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Biomedical subjects

T Yamaji

Publications and source records attributed to T Yamaji.

At least 37 records · Page 2Linked to original sources
PubMed1997

Genotype analysis of prepro-vasopressin signal peptide in vasopressin-producing and -non-producing lung tumors.

A polymorphism in the nucleic acid sequence encoding the signal peptide of the human prepro-vasopressin (AVP) has been reported in an AVP producing small cell lung carcinoma (SCLC) cell line. The difference predicts expression in tumor cells of a variant signal peptide with Pro for Leu 11. To clarify whether this difference is required for AVP secretion from SCLC cells and/or reflects increased mutagenesis in malignant tumors, the exon encoding the signal peptide of prepro-AVP in two AVP producing SCLC and 9 non-producing lung tumors was amplified using polymerase chain reaction. The variant sequence was neither found by direct sequencing nor by restriction enzyme analysis. These results suggest that similar to the hypothalamus the normal signal peptide is functional in tumor cells and that the variant signal peptide is not a prerequisite for AVP secretion from SCLC cells.

Animals↗
PubMed1997

Synthesis of a new potent anti-angiogenic agent, 17 alpha-acetoxy-9 alpha-fluoro-6 alpha-methylprogesterone (9 alpha-fluoromedroxyprogesterone acetate [FMPA]).

A new anti-angiogenic agent, 17 alpha-acetoxy-9 alpha-fluoro-6 alpha-methylprogesterone (9 alpha-fluoromedoroxyprogesterone acetate [FMPA, 9] was synthetized in a 10-step sequence. FMPA (9) had about two orders of magnitude stronger anti-angiogenic activity than medroxyprogesterone acetate (MPA), as estimated in a bioassay involving chorioallantoic membranes of growing chick embryos.

Animals↗
PubMed1997

Interaction of osmotic and nonosmotic stimuli in regulation of vasopressin secretion in hypoosmolar state of man.

Vasopressin (AVP) secretion is principally under osmotic regulation, which is altered by nonosmotic stimuli. It is known that the manner of osmotic regulation of AVP secretion in hypoosmolar state of man consists of four types. The types have (A) random changes in plasma AVP without relation of plasma osmolality; (B) plasma AVP secretion correlated closely to plasma osmolality with a low osmotic threshold for AVP release; (C) nonsuppressible AVP secretion with normal osmotic release of AVP; (D) no abnormalities in AVP secretion. In this study, we found an entirely different type of AVP secretion from the above types in six patients with hyponatremia resulting from various causes during infusion of 5% hypertonic saline. To clarify the mechanism underlying the AVP secretion, we analyzed the interaction between osmotic and nonosmotic stimuli of AVP secretion in these patients. Despite hyponatremia, plasma AVP levels in all patients were not suppressed, which was attributed at least in part to the presence of nonosmotic stimuli for AVP release. These stimuli include nausea, hypotension, blood volume contraction, glucocorticoid deficiency or their combinations. Hypertonic saline infusion increased both serum sodium concentrations and plasma osmolality, although to subnormal levels, and concomitantly, alleviated some of the nonosmotic stimuli for AVP release formerly present in these patients. However, plasma AVP concentrations decreased rapidly during the infusion and reached the nadir in all patients. This phenomenon may be due to alleviation of nonosmotic stimuli for AVP release. Thus, the findings indicate that the potentiating effect of nonosmotic stimuli for AVP secretion may modify the osmotic regulation of AVP secretion in hypoosmolar state, resulting in the type of AVP secretion in this study.

Aged↗
PubMed1996

Medial collateral ligament healing one year after a concurrent medial collateral ligament and anterior cruciate ligament injury: an interdisciplinary study in rabbits.

The optimal treatment for concurrent injuries to the medial collateral and anterior cruciate ligaments has not been determined, despite numerous clinical and laboratory studies. The objective of this study was to examine the effect of surgical repair of the medial collateral ligament on its biomechanical and biochemical properties 52 weeks after such injuries. In the left knee of 12 skeletally mature New Zealand White rabbits, the medial collateral ligament was torn and the anterior cruciate ligament was transected and then reconstructed. This is an experimental model previously developed in our laboratory. In six rabbits, the torn ends of the medial collateral ligament were repaired, and in the remaining six rabbits, the ligament was not repaired. Fifty-two weeks after injury, we examined varus-valgus and anterior-posterior knee stability; structural properties of the femur-medial collateral ligament-tibia complex; and mechanical properties, collagen content, and mature collagen crosslinking of the medial collateral ligament. We could not detect significant differences between repair and nonrepair groups for any biomechanical or biochemical property. Our data support clinical findings that when the medial collateral and anterior cruciate ligaments are injured concurrently and the anterior cruciate ligament is reconstructed, conservative treatment of the ruptured medial collateral ligament can result in successful healing.

