Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 109 records · Page 6Linked to original sources

PubMed2000

Retinoidal pyrimidinecarboxylic acids. Unexpected diaza-substituent effects in retinobenzoic acids.

Several pyridine- and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]pyri dine-3-carboxylic acid (2b) and 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]py ridine-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)a mino]pyrimidine-5-carboxylic acid (PA013, 10e) is most active retinoid synergist in HL-60 assay.

Animals↗

PubMed2000

[Preparation of novel specific aminopeptidase inhibitors with a cyclic imide skeleton].

The studies on both structure-activity relationship study and identification of the target enzyme of novel nonpeptide aminopeptidase inhibitors with cyclic imide skeleton are reviewed. Some N-phenylphthalimide or N-phenylhomophthalimide derivative showed potent protease inhibitory activity in an assay system using human acute lymphoblastic leukemia cells, Molt-4, with alanin-4-methylcoumaryl-7-amide (ala-AMC) as a substrate. Especially, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22) (3) was found to be the most potent inhibitor and further it showed potent tumor-cell invasion inhibitory activity that is more effective than potent peptide aminopeptidase inhibitors such as bestatin (1) or actinonin (2). For the further investigation of this novel protease inhibitory activity, we have carried out the structural development of PIQ-22 (3) and it is assumed that tautomerism of imidobenzoylketone in cyclic imide structure may be related to the inhibitory activity. The requirement for the activity of electron donating groups such as NH2 or OH to the condensed phenyl ring in phthalimide inhibitors also supports this possibility. The target aminopeptidase of PIQ-22 was identified as puromycin-sensitive aminopeptidase (PSA), by N-terminal amino acid sequencing, and by comparison with chromatographic behavior and substrate-selectivity, and so on. Lineweaver-Burk plot showed that PSA is inhibited by PIQ-22 (3) in a noncompetitive manner while puromycin (83) and bestatin (1) inhibit PSA competitively.

Aminopeptidases↗

PubMed2000

[Chemical control of cell differentiation of human myeloleukemia K562 cell line].

Human myeloid leukemia K562 cells can be induced to differentiate to mature cells bidirectionary, i.e., hemin induces erythroid differentiation, while 12-O-tetradecanoylphorbol 13-acetate (TPA) induces differentiation to monocytes. The differentiation-inducing activity of various hemin-related compounds suggested certain structural requirements for the activity: 1) the iron moiety of hemin is not essential, and 2) the propionic acid side chains of hemin play an important role in the differentiation and induction. In addition, we have examined the influence of some bioresponse-modifying factors on hemin/protoporphyrin IX-induced differentiation of K562 cell line. Retinoids and tubulin-disruptors, themselves did not induce differentiation, enhanced hemin/protoporphyrin IX-induced differentiation of K562 cells. We also examined the possible involvement of peripheral-type benzodiazepine receptor (PBR) in hemin/protoporphyrin IX-induced differentiation on K562 cell lines. The PBR specific ligands modified hemin-induced differentiation. These results suggest a requirement for retinoids (or retinoids-like cofactors) for hemin/protoporphyrin IX-induced differentiation of K562 cells and the involvement of PBR in erythroid differentiation of K562 cell line. Further we showed that TPA suppresses hemin-induced erythroid differentiation of K562 cells, while retinoids augment it. TPA is a potent inducer of heme oxygenase (HO), which catabolizes heme to biliverdin. An HO inhibitor, tin protoporphyrin (SnPP), suppresses TPA-induced K562 cell differentiation to monocytes. It was also found that cotreatment of K562 cells with SnPP and TPA induces erythroid differentiation of K562 cells, though SnPP alone or TPA alone does not induce erythroid differentiation, suggesting a role of HO in the directional switch of differentiation.

Cell Differentiation↗

PubMed2000

Distribution and developmental change of lymphoid tissues in the chicken proventriculus.

