI revealed a 14 x 12 x 10 mm mass lesion in the pituitary gland. She had hypertension and echocardiography showed an increase in left ventricular wall thickness. Electric cardiography showed the presence of frequent VPCs and 24-h Holter monitoring revealed 24,277 beats of multifocal VPCs/24 h. She was treated with 300 microg/day of octreotide for four weeks before transsphenoidal surgery. After octreotide treatment, GH and IGF-1 were suppressed to 1.8 ng/ml and 145.3 ng/ml respectively, and the tumor size was remarkably reduced. Furthermore, the number of VPCs was also dramatically reduced to 2062 VPCs/24-h (8.5% of pretreatment) with 24-h Holter monitoring. This case shows that VPCs of acromegalic patients can be controlled by suppressing GH and IGF-1 with octreotide, and this agent is useful for reducing both tumor size and frequency of VPCs prior to surgery.

Acromegaly↗
PubMed2000

Cavernous sinus invasion and tumor proliferative potential of growth hormone-producing pituitary tumors.

PURPOSE: Surgical removal of growth hormone-producing pituitary adenomas (GHomas) becomes difficult when they invade the cavernous sinus (CS). We investigated the relation among tumor proliferative potential, tumor volume and invasion of GHomas to CS. MATERIALS & METHODS: 15 patients with GHoma aged 20-59 years were enrolled. The volumes of the adenomas were calculated from MR images and the extension to CS was classified into 5 grades according to Knosp's grading system. The immuno-histochemical staining for anti-Ki-67 monoclonal antibody (MIB-1) was performed and the proliferative potential of GHomas was determined as the percentage of MIB-1 labeled nuclei (MIB-1 index). The volume, MIB-1 index and pre-operative growth hormone (GH) level were compared with CS invasion by single and multiple regression analyses. RESULTS: With single regression analyses, CS invasion was significantly correlated with both the volume (r=0.69, p<0.01) and MIB-1 index (r=0.73, p<0.01), but not with the GH level (r=0.42, p=0.12). The volume and MIB-1 index showed a weak correlation but it was not significant (r=0.52, p=0.06). With multiple regression analysis, CS invasion was well explained by the volume and MIB-1 index of GHomas (r=0.82, p<0.01). About 66% of CS invasion was explained by these two factors. CONCLUSIONS: In view of these results, not only the volume but also the speed of growth are important for GHomas to invade CS. GHomas with a high MIB-1 index may, even if they are small, more readily invade CS and need closer post-operative hormonal and neuroimaging studies.

Adenoma↗
PubMed1999

A novel chromosomal locus of enteropathogenic Escherichia coli (EPEC), which encodes a bfpT-regulated chaperone-like protein, TrcA, involved in microcolony formation by EPEC.

The bfpTVW operon, also known as the per operon, of enteropathogenic Escherichia coli (EPEC) is required for the transcriptional activation of the bfp operon, which encodes the major subunit and assembly machinery of bundle-forming pili (BFP). An immobilized T7-tagged BfpT fusion protein that binds specifically to upstream promoter sequences of bfpA and eae was used to 'fish out' from a promoter library other EPEC chromosomal fragments that are bound by the BfpT protein. After screening for promoters exhibiting bfpTVW-dependent expression, one was identified that was positively regulated by bfpTVW and that is not present in the chromosomes of two non-virulent E. coli laboratory strains, DH5alpha and HB101. Further analysis of this positively regulated promoter in EPEC showed that it resided within a 4.9 kb sequence that is not present in E. coli K12. This locus, located downstream of the potB gene, was found to contain four open reading frames (ORFs): bfpTVW-activated promoter was localized upstream of ORF1. An ORF1 knockout mutant produced less of the BFP structural subunit (BfpA) and formed smaller than normal adherent microcolonies on cultured epithelial cells; however, this mutation did not affect bfp transcription. An ORF1-His6 fusion protein specifically bound the preprocessed and mature forms of the BfpA protein and thus appears to stabilize the former within the cytoplasmic compartment. ORF1 therefore is a newly isolated EPEC chromosomal gene that encodes a chaperone-like protein involved in the production of BFP. Hence, ORF1 was designated trcA (bfpT-regulated chaperone-like protein gene). The TrcA protein also specifically bound 39 kDa and 90 kDa proteins that are expressed by EPEC but not by E. coli K12. The 90 kDa protein was revealed to be intimin, a protein product of the eae gene, which is required for the EPEC attaching/effacing phenotype, suggesting a direct interaction of TrcA with intimin in the cytoplasmic compartment.

