E2F activity is regulated by cell cycle-dependent changes in subcellular localization.

E2F directs the cell cycle-dependent expression of genes that induce or regulate the cell division process. In mammalian cells, this transcriptional activity arises from the combined properties of multiple E2F-DP heterodimers. In this study, we show that the transcriptional potential of individual E2F species is dependent upon their nuclear localization. This is a constitutive property of E2F-1, -2, and -3, whereas the nuclear localization of E2F-4 is dependent upon its association with other nuclear factors. We previously showed that E2F-4 accounts for the majority of endogenous E2F species. We now show that the subcellular localization of E2F-4 is regulated in a cell cycle-dependent manner that results in the differential compartmentalization of the various E2F complexes. Consequently, in cycling cells, the majority of the p107-E2F, p130-E2F, and free E2F complexes remain in the cytoplasm. In contrast, almost all of the nuclear E2F activity is generated by pRB-E2F. This complex is present at high levels during G1 but disappears once the cells have passed the restriction point. Surprisingly, dissociation of this complex causes little increase in the levels of nuclear free E2F activity. This observation suggests that the repressive properties of the pRB-E2F complex play a critical role in establishing the temporal regulation of E2F-responsive genes. How the differential subcellular localization of pRB, p107, and p130 contributes to their different biological properties is also discussed.

Isolevuglandins as a gauge of lipid peroxidation in human tumors.

The cellular production of free radicals or reactive oxygen species (ROS) can lead to protein, lipid or DNA modifications and tumor formation. The cellular lipids undergo structural changes through the actions of enzymes (e.g. cyclooxygenases) or free radicals to form a class of compounds called Isolevuglandins (IsoLGs). The recruitment and continued exposure of tissue to ROS and IsoLGs causes increased cell proliferation, mutagenesis, loss of normal cell function and angiogenesis. The elevated concentration of ROS in cancerous tissues suggests that these mediators play an important role in cancer development. We hypothesized that tumors with elevated ROS levels would similarly possess an increased concentration of IsoLGs when compared with normal tissue. Using D11, an ScFv recombinant antibody specific for IsoLGs, we utilized immunohistochemistry to visualize the presence of IsoLG in human tumors compared to normal adjacent tissue (NAT) to the same tumor. We found that IsoLG concentrations were elevated in human breast, colon, kidney, liver, lung, pancreatic and tongue tumor cells when compared to NAT and believe that IsoLGs can be used as a gauge indicative of lipid peroxidation in tumors.

Regulation of electrical activity and neuronal excitability in Helisoma trivolvis by carbon monoxide.

Carbon monoxide (CO), like other gaseous neuromodulators, has a dual nature as both a toxic gas and a physiologically relevant signaling molecule. In the nervous system, high concentrations of CO can lead to neuronal injury while lower concentrations are found to be neuroprotective. The number of cellular targets affected by physiological concentrations of CO is rapidly growing and includes ion channels in various cell types. The modulation of ion channels by CO in neurons, however, and the effect it has on neural activity are incompletely understood. Here, the well-characterized buccal neurons, B5 and B19, of the freshwater snail, Helisoma trivolvis, were used to investigate the role that CO plays in regulating spontaneous firing activity and neuronal excitability. Neurons were studied in single-cell culture, thereby removing other signals normally present in the intact nervous system and allowing for the optimal characterization of physiological effects of CO. We found that the CO donor molecule, carbon monoxide releasing molecule-2 (CORM-2), hyperpolarized the resting membrane potential of B5 neurons and silenced their spontaneous firing activity. These effects were mediated through the inhibition of a persistent sodium current. CORM-2 also inhibited neuronal excitability. This effect was mediated by the inhibition of voltage-gated calcium channels by CO. The general findings of CO acting as a hyperpolarizing signal and an inhibitor of neuronal excitability extended to B19 neurons. Taken together, these findings suggest that CO is a potent modulator of ion channels with broad implications for the modulation of neural activity in a wide range of neuron-types.

