Genetically regulated human (T,G)-AL specific helper T cell replacing factors possess HLA-DR and Vh determinants

Human (T,G)-AL specific T cell helper factors secreted by in vitro activated peripheral blood lymphocytes of normal donors were characterized. Factors were passed through columns of Sepharose coupled either to antibodies against human immunoglobulin or antibodies against the variable region of the heavy (V_h) and light (V_l) chains of human immunoglobulin. In addition, the same factors were applied to columns of Sepharose coupled to anti-HLA-DR antibodies or to monoclonal antibodies against human Ia or β₂-microglobulin. The activity of the antigen specific factors was removed by the anti-V_h antibodies and not by anti-V_l or anti-human immunoglobulin antibodies. The factors passed through Sepharose coupled to anti-DR antibodies could be removed and eluted from columns of anti-DR antibodies relevant to the donors' DR antigens. The same factors were also removed by a monoclonal antibody (anti-Ia) which recognizes a monomorphic determinant on HLA-DR, but not by monoclonal anti-β₂-microglobulin. The results suggest that the genetically regulated (T,G)-AL specific helper factors possess HLA-DR as well as V_h determinants in their active moiety.     

Clamp loading,unloading and intrinsic stability of the PCNA, β and gp45 sliding clamps of human,E. coli and T4 replicases

Background: The high speed and processivity of replicative DNA polymerases reside in a processivity factor which has been shown to be a ring-shaped protein. This protein (‘sliding clamp’) encircles DNA and tethers the catalytic unit to the template. Although in eukaryotic, prokaryotic and bacteriophage-T4 systems, the processivity factors are ring-shaped, they assume different oligomeric states. The Escherichia coli clamp (the β subunit) is active as a dimer while the eukaryotic and T4 phage clamps (PCNA and gp45, respectively) are active as trimers. The clamp can not assemble itself on DNA. Instead, a protein complex known as a clamp loader utilizes ATP to assemble the ring around the primer-template. This study compares properties of the human PCNA clamp with those of E. coli and T4 phage. Results: The PCNA ring is a stable trimer down to a concentration below 100 nm (K_d ≈ 21 nm ). On DNA, the PCNA clamp slides freely and dissociates from DNA slowly (t_1/2 ≈ 24 min). β is more stable in solution (K_d < 60 pm ) and on DNA (t_1/2 ≈ 1 h) than PCNA which may be explained by its simpler oligomeric state. The T4 gp45 clamp is a much less stable trimer than PCNA (K_d ≈ 250 nm ) and requires association with the polymerase to stabilize it on DNA as observed previously. The consequence of this cooperation between clamp and polymerase is that upon finishing a template and dissociation of the polymerase from DNA, the gp45 clamp spontaneously dissociates from DNA without assistance. However, the greater stability of the PCNA and β clamps on DNA necessitates an active process for their removal. The clamp loaders (RF-C and γ complex) were also capable of unloading their respective clamps from DNA in the presence of ATP. Conclusions: The stability of the different clamps in solution correlates with their stability on DNA. Thus, the low stability of the T4 clamp explains the inability to isolate gp45 on DNA. The stability of the PCNA and β clamps predicts they will require an unloading factor to recycle them on and off DNA during replication. The clamp loaders of PCNA and β double as clamp unloaders presumably for the purpose of clamp recycling.     

Of markets,technology, patients and profits

In this paper I: (1) Describe something of the present situation in the United States and briefly contrast this with the state of affairs in other nations of the industrialised world. I emphasise health care but also allude to other social conditions: health care is merely one institution of a society and, just as do its other institutions, the system of health care reflects the basic world-view of that society. (2) Sketch the world-view and the philosophy which underwrites the use of a market system in distributing what are acknowledged to be critically important social goods like health care and higher education. I show that a well-functioning market can indeed be useful when it comes to distributing some, but not when distributing other goods. (3) Suggest that when competition and the market are used to regulate health care, technology—instead of being used to benefit patients—is apt to be used primarily to maximise individual profit: it becomes a weapon between what is often painted as warfare among health care providers and institutions. I argue that this state of affairs is based on an undue emphasis upon the demands of individual freedom to the detriment of the community. Finally (4) I suggest an alternative approach to balancing individual with communal interests, an approach which is neither based on a predominance of one with neglect of the other, nor on a dialectic balance between them, but rather upon an approach which sees both individual and communal interests as modifying forces in a complex homeostatic balance. Individual success, in any civilised sense of the term, is possible only in a viable and well-functioning community, and a well-functioning community is not possible without individual success: the two are inevitably interdependent and linked.     

Multivariate Analysis of Left Ventricular Mass Determinants in Adults: Different Patterns in Men and Women

Echocardiographic left ventricular mass (LVM) estimates are strong predictors of subsequent mortality and cardiovascular events. It is known that blood pressure (BP), weight (WT), and age are significantly correlated with LVM. We hypothesized that stroke volume (SV) measured by Doppler echocardiography would also be correlated with LVM. Two hundred and thirteen patients referred for routine echocardiography had determination of LVM, cuff BP, and Doppler SV. Those with localized LV disease, valvular disease, or cor pulmonale were excluded. In both men and women, systolic BP (SBP) was more closely correlated with LVM than was diastolic blood pressure or mean arterial pressure, and SV was more closely correlated with LVM than cardiac output or cardiac index. Stepwise regression, followed by multiple regression showed that four variables (WT, SV, SBP, and AGE) explained 32.3% of the variability in LVM in men and 48.5% of the variability in LVM in women. WT and SV were significant determinants of LVM in both men and women. Age was also significant in men and SBP was also significant in women. For both men and women, SV was more significantly correlated with LVM than was SBP. The changes in LVM associated with 1 SD increments of SV and SBP, respectively, were 8 and 5 g for men and 13 and 11 g for women. We conclude that men and women have different patterns of variables influencing LVM. Doppler echocardiographic SV is a newly described determinant of LVM that has a greater correlation with LVM than does SBP. This study reemphasizes the importance of WT as the major determinant of LVM. (ECHOCARDIOGRAPHY, Volume 13, January 1996)     

Comparison of postoperative complications following radical and modified radical mastectomy

A retrospective study was carried out by reviewing the files of 100 patients who had undergone radical mastectomy and 100 patients who had undergone modified radical mastectomy from 1966 to 1975 for the purpose of comparing early and late complications. In each group, 80 patients were involved in long-term follow-up. Immediate postoperative complications—notably seromas, wound infection, and flap necrosis—were found to be considerably fewer following modified radical mastectomy. There was also a significantly lower incidence of late complications, such as limb edema and recurrent infection, after modified radical mastectomy. Since the cure rates achieved by the two radical mastectomy procedures appear to be similar, it is concluded that modified radical mastectomy is the procedure of choice in stages I and II cancer of the breast.

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Résumé Nous avons relevé les dossiers de 100 patientes traitées par mammectomie radicale conventionelle et de 100 patientes traitées par mammectomie radicale modifiée et avons comparé les complications post-opératoires observées dans les 2 groupes. Toutes les patientes furent opérées entre 1966 et 1975. Dans chaque groupe, nous avions un recul suffisant chez 80 patientes pour évaluer les résultats à long terme. Les complications post-opératoires, immédiates (sérÔmes, infections de plaie, nécrose de greffe cutanée) ou tardives (lymphoedème du bras, infections à répétition), furent beaucoup plus rares après mammectomie radicale modifiée. Etant donné que les taux de guérison obtenus avec ces 2 opérations semblent Être les mÊmes, nous en concluons que la mammectomie radicale modifiée est l'opération de choix pour traiter les cancers du sein au stade I et II.