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Biomedical subjects

Y Yoshimoto

Publications and source records attributed to Y Yoshimoto.

At least 181 records · Page 10Linked to original sources

Nonsteroidal antiinflammatory agents. 2. Synthesis of 4',5-disubstituted 3-biphenylylacetic acids and their derivatives with antiinflammatory and analgesic activities.

A series of 5',5-disubstituted 3-biphenylylacetic acids (5a-n) and several alpha-methyl derivatives (5o-v) were prepared as analogues of a newly developed nonsteroidal antiinflammatory agent, 5'-chloro-5-methoxy-3-biphenylylacetic acid [1 (DKA-9), R = 4-C1Ph; R' = Me], and evaluated for antiinflammatory and analgesic activities using both carrageenan rat paw edema and AcOH writhing assays. Among them, 5-fluoro-3-biphenylylacetic acid (5m) showed the highest antiinflammatory activity, while 2-(3-biphenylyl)propionic acid (5o) showed the highest analgesic activity. However, they were less potent than 1 (R = 4-C1Ph; R' = Me) in these assays.

Analgesics↗

Nonsteroidal antiinflammatory agents. 3. Synthesis of the positional isomers of 4'-chloro-5-methoxy-3-biphenylylacetic acid and their antiinflammatory and analgesic activities.

The positional isomers 3a-i of 4'-chloro-5-methoxy-3-biphenylylacetic acid [1 (DKA-9), R = 4-ClPh; R' = MeO] which is a newly developed nonsteroidal antiinflammatory agent, have been prepared and evaluated for antiinflammatory and analgesic activities using both the carrageenan-induced rat paw edema and AcOH writhing assays. The 3- and 4-biphenylylacetic acids 3a,d, which closely resemble 1 (R = 4-ClPh, R' = MeO) structurally, showed, by far, excellent activities compared with the other isomers in these assays. However, none of the compounds tested was more active than 1 (R = 4-ClPh; R' = MeO). In this series of compounds, structural requirements for good antiinflammatory activity seemed to be parallel to those for analgesic activity.

Animals↗

Qualitative and quantitative analyses of human chorionic gonadotropin and its subunits produced by malignant tumors.

Human chorionic gonadotropin (hCG) and its subunits in plasma, urine, ascites, and tumor extracts from four patients with hCG-producing tumors (undifferentiated cell carcinoma and choriocarcinoma of the bladder, malignant teratoma of the retroperitoneum, and pancreatic carcinoma) were measured by the radioimmunoassays specific to each component. While both free alpha and beta subunits as well as the whole molecule of hCG were found in all these samples, the proportion of beta subunit was much higher in these tumor extracts than in the placental extracts. Since the alpha and beta subunits are known to be translated from separate mRNAs, such increase of subunit is probably due to the predominant increase of mRNA encoding beta subunit of hCG in the hCG-producing tumors. Gel filtration of the extracts of these four tumors on Sephadex G-100 and G-150 columns demonstrated a heterogeneity of hCG, alpha, and beta subunits in these tumor extracts, and the elution profiles of plasma, urine and tumor extracts were slightly different. Lower molecular weight forms of hCG and its beta subunit were present in all urine samples. The significance of these heterogeneities remains to be elucidated.

Adult↗

Tension generation by actomyosin thread from a non-muscle system.

A suitable motility model reconstituted from non-muscle contractile proteins should offer a powerful tool for analysing the molecular events in cell motility. Actomyosin thread has been thought to be such a model. As far as non-muscle motile systems are concerned, however, only a very limited number of experiments have been done in this direction. No direct measurement of the tension produced by non-muscular actomyosin thread has been reported in spite of its importance for quantitative studies. We now report that a segment of actomyosin thread of Physarum polycephalum can generate a considerable amount of tension, which is a function of the micromolar concentration of ATP. The maximum isometric tension was a high as 10 g cm-2 at 10 microM ATP.

Actomyosin↗

Clofibrate-induced myopathy in patients with diabetes insipidus.