Cross-antigenicity between the scabies mite, Sarcoptes scabiei, and the house dust mite, Dermatophagoides pteronyssinus.

This study demonstrated that antigens of the parasitic mite Sarcoptes scabiei (SS) cross-react with antigens of the house dust mite Dermatophagoides pteronyssinus (DP). Crossed immunoelectrophoresis (CIE) reaction of SS extract with rabbit anti-DP serum resulted in multiple immunoprecipitates. Reciprocal CIE reactions gave similar results. Immunoprecipitates from both reactions bound IgE in the sera of dust-mite-sensitive patients who had no history of scabies. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved protein/peptide bands of both SS and DP also bound serum IgE from dust-mite-allergic patients following immunoblotting. Non-allergic control sera gave no IgE binding to either SS or DP antigens. These results indicate that patients with atopy to dust mites exhibit circulating antibodies built to DP but that recognize determinants on SS antigens. It is highly probable that scabietic patients build antibodies to SS antigens that also recognize DP antigens. These results raise questions concerning the reported isotypic antibody responses to SS because the sensitivity of scabietic patients to house dust mites has not been previously evaluated. This cross-reactivity may play an important role in the susceptibility to scabies and its clinical manifestations.

Granulomatous vasculitis associated with herpes virus: a persistent, painful, postherpetic papular eruption.

Cutaneous granulomatous vasculitis manifesting as a postherpetic reaction pattern is uncommon hand has previously been reported as a delayed complication of varicella-zoster virus infection. We describe three patients who had persistent, painful, postherpetic papules in a zosteriform distribution that histologically demonstrated a small vessel granulomatous vasculitis. Herpes simplex virus DNA detected by the polymerase chain reaction technique was demonstrated in two cases.

Does noise stress modulate effects of smoking/nicotine? Mood, vigilance, and EEG responses.

Effects of smoking multiple cigarettes on EEG, vigilance, and subjective state were assessed in a repeated measures design where noise level (high versus minimal) was crossed with nicotine dose (quasi-ad lib own versus 1.0 mg FTC nicotine machine-delivered dose versus 0.05 mg FTC nicotine machine-delivered dose). Vigilance was increased by nicotine, but not by noise and there was no noise by dose interaction. Effects of nicotine on EEG varied as a function of dose, noise, hemisphere, time, and eyes-open versus eyes-closed condition. Smoking normal nicotine delivery (0.9-1.1 mg FTC-estimated) cigarettes resulted in decreases in percentages of delta and theta EEG magnitude and increased percentage beta-1 EEG magnitude across conditions and time. Changes in alpha and theta magnitude were dependent on eyes being open versus closed. Hemispheric asymmetries varied as a function of noise and time. Consistent with inverted "U" models, effects of nicotine on EEG were clearly stimulant during the quiet conditions while there were minimal to no differences between nicotine doses during the high-noise conditions. The failure of nicotine to modify mood is interpreted in terms of bioinformational models of nicotine's subjective effects.

Skin test and radioallergosorbent test characteristics of scabietic patients.

The scabies mite Sarcoptes scabiei and the Dermatophagoides house dust mites (HDM) are related phylogenetically and are the sources of several cross-reactive antigens. The purpose of this study was to investigate the immune response to S. scabiei and HDM in scabietic patients. Skin test sensitivity and serum IgE to both S. scabiei and HDM were determined for patients who had or previously had confirmed ordinary scabies. A retrospective group included nine subjects who had received successful treatment three weeks to one year prior to the study. A prospective group included 16 subjects with active scabies. Allergic histories were obtained, serum was collected, and skin prick tests (SPTs) were performed at enrollment for all and periodically over the next 12 months for the prospective patients. None of the individuals in either group reported a known sensitivity to HDM. Six of the nine retrospective patients were SPT positive to both S. scabiei and HDM and two of these showed circulating IgE specific for these antigens. At diagnosis, 13 of 16 patients with active scabies were SPT positive to S. scabiei and 12 of these were also SPT and/or radioallergosorbent test positive to HDM. Six patients had circulating IgE directed at both S. scabiei and HDM antigens while one subject had IgE to S. scabiei only and another had IgE directed at HDM only. Twelve of the 15 subjects tested also showed IgE and/or IgG binding to one or more bands on Western blots of an S. scabiei-specific protein fraction. This study indicated that approximately half of the patients with active scabies had S. scabiei- and HDM-specific circulating IgE while most patients cured of scabies lacked S. scabiei- and HDM-specific serum IgE. The data also suggested that antibodies to S. scabiei in scabietic patients also recognize HDM; however, some antibodies were directed at scabies-specific antigens.

