The effect of hypoxia on acquired drug resistance and response to epidermal growth factor in chinese hamster lung fibroblasts and human breast-cancer cells in vitro

Prolonged hypoxia induced transient drug resistance in Chinese hamster lung fibroblasts. Previously hypoxic cells were resistant to adriamycin and resistant to etoposide. Complete recovery of etoposide sensitivity was observed following re-aeration for 24 hr. A change in P-glycoprotein expression was unlikely to contribute to the resistance caused by hypoxia, since adriamycin resistance was not reversed by verapamil. However, alteration in the plasma membrane structure may be involved, since previously hypoxic cells were resistant to extracellular superoxide radical generated by the addition of xanthine/ xanthine oxidase. In contrast, adriamycin sensitivity was not altered by hypoxia in 3 human breast-cancer cell lines. MDA-468 and MCF-7/Adr differed in their response to EGF, independent of the presence of hypoxia. These results suggest that hypoxic-stress-induced drug resistance is not generalized.     

Antimicrobial properties of heartwood,bark/sapwood and leaves of Juniperus species

Hexane and methanol extracts of heartwood, bark/sapwood and leaves of twelve taxa of Juniperus from the United States were assayed for antifungal and antibacterial activities. The hexane extract of the heartwood of several junipers appeared comparable in antibacterial activity to streptomycin. Antibacterial activity of the hexane extracts from the bark/sapwood of J. monosperma and J. californica were comparable to streptomycin. No appreciable antibacterial activities were found in the leaf extracts from any species examined. No antifungal activities comparable to amphotericin B were found in either hexane or methanol extracts of the heartwood nor from the bark/sapwood. Antifungal activity against Cryptococcus neoformans comparable to amphotericin B was found in the hexane extract of the leaves of J. occidentalis var. australis. The methanol extracts from the leaves of J. osteosperma and J. californica had antifungal activities comparable to amphotericin B against Trichophyton mentagrophytes.     

Matrix regulation of skeletal cell apoptosis II: role of Arg-Gly-Asp-containing peptides.

This investigation was based on the assumption that arg-gly-asp (RGD)-containing peptides are released from the extracellular matrix of bone and cartilage during the remodeling cycle. We asked the question: Can RGD peptides influence skeletal cell viability? Primary human osteoblasts, mouse MC-3T3-E1 cells, and chick chondrocytes were incubated with purified RGD-containing peptides and cell viability was determined. The RGD peptide did not kill osteoblasts, chondrocytes, or MC-3T3-E1 cells. In contrast, RGDS and GRGDSP peptides killed all three cell types. Osteoblast death was quite rapid, occurring within 6 h of treatment. transferase uridyl mediated nick end labeling (TUNEL) and transmission electron microscopy (TEM) analysis indicated that death was mediated by apoptosis. To learn if mitochondria transduced the death signal, cells were treated with RGDS and organelle function was evaluated using a voltage-sensitive fluorescent probe. It was observed that there was no net loss of fluorescence and, hence, it was concluded that mitochondria were not the primary effectors of the apoptotic response. Experiments were performed with enzyme inhibitors to determine the import of the caspase pathway on RGDS-mediated osteoblast apoptosis. Results of these studies, as well as a study conducted using a fluorescent substrate, pointed to caspase 3 mediating the effector stage of the apoptotic process. Finally, using a purified labeled-RGDS peptide, we showed that the molecule was not restricted by the plasma membrane because it was accumulated in the cytosolic compartment. Results of the investigation support the view that resorption of the extracellular matrix generates peptide products that can induce apoptosis of vicinal cells.     