Adhesins, Bacterial↗
PubMed1999

Complete nucleotide sequence of the prophage VT2-Sakai carrying the verotoxin 2 genes of the enterohemorrhagic Escherichia coli O157:H7 derived from the Sakai outbreak.

The enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain RIMD 0509952, derived from an outbreak in Sakai city, Japan, in 1996, produces two kinds of verotoxins, VT1 and VT2, encoded by the stx1 and stx2 genes. In the EHEC strains, as well as in other VT-producing E. coli strains, the toxins are encoded by lysogenic bacteriophages. The EHEC O157:H7 strain RIMD 0509952 did not produce plaque-forming phage particles upon inducing treatments. We have determined the complete nucleotide sequence of a prophage, VT2-Sakai, carrying the stx2A and stx2B genes on the chromosome, and presumed the putative functions of the encoded proteins and the cis-acting DNA elements based on sequence homology data. To our surprise, the sequences in the regions of VT2-Sakai corresponding to the early gene regulators and replication proteins, and the DNA sequences recognized by the regulators share very limited homology to those of the VT2-encoding 933W phage carried by the EHEC O157:H7 strain EDL933 reported by Plunkett et al. (J. Bacteriol., p1767-1778, 181, 1999), although the sequences corresponding to the structural components are almost identical. These data suggest that these two phages were derived from a common ancestral phage and that either or both of them underwent multiple genetic rearrangements. An IS629 insertion was found downstream of the stx2B gene and upstream of the lysis gene S, and this might be responsible for the absence of plaque-forming activity in the lysate obtained after inducing treatments.

Bacterial Toxins↗
PubMed1999

MRI detection of suprasellar germinoma causing central diabetes insipidus.

This is a case report of an 18-year-old man with central diabetes incipidus (DI). An MRI done three months after the onset of the DI did not disclose a responsible lesion. Four months later, a second MRI showed the location of the tumor origin at the upper pituitary stalk and median eminence. Eight months later, the tumor occupied the hypothalamic area. The tumor became large and contrast-making enough to be visible on MRI between 3 and 4 months after the onst of DI. Besides the suprasellar tumor, another mass was noted in the pineal region. The growth pattern of the latter mass corresponded well to that of the former. Although the MRI is a sensitive diagnostic tool for the detection of intracranial tumors, no adequate rationale has been given as to how the MRI might be repeated for children and adolescents who have been diagnosed as having the central DI, when their initial MRIs may have been normal. In our patient, the superconductive thin slice MRI revealed the suprasellar germinoma 4 months after the onset. The suprasellar and pineal tumors in this report originated and developed simultaneously. This may indicate a multi-center origin of the tumor. Another possibility is a very early dissemination from the onset of the tumor development.

Adolescent↗
PubMed1998

Maxadilan is a specific agonist and its deleted peptide (M65) is a specific antagonist for PACAP type 1 receptor.

Maxadilan is a potent vasodilator peptide isolated from salivary glands extracts of the hematophagous sand fly. Recently, it was demonstrated that maxadilan binds to PACAP receptor type 1 in mammals, although maxadilan has no significant amino acid sequence homology with PACAP. In the present study, we demonstrated that maxadilan is a specific agonist of PACAP type 1 receptor (PACAP/VIP receptor 1; PVR1) as determined by the binding assay of [125I]PACAP27 and cAMP accumulation using CHO cells stably expressing PVR1, VIP1 receptor (PVR2), and VIP2 receptor (PVR3), and that the deleted peptide (#25-41) of maxadilan (termed as M65) is a specific antagonist of PVR1. In addition, maxadilan shares the binding sites for PACAP and stimulates cAMP in cultured rat cortical neurons. VIP stimulates cAMP accumulation probably through the binding to PVR1 since M65 blocks the VIP-induced cAMP accumulation in cultured rat cortical neurons.

