Pulmonary kinetics of 13N-ammonia in smoking subjects--a quantitative study using dynamic PET]

To evaluate the effect of smoking on nonrespiratory function in the lung, a dynamic PET with 13NH3 in the lung was performed in 18 normal volunteers without lung disease nor congestion (9 non-smokers, 4 exsmokers, 5 smokers). After intravenous bolus injection of 13NH3, twenty serial 5.5-second scans followed by six 30-second scans were performed. Regions of interests were assigned on the ventral, lateral and dorsal part of the right lung and time-activity curves were generated through 26 images. The activity curve demonstrated a biexponential clearance from the lung with fast and slow component. The retention fraction (RF), fractional size of the slow component, was calculated, and the half-times (t 1/2) of both components were also evaluated. A significant increase of RF and prolongation of t 1/2 of slow component were observed in smokers compared to non-smokers and exsmokers. However, no significant difference of RF nor t 1/2 of both components was observed between non-smokers and exsmokers. These results suggest that long term smoking may modify the pulmonary kinetics of 13NH3, but the change is reversible after cessation of smoking for one year or longer.     

Internal and external information processing by lateral hypothalamic glucose-sensitive and insensitive neurons during bar press feeding in the monkey

Single neuron activities in the lateral hypothalamic area (LHA) were recorded during bar press feeding task in the monkey. First registered neurons were sorted into 2 groups, glucose-sensitive (GS) and glucose-insensitive (GIS) neurons, depending on their glucose sensitivity. Then firing variations to feeding, electrophoretically applied catecholamines and opiate, and to odor and taste stimuli were investigated. GS neurons responded to dopamine, noradrenaline and morphine more often than GIS neurons. In feeding task GS neurons responded during bar press (BP) and reward (RW) periods with long-lasting inhibition of firing and at cue tone (CT) with transient inhibition, while GIS neurons responded during BP and RW periods mainly with excitation and at cue light (CL) with excitation. A majority of GS neurons responded to both odor and taste stimuli more often than GIS neurons. Data suggest that these two kinds of neurons in the LHA may be involved in different functional aspects of feeding: GS neurons, mainly in internal information processing and reward mechanism, and GIS neurons, in external information processing and motor aspects.     

Comparison of the size of neuronal and non-neuronal histamine pools in the brain of different rat strains

Summary The size of the neuronal and non-neuronal histamine pools in the brain of three different strains of rats was measured by assuming that the -fluoromethylhistidine-induced maximal decrement of histamine represents the size of the neuronal pool. Although the total histamine levels in the brain showed a considerable interstrain variation, no significant interstrain difference was observed in the neuronal histamine level. These results suggest that the size of the neuronal histamine pool in the brain is relatively stable, whereas the size of the non-neuronal histamine pool is variable.     

Age-related decrease of 11C-N-methylspiperone in vivo binding to human striatum detected by PET

The effect of aging on 11C-N-methylspiperone binding to living human striatum was demonstrated using positron emission tomography. The 11 normal volunteers (22 to 72 years old) participated in this study. The uptake of 11C-N-methylspiperone in the brain following intravenous injection was highest in the striatum in individual subject. And the uptake in the striatum only gradually increased until the end of the study. The uptake of 11C-N-methylspiperone in cerebellum peaked within 10 minutes following injection and then rapidly dropped. The association rate constant "k3" was calculated from the slope of the radioactivity-ratio of striatum to cerebellum versus the equivalent time. The equivalent time was calculated from the radioactivity of cerebellum as an input function. The exponential decrease of the k3 value with aging was observed. The k3 value of the youngest subject (22 years old, male) was 0.035/min, while that of the oldest one (72 years old, male) was found to be 0.020/min. These data suggested that the dopaminergic activity through D2 dopamine receptors reduces with aging in human striatum.     

Discrete breakpoint mapping and shortest region of overlap of chromosome arm 1q gain and 1p loss in human hepatocellular carcinoma detected by semiquantitative microsatellite analysis

Recurrent chromosomal gain at 1q is one of the most common features of human hepatocellular carcinoma (HCC), but how the gain at 1q contributes to hepatocarcinogenesis is still unclear. To identify the target genes, precise determination of the shortest region of overlap (SRO) and of breakpoints is necessary. Similarly, the role of loss at 1p, which is also a major cytogenetic aberration in HCC, needs to be determined. Fifty HCCs were examined with the aid of 59 microsatellite markers distributed throughout both arms of chromosome 1. To detect allelic gain effectively, the cutoff value of the allelic imbalance index was set at 0.70. Alleles showing imbalance were subjected to multiplex PCR, using a retained allele as an internal control, to determine whether the imbalance was the result of chromosomal gain or loss. The SRO of the gains was defined as D1S2878-D1S2619 (1q23.-q25.3, 16.9 Mb), which involved 36 cases (72%). Gains in the number of copies of certain oncogenes within this region seemed to be critical for the pathogenesis of HCC. In contrast, the centromeric breakpoints of these gains varied, but they tended to occur mainly in the pericentromeric region (26 of 50 cases, 52%). Rearrangement of specific genes associated with the gains is unlikely. On the other hand, the SRO of deletion was defined as D1S2893-D1S450 (1p36.32-p36.22, 5.1 Mb). Four known putative tumor-suppressor genes (TP73, RIZ1, NBL1/DAN, and CDKN2C) were outside the SRO, suggesting the presence of other candidate genes with critical roles in hepatocarcinogenesis.     

Relationships between Responsiveness of the Bronchi to Acetylcholine and Cyclic AMP Response of Lymphocytes to Beta1- and Beta2-Adrenergic Receptor Stimulation in Patients with Asthma

Decreased response of beta-adrenergic receptor has been considered to he one of the causes of increased responsiveness of the bronchi in asthma. Since beta-adrenergic receptor has two subtypes, beta₁ and beta₂, and the bronchodilating effect of beta stimulants is mediated by beta₂-receptor, responsiveness of the bronchi is expected to correlate to the cyclic AMP response of lymphocytes to a beta₂-stimulant. Responsiveness of the bronchi was expressed as respiratory threshold to acetylcholine (RT-Ach), which was the minimal concentration of acetylcholine solution to cause an initial decrease of FEV₁ of more than 20% of the baseline value. Beta₁ and heta₂-responses were expressed as the increments of cyclic AMP content of 10⁶ lymphocytes incubated with norepinephrine (beta₁-stimulant) and salbutamol (beta₂-stimulant).
RT-Ach showed a significant correlation with the beta₂-cyclic AMP response of lymphocytes, but not with the beta₁ -response among patients with asthma. Sixteen symptomatic patients on continuous beta-stimulants showed lower RT-Ach value and diminished beta₂-receptor activity of lymphocytes compared with 14 patients in remission. These results suggest that selective beta₂-adrenergic blockade may he one of the causes of bronchial hypersensitivity in asthma, though it should be noted that in this study beta-adrenergic responses were examined in lymphocytes and were compared with the responsiveneness of the bronchi. Possible beta-receptor subsensitivity induced by administration of beta-stimulants is discussed.     

Chymase participates in chronic dermatitis by inducing eosinophil infiltration

An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis.