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D Mack

Publications and source records attributed to D Mack.

At least 91 records · Page 5Linked to original sources
PubMed1995

Five-year results of a phase II study with low-dose bacille Calmette-Guerin therapy in high-risk superficial bladder cancer.

OBJECTIVES: Numerous studies have shown bacille Calmette-Guérin (BCG) to be an effective prophylactic and therapeutic agent for superficial transitional cell carcinoma of the bladder. The high-grade T1 lesion treated by transurethral resection alone is reported to progress to muscle invasion in 30% to 50% of the patients. Until now, optimal treatment schedule and optimal dose have not been defined. As suggested by Pagano's group, we used BCG in a lower dose than hitherto usual in our high-risk cancer patients. METHODS: Five years ago, we treated 32 Stage T1 cancer patients who were described as at high risk based on the criteria of histologic grade 3 in 21 patients, grade 2, but multiple in 11 patients, and with carcinoma in situ in 17 patients. Follow-up ranged from 51 to 63 months, with a mean of 57 months. We used BCG strain Pasteur Paris 75 mg weekly for 6 weeks and then maintenance therapy monthly for the first year and every 3 months for the second year. Complete remission was defined as negative cystoscopy, biopsy, and cytology. RESULTS: After a single 6-week course of BCG, 25 patients had negative cytology and biopsy findings after 3 months; 2 other patients needed a second 6-week cycle of BCG, for an overall response rate of 80%. Five patients underwent cystectomy because of multiple recurrences and tumor progression. After 2 years of follow-up, but under continuing maintenance therapy, 3 additional patients had tumor recurrences and also underwent cystectomy. Now, after 5 years' follow-up, the overall progression rate to cystectomy was 25% (8 of 32 patients), but none of the patients had progression to metastasis. Treatment-related toxicity did not appear to be lower at a lower dose of BCG. CONCLUSIONS: Low-dose BCG therapy is also an effective treatment in high-risk T1 bladder cancer (especially with maintenance therapy and short-term evaluations of the patients always by the same controlling physician) to prevent progression and recurrence and to preserve bladder function.

Aged↗
PubMed1995

Low-dose bacille Calmette-Guérin (BCG) therapy in superficial high-risk bladder cancer: a phase II study with the BCG strain Connaught Canada.

OBJECTIVE: To evaluate low-dose bacille Calmette-Guérin (BCG) therapy, with the Connaught Canada strain, in patients with superficial transitional cell carcinoma (STCC) of the urinary bladder. PATIENTS AND METHODS: Between September 1990 and December 1992 25 patients were entered into a phase II study to evaluate the feasibility, response and toxicity of BCG immunotherapy for patients with high-risk STCC. Therapy consisted of six, weekly instillations of 27 mg (3 x 10(8) colony-forming units) of the BCG strain Connaught Canada. Maintenance therapy was administered monthly for 1 year with the same dosage. RESULTS: Of 25 eligible patients, 84% had complete responses after the initial cycle with low-dose BCG and had stable disease. Four patients had no response, three of whom subsequently underwent radical cystectomy. The mean length of follow-up was 30.8 months (25-36). Toxicity included profound local reactions such as severe dysuria, frequency and gross haematuria. No systemic infections, except fever, were seen; none of the patients needed isoniazid. All reactions were treated symptomatically. CONCLUSIONS: The results of this study suggest that low-dose BCG with the strain Connaught Canada can be successfully used in the treatment of patients with high-risk STCC. Toxicity was not reduced substantially by the lower dosage of BCG used.

Administration, Intravesical↗
PubMed1994

Characterization of different oligomeric species of the Yersinia enterocolitica outer membrane protein YadA.

