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Biomedical subjects

K Jacobson

Publications and source records attributed to K Jacobson.

156 records · Page 9Linked to original sources

Effect macrophage activation on infection with Treponema pallidum.

Infection of rabbits with Treponema pallidum induces nonspecific acquired cellular resistance (ACR) to Listeria monocytogenes. This resistance can be adoptively transferred using thymus-dependent lymphocytes. Since infections that induce ACR are usually brought under control by cellular mechanisms, we sought to determine whether induction of ACR in rabbits stimulates resistance to challenge with T. pallidum. When BCG-infected rabbits which suppressed the growth of Listeria were challenged intravenously with T. pallidum, lesions appeared at the same time and progressed in a fashion similar to that in non-BCG-infected controls. There was a tendency for syphilitic lesions to disseminate more widely in BCG-infected animals and for the lesions to necrose more rapidly in controls. T. pallidum may resist phagocytosis by macrophages, as has been suggested previously, or macrophages may fail to be activated locally in the dermis. Although syphilitic infeciton appears to stimulate ACR, activation of the macrophages may not contribute significantly to the ability of the host to suppress T. pallidum.

Animals↗

New evidence for the non-infectivity of Treponema pallidum for mice.

We have recently shown that syphilitic rabbits are resistant to challenge with Listeria monocytogenes. This resistance was thought to reflect stimulation of cell-mediated immunity by active infection with Treponema pallidum. We now report data which show that the growth of Listeria was not suppressed in mice inoculated with T. pallidum. Re-inoculation with T, pallidum or with a large dose of an avirulent treponeme also failed to suppress the growth of Listeria. These results contrast with those obtained in rabbits and provide additional evidence that T. pallidum is not infective for the mouse.

Animals↗

Surface properties of phorbol esters and their interaction with lipid monolayers and bilayers.

The potent tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) is surface active and was found to occupy a limiting area of 62 sq A/molecule in monolayers at the air-water interface. The interfacial tension of aqueous TPA solutions is decreased by increasing the bulk-phase TPA concentrations up to 2 x 10(-6) M,beyond which no further decreases were observed. This concentration is in agreement with the apparent solubility limit previously obtained. The apparent aqueous solubility limit of the more hydrophobic phorbol-didecanoate is 5 x 10(-8) M. Interaction of TPA with egg phosphatidylcholine monolayers at the air-water interface was shown by an increase in the surface pressure of the monolayer from 22 dynes/cm, initial film pressure, to 34 dynes/cm 90 min after introduction of TPA into the aqueous subphase. It was shown by gel filtration chromatography that a similar phorbol derivative, tritiated phorbol-didecanoate, binds to phospholipid vesicles. Differential scanning calorimetry also indicated that the addition of either TPA or an inactive stereoisomer, 4-alpha-phorbol-didecanoate, to phospholipid bilayers results in a marked reduction of the enthalphy of the minor transition of dipalmitoylphosphatidylcholine liposomes. Several fluorescence polarization probes for membrane fluidity indicate that TPA does not affect this membrane parameter. Further, the presence of TPA induces no measurable change in the cation permeability of phospholipid vesicles, the conductance of planar bilayer membranes, or the electrophoretic mobility of negatively charged liposomes. The lack of a specific effect with bilayers alone, combined with the documented physiological effects at low TPA concentrations, point to the possibility of a specific membrane component as the receptor for TPA at the plasma membrane.

Binding Sites↗

Induction of acquired cellular resistance following transfer of thymus-dependent lymphocytes from syphilitic rabbits.

Syphilitic rabbits have previously been shown to resist challenge with Listeria monocytogenes. Thirty days after rabbits were infected with Treponema pallidum, transfer of 4 to 6 times 10-8 viable spleen cells along with T. pallidum conferred resistance to Listeria on normal recipients. Treatment of the spleen cells with anti-thymus serum and complement inhibited or abolished their ability to transfer resistance to Listeria. These results support the hypothesis that the ability of syphilitic rabbits to suppress the growth of Listeria reflects stimulation of cell-mediated immunity during active infection with T. pallidum.

Animals↗

The membrane disordering effect of ethanol on neural crest cells in vitro and the protective role of GM1 ganglioside.

