The Stockholm breast cancer screening trial — 5-year results and stage at discovery

In screening programmes it is important to assess a preliminary effectiveness of the screening method as soon as possible in order to forecast survival figures. In March 1981 a controlled single-view mammographic screening trial for breast cancer was started in the south of Stockholm. The population invited for screening mammography consisted of 40,000 women aged 40–64 years, and 20,000 women served as a well-defined control group. The main aim of the trial was to determine whether repeated mammographic screening could reduce the mortality in the study population (SP) compared to the control population (CP).The cumulative number of advanced mammary carcinomas in the screening and the control populations from the first five years of screening have shown a tendency towards more favourable stages in the screened population aged 40–64 years. A breakdown by age suggests an effect in age group 50–59 years, but not yet in age groups 40–49 and 60–64 years.When comparing the rates of stage II+ cancer, an increased number is found in the study group. As the total rate of breast cancer is higher in SP than in CP, there ought to be a concealed group of stage II+ cancers in the CP which makes the comparison biased. A new approach has been designed, where an estimation of the hidden number of stage II+ cancers in CP is added to the clinically detected cases, and in this respect a comparison has shown a decrease in the cumulative number of advanced cancers in the SP in relation to the CP (p<0.05). According to this it could be important to add the estimated number of undetected, hidden cases in the control group in order to utilize the difference in detection rate in the screening- and control group respectively.     

Abrogation of adriamycin-induced cardiotoxicity by selenium in rabbits.

Adriamycin-induced cardiomyopathy in rabbits was produced by intravenous injections of the drug with a short therapeutic schedule (3 mg/kg body wt administered as four intermittent doses). Animals receiving selenium supplementation of Adriamycin showed preservation of the normal pattern of the heart histologic picture. The protective effect of selenium was accompanied by increased selenium levels in the plasma and the heart muscle. An eventual interaction between the antitumor effect of Adriamycin and the protective effect of selenium was ruled out by in vitro experiments using the L1210 cell line. Selenium did not abrogate the antiproliferative effect of Adriamycin when the cells were treated simultaneously with both agents. The results from this study indicate that Adriamycin-induced cardiotoxicity could be prevented by selenium if the animals were pretreated with selenium, rather than simultaneous administration of both agents. The mechanism of this effect is not entirely understood.     

The Genée-Wiedemann syndrome,an acrofacial dysostosis—further observation

We report on a consanguineous Brazilian couple whose 2 children had tibial aplasia-ectrodactyly. Femoral bifurcation was present in one of the affected children. The relationship of tibial aplasia-ectrodactyly to the Gollop-Wolfgang complex is discussed. Clinical and genetic aspects of the conditions involving tibial aplasia and femoral bifurcation are discussed.     

Immunolocalization of lamins and nuclear pore complex proteins by atomic force microscopy

The nuclear envelope functions as a selective barrier separating the nuclear from the cytosolic compartment. Nuclear pore complexes (NPCs) mediate nuclear import and export of macromolecules and, therefore, are potential regulators of gene expression. In this study we applied atomic force microscopy (AFM) to visualize the three dimensional (3D) structure of individual NPCs in the absence and presence of two different antibodies, one directed against a pore protein (gp62) and another directed against Xenopus lamin LIII, a component of the nuclear lamina, a filament meshwork localized on the nucleoplasmic side of the nuclear envelope (NE) adjacent to and interacting with NPCs. Using 12-nm gold-labelled secondary antibodies and transmission electron microscopy we could clearly localize the primary single anti-gp62 antibody on NPCs and the primary single anti-LIII antibody between NPCs. Using AFM, the secondary antibodies against anti-gp62 could be detected as particles 7 nm in height on the nucleoplasmic face of NPCs. The secondary antibodies against anti-LIII could be clearly identified between NPCs. The secondary antibodies, attached to a 12-nm colloidal gold particle and visualized on glass, revealed similar shapes and heights as found on NEs. According to the 3D images, the volume of a single gold particle conjugated with secondary antibodies was 10 203 nm³. This volume is equivalent to the volume of 38 IgG molecules associated with one individual gold particle. A similar volume of 11 987 nm³ was calculated from a model assuming that the 150-kDa IgG molecules perfectly cover the spherical gold particle. We conclude that AFM can be used for identifying antibodies or other macromolecules associated with biomembranes.     

Heterologous radioimmunossay of monkey alpha-fetoprotein.

Immunoelectrophoresis showed that rabbit anti-human alpha-fetoprotein (AFP) cross-reacts with monkey AFP which was not detectable in the serum from an adult non-pregnant monkey. A heterologous radioimmunoassay of monkey AFP was developed using this antiserum which circumvented the need for purified monkey AFP. The radioimmunoassay is of sufficient sensitivity to measure AFP in maternal and fetal serum and amniotic fluid in the rhesus monkey.     