The oligomeric structure of the plasmid-encoded outer membrane protein YadA of Yersinia enterocolitica was studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and sucrose gradient sedimentation, respectively. The apparent molecular weight (M(r)) of the oligomeric 200-kDa YadA species detected by SDS-PAGE varied from 152,000 to 240,000 depending on the respective acrylamide concentration. The atypical electrophoretic behavior of the 200-kDa YadA species results form an exceptionally high relative free mobility as revealed by the Ferguson plot. In contrast, the apparent M(r) of 53,000 of the YadA monomer was independent of the acrylamide concentration. An additional oligomeric 116-kDa YadA species was detected by SDS-PAGE when membrane preparations of Y. enterocolitica were solubilized in SDS at 37 degrees C. The gel-purified 116-kDa YadA species was completely converted to the 200-kDa species by heating at 100 degrees C and to the monomeric form (M(r) 53,000) by heating in the presence of 10 M urea without reducing agents, respectively. This suggests that the 116-kDa YadA species represents the native oligomeric form of YadA, whereas the 200-kDa species is only generated from native YadA during denaturation in SDS. The significance of the 116-kDa YadA species is also supported by the rather slow sedimentation at about 6 S of detergent-solubilized YadA in sucrose gradients, which probably contains only two or three monomers.

Adhesins, Bacterial↗
PubMed1994

The effect of active immunization against gonadotropin-releasing hormone on the ultrastructure of the rat ventral prostate.

To evaluate the effects of active immunization against gonadotropin-releasing hormone (GnRH) on the ultrastructure of the rat ventral prostate, male Sprague-Dawley rats received three consecutive intramuscular injections of 10 micrograms/100 g body weight (D-Lys6)-GnRH-diphtheria toxoid conjugate (GnRH-DT vaccine). Following immunization, test animals developed sufficiently high antibody titres to block the pituitary gonadal axis. Consequently testosterone values dropped to the levels in castrates. This therapy leads to atrophy of the prostate. Following immunization a strong immunological response, indicating the presence of considerable amounts of a GnRH-like peptide, was observed in the ventral prostates as early as 14 days after the first injection of GnRH-DT. Immunoneutralisation of GnRH-like activity may contribute to the effects observed.

Animals↗
PubMed1994

In vitro effects of artemisinin ether, cycloguanil hydrochloride (alone and in combination with sulfadiazine), quinine sulfate, mefloquine, primaquine phosphate, trifluoperazine hydrochloride, and verapamil on Toxoplasma gondii.

The in vitro effect of the following antimicrobial agents on Toxoplasma gondii tachyzoites were studied: artemisinin ether (arteether), cycloguanil hydrochloride (cycloguanil), mefloquine, primaquine phosphate, and quinine sulfate, as well as the calcium channel blocker verapamil and the calmodulin inhibitor trifluoperazine hydrochloride. Arteether at > or = 0.5 micrograms/ml and cycloguanil at > or = 1.0 micrograms/ml inhibited T. gondii in vitro. Cycloguanil (2.5 micrograms/ml) combined with a noninhibitory concentration of sulfadiazine (25 micrograms/ml) inhibited T. gondii more than cycloguanil alone. Neither primaquine phosphate, mefloquine, nor quinine sulfate had an inhibitory effect on intracellular T. gondii. Verapamil and trifluoperazine hydrochloride were not inhibitor at lower physiologic concentrations, but higher physiologic concentrations were toxic to cell cultures in vitro and therefore our assay could not be used to assess their effects.

Animals↗
PubMed1994

Characterization of transposon mutants of biofilm-producing Staphylococcus epidermidis impaired in the accumulative phase of biofilm production: genetic identification of a hexosamine-containing polysaccharide intercellular adhesin.

