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Akira Teramoto

Publications and source records attributed to Akira Teramoto.

At least 19 recordsLinked to original sources
PubMed2026

What do you mean by PitNETs in WHO Classification 2022?

This review is aimed at clarifying the background and the meaning of new terminology "pituitary neuroendocrine tumours" (PitNETs) in WHO Classification 2022. The PitNETs share the unique structures of secretory granules (SG) with other neuroendocrine tumors, the good example of which is the pancreatic NETs which are now considered to be potentially aggressive, i.e., invasive and metastatic. The PitNETs share these features of pancreatic NETs and now are considered to be potentially aggressive tumors. The PitNETs are classified according to the functions (hormones) and transcription factors, PIT1, TPIT and SF1. The PitNETs are usually slow growing tumors with generally low (<3%) Ki-67 indices. PitNETs show some morphologic features which are more closely related to aggressive growths, such as Crooke cells. The questions how those particular PitNETs are aggressive have been approached by molecular techniques such as single cell RNA seq to clarify the genomic heterogeneity and the biology of individual tumor cells. It is expected that the PitNETs will be clarified and classified with more biologically and therapeutically oriented manner.

Neuroendocrine neoplasms (NEN)↗
PubMed2006

Enhancement of pituitary adenoma cell invasion and adhesion is mediated by discoidin domain receptor-1.

The discoidin domain receptor-1 (DDR1) tyrosine kinases are a family of cell surface receptors that bind to several types of collagen and facilitate cell adhesion that is known association with several cancers. However, no previous study has examined the expression and function of DDR1 in pituitary adenoma. Tissue microarray analysis of DDR1 expression levels in 52 pituitary adenoma tissues revealed that DDR1 expression was significantly related to hormonal background (Kruskal-Wallis test; P < 0.0001). To further elucidate the function of DDR1 in pituitary adenoma, we developed DDR1 over- and under-expressing cell lines using DDR1 clone transfection and short interfering ribonucleic acids (siRNA)-based DDR1 gene silencing, respectively, in a human pituitary adenoma cell line (HP-75). Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting confirmed that expression of both DDR1 isoforms (DDR1a and DDR1b) was elevated by clone transfection and diminished by siRNA. Matrigel invasion assays revealed that cell invasion was increased in HP-75 cells over-expressing DDR1 and decreased in cells under-expressing DDR1. Consistent with this, zymography revealed that the activation levels of matrix metalloproteinase (MMP)-2 and -9 were increased and decreased in cells over- and under-expressing DDR1, respectively. Examination of in vitro cell adhesion to collagen types I, II, III, and IV with respect to MMP-2 and -9 expression revealed that DDR1 regulated cell adhesion to collagen type I, which was responsible for accelerating secretion of MMP-2 and -9 in DDR1 over-expressing cells. Taken together, these results strongly suggest that DDR1 mediates cell invasion-related signaling between collagen type I and MMP-2 and -9 in pituitary adenoma cells.

Adenoma↗
PubMed2006

Anti-apoptotic action by hypoxia inducible factor 1-alpha in human pituitary adenoma cell line, HP-75 in hypoxic condition.

Hypoxia-inducible factor-1 (HIF-1) alpha is the major transcription factor involved in the adaptive response to hypoxia. The purpose of this study was to investigate whether HIF 1-alpha protects HP75 cells, pituitary adenoma cell line from hypoxia induced apoptosis. HP75 was transfected with siRNA targeting HIF 1-alpha mRNA sequences or scrambled RNA duplexes, followed by subjected to hypoxia (1% oxygen) for 24 h, compared with normoxia (21%). The efficacy of RNAi was assessed via real-time RT-PCR and immunohistochemistry. Apoptosis was determined by Tdt-mediated dUTP nick end-labeling (TUNEL) assay and agarose gel electrophoresis. Membrane cDNA microarray was examined to detect gene profiling among the cell in normoxia, hypoxia, or hypoxia following the RNAi. A significantly greater proportion of HP75 cells transfected with specific siRNA duplexes and subsequently exposed to hypoxia demonstrated apoptosis to a large extent when compared with non-transfected cells. Transfection with specific siRNA duplexes knocked down HIF 1-alpha mRNA and protein expression in hypoxia-exposed cells by approximately 80%, whereas transfection with scrambled siRNA duplexes had no noticeable effect on HIF 1-alpha expression. Microarray analysis indicated that HIF1-alpha down-regulated caspase-10. These findings strongly suggest that HIF 1-alpha exerts an antiapoptotic role in HP75 in hypoxia.

