Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium.

The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort among academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g., clinical diagnosis, treatment history, and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays.

Photodegraded nifedipine stimulates uptake and retention of iron in human epidermal keratinocytes.

Photodegraded nifedipine has been shown to increase uptake of nontransferrin bound iron into erythroid cells. If iron could be loaded into keratinocytes, it might be possible to exploit epidermal desquamation for the purpose of eliminating potentially toxic amounts of iron from the body. We investigated the ability of photodegraded nifedipine to stimulate iron transport and accumulation in human epidermal keratinocytes. Nifedipine was degraded to its nitroso derivative by exposure to sunlight. 59Fe uptake was measured in keratinocyte monolayers, and total iron content was measured in stratified epidermal cultures. Photodegraded nifedipine increased iron uptake into keratinocytes 80-fold compared to controls. The effect of photodegraded nifedipine on iron uptake was rapid, was concentration dependent and occurred at physiologically relevant concentrations of nonprotein-bound iron. Stimulation of iron uptake by photodegraded nifedipine was independent of transferrin and worked equally well in the presence or absence of serum proteins. Iron content in keratinocytes was increased 3-fold by four daily treatments with photodegraded nifedipine. The increased iron content resulting from photodegraded nifedipine treatment was retained during a 4 d washout period. Photodegraded nifedipine may be a way delivering clinically significant amounts of iron to the epidermis.

Word fluency generation skills of head-injured patients in an acute trauma center.

Two hundred-eighteen acutely brain-injured trauma patients with confirmed diagnosis of initial closed head injury completed two types of word fluency generation tasks, animal naming and single-letter-based word generation. Numbers of responses and inferred strategy utilizations were examined and compared with established norms for non-brain-injured individuals using frequency counts and chi 2 analyses. Significant differences were noted in response quantity and quality between closed head-injury patients and normals. A positive relationship was noted between level of cognitive functioning and number of word associates generated. Same initial consonant-vowel syllable (see-seed), semantic association (ship-sail), and same initial consonant-consonant blend (tree-trick) strategies were used by all subjects regardless of severity of injury. Quantitative and qualitative differences were noted as a function of severity of cognitive disruption.

Potentiation of systemic morphine analgesia in humans by proglumide, a cholecystokinin antagonist.

Proglumide, a cholecystokinin antagonist, potentiates analgesia produced in rats by morphine and endogenous opiates, and appears to reverse tolerance in rats to opiate analgesia. Therefore, proglumide and other cholecystokinin antagonists may be clinically valuable. We have tested proglumide's possible opiate analgesic potentiating effects by examining, in volunteers, the effects of morphine and proglumide on human pain visual analogue scale responses to 45-51 degrees C skin temperature stimuli. Proglumide (50-100 micrograms intravenously) potentiated both the magnitude and duration of analgesia produced by small doses of morphine. This study provides indirect evidence for a cholecystokinin-opiate interaction in humans. Therefore, cholecystokinin antagonists such as proglumide may serve to potentiate exogenous or endogenous opiate action.

A psychophysical analysis of morphine analgesia.

Intravenous administration of 0.04-0.08 mg/kg morphine sulfate reduced both sensory intensity and unpleasantness visual analogue scale (VAS) responses to graded 5 sec nociceptive temperature stimuli (45-51 degrees C) in a dose-dependent manner. The lower doses of morphine (0.04 and 0.06 mg/kg) resulted in statistically reliable reductions in affective but not sensory intensity VAS responses, possibly reflecting supraspinal effects on brain regions involved in affect and motivation. However, the highest dose of morphine tested (0.08 mg/kg) reduced both sensory and affective VAS responses to graded nociceptive stimuli as well as VAS sensory responses to first and second pain evoked by brief heat pulses. Morphine also had an especially potent inhibitory effect on temporal summation of second pain that is known to occur when intense nociceptive stimuli occur at rates greater than 0.3/sec. The results support current hypotheses about neural mechanisms of narcotic analgesia and further clarify the relative effects of morphine on sensory and affective dimensions of experimental pain. The derived morphine dose-analgesic response functions also provide a reference standard for quantitatively comparing magnitudes of different CNS-mediated forms of analgesia.

Maternal rejection and children's intensity. Implications for sex differences in affective development.

The interaction between intensity and activity of children and their mothers' rejective attitude is studied. It appears that hostile mothers fault their daughters for their intensity in a much more direct manner than their sons. It is suggested that this differential attitude is of consequence in the development of women and men in our society.