Stability of insulin mixtures in disposable plastic insulin syringes

The miscibility of short and long acting porcine, human and bovine insulins has been investigated using HPLC. Soluble insulin is rapidly lost from solution when mixed with both isophane and zinc insulin, although the mechanism may be different in these two cases. The time for up to 50% or more to be lost is often less than 2 min. The percentage lost is dependent upon the ratio of the mixture and the type and origin of the insulin. In the case of soluble: zinc mixtures it is greatest for porcine and least for bovine, in the case of soluble: isophane mixtures it was least for human and greatest for bovine. The greater the original amount of soluble insulin present the less the loss. The results help explain recent clinical reports that mixtures of soluble and zinc insulins fail to achieve satisfactory control of post-prandial blood sugar levels.     

Nontraumatic intracerebral hemorrhage in young adults

We reviewed our experience with 72 patients, aged 15 to 45 years, who were hospitalized for nontraumatic intracerebral hemorrhages (ICHs) between 1978 and 1985. Evaluation included arteriography in 61 patients. Computed tomography demonstrated 41 lobar, 11 putaminal, four thalamic, four pontine, four intraventricular, two caudate, two midbrain, two cerebellar, one globus pallidum, and one corpus callosum hemorrhage. Forty-three patients, with either progressive neurologic deterioration, arteriovenous malformations (AVMs), or saccular aneurysms underwent surgery. The overall in-hospital survival, including those patients treated medically, was 87.5%. A presumed cause for the ICH was found in 55 (76.4%) patients. The main causes were ruptured arteriovenous malformations (21), hypertension (11), ruptured saccular aneurysms (seven), and sympathomimetic drug abuse (five). Surgical explorations demonstrated a necrotizing angiitis in one patient and arteriovenous malformations in two patients who had negative arteriograms. Young patients with nontraumatic ICHs represent a heterogeneous group. A cause can be established in most patients. Arteriovenous malformations account for less than one third of the hemorrhages in young adults, and other causes should be sought.     

Induction of oral cavity tumors in F344 rats by tobacco-specific nitrosamines and snuff

The tumorigenic activities toward the oral cavity of snuff, its extracts, and two of its major nitrosamines, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were evaluated in male F344 rats. In one protocol, groups of 21-30 rats were treated beginning at age 10 weeks by chronic application to the oral cavity for 131 weeks of either H2O, an H2O extract of snuff, an H2O extract of snuff enriched with ten times its indigenous concentration of NNN and NNK, or with NNN and NNK in H2O. The incidence of oral cavity tumors in the rats treated with NNN and NNK was 8 of 30, compared to 0 of 30 in controls (P less than 0.05). These results demonstrate that NNN and NNK can induce tumors locally in the oral cavity of F344 rats. Oral cavity tumors were also observed in 3 of 30 rats treated with snuff extract enriched with NNN and NNK, but not in the rats treated with snuff extract alone. In a second protocol, a test canal was surgically created in the lower lip of groups of 21-32 rats, and either snuff, H2O-extracted snuff, or snuff enriched with its own H2O extract was inserted in the test canal 5 times weekly for 116 weeks. A group of 10 control rats had surgery only. Among the 32 rats treated with snuff, 3 had oral cavity tumors; one was a squamous cell carcinoma originating in the test canal and invading the gingiva, one was a papilloma of the test canal, and one was a papilloma of the hard palate. Oral cavity tumors were also observed in 2 of 21 rats treated with H2O-extracted snuff and 1 of 32 rats treated with snuff enriched with its H2O extract. Oral tumors were not observed in control rats. The results of this study indicate that snuff and individual nitrosamines present in snuff can induce oral cavity tumors in F344 rats and support the epidemiological observations which indicate that snuff dipping causes oral cancer in man.     

The Development and Teaching of the Ethical Principles and Guidelines for Family Scientists*

This article describes the development of the Ethical Principles and Guidelines for Family Scientists that the National Council on Family Relations Board of Directors unanimously approved. Furthermore, it discusses the importance of ethics education for family professionals and provides suggestions for educators. Finally, the ethical principles and guidelines are delineated. We argue that the development of a scholarship on ethics education is important for current and future family scientists.