Natural killer cell regulation of implantation and early lung growth of H-ras-transformed 10T1/2 fibroblasts in mice

We examined the relative role of the natural killer (NK) cell and H-ras gene in controlling metastasis formation using a novel assay for quantitating viable tumor cells entering and surviving in the lung for up to 13 days following i.v. tumor inoculation. This assay utilized the resistance to G418 sulfate conferred by transfection of the neoR gene into 10T1/2 fibroblasts along with activated H-ras. We had previously shown that the metastatic efficiency of T-24-H-ras-transformed 10T1/2 fibroblasts correlated with H-ras expression at the RNA level. In this paper we show that the NK cell could recognize H-ras-transformed fibroblasts in vivo and control experimental metastasis formation using NK-suppressed and -activated syngeneic C3H recipients. Evaluation of NK sensitivity in vitro of individual lines did not predict metastatic ability. However, NK susceptibility in vitro did inversely correlate with the ability of tumor cells to arrest and survive in the lung for the first 48 h after i.v. inoculation. Although the level of H-ras RNA correlated with the ultimate metastatic potential, it did not correlate with the initial rate of tumor cell pulmonary retention or clearing. Over the next 10 to 12 days, however, we detected a preferential survival and outgrowth of high H-ras-expressing variants, which correlated well with the ultimate metastatic ability but not NK susceptibility. These observations argue that the NK cell has its major effect early in the course of the disease, while subsequent tumor growth occurs preferentially in high H-ras-expressing cell lines.     

Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

Horner syndrome

Horner syndrome is an uncommon but important clinical entity, representing interruption of the sympathetic pathway to the eye and face. Horner syndrome is almost always diagnosed clinically, though pharmacological testing can be used to confirm the diagnosis. Imaging modalities such as PET, CT and MRI are important components of work‐up for patients presenting with acquired Horner syndrome. Our patient’s presentation with Horner syndrome unmasked the causative superior sulcus squamous cell carcinoma and a coincidental lower lobe adenocarcinoma. Successful radical treatment of these cancers resulted in complete resolution of the syndrome and disease‐free survival at 18 months. We review the anatomy and pathophysiology underlying this and other causes of Horner syndrome.     

Urinary monoamine metabolites as indices of mental stress in healthy males and females

Concentrations of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), the dopamine metabolite homovanillic acid (HVA) and the noradrenaline metabolite 4-hydroxy-3-methoxyphenyl glycol (HMPG) were determined in urine samples from healthy male and female students by mass fragmentography. Urine samples were obtained after a demanding examination (mental stress) and a day of ordinary school work (control condition). Self-ratings were obtained of feelings induced by the examination, and of habitual psychosomatic symptoms. The results for both sexes showed that the examination stress induced a significant increase of HVA and HMPG excretion, but not of 5-HIAA. The males excreted significantly more of each of the metabolites than the females. The pattern of correlations between metabolite levels and psychological and psychosomatic variables were strikingly different for the two sexes.     

氯仿重结晶棉酚的质量研究

报道了氯仿重结晶的棉酚的化学性质,样品在不同温度下干燥恒重后,经熔点、薄层层析、紫外光谱、红外光谱、X-射线衍射、热重量分析、元素(C,H,Cl)分析及棉酚合量测定等一系列的分析,确证了在60℃以下棉酚与氯仿成溶剂化物(solvate)。随着干燥温度的升高或在室温长时间的贮存,此现象逐渐消失,100℃真空干燥恒重后成为纯棉酚。     

Alpha-tocopherol and beta-carotene do not protect marmosets against the dopaminergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Idiopathic Parkinson's disease (PD) may possibly be caused by one or more unidentified neurotoxins present in the environment, or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in humans, lower primates and mice that closely resemble those found in PD. Because the mechanisms of neuronal damage in both idiopathic PD and in the MPTP model of PD may involve free radical formation in the substantia nigra, antioxidants might protect dopaminergic neurons. Previously, we found that both alpha-tocopherol and beta-carotene partially protected mice against MPTP. However, in the experiments described in this paper, neither alpha-tocopherol nor beta-carotene, each administered in massive doses, had any demonstrable protective effect for dopaminergic nigrostriatal neurons in marmosets injected with low doses of MPTP. Without more knowledge about the identity of the neurotoxin(s) causing idiopathic PD, and their mechanism of action, it is not possible at this time to predict whether these 2 antioxidants might be clinically useful in preventing or ameliorating PD.     

Metabolism of methotrexate and gamma-tert-butyl methotrexate by human leukemic cells in culture and by hepatic aldehyde oxidase in vitro

The cellular uptake and metabolism of methotrexate (MTX) and gamma-tert-butyl methotrexate (TBM) were compared in CEM human leukemic lymphoblasts and a highly MTX-resistant subline (CEM/MTX) in which MTX uptake is defective. The CEM/MTX cells were found previously to be as sensitive as the parent line to TBM. While MTX was polyglutamylated extensively in the CEM cells, giving abundant levels of non-effluxing conjugates, polyglutamylation in CEM/MTX cells was reduced severely, even after exposure to a high MTX concentration (100 microM) in the medium. This treatment provided free intracellular MTX in greater than 100-fold excess over the dihydrofolate reductase level. In contrast to MTX, the ester TBM was unmetabolized in either cell line. Uptake levels after incubation of CEM and CEM/MTX cells with 2 microM TBM for 24 hr were 17 and 15 pmol/mg protein respectively. Thus, TBM accumulated equally in both cells and was well retained despite the lack of polyglutamylation. These results, together with the previously observed affinity of the drug for dihydrofolate reductase, provide a plausible rationale for the comparable sensitivity of CEM and CEM/MTX cells to TBM. Experiments were also performed to determine the susceptibility of TBM to metabolic detoxification by hepatic aldehyde oxidase. Km values were 8-fold lower for TBM than for MTX in assays using an enzyme preparation from rabbit liver, and Vmax values were 8-fold higher. Neither MTX nor TBM was oxidized to its 7-hydroxy derivative in intact CEM or CEM/MTX cells. Because TBM is capable of overcoming at least one of the modalities of MTX resistance, defective polyglutamylation, and may be more efficiently detoxified than MTX by the action of hepatic aldehyde oxidase, it has the potential to be a useful agent for the treatment of MTX-resistant tumors.