Clofibrate has been considered to be a relatively safe antidiuretic in the treatment of diabetes insipidus. However, we have recently had four cases of clofibrate-induced myopathy in patients with diabetes insipidus due to hypothalamic lesions. Physicians should therefore be aware of its occurrence and carefully monitor serum levels of CPK, GOT and GPT during the treatment of diabetes insipidus with clofibrate, especially in patients with associated hypothyroidism, latent or overt, which possibly favors the development of myopathy.

Adolescent↗

Human chorionic gonadotropin--like material: presence in normal human tissues.

With the use of radioreceptor assay for gonadotropin and a beta-chain radioimmunoassay for human chorionic gonadotropin (hCG), we have been able to demonstrate the presence of hCG-like material in all normal human tissues tested. This activity was completely absorbed by a hCHG-antibody affinity column and was demonstrated to have altered carbohydrate content by studies showing this material did not bind to concanavalin A (con A)-Sepharose affinity columns. In identical studies greater than 90% of placental hCG was bound to con A. However, if placental hCG is rendered carbohydrate free it also does not bind to con A. It is known that carbohydrate-free hCG is cleared rapidly from the circulation and thus possesses little or no biological potency in vivo. Accordingly, we hypothesize: (1) that this hCG-like material in normal tissues has the protein structure of hCG but does not possess the carbohydrate moieties of placental hCG and probably has little or no bioactivity in vivo and (2) that the trophoblastic cell is not unique in its ability to synthesize hCG but has developed the ability to glycosylate hCG, transforming a ubiquitous cellular protein into a hormone, hCG might better be called human cellular gonadotropin.

Chorionic Gonadotropin↗

Multiple-hormone producing lung carcinoma.

Endocrine and immunohistochemical studies were performed in a patient with lung cancer associated with gynecomastia. Elevated level of human chorionic gonadotropin (hCG) in plasma and mild hyperadrenocorticism were demonstrated by hormone assays. Postmortem examination proved the existence of anaplastic small cell carcinoma of the lung mixed with a feature of chorioepithelioma. The presence of significant amounts of adrenocorticotropic hormone (ACTH), beta-melanocyte stimulating hormone (beta-MSH), calcitonin, gastrin, hCG, hCG-alpha, hCG-beta and human chorionic somatomammotropin (hCS) in tumor tissues was demonstrated by radioimmunoassays, bioassay and immunohistochemical techniques. We present here a unique case of multiple hormones producing tumor elaborating both hormones of amine precursor uptake and decarboxylation (APUD) series (ACTH, beta-MSH, calcitonin and gastrin) and of placental origin (hCG, hCG-alpha, hCG-beta and hCS).

Adrenocorticotropic Hormone↗

Improved method of purifying some radiolabeled glycopeptide hormones.

We describe a simplified method for purifying radiolabeled glycopeptide hormones (thyrotropin, lutropin, follitropin, and human choriogonadotropin), which results in preparations of over 95% immunoreactivity. This method is based on competitive elution from columns of the plant lectin, concanavalin A, and is applicable to glycopeptide hormones derived from several species.

Chorionic Gonadotropin↗

Human chorionic gonadotropin-like substance in nonendocrine tissues of normal subjects.

By means of two assay systems, a beta chain human chorionic gonadotropin radioimmunoassay and a radioreceptor gonadotropin assay, a chorionic gonadotropin-like substance was demonstrated in extracts of liver and colon obtained at autopsy from three patients who died of nonneoplastic disease. In contrast to placental chorionic gonadotropin, colon and liver chorionic gonadotropin was not bound to concanavalin A-Sepharose columns, indicating that this substance possessed little or no carbohydrate. Previous workers demonstrated that desialylated human chorionic gonadotropin possesses little or no bioactivity in vivo but retains full radioreceptor and radioimmunoassay activity in vitro. Our data suggest that the genome responsible for the human chorionic gonadotropin production is not completely suppressed in adult nonendocrine tissues, and that the chorionic gonadotropin produced by colon and liver has little or no bioactivity in vivo because of its low carbohydrate content. Since many normal tissues produce chorionic gonadotropin, bioactivity may be modulated by regulation of carbohydrate content.

Chorionic Gonadotropin↗