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Biomedical subjects

T Fukami

Publications and source records attributed to T Fukami.

At least 55 records · Page 3Linked to original sources
PubMed1992

Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor.

We describe novel potent endothelin (ET) antagonists that are highly potent and selective for the ETA receptor (selective to ET-1). Of the synthetic analogs based on ETA antagonist BE-18257A isolated from Streptomyces misakiensis (IC50 value for ETA receptor on porcine aortic smooth muscle cells (VSMCs); 1.4 microM), the compounds BQ-123 and BQ-153 greatly improved the binding affinity of [125I]ET-1 for ETA receptors on VSMCs (IC50; 7.3 and 8.6 nM, respectively), whereas they barely inhibited [125I]ET-1 binding to ETB receptors (nonselective with respect to isopeptides of ET family) in the cerebellar membranes (IC50; 18 and 54 microM, respectively). Associated with the increased affinity for ETA receptors, these peptides antagonized ET-1-induced constriction of isolated porcine coronary artery. However, there was a small amount of ET-1-induced vasoconstriction resistant to these antagonists, which paralleled the incomplete inhibition of [125I]ET-1 binding in the membrane of the aortic smooth muscle layer. These data suggest that the artery has both ETA and ETB receptors responsible for ET-1-induced vasoconstriction. The antagonists shifted the concentration-response curve to the right for ET-1 in the coronary artery, and increased the apparent dissociation constant in the Scatchard analysis of [125I]ET-1 binding on the VSMCs without affecting the binding capacity, indicative of the competitive antagonism for ETA receptor. In conscious rats, pretreatment with the antagonists markedly antagonized ET-1-induced sustained pressor responses in dose-dependent fashion without affecting ET-1-induced transient depressor action, suggesting that the pressor action is mediated by ETA receptors, while the depressor action is mediated by ETB receptors. In addition, pretreatment with the potent antagonists prevented ET-1-induced sudden death in mice. Thus, these potent ETA antagonists should provide a powerful tool for exploring the therapeutic uses of ETA antagonists in putative ET-1-related disorders.

Amino Acid Sequence↗
PubMed1992

Analysis of responses to endothelins in isolated porcine blood vessels by using a novel endothelin antagonist, BQ-153.

We examined the effects of a novel ETA-selective endothelin (ET) antagonist, BQ-153, on vascular responses to ET-1 and ET-3 in isolated porcine coronary and pulmonary blood vessels, to clarify the roles of ET receptor subtypes in the regulation of vascular smooth muscle tension. With endothelium-denuded vascular tissues, the concentration-contraction curve (CCC) for ET-1 appeared as a single sigmoidal shape for all types of tissue. The CCC for ET-1 was antagonized by BQ-153 (2 and 10 microM) in all tissues, but part of the contraction was resistant. The CCC for ET-3 usually consisted of two different phases with higher (first phase) and lower (second phase) sensitivities to the peptide. Only the second phase of CCC for ET-3 was completely inhibited by BQ-153 (2 microM) in all tissues, while the first phase was resistant. The BQ-153-resistant contractile phases of ET-1 and ET-3-induced vasoconstriction appeared to have similar sensitivity in all tissues, and the contractile activity varied with each type of tissue. With endothelium-intact materials, the potencies of ET-1 and ET-3 for endothelium-dependent vasorelaxation in pulmonary artery were almost equivalent. BQ-153 (10 microM) did not inhibit ET-induced vasorelaxation. These results indicate that ET-induced vasoconstriction is mediated not only through ETA but also through ETnonA (probably ETB), and that the relative proportions of the ET-receptor subtypes mediating contractions vary in different vascular areas. In addition, results showed that ET-induced endothelium-dependent vasorelaxation is mediated through ETB.

Animals↗
PubMed1992

In vitro biological profile of a highly potent novel endothelin (ET) antagonist BQ-123 selective for the ETA receptor.

