Transplantability of human head and neck squamous cell carcinomas in athymic nude mice

Tumor material from 91 patients with squamous cell carcinoma of the head and neck was transplanted subcutaneously in athymic nude mice. In the first (man to mouse) passage, the calculated mean probability of tumor take in a single mouse was 11%. The probability of growth in the first passage was significantly better for moderately and poorly differentiated tumors than for well-differentiated tumors. Also, the implantation of lymph node material resulted in a significantly better tumor take rate than material taken from a primary tumor. Transplantability was not dependent on the following characteristics: localization, T or N stage of the tumor, or the sex of the patients. Once growth was established, all variables studied had no influence on the probability of growth in the subsequent mouse passages. A relationship between tumor growth in nude mice and patient prognosis could not be found. When transplanting head and neck squamous cell carcinoma in nude mice, it has to be recognized that some tumor characteristics will influence the success of tumor growth.     

Neuropsychological predictors of self-neglect in cognitively impaired older people who live alone.

OBJECTIVE: The authors examined the accuracy of certain neuropsychological tests in the prediction of harm resulting from self-neglect in cognitively impaired seniors who lived alone. METHODS: The study included 130 participants, aged 65 and older, who scored less than 131 on the Dementia Rating Scale. Neuropsychological tests were administered at baseline, resulting in eight predictive scores. Informants and primary care physicians provided information about harm that occurred to the participants during the 18-month prospective follow up. An incident was defined as harmful if it occurred as the result of self-neglect or disorientation and resulted in physical injury or property loss or damage and required emergency interventions. Proportional hazard regression analysis was conducted to examine the predictive relationship between the eight neuropsychological tests and time to incident harm with age, sex, education, the Charlson Comorbidity Index, and the Mini-Mental State Examination included in the model as covariates. RESULTS: Twenty-seven participants experienced harm during the 18-month follow-up period. A proportional hazards model indicated that three neuropsychological tests, which measured recognition memory, executive functioning, and conceptualization, were independent risk factors for harm. CONCLUSIONS: These findings provide insight into why harm occurred in these cognitively impaired elders who lived alone. They also support the ecologic validity of these tests and suggest directions for the development of intervention strategies for harm prevention.     

Dopaminergic modulation of bulbofugal projections in the rat olfactory tubercle

Neuronal activities following olfactory bulb electrical stimulation were examined before and after administration of dopamine and dopamine antagonist in the rat olfactory tubercle. The inhibitory response to olfactory bulb stimulation was attenuated by systemic haloperidol administration, but the excitatory response to olfactory bulb stimulation rarely was modulated. Topical application of dopamine by iontophoresis extended the duration of inhibition in 56% of the neurons sampled and diminished it in 25%; the excitatory response was modulated in 42% of neurons, most of which were attenuated. These findings suggest that dopamine in the olfactory tubercle could be involved in modulations of neuronal activities related to olfactory transduction.     

EBV+ B Lymphoma Cell Lines from Patients with Post-Transplant Lymphoproliferative Disease Are Resistant to TRAIL-Induced Apoptosis

Lymphomas associated with post-transplant lymphoproliferative disease (PTLD) represent a significant complication of immunosuppression in transplant recipients. In immunocompetent individuals, EBV-specific cytotoxic T lymphocytes (CTL) prevent the outgrowth of activated B lymphoblasts through apoptosis induction. Soluble versions of TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL) can induce apoptosis in numerous tumor cell types. Given the therapeutic potential of TRAIL, we examined the sensitivity of EBV⁺ spontaneous lymphoblastoid cell lines (SLCL) derived from patients with PTLD to treatment with soluble TRAIL. Despite abundant expression of TRAIL receptors (TRAIL-R), resistance to TRAIL-induced apoptosis was observed in all SLCL examined. This resistance could not be overcome by concomitant treatment with several pharmacological agents. Unlike BJAB positive control cells, for each SLCL tested, cleavage and activation of caspase 8 was inhibited due to failed recruitment of FADD and caspase 8 to TRAIL receptors upon stimulation. Further indicative of a proximal defect, TRAIL receptor aggregation could not be detected on the cell surface of SLCL following ligand engagement. These results suggest that the use of TRAIL for eliminating PTLD-associated tumors may be of limited clinical utility, and illustrate another mechanism by which EBV⁺ B lymphoma cells can evade tumor surveillance at the level of death receptor signaling.     

Occult metastatic neck disease: detection with US and US-guided fine-needle aspiration cytology

The authors performed a prospective study of the value of ultrasonography (US) and US-guided fine-needle aspiration cytology (FNAC) for assessment of N0 lesions in the neck. Preoperative US was performed in 107 patients with squamous cell carcinoma of the head and neck, who underwent 132 elective neck dissections. During the US examination of the last 54 patients, who underwent 70 elective neck dissections, US-guided FNAC was performed. US alone was found to be an unreliable method for detecting occult lymph node metastasis; the accuracy never exceeded 70% (93 of 132), with a sensitivity of 60% (32 of 53) and a specificity of 77% (61 of 79). In contrast, US-guided FNAC had an accuracy of 89% (62 of 70), a sensitivity of 76% (25 of 33), and a specificity of 100% (37 of 37). Because of the high sensitivity and specificity of US-guided FNAC for the assessment of the N0 neck, this modality may play an important role in directing treatment of these patients in the future.     

Novel quinuclidine-based ligands for the muscarinic cholinergic receptor

Recent clinical studies on Alzheimer's patients have implied that only agents displaying high efficacy at the cortical muscarinic receptor have yielded encouraging results. This paper describes the design, synthesis, and biochemical characterization of novel quinuclidine-based muscarinic agonists which can readily penetrate into the central nervous system and which are capable of displaying high efficacy at cortical sites. With use of a biochemical assay capable of measuring receptor affinity and predicting cortical efficacy, it has been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent with recent molecular biology studies, structure-activity trends are interpreted in terms of separate binding sites for agonists and antagonists with H-bonding interactions characterizing agonist behavior and lipophilic binding characterizing antagonist behavior. Thus the aminooxadiazole moiety has structural features which are optimized for an agonist profile.