In the chicken proventricular mucosa, aggregations of lymphocytes were localized in three different sites of the lamina propria, namely, underneath the surface epithelium, near the duct orifice of the deep proventricular gland, and in the gland tissue itself. In the lymphoid masses underneath the surface epithelium and in those near the duct orifice, CD4+ T lymphocytes and TCR2+ T lymphocytes occupied their central part, and B lymphocytes were localized in the periphery. CD8+ T lymphocytes and TCR1+ lymphocytes were evenly distributed in the masses. Infiltration of lymphocytes into these sites was first observed on the 20th embryonic day. At 1 week after hatching, CD3+ lymphocytes began to occupy the central area of the masses and His-C1+ B lymphocytes tended to be located in the periphery. Ultrastructurally, M cells were found neither in the epithelium of the mucosa nor in that of the excretory duct close to the lymphoid masses. In the deep proventricular gland, the lymphoid masses had a germinal center consisting of B lymphocytes, surrounded by the T lymphocyte-rich periphery. These masses were first recognized at the 3rd post-hatching week, presumably being formed against possible antigens invading into the lumen of the proventricular gland. On the other hand, the lymphoid masses beneath the surface epithelium and those near the duct orifice existing before the hatching period were considered to be prepared to establish the local mucosal immune barriers against the expectant antigenic invasion.

Animals↗

PubMed2000

Serum progesterone and estradiol-17beta concentrations in captive and free-ranging adult female japanese black bears (Ursus thibetanus japonicus).

Progesterone (P4) and estradiol-17beta (E2) concentrations were measured in serum samples obtained from 23 captive and 23 free-ranging adult female Japanese black bears. We then determined the relationship between changes in these sex steroid hormones and pregnancy. In all captive bears, which included animals of both known and unknown reproductive status, serum P4 concentrations were low from April to July, then tended to become higher after August. The levels then became much higher still in November and December, but returned to low levels in March. Serum P4 concentrations in eight captive pregnant bears, which had parturitions the following spring, increased gradually from August (0.5-2.4 ng/ml) to October (0.9-3.6 ng/ml), and achieved significantly higher maximum levels in December (7.2-18.0 ng/ml). Thereafter, serum P4 concentrations tended to decrease (3.5-6.4 ng/ml in January and 0.3-0.7 ng/ml in March). In all captive bears, serum E2 concentrations varied from April to October but showed low levels in November and December, and became high in January. Serum E2 concentrations in the eight pregnant bears were high in May (95.6-191.4 pg/ml) and varied from August to October (35.6-143.3 pg/ml). Subsequently, serum E2 concentrations in December dropped to significantly lower minimum levels (5.3-11.9 pg/ml) and increased again in January (67.6-153.1 pg/ml). Among the free-ranging bears, the data on serum P4 concentrations in eight bears led to expectations of pregnancy, whereas serum E2 concentrations showed no distinct evidence related to pregnancy. These results, particularly in captive pregnant bears, indicate that a marked increase of P4 in December might be accompanied by reactivation of the corpus luteum preceding implantation. Furthermore, changes in E2 concentrations suggested the possibility that a decline in December and an increase in January are associated with implantation and parturition, respectively.

Animals↗

PubMed2000

Detection of exogenous growth hormone (GH) administration by monitoring ratio of 20kDa- and 22kDa-GH in serum and urine.

We previously demonstrated that individual subjects have fairly constant ratios of serum concentrations of 20 kDa- (20K) and 22 kDa-GH (22K). The aim of this study is to demonstrate the possibility of utilizing the changes in the ratio of 20K/22K for detecting the exogenous administration of 22K. A male patient with idiopathic dilated cardiomyopathy (age 51) received 22K (4U, s.c.) every other day. The concentrations of 20K and 22K in serum and urine were measured using enzyme-linked immunosorbent assays before and after administration. The administration of 22K increased total GH concentration, and markedly decreased the ratio of 20K/22K in serum, especially 2-10 h after the administration. From calculations, it became clear that the concentration of exogenous 22K reached a peak between 2-4 h after the administration and decreased to a negligible level after 24 h. The ratio of 20K/22K in the 0-24 h urine was 5 times lower than that in the 24-48 h urine. These data suggest that, by monitoring the ratio of 20K/22K in serum or urine, it is possible to determine whether or not GH has been externally administered and to calculate the serum GH that has been administered.

Cardiomyopathy, Dilated↗

PubMed2000

Serum concentrations of 20K human growth hormone in normal adults and patients with various endocrine disorders. Study Group of 20K hGH.