Adaptation, Physiological↗
PubMed2006

[Cushing disease].

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Diagnosis, Differential↗
PubMed2006

[Nelson's syndrome].

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Diagnosis, Differential↗
PubMed2006

Phosphorylation of cAMP response element binding protein (CREB) as a marker of hypoxia in pituitary adenoma.

Hypoxia appears to be causatively related to pituitary adenoma. Currently, no biomarkers are available for the postoperative assessment of hypoxia in patient samples. Since the cAMP response element binding protein (CREB) is phosphorylated under hypoxic conditions, we examined whether CREB phosphorylation levels may be exploited as a novel biomarker for hypoxia in pituitary adenoma tissues. HP-75 human pituitary adenoma cells were incubated in 21% or 1% oxygen (normoxia and hypoxia, respectively), and Western blotting was employed to compare the levels of CREB and phosphorylated CREB (p-CREB). Our results show that p-CREB levels are significantly elevated under 1% oxygen, whereas the total CREB concentration remains unchanged. We further tested whether this phosphorylation is applicable as a marker of hypoxia in pituitary adenoma tissues removed by transsphenoidal surgery from 45 patients (32 females and 13 males, 22-78 years old). Fluorescence double immunohistochemistry data revealed that p-CREB in adenoma tissues is significantly elevated, and displays a positive correlation with Knosp grading (Spearman rank correlation; P = 0.0483, r = 0.3412), but no significant association with tumor subtype (Kruskal-Wallis analysis, CREB, P = 0.1072; p-CREB, P = 0.1888; phosphorylation ratio, P = 0.4916). Our findings collectively suggest that CREB phosphorylation may be employed as an in situ marker for hypoxia. Moreover, hypoxia and/or phosphorylation of CREB are associated with the cell invasiveness of pituitary adenomas.

Adenoma↗
PubMed2006

Does the prevalence of gsp mutations in GH-secreting pituitary adenomas differ geographically or racially? Prevalence of gsp mutations in Japanese patients revisited.

OBJECTIVE: The prevalence of gsp mutations in GH-secreting pituitary adenomas was thought to differ geographically or racially, given its exceptionally lower incidence among Japanese patients (4.4-9.3%) compared to other regions (30-50%). However, this notion is now being challenged after a recent paper reported a 53.3% incidence among Japanese with acromegaly. We have since re-evaluated the prevalence of gsp mutations on a larger scale. PATIENTS: One hundred Japanese acromegaly patients with surgically confirmed GH-secreting pituitary adenomas were enrolled. METHODS: mRNAs from primary cultured adenomas were used for reverse transcriptase-polymerase chain reaction and direct sequencing of the Gsalpha subunit. Patient data were reviewed from medical charts. RESULTS: There were 53 gsp mutations (53%), consisting of 42 Arg201Cys, one Arg201His, one Arg201Ser, 8 Gln227Leu, and one Gln227Arg mutation. Age at operation, sex ratio, basal serum GH and IGF-I levels were no different with or without the mutations. In contrast, patients responded differently to most dynamic tests with statistical significance: serum GH levels in gsp-positive patients had blunted response to GHRH, were well suppressed by bromocriptine, and had higher rates of paradoxical response to TRH. Notably, paradoxical response to LHRH was observed exclusively in gsp-negative patients. Octreotide suppressed GH levels strongly regardless of gsp status. These clinical characteristics are similar to those of Caucasian patients. CONCLUSION: We conclude that the prevalence of gsp mutations in Japanese acromegaly patients is comparable to those of other reports from various regions. Therefore, Japanese patients do not stand as an example for geographical or racial difference in the prevalence of gsp mutations in GH-secreting pituitary adenomas.

Acromegaly↗
PubMed2006

Internal carotid artery stenosis due to atherosclerotic plaque damage after whiplash injury.

Blunt traumatic occlusion or stenosis of the internal carotid artery is a rare complication of whiplash injury and may not be recognized until the onset of neurological symptoms. The clinical course can vary considerably, with regard to both the symptoms and the interval between injury and manifestation. A dissecting aneurysm and intimal tear are usually observed after blunt internal carotid artery injury. Atherosclerotic plaque is often observed in the cervical internal carotid artery and carotid bifurcation, but involvement of plaque has been confirmed in relatively few cases of blunt traumatic internal carotid injury. We describe a 58-year-old man who developed cerebral embolism due to intraplaque thrombus after a minor whiplash injury and was successfully treated with carotid endarterectomy. Because thrombosis occurred within the atherosclerotic plaque, we named the mechanism of this case "plaque injury".

Carotid Artery Diseases↗
PubMed2006

Functional and morphological changes in the hypothalamus-pituitary posterior lobe system after hypophysectomy in the dog.

Acute diabetes insipidus-like symptoms have been reported as a complication after hypophysectomy in dogs. These symptoms are believed to be the consequence of deficiency of arginine vasopressin (AVP) secretion. The symptoms spontaneously resolve within 2 weeks, but the mechanism is unclear. In the present study, AVP secretion related to increases in Na+ concentration and serum osmotic pressure was measured, and immunohistochemical analysis in the paraventricular and supraoptic nuclei was performed after hypophysectomy in normal dog. In the hypertonic saline test, the plasma AVP concentration slightly increased in hypophysectomized dogs, although the increase was markedly smaller than that in normal dogs. An immunohistochemical study of the hypothalamus nucleus revealed that, AVP-positive cells tended to decrease after hypophysectomy. It suggests that excision of the posterior lobe by surgery injured the axon of magnocellular neuron in the hypothalamus. A decrease in the function and the number of AVP-producing and -secreting magnocellular neurons after hypophysectomy, suggests that the clinical improvement of postoperative diabetes insipidus-like symptoms may not be related to the recovery of AVP secretion.

Animals↗
PubMed2006

Immunonegative "null cell" adenomas and gonadotropin (Gn) subunit (SUs) immunopositive adenomas share frequent expression of multiple transcription factors.

The differentiation of pituitary cells and human pituitary adenomas follow three cell lineages: GH-PRL-TSH, ACTH, and FSH/LH, which are regulated by a combination of various transcription factors and co-factors. We have used RT-PCR and immunohistochemistry to show that immunonegative, "null cell" adenomas are equipped with multiple transcription factors and co-factors. The "null cell" adenomas showed similar frequencies of transcription factors as did the gonadotropin subunit (GnSU)-positive adenomas, with the exception that there were fewer instances of SF1 in the former. We speculate, therefore, that null cell adenomas and GnSU-positive adenomas share common molecular mechanisms in functional differentiation, even though the former do not produce hormones. From the high frequency of various transcription factors, we also speculate that both null cell adenomas and GnSU-positive adenomas are derived from "committed" pituitary progenitor stem cells. The questions, why a certain proportion of these pituitary tumor groups lack hormone production and why they are molecularly more committed to Gn transcription, remain to be further investigated.

Adenoma↗
PubMed2006

PTTG overexpression is correlated with angiogenesis in human pituitary adenomas.

Human pituitary tumor transforming gene (hPTTG1) was recently identified as a protooncogene, which is a regulator of the cell cycle, as a homolog of yeast securin and a transcriptional activator of several angiogenic factors. Here we examined the relationships of hPTTG1 expression with cell proliferation, expression of the angiogenic factor, VEGF (vascular endothelial growth factor), and numbers of the blood vessels in the normal and/or adenomatous pituitary. With the exception of TSHoma, the expression of hPTTG1 was significantly higher in pituitary adenomas than in the normal pituitary gland. The cell proliferation activity was higher in pituitary adenomas than in the normal pituitary. Pituitary cell proliferation was significantly correlated with the level of hPTTG1 expression in the normal pituitary tissue, but there was no such correlation in the adenomas. The significant correlation of hPTTG1 with the VEGF expression and the numbers of the blood vessels was elucidated in pituitary adenomas. It is particularly noteworthy that immunohistochemical double staining indicated co-localization of VEGF in many hPTTG1-positive tumor cells. In conclusion, higher levels of hPTTG1 expression contribute to the pathobiology of pituitary adenomas by promoting angiogenesis rather than by activating cell proliferation, whereas hPTTG1 expression is related to mitotic activity in the normal pituitary gland.

Adenoma↗
PubMed2006

Clinical characteristics, etiologies and pathophysiology of patients with severe short stature with severe GH deficiency: questionnaire study on the data registered with the foundation for growth science, Japan.

In this study, we sent questionnaires to doctors treating severe short stature with severe GH deficiency (GHD) (height SDS (HtSDS) below -4 and all peak GH to provocative stimuli below 2 micro/L) (abbreviated as Severe Case), and obtained effective replies of 51 cases. The clinical characteristics, etiologies, and pathophysiology of these patients were examined. Among the 51 Severe Cases no consanguinity was observed, 44 were IGHD (24 males and 20 females), 3 were GH-1 gene deletion, 2 were Pit-1 gene mutation, and 2 were achondroplasia. HtSDS in these Severe Cases was already remarkably low at 12 (-3.0) and 24 months old (-3.9), while their birth weight and birth length were within normal ranges. Among 44 patients with IGHD, 12 were isolated GHD, and the remaining 32 were combined pituitary hormone deficiency (CPHD). Pituitary MRI was undergone in 25 idiopathic GHD, and abnormal findings (pituitary atrophy, interruption of stalk, and ectopic posterior lobe) were observed in 21 patients with CPHD. More than half of these patients had the history of breech delivery. Three patients with GH-1 gene mutation showed normal pituitary MRI, whereas one of two patients with Pit-1 mutation showed pituitary atrophy and narrowing of pituitary stalk. In conclusion, Severe Cases tended to have CPHD, and the incidence of Severe Case was only 0.6% of total IGHD. Although GHD due to genetic disorders is considered to be extremely rare (0.06% of total IGHD), the incidence reaches high levels (9.8%) among Severe Cases. Growth disorders in these Severe Cases seem to occur soon after delivery. Much earlier diagnosis and hGH treatment are desirable to attain better final height in the Severe Cases. GH-1 and Pit-1 gene analyses are crucial, when genetic abnormalities other than achondroplasia are suspected.

Achondroplasia↗
PubMed2006

Persistent primitive trigeminal artery aneurysm associated with cerebellar hemangioblastoma. Case report.

A 72-year-old man presented with a cerebellar vermian tumor manifesting as headaches and vertigo. Angiography disclosed a vascular tumor fed by the superior cerebellar artery and an aneurysm of a primitive trigeminal artery. The patient underwent right occipital craniotomy to remove the highly vascular tumor via an occipital transtentorial approach. Association of a cerebral aneurysm with a hemangioblastoma has been reported previously in only five cases. Only three aneurysms were located on the feeding artery. The aneurysm in this case was not on the feeding artery. Simple coincidence might account for this case.

Aged↗
PubMed2006

Resection of arteriovenous malformation in a patient with hemophilia type A.

A 34-year-old man with hemophilia type A presented with a huge intracerebral hematoma (ICH) in the left frontoparietal lobe due to rupture of an arteriovenous malformation (AVM). Angiography demonstrated the AVM in the frontoparietal lobe fed by the anterior cerebral arteries and the middle cerebral arteries, with a vein draining into the superior sagittal sinus. He developed signs of cerebral herniation due to the huge ICH. An emergent operation was performed to reduce intracranial pressure and to stop bleeding from the AVM under continuous administration of factor VIII. To prevent postoperative hemorrhage, aggressive blood pressure control and continuous administration of factor VIII were performed for 10 days. His neurological status improved so that he could hold a simple conversation. Continuous administration of factor VIII during surgery and intensive intra- and postoperative therapy resulted in a favorable outcome for this patient with hemophilia type A.

Adult↗
PubMed2006

Cardiopulmonary hemodynamic changes during acute subdural hematoma evacuation.