The teratogenic effect of ethanol appears to be related to excessive cell death in selected cell populations including craniofacial neural crest. Because there is a large body of evidence suggesting that a primary site of action of ethanol is at the membrane level, the current study was designed to examine and attempt to ameliorate ethanol-induced neural crest cell membrane changes that proceed cell death. To this end, neural crest cells were grown as primary cultures from mouse cranial neural tube be explants. In these cultured cells, the relationships between changes in membrane lipid lateral mobility (a measure of membrane fluidity) as determined using the technique of fluorescence recovery after photobleaching (FRAP), ethanol-induced cell death, and the protective role of GM1 ganglioside were examined. A dose-response study showed that treatment with 50, 100, 150, or 200 mM ethanol respectively, for 24 h was positively correlated with membrane lipid lateral mobility and negatively correlated with cell viability. Pre- or co-treatment of the cells with GM1 ganglioside diminished the ethanol-induced increases in membrane fluidity and decreases in cell viability. The results of this study suggest that change in membrane fluidity can account, in part, for ethanol-induced neural crest cell death and that the protection conferred by GM1 ganglioside may result from membrane stabilization and subsequent preservation of the biophysical properties and biological function of the ethanol-exposed cell membranes.

Abnormalities, Drug-Induced↗

Patients' diets and preferences in a pediatric population with inflammatory bowel disease.

PURPOSE: To determine the dietary practices of the pediatric inflammatory bowel disease population at the Children's Hospital of the Hamilton Health Sciences Corporation and the reported effectiveness of those diets. PATIENTS AND METHODS: A questionnaire mailed to 153 pediatric patients was returned by 125 patients (76 Crohn's disease [CD] and 49 ulcerative colitis [UC] patients)--an 82% response rate. RESULTS: The median age of respondents was 13 years, and 62% were male. Ninety per cent and 71% of CD and UC patients, respectively, had changed their diets since diagnosis. Caloric supplements (eg, BOOST [Mead Johnson Nutritionals]), sole source nutrition, low fibre and lactose-free diets were used by more than 15% of CD patients, whereas lactose-free, nonspicy, low acid, additive-free, caloric supplement and low fibre diets were used by more than 15% of UC patients. A diet supplement was more commonly used in CD patients (P < 0.05) and an additive-free diet in UC patients. Corn and corn products, nuts, milk and bran were avoided by more than 20% of CD and UC patients; however, more CD than UC patients avoided corn and corn products. In addition, UC patients (more than 20%) also avoided tomato, other dairy (nonfluid milk-based products and foods containing milk products), chocolate, cheese, wheat, tomato sauces and fruit juice. A benefit was reported for 103 of 141 reported diets, with the most commonly alleviated symptoms being abdominal pain, diarrhea and flatulence. CONCLUSION: Many children with inflammatory bowel disease have altered their diets to manage their disease and have attributed symptomatic relief to these diets.

Adolescent↗

Susceptibility surveillance among gram-negative bacilli at a cancer center.

We conducted a survey of susceptibility among 758 gram-negative bacilli (GNB; collected from cancer patients over a 3-month period) to commonly used antibiotics. The overall resistance among GNB was least for piperacillin/tazobactam and meropenem (5 and 6%, respectively) followed by cefepime (8%), imipenem (9%), amikacin (12%), ofloxacin (13%), ciprofloxacin, ceftazidime and ticarcillin/clavulanate (14% each), aztreonam (18%) and tobramycin (24%). In comparison to data on antibiotic resistance to ceftazidime, imipenem, ciprofloxacin and aztreonam in similar studies in 1985 and 1994, resistance has significantly increased to all four antibiotic classes. Based on our current study, meropenem, cefepime, imipenem and piperacillin/tazobactam would be the most appropriate choices in our institution for empiric therapy of GNB infections in febrile neutropenic patients.

Anti-Bacterial Agents↗

Loracarbef (LY163892) versus amoxicillin/clavulanate in bronchopneumonia and lobar pneumonia.

In a single-blind study, 134 patients with bronchopneumonia or lobar pneumonia were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate three times daily for 10 to 14 days. Treatment efficacy was evaluated in 38 patients treated with loracarbef and in 39 treated with amoxicillin/clavulanate in whom pre-treatment positive cultures of pathogens susceptibile to the study drugs were isolated. Streptococcus pneumoniae and Haemophilus influenzae were cultured as single pathogens in 40.3% of the evaluable patients. Among the evaluable patients, 100% of the loracarbef group and 92.3% of the amoxicillin/clavulanate group had a favorable clinical response (cure or improvement). Bacteriologic response was favorable and the pathogen was eliminated or presumed eliminated in 97.4% of the loracarbef-treated patients and in 92.3% of the amoxicillin/clavulanate-treated patients. Treatment was discontinued in one loracarbef-treated patient because Ludwig's angina, unrelated to the study drug, was diagnosed and in five amoxicillin/clavulanate-treated patients because of diarrhea (two patients), rash (two patients), and nausea and vomiting (one patient). Diarrhea, the most frequently cited adverse event, was reported by 6.1% of the loracarbef-treated patients and 11.8% of the amoxicillin/clavulanate-treated patients. Asthenia was reported by 0% and 8.8% of the loracarbef and amoxicillin/clavulanate patients, respectively. It is concluded that both loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute bacterial pneumonia.

Amoxicillin↗