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C Nathan

Publications and source records attributed to C Nathan.

At least 127 records · Page 7Linked to original sources
PubMed1987

Activation of mouse peritoneal macrophages by monoclonal antibodies to Mac-1 (complement receptor type 3).

Several features of activation of mouse peritoneal macrophages were elicited by 1-2-d exposure to submicrogram concentrations of anti-Mac-1 (M1/70), a rat monoclonal antibody that reacts with the alpha chain of complement receptor type 3 (Mac-1). The changes induced included enhanced capacity to secrete H2O2 when triggered with PMA, decreased secretion of proteins, increased expression of Ia antigen and decreased phagocytosis of particles. These changes closely resembled those induced by rIFN-gamma in type, extent, and time course. The concentration of M1/70 IgG resulting in 50% of the maximal activation of macrophage H2O2-releasing capacity averaged 0.18 +/- 0.03 micrograms/ml. This activation was not blocked by anti-FcR mAb, and could be reproduced with M18/2, a mAb against beta chain of Mac-1, suggesting that a direct ligation of Mac-1 with mAb was responsible for the activation. Neither depletion of T cells nor addition of neutralizing Abs to IFN-gamma or TNF-alpha prevented M1/70-mediated macrophage activation. Moreover, F(ab')2 of M1/70, or plating of macrophages on C3bi-coated surfaces, inhibited the activation of macrophages by rIFN-gamma. These findings suggest that Mac-1 (CR3) may play an important role in macrophage activation.

Animals↗
PubMed1987

Patients' endogenous flora as the source of "nosocomial" Enterobacter in cardiac surgery.

We prospectively studied Enterobacter colonization in cardiac surgery patients receiving cefazolin prophylaxis. Fifty-eight (67%) of 87 patients became colonized, 28 by the time of admission to a Cardiac Surgery Intensive Care Unit. Enterobacter cloacae was four times more prevalent than Enterobacter aerogenes. We found increased Enterobacter colonization, after prophylaxis, in 45% of surgery patients. None of 25 control patients, who underwent coronary angioplasty and received no antibiotic prophylaxis, showed increased colonization (P = .001). Both groups had similar baseline rates of Enterobacter carriage. Typing showed 50 distinct strains of E. cloacae and 11 of E. aerogenes; 25% of patients carried greater than or equal to 2 strains simultaneously. In the nine cases of horizontal transmission, source patients were intubated for greater than or equal to 5 days and had heavy throat carriage of Enterobacter. No environmental sources of transmission were found. Clinical Enterobacter infection developed in 12 patients; at least nine of these were infected with a strain that had been isolated by surveillance culture. We conclude that Enterobacter, part of the patients' endogenous flora, becomes an important pathogen when amplified by prophylactic antibiotics and is less often transmitted horizontally.

Aged↗
PubMed1987

In vitro susceptibility of nosocomial Pseudomonas aeruginosa, enterobacteriaceae, and staphylococci to ciprofloxacin and ten other broad-spectrum antibiotics.

We determined microdilution minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for ciprofloxacin and 10 beta-lactam and aminoglycoside antibiotics against 329 unique nosocomial isolates of Pseudomonas aeruginosa, citrobacter, enterobacter, serratia, and staphylococci. All were susceptible to ciprofloxacin, including 109 aminoglycoside-resistant gram-negative bacilli and 59 oxacillin-resistant staphylococci. Ciprofloxacin was generally 2-4 fold less active against aminoglycoside-resistant isolates than against their aminoglycoside-susceptible counterparts.

Aminoglycosides↗
PubMed1986

Extended use of disposable pressure transducers. A bacteriologic evaluation.

In a prospective randomized study, contamination rates of disposable pressure transducers changed every two days (n = 81) were compared with those changed at four (n = 26) or eight days (n = 50); the mean daily incidence of contamination was 3% for each group. After four days of use, the cumulative prevalences of contamination were similar. However, after eight days, the cumulative prevalence was significantly higher in transducers used without change (6.9%) than in those changed every two days (2.9%). Gram-negative bacilli were present in 63% of contaminated transducers; over half were from the patients' own flora. The only definite transducer-related bacteremia occurred on a day of initial contamination and should have been unaffected by the interval of change. Routine use of disposable transducers can be safely extended to four days, even in a busy intensive care unit.

Bacteria↗
PubMed1985

Occult aminoglycoside resistance in Pseudomonas aeruginosa: epidemiology and implications for therapy and control.

The epidemiology of aminoglycoside-resistant Pseudomonas aeruginosa was evaluated in an intensive care unit (ICU) with serial surveillance cultures of throat and rectum. Bacterial population analysis performed by replica plating of primary isolation plates onto gentamicin-containing agar revealed the presence of resistant subpopulations in the initial isolates from 41 (71%) of 58 consecutive assessable patients; these isolates were stably resistant and proportionately less susceptible to other aminoglycosides. An increase in resistant subpopulations occurred during the ICU stay in 34% of 38 colonized patients cultured serially as opposed to none of 23 followed after ICU discharge (P = .0008). Isolates of P. aeruginosa from patients who received aminoglycosides in the ICU were more likely to show an increase in resistance than were isolates from other patients (55% vs. 11%; P = .005); decreasing resistance after ICU discharge followed discontinuation of antibiotic administration. ICU mortality was higher in patients with increasingly resistant subpopulations (69% vs. 16%; P = .0004). The difficulty in treating infections with P. aeruginosa and in controlling drug resistance likely relates to the common carriage of clinically undetected resistant subpopulations that emerge during therapy.