Animals↗
PubMed1996

A naturally occurring 46-amino acid deletion of cytidine monophospho-N-acetylneuraminic acid hydroxylase leads to a change in the intracellular distribution of the protein.

Cytidine monophospho-N-acetylneuraminic acid (CMP-NeuAc) hydroxylase is a key enzyme for the expression of N-glycolylneuraminic acid. The molecular cloning of this enzyme from mouse liver has been described in our previous report (Kawano T, Koyama S, Takematsu H, Kozutsumi Y, Kawasaki H, Kawashima S, Kawasaki T, Suzuki A (1995) J Biol Chem 270: 16458-63). During the cDNA cloning, a cDNA containing a truncated open reading frame (ORF) was isolated. This clone encodes a protein of 531 amino acids which lacks 46 amino acids in the middle of the normal full-length protein. The percentage of this mRNA containing the truncated ORF out of the total population of CMP-NeuAc hydroxylase mRNA in various mouse tissues was about 10-25%. The truncated protein was expressed in COS-1 cells, but did not show any enzymatic activity. The truncated protein was localized to the region which appeared to be the endoplasmic reticulum, whereas the full-length protein with normal enzymatic activity was detected in the cytosol. These data suggest that this naturally occurring 46-amino acid deletion leads to a change in the intracellular distribution of CMP-NeuAc hydroxylase, and a loss in the activity of this enzyme.

Amino Acid Sequence↗
PubMed1996

Differences in response of thyrotropin to 3,5,3'-triiodothyronine and 3,5,3'-triiodothyroacetic acid in patients with resistance to thyroid hormone.

This study investigated the response of TSH secretion to 3,5,3'-triiodothyronine (T3) and 3,5,3'-triiodothyroacetic acid (Triac) in patients with resistance to thyroid hormone, and compared the responses with those in patients with TSH-secreting pituitary adenoma and normal subjects. A short-term administration of 75 microg of T3 daily for 7 days suppressed serum TSH concentrations almost completely in normal subjects, but suppressed TSH only partially in patients with resistance to thyroid hormone and TSH-secreting pituitary adenoma. A single-dose administration of 75 microg of T3 gave similar results in regard to TSH suppressibility in these three subjects groups. In contrast, a single-dose administration of 1.4 mg of Triac remarkably suppressed serum TSH concentrations after 2 hours in not only normal subjects (-34 +/- 11% [mean +/- SD] from the basal value) but also in patients with resistance to thyroid hormone (-31 +/- 9%), and this TSH suppression continued for 4 hours. After 24 hours, this TSH suppression persisted in normal subjects (-62 +/- 12%) but was relieved in patients with resistance to thyroid hormone (-23 +/- 14%). After the Triac administration, molar ratios of alpha-subunit to TSH in serum were decreased in patients with TSH-secreting pituitary adenoma but increased in patients with resistance to thyroid hormone. Because the Triac therapy for patients with resistance to thyroid hormone suppressed pituitary-TSH secretion during the early phase of drug ingestion, this drug should be given several times within a day to obtain continuous TSH-suppressive effects.

Adenoma↗
PubMed1996

Effects of clomipramine and verapamil on 5-HT-induced intracellular calcium changes in individual C6 rat glioma cells.

The effects of antidepressants and calcium (Ca2+) antagonists on serotonin (5-HT)-induced Ca2+ increase were investigated in single C6BU-1 glioma cells with digital imaging microscopy. Application of 5-HT (100 nM-100 microM) caused a rapid and reversible rise of intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner. In the absence of extracellular Ca2+, the sustained phase of the [Ca2+]i response was strongly reduced, which was greater than the suppression of the initial peak. This suggests that the peak value is mainly due to internal Ca2+ storage sites, and the sustained phase is mainly composed of Ca2+ influx. The sustained phase was significantly attenuated by 100 nM clomipramine and verapamil. The present findings demonstrate that clomipramine and verapamil, in their therapeutic concentrations, have a common action of inhibiting Ca2+ influx, and suggest that the calcium antagonistic effect may play an important role in clinical effects of antidepressants.

Animals↗
PubMed1996

Effects of carbamazepine and sodium valproate on 5-HT-induced calcium increase in individual C6 rat glioma cells.

The effects of drugs for affective disorders on the sustained phase of serotonin (5-HT)-induced calcium (Ca2+) response were investigated in single C6BU-1 glioma cells with digital imaging microscopy. The sustained phase was significantly attenuated by 32 microM carbamazepine and 320 microM sodium valproate as well as 100 nM clomipramine and verapamil, whose effects we evaluated in our previous report. The present findings demonstrate that drugs for affective disorders, in their therapeutic concentrations, have common action of inhibiting Ca2+ influx, and suggest that the Ca2+ antagonistic effect may play an important role in the mechanism of the action sites of the drugs for affective disorders.