Amino Acid Sequence↗
PubMed1998

Intersubunit interaction between transmembrane helices of the bacterial aspartate chemoreceptor homodimer.

The transmembrane domain that connects the extracellular and intracellular domains of cell-surface receptors must play a critical role in signal transduction. Here, we report studies of the interaction between the transmembrane helices (TM1 and TM2) of the Escherichia coli aspartate chemoreceptor (Tar). Tar exists as a homodimer regardless of its state of ligand occupancy. A particular residue substitution in TM1 (A19K) abolishes the signaling ability of Tar. This signaling defect can be suppressed by single residue substitutions in TM2 (W192R, A198E, V201E, and V202L). We have found that these suppressors can be divided into two groups. A198E and V201E (class 1) almost completely suppress the defects caused by A19K, and this suppression occurs between two subunits of the Tar dimer. In contrast, W192R and V202L (class 2) fail to suppress some signaling defects, and their suppression does not occur between subunits. Because disulfide-crosslinking studies predict that residues 198 and 201 point toward residue 19 of the partner subunit, we propose that the class 1 suppressors form an intersubunit salt bridge with Lys-19. Indeed, A19K was suppressed by several additional aspartate or glutamate substitutions on the same face of TM2 occupied by residues 198 and 201. None of these intersubunit salt bridges perturb signaling function, suggesting that the mechanism of transmembrane signal propagation does not involve large displacements (such as extensive rotation) of the TM1 and TM2 helices relative to each other.

Amino Acid Substitution↗
PubMed1998

Activation of cyclin-dependent kinase 2 (Cdk2) in growth-stimulated rat astrocytes. Geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E gene expression.

The role of the mevalonate cascade in the control of cell cycle progression in astrocytes has been investigated. Serum stimulation of rat astrocytes in primary culture induces the expression of cyclin E followed by the activation of cyclin-dependent kinase 2 (Cdk2) during G1/S transition. The expression of p27, cyclin D1, and the activities of Cdk4 and Cdk-activating kinase (CAK), composed of Cdk7 and cyclin H, were not affected. Serum did, however, stimulate the expression of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase mRNA at mid-G1 phase. Moreover, an inhibitor of HMG-CoA reductase, pravastatin, reduced cyclin E expression and Cdk2 activation and caused G1 arrest in the astrocytes. In contrast, mevalonate and its metabolite, geranylgeranylpyrophosphate (GGPP) but not farnesylpyrophosphate (FPP), reversed the inhibitory effects of pravastatin on cyclin E expression and Cdk2 activation and allowed G1/S transition. Rho small GTPase(s) were geranylgeranylated and translocated to membranes in the presence of GGPP during G1/S transition. The effect of GGPP on cyclin E expression was abolished by botulinum C3 exoenzyme, which specifically inactivates Rho. These data indicate that geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E expression, Cdk2 activation, and G1/S transition in rat astrocytes.

ADP Ribose Transferases↗
PubMed1998

Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates mitogen-activated protein kinase (MAPK) in cultured rat astrocytes.

Astrocytes, a subtype of glial cells, have been demonstrated to have an abundant number of receptors for pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide of the VIP/secretin family which stimulates cAMP accumulation 1000 times more potent than VIP in astrocytes. PACAP is reported to stimulate the proliferation of astrocytes at low concentrations at which it does not yet stimulate the cAMP accumulation. In the present study, we examined the effect of PACAP on the activation of mitogen-activated protein kinase (MAPK), one of the important intracellular signals for the proliferation, and compared it with that of epidermal growth factor (EGF). To investigate the activation of MAPK, we focused on ERK2, one of MAPK, in cultured rat astrocytes. The activation of ERK2 was determined by immunoblotting and measurement of the activity in terms of the phosphorylating activity of immunoprecipitates with MAPK antibody on myelin basic protein. One pM of PACAP38 temporarily activated ERK2 at 10 min. In contrast, EGF activated ERK2 from 10 min to 60 min continuously. As for the dose-response effect, PACAP stimulated ERK2 at as low a concentration as 10-14 M and peaked at 10-12 M. Thereafter, its activating effect gradually decreased at 10-10 M and returned to the basal level at 10-8 M, forming a bell-shaped dose-dependency. Neither an inhibitor of PKA (H89) nor inhibitors of PKC (staurosporine and calphostin C) had any effect on the ERK2 activation induced by 1 pM PACAP38. Dibutyryl cAMP suppressed ERK2 activity in a dose-dependent manner. These data clearly demonstrated that PACAP stimulates MAPK in both a PKA- and a PKC-independent manner in cultured rat astrocytes.

