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Biomedical subjects

D Mack

Publications and source records attributed to D Mack.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Complicated amebic liver abscess--course and therapy].

We report on a case of an amoebic liver abscess acquired during a holiday in Bali. Transdiaphragmatic migration and consecutive atelectasis of the right lung caused respiratory insufficiency, requiring immediate surgical intervention. Complications consisted of massive bleeding into the colon concomitant with a reactivated CMV-infection. In addition, toxins of Clostridium difficile and enterohaemorrhagic E. coli were seen in the faeces. In contrast to the majority of uncomplicated cases of amoebic liver abscess, usually treated with amoebicidal drugs only, surgical intervention was clearly indicated in our patient.

Combined Modality Therapy↗
PubMed1997

Long-term follow-up after open perineal cryotherapy in patients with locally confined prostate cancer.

OBJECTIVE: Appropriate therapies for locally confined adenocarcinoma of the prostate are available-but there is as yet no gold standard of therapy. For that reason, old therapeutic regimens are being revised. One such regimen is cryotherapy. METHODS: Between 1976 and 1989, 1,250 patients were seen with newly diagnosed prostate cancer. Sixty-six patients of stages T1c (n = 3), T2a (n = 32), T2b (n = 9), T2c (n = 11), T3a (n = 4), T3b (n = 5) and T3c (n = 2) were treated by open perineal cryotherapy. Mean age was 68 years. Three months after surgery, transurethral resection of the prostate and/or perineal biopsy was performed. RESULTS: In 66% of patients with stages T1c-T2b and in 87% of patients with stages T2c-T3c, positive biopsies were obtained. To date, 28 patients have died between 3 and 16 years after cryotherapy, with a mean survival of 7.2 years. The mean follow-up period of survivors (38 patients) is 8.5 years. Complications were: stress-incontinence in 10%, impotence in 10% and temporary rectoperineal fistula in 8%. CONCLUSIONS: Cryosurgery is an effective treatment for locally confined prostate cancer. With improvement of the procedure, clinical outcome may also improve.

Adenocarcinoma↗
PubMed1997

2,2'-Dithiobisbenzamides and 2-benzisothiazolones, two new classes of antiretroviral agents: SAR and mechanistic considerations.

Substituted 2,2'-dithiobisbenzamides and 2-benzisothiazolones were prepared and shown to possess low microM activity with high therapeutic indices against HIV-1, HIV-2 and SIV in cell culture. The mechanism of antiviral action was determined to be directed toward the nucleocapsid protein (NCp7), which contains two zinc fingers and plays vital roles in the viral life cycle. The "active sulfides" of this study cause the extrusion of zinc from these zinc fingers. Structure-activity relationships of the 2,2'-dithiobisbenzamides reveal that the disulfide bond and the ortho benzamide functional groups are essential for activity, with the best compounds having a carboxylic acid, carboxamide, or sulfonamide substituent. The 2-benzisothiazolones are formed from the disulfides both chemically and in vivo and their SAR mimics that of the 2,2'-dithiobisbenzamides. The antiviral activity of the disulfides may require cyclization to the isothiazolones. Two agents, PD 159206 and PD 161374, which showed good antiviral activity, physical properties, and excellent pharmacokinetics in mice, were selected for advanced studies.

Alkylation↗
PubMed1996

Eye manifestations of congenital toxoplasmosis.

PURPOSE: To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. METHODS: In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). RESULTS: Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median), and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

Adolescent↗
PubMed1996

Quality of life in patients undergoing bacille Calmette-Guérin therapy for superficial bladder cancer.

OBJECTIVE: To determine the impact of post-operative education about bladder cancer and topical immunotherapy on the physical, psychological and social well-being of patients with superficial bladder cancer. PATIENTS AND METHODS: Eighty-five patients (mean age 59 years, range 26-85, 64 men and 21 women) receiving topical immunotherapy were questioned during the initial cycle of treatment and during maintenance therapy with bacille Calmette-Guérin (BCG). Patients completed a questionnaire on their quality of life when they commenced treatment and twice more during maintenance therapy. RESULTS: Psychological distress and physical symptoms were intense when the diagnosis of bladder cancer was revealed to the patients, despite the knowledge that this cancer is usually curable. The overall quality of life, condition of health and sexual activity were mostly only moderate, were poor during initial therapy and better during 3-monthly maintenance therapy. CONCLUSION: In general, the quality of life of these patients is characterized by the disruption of their lifestyle and marked by change in their circumstances. It is the responsibility of the urologist to take the necessary time to educate, comfort and motivate such patients with superficial bladder cancer.

Adult↗
PubMed1996

Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception.

Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

Animals↗
PubMed1996

Association of biofilm production of coagulase-negative staphylococci with expression of a specific polysaccharide intercellular adhesin.

An association between adherent biofilm production on tissue culture plates and expression of a specific polysaccharide intercellular adhesion (PIA), which is functionally involved in cell clustering, was investigated for 179 Staphylococcus epidermidis isolates. Of the S. epidermidis strains, 50.8% were biofilm producers (A570 of > 0.1). There was a significant positive association between biofilm production and PIA expression: 86.8% of biofilm-producing S. epidermidis strains produced PIA as detected with a specific coagglutination assay. In contrast, 88.6% of the biofilm-negative isolates did not express PIA (P < .001). A linear association between the amount of PIA produced as detected by inhibition ELISA and the amount of biofilm produced was established for 49 S. epidermidis strains, representing a continuum from biofilm-negative to strongly biofilm-producing (r = .81, P < .001). Apparently, PIA is important for biofilm accumulation in the majority of clinical S. epidermidis isolates.

Adhesins, Bacterial↗
PubMed1996

Molecular basis of intercellular adhesion in the biofilm-forming Staphylococcus epidermidis.

The Staphylococcus epidermidis genes icaABC are involved in the synthesis of the polysaccharide intercellular adhesin (PIA), which is located mainly on the cell surface, as shown by immunofluorescence studies with PIA-specific antiserum. PIA was shown to be a linear beta-1,6-linked glucosaminoglycan composed of at least 130 2-deoxy-2-amino-D-glucopyranosyl residues of which 80-85% are N-acetylated, the rest being non-N-acetylated and positively charged. A transposon insertion in the icaABC gene cluster (ica, intercellular adhesion) led to the loss of several traits, such as the ability to form a biofilm on a polystyrene surface, cell aggregation, and PIA production. The mutant could be complemented by transformation with the icaABC-carrying plasmid pCN27. Transfer of pCN27 into the heterologous host Staphylococcus carnosus led to the formation of large cell aggregates, the formation of a biofilm on a glass surface, and PIA expression. The nucleotide sequence of icaABC suggests that the three genes are organized in an operon and that they are co-transcribed from the mapped icaA promoter. IcaA contains four potential transmembrane helices, indicative of a membrane location. The deduced IcaA sequence shows similarity to those of polysaccharide-polymerizing enzymes, the most pronounced being with a Rhizobium meliloti N-acetylglucosaminyltransferase involved in lipo-chitin biosynthesis (22.5% overall identity and 37.4% overall similarity). This similarity suggests that IcaA has N-acetylglucosaminyltransferase activity in the formation of the beta-1, 6-linked N-acetyl-D-glucosaminyl polymer. IcaB is secreted into the medium and contains a typical signal peptide. IcaC is hydrophobic and contains six predicted transmembrane helices distributed over its entire length, typical for an integral membrane protein. Neither IcaB nor IcaC shares similarity with known proteins, and their function is unknown. Inactivation of icaA, icaB, or icaC in pCN27 led to the complete loss of the intercellular adhesion phenotype in S. carnosus, suggesting that all three genes are involved in intercellular adhesion, PIA expression, and translocation.

Bacterial Adhesion↗
PubMed1996

The intercellular adhesin involved in biofilm accumulation of Staphylococcus epidermidis is a linear beta-1,6-linked glucosaminoglycan: purification and structural analysis.

The primary attachment to polymer surfaces followed by accumulation in multilayered cell clusters leads to biofilm production of Staphylococcus epidermidis, which is thought to contribute to virulence in biomaterial-related infections. We purified a specific polysaccharide antigen of biofilm-producing S. epidermidis 1457 and RP62A, which was recently shown to have a function in the accumulative phase of biofilm production by mediating intercellular adhesion (D. Mack, M. Nedelmann, A. Krokotsch, A. Schwarzkopf, J. Heesemann, and R. Laufs, Infect. Immun. 62:3244-3253, 1994). Following Sephadex G-200 gel filtration, this antigen was separated by Q-Sepharose chromatography into a major polysaccharide, polysaccharide I (> 80%), which did not bind to Q-Sepharose, and a minor polysaccharide, polysaccharide II (< 20%), which was moderately anionic. As shown by chemical analyses and nuclear magnetic resonance spectroscopy, polysaccharide I is a linear homoglycan of at least 130 beta-1,6-linked 2-deoxy-2-amino-D-glucopyranosyl residues. On average, 80 to 85% of them are N acetylated; the rest are non-N-acetylating and positively charged. Chain cleavage by deamination with HNO2 revealed a more or less random distribution of the non-N-acetylated glucosaminyl residues, with some prevalence of glucosaminyl-rich sequences. Cation-exchange chromatography separated molecular species whose content of non-N-acetylated glucosaminyl residues varied between 2 and 26%. Polysaccharide II is structurally related to polysaccharide I but has a lower content of non-N-acetylated D-glucosaminyl residues and contains phosphate and ester-linked succinate, rendering it anionic. Enzyme-linked immunosorbent assay inhibition with various monosaccharides revealed the beta-anomeric form and the acetylated amino group of the D-glucosaminyl residues as important for reactivity with the specific antiserum. The unbranched polysaccharide structure favors long-range contacts and interactions between polysaccharide strands and the cell wall and/or lectin-like proteins, leading to intercellular adhesion and biofilm accumulation. The structure of the polysaccharide is, so far, considered to be unique and, according to its function, is referred to as S. epidermidis polysaccharide intercellular adhesin (PIA).