Successful pregnancies from men with retrograde ejaculation with the use of washed sperm and gamete intrafallopian tube transfer (GIFT).

Viable sperm were collected from men suffering from retrograde ejaculation by the technique of rapid washing of semen/urine in a buffered collection solution. The utilization of washed semen/urine from two men with retrograde ejaculation in the GIFT procedure lead to successful conceptions and the birth of two healthy female babies. Thus, the technique of rapid washing of sperm from retrograde ejaculating men coupled with GIFT represents a viable alternative for the attainment of pregnancy.

Primary cutaneous phaeohyphomycosis caused by Drechslera spicifera.

A primary cutaneous lesion in a 5-year-old boy who had recently received chemotherapy for acute lymphocytic leukemia was found to be caused by a dematiaceous fungus, Drechslera spicifera. The lesion was an erythematous macule that rapidly developed necrotic ulcerations. The fungus, which is commonly found in soil and as a plant pathogen, was isolated from cultures of the lesion and from an excisional biopsy specimen. Hyphae and swollen hyphal cells resembling chlamydospores were observed in the biopsy specimen. Septate pigmented hyphae were found in the tissue, which is consistent with phaeohyphomycosis. Resolution of the infection occurred following excisional biopsy and systemic amphotericin B therapy. There was a concomitant recovery from neutropenia.

Behavior therapy techniques in treatment of exfoliative dermatitis.

We report here a case study in which behavior therapy techniques were used to treat the persistent and severe scratching of a patient with long-standing exfoliative dermatitis. A multiple-baseline clinical design across different body areas was used to evaluate the behavioral treatment program. This program consisted of (1) training the patient to monitor his scratching behavior and to use an incompatible response and distraction procedure contingent on the occurrence of scratching, and (2) differential attention by the therapist, so that the therapist's attention was contingent on intervals of nonscratching, and the therapist ignored the patient when he did scratch. The results indicated that the program was effective in almost completely eliminating scratching when a variety of therapists were and were not present. This suggests that the procedures used might easily be taught to the nursing staff.

Enhancement of attention processing by Kantroll in healthy humans: a pilot study.

This is the first report in humans of the effects of daily ingestion of a specific amino acid mixture, Kantroll, on cognitive event-related potentials (ERPs) associated with performance. Cognitive ERPs were generated by two computerized visual attention tasks, the Spatial Orientation Task (SOT) and Contingent Continuous Performance Task (CCPT), in normal young adult volunteers, where each subject acted as his own control for testing before and after 28-30 days of amino acid ingestion. A statistically significant amplitude enhancement of the P300 component of the ERPs was seen after Kantroll for both tasks, as well as improvement with respect to cognitive processing speeds. The enhancement of neurophysiologic function observed in this study on normal controls is consistent with the facilitation of recovery of individuals with RDS (i.e., substance use disorder, ADHD, carbohydrate bingeing) following the ingestion of the amino acid supplement, Kantroll, and warrants additional placebo-controlled, double-blind, studies to confirm and extend these results.

EEG, physiology, and task-related mood fail to resolve across 31 days of smoking abstinence: relations to depressive traits, nicotine exposure, and dependence.

Changes in task-related mood and physiology associated with 31 days of smoking abstinence were assessed in smokers, 34 of whom were randomly assigned to a quit group and 22 to a continuing-to-smoke control group. A large financial incentive for smoking abstinence resulted in very low participant attrition. Individuals were tested during prequit baselines and at 3, 10, 17, and 31 days of abstinence. Abstinence was associated with decreases in heart rate and serum cortisol, a slowing of electroencephalogram (EEG) activity, and task-dependent and trait-depression-dependent hemispheric EEG asymmetries. Differences between the quit group and the smoking group showed no tendency to resolve across the 31 days of abstinence. Trait depression and neuroticism correlated with increases in left-relative-to-right frontal EEG slow-wave (low alpha) activity at both 3 and 31 days of abstinence. In contrast, prequit nicotine intake and Fagerström Tolerance scores correlated with alpha asymmetry and with greater EEG slowing only at Day 3. Thus, the effects of smoking abstinence appear to last for at least several months.

Relapsing polychondritis. A case report and literature review.

Relapsing polychondritis is a systemic disorder characterized by recurrent inflammation and degeneration of cartilaginous tissue. The eyes, ears, nose, larynx, trachea, and articular areas are commonly involved. While ocular involvement, hearing, and vestibular dysfunction are frequently present, aortic valve and root disease as well as vasculitis also may occur. While the cause remains unknown, an autoimmune pathogenesis appears likely. Thus, dapsone and/or systemic corticosteroids remain the predominant effective therapies. Another case of relapsing polychondritis with an associated vasculitis syndrome is presented as well as a review of the current literature.

Multiple epitheliomata cuniculata occurring in a mutilating keratoderma.

We report on a young man with a congenital mutilating keratoderma in whom three epitheliomata cuniculata occurred during a two-year period. The clinical findings, associated disease states, and treatment of epithelioma cuniculatum (EC) are reviewed.

Lipedematous alopecia.

Lipedematous alopecia is an unusual disorder characterized by short, brittle scalp hairs associated with thickening of the scalp by adipose tissue. All except one reported case have been in African-American females. It is our purpose to report the seventh case of this condition.

Infestivity of Psoroptes cuniculi in rabbits.

Starving Psoroptes cuniculi were found to survive off the host for 4 to 21 days at relative humidities between 20% and 99% and temperatures between 5 and 30 C. Within these extremes, survival was greatest at low temperature and high relative humidity (RH). Mites were infestive for at least 50% of their survival times and may have infested new hosts in contaminated facilities. A temperature of 40 C and 20% RH maintained for 24 hours caused 100% mortality in test mites. Other selected combinations of temperature above 40 C and RH less than or equal to 75% also caused 100% mortality in 2 days or less. These conditions could be used to control these mites in vacated contaminated premises.

Symptomatic dermographism.

Urticaria is caused by physical factors in almost 12 percent of cases. These factors include pressure. Dermographism is the appearance of whealing and erythema within minutes where skin has been exposed to pressure or mechanical irritation. Symptomatic dermographism is present when "normal" pressures, such as those encountered in the activities of daily living, cause urticaria. Individuals with symptomatic dermographism can be shown to have a lower pressure threshold for the production of dermographism than normal individuals. A case of symptomatic dermographism is presented, and the differential diagnosis is discussed.

A model for the development of the CNS role in adolescent health promotion self-care.

A meaningful definition of the CNS has been difficult to express because of the versatility of the role, yet a clear understanding of the role responsibilities is essential to ensure successful implementation of the CNS position within a select client population. Adolescence is a period in the life-span that represents such a population. Adolescents undergo certain cognitive changes that render them vulnerable to health-damaging behaviors often initiated during this stage of development. Health promotion self-care strategies by the CNS are important in helping the young person incorporate positive health practices in daily activities. A conceptual model, based on Orem's general theory of nursing, has been developed through literature review and refined through practical application. It is presented as a framework by which health promotion needs of the adolescent may be predicted, recognized, and satisfied through components of the CNS role, the basic concepts of Orem's model, and characteristics of adolescent cognitive development.