The development of resistance to carcinogen-induced cytotoxicity in hamster embryo cultures.
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Biomedical subjects
Publications and source records attributed to L Diamond.
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When the hamster cell lines BHK21 and Nil-2 were infected at a multiplicity of 100 with the adenovirus 7-simian virus 40 (SV40) hybrid (strain LLE46), SV40 T antigen was induced in 0.1 to 6% of the cells during the first 96 hr postinfection, morphological changes occurred 3 to 7 weeks later, and eventually all the cells contained SV40 T antigen, but no adeno 7 T antigen. Results were similar when primary and secondary monolayer cultures of hamster embryo (HE) cells were infected with the adeno 7-SV40 hybrid, and when primary HE cells were infected with SV40. However, infection of BHK21, Nil-2, and secondary HE cells with the same multiplicity of SV40 did not induce SV40 T antigen or morphological transformation. This suggests that the target cells required for infection with SV40 virions, but not those required for infection with the hybrid, are lost or altered in secondary HE cultures and in the two cell lines. In most of the virus-host cell systems in which SV40 T antigen and transformation were induced, there was a decrease in the number of T antigen-positive cells after the initial infection. This was followed by a lag period of up to 2 months before the onset of a progressive increase in the number of positive cells. The beginning of the rise in T antigen production coincided with the first morphological changes.
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BACKGROUND: Lymphatic mapping and sentinel node biopsy in breast cancer aims to allow lymph node negative women to avoid axillary clearance by providing a minimally invasive means of staging the axilla. However, before its implementation into routine clinical practice, initiating departments must verify their expertise in each of the surgical, radiological and pathological components necessary for its successful performance. Here, we present our validation experience. METHODS: Thirty patients with breast cancer of any stage (but without clinical axillary lymphadenopathy) undergoing definitive resection of their primary tumour underwent lymphatic mapping (using blue dye alone or in combination with radioisotope) and sentinel node biopsy concurrent with standard level II axillary clearance over a ten month period. RESULTS: All patients had sentinel nodes identified intraoperatively. The sentinel node in 29 patients correctly predicted the status of axillary involvement. One patient had non-sentinel nodal disease without metastases being identified in their sentinel node. Such a single false negative out of thirty patients is considered acceptable by current guidelines. CONCLUSION: Validation of expertise in sentinel node identification and analysis is feasible over a relatively short period of time in a regional symptomatic breast unit. We now feel confident in offering this procedure to selected patients with breast cancer in our catchment area in place of routine axillary clearance.
The ability of substance P to mimic vagally mediated nonadrenergic bronchodilation was assessed in vivo in anesthetized, paralyzed, artificially ventilated cats. Infusion of the peptide at a rate of 10 micrograms kg-1 min-1 for 10 minutes did not attenuate the increase in pulmonary resistance evoked by efferent vagal stimulation. Similarly, when administered as an aerosol (1-15 breaths of a 100 micrograms ml-1 aqueous solution) or by bolus intravenous injection, substance P failed to reverse the increase in pulmonary resistance maintained by a continuous intravenous infusion of 5-hydroxytryptamine. These results indicate that substance P is unlikely to be the neurotransmitter responsible for mediating nonadrenergic inhibitory responses in feline airways.
Relaxations of the feline intrapulmonary bronchus (IPB) induced by VIP or nonadrenergic noncholinergic (NANC) inhibitory nervous stimulation were unaffected by the VIP receptor antagonist [Ac-Tyr1,D-Phe2]-GRF (1-29) (30 microM). A second VIP antagonist, [pCl-D-Phe6,Leu17]-VIP (30 microM), also had no effect on NANC relaxation responses or IPB sensitivity to VIP. However, responses to three of the four highest VIP concentrations were inhibited by this antagonist. These results indicate that [Ac-Tyr1,D-Phe2]-GRF (1-29) and [pCl-D-Phe6,Leu17]-VIP are not effective competitive antagonists of VIP receptors in feline airways and, hence, have but limited applicability in determining the role of VIP in mediating airway NANC inhibitory responses in this tissue.
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1. The effects of isosmotic substitution of choline for sodium on resting tension and on relaxation after noradrenaline-induced contraction was studied in rabbit isolated aortic strips immersed in Hepes-buffered physiologic salt solution (PSS) warmed to 37 degrees C and gassed with 100% O2. 2. Isosmotic substitution of choline for sodium produced a sustained increase in resting tension which effectively prevented any evaluation of the influence of sodium on relaxation. The increase in resting tension was insensitive to 10(-8) mol/l atropine but was abolished by 10 min exposure to calcium-free PSS prior to replacement of sodium. 3. Under sodium-calcium free conditions which eliminated the increase in resting tension observed in sodium-free PSS, stimulation with 10(-5) mol/l noradrenaline initiated contractions that were 55 +/- 7.5% of the control response in normal PSS. Washout of noradrenaline with sodium-calcium-free PSS failed to produce any decrement in tension. However, restoration of the normal sodium resulted in gradual relaxation. 4. These results suggest that sodium is required for relaxation after noradrenaline-induce contraction of arterial smooth muscle.
Eglin-c, a compound that inhibits rat elastase but has little effect on porcine pancreatic elastase (PPE), was employed to examine the role of endogenous elastase in PPE-induced emphysema. Twenty-four female Long-Evans rats were divided into three groups: control (n = 8), PPE (n = 9), and PPE + eglin-c (n = 7). Eglin-c (9 mg/rat) was intratracheally instilled 3 days after PPE treatment, twice weekly, until 3 days before pulmonary function testing. Function tests and lung fixation for morphometric analysis were carried out 15-34 days after PPE treatment. Intratracheal instillation of PPE (400 IU/kg) produced significant increases in functional residual capacity, dynamic and quasi-static compliances, total lung capacity (TLC), and mean linear intercept (MLI), as well as a significant decrease in carbon monoxide diffusion coefficient. However, no significant alterations in quasi-static compliance, TLC, or MLI were found in animals treated with PPE and eglin-c. Three additional groups were used to examine the effects of intratracheal instillation of saline or eglin-c: control (n = 9), saline (n = 8), and eglin-c (n = 10). No significant change in any respiratory parameter was found in either the saline or the eglin-c group, indicating no detectable alteration in pulmonary function caused by either the intratracheal procedure or eglin-c. These data suggest that endogenous elastase is an important contributing factor in the development of PPE-induced emphysema in the rat.
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