The novel endothelin (ET) receptor antagonists BE-18257A and BE-18257B were isolated from the fermentation products of Streptomyces misakiensis. The above-mentioned compounds inhibited [125I]ET-1 binding to ETA receptors (selective for ET-1) on porcine aortic vascular smooth muscle cells (VSMCs) with IC50 values of 1.4 and 0.47 microM, respectively. [125I]ET-1 binding to ETB receptors (nonselective to ET isopeptides) in cerebellar membranes was not inhibited by either of these compounds even at 100 microM. The synthesized analogue BQ-123 induced extremely potent inhibition of [125I]ET-1 binding to ETA receptors (IC50 of 7.3 nM), but it barely inhibited [125I]ET-1 binding to ETB receptors (IC50 of 18 microM) and binding of various other peptides to their receptors. BQ-123 shifted the concentration-response curve for ET-1 toward the right in porcine isolated coronary arteries, indicative of competitive antagonism for the ETA receptor. However, there was a small amount of BQ-123-insensitive vasoconstriction that paralleled the incomplete inhibition of [125I]ET-1 binding in the membrane of the vascular smooth muscle layer. These data suggest that the artery contracts via both ETA and ETB receptors and that BQ-123 selectively inhibits ETA-mediated contraction. Furthermore, BQ-123 revealed large tissue and species differences in the distribution of ETA receptors. Thus, the potent ETA antagonist BQ-123 should be useful in clarifying the (patho)physiological roles of ETA receptors.

Amino Acid Sequence↗
PubMed1991

[Abdominal metastasis of a pineal region tumor through ventriculoperitoneal shunt. Case report].

An 18-year-old male was admitted with headache, nausea, and vomiting. Computed tomography (CT) revealed an enhanced tumor of the pineal region and hydrocephalus. The tumor was partially resected via a parieto-occipital craniectomy. The histological diagnosis was germinoma. No serum tumor markers such as alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were detectable. A ventriculo-peritoneal (V-P) shunt was emplaced and radiation therapy (whole brain 59 Gy) given. The tumor and the hydrocephalus regressed completely and he returned to work. Six years later, he experienced constipation and general fatigue. CT and echotomography of the abdomen showed a large peritoneal tumor and ascites. Laboratory investigation demonstrated serum levels of AFP 7640 ng/ml and HCG 150 IU/l, and high ascitic levels of AFP 12,890 ng/ml and HCG 1030 IU/l. AFP and HCG levels regressed after combined chemotherapy. However, he died due to leukopenia and pneumonia. Autopsy found no metastasis of tumor cells to the central nervous system. The peritoneal cavity contained hemorrhagic fluid and a large tumor 4100 g in weight. The tip of the V-P shunt tube was in front of the tumor. No neoplasm was found in the testis, retroperitoneal cavity, thymus, and other organs. The microscopic appearance of the peritoneal tumor was different to the first pineal tumor. The neoplasm was confirmed as a mixed germ cell tumor with teratoma components and suspected to be a metastasis of the pineal tumor through the V-P shunt system.

Abdominal Neoplasms↗
PubMed1991

[Delayed evolution of post-traumatic contralateral extracerebral hematoma after evacuation of initial hematoma].

105 patients over a 5-year period underwent emergency evacuation of traumatic intracranial hematomas. Seven (6.7%) developed delayed contralateral extracerebral hematomas (5 epidural and 2 subdural hematomas). These hematomas were insignificant or not present on initial computed tomography (CT) scan, but repeat CT scan after craniotomy showed sizable hemorrhage. In one patient, neurological deterioration heralded the delayed onset. In one case, intraoperative ultrasound imaging disclosed an epidural hematoma. Ultrasound examination is recommended in cases with a skull fracture contralateral to the initial hemorrhage.

Adolescent↗
PubMed1989

[A case of epidermoid in the fourth ventricle associated with bronchial asthma-like symptom].

A case of large epidermoid located in the fourth ventricle is presented, and the patient's uncommon symptomatology of bronchial asthma-like episode is discussed. The value of magnetic resonance imaging (MRI) is also emphasized in the diagnosis of intracranial epidermoid. A 41-year-old male noticed nausea and vomiting on getting up in the morning about 5 years ago. This was followed by bronchial asthma-like dyspnea one year later. About one week prior to admission, headache and gait disturbance started. On neurological examination, he had choked disk and horizontal nystagmus at lateral gaze bilaterally. His gait was slightly ataxic. Computerized tomography (CT) showed a low density mass with a sharp and irregular margin in the mid-portion of the posterior fossa. That lesion was not enhanced with contrast medium. The MRI appearance was that of an inhomogenous and low signal intensity mass with a slightly irregular margin on T1-weighted spin echo (SE) sequences using TR500 msec/TR30 msec (TR500/TE30). The tumor extended into the aqueduct upward and the C1 level of spinal column downward. T2-weighted SE sequences using TR2000/TE90 showed an inhomogenous and high intensity mass with an irregular margin more apparent than in normal brain tissue. The patient was tentatively diagnosed as having a large fourth ventricle tumor. Suboccipital craniectomy was carried out on 4, March, 1988. The tumor was removed totally and histologically, it turned out to be epidermoid. He was discharged without neurological deficit 2 months after surgery. First, with respect to clinical symptomatology, as specified by Bailey, it is characterized by difficulty in standing or walking, vertigo, and less constantly, psychic disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Chemical structure of a new modified nucleoside located in the anticodon of Bombyx mori glycine tRNA2.

There are two species of glycine tRNA, tRNA(1Gly) and tRNA(2Gly), in the posterior silk glands of Bombyx mori. The first positions of their anticodons are guanosine and an unknown nucleoside for tRNA(1Gly) and tRNA(2Gly), respectively. This new nucleoside was isolated and the chemical structure was analyzed by thin layer chromatography and by UV, 1H-NMR, field desorption mass, and ORD spectroscopic measurements. The structure characterized by physical methods was finally confirmed by synthesis to be 5-((S)-carboxy(hydroxy) methyl)uridine methyl ester.

Animals↗
PubMed1988

Anti-tumor effect of dithiole compounds.

A series of dithiole compounds, N-(1,3-dithiole-2-ylidene)-N,N-dialkyl-ammonium salts, was synthesized and tested for anti-tumor activity. Most of them exhibited a potent cytotoxic activity against cultured cells at IC50 concentrations less than 1 micrograms/ml. They were also effective in increasing the life-span of mice bearing L1210 leukemic cells. Their anti-tumor activities both in vitro and in vivo were related to the length of alkyl chain moieties, among which EX-015, having n-decyl chains, was found to be most effective in vivo; EX-015 prolonged the survival time of mice implanted with L1210 cells by 69% when given once daily for 5 days at 0.8 mg/kg. In addition, EX-015 inhibited the RNA and protein syntheses of L1210 cells, but less so with the DNA synthesis.

Animals↗
PubMed1987

Spectroscopic properties of fluorescein in living lymphocytes.

Detailed studies have been performed on various spectroscopic properties such as time dependence and excitation wavelength dependence of the fluorescence anisotropy for fluorescein molecules introduced into rat thymus lymphocytes. Experimental results have been found to be well interpreted in terms of the coexistence of two types of dye molecules, i.e., free and bound molecules. The fluorescence spectrum of only the bound molecules has been obtained from the difference in the time-resolved spectra of fluorescence with two polarization directions. The time gate has been set at a sufficiently late time after the excitation, so that the polarization memories of the free molecules are lost. The spectrum thus determined agrees very well with that calculated from the spectral data in the stationary condition. From the above results, we come to the conclusion that the main factors which determine the fluorescence anisotropy inside the cell are the fraction and the anisotropy of the bound dye molecules. Finally, we discuss how these factors are related to biological quantities.

Animals↗
PubMed1986

[A case of unruptured A1 aneurysm causing ischemic compression to the medial proximal striate artery].

A 58-year-old female was admitted to our hospital because of weakness of the right lower extremity and dysesthesia of the right upper extremity. From her clinical symptoms the patient was tentatively diagnosed as having a sort of cerebral infarction and treated with administration of urokinase and antiplatelet agents. However, angiographical examination revealed a unruptured aneurysm of the A1 portion of the left anterior cerebral artery. Preoperative angiogram showed that the dome of the aneurysm compressed one of the neighboring perforating artery which arose from adjacent to the neck of the aneurysm. The patient underwent neck clipping of aneurysm successfully. During the operation, the perforator was hardly adhered to the dome of the aneurysm. So, careful dissection was made only around the neck and the perforator was spared. Her symptoms were disappeared immediately after surgery. The perforator was demonstrated with better filling in the postoperative angiogram than that in the preoperative angiogram. The pathomechanisms of cerebral ischemia caused by unruptured aneurysm were reviewed on the literature. Most of the cases were caused by release of fragmental thrombi from a large aneurysm. There was a very exceptional case whose symptoms had seemed to be related to the direct compression of the neighboring perforator by the aneurysm. The compressed perforator in this case was seemed to be corresponded with the medial proximal striate artery stated by Yaşargil.

Brain Ischemia↗
PubMed1984

[Urinary phosphate and cyclic adenosine monophosphate response to intravenous administration of synthetic human parathyroid hormone-(1-34) in idiopathic hypoparathyroidism, pseudohypoparathyroidism, pseudopseudohypoparathyroidism and normal subjects].

