In vitro studies of the antitumor effect of melphalan and analogous aniline mustard derivatives

Melphalan and analogous aniline mustard derivatives were tested on antitumor activity in vitro. All compounds showed similar antiproliferative effects against melanoma B16, sarcoma 180 and leukemia P388D1. Thus, the singular clinical efficiency of melphalan may not simply be explained by a selective uptake employing amino acid carrier systems of tumor cells.     

Prediction of Remission of Acute Posttraumatic Stress Disorder in Motor Vehicle Accident Victims

One hundred forty five individuals who sought medical attention as a result of a motor vehicle accident (MVA), and who were initially assessed 1 to 4 months post-MVA, were followed up prospectively for 6 months to determine how many of the 55 with posttraumatic stress disorder (PTSD) and the 43 with sub-syndromal PTSD would remit and what variables would predict remission. Thirty (55%) of those with initial PTSD had remitted at least in part by 6 months while 67% of those with sub-syndromal PTSD had remitted (and 5% had worsened). Four variables, including severity of initial symptoms, degree of initial physical injury, relative degree of physical recovery by 4 months and whether a close family member suffered a trauma during the follow-up interval, combined to classify 6-month clinical status of 84% of those with initial PTSD secondary to MVAs.     

Expression of S14-mRNA and its translational product in differentiating 3T3-L1 cells

During adipogenic conversion of 3T3-L1 cells S14-mRNA increased from undetectable levels in preadipocytes to high levels in differentiated adipocytes (adipocyte-like cells). In vitro translation of hybrid-selected S14-mRNA revealed an identical protein in 3T3-L1 adipocytes and in rat liver with regard to migration properties in two-dimensional gel electrophoresis. No translation product was found in 3T3-L1 preadipocytes. In conclusion, protein-S14 is very similar or even identical in rat lipogenic tissues and in 3T3-L1 adipocytes. Therefore, this cell line can be employed to elucidate further physiological aspects of protein-S14.     

The collagen-like component of the complement system, C1q, is recognized by 7 S autoantibodies and is functionally impaired in synovial fluids of patients with rheumatoid arthritis.

Cross-reactivity between type II collagen (CII) and C1q, the collagen-like subunit of the first component of complement, has been demonstrated in synovial fluid (SF) from rheumatoid arthritis (RA) patients. Many authors have studied autoimmunity to CII in RA, but little work has been done on autoimmunity to C1q in RA. In the data presented here, we have been able to show that in addition to native C1q, an altered form of C1q is present in SF from RA patients. Furthermore, a low molecular weight form of C1q is present in RA SF, although its role, if any, in the pathogenesis of RA is unclear. The presence in these RA SF of C1q-specific antibodies (IgG and IgM) has been studied and we have partially characterized the antibody moieties involved. As well as binding to C1q and fragments representing the collagen-tails from C1q, 7 S IgG autoantibodies against C1q also bind to a C1q molecule altered in vitro by incubation with reactive oxygen species and to the non-apeptide KGEQGEPGA (representing residues 26-34 from the C1q A-chain), which has previously been shown to suppress the onset of CII-induced arthritis in an animal model.     

Insoluble polyanions as activators of both pathways of complement

Soluble polyanions, e.g. dextran sulphate, are known to interact with components of the classical pathway of complement and also to activate the alternative pathway (APC).† Insoluble polyanions offer the opportunity to isolate and to characterize intermediates of the reaction sequence. Sephadex, an insoluble, crosslinked dextran, was substituted with sulphate groups using chlorosulphonic acid. The sulphated Sephadex (SS) activated the APC in normal and in C4-deficient-guinea-pig serum as shown by haemolytic and immunochemical methods. After incubation of SS with normal guinea-pig serum, a C3-cleaving enzyme bound to the SS particles was present. This enzyme was inhibited by antisera against the components C2 and C4. Anti-serum against factor B or anti-C3-Fab had no inhibitory effect. Incubation at 37° inactivated the enzyme; activity was restored by incubation with C2, but not with factors B and D of the APC. These results suggest the presence of the C[unk]42-enzyme bound to the SS particles after incubation with normal serum. However, preincubation of SS with C4 deficient serum did not yield an enzyme which could act on purified C3, but enzymatic activity cleaving C4 and C2 was present, indicating that binding and activation of C1 had occurred. Utilizing purified C[unk]1, it was shown that SS binds purified C[unk]1 in a functionally active state. These data indicate that the polyanion SS has a dual function: SS activates both the APC and the classical sequence. Thus, the chemically simple, ester-linked, anionic sulphate groups, distributed along crosslinked polysaccharide chains, are sufficient to be recognized as initiating signal for both pathways of complement.     

Once-daily oral gatifloxacin vs. three-times-daily co-amoxiclav in the treatment of patients with community-acquired pneumonia

A double-blind, double-dummy, multicentre, multinational, parallel-group study was designed to establish proof of equivalence between oral gatifloxacin and oral co-amoxiclav in the treatment of 462 patients with mild-to-moderate community-acquired pneumonia. Eligible patients were randomised equally to either gatifloxacin 400 mg once-daily plus matching placebo for 5-10 days, or amoxycillin 500 mg + clavulanic acid 125 mg three-times-daily for 5-10 days. The primary efficacy endpoint was clinical response (clinical cure plus improvement) at the end of treatment. Overall, a successful clinical response was achieved in 86.8% of gatifloxacin-treated patients, compared with 81.6% of those receiving co-amoxiclav, while corresponding rates of bacteriological efficacy (eradication plus presumed eradication) were 83.1% and 78.7%, respectively. The safety and tolerability profile of gatifloxacin was comparable to that of co-amoxiclav, with adverse gastrointestinal events, e.g., diarrhoea and nausea, being the most common treatment-related adverse events in both groups. The study showed no evidence of gatifloxacin-induced phototoxicity, musculoskeletal disorders, or hepatic and renal problems. Overall, this study showed that gatifloxacin was equivalent clinically to a standard course of co-amoxiclav in patients with community-acquired pneumonia, and that gatifloxacin was safe and well-tolerated.