Animals↗
PubMed1995

Sandwich immunoassay specific for the N-terminal sequence of osteocalcin.

A monoclonal antibody (10B) against the N-terminal sequence of human osteocalcin was selected to characterize its epitope and species specificity. The cross-reactivity of 10B with human and rat osteocalcin demonstrated that the reactivities of 10B with both human and rat osteocalcins were very similar. The pin technology method was used to determine the epitope and clearly demonstrated that the epitope recognized by 10B was localized to residues 12-16, the sequence of which is identical in rat and human osteocalcin molecules. This monoclonal antibody was found to be useful for designing region-specific sandwich immunoassay systems for human and rat N-terminal osteocalcin (N-OC) molecules using rabbit anti-hN20 and anti-rN20 polyclonal antibodies, respectively. The osteocalcin levels in serum determined by this N-OC method were stable during prolonged storage at 25 degrees C and the method could be usefully applied in the development of immunoassay systems for many osteocalcin molecules from many other species.

Amino Acid Sequence↗
PubMed1995

Cyclic GMP generation mediated by 5-HT-2 receptors via nitric oxide-dependent pathway and its effect on the desensitization of 5-HT-2 receptors in C6 glioma cells.

Serotonin (5-HT)-2 receptor-mediated cGMP generation was investigated in comparison with calcium (Ca2+) mobilization in C6 glioma cells. 5-HT enhanced cGMP generation, and risperidone and ketanserin potently blocked the response. These results indicate that 5-HT-2 receptors are responsible for the cGMP generation. 5-HT-induced cGMP production was completely abolished by BAPTA, an intracellular Ca2+ chelating agent, or NG-mono-methyl-L-arginine(NMMA), a nitric oxide synthase (NOS) inhibitor, suggesting that 5-HT-induced cGMP generation was through nitric oxide (NO)-dependent pathway. 5-HT (10 microM)-elicited Ca2+ mobilization and cGMP generation were reduced to 40 and 15% after pretreatment with 10 microM 5-HT for 4 hours. NMMA did not modify 5-HT-induced desensitization of either Ca2+ mobilization or cGMP generation, suggesting that NO pathway is independent of the desensitization. The present study has demonstrated the nature of 5-HT-2 receptor-mediated cGMP generation in C6 glioma cells.

Animals↗
PubMed1995

Discordant findings between krypton-81m gas and Tc-99m labeled ultrafine aerosol lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis.

Technegas, a newly developed ultra-fine dry dispersion of Tc-99m labeled carbon with a particle size of approximately 5 nm to 20 nm, possesses the properties for lung ventilation imaging using SPECT. The authors observed a discrepancy between krypton-81m gas and technegas lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis who demonstrated heterogeneously decreased distribution of technegas without regions of high count density (focal hot spots) of tracer in their lungs in spite of the almost homogenous distribution of krypton-81m gas. This finding could be explained by the duration of radioactive gas inhalation. Technegas lung ventilation SPECT images reflected lung ventilation with tidal breathing. Conversely, Kr-81m gas lung ventilation SPECT images reflected not only lung ventilation, but also lung volumes. These two radioactive agents for lung ventilation SPECT show different findings.

Administration, Inhalation↗
PubMed1995

Hyponatremia and osmoregulation of vasopressin secretion in patients with intracranial bleeding.

To clarify the cause and pathophysiology of hyponatremia after intracranial bleeding, we analyzed the possible causative factors, and examined the response of vasopressin (AVP) secretion to osmotic stimulus in six patients. Despite hyponatremia, urinary sodium excretion persisted, with urinary osmolality exceeding plasma osmolality. Serum levels of urea nitrogen, creatinine, and uric acid were not elevated in any of them. PRA was normal or subnormal in four patients, and all had normal adrenocortical and thyroid functions. Although these laboratory findings may support the diagnosis of the syndrome of inappropriate antidiuretic hormone secretion, the cause of hyponatremia in our patients was attributed to excessive renal excretion of sodium, because water load performed in an euvolemic state showed no impairment in diuresis, and replenishment of sodium without water restriction improved hyponatremia as well as clinical conditions. Plasma AVP levels relative to plasma osmolality in these patients were constantly elevated. When challenged by an osmotic stimulus, AVP secretion increased with increasing plasma osmolality in one patient, but no consistent pattern of AVP secretion was observed in others. The potentiating effect of hypovolemia on osmotic secretion of AVP was not demonstrated in any of the patients. These results show that hyponatremia after intracranial bleeding with clinical features almost indistinguishable from those of syndrome of inappropriate antidiuretic hormone secretion may result from an impaired renal sodium-conserving mechanism of unknown cause. Persistent AVP secretion without an alteration in the sensitivity of the osmostat in this pathological state may be due to an incomplete suppression by plasma hypotonicity per se of the baroreceptor-mediated stimulation of AVP release.

