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Biomedical subjects

M Yamato

Publications and source records attributed to M Yamato.

At least 109 records · Page 6Linked to original sources
PubMed1987

Immunological studies on delayed hypersensitivity to phenytoin--I. A new method for preparing phenytoin antiserum.

The present study was initiated to produce an antiserum to phenytoin with high specificity and sensitivity which would be suitable not only for determination of blood phenytoin concentration but also for induction of a hypersensitivity reaction to phenytoin in experimental animals. p-Aminophenytoin was synthesized and identified by means of IR, 1H-NMR and mass spectroscopy. BSA-phenytoin conjugate was prepared by using p-aminophenytoin, BSA and, as a coupling reagent, glutaraldehyde. Satisfactory response to immunization was achieved at a 9.8:1 molar ratio of p-aminophenytoin to BSA. The antiserum obtained from rabbits immunized with BSA-phenytoin conjugate exhibited practically no cross-reactivity with either phenytoin metabolites or other anti-epileptic drugs, indicating that this antiserum provides sufficiently high specificity. In our experiments, the lower limit for detecting phenytoin was 2 ng using RIA, whereas 200 ng was the minimum amount detectable by HPLC. Thus, by a difference of two orders of magnitude, the present RIA method shows a much higher sensitivity than that of HPLC, though we found a good correlation of simultaneous determinations of serum phenytoin between the two methods. Reproducibility of phenytoin determination in plasma was confirmed by calculating the coefficient of variance. The values were less than 10%.

Animals↗
PubMed1987

Synthesis and antitumor activity of tropolone derivatives. 4.

Modifications of monotropolone 2 having poor potency against P388 in mice were studied. The alpha-ethoxy group of 2, prepared from hinokitiol and benzaldehyde diethyl acetal, was replaced with a phenolic or heteroaromatic compound by heating 2 with the appropriate nucleophile. Structure-activity relationships indicated that an acidic hydroxyl and a proton-accepting group situated in the neighboring position, which permits the formation of a chelate with a metal ion, contributed to enhanced activity. Among the compounds studied, the 8-hydroxyquinoline analogue 10f was the most favorable compound.

Animals↗
PubMed1987

Synthesis and antitumor activity of tropolone derivatives. 5.

As part of a study on the structure-activity relationship of antitumor-active tropolone derivatives, a series of bistropone analogues, related to potently active bistropolone 1a, were synthesized and tested for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. The methoxytropones 3 and 5, hydroxytropothione 10, and (N-methylamino)tropones 12 and 13 were inactive in both systems. Methoxytropone 6 exhibited weak activity, whose potency was equal to that of monotropolone 2a.

Animals↗
PubMed1987

Synthesis and antitumor activity of tropolone derivatives. 6. Structure-activity relationships of antitumor-active tropolone and 8-hydroxyquinoline derivatives.

The bis derivative 6 of 8-hydroxyquinoline, which, like tropolones, readily forms a chelate, was synthesized and found to have high potency (dose = 12.5 mg/kg, T/C % = 164) against leukemia P388 in mice approximately equivalent to that of the bistropolone 1b. 8-Hydroxyquinoline analogues with broad structural variation were synthesized and their structure-activity relationships followed the same pattern as in the tropolone series. In addition, the bistropolones 1a-e were tested for their ability to bind to tubulin and found to have no such property. The results of this study suggested that bistropolone and bis(8-hydroxyquinoline) derivatives must form a chelate with the metal necessary for the enzyme, such as ribonucleotide reductase, which catalyzes the DNA biosynthetic pathways.

Animals↗
PubMed1986

Synthesis and antitumor activity of tropolone derivatives. 3.

As part of a study on the antitumor activities of tropolone derivatives prepared from hinokitiol, which naturally occurs in the plants of Chamaecyparis species, effects of aromatic substituents of alpha,alpha-bis(7-hydroxy-5-isopropyltropon-2-yl)toluenes on the activity were examined. Several of the compounds showed high potency in the P388 leukemia assay. 4-Hydroxy analogue 4d showed the most potent activity (T/C = 195%) at a 5 mg/kg dose. The introduction of large-size substituents, of which the steric influence prevents coplanarity of the substituted aromatic function, resulted in a remarkable decrease in the potency. X-ray structural analysis of highly potent 4-methoxy analogue 4b was undertaken.

Animals↗
PubMed1986

Takayasu arteritis: radiographic and angiographic findings in 59 patients.

