Exogenous lung surfactant: effect on radiographic appearance in premature infants

At birth, premature infants of 25-29 weeks gestation, at high risk for development of neonatal respiratory distress syndrome (RDS), were given a single dose (90 mg) of calf lung surfactant extract (CLSE) by intratracheal instillation. The frequency and severity of RDS were assessed with use of a simple radiographic scoring system in which pulmonary parenchymal densities and the prominence of the air-bronchogram effect were used as indicators of widespread atelectasis. Radiographs were obtained in surfactant-treated and control infants within the first 90 minutes of life as part of an initial evaluation of their pulmonary status. Subsequent examinations were performed at less than 24 hours and less than 48 hours of age. Radiographic assessment of lung disease compared consistently with coordinated data on oxygen and mean airway pressure requirements of the infants. Both indicated a significantly decreased frequency and severity of RDS in the infants treated with surfactant. The results provide supporting evidence of the effectiveness of exogenous lung surfactant replacement in mitigating RDS in very premature infants.     

Suppression of natural killer cell activity and T cell proliferation by fresh isolates of human cytomegalovirus

Human cytomegalovirus (HCMV) infections are commonly associated with immunosuppression. A direct effect of this virus on lymphocyte functions in vitro, however, has not been shown. We have been investigating the effects of low-passage, fresh isolates of HCMV (cell-free and cell-associated) on natural killer cell (NK) activity and T cell proliferation. Cell-associated, low-passage isolates of HCMV markedly depressed NK activity. Suppression of NK activity was clearly manifested only after seven days of culture and could not be correlated with titer of virus or cell viability. Addition of interferon-alpha (IFN-alpha) but not interleukin-2 (IL-2) partially reconstituted the response, whereas depletion of infected monocytes prevented inhibition of NK-mediated lysis. The effects of cell-free and cell-associated isolates of HCMV on T cell proliferation differed in several respects from suppression of NK activity. Both cell-associated and cell-free isolates of HCMV completely abrogated antigen-specific and mitogen responses. This effect was apparent after only three days of culture with virus and was not reversed by either IFN or IL-2. Cell-associated strain AD169 also induced suppression but to a lesser extent. From observations reported here and other data, we suggest that HCMV can cause direct suppression of lymphocyte functions.     

The effects of (R)-N-(1-methyl-2-phenylethyl) adenosine (L-PIA), a standard A1-selective adenosine agonist on rat acute models of inflammation and neutrophil function

L-PIA, a standard A₁-selective adenosine agonist, was evaluated orally in carrageenan (CRG)- and reverse passive arthus-pleurisy. White blood cell (WBC) and exudate accumulation were assessed four hours after induction of the inflammatory response. L-PIA inhibited WBC accumulation in both models with ID₅₀'s of 4.37 and 4.42 mg/kg, respectively. In contrast, exudate was inhibited by L-PIA only in the CRG pleurisy model (ID₅₀=1.01 mg/kg). In mechanistic studies, L-PIA reversed the drop in circulating neutrophil count which occurred within 15 minutes after CRG injection, suggesting that L-PIA may inhibit adhesion of the cells to the endothelium. The effects of L-PIA on several parameters of rat neutrophil function were determined. Enzyme release, O ₂ ^– , TXB₂, and LTB₄ production were monitored in response to FMLP and opsonized zymosan (SOZ) stimulation. At high concentrations L-PIA had a mild inhibitory effect on O ₂ ^– release in response to FMLP and had a moderate effect on arachidonic acid metabolite production, in response to both stimuli. The other response were unaffected. These results suggest that L-PIA may prevent diapedisis or neutrophil adhesion to the endothelium, but has a minimal effect on enzyme release O ₂ ^– , LTB₄ and TXB₂ production.     

The phosphatidylinositol response of chondrocytes in culture

This study examined the phosphatidylinositol (PI) response in chondrocytes. The levels of 3H-inositol phosphates (IPs) were measured in guinea pig chondrocyte cultures labelled with 3H-myo-inositol and exposed to various inflammatory mediators and known agonists of the PI response, including bradykinin, carbachol, histamine, A23187, or recombinant human interleukin-1 beta. Of the mediators used to stimulate the PI response in chondrocytes, only bradykinin was effective. The bradykinin treated cells had higher levels of IPs (37-fold) than the controls. The PI response to bradykinin was dose and time dependent.     

Characterization of erythrocyte membrane-associated enzymes (glyceraldehyde-3-phosphate dehydrogenase and phosphoglyceric kinase).

The purpose of our study was to determine why several of the glycolytic enzymes of the erythrocyte have the propensity for adhering to erythrocyte membranes while others do not. Two of these membrane-associated enzymes, glyceraldehyde phosphate dehydrogenase (GAPD) and phosphoglyceric kinase (PGK), have been shown to have controlling functions on intra-erythrocytic glycolysis and sodium-potassium transport. In order to test the hypothesis that the membrane-associated fraction of these enzymes consisted of isozymes with increased capacity to become membrane associated, the enzymes from cytosol or membrane sources were partially purified and characterized. Determination of molecular weight by gel filtration chromatography, measurement of certain kinetic parameters, and the curves relating to pH optimal activity indicated that there were no measurable differences between membrane and cytosol PGK and membrane and cytosol GAPD. It was possible to raise inhibitory antibodies to GAPD in certain species of mice, and these antibodies did not distinguish between GAPD isolated from either membrane or cytosol sources. GAPD was firmly bound to membranes and the membrane-associated fraction counted for approximately 60 per cent of total erythrocytic enzyme. Membrane-associated PGK was only loosely adherent, and accounted for only 1 per cent of the total erythrocytic enzyme. The reasons for membrane association have yet to be determined, but these inward facing membrane-associated enzymes appear to function by carrying the organization of the membrane into the cell interior.     

Concordance of Gleason grading with three-dimensional ultrasound systematic biopsy and biopsy core pre-embedding

Purpose

To determine the value of a three-dimensional (3D) greyscale transrectal ultrasound (TRUS)-guided prostate biopsy system and biopsy core pre-embedding method on concordance between Gleason scores of needle biopsies and radical prostatectomy (RP) specimens.

Methods

Retrospective analysis of prostate biopsies and subsequent RP for PCa in the Jeroen Bosch Hospital, the Netherlands, from 2007 to 2016. Two cohorts were analysed: conventional 2D TRUS-guided biopsies and RP (2007–2013, n = 266) versus 3D TRUS-guided biopsies with pre-embedding (2013–2016, n = 129). The impact of 3D TRUS-guidance with pre-embedding on Gleason score (GS) concordance between biopsy and RP was evaluated using the κ-coefficient. Predictors of biopsy GS 6 upgrading were assessed using logistic regression models.

Results

Gleason concordance was comparable between the two cohorts with a κ = 0.44 for the 3D cohort, compared to κ = 0.42 for the 2D cohort. 3D TRUS-guidance with pre-embedding, did not significantly affect the risk of biopsy GS 6 upgrading in univariate and multivariate analysis.

Conclusions

3D TRUS-guidance with biopsy core pre-embedding did not improve Gleason concordance. Improved detection techniques are needed for recognition of low-grade disease upgrading.

     

Effect of long-acting calcium entry blocker (anipamil) on blood pressure, renal function and survival of uremic rats.

To assess more completely the long-term effect of a long-acting calcium channel blocker, anipamil was given p.o. to rats with subtotal (five-sixths) nephrectomy. The mortality rates in anipamil-treated and control groups were 5% and 20%, respectively, at 6 weeks after separation (P less than .01) and 10% and 55%, respectively, at 10 weeks after separation (P less than .01). Mean arterial blood pressure was also more well controlled in the anipamil-treated group (144 +/- 36 vs. 192 +/- 35 mm Hg; n = 20; P less than .05 at week 5). In paired experiments, the degree of renal impairment in the placebo- and anipamil-treated groups, just before the onset of preterminal azotemia, was determined. Rats that were treated with anipamil had lower serum creatinine concentrations, compared with the placebo controls, at 4 to 6 weeks after separation (0.55 +/- 0.02 vs. 0.87 +/- 0.02 mg/100 ml; P less than .05). To dissociate this beneficial effect of anipamil from mean arterial blood pressure control, experiments were also performed to assess the effects of hydralazine on the remnant kidney model of chronic renal failure. Rats with remnant kidneys were divided into three groups and treated with anipamil (2 mg/kg/day), hydralazine (80 mg/liter in drinking water) or control. The anipamil-treated group exhibited significantly greater protection of renal function than did the hydralazine-treated group for the same level of blood pressure control. Thus, a long-acting calcium channel entry blocker such as anipamil may afford an additional cytoprotective effect in the prevention of progression of chronic renal failure beyond the antihypertensive effects of the agent.     

Immune predispositions for cytomegalovirus retinitis in AIDS. The HNRC Group.

CMV retinitis develops in approximately 28-35% of all AIDS patients at later stages of disease, often leading to blindness. To determine whether the subset of AIDS patients who developed CMV retinitis (CMV-R) were immunologically predisposed, T cell proliferation responses to CMV were examined prospectively in an HIV infected, HLA typed, longitudinal study population. Individuals who developed CMV-R had significantly lower T cell proliferation responses to CMV, both early and late in disease, compared to CD4 matched controls who have not developed CMV-R. Since HLA proteins influence T-cell recognition, phenotypes of 21 CMV-R patients were examined to determine whether certain HLA alleles were associated with low immune response and predisposed AIDS patients to CMV-R. HLA DR7 and B44 were at increased (nearly twice the expected) frequency in those with CMV-R. The combined association of either B44, 51 or DR7 with CMV-R was highly significant (P = .008, relative risk of CMV-R = 15) with correction for multiple comparisons. Low immune responses were twice as frequent in those with (61%) compared to those without (30%) predisposing alleles. Thus, AIDS patients with immunogenetically related hyporesponsiveness to CMV antigens may be at increased risk of retinitis.