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Biomedical subjects

H He

Publications and source records attributed to H He.

266 records · Page 15Linked to original sources
PubMed1989

Relationships between structure and biological activity of the mycolic acid-containing glycolipids from Nocardia asteroides "sensu stricto" and related species.

To reveal the taxonomical situation of Nocardia asteroides "sensu stricto", we compared the mycolic acid and mycolic acid-containing glycolipid composition and their granulomagenic activities in mice. The major glycolipids were glucose mono- and dimycolate, trehalose mono- and dimycolate and several unknown glycolipids, commonly, although the relative amount differed from strain to strains. On the other hand, molecular species composition of mycolic acids differed distinctively among the three closely related species: N. asteroides "sensu strico", N. farcinica and N. nova. GC/MS analysis showed the most abundant species of mycolic acids were C50(52) in N. asteroides, C54(52) in N. farcinica and C58(56) in N. nova, respectively with a different alpha-alkyl branch. Glucose mycolate and trehalose dimycolate possessing C50 mycolic acid showed a strong activity for granuloma formation in mice.

Animals↗
PubMed1988

Natural history of early esophageal squamous carcinoma and early adenocarcinoma of the gastric cardia in the People's Republic of China.

Ninety cases of early esophageal squamous carcinoma (EESC) and 27 patients with early adenocarcinoma of the gastric cardia (EAGC), who for various reasons refused surgical treatment, radiotherapy or chemotherapy, were followed up endoscopically and roentgenologically for 19 to 78 months. Of the 90 cases with EESC, 52 (58%) were still found to have superficial mucosal lesions, 8 cases progressed to an advanced stage, 27 died of cancer with an average survival time of 53.2 months, and 3 died of other non-malignant diseases. The estimated median survival time of EESC is about 75 months. Among 21 patients with EAGC, 8 (30%) were still presenting with superficial malignant changes, 6 cases progressed to advanced cancer, 11 died of carcinoma with an average survival time of 53.3 months, and 2 died of non-malignant diseases. The estimated median survival time of EAGC is about 73 months. The period for a carcinoma in situ of the esophagus and the gastric cardia to progress to an advanced stage appears to be 4-5 years.

Adenocarcinoma↗
PubMed1982

Endoscopic diagnosis of 115 cases of early esophageal carcinoma.

Mass surveys of a population of 28,139 people in high-risk areas for esophageal carcinoma in Henan Province were carried out using the methods of esophageal exfoliative cytology, reontgenology and fiberendoscopy, between January 1978 and May 1981. 115 cases of early esophageal cancer comprising 64 males and 51 females were found. This paper reports on the results of the fiberendoscopic examination of these 115 cases of early esophageal carcinoma followed-up at regular intervals. On the basis of clinical, laboratory, and endoscopic findings, esophageal carcinoma of early stage can be divided into four types including the congestive type, erosive type, plaque-like type and polypoid type. All results were obtained on the basis of a follow-up observation period of 19-42 months. It was shown that the evolution of esophageal cancer in situ to an advanced cancer probably takes 3-4 years. Therefore, esophageal carcinoma could be reasonably considered to be a chronic disease of relatively slow growth. In order to make complete cure of such a "poor-prognosis" disease possible, early diagnosis established in good time using all the methods mentioned, is essential.

Adult↗
PubMedDate not supplied

An anti-Ras cancer potential of PP1, an inhibitor specific for Src family kinases: in vitro and in vivo studies.

BACKGROUND: We previously found that both PAK, a Rac/CDC42-activated Ser/Thr kinase, and its binding partner PIX are required for malignant transformation caused by oncogenic Ras mutants, such as v-Ha-Ras. Furthermore, oncogenic Ras requires an autocrine pathway to activate PAK. This pathway involves at least two distinct receptor kinases: EGF receptor (ErbB1) and ErbB2. Interestingly, both of these kinases are known to activate Src family kinases that phosphorylate CAT, another binding partner of PIX. PURPOSE: The major aim of this study was to determine whether Src family kinases are required for both Ras-induced PAK activation and malignant transformation. For this purpose, we used PP1, an inhibitor specific for Src family kinases, which does not inhibit either EGF receptor or ErbB2. METHODS AND RESULTS: We studied the effect of PP1 on the anchorage-dependent growth of normal and v-Ha-Ras transformed NIH 3T3 fibroblasts, PAK activation and anchorage-independent growth of Ras transformants, and development of Ras-induced sarcomas in nude mice. We found that PP1 (10 nM) strongly inhibits PAK activity in Ras transformants. PP1 at this concentration is known to inhibit c-Fyn kinase, but not c-Src kinase, and none of the three known Src family kinases (c-Src, c-Fyn, and c-Yes) expressed in fibroblasts is activated by v-Ha-Ras. Thus, it is most likely that the primary target of this drug is an as yet unidentified Ras-activated Tyr (Y) kinase or kinases, which we call "Ray." Although PP1 has no effect on their anchorage-dependent growth, it significantly inhibits their anchorage-independent growth in soft agar, as well as a rapid growth of Ras-induced sarcomas in mice. CONCLUSION: Like EGF receptor and ErbB2, a member of Src family kinases (most likely a new Src-related kinase called "Ray") is essential for the Ras-induced activation of PAK and the malignant transformation both in vitro and in vivo. These findings suggest that PP1 and other inhibitors specific for Src family kinases are potentially useful for the treatment of Ras-associated cancers.