Aged↗
PubMed1994

Inhibition of growth of human small cell lung cancer by bromocriptine.

Bromocriptine, a dopaminergic agonist, inhibited the growth of human small cell lung cancer (SCLC) implanted as tumor xenografts in athymic nude mice; the effect was dose dependent. In mice bearing a SCLC with ectopic vasopressin production, plasma levels of human vasopressin-associated neurophysin decreased concomitantly. Electron microscopy of tumor tissues revealed marked degenerative changes, including pyknosis, densely aggregated chromatin masses, and vacuolization of cytoplasm after bromocriptine treatment. When a SCLC cell line, NCI-H69, was grown in semisolid medium, bromocriptine inhibited its clonal growth in a dose-related manner. Coincubation with dopamine D2 receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D2 receptor ligand, [125I]iodosulpride, showed high affinity binding sites on the membranes of SCLC cells. These results indicate that SCLC cells are enriched with dopamine D2 receptors, which may mediate the growth-inhibitory effect of bromocriptine on SCLC. Dopaminergic agonists may be useful in the medical treatment of SCLC.

Animals↗
PubMed1994

Endothelin-1 as an aggravating factor of disseminated intravascular coagulation associated with malignant neoplasms.

BACKGROUND: Vascular endothelial damage may play an important role in the pathophysiology of disseminated intravascular coagulation (DIC), a frequent complication of malignant neoplasms. It may mediate a variety of triggering events to initiate DIC and platelet aggregation, which in turn leads to additional endothelial destruction. If so, endothelin-1 (ET-1), the most potent vasoconstrictor of naturally occurring pressor substances known, may leak from injured endothelial cells and aggravate the disease process. METHODS: The study included 36 patients with various malignant neoplasms in whom DIC developed. The authors measured plasma levels of ET-1 and big ET-1, a precursor peptide of ET-1, in these patients and compared them with other laboratory abnormalities during the course of DIC. RESULTS: Plasma ET-1 and big ET-1 levels were elevated in most patients with DIC. When compared with the results of other diagnostic tests, elevated plasma big ET-1 was the most frequently found abnormality associated with DIC. Elevation of plasma ET-1 and big ET-1 levels was closely related to the initiation and progression of DIC and provided a higher degree of sensitivity and specificity than did other indicators in assessing patients with cancer and DIC. CONCLUSIONS: Vascular endothelial damage with the resultant increases in plasma ET-1 and big ET-1 levels is universally associated with DIC caused by malignancy. Excessive secretion or leakage of ET-1 and big ET-1 from injured endothelial cells may cause vasospasm and aggravate the DIC process by facilitating the formation of intravascular microthrombi, ultimately leading to ischemic end-organ dysfunction. Plasma ET-1 and big ET-1 are sensitive and specific markers for vascular endothelial injury in DIC.

Adult↗
PubMed1994

Endothelin-1 and big endothelin-1 in NIDDM patients with and without microangiopathy.

To examine a possible role for endothelin-1 in the pathophysiology of diabetic microangiopathy, we measured plasma levels of endothelin-1 and big endothelin-1, a precursor peptide of endothelin-1, in 33 untreated patients with non-insulin-dependent diabetes mellitus. There was no significant difference among the mean plasma endothelin-1 concentrations in 18 patients with microangiopathy, in 15 patients without microangiopathy and in 33 age-matched normal subjects. In contrast, the mean plasma big endothelin-1 concentration in patients with microangiopathy was significantly higher than in those without microangiopathy or in normal subjects. As a consequence, the mean big endothelin-1 to endothelin-1 ratio in patients with microangiopathy was significantly higher than in the other two groups. There was no significant correlation between plasma levels of endothelin-1 or big endothelin-1 and fasting blood glucose, HbA1c, mean blood pressure, or period of duration of diabetes mellitus in the patient groups. The results indicate that elevation of plasma big endothelin-1 levels with diminished conversion of big endothelin-1 to endothelin-1 is associated with diabetic microangiopathy, which may be the effect rather than the cause of endothelial dysfunction.

Adult↗
PubMed1993

Spontaneous remission in Cushing's disease.

Two patients with Cushing's disease underwent spontaneous clinical and biochemical remission following a period of secondary adrenal insufficiency. One of the patients was untreated, while the other had been treated with partial bilateral adrenalectomy before. Both patients underwent remission shortly after the administration of dexamethasone for diagnostic purposes and remained symptom free for 2 and 3 years, respectively, which was followed by relapse of the disease. We conclude that although resolution of Cushing's disease may occur spontaneously, probably by hemorrhagic infarction of corticotroph microadenomas, careful follow-up studies are required since the relapse of the disease occurs later in some patients.

Adrenalectomy↗