Aminoglycosides↗
PubMed1985

Hydrogen peroxide from cellular metabolism of cystine. A requirement for lysis of murine tumor cells by vernolepin, a glutathione-depleting antineoplastic.

The sesquiterpene lactone antineoplastic vernolepin acutely depletes murine tumor cell glutathione (GSH), and lyses the cells by an unknown mechanism that is enhanced synergistically by inhibition of GSH synthesis with buthionine sulfoximine (BSO) (Arrick et al. 1983. J. Clin. Invest. 71:258). We found here that lysis of P815 mastocytoma cells by vernolepin, with or without BSO, required cystine in the culture medium. Addition of catalase markedly suppressed vernolepin-mediated cytolysis in cystine-containing media, suggesting the involvement of hydrogen peroxide in the cytolytic action of vernolepin. Consistent with this, inhibition of tumor cell glutathione disulfide reductase with 1,3-bis(2-chloroethyl)-1-nitrosourea or inhibition of endogenous catalase with aminotriazole synergistically augmented cytolysis by vernolepin. Moreover, H2O2 was released by suspensions of P815 cells in cystine-containing buffer (63 pmol/10(6) cells X h). Omission of cystine reduced the rate of H2O2 accumulation 10-fold. No H2O2 was detected without cells. Cytolysis by vernolepin could be restored in cystine-deficient medium by several other disulfides, themselves noncytolytic, such as disulfiram and oxidized Captopril, as well as by cysteine. In contrast, withholding two other essential amino acids (leucine or tryptophan) or adding cycloheximide did not interfere with cytolysis by vernolepin. These results suggest that cellular uptake of disulfides of physiologic and pharmacologic interest may be followed by their intracellular reduction and autooxidation with generation of H2O2. This previously unrecognized source of intracellular oxidant stress may be an important component of injury to GSH-depleted cells.

Animals↗
PubMed1984

Epidemiology of endemic Pseudomonas aeruginosa: why infection control efforts have failed.

The epidemiology of Pseudomonas aeruginosa was evaluated in an intensive care unit for a period of six months by means of serial surveillance and environmental cultures. One hundred (37%) of 270 patients were noted to be colonized: 63 at the time of their admission and 37 during their stay on the unit. Colonization at the time of admission was associated with length of hospitalization before admission to the intensive care unit, age, gastrointestinal disease, and prior use of antibiotics. The strains acquired on the intensive care unit represented several different serotypes, with little clustering; the source of most strains was not found. In only 12 cases did the acquisition of P. aeruginosa appear to represent cross-infection; the use of barrier isolation could have prevented at most five of these cases. Undetected endogenous gastrointestinal carriage may have been responsible for many other apparent acquisitions. Clinical infection in association with preceding gastrointestinal colonization developed in 20 patients. The data indicate that traditional control measures aimed at the prevention of exogenous acquisition of P. aeruginosa are unlikely to have an impact on the overall incidence of infection and that efforts to prevent infection in patients who are already colonized are necessary.

Communicable Disease Control↗
PubMed1984

Association of infection caused by Pseudomonas aeruginosa serotype O11 with intravenous abuse of pentazocine mixed with tripelennamine.

From July 1979 to June 1983, 25 of 40 intravenous drug addicts with systemic infections had Pseudomonas aeruginosa as the etiological agent; by 1982, P. aeruginosa had replaced Staphylococcus aureus as the most common pathogen. At least 21 of the 25 addicts with P. aeruginosa infection abused pentazocine mixed with tripelennamine (commonly known as T's and blues) compared with 6 of 15 addicts infected with other pathogens (P = 0.006). Of the 25 P. aeruginosa isolates, 23 were of serotype O11. Phenotypic patterns in isolates from addicts and in 22 serotype O11 control isolates from nonaddicts were determined by pyocin and electrophoretic enzyme typing, as well as by susceptibility to heavy metals and antibiotics. Of 25 isolates from addicts, 20 were identical or differed by only one marker, whereas the 22 nonaddict serotype O11 isolates were distributed among 17 distinct phenotypic patterns. We postulate that the emergence of P. aeruginosa as the major cause of deep infection in addicts is a consequence of contamination of their paraphernalia during preparation of pentazocine and tripelennamine for self-injection. The phenotypic similarity among isolates from addicts may reflect acquisition from related environmental sources and an unusual ability of certain serotype O11 strains to survive preparation of the drugs or to be invasive.

Drug Contamination↗
PubMed1984

Pseudomonas in the sinks in an intensive care unit: relation to patients.

Sink drains in a medical-surgical intensive care unit (ICU) were cultured during six consecutive weeks as part of a seven month prospective study of acquisition of Pseudomonas aeruginosa by ICU patients. Isolates were typed serologically and by aminoglycoside and chlorhexidine susceptibility patterns. All 11 sinks contained multiple strains of P aeruginosa; some strains persisted for weeks while others were isolated once. Of the sink isolates 56% had high level resistance to gentamicin and tobramycin whereas none of the strains found in patients. In sink isolates chlorhexidine resistance correlated with aminoglycoside resistance and with the presence of a chlorhexidine dispenser at a sink. The sequence of recovery of phenotypically similar isolates suggested that sinks were the source of at most two acquisitions of P aeruginosa by patients during the six weeks. Our study confirms that sinks may be reservoirs for large numbers of highly resistant P aeruginosa but are rarely the source of organisms colonising patients in our ICU.

Aminoglycosides↗
PubMed1983

Broad-spectrum beta-lactam resistance in Enterobacter: emergence during treatment and mechanisms of resistance.

Of three patients with Enterobacter mediastinitis treated with cefamandole, two failed initial treatment due to emergence of strains resistant to cefamandole and third generation cephalosporins. Extracts of the sensitive strains showed inducible hydrolysis of cephalothin; resistant strains (wild and laboratory derived) showed constitutive hydrolysis of cephalothin and cefamandole and bound but did not hydrolyze cefotaxime and latamoxef (moxalactam). In one mutant, increased latamoxef resistance appeared due to non-enzymatic mechanism(s). The Enterobacter strain from the patient who was treated successfully with cefamandole yielded only low level resistant mutants with lower cephalosporin binding than obtained with the other strains.

Anti-Bacterial Agents↗
PubMed1982

Gentamicin-resistant staphylococci as hospital flora: epidemiology and resistance plasmids.

In 1979, gentamicin-resistant (Gmr) Staphylococcus aureus was recovered from the clinical specimens of 22 epidemiologically unrelated hospitalized patients; 78% of the patients evaluated were also colonized with Gmr coagulase-negative staphylococci. Endonuclease fingerprinting was used to compare the Gmr plasmids within pairs of isolates of S. aureus and coagulase-negative staphylococci recovered from nine patients. Plasmids differed between pairs but were concordant within four pairs. Thus, in vivo interspecific plasmid transfer, although infrequent, may be important in the sporadic occurrence of Gmr S. aureus. To define the epidemiology of endemic Gmr coagulase-negative staphylococci, culture surveys were performed over two years. Gmr coagulase-negative staphylococci were acquired by 80% of the infants in a special-care nursery that previously had an outbreak of Gmr S. aureus. Among adult inpatients, a 48% colonization rate was related to prior exposure to antibiotics. In contrast, no colonization was found in outpatients or antepartum mothers.

Adult↗
PubMed1982

Structural and phenotypic varieties of gentamicin resistance plasmids in hospital strains of Staphylococcus aureus and coagulase-negative staphylococci.

We previously described a neonatal nursery epidemic of infections caused by a single strain of Staphylococcus aureus bearing a gentamicin resistance plasmid (Vogel et al., Antimicrob. Agents Chemother. 13:466-472, 1978). The same plasmid was present in two isolates of Staphylococcus epidermidis from the patients in this nursery and was transferable interspecifically from either S. aureus or S. epidermidis. During the ensuing 3 years, in the absence of further epidemics, we collected 162 gentamicin-resistant strains of S. aureus and coagulase-negative staphylococci from patients distributed throughout our hospital. Gentamicin resistance plasmids obtained from 41 representative S. aureus and coagulase-negative staphylococcal strains differed as determined by phenotypic and molecular analyses from the plasmid in the neonatal nursery epidemic. Nevertheless, these plasmids were structurally related to each other and to the plasmid of the original epidemic. Our results suggest an evolutionary relationship among these plasmids and support the hypothesis of a genetic reservoir of gentamicin resistance in coagulase-negative staphylococci transferable to S. aureus.

Coagulase↗
PubMed1980

Role of activated macrophages in antibody-dependent lysis of tumor cells.

Treatment of mice with Bacille Calmette-Guérin (BCG) or C parvum activates their peritoneal macrophages to release increased amounts of H2O2, and thereby to lyse extracellular tumor cells, in response to a pharmacologic agent, phorbol myristate acetate (PMA) (1-3). In the present study, the same bacterial vaccines activated peritoneal cells to become cytolytic to lymphoma cells sensitized with alloantiserum, in the absence of PMA. Resident peritoneal cells, or those elicited with thioglycollate broth, were ineffective, not only in PMA-induced lysis, but also in antibody-dependent lysis of tumor cells. The cytolytic effect of BCG peritoneal cells toward sensitized tumor cells appeared to be mediated mostly by macrophages. Cytotoxicity was immunologically specific, contact dependent, rapid, and efficient. Phagocytosis of intact tumor cells was not involved. Alloantiserum-dependent cytolysis was specifically blocked by the Fab fragment of a monoