Search PubMed⌕ Search

Biomedical subjects

A Teramoto

Publications and source records attributed to A Teramoto.

At least 19 recordsLinked to original sources
PubMed1997

Inactivation of the tumor suppressor gene on 11q13 in brothers with familial acrogigantism without multiple endocrine neoplasia type 1.

Two of three brothers (the second and third brothers) and their uncle (their mother's brother) presented acrogigantism without multiple endocrine neoplasia type 1 (MEN 1). An invasive macroadenoma was found in the second brother, and it was histologically confirmed as a sparsely granulated GH cell adenoma. Two distinct microadenomas were found in the third brother, and these were histologically diagnosed as a mixed GH cell and PRL cell adenoma and a sparsely granulated GH cell adenoma, respectively. The loss of heterozygosity (LOH) was analyzed in two adenomas (GH cell adenoma from the second brother and a mixed GH cell and PRL cell adenoma from the third brother) by determining microsatellite polymorphisms of DNAs from tumors and patients' leukocytes. The LOH was found on the chromosome 11q13, whereas LOH was not detected on 1p31-36, 2p, 3p, 4, 5, 6p, 7, 8, 9p21-22, 12p, and 19q13 in both pituitary adenomas examined. The haplotype analysis showed that the same haplotype on 11q13 was found in their mother and the unaffected first brother as well as in the affected uncle and two brothers. The deleted alleles on chromosome 11q13 in the tumors of two affected brothers were, however, restricted to those transmitted from their unaffected father. These data suggest that inactivation of the MEN 1 gene or other tumor suppressor genes on chromosome 11q13 plays an important role for the development of our familial acrogigantism without MEN 1.

Adenoma↗
PubMed1996

Corticotropin-releasing hormone excites adrenocorticotropin-secreting human pituitary adenoma cells by activating a nonselective cation current.

The mechanisms of corticotropin-releasing hormone (CRH) induced excitation of ACTH-secreting adenoma cells were investigated using the perforated whole-cell clamp technique and intracellular Ca2+ concentration ([Ca2+]i) measurement. CRH depolarized ACTH-secreting adenoma cells by activating a nonselective cation current that showed slight inward rectification. This channel did not seem to be a member of the Ca(2+)-activated cation currents because it was activated even when the [Ca2+]i was chelated below 50 nM. The activation of the current was induced by protein kinase A-mediated pathways. By [Ca2+]i measurement, CRH increased [Ca2+]i of these cells dependently on voltage-gated Ca2+ current. This CRH-induced [Ca2+]i increase was abolished in Na(+)-free extracellular solution, but was not abolished by the addition of 5 microM tetrodotoxin to the extracellular solution. CRH-induced ACTH secretion from the cultured adenoma cells was also abolished in Na(+)-free extracellular solution, but not in tetrodotoxin-containing extracellular solution. These data indicate that a Na+ current (maybe the nonselective cation current) other than voltage-gated Na+ current plays an important role in CRH-induced [Ca2+]i increase and ACTH secretion. CRH also activated a nonselective cation current in nonadenoma human corticotrophs, suggesting that the activation of a nonselective cation current is a physiological mechanism of CRH-induced excitation in human corticotrophs.

Adenoma↗
PubMed1996

Management of huge pituitary adenomas.

Management of huge pituitary adenoma (more than 5 cm in diameter) is one of the most important issues on the treatment of pituitary tumors. We have analyzed the therapeutic modality and the result of our cases. From 1967 to 1983, 50 patients with huge adenoma (14.1%) out of a total 354 pituitary adenomas were surgically treated. The operative mortality was 25% for radical transcranial (TC) approach (10/40), 14% (1/7) for transsphenoidal (TS) approach and 0% (0/3) for combined two stage operations. From long-term follow-up, excellent prognoses were observed in only 44% of the patients treated by radical TC operation. After 1984, we have employed partial removal by TS surgery at the first stage, followed by reoperation by TS or TC surgery with or without radiotherapy or bromocriptine in case by case. Seventeen huge pituitary adenomas out of a total 700 pituitary adenomas were operated. There was no mortality nor major complications. The two stage operation with initial TS surgery is recommended for the management of huge pituitary adenomas.

Adenoma↗
PubMed1996

A case of pituitary somatotroph adenoma with concomitant secretion of growth hormone, prolactin, and adrenocorticotropic hormone--an adenoma derived from primordial stem cell, studied by immunohistochemistry, in situ hybridization, and cell culture.

Somatotroph adenomas often secrete prolactin (PRL) besides growth hormone (GH) and are sometimes immunostained for other anterior pituitary hormones or their subunits, such as thyroid-stimulating hormone (TSH) beta-subunit and glycoprotein hormone alpha-subunit (alpha SU). However, somatotroph adenomas showing hypersecretion of adrenocorticotropic hormone (ACTH) are extremely rare. There have been, to our knowledge, only five published reports on somatotroph adenomas accompanied by excessive ACTH secretion. Here we report a case of intracavernously invading somatotroph macro-adenoma with high serum GH, PRL, and ACTH levels. We examined the case using immunohistochemistry (IHC), in situ hybridization (ISH), and cell culture, and confirmed GH, PRL, and ACTH, as well as alpha SU, production, and the expression of Pit-1 protein by the adenoma, which is known as a transcriptional factor for GH, PRL, and TSH, not for ACTH. Therefore, the presence of unknown transcriptional factor other than Pit-1, common to GH, PRL, and ACTH, may be speculated to be expressed in this adenoma. In our previous study, we had found plurihormonal mRNA expression, especially for ACTH, the beta-subunit of follicle-stimulating hormone and luteinizing hormone in some somatotroph adenomas, using non-radio-isotopic ISH, and suggested that these adenomas might be derived from plurihormonal primordial stem cells. Our present case is significant from the viewpoint of histogenesis of pituitary adenomas, because it further supports the cell origin of somatotroph adenomas from plurihormonal primordial stem cells, and moreover it suggests the presence of unknown transcriptional factor other than Pit-1, common to GH, PRL, and ACTH.

Adenoma↗
PubMed1996

Clinical and cytofunctional classification of pituitary adenomas: proposal of a new classification.

Recent methodological advances in immunohistochemistry, ultrastructural techniques, hormonal assays, resolution imaging and molecular biology techniques have provided new insights into the pathology, function and cytogenesis of pituitary adenomas. Pituitary adenomas have been classified historically on the basis of tinctorial affinities, followed by the basis of ultrastructure and immunohistochemistry. The current development of technologies necessitate the new classification of pituitary adenomas which integrates these numerous parameters as well as the clinical manifestations. For this purpose, we suggest a new clinico-cytofunctional classification of pituitary adenomas, which is based on these clinical manifestations and integrates the information on biology, imaging function and ultrastructure. This classification which corresponds to current advances will not only provide pertinent clinical data but facilitate better understanding of the biology and nature of these complexed lesions.

Adenoma↗
PubMed1996

In situ hybridization analysis of Pit-1 mRNA and hormonal production in human pituitary adenomas.

The pituitary-specific transcriptional factor, Pit-1, is a member of the POU-domain family which has a role in the development and differentiation of three pituitary cell types: somatotrophs, lactotrophs, and thyrotrophs. Recent investigations have suggested the involvement of specific regulation of Pit-1 transcripts in human pituitary adenomas. In this study, we analyzed the expression of Pit-1 gene and Pit-1 product in various human pituitary adenomas using in situ hybridization (ISH) and immunohistochemistry (IHC). Northern hybridization analysis revealed 2.4- and 4.1-kb Pit-1 transcripts in normal pituitary, growth hormone (GH)-, prolactin (PRL)- and thyrotropin (TSH)-secreting adenomas. By ISH analysis, Pit-1 mRNA was detected in 42 (84%) of 50 adenomas. The highest incidence was observed in 15 GH-secreting adenomas and 8 TSH-secreting adenomas, in which Pit-1 mRNA was detected in all cases. Pit-1 mRNA expression was detected in 11 (85%) of 13 PRL-secreting adenomas. In 12 clinically non-functioning adenomas, Pit-1 mRNA was also present in 8 cases, and 5 of these were associated with immunohistochemical expression of Pit-1 product. By combined ISH and IHC, Pit-1 mRNA was often colocalized with GH, PRL or TSH beta immunoreactivities and sometimes colocalized with alpha-subunit of glycoprotein (alpha SU) immunoreactivity. The expression of Pit-1 mRNA in various cell types of human pituitary adenomas in addition to GH, TSH beta and PRL immunoreactivities suggests that Pit-1 may play a role in functional development of pituitary adenomas, including clinically non-functioning adenomas. However, some additional transcriptional factors or enhancers may be required.

Adenoma↗
PubMed1996

Application of catalyzed signal amplification in immunodetection of gonadotropin subunits in clinically nonfunctioning pituitary adenomas.

Pituitary adenomas that are characterized by the absence of a particular clinical syndrome and the absence of excessive hormone secretion have been classified as nonfunctioning adenomas. Recent development of immunohistochemical analysis and hormonal assay have suggested that many of these tumors have function to secret the gonadotropin subunits. A novel procedure biotin amplification in immunohistochemistry, catalyzed signal amplification (CSA) has been reported recently. In this study, the authors applied this new method to tissues from 50 cases of clinically nonfunctioning adenomas. These cases had no evidence of endocrinological signs by hormone secretion. When the CSA system was applied in normal pituitary gland, each of subunits was positive even when the antibody was diluted 1:1,000,000, which is 1,000 folds of standard indirect immunoperoxidase method. Immunohistochemical staining by indirect immunohistochemical method revealed that all 50 adenomas were negative for all the anterior hormones, including growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), beta-subunit of luteinizing hormone (LH beta), follicle-stimulating hormone (FSH beta), thyroid stimulating hormone (TSH beta), and a-subunit of glycoprotein (alpha SU). Using avidin-biotin complex (ABC) method, two cases were positive for FSH beta and four cases were positive for alpha SU, respectively, and the immunopositivities were observed weakly in scattered cells. By CSA system, 26 cases of 50 nonfunctioning adenoma were positive for FSH beta, 16 cases were positive for LH beta, and 29 cases were positive for alpha SU, respectively. The immunoreactivities were clearly observed in cytoplasm of many adenoma cells. This amplification procedure provides a means of greatly increasing the sensitivity of the immunohistochemistry including subunits of glycoproteins that are difficult to detect by previous indirect immunoperoxidase method or ABC method. This amplification procedure provides a great increase in the sensitivity of the immunohistochemistry for the detection of gonadotropin subunits and suggest that significant proportion of the nonfunctioning adenomas are gonadotropin subunit producing adenomas.

Adenoma↗
PubMed1996

In vitro inhibition of cell proliferation, viability, and invasiveness in U87MG human glioblastoma cells by estramustine phosphate.

OBJECTIVE: Several determinants of cell motility are highly dependent on the cytoskeleton, in particular, microtubules. To our knowledge, there have been no previous reports regarding the anti-invasive ability by an antimicro-tubule agent, estramustine phosphate (EMP), on glioblastoma cell lines. We investigated the modulated cell proliferation and invasiveness by EMP in vitro. METHODS: We determined the relative survival rate by cell proliferation assay and the percent survival fraction by monotetrazolium assay. Furthermore, an invasion index was used to quantify the migrating and invasive potential of the human glioblastoma cell line, U87MG, in Boiden's chamber with reconstituted basement membrane (Matrigel; Collaborative Research, Lexington, MA). RESULTS: We found that 0.5 mumol/L EMP had no effect in any of the assays. Concentrations of 1, 5, and 10 mumol/L demonstrated a concentration- and time-dependent depression in all of the assays. A range of drug concentration of EMP, 1 to 10 mumol/L, in which cell invasiveness was successfully inhibited, was comparable with antiproliferative capacity. CONCLUSION: The data add to the findings that EMP not only offers selective antiproliferative activity against glioblastoma but also reduces invasiveness, consistent with its main mechanism of action. Such findings form the basis for the development of agents that use non-DNA targets for the treatment of glioblastomas and may improve control over tumor proliferation and invasion.

Antineoplastic Agents, Alkylating↗
PubMed1996

GHRH activates a nonselective cation current in human GH-secreting adenoma cells.

Electrophysiological responses induced by human (h) growth hormone-releasing hormone (GHRH) were analyzed using the perforated whole cell clamp technique in human growth hormone (GH)-secreting adenoma cells. Application of hGHRH depolarized the membrane by increasing Na+ conductance. The reversal potential of the hGHRH-induced current was -20 to 0 mV. The channel was permeable to Na+, Li+ and K+ but not to TMA+. These properties were compatible with those of nonselective cation channels. Similar nonselective cation current was activated by 8-bromoadenosine 3',5'-cyclic monophosphate and forskolin, and the activation of the hGHRH-induced current was inhibited by protein kinase A (PKA) inhibitors, (R)-p-adenosine 3',5'-cyclic monophosphate and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoleinsulfonamide, and PKA inhibitor peptide PKI-(5-24), indicating that hGHRH-induced current was activated by PKA. Cholera toxin pretreatment eliminated the hGHRH-induced current, suggesting that Gs is involved in the activation of this current. This current became irreversible when the cells were pretreated with okadaic acid, suggesting that the recovery of the hGHRH-induced current was mediated by a serine/threonine protein phosphatase. GHRH-induced GH secretion was inhibited in Na+-free medium, suggesting the importance of the nonselective cation current on hGHRH-induced GH secretion. In human GH-secreting nonadenoma cells, hGHRH increased Na+ conductance, as was the case in GH-secreting adenoma cells.

Adenoma↗
PubMed1996

A study of anterior pituitary hormones secretion in patients with glioma receiving interferon-beta treatment.

Human interferon beta (IFN-beta) has been used for the treatment of patients with benign and malignant astrocytomas. The effect of IFN-beta on pituitary function, however, has not been precisely evaluated before. In this study the serum levels of various anterior pituitary hormones including GH, PRL, ACTH, and TSH were measured to determine the effects of IFN-beta on pituitary endocrine function in 19 consecutive glioma patients receiving IFN-beta. Daily doses of 3 x 10(6) U of IFN-beta were administered as a 30-min intravenous drip infusion beginning at 0800 h every morning during the first week and then 4 times a week for additional 6 weeks. Blood samples were taken on the day prior to administration as controls (0900 h and 1500 h), and on the first day of administration (0900 h and 1500 h) and after 7 days of administration (0900 h) in order to determine the acute and chronic or integrated effects of IFN-beta on the above pituitary hormones. No significant change in serum concentrations of any of the pituitary hormones examined was observed, suggesting that human natural IFN-beta used for the treatment of gliomas has no significant effect on the secretion of these hormones from the pituitary in these patients.

Adolescent↗
PubMed1996

Spontaneous intraventricular hemorrhage caused by lateral ventricular meningioma--case report.

A 39-year-old female presented with acute intraventricular hemorrhage manifesting as sudden onset of headache associated with gradually progressing somnolence and left oculomotor nerve paresis. Intraventricular hemorrhage occurred from a meningioma of the lateral ventricle. Computed tomography and magnetic resonance (MR) imaging revealed intraventricular hemorrhage and a mass in the right trigone. The tumor was totally removed. Her postoperative course was uneventful except for left homonymous hemianopia. The histological diagnosis was fibroblastic meningioma. The MR imaging was highly suggestive of hemorrhage from the tumor periphery.

Adult↗
PubMed1996

Expression of human Pit-1 product in the human pituitary and pituitary adenomas. Immunohistochemical studies using an antibody against synthetic human Pit-1 product.