The 20K hGH isoform is produced by alternative splicing of GH mRNA, and comprises approximately 10% of all GH in the pituitary. The physiological role of 20K hGH remains to be determined partly because of the lack of a simple and specific assay. We have established sensitive enzyme-linked immunoadsorbent assays (ELISAs) specific to 20K and 22K hGH. The serum levels of 20K hGH after overnight fasting was 118 +/- 178 pg/mL (N=282) in normal women, significantly higher than in normal men (64 +/- 170 pg/mL, N=226). However, there was no difference in the proportion of 20K hGH to 20K plus 22K hGH between men (6.3 +/- 2.6%, N=176) and women (6.3 +/- 2.1%, N = 263). No correlation was detected between the ratio of 20K hGH and age, body height, body weight or body fat mass in normal subjects. The proportion of 20K hGH was significantly (P < 0.001) higher in patients with active acromegaly (9.2 +/- 2.2%, N=33) and in patients with anorexia nervosa (9.0 +/- 1.9, N=8), both of which are characterized by chronic elevation of circulating GH levels. The proportion of the 20K hGH in successfully treated acromegalic patients did not differ from that in normal subjects, suggesting that GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or chronic excess of 22K hGH altering the metabolic clearance rate of 20K hGH. The values in patients with adult growth hormone deficiency (GHD), hyperthyroidism, primary hypothyroidism, or GH-independent short stature did not differ from those in normal subjects. The 20K ratio did not change after acute GH provocative tests such as insulin tolerance test and GRH test. These results suggest that secretion of 20K hGH from the pituitary is under the same control as that of 22K hGH.

Acromegaly↗

PubMed2000

Usefulness of beta blocker therapy in patients with Takayasu arteritis and moderate or severe aortic regurgitation.

The objective of the present study was to evaluate the benefit of beta-blocker therapy for patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. Clinical and echocardiographic evaluation was performed in 20 Japanese women in a follow-up period of 7.0 +/- 2.0 years. The patients were divided into 2 groups: Group A (n=10) patients who did not receive beta-blockers, and Group B (n=10) patients treated with long-term (5.1 +/- 1.6 years) therapeutic doses of beta-blockers. Left ventricular wall thickness increased significantly in all Takayasu patients who did not receive beta-blockers. Consequently, a remarkable increment in left ventricular mass took place (232 +/- 59 to 361 +/- 79 g; p < 0.005). In the same group, progressive worsening of the symptoms, with no reduction in the percent fractional shortening, was observed in 2 patients, while reduction of this last index was present in 1 asymptomatic patient. On the other hand, among the patients who were treated with beta-blockers, left ventricular mass still increased in 6 cases, while it clearly decreased in the other 4 cases (290 +/- 171 to 284 +/- 61 g; NS). The increment in wall thickness or left ventricular mass observed among patients with beta-blocker therapy was clearly less than the one registered among those who had not received beta-blockers. Furthermore, no worsening of the symptoms and/or left ventricular performance was observed during the follow-up period for patients receiving beta-blockers. We conclude that beta-blocker therapy can slow and even reverse the progression of left ventricular hypertrophy in patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. The mechanism still needs to be elucidated. We believe an effective reduction in the excessive afterload imposed on the left ventricle to be most likely responsible, but cardiac beta-receptor up-regulation might also be involved. Deterioration of the clinical status and/or impairment of left ventricular function were not associated with beta-blocker therapy in our patients. Therefore, these agents can be used safely alone or in addition to standard anti-hypertensive therapy when attempting to reduce excessive afterload, in spite of the presence of severe aortic regurgitation.

Adrenergic beta-Antagonists↗

PubMed2000

Influence of exposure to new circumstances on pharmacokinetics of plasma drugs concentrations in rats.

The influences of emotional changes induced by being exposed to a new environment on the pharmacokinetics of plasma drug concentration were studied in male Wistar rats. Transfer from a familiar home cage to a new home cage was considered to induce psychological (non-physical) emotional changes. First, nicorandil and zonisamide, drugs that act on the peripheral system and central nervous systems, were used, respectively. Immediately after oral administration of nicorandil (10 mg/kg) or zonisamide (50 mg/kg), the animals were transferred to new home cages. Plasma nicorandil and zonisamide concentrations were determined by high-performance liquid chromatography at 1 and 4 h after administration. Plasma nicorandil concentration in the group transferred to new home cages was significantly decreased relative to levels in the non-transferred control group. However, zonisamide concentrations were unchanged. These findings suggest that the pharmacokinetics of nicorandil, but not those of zonisamide, tend to be influenced by non-physically induced emotional changes.

Animals↗

PubMed2000

Magnetic resonance imaging findings in primary amyloidosis-associated arthropathy.

The MRI findings of amyloid arthropathy associated with primary amyloidosis are presented here possibly for the first time in the literature. Two types of lesions are noted: (1) capsular and tendon lesions; these regions are thickened, hypointense and enhanced by gadolinium (Gd) on T1 weighted imaging (T1WI), and hyperintense on T2 weighted imaging (T2WI), and (2) periarticular and osseous lesions; these regions appear to be tumor-forming and hypointense on both T1WI and T2WI and are not enhanced by Gd. It is necessary to differentiate these findings from other diseases such as chondrosarcoma, rhabdomyosarcoma and chronic inflammatory lesions such as tuberculosis.

Amyloidosis↗

PubMed2000

Assessment of magnesium status in patients with bronchial asthma.

To elucidate the contribution of magnesium to bronchial hyperreactivity in patients with stable bronchial asthma, magnesium concentrations in serum (S-Mg), erythrocytes (R-Mg), and lymphocytes (L-Mg) were measured in 25 patients with bronchial asthma (BA group) and 9 age-matched healthy subjects (control group). A parenteral magnesium loading test, a continuous low-dose magnesium infusion of 0.2 mEq/kg over 4 hr, was performed in 10 of 25 asthmatic patients and in the control group. R-Mg was significantly lower in the BA group than in the control group (4.96 +/- 0.47, 6.13 +/- 0.62 mEq/L, p < 0.001, respectively), although S-Mg (2.4 +/- 0.1, 2.4 +/- 0.2 mg/dL) and L-Mg (1.28 +/- 0.26, 1.15 +/- 0.13 microg/mg/protein) were not significantly different between the two groups. Magnesium deficiency in total body stores was revealed in 40% of patients (4/10 patients) and 11% of control subjects (1/9 subjects) by parenteral magnesium loading test. The ratio of magnesium retention to urinary excretion through the parenteral magnesium loading test showed a significant inverse correlation with R-Mg (r = -0.78, p < 0.01). Bronchial reactivity to inhaled methacholine had a significant inverse correlation with R-Mg (r = -0.42, p < 0.05). We conclude that 40% of asthmatic patients demonstrated magnesium deficiency, and that the low magnesium concentration in erythrocytes reflects decreased magnesium stores in patients with bronchial asthma.

Adolescent↗

PubMed2000

Structures of ADP-ribosylated rifampicin and its metabolite: intermediates of rifampicin-ribosylation by Mycobacterium smegmatis DSM43756.

23-(O-ADP-Ribosyl)rifampicin [RIP-TAs (3, Na+ form), RIP-TAf (4, H+ form)] was obtained as an intermediate in the conversion process of rifampicin (1) to RIP-Mb (2) that is mediated by cell homogenates of Mycobacterium smegmatis DSM43756 or of Escherichia coli carrying a mycobacterial mono(ADP-ribosyl) transferase gene, in the presence of NADH. 23-[O-(5'-Phosphoribosyl)]rifampicin (5, RIP-TAp) was also obtained by the reaction of rifampicin with NADH in the presence of a homogenate of M. smegmatis. The structures of 3, 4, and 5 were determined by means of MS and NMR analyses.

ADP Ribose Transferases↗

PubMed2000

[Anesthetic management of a patient with hemophilia A for left modified Blalock-Taussig shunt].

We gave anesthesia to a patient with hemophilia A for left modified Blalock-Taussig shunt. The patient was a twenty five-day-old boy with pulmonary atresia. We performed the bolus injection test of factor VIII concentrate in preoperative period. His factor VIII activity increased from 9.3 to 113.3% after a bolus injection of 165 units. To keep his factor VIII activity above 80% in perioperative period, a bolus of 125 units of recombinant factor VIII concentrate was injected at anesthesia induction, 125 units 2 hours after the start of the operation, and 125 units 6 hours after the end of the operation. Factor VIII activity 2 hours after anesthesia induction increased only 37.8%, and we had to infuse recombinant factor VIII concentrate additionally. We measured factor VIII activity during operation, and he finally received total of 415 units of factor VIII concentrate. Hydroxyethyl starch infusion, blood transfusion and bleeding in the perioperative period might have caused the factor VIII activity to decrease beyond our expectation. We should infuse factor VIII concentrate properly measuring the factor VIII activity during this operation.

