Weibel-Palade bodies in endothelial cells as a marker for angiogenesis in brain tumors

A transmission electron microscope study was made of eight childhood brain tumors divided up into three zones, center, edge, infiltrating zone, and also of adjacent "normal-looking" brain. In seven of eight tumors, the numbers of Weibel-Palade bodies in endothelial cells were significantly increased in peripheral zones compared with central zones. A similar significant increase was observed after treatment of chick chorioallantoic membranes with tumor angiogenesis factor. It is suggested that large numbers of Weibel-Palade bodies may be a marker for proliferating endothelial cells in vivo.     

Quantitation of extracts containing tumour angiogenesis factor (TAF) by radioimmunometric and radioimmunoassays

An antiserum which is able to inhibit TAF-induced neovascularization in vivo (TAF antiserum) was used to develop two quantitative assays for TAF-containing tumour extracts (tumor TAF). 1) Radioimmunometric assay (RIMA): the IgG of the TAF antiserum was labelled with 125I. An excess of 125I-IgG was incubated with increasing concentrations of tumour TAF and the antigen-bound fraction was precipitated by addition of Clq. 2) Radioimmunoassay (RIA): an excess of iodinated antigen (tumour TAF) was incubated with TAF antiserum diluted so that binding in the absence of unlabelled antigen represented 70-80% of the maximum binding. When tumour TAF was added, competition between labelled and unlabelled antigen for the TAF antibody binding sites resulted in displacement of the former by increasing concentrations of the latter. A second antibody was used to precipitate the bound labelled antigen. Of the two assays, the RIMA was the more sensitive and, due to the lack of a purified antigen, allowed standardization of the results in a more accurate manner. Our data show that there was a good correlation between the ability of tumour TAF to induce angiogenesis in vivo and the degree of antiserum binding detected in vitro by both assays. Preparations containing TAF, whatever the source (i.e. human or animal tumours or tissue culture) shared common antigenic determinants. It is suggested that the quantitative assays should prove valuable in determining the clinical relevance of TAF as a tumour marker.     

Small renal carcinoma with large retroperitoneal hemorrhage: Diagnostic considerations

Two cases of small peripheral papillary renal carcinoma causing large spontaneous perirenal hemorrhages are presented. The value and limitations of computerized tomography, ultrasonography, arteriography, and percutaneous aspiration biopsy in these cases are discussed. The need for careful explorative surgery and dissection of the specimen is emphasized. Excretory urography should be the first examination in all patients with renal pain and signs of internal bleeding. Arteriography should be done when the diagnosis is not evident.     

The application of population pharmacokinetic analysis to large scale clinical efficacy trials

Summary Results have been presented that demonstrate the ability to conduct population pharmacokinetic analysis as a component of clinical efficacy and safety trials. This method of analysis offers the potential to determine the pharmacokinetics of a drug in the actual patients receiving medication and to evaluate relationships between pharmacokinetics and drug action. However, active involvement in the protocol design, and data collection process are required to ensure the quality of the resultant data set.     

The Structure of Celiprolol

The crystal structure and nuclear magnetic resonance (NMR) spectra and assignments of celiprolol, N-[3-acetyl-4[3-[N-t-butylamino-2-hydroxypropoxy]phenyl]-N, N-diethylurea, are reported. Celiprolol crystallizes in the monoclinic space group, P2_l/a, with a = 9.081(2), b = 13.800(4), and c = 17.471(5) Å and = 95.04(2)°. Structure was solved by direct methods; structure refinement to R of 0.058. Intermolecular hydrogen-bonding in the crystal is discussed. The ¹H, ¹³C, and two-dimensional (2D) NMR spectra of the hydrochloride have been obtained and definitive signal assignments made.     

Interstitial pulmonary macrophages produce platelet-derived growth factor that stimulates rat lung fibroblast proliferation in vitro.

Alveolar macrophages from humans and several animal species produce factors in vitro that modulate fibroblast growth and have been proposed as mediators of interstitial pulmonary fibrosis. Pulmonary interstitial macrophages (IMs) have not been studied previously in this regard. Pulmonary IMs were isolated from prelavaged rat lungs by enzymatic digestion of tissue and subsequent differential adherence of cells to culture dishes. The ability of IMs to release modulators of fibroblast growth into the culture medium was assessed by measuring [3H]thymidine incorporation into DNA and/or nuclear labeling of early-passage rat lung fibroblasts exposed to medium conditioned by IMs. The percentages of nuclei labeled in fibroblast cultures exposed to interstitial macrophage-conditioned medium (IMCM) alone did not significantly differ from that observed in controls, but fibroblasts exposed to IMCM supplemented with 2% platelet-poor plasma showed a 2.6-fold increase in labeling, indicating that IMCM contains predominantly "competence" growth factor activity. Similar results were obtained using purified human platelet-derived growth factor (PDGF). The level of growth factor activity released by IMs increased in cells that had phagocytized iron spheres during the culture period. In addition, fractionation of IMCM by high-performance liquid chromatography demonstrated most of the growth factor activity at a relative molecular mass of about 35 kd. Subsequent quantitative analysis of the fractions by an enzyme immunoassay for PDGF demonstrated that IMCM contains a homologue of human PDGF. These results show that IMs are capable of producing a PDGF-like growth factor for autologous fibroblasts and that release of this factor is enhanced by exposure to an insoluble inorganic particle. Because PDGF is a potent growth factor for fibroblasts and is released by IMs, it is essential to ask in future studies whether this or similar macrophage products play a significant role in mediating fibroblast proliferation in vivo.     