The aim of this study was to clarify the mechanism of hemodynamic changes leading to intraoperative hypotension during evacuation of acute subdural hematoma. To our knowledge, little data is available about the mechanism of hemodynamic changes during surgical interventions to decrease intracranial pressure after severe head injury. The influence of preoperative hypotension on intraoperative hypotension was examined. Hemodynamic studies (pulmonary artery catheterization) were carried out in 15 patients before and after acute subdural hematoma evacuation. All patients were assessed for hemodynamic parameters, evacuated hematoma volume, and intracranial pressure measurements. Comparison between just before and after evacuation of the hematoma showed that the mean arterial pressure, pulmonary arterial pressure, systemic vascular resistance, pulmonary vascular resistance, central venous pressure, and pulmonary capillary wedge pressure all decreased after hematoma evacuation. However, the cardiac index was unchanged after hematoma evacuation. Mean arterial blood pressure is dependent on the cardiac index and vascular resistance, so the decrease in arterial blood pressure during hematoma evacuation was the result of a decline in vascular resistance. The influence of preoperative blood pressure on intraoperative hemodynamic changes was analyzed by dividing the patients into two groups, the preoperative hypotension group and preoperative nonhypotension group. The decrease in mean arterial blood pressure was more marked in the preoperative hypotension group than in the preoperative nonhypotension group. Intraoperative hypotension during evacuation of acute subdural hematoma is caused by a decrease in vascular resistance. Preoperative hypotension is a also risk factor for intraoperative hypotension.

Adult↗
PubMed2006

Increased regional interleukin-4 during the acute stage of severe intracranial disorders.

Interleukin (IL)-4 levels in the internal jugular vein were measured during the acute stage in patients with head injuries, subarachnoid hemorrhage, or intracerebral hemorrhage to investigate the prognostic value. Levels of IL-4, interferon (IFN)-gamma, glucose, and lactate, and oxygen saturation were measured in the internal jugular vein to investigate cerebral local reactions and in the radial artery as a control at admission and 4 hours after onset. The subjects were divided into a survival group and a deceased group. IL-4 levels were high in the internal jugular veins and arterio-jugular venous differences in oxygen content (AjDO(2)) were low at 4 hours after onset in the deceased group. Increased glucose and lactate levels were found at 4 hours after onset in the deceased group. No significant difference was found for IFN-gamma. The severity of cerebral disorders evaluated using AjDO(2) showed a negative correlation with intracerebral IL-4 level. This finding suggests that secretion of IL-4, which has a neuroprotective effect, may increase with the severity of neuropathy and may be useful as a prognostic index.

Case-Control Studies↗
PubMed2006

Effect of mitotane on pituitary corticotrophs in clinically normal dogs.

OBJECTIVE: To evaluate the effects of mitotane administration on the function and morphology of pituitary corticotrophs in clinically normal dogs. ANIMALS: 12 clinically normal adult Beagles. PROCEDURES: Dogs were randomly assigned to the control group or the mitotane treatment group. In mitotane treatment group dogs, mitotane was administered for 1 month. In both groups, ACTH stimulation testing and corticotrophin-releasing hormone (CRH) stimulation testing were performed. Magnetic resonance imaging (MRI) of the pituitary gland and brain was performed in mitotane treatment group dogs before and after administration of mitotane. After CRH stimulation testing and MRI, dogs were euthanatized and the pituitary gland and adrenal glands were excised for gross and histologic examination. RESULTS: ACTH concentrations in mitotane treatment group dogs were significantly higher than in the control group dogs following CRH stimulation. Magnetic resonance imaging revealed that pituitary glands were significantly larger in treatment group dogs after administration of mitotane, compared with before administration. On gross and histologic examinations, the adrenal cortex was markedly atrophied. Immunohistochemistry revealed hypertrophy of corticotrophs in pituitary glands of mitotane treatment group dogs. CONCLUSIONS AND CLINICAL RELEVANCE: These findings indicate that inhibition of the adrenal cortex by continuous administration of mitotane leads to functional amplification and morphologic enhancement of corticotrophs in clinically normal dogs. In instances of corticotroph adenoma, hypertrophy of individual corticotrophs induced by mitotane may greatly facilitate enlargement of the pituitary gland and increases in ACTH secretion.

Adrenocorticotropic Hormone↗