3T3 Cells↗
PubMedDate not supplied

Signal therapy for RAS-induced cancers in combination of AG 879 and PP1, specific inhibitors for ErbB2 and Src family kinases, that block PAK activation.

BACKGROUND: Both EGF family ligands and ErbB family receptor kinases act upstream of RAS to induce mitogenesis of normal cells, such as NIH 3T3 fibroblasts. However, oncogenically mutated RAS, such as v-Ha-RAS is constitutively activated and therefore no longer requires these ligands or receptors for its activation. Nevertheless, it up-regulates the expression of these EGF family ligands. To understand the biologic significance of RAS-induced up-regulation of these ligands in both RAS-induced PAK activation and malignant transformation, we have conducted the following studies, based on the previous observations that (1) the N-terminal SH3 domain of PIX selectively binds a Pro-rich domain of 18 amino acids of PAKs, CDC42/Rac-dependent Ser/Thr kinase family, and (2) this specific interaction is essential for both PAK activation and membrane ruffling RESULTS: Using four distinct, cell-permeable, and highly specific inhibitors, namely WR-PAK18, which blocks the PAK-PIX interaction; AG 1478, which inhibits ErbB1 kinase activity; and AG 825 or AG 879, which inhibits ErbB2 kinase activity, we demonstrate that (1) the PAK-PIX interaction is essential for v-Ha-RAS-induced malignant transformation; (2) v-Ha-RAS requires not only ErbB1 but also ErbB2, which are activated through two independent autocrine pathways to induce both the PIX/Rac/CDC42-dependent PAK activation and malignant transformation in vitro; and (3) a combination of AG 879 and the Src family kinase-specific inhibitor PP1 suppresses almost completely the growth of RAS-induced sarcomas in nude mice. CONCLUSION: These findings not only change our conventional view on the role of these RAS-inducible ligands and ErbB family receptors (serving as RAS activators) but also suggest a new avenue for the treatment of RAS-associated cancers by a combination of inhibitors specific for ERbB, Src, or PAK family kinases.

3T3 Cells↗
PubMedDate not supplied

Pharmacogenetic explanation for excessive beta-blockade following timolol eye drops. Potential for oral-ophthalmic drug interaction.

OBJECTIVE: To determine whether the effects of topically administered timolol in an individual would be dependent on the presence or absence in that individual of the P-450 enzyme CYP2D6 and whether the effects of topically administered timolol would be increased and its metabolism decreased by the oral administration of quinidine, a known inhibitor of CYP2D6. DESIGN: Single-blind randomized crossover comparison of topical timolol, placebo, and the effects of inhibition of timolol metabolism by oral quinidine. SETTING: Clinical research center of an academic medical center. PARTICIPANTS: Eight male extensive metabolizers (EMs) and five male poor metabolizers (PMs) of debrisoquin. INTERVENTION: Two drops of 0.5% timolol or artificial tears were administered into each nostril in random order, and placebo or 50 mg of quinidine was administered orally to the EMs in random order, followed 30 minutes later by either the timolol or placebo drops. MAIN OUTCOME MEASUREMENT: Plasma timolol concentrations were measured by high-pressure liquid chromatography, while the extent of beta-blockade was determined by the suppression of exercise-induced rise in heart rate. RESULTS: The exercise heart rate was reduced following timolol eye drops compared with placebo in both EMs (P < .001) and PMs (P < .001) with significantly greater heart rate reduction (P = .01) and higher plasma timolol concentration in PMs compared with EMs (P = .03). Administration of quinidine with timolol eye drops to EMs resulted in a further significant reduction in heart rate (P = .02) and increase in plasma timolol concentration (P = .04). CONCLUSIONS: An individual's debrisoquin phenotype is an important determinant of beta-blockade following timolol eye drops, and metabolism of timolol is inhibited and beta-blockade increased by coadministration of oral quinidine. Clinicians should be aware of the potential for drug interactions that occur when orally administered drugs inhibit the metabolism of a topically administered drug.

Administration, Oral↗