The primary attachment to polymer surfaces followed by accumulation in multilayered cell clusters leads to production of Staphylococcus epidermidis biofilms, which are thought to contribute to virulence in biomaterial-related infections. We isolated Tn917 transposon mutants of biofilm-producing S. epidermidis 13-1, which were completely biofilm negative. In pulsed-field gel electrophoresis no obvious deletions of the mutants were noted. The Tn917 insertions of mutants M10 and M11 were located on different EcoRI fragments but on identical 60-kb SmaI and 17-kb BamHI chromosomal fragments. Linkage of transposon insertions of mutants M10 and M11 with the altered phenotype was demonstrated by phage transduction, whereas the several other mutants apparently represented spontaneous variants. In a primary attachment assay with polystyrene spheres, no significant difference between any of the mutants and the wild type could be detected. Cell clustering as an indication of intercellular adhesion, which is a prerequisite for accumulation in multilayered cell clusters, was not detected with any mutant. These results demonstrate that the mutants were impaired in the accumulative phase of biofilm production. Mutants M10 and M11 did not produce detectable amounts of a specific polysaccharide antigen (D. Mack, N. Siemssen, and R. Laufs, Infect. Immun. 60:2048-2057, 1992), whereas substantially reduced amounts of antigen were produced by the spontaneous variants. Hexosamine was determined as the major specific component of the antigen enriched by gel filtration of biofilm-producing S. epidermidis 1457 because almost no hexosamine was detected in material prepared from the isogenic biofilm-negative transductant 1457-M11, which differentiates the antigen from other S. epidermidis polysaccharide components. Our results provide direct genetic evidence for a function of the antigen in the accumulative phase of biofilm production by S. epidermidis by mediating intercellular adhesion.

Antigens, Bacterial↗
PubMed1994

Diagnostic problems of urine cytology on initial follow-up after intravesical immunotherapy with Calmette-Guérin bacillus for superficial bladder cancer.

After transurethral resection or biopsy, patients with recurrent bladder cancer or in situ carcinoma were given topical immunotherapy with low-dose Calmette-Guérin bacillus (BCG). In the recurrence-free interval they were treated with BCG monthly for 1 year and then every 3 months for the next year. Cytological analysis was always performed concomitant with the administration of immunotherapy. In order to evaluate the therapeutic success, cystoscopy and biopsy were performed after the first cycle of BCG and then every 3 months. At the start of topical therapy with BCG, a great increase in the number of inflammatory cells was seen. In urothelial cells the nuclei were enlarged; they were hyperchromatic with sometimes increased and prominent nucleoli, anisocaryosis and a distorted nucleus-plasma ratio. These cytological findings were also made 1 year after initial therapy and slowly diminished in the 2nd year during immunotherapy at 3-month intervals. The accuracy of urine cytology for carcinoma in situ is 80%. Interpretation of cytology in the recurrence-free interval was impaired. When doubtful, the recurrence of a carcinoma in situ under maintenance therapy with BCG must be proved by biopsy.

Administration, Intravesical↗
PubMed1993

Antibodies to Toxoplasma gondii major surface protein (SAG-1, P30) inhibit infection of host cells and are produced in murine intestine after peroral infection.

Monoclonal and polyclonal, monospecific antibodies to the major surface antigen of Toxoplasma gondii (SAG-1, P30) inhibit infection of human fibroblasts and murine enterocytes. Fab prepared from polyclonal, monospecific antibody to P30 also have this inhibitory effect on invasion, which indicates that this antibody directly blocks parasite infection of host cells rather agglutinating the parasite. Antibodies to another surface protein (P22) did not alter in vitro infection. If the inhibitory effect of antibody to P30 was due to steric hindrance or complexing of surface epitopes contiguous to P30, antibodies to other surface epitopes would also be inhibitory and they are not. Urea treatment of antibody (which permits discrimination of high and low avidity antibody) did not alter the effect of anti-P30 antibody. This observation indicates that the effect of the antibody to P30 was not an artifact of differences in the avidity of the antibody to P22 and P30. Heat inactivated antisera from mice infected with either RH or PTg strain T. gondii (P30+) inhibit infection of fibroblasts when challenged with autologous wild-type parasites by 87 and 40%, respectively. In contrast, these antisera have little inhibitory effect (13 and 19%, respectively) against infection of human fibroblasts by a P30-deficient mutant (PTgB). Antisera raised to the P30-deficient mutant had no significant effect on infection of cells by wild-type strains that have surface P30. The neoglycoprotein, BSA-glucosamide, competitively blocks infection of human fibroblasts by P30+ tachyzoites with surface P30 in higher level than those without surface P30. This observation indicates that there is likely to be a glycosylated host cell receptor to which T. gondii's major surface Ag SAG-1 (P30) binds. Mice infected perorally develop intestinal IgA antibody to the major 30-kDa epitope of T. gondii. Thus, the major surface epitope of T. gondii, SAG-1 (P30), has an important, functional role in infection of host cells by T. gondii and elicits an intestinal antibody response after peroral infection.