Elevated rubella antibodies in patients with chronic liver disease

Patients with autoimmune chronic active hepatitis (AICAH) and certain other chronic liver disorders often have very high titres of haemagglutination -inhibition (HI) antibodies to rubella virus. In this study it is shown, using floatation centrifugation, that the high rubella HI reactivity is not caused by nonspecific lipoprotein inhibitors but rather by antibodies specific for the rubella haemagglutinin (E1 glycoprotein). After sucrose density gradient ultracentrifugation of sera the major HI reactivity was recovered in the IgG containing fractions. The IgG antibody fraction was strongly reactive by an indirect enzyme-linked immunosorbent assay (ELISA). Higher prevalence and titres of rubella antibodies were also demonstrated by the complement fixation (CF) test using a haemagglutinin-free antigen, and by an indirect haemagglutination (IHA) test (Rubacell) using a cell-associated antigen which is distinct from the antigens used in the HI and CF tests. This high rubella antibody response is therefore demonstrated using three distinct antigen-antibody systems. By means of absorption experiments and radioimmunoprecipitation assays the coating antigen used in the IHA test was shown to reside in the E2 glycoprotein. The cause of this enhanced antibody response to rubella virus structural proteins remains elusive. © 1994 Wiley-Liss, Inc.     

Linomide,a novel immunomodulator that prevents death in four models of septic shock

Intravenous injections of 50 μ.g Staphylococcus aureus enterotoxin B (SEB) or bacterial lipopolysaccharide (LPS) are lethal, provided that mice are simultaneously sensitized with either N-galactosamine (GalN) or the anti-glucocorticoid RU-38486. Similar to the synthetic glucocorticoid (GC) receptor agonist dexamethasone, pharmacological doses of the immunomodulator linomide (quinoline-3-carboxamide) prevent death in all four models of lethal septic shock (LPS + GalN, LPS + RU-38486, SEB + GalN, and SEB + RU-38486) and inhibit the secretion of tumor necrosis factor, one of the major intermediate effector molecules of SEB and LPS toxicity. In this system, cyclosporine A (CsA), although effective in suppressing SEB toxicity, fails to counteract the lethal effect of LPS. This observation, together with the fact that linomide acts in the presence of excess amounts of GC receptor antagonist, indicates that linomide functions in a different way to that of known immunosuppressive agents like CsA and GC.     

Characterization of an IgA receptor from group B streptococci: specificity for serum IgA

Some strains of group B streptococci express a cell surface protein which binds IgA. This report describes some properties of such an IgA receptor and compares it with a previously described IgA receptor from group A streptococci. The group B receptor was released in an almost pure form from bacteria incubated at elevated pH, and could be isolated by IgA-Sepharose affinity chromatography. The sequence of the N-terminal 19 amino acid residues was unique. The receptor preferentially binds IgA of human origin, as shown in immunoblotting experiments with purified IgA from nine different species. The affinity constant of the purified receptor for serum IgA was determined to be 3.5 x 10(8) M-1, but for secretory IgA it was too low to allow determination. This result indicates that secretory component and/or J chain interferes with the binding of IgA to this type of bacterial receptor, which may be one of the physiological functions of these polypeptides. A reduction in affinity was also observed for another complexed form of IgA, alpha 1-microglobulin-IgA. The group B receptor is antigenically unrelated to the IgA receptor from group A streptococci (protein Arp), but competitive inhibition experiments indicate that they bind to the same region in IgA. The implications of these findings, and the biological role of bacterial IgA receptors, are discussed.     

Quantitative Studies on the Proliferation and Differentiation of Antibody-Forming Cells in Lymph

The transforming cells that appear in the efferent lymph from a lymph node responding to an antigenic challenge are part of a heterogeneous population which changes as the response progresses. Some cells containing small amounts of antibody appear early in the response and these cells have the cytologic characteristics of small and medium lymphocytes. They are, however, actively synthesizing DNA. As the immune response progresses, the antibody content of the cells in lymph increases. When incubated in vitro, cells in lymph appearing late in the response released 20 times more antibody per cell than those appearing early in the response. Large blast cells are the predominant antibody-forming cell in lymph. At the peak of a secondary challenge with horseradish peroxidase, up to 40% of the cells in lymph may be blast cells and, of these, two-thirds may contain specific antibody. It seems probable that most if not all of the blast cells responding to the antigen are involved directly in antibody and DNA synthesis. Cells in all stages of ultrastructural differentiation, and even mature plasma cells, were found to incorporate ³H-thymidine into their nuclear DNA.     

SEM of the proximal tubule of the adult rabbit kidney

The present study utilizes the scanning electron microscope (SEM) to reveal the surface morphology of proximal tubular cells and the parietal cells of Bowman's capsule of the adult rabbit nephron. To facilitate the examination of the basal surface of these cells, proximal tubules were dissected free and treated with collagenase to remove the basememt membrane. Other blocks of tissue were cryofractured to expose the lateral cell surfaces of the proximal tubules. Our investigation has shown that the lateral and basal surfaces of both the convoluted and straight segments of the proximal tubule have numerous processes. However, the arrangement and degree of branching is distinctly different in the two segments. The convoluted segment has large lateral ridges which form at the base of the microvilli and fan out to divide into lateral-basal processes. Many of the lateral-basal processes reach the basement membrane intact, interdigitating with complementary processes from adjacent cells. However, some of the lateral-basal processes branch into short, knobby projections (basal villi) which may also reach the basement membrane. Patches of basal villi are interspersed between broad regions of interdigitating lateralbasal processes. Therefore, in the convoluted segment, the lateral-basal processes form the major part of the basal cell surface. In tubular cells of the pars recta, unlike convoluted tubular cells, the majority of the ridges remain unbranched and pass directly to the basal surface where they divide into elaborate basal villi. Thus the basal surface of the pars recta cells is highly complex, appearing leaf-like, being a composite of numerous basal villi with a few lateral ridges. The basal surface of some parietal cells of Bowman's capsule have parallel ridges, which results in patches of striations.