The response to exogenous parathyroid hormone (PTH) with urinary excretion of phosphate and cyclic adenosine monophosphate (cAMP) was tested by the use of synthetic human parathyroid hormone (1-34) [hPTH-(1-34)] on 59 patients with hypocalcemia and normal or high serum inorganic phosphorus and normal renal function without a history of parathyroidectomy for differentiation between idiopathic hypoparathyroidism (IHP), pseudohypoparathyroidism (PHP) and related diseases along with 18 normal subjects. A positive phosphaturic response to exogenous PTH was defined as the increment of 2 hours phosphate excretion (delta P) of more than 35 mg. A positive urinary cAMP response to exogenous PTH was defined as the increment by more than 1 mumole per one hour (delta cAMP) and the increase of 1 hour excretion by more than 10 times. Increments of 2 hours urinary phosphate excretion in response to hPTH-(1-34) 100 units were 60.5 +/- 7.7 mg (mean +/- SEM) in 27 patients with IHP, 23.5 +/- 5.9 mg in 21 patients with PHP type I and 24.9 +/- 4.0 mg in 17 normal subjects. Increments of 1 hour urinary cAMP excretion in response to hPTH-(1-34) 100 units were 12.0 +/- 1.5 mumole in 27 patients with IHP, 0.33 +/- 0.10 mumole in patients with PHP type I and 23.6 +/- 5.8 mumole in 15 normal subjects. Ratios of 1 hour urinary cAMP excretion were 97 +/- 10 in 27 patients with IHP, 3.6 +/- 0.5 in 21 patients with PHP type I and 54 +/- 14 in 15 normal subjects. Positive phosphaturic and negative urinary cAMP response was encountered in 3 out of 21 patients with PHP type I in response to hPTH-(1-34). This exaggerated phosphaturic response should be considered as due to the influence of treatment with Ca or vitamin D derivatives.

Adolescent↗
PubMed1984

Exploration of the pituitary stalk and gland by high-resolution computed tomography. Comparative study of normal subjects and cases with microadenoma.

By means of high-resolution CT, pituitary stalks and glands were demonstrated in 189 normal subjects and in six patients with microadenomas. In the horizontal view and in reconstructed coronal and sagittal projections, the normal stalks and glands showed homogeneous enhancement with the contrast medium. On metrizamide CT, the stalks and glands were demonstrated in high-density areas as a "defect". The detection-rate of the stalks and glands was more than 93.6% in all dimensions on enhanced CT and 100% on metrizamide CT. On reconstructed sagittal projections, there was a tendency for the glands to decrease in size with advancing age. Under the age of 29, especially in females, most of the glands were demonstrated as an oval area that filled the sella turcica. After the age of 50, the gland frequently was flattened with enlargement of the CSF space within the sella turcica, giving an appearance reminiscent of the "empty sella". Of six patients with microadenomas, five presented the appearance of oval gland, and one showed visualization of CSF space in the anterosuperior portion of the sella turcica. On reconstructed coronal projections, the angle of inclination of stalks was 1.5 +/- 1.2 degrees in normal subjects and 9.3 +/- 2.4 degrees in patients with microadenomas.

Adenoma↗
PubMed1984

Long-term follow-up review of cases of Parkinson's disease after unilateral or bilateral thalamotomy.

Follow-up reviews were carried out on 86 of 103 patients with Parkinson's disease who underwent unilateral or bilateral ventrolateral (VL) thalamotomy in the period from 1964 to 1969. Of these 86 patients, 64 received unilateral surgery, and 22 bilateral surgery. The follow-up periods were at least 10 years from the operation (from the second intervention in cases with bilateral procedures). In the group that received unilateral surgery, no progression after surgery was seen in three of six patients classified preoperatively in Grade I (Hoehn and Yahr's Grade 1), nine of 20 patients in Grade IIa (Hoehn and Yahr's Grade 2), 13 of 23 patients in Grade IIb (Hoehn and Yahr's Grade 3), and six of 15 patients in Grade III (Hoehn and Yahr's Grade 4). In the group that received bilateral surgery, one of three patients in Grade I and one of 11 patients in Grade IIa before the second intervention maintained continuous full social activities for over 10 years after the second surgery without any medication. In addition, eight of 11 patients classified preoperatively in Grade IIa and five of eight patients in Grade IIb seemed to show no progression after the second operation; four of 22 patients stopped taking their medication because of improvement in their symptoms. No patient who received bilateral surgery had progression of the disease to death. Observations suggested the efficacy of thalamic surgery, not only for improvement of motor symptoms but also for reducing progression of the disease, although no control study was made. Thalamotomy is still used to treat Parkinson's disease as an alternative to current medical treatments, such as L-dopa therapy.

Adult↗