Acetylglucosamine↗
PubMed1996

Identification of the bud emergence gene BEM4 and its interactions with rho-type GTPases in Saccharomyces cerevisiae.

The Rho-type GTPase Cdc42p is required for cell polarization and bud emergence in Saccharomyces cerevisiae. To identify genes whose functions are linked to CDC42, we screened for (i) multicopy suppressors of a Ts- cdc42 mutant, (ii) mutants that require multiple copies of CDC42 for survival, and (iii) mutations that display synthetic lethality with a partial-loss-of-function allele of CDC24, which encodes a guanine nucleotide exchange factor for Cdc42p. In all three screens, we identified a new gene, BEM4. Cells from which BEM4 was deleted were inviable at 37 degrees C. These cells became unbudded, large, and round, consistent with a model in which Bem4p acts together with Cdc42p in polarity establishment and bud emergence. In some strains, the ability of CDC42 to serve as a multicopy suppressor of the Ts- growth defect of deltabem4 cells required co-overexpression of Rho1p, which is an essential Rho-type GTPase necessary for cell wall integrity. This finding suggests that Bem4p also affects Rho1p function. Bem4p displayed two-hybrid interactions with Cdc42p, Rho1p, and two of the three other known yeast Rho-type GTPases, suggesting that Bem4p can interact with multiple Rho-type GTPases. Models for the role of Bem4p include that it serves as a chaperone or modulates the interaction of these GTPases with one or more of their targets or regulators.

Amino Acid Sequence↗
PubMed1996

Treatment of prostate cancer with gonadotropin-releasing hormone analogue: effect on lipoprotein[a].

Because of its association with cardiovascular disease, lipoprotein[a] (Lp[a]) has attracted the interest of the medical community. Even though serum concentrations of Lp[a] are mainly controlled by the apolipoprotein[a] gene locus, hormonal and metabolic factors, including manipulations of sex hormone levels, have been associated with changes in Lp[a] levels. We report here that the GnRH analog buserelin reduced concentrations of Lp[a] by 48% in elderly males suffering from cancer of the prostate. In contrast, apolipoprotein B levels increased during treatment, whereas other lipid factors, including serum cholesterol, triglyceride, high and low density lipoprotein cholesterol, and apolipoprotein A-I, were not affected. Although the study does not exclude a specific Lp(a)-lowering effect of buserelin, our results suggest that GnRH analogs may reduce Lp[a] levels in the circulation.

Aged↗
PubMed1995

Effect of a pneumoperitoneum on the extent and severity of peritonitis induced by gastric ulcer perforation in the rat.

Laparoscopic surgical repair of perforated gastroduodenal ulcer is technically feasible. To study the effect of a pneumoperitoneum on the extent and severity of peritonitis this animal study was devised. In rats gastric ulceration was induced by instillation of ethanol (50%, 2 ml) and followed by gastrotomy to simulate perforation. Animals were randomly allocated to pneumoperitoneum (PP) and control groups. In PP groups CO2 was insufflated intraperitoneally 6, 9, 12, and 24 h after gastrotomy. In controls the abdomen was only punctured. Animals were sacrificed 5 h after the end of PP or abdominal puncture. Blood cultures and intraabdominal swabs were assessed. A peritonitis severity score (PSS) based on histologies from peritoneum, liver, left kidney, spleen, and first jejunal loop was estimated. Six and 9 h after gastrotomy no significant differences between the PP and control groups were observed; 12 h after gastrotomy cultures of blood samples and abdominal swabs were positive in 67% and 75% in the PP group compared to 42% (P < 0.05), and 42% (P < 0.05) in controls. The mean PSS was 20.8 (standard deviation [SD] 2.2) in the PP group compared to 11.3 (1.5) (P < 0.01) in controls; 24 h after gastrotomy cultures of blood samples and abdominal swabs were positive in 83% and 100% in the PP group compared to 42% (P < 0.05) and 50% (P < 0.01) in controls. The mean PSS was 22.1 (1.5) in the PP group compared to 11.8 (2.4) (P < 0.01) in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