Fifty-nine patients (57 females, two males) with Takayasu arteritis were retrospectively evaluated. Chest radiographs were abnormal in 68% of patients in whom they were obtained (n = 49). Aortic contour changes and calcification were frequent findings. Sixty-eight percent of patients who underwent total aortography (n = 50) had panaortitis, and 28% had involvement confined to the thoracic aorta and/or its branches. Stenosis was the most common angiographic finding in the aorta and its branches, but occlusion (n = 4), aneurysm (n = 3), and dilatation (n = 15) were not infrequent. Adventitial vascular structures (the vasa vasorum) were seen in three cases. Eighty-six percent (n = 21) of pulmonary arteriograms showed abnormalities. Occlusion was by far the most common finding. There was no predilection for any lobe nor correlation with systemic arteritis. It was concluded that Takayasu arteritis characteristically involves the systemic and the pulmonary arteries independently. Total aortography and pulmonary arteriography are necessary to diagnose and evaluate the extent of the disease.

Adolescent↗
PubMed1986

Biosynthesis of valanimycin.

In the biosynthesis of valanimycin, valine is mostly incorporated into the isobutyl moiety of the antibiotic. The alpha-substituted acrylic moiety of valanimycin is derived from alanine. However, a part of alanine is metabolized into valine, thus incorporated also into the isobutyl moiety. Anaerobic conditions and some reducing agents strongly inhibit the biosynthesis.

Alanine↗
PubMed1986

Isolation and properties of valanimycin, a new azoxy antibiotic.

Valanimycin, a new azoxy antibiotic, was isolated from culture broths of a streptomycete. Valanimycin is an unstable oil at room temperature and active against some Gram-positive and Gram-negative bacteria, mouse leukemia L1210 cells in cultures, and prolongs the life span of mice inoculated with Ehrlich carcinoma or L1210.

Animals↗
PubMed1986

K-4, a novel inhibitor of angiotensin I converting enzyme produced by Actinomadura spiculosospora.

A novel inhibitor of angiotensin I converting enzyme (ACE), named K-4, was isolated from the culture broth of Actinomadura spiculosospora nov. sp. K-4. The K-4 was an oligopeptide containing L-phenylalanine with (R)-1-amino-2-(4-hydroxyphenyl)ethylphosphonic acid as the C-terminal residue. The compound proved to be a specific and reversible inhibitor of ACE with the inhibition constant (Ki) of 0.18 microM, and inhibited ACE non-competitively by use of hippuryl-L-histidyl-L-leucine (HHL) as a substrate. When administrated intravenously to rats, K-4 inhibited the pressor response to angiotensin I.

Angiotensin I↗
PubMed1986

K-26, a novel inhibitor of angiotensin I converting enzyme produced by an actinomycete K-26.

A novel inhibitor of angiotensin I converting enzyme (ACE), designated K-26, was isolated from the broth filtrate of an actiomycete K-26. K-26 is a water soluble, acidic peptide composed of an equal mol of L-isoleucine, L-tyrosine and 1(R)-1-amino-2-(4-hydroxyphenyl)-ethylphosphonic acid. The IC50 of K-26 for ACE inhibition was 6.7 ng/ml when hippuryl-L-histidyl-L-leucine was used as a substrate of ACE. K-26 possesses hypotensive activity in vivo.

Actinomycetales↗
PubMed1985

Cytohistochemical studies on estrogen receptors of breast cancer tissue using an immunoperoxidase technique.

The estrogen receptors (ER) in breast cancer tissues were investigated in 122 patients using an immunoperoxidase method. ER (+) were evident in 77 of 122 patients (63.1 per cent). If classified according to pre- and postmenopausal subjects. ER (+) was seen in 61.4 per cent and ER (-) in 32.9 per cent before menopause, and ER (+) in 65.4 per cent and ER (-) in 30.8 per cent after menopause with no marked difference between the two. If classified according to histological type, ER (+) was seen in 72.3 per cent of those with papillotubular carcinoma and in 62.0 per cent of those with scirrhous carcinoma, whereas ER (-) was seen in 44.9 per cent of those with medullary tubular carcinoma. ER (+) was seen in carcinoma with apocrine metaplasia, lobular carcinoma and Paget's carcinoma. Concerning the relationship between primary tumors and metastatic lymph nodes, ER (+) for both was seen in 20 of 41 patients (48.8 per cent) whereas ER (-) for both was found in 9 of 41 patients (22.0 per cent). Four patients with local recurrences had a positive ER (+) at the beginning of treatment, but the ER became negative after hormonal treatment and chemotherapy.

Breast Neoplasms↗
PubMed1985

Synthesis and antitumor activity of tropolone derivatives. 2.

Structural requirement for antitumor activity of tropolone derivatives 2-4 was explored. Isochroman derivatives (6-17, 20, and 23) and alpha, alpha-disubstituted compounds 26-30 were synthesized and their antitumor activities were tested. These nontroponoid derivatives were all inactive, implying that a tropolone ring is essential for the activity. Several compounds related to the monotropolone analogue 3 were synthesized. Among them, 31-33 showed significant activity, but their potencies were considerably weaker than those of binary tropolone analogues 4.

Animals↗