Animals↗
PubMed1992

Evidence for heat-stable liver cytosol substance(s) capable of causing oxidative activation of fructose 1,6-bisphosphatase.

The endogenous fructose 1,6-bisphosphatase (FBPase) in chicken liver extract undergoes a drastic increase in activity if the pH of the extract is in the alkaline range. Greater and more consistent activation occurs when purified FBPase, placed inside dialysis sack, is incubated in liver extract. Maximal activation (over 16-fold) is accompanied by the disappearance of 4 highly reactive sulfhydryl groups (SH) per molecule of enzyme. The activating effect of the extract remains essentially unchanged after heating to 100 degrees C. Activation can be reversed by dithiothreitol. These data show the existence in liver cytosol of heat-stable substance(s) capable of activating FBPase presumably by forming disulfide bonds with the enzyme's highly reactive SH groups.

Animals↗
PubMed1992

Experimental Yersinia enterocolitica infection in rats: analysis of the immune response to plasmid-encoded antigens of arthritis-susceptible Lewis rats and arthritis-resistant Fischer rats.

Recently, experimentally Yersinia-induced arthritis in Lewis and SHR rats has been described as a potential animal model for analyzing the pathomechanism of reactive arthritis (Toivanen et al. 1986; Hill and Yu 1987). We could confirm that Lewis but not Fischer rats develop aseptic arthritis about 2 weeks after an intravenous inoculation of Yersinia enterocolitica, serotype 0:8 (Hill and Yu 1987). Moreover, we compared the antibody response to virulence-associated Yersinia antigens (Yops) of experimentally infected Lewis rats with that of Fischer rats using an enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The ELISA results revealed a more rapid and vigorous specific IgG, IgA and IgM response for Lewis rats than for Fischer rats in the early state of infection. As demonstrated by immunoblotting, the IgG response was directed predominantly against the plasmid-encoded YopM, YopH, YopD and the V-antigen during the acute phase followed by antibodies against YopE and YadA. Although both rat strains seroconverted against this set of antigens, IgG antibodies to YadA were more prevalent and of higher titer in arthritis-susceptible rats compared to arthritis-resistant rats.

Animals↗
PubMed1992

Analysis of a measles outbreak in Kent County, Michigan in 1990.

New recommendations from the Immunization Practices Advisory Committee call for a second dose of measles vaccine for school age children. The purpose of this paper is to demonstrate the need for additional measures for the protection of preschool age children. A hospital-based measles outbreak of 25 cases in Kent County, MI, in 1990 provided an opportunity to study measles transmission to preschool age children. Twenty-two (88%) were people who had never received measles vaccine. Twelve of the cases were unvaccinated preschoolers, seven of whom were older than 15 months. Three nonvaccinated, but eligible people (one philosophic exemption and two vaccine-eligible preschoolers) were the source of most of the other cases. One school age unvaccinated child died of measles pneumonitis. A telephone survey indicated that improved public education regarding indications and contraindications to vaccination might encourage vaccination of children according to public health recommendations.

Adolescent↗
PubMed1992

Levels of pyrimethamine in sera and cerebrospinal and ventricular fluids from infants treated for congenital toxoplasmosis. Toxoplasmosis Study Group.