Anastomosis, Surgical↗

PubMed2000

[Left atrial pressure gradient and right heart failure secondary to compression of the left atrium by a huge ascending aortic aneurysm: a case report].

A 71-year-old man was admitted to our department with congestive heart failure on June 28, 1998. He previously had an aortic valve replacement because of aortic regurgitation probably due to annuloaortic ectasia in 1984. Thoracic aortic aneurysm was identified during the postoperative course. Magnetic resonance imaging showed a huge saccular ascending aortic aneurysm of 12 x 11.5 x 9.5 cm size, which had severely compressed the left atrium. Doppler echocardiography documented an accelerated flow (2.2 m/sec) in the left atrium in early diastole. The calculated pressure gradient was 19 mmHg. All pressures in the right heart system were elevated. This is the first case of pulmonary hypertension and right heart failure secondary to compression of the left atrium in a patient with thoracic aortic aneurysm.

Aged↗

PubMed2000

[Malignant lymphoma at the cavernous sinus].

A 71-year-old man developed general fatigue, appetite loss, and headache. Two months later, he noticed diplopia. Examination demonstrated reduced visual acuity and complete ophthalmoplegia of the left eye. Brain MRI disclosed a mass that extended from bilateral cavernous sinus to the clivus. There were left cervical lymphadenopathy and a right abdominal mass. A needle biopsy of the abdominal mass revealed non-Hodgkin lymphoma. Although malignant lymphoma at the cavernous sinus is not common, it should be an important consideration in the differential diagnosis of mass at the cavernous sinus.

Aged↗

PubMed2000

Application of cis-2-amino-3,3-dimethyl-1-indanol as an efficient chiral auxiliary to the asymmetric Ireland-Claisen rearrangement. Improvement of the diastereoselectivity by combinational use of chlorodimethylsilane as a silylating agent

The asymmetric Ireland-Claisen rearrangement of allyl carboxylates having a chiral substituent at the alpha-position of the carboxylate part gave the desired products with excellent diastereoselectivity, when an oxazolidinone, which was prepared from a non-natural chiral auxiliary, (1R,2S)-cis-2-amino-3,3-dimethyl-l-indanol, was used as the chiral substituent. Furthermore, the diastereoselectivity was improved by using chlorodimethylsilane as a silylating agent of the intermediary enolates.

Journal Article↗

PubMed2000

[A case of angiosarcoma in retroperitoneal cavity].

We report a case of angiosarcoma in the retroperitoneal cavity. A 66-year-old man was admitted to our hospital with the complaint of chest discomfort. Imaging studies including computed tomography scan and magnetic resonance imaging revealed a large solid retroperitoneal mass adjacent to the bladder. There was no evidence of metastasis. The tumor was surgically resected and histopathologically diagnosed as angiosarcoma from the positive staining for VIIIth factor, mitotic figures and abnormal endothelial cells. Six months after surgery, local recurrence adjacent to the bladder appeared. We resected the mass and started adjuvant therapy using Interleukin-2. However, he died of progressed disease one year after the first operation.

Aged↗

PubMed2000

[Chronic encapsulated intracerebral hematoma in thalamus with incongruous right homonymous hemianopia: a case report].

We presented a patient with chronic encapsulated intracerebral hematoma. This 49-year-old woman suffered from visual disturbance, and slowly progressive right hemiparesis, sensory disturbance of the right extremities and incongruous right homonymous hemianopia over 2 months. Computed tomography scanning showed high density area and ring enhancement, and magnetic resonance imaging revealed mixed intensity on T1 and T2-weighted images in her left thalamus and internal capsule. Angiographic studies revealed no vascular anomaly or tumor stain. The pathologic pictures indicated well-encapsulated hematoma containing fresh and old hematomas in the left thalamus. Most reported cases of this disease had hematomas in the subcortex and no cases had similar visual disturbance. This report was prepared because this condition is uncommon and may remain unrecognized.

Cerebral Hemorrhage↗