OBJECTIVE: Pit-1, a member of a family of the POU-domain DNA binding factors, has been known as a pituitary-specific transcriptional factor that regulates functional differentiation toward somatotrophs, lactotrophs, and thyrotrophs in the rodent pituitary gland. The aim of this study is to elucidate the role of human Pit-1 (hPit-1) protein in the differentiation of human pituitary adenomas, using immunohistochemistry. DESIGN: Anti-human Pit-1 polyclonal antibody against synthetic peptide was applied to perform the avidin-biotinperoxidase complex method on paraffin sections of 75 surgically obtained pituitary adenomas and 12 nontumorous human pituitaries obtained at autopsy. RESULTS: In normal human pituitary glands, many cells were positive for hPit-1 product in the nuclei of somatotrophs, lactotrophs, and somatomammotrophs. Among 75 pituitary adenomas, hPit-1 product was expressed in 55 adenomas (73.3%). All (100%) of the growth hormone-positive and thyrotroph cell adenomas were positive for hPit-1 product. Unexpectedly, expression of hPit-1 was found in a limited number of adrenocorticotropic hormone-producing adenomas and clinically nonfunctioning adenomas, including gonadotroph cell adenomas, although localization was found only in occasional cells. CONCLUSIONS: The invariable expression of hPit-1 protein in growth hormone-positive adenomas and thyroid-stimulating hormone-positive adenomas may suggest the role of Pit-1 protein in specific differentiation of the adenoma cells. The expression of hPit-1 in various other types of adenomas may indicate the involvement of other unidentified transcription factors or specific mediators that have roles in these differentiations. Our observation may provide some insight into the origin of cell types of some clinically nonfunctional adenomas.

Adenoma↗
PubMed1996

Expression of Pit-1 and estrogen receptor messenger RNA in prolactin-producing pituitary adenomas.

The pituitary-specific transcriptional factor, Pit-1, is a member of the POU-domain family, which has a role in the development and differentiation of three pituitary cell types: somatotrophs, lactotrophs, and thyrotrophs. Recently, specific DNA-dependent interactions have been observed between Pit-1 and nuclear receptors, including: thyroid hormone receptor; retinoic acid receptor; glucocorticoid receptor; and estrogen receptor (ER). The cooperative interaction between Pit-1 and ER required for prolactin enhancer activity in rat pituitaries has been suggested. We analyzed the expression of Pit-1 messenger ribonucleic acid (mRNA) and ER mRNA in 15 human prolactin-producing adenomas using nonradioisotopic in situ hybridization. Their products were also studied by immunohistochemical analysis. Pit-1 mRNA was detected in 12 (80%) of 15 prolactin-producing adenomas. On the other hand, ER mRNA was detected in 14 (94%) of adenomas studied. mRNAs of Pit-1 and ER were detected more frequently than immunohistochemical expression of their products. By combined in situ hybridization and immunohistochemical examination, Pit-1 mRNA and ER mRNA were often colocalized with prolactin immunoreactivities. The colocalizations of Pit-1 mRNA and ER protein were observed in adenoma cells. The high incidence of the expression of ER mRNA in prolactin-producing adenomas may suggest cooperative interactions between Pit-1 and ER in functional differentiation and development of prolactin-producing adenomas.

Adolescent↗
PubMed1996

[Changes in arterial ketone body ratio (AKBR) in subarachnoid hemorrhage patients].

The arterial ketone body ratio (AKBR) is considered an accurate index of the functional reserve of the liver, and its validity has been confirmed in the field of abdominal surgery. We found low AKBR values subarachnoid hemorrhage patients and discuss the clinical significance of this finding in this paper. Twenty-eight patients with subarachnoid hemorrhage treated at our institution were included in this study. Their ages ranged from 26 to 81 years old (average: 61.5 years). According to the WFNS classification 12 cases were grade I, II, or III, and 16 were grade or IV V. Surgical clipping was performed in 23 of these cases, within 2 days after symptoms of subarachnoid hemorrhage appeared. There were eight cases of symptomatic vasospasm and three cases of re-ruptured aneurysm. Outcome was classified according to the Glasgow Outcome Scale (GOS) as: good recovery (GR), moderately disabled (MD), severely disabled (SD), vegitative survival (VS), and dead (D). Using these criteria, the outcome of these patients was as follows: GR or MD in 10 cases, SD or VS in 8 case, and D in 10 cases. Ten healthy adults were chosen as controls. We collected arterial blood samples on days 1, 2, 3, 7, 10 and 14 after the onset of symptoms (day 0) and measured the following: 1, beta-hydroxybutyrate; 2, acetoacetate; 3, epinephrine; and 4, norepinephrine. On day 0 total ketone body levels were higher (165.6 +/- 119.9 mumol/l), and AKBR values (0.65 +/- 0.24) were significantly lower than in the control group (2.50 +/- 1.09) (p < 0.001), while both epinephrine and norepinephrine levels were significantly higher, 506.5 +/- 200.3 pg/ml and 899.5 +/- 221.4 pg/ml, respectively. The AKBR value was 0.90 +/- 0.27 on day 1, 1.11 +/- 0.4 0 on day 2, and increased thereafter. The average AKBR value exceeded 1.0 on day 2 in the ten GR and MD cases. In the SD and PVS cases, however, it exceeded 1.0 on day 3, but in the D patients it never exceeded 1.0 and instead was significantly lower. AKBR values are known to decrease not only in hepatic failure, but in cases in which the liver energy charge is reduced, such as shock and hypoxemia, but no investigations have ever been performed to determine whether AKBR is altered in cerebrovascular disease. In this study, we found that AKBR values were lower in subarachnoid hemorrhage, presumably due to the reduced hepatic blood flow caused by the increased levels of epinephrine and norepinephrine. In addition, our findings suggested that the fluctuations in AKBR values were correlated with the outcome of subarachnoid hemorrhage patients.

Adult↗
PubMed1995

Dielectric study of the cooperative order-disorder transition in aqueous solutions of schizophyllan, a triple-helical polysaccharide.

Schizophyllan exists in aqueous solution as a triple helix, which is intact at room temperature. Its aqueous solution forms some ordered structure at low temperatures but undergoes a sharp transition to a disordered structure as the temperature is raised. The transition temperature Tc is about 7 and 18 degrees C for H2O and D2O solutions, respectively. This transition was followed by time-domain reflectometry to investigate dynamic aspects of the transition. In addition to a major peak around 10 GHz, the dielectric dispersion curve of a 20 wt % schizophyllan in D2O exhibited a small peak around 100 MHz below Tc and around 10 MHz above Tc. The major peak is due to bulk water, whereas the 100 MHz peak is assigned to "bound" or "structured" water, and that around 10 MHz to side-chain glucose residues. However, unlike usual bound water reported for biopolymer solutions, this "structured" water disappears abruptly when the temperature becomes close to Tc without accompanying a conformational transition of the main chain. The above assignment is consistent with the structure of the ordered phase derived from previous static data that it consists of side-chain glucose residues along with nearby water molecules surrounding the helix core that are interacting with each other loosely through hydrogen bonds, and spreads radially only a layer of one or two water molecules but a long distance along the helix axis.

Carbohydrate Conformation↗
PubMed1995

Changes in the ultrastructural distribution of prolactin and growth hormone mRNAs in pituitary cells of female rats after estrogen and bromocriptine treatment, studied using in situ hybridization with biotinylated oligonucleotide probes.

The expression and distribution of prolactin (PRL) mRNA and their alterations induced by estrogen and bromocriptine were investigated using non-radioisotopic in situ hybridization (ISH) at the electron microscopic (EM) level. Our EM-ISH studies using biotinylated oligonucleotide probes showed that estrogen induced whirling changes of the rough endoplasmic reticulum (RER) of female rat PRL cells and increased transcription of PRL genes located on the polysomes of the whirling RER. The presence of mammosomatotroph cells in the rat pituitary gland was also verified in our EM-ISH studies. After bromocriptine administration, PRL cells contained many secretory granules due to the inhibition of secretion. Pre- and post-embedding EM-ISH and northern hybridization studies revealed that bromocriptine induced the distorted, vesiculated, and dilated RER, and also the suppressed PRL mRNA expression. The activity of protein kinase C (PKC), which mediates PRL gene expression, tended to be elevated by estrogen and suppressed by bromocriptine. Therefore, it is considered that the ultrastructural and quantitative changes in PRL mRNA expression evoked by estrogen and bromocriptine may be mediated by the intracellular signal transduction system, including PKC.

Animals↗