Pyrimethamine levels in sera, cerebrospinal fluid (CSF), and ventricular fluid were measured by using reversed-phase high-pressure liquid chromatography. The specimens were from 37 infants receiving pyrimethamine for treatment of suspect or proven congenital toxoplasmosis. Pyrimethamine half-life in serum was 64 +/- 12 h when determined by study of terminal-phase kinetics of samples obtained from nine babies. This half-life was significantly different (P = 0.008) from the pyrimethamine half-life (33 +/- 12 h) determined by terminal-phase kinetics for two babies of the same age taking phenobarbital. Serum pyrimethamine levels at various intervals after dosages of pyrimethamine were also lower for infants receiving phenobarbital. Levels measured in sera from babies taking the same dose of pyrimethamine throughout their first year of life did not appear to vary significantly over time or at different ages (P greater than 0.05). Mean +/- standard deviation serum levels 4 h after a pyrimethamine dose were 1.297 +/- 0.54 micrograms/ml for babies taking 1 mg of pyrimethamine per kg of body weight daily and 0.7 +/- 0.26 microgram/ml for babies taking 1 mg/kg each Monday, Wednesday, and Friday. Levels in CSF were approximately 10 to 25% of concomitant levels in serum. Serum folate levels for infants who took 0.64 to 1.7 mg leukovorin per kg ranged from 33 to 663 ng/ml. To determine whether the levels of pyrimethamine in serum and CSF of treated infants were in a range that affected the most virulent, rapidly replicating, and standard laboratory strain of Toxoplasma gondii, effects of various concentrations of pyrimethamine and sulfadiazine on replication of T. gondii in vitro were assessed. The levels of the antimicrobial agents effective in vitro were in the range of levels of pyrimethamine achieved in sera and CSF. Although folinic acid could inhibit the therapeutic effect of pyrimethamine and sulfadiazine in vitro, inhibition was noted only at levels (> or = 4,800 ng/ml) that were considerably higher than the folate levels found in the treated infants' sera.

Chromatography, High Pressure Liquid↗
PubMed1992

Parallel induction by glucose of adherence and a polysaccharide antigen specific for plastic-adherent Staphylococcus epidermidis: evidence for functional relation to intercellular adhesion.

The initial attachment and the accumulation of Staphylococcus epidermidis on polymer surfaces in multilayered cell clusters embedded in amorphous slime, which together lead to the plastic-adherent phenotype detected by the adherence assay used in this study, have been proposed to be major virulence factors of these bacteria. An antigen specific for plastic-adherent S. epidermidis strains was detected by an indirect immunofluorescence test using absorbed antiserum raised against the strongly plastic-adherent S. epidermidis 1457. A coagglutination assay was established, which allowed the quantitation of the antigen in bacterial extracts under different physiologic growth conditions. Expression of the antigen and of plastic adherence depended significantly on the presence of glucose in the growth medium. Parallel to increased plastic adherence, a 32- to 64-fold increase in the amount of the antigen was detected in bacterial extracts of cells grown in tryptone soya broth (TSB) compared with that in extracts of cells grown in TSB lacking glucose. A parallel time-dependent increase of plastic adherence and expression of the antigen was observed after stimulation by glucose of stationary-phase cultures of plastic-adherent S. epidermidis strains grown in TSB lacking glucose. The antigen consisted most probably of polysaccharide, because its immunologic reactivity was completely abolished by periodate oxidation but was resistant to protease digestion. A significant proportion of cells of plastic-adherent as compared with nonadherent S. epidermidis strains grown in TSB were located in large cell clusters exceeding 50 cells, which completely disintegrated after periodate oxidation of the cell preparations. Periodate oxidation of adherent bacterial films in situ led to release of the adherent cells from the plastic surface. These results strongly indicate a functional relation of the antigen to adherence of S. epidermidis to polymer surfaces, most probably by mediating intercellular adhesion of cells leading to accumulation in multilayered cell clusters.

Agglutination↗