Absence of simian virus 40 (SV40) DNA in lymphoma samples from Tasmania, Australia

AIMS: It has been postulated that the recent world-wide increase in the incidence of non-Hodgkin's lymphoma (NHL) may have been caused by human infection with simian virus 40 (SV40) (a lymphotropic monkey virus that was introduced to man from contaminated poliovirus vaccines between 1955 and 1963); therefore, we set out to determine the incidence of SV40 DNA positivity in lymphoma samples from patients in Tasmania, Australia. METHODS: One hundred lymph node samples, 50 from patients with lymphomas and 50 from controls, were tested using PCR amplification of three SV40-specific primer pairs followed by dot-blot hybridisation. RESULTS: All of the samples tested contained amplifiable DNA, but none contained amplifiable SV40 sequences with any of the primer sets used. CONCLUSIONS: Our results demonstrate absence of SV40 in the lymphoid tissues of our study population in Tasmania, Australia. SV40 does not explain the increasing incidence of NHL in our population.     

Differential effects of (S)- and (R)-enantiomers of albuterol in a mouse asthma model

BACKGROUND: (R)- and (S)-Enantiomers of albuterol likely exert differential effects in patients with asthma. The (R)-enantiomer binds to the beta2-adrenergic receptor with greater affinity than the (S)-enantiomer and is responsible for albuterol's bronchodilating activity. (S)-Albuterol augments bronchospasm and has proinflammatory actions. OBJECTIVE: The study aim was to determine whether the (S)-enantiomer, in contrast to the (R)-enantiomer, has adverse effects on allergic airway inflammation and hyperresponsiveness in a mouse asthma model. METHODS: Mice sensitized to ovalbumin (OVA) intraperitoneally on days 0 and 14 were challenged with OVA intranasally on days 14, 25, and 35. On day 36, 24 hours after the final allergen challenge, the effect of the (R)- and (S)-enantiomers of albuterol (1 mg x kg(-1) x d(-1) administered by means of a miniosmotic pump from days 13-36) on airway inflammation and hyperreactivity was determined. RESULTS: In OVA-sensitized/OVA-challenged mice, (R)-albuterol significantly reduced the influx of eosinophils into the bronchoalveolar lavage fluid and airway tissue. (R)-Albuterol also significantly decreased airway goblet cell hyperplasia and mucus occlusion and levels of IL-4 in bronchoalveolar lavage fluid and OVA-specific IgE in plasma. Although (S)-albuterol significantly reduced airway eosinophil infiltration, goblet cell hyperplasia, and mucus occlusion, it increased airway edema and responsiveness to methacholine in OVA-sensitized/OVA-challenged mice. Allergen-induced airway edema and pulmonary mechanics were unaffected by (R)-albuterol. CONCLUSION: Both (R)- and (S)-enantiomers of albuterol reduce airway eosinophil trafficking and mucus hypersecretion in a mouse model of asthma. However, (S)-albuterol increases allergen-induced airway edema and hyperresponsiveness. These adverse effects of the (S)-enantiomer on lung function might limit the clinical efficacy of racemic albuterol.     

Role of diurnal variation and receptor specificity in the opioidergic regulation of food intake in free-fed and food-deprived rats.

The effects of opioid agonists, morphine (MOR) and ketocyclazocine (KCZ), and antagonists, naltrexone (NALTX) and Mr2266, were investigated on food intake under various conditions, i.e., during light and dark phases of diurnal cycle and free-fed and fasting states in rats. NALTX showed a greater anorexic effect during dark phase, whereas Mr2266 produced such effect during light phase. This suggests that mu-receptors play a major role during dark phase while kappa-receptors are more important in light phase. The comparison of effects of different opioidergic drugs in fasted and free-fed rats showed that NALTX and Mr2266 reduced the elevated basal food intake in 18-h fasted rats to free-fed control levels. Therefore, it appears that enhanced endogenous mu- and kappa-directed neural mechanisms are one of the factors responsible for enhancing food intake in fasted rats. Differential role of MOR and KCZ on food intake in free-fed and fasted rats is also indicated in our study. Both agonists produced a biphasic response in fasted rats, i.e., hyperphagia (0-1 h) followed by hypophagia (1-6 h). However, a generalized hyperphagic effect is observed in free-fed rats (except during 3-6 h by MOR). The initial hyperphagic effect is more prominent in fasted rats which may be due to additive effects of endopioid mechanisms. Specificity of the response at various intervals is confirmed by blockade with NALTX and Mr2266. NALTX appears more potent than Mr2266 in antagonising the effects of MOR but markedly less potent than Mr2266 in inhibiting the effects of KCZ. This suggests that both MOR and KCZ have a mu as well as kappa component in food intake response.     

Second Thoughts: Multiple P300s Elicited by a Single Stimulus

In a previous report (Johnson & Donchin, 1978), we manipulated the discriminability of tone pairs that delivered feedback information in a time-estimation paradigm. As in other experiments using feedback stimuli, the event-related potentials elicited by these stimuli did not return to baseline in the 800-ms poststimulus interval. Since we were interested in this “Slow Wave'’activity, the poststimulus interval was lengthened to 1500 ms. Averages revealed that a second positive peak was present for some of the individual subjects. To investigate this activity further, the filtered singletrial waveforms were inspected visually. These data were characterized by the presence of one, and occasionally two, positive peaks, with highly variable latencies, following the P300. These peaks were indistinguishable in frequency and general appearance from the P300s elicited by the feedback stimuli. After latency adjusting the waveforms on the peak of the second positive wave, amplitude and latency were quantified. Whereas P300 amplitude was directly related to stimulus discriminability and positive feedback elicited larger P300s than negative feedback, the amplitude of the second positive wave was constant across levels of discriminability and the same for both types of feedback. In contrast, the latencies of both waves were inversely related to stimulus discriminability and shorter following positive feedback than negative feedback. Evidence is presented to support our contention that these additional positive peaks represent P300 activity. The data are discussed in terms of what these multiple P300s reveal about human information processing.     

Virilism as a late manifestation in the Bardet-Biedl syndrome

The second case of virilism as a late manifestation of Bardet-Biedl syndrome (BBS) is described, with endocrine and histological evaluation. Both cases manifested ovulatory cycles and developed virilism in adulthood. Elevated plasma testosterone and 17-OH-progesterone were not suppressed by dexamethasone but were suppressed by medroxyprogesterone acetate. Peripheral and ovarian venous blood obtained at the time of surgery demonstrated a marked gradient for testosterone in both ovaries and for progesterone in the ovary bearing the corpus luteum. Histological evaluation of the ovaries demonstrated bilateral ovarian stromal hyperplasia with focal hyperthecosis. Bilateral ovariectomy resulted in complete correction of the endocrine abnormality, although the established hirsutism remains a mark of previous androgen excess.     

Distinct hemagglutinin and neuraminidase epitopes involved in antigenic variation of recent human parainfluenza virus type 2 isolates.

A panel of fourteen neutralizing anti-HN monoclonal antibodies (mAbs) to the prototype Greer strain of human parainfluenza virus type 2 (PI2) was used to determine the extent of antigenic variation in recent virus isolates. Competitive binding analysis with the mAbs indicated the presence of at least five distinct antigenic sites (I to V) on the HN glycoprotein molecule. MAbs recognizing different antigenic sites were found to be associated with the hemagglutinin (sites I, IV and V), hemagglutinin and neuraminidase (site II), or neuraminidase (site III) activities. The location of two distinct epitopes identifying the neuraminidase sites (II and III) was further verified from the generation of escape mutants. Antibodies directed to sites I and III failed to show any detectable binding or neutralizing activity against a number of natural PI2 virus isolates collected in Texas between 1986 and 1987. Interestingly, these natural variants, unlike the prototype virus, did not show any detectable neuraminidase activity with fetuin as a substrate and the enzyme activity was only detected with N-acetylneuramin-lactose as an alternative substrate. Despite the observed variation in the antigenic sites, primary infection with the prototype virus or the natural variants generated a protective immune response against challenge infection with the other virus strains.     

Effects of placentation on selected type A behaviors in adult males in the national heart,lung, and blood institute (NHLBI) twin study

A dermatoglyphic index derived from monozygotic (MZ) twins of known placental type was used to estimate placentation retrospectively in a sample of adult male MZ twins. Examination of behavioral test scores with respect to placentation showed that the within-pair difference of most measures of type A behavior was smaller in presumed monochorionic than presumed dichorionic pairs. Measures of cognitive function and hostility were not related to placental type. Intraclass correlations in the monochorionic subgroup of MZ twins were greater than the correlations reported for the full sample of MZ twins. The trends were strongest for the Adjective Check List scales taken at two different exams 5 years apart and, to a lesser extent, for the Framingham type A scale. Our results are most consistent with greater intrauterine environmental covariance in monochorionic MZ twins as an explanation for inflation of the MZ twin correlation relative to dizygotic (DZ) correlation reported for some type A measures.     

Molecular cloning and sequence analysis of the fusion glycoprotein gene of human parainfluenza virus type 2

A cDNA clone containing a 2.0-kb insert was identified as the human parainfluenza virus type 2 (PI2) fusion glycoprotein gene by hybridizing with a viral RNA probe and a synthetic oligonucleotide derived from a conserved sequence found in other paramyxovirus fusion protein genes. The complete nucleotide sequence of the glycoprotein gene was determined by the dideoxynucleotide sequencing procedure and found to contain a single, large open reading frame encoding a protein of 551 amino acids with a calculated molecular weight of 59,664. Comparison of the P12 fusion protein with those of other paramyxoviruses indicated similarities in overall length, N-terminal signal peptide sequence (amino acids 7 to 25), C-terminal membrane-spanning region (amino acids 486 to 513), and a highly conserved fusion sequence region at the N-terminus of the F1 subunit (amino acids 107 to 132).