Development of enhanced blood flow responses to prostaglandin E1 in carrageenan-induced granulation tissue

The distribution of cardiac output (c.o.) was measured by the radioactive microsphere method in rats at different time intervals after the implantation of carrageenanimpregnated sponges. The amount of blood distributed to the developing granulomata increased from day 5 after sponge implantation to day 7, but showed no further increase at day 10. A similar pattern in blood flow was observed in the skin covering the granulomata. Injection of PGE₁ (100 ng) into the sponges led to an increase in blood flow, the magnitude of which became gradually larger between days 5 and 10. A similar, though less marked increase in sensitivity to PGE₁ was observed in the skin covering the granulomata, PGE₁ causing a significant increase in blood flow to the skin on day 10. These changes in sensitivity to exogenous PGE₁ may be due to decreasing levels of endogenous PGE and/or maturation of the newly formed blood vessels in the granulation tissue.     

The corpus luteum of the guinea pig. Fine structure at the time of maximum progesterone secretion and during regression

This report describes the fine structure of guinea pig luteal cells during the period of maximum progesterone secretion and throughout involution, in ovaries that have been fixed by perfusion, a technique that provides optimal preservation of steroid-secreting tissues. Smooth endoplasmic reticulum (smooth ER), a prominent organelle in these cells, is particularly well preserved by this method of fixation. During the time of maximal progesterone secretion, luteal cells contain abundant tubules and cisternae of smooth ER, many mitochondria, a well-developed Golgi complex and some lipid droplets. This fine structural picture is consistent with active steroidogenesis. Autophagy plays an important role in the regression of luteal cells in the corpus luteum. The onset of luteolysis is marked by the appearance of structurally complex autophagic vacuoles, one of which has not been described previously in luteal cells. This autophagic vacuole seems to originate from GERL (Golgi-endoplasmic reticulum-lysosomes) as a cup-shaped structure, which subsequently increases in size and complexity. Regressing luteal cells also contain increased numbers of both dense bodies (lysosomes) and lipid droplets, and exhibit changes in nuclear and mitochondrial morphology. In contrast to previous reports in the literature, changes in the morphology of smooth ER were not observed as a characteristic feature of involution in corpora lutea of guinea pigs in the present study. Advanced regression of luteal cells is characterized by multiple fusion of lipid droplets and a decrease in the amount of smooth ER. Another mechanism active in the breakdown of the corpus luteum is the phagocytosis of luteal cells by macrophages. Although present at all stages, macrophages are most abundant in older corpora lutea, where they often surround dead or dying luteal cells.     

Sn-chlorin e6 antibacterial immunoconjugates. An in vitro and in vivo analysis.

Monoclonal antibody-Sn-chlorin e6 immunoconjugates were prepared by the site-selective covalent modification of the monoclonal oligosaccharide moiety. By carefully controlling the reaction conditions and introducing triethanolamine groups as axial ligands of the Sn moiety, conjugates with in vivo biodistribution properties similar to underivatized IgG were prepared. By varying the reaction conditions, conjugates were reproducibly prepared with a range of photosensitizer to mAb molar ratios from 1.6 to 10. Based on a competitive inhibition radioimmunoassay, conjugates prepared by this method showed selectivity and binding affinity comparable to the unmodified antibody. The immunoconjugates had only slightly lower singlet oxygen yields than that observed with the Sn-chlorin e6 precursor indicating that negligible aggregation or structural modification of the chromophores occurred during the synthesis process. In vitro cell killing experiments demonstrated that all conjugates possessed significant cytotoxic activity. Biodistribution studies in mice showed that conjugates prepared with axial ligands had significant serum retention 24 h after injection while conjugates prepared without the triethanolamine ligand were much more rapidly cleared. In vivo specificity was demonstrated using rats infected with Fisher immunotype I P. aeruginosa at a site in the left posterior thigh muscle. Target to background ratios exceeded 60 at 120 h after conjugate injection of the specific immunoconjugate, compared to a ratio of only 6 for a non-specific mouse IgG conjugate. Biodistribution patterns at 120 h post injection indicate that the conjugates were both biologically active and structurally intact.     

Interferon Production by Macrophages from Adult and Newborn Rabbits Bearing Fibroma Virus-Induced Tumors

Tumors were induced in adult and newborn rabbits by inoculation of fibroma virus. After 10 to 14 days, oil-induced peritoneal macrophages were harvested, purified, and tested in vitro for interferon synthesis after stimulation with specific and nonspecific viruses. Peritoneal macrophages from adult rabbits that had initiated tumor regression produced high levels of interferon (titers ranged from 160 to 640) after stimulation with fibroma virus, whereas macrophages from normal adult rabbits failed to produce significant levels of interferon under the same conditions (titers ranged from <10 to 10). Furthermore, fibroma-immune macrophages responded to vaccinia virus and Newcastle disease virus with higher levels of interferon than did normal macrophages. In contrast, macrophages from newborn tumor-bearing rabbits that showed no evidence of tumor regression failed to respond to fibroma virus stimulation with higher levels of interferon (titers ranged from <10 to 10). These macrophages did, however, yield significantly more interferon than newborn control macrophages when stimulated with a good interferon inducer, Newcastle disease virus (titers ranged from 10 to 80). These data suggest that interferon production may be an expression of macrophage activation to fibroma antigens and that macrophage activation is impaired in newborn rabbits with progressive growing tumors.     

Prevention for preschoolers at high risk for conduct problems: immediate outcomes on parenting practices and child social competence.

This study investigated the immediate impact of an 8-month center- and home-based prevention program for preschoolers at high risk for conduct problems. We report immediate program effects on observed and self-rated parenting practices and observed child behavior with peers. Ninety-nine preschool-age siblings of adjudicated youths and their families were randomly assigned to an enhanced version of the Incredible Years Series (Webster-Stratton, 1989; n = 50) or to a no-intervention control condition (n = 49). In an intent-to-treat design, the intervention yielded significant effects on negative parenting, parental stimulation for learning, and child social competence with peers. Improvements in negative parenting, stimulation for learning, and child social competence support the potential of the intervention to prevent later conduct problems in high-risk children.     

Cholesterol screening in general practice

Serum cholesterol levels were measured in 250 men and 250 women aged 25-60 years attending a general practice. Seventy three per cent of the sample had levels above 5.2 mM and of these 98 patients agreed to follow a low cholesterol/low saturated fat diet for six months. The overall reduction in serum cholesterol level among these patients was 13%, suggesting that lipid screening in general practice could be worthwhile.