Animals↗
PubMed1998

Geranylgeranylpyrophosphate plays a key role for the G1 to S transition in vascular smooth muscle cells.

Pravastatin, a HMG-CoA reductase inhibitor was found to inhibit DNA synthesis of vascular smooth muscle cells (VSMC) in a dose-dependent manner. Flow cytometric analysis demonstrated that pravastatin induced G1 arrest. Mevalonate restored the inhibitory effect of pravastatin on DNA synthesis and on cell cycle progression, suggesting the importance of mevalonate itself and/or its metabolites in VSMC proliferation. The major intermediate metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP), farnesyl pyrophosphate (FPP) and IPP (isopentenyl pyrophosphate) were prepared in the form of liposomes, and the effects of GGPP, FPP and IPP on pravastatin induced inhibition of VSMC proliferation and G1 arrest were examined. Only GGPP restored the pravastatin-induced inhibition of DNA synthesis and G1 arrest. Pravastatin inhibited translocation of Rho small GTPase from cytosol to membrane. By the addition of GGPP, Rho small GTPase are geranylgeranylated and translocated to membranes during G1/S transition. These data suggest that GGPP, rather than FPP or IPP, is an essential metabolite among mevalonic acid metabolites for VSMC proliferation and the G1/S transition.

Animals↗
PubMed1997

Geranylgeranylpyrophosphate, a metabolite of mevalonate, regulates the cell cycle progression and DNA synthesis in human lymphocytes.

We investigated the role of the intrinsic mevalonate cascade in DNA synthesis and cell cycle progression in human peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin (PHA). PHA stimulated the expression of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase mRNA prior to the DNA synthesis (S phase). Pravastatin, an HMG-CoA reductase inhibitor, inhibited DNA synthesis and blocked the entry to S phase in PHA-stimulated PBMC. Mevalonate restored these inhibitory effects. Thus, we examined two major metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP) and farnesyl-pyrophosphate (FPP), using a novel liposome system for uptake into the cells. GGPP, not FPP, restored the pravastatin-induced inhibitions. These data indicated that 1) the intrinsic mevalonate cascade plays critical roles for the entry to S phase and DNA synthesis, and that 2) GGPP is an essential metabolite of mevalonate cascade for cell cycle progression in PBMC stimulated by PHA.

Acyl Coenzyme A↗
PubMed1997

Geranylgeranylated rho small GTPase(s) are essential for the degradation of p27Kip1 and facilitate the progression from G1 to S phase in growth-stimulated rat FRTL-5 cells.

Cyclin-dependent kinase (Cdk) enzymes are activated for entry into the S phase of the cell cycle. Elimination of Cdk inhibitor protein p27Kip1 during the G1 to S phase is required for the activation process. An inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase prevents its elimination and leads to G1 arrest. Mevalonate and its metabolite, geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, restore the inhibitory effect of pravastatin on the degradation of p27 and allow Cdk2 activation. By the addition of geranylgeranyl pyrophosphate, Rho small GTPase(s) are geranylgeranylated and translocated to membranes during G1/S progression. The restoring effect of geranylgeranyl pyrophosphate is abolished with botulinum C3 exoenzyme, which specifically inactivates Rho. These results indicate (i) among mevalonate metabolites, geranylgeranyl pyrophosphate is absolutely required for the elimination of p27 followed by Cdk2 activation; (ii) geranylgeranylated Rho small GTPase(s) promote the degradation of p27 during G1/S transition in FRTL-5 cells.

Animals↗