Knowledge and perceptions of residents regarding case management of acute diarrhea.

The knowledge and perceptions about case management of acute diarrhea were studied amongst 330 resident doctors working in Pediatric Departments of various Medical Colleges in the country. Our observations highlight the inadequacies in the medical curriculum and deficient clinical training in the management of acute diarrhea in the teaching institutions. Knowledge of signs of dehydration was correctly perceived by only 79.8% interns, 80.9% house physicians and 81.1% postgraduate students. It was appalling to observe that despite spending 1-3 years in pediatric wards, the knowledge and perceptions of postgraduate students had not significantly improved. On the contrary, the responses of postgraduate students were poorer as compared to interns in their perceptions of use of ORT in moderate dehydration (p less than 0.005) and in presence of vomiting (p less than 0.05). Adequate thrust on diarrhea and its management during undergraduate as well as during postgraduate teaching and proper training in diarrhea case management with "hands on training" needs to be viewed as a priority in the teaching institutions.     

Rejection of bone marrow cell allografts by natural killer cell subsets: 5E6+ cell specificity for Hh-1 determinant 2 shared by H-2d and H-2f.

The 5E6 antigen, defined by anti-5E6 mAb, is expressed on one-half of murine natural killer (NK) cells, and we have previously demonstrated (C. L. Sentman et al., J. Exp. Med. 1989. 170: 1991) that 5E6+ NK cells are necessary for the rejection of BALB/c (Hh-1d) but not C567BL/6 (Hh-1b) bone marrow cells (BMC). In experiments described here, we have characterized the specificity of 5E6+ and 5E6- NK cell subsets for hemopoietic histocompatibility-1 (Hh-1) antigens. Prospective recipient mice were treated with anti-5E6 mAb and challenged with BMC from a variety of donors. In addition, H-2d/Hh-1d C.B-17 scid 5E6+ or 5E6- NK cells were adoptively transferred into irradiated, NK cell-depleted hosts and challenged with H-2b/Hh-1b BMC. The data indicate that the 5E6+ NK cells are necessary for the rejection of only those BMC that express the Hh-1 determinant 2 shared by H-2d and H-2f haplotypes of strains BALB/c (d), A.Ca (f), and B10.M (f). No reactivity to other Hh-1 antigens resides in the 5E6+ population. In contrast, the ability of NK cells to lyse H-2d or H-2b tumor cells was independent of 5E6 expression. These results suggest that the 5E6 molecule is likely to be important in the specific recognition and rejection of BMC that express Hh-1 determinant 2, and is probably not involved in recognition of "tumor target cell structures".     

Telelithotripsy in the treatment of staghorn nephrolithiasis in children using the URAT-P lithotriptor]

The paper presents the results of telelithotripsy monotherapy for 34 staghorn stones in 32 nephrolithiasis children carried out at the RSFSR Research Institute of Urology, Moscow. Commonest manifestations of the disease were leukocyturia (87.5% of cases) and Proteus bacteriuria (31.8% of cases). Basing on roentgenological findings, the stones were classified into 3 groups: initial (K1), incomplete (K2) and complete (K3). All the children underwent treatment on Soviet lithotriptor "URAT-P" under a delicate regime using different techniques of disintegration which started from the periphery and advanced to the pelvic part of the calculus. No pretreatment drainage of the pelvicaliceal system was performed. The intended staged disintegration of the stones was achieved in 94.2% of cases at 2.4 sessions, on the average, and overall number of impulses 1973.1 per each stone. At discharge 76.4% of the children were free of the main mass of the stone dust. Acute pyelonephritis which appeared the most frequent postoperative complication developed in 7.8% of the patients one of which required open nephrostomy and one percutaneous puncture nephrostomy. Other cases were treated by specific antimicrobial therapy. Complete series of investigations in the postoperative period did not reveal any intra- or pararenal hematomas. Radioisotopic renography revealed improvement in renal function in 62% of cases in early postoperative follow-up. Thus, 93.8% of children with stag-horn stones were spared of traumatic operative intervention or invasive manipulations. This makes the method of telelithotripsy a valuable therapeutic tool in childhood staghorn nephrolithiasis.     

Isokinetic trunk strength and lumbosacral range of motion in elite female field hockey players reporting low back pain

This study was funded, in part, by a Small Faculties Grant from the University of Alberta. Physical therapists have reported an increased incidence of low back pain (LBP) in female field hockey (FH) players, commonly accompanied by decreased trunk range of motion (ROM) and strength. The purpose of this study was to compare lumbosacral sagittal ROM and isokinetic trunk strength in three groups of women: 1) FH athletes with a history of chronic LBP, 2) pain-free FH athletes, and 3) an age-matched, healthy nonathletic control group. Photographs (35 mm) of subjects wearing spinal motion markers were used to determine the limits of lumbosacral saggital ROM in standing. Eccentric and concentric isokinetic trunk flexion and extension torques were measured in sitting through 60 degrees of trunk movement using a Kin-Com dynamometer set at 60 degrees /sec. The ANOVA showed that the pain group had 12 degrees and 18 degrees less extension (p < .01), as well as 18 degrees and 24 degrees less total ROM (p < .001) than the pain-free and control groups, respectively. Only peak (p < .001) and average (p < .03) eccentric extension torques were weaker in the pain group than in the nonathletic control group. These results suggest that physical therapists should perform preseason screening of trunk strength and lumbosacral ROM. In-season trunk extension stretching and strengthening is needed in the training regimes of these athletes. J Orthop Sports Phys Ther 1992;16(3):129-135.