P2U-purinergic receptor activation mediates inhibition of cAMP accumulation in cultured renal mesangial cells

Extracellular ATP has been reported to exert mitogenic and contractile effects on cultured renal mesangial cells (MCs). Since it is possible that these actions involve changes in the cAMP second messenger system, we examined the effect of extracellular nucleotides on the accumulation of cAMP in rat MCs. ATP, UTP and adenosine 5'-0-(3-thio)triphosphate (ATP gamma S) (100 microM) had no significant effects on baseline cAMP levels, but inhibited forskolin-stimulated accumulation of cAMP by 21-75% in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Maximal inhibitory effects were observed at 100 microM of ATP gamma S with a threshold dose of 1 microM. ATP gamma S, ATP and UTP were the most potent inhibitors indicating stimulation of the P2u receptor. The P2x agonists adenosine 5'-(alpha, beta-methylene) triphosphate and adenosine 5'-(beta, gamma-methylene) triphosphate, and the P2y agonist 2-methylthio-ATP did not affect cAMP accumulation. Treatment with the P2 receptor antagonist suramin (200 microM) reduced the inhibition by 58%. The inhibitory effects of the nucleotides were significantly attenuated by preincubation with pertussis toxin (10-100 ng/ml). Inhibition of phospholipase C and protein kinase C did not prevent the inhibitory effect of the nucleotides. Inhibitors of forskolin-stimulated cAMP accumulation had different effects on DNA synthesis in cultured MCs as measured by 3H-thymidine uptake at 48 h: ATP, ATP gamma S and the inhibitor of adenylyl cyclase, SQ 22536, stimulated DNA synthesis in MCs, while UTP showed no significant mitogenic effect. Agents which increased baseline levels of intracellular cAMP (forskolin, IBMX, dibutyryl-cAMP) significantly diminished DNA synthesis in MCs. The results indicate that the P2u-purinergic receptor mediates inhibition of forskolin-induced cAMP accumulation which is likely due to inhibition of adenylyl cyclase. This effect appears to be partially mediated by PTX-sensitive G proteins. While the increase in cAMP accumulation is anti-mitogenic, inhibition of cAMP accumulation by P2u receptors is not correlated with MC growth control. Thus, additional mechanisms other than inhibition of cAMP accumulation by P2u receptors are likely to be involved in the mitogenesis of extracellular ATP.     

A mixed-signal RAM decision-feedback equalizer for disk drives

A mixed-signal RAM decision-feedback equalizer (DFE) that operates at 90 Mb/s is described. In the analog domain, the DFE subtracts intersymbol interference caused by the past four outputs. The equalized signal is fed into a nonuniform flash analog-to-digital converter (ADC) to produce the decision output and error signal used to adapt the RAM contents in the digital domain. With a 5 V supply voltage, the power dissipation is 260 mW during steady-state operation. The active area is 4.5 mm² in a 1 μm CMOS process     

Traffic officers'' attitudes toward blood alcohol law enforcement

Research findings in other countries suggest that drinking driving laws could be much better enforced even without resorting to special patrols or random checks. It has been reported that law enforcement officers apprehend or breath test only a small fraction of the potentially impaired drivers that they normally encounter on patrol. This survey of New Zealand traffic officers was designed to determine the extent to which this was the case here, and what were the major disincentives to breath testing. Traffic officer responses, obtained on an anonymous questionnaire, suggested that there were not so many missed opportunities as had been suggested by others, but that there was a great deal of variability in the number of drinking drivers detected by different officers. This was confirmed by the actual distribution of breath testing activity, which was markedly different in shape (positively skewed) compared to the distribution of traffic enforcement activities in general. Several clues from the disincentives cited on the questionaire suggested that there are major deterrents to a greater degree of alcohol enforcement activity on the part of most officers. These are discussed in terms of potential legislative changes, and in relation to the changes introduced in the 1978 Transport Act Amendment.     

Passive immune protection of turkeys against Coryza

Antisera made against whole cells of Bordetella avium protected turkeys against disease signs of turkey coryza, but antiserum against the dermonecrotic heat-labile toxin (DHLT) did not. Neither antiserum against whole cells nor antiserum against DHLT protected turkeys against colonization of the trachea by B. avium. At least 25 bands in whole cell lysate of B. avium separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) reacted in immunoblots with protective antiserum. These bands occurred at < 40 kDa and > 105.3 kDa. DHLT had an isoelectric point (pI) in the range pH 6.3-6.7. Following SDS-PAGE of isoelectric-focused fractions, two bands were recognized by anti-DHLT with immunoblots of pI 6.3, pI 6.5, and pI 6.7 fractions separated by SDS-PAGE.     

The COMMIT dental model: tobacco control practices and attitudes

The National Cancer Institute's program to help dentists reduce tobacco use among their patients is part of the Community Intervention Trial for Smoking Cessation, a 22-community, randomly controlled trial of an intervention program for smoking cessation. Results of COMMIT baseline surveys of dentists in the 11 intervention communities are presented.     

Quality of life following percutaneous transluminal angioplasty for claudication

Basal cell carcinoma (BCC) is the most common type of skin cancer and the incidence of BCC is expected to rise, with increased demand on dermatology resources. Little is known of the effect on people's lives of having skin cancer. The aim of this study was to quantify the handicap caused gy basal cell carcinomas before and after therapy. Forty-four patients (22 males, mean age = 65 yrs, range = 35-81 yrs) with 48 BCCs were recruited and 37 patients completed the study. Each patient completed the UK Sickness Impact Profile (UKSIP) and the Dermatology Life Quality Index (DLQI) at the initial visit to the dermatology clinic, 1 week after treatment and 3 months after treatment. Lesions had been present for a mean of 25 months (range = 1-240 months), their mean diameter was 9.6mm (range = 3-35mm) and the sites were head and neck (79%), trunk (17%) and limbs (4%). There was no relationship between the quality of life score and size of lesion. Overall the scores at presentation were very low, rising 1 week after treatment and falling to below the initial scores at 3 months (mean UKSIP 0.4%, 0.7%, 0.13%; mean DLQI 5.3% 8.7%, 1.2%). BCCs cause little handicap. This may explain the delay in seeking medical attention and should be considered in planning public health education about BCCs.     

A contingency-based approach for assessing policies on aging

The analysis of genomic DNA fragment patterns has revealed as a powerful tool for strain discrimination in Staphylococcus aureus; for use as an epidemiological marker, stability during the course of an outbreak is an essential prerequisite. Genomic DNA fragment patterns (SmaI restriction, pulsed-field electrophoresis) of four different epidemic MRSA strains were compared along with intra- and interhospital and country-wide spread over more than 12 months in Germany. Strain I was isolated from infections in 8 hospitals. In one hospital a subclone arised which differed from the original strain by 4 fragments. Strain II was spread among 4 hospitals, isolates from three of these hospitals exhibited a variability of one to three fragments in the 150-200 kb range. Two hospitals in the Hannover-area were affected by strain III; in 17 isolates of this strain a variability up to three fragments was found in the 170-200 kb range. Strain IV was isolated from 19 cases of infections in 3 hospitals in Berlin. The fragment patterns were completely stable. When S. aureus strains are typed by genomic DNA fragment patterns, a variability in a definite range of molecular masses during the course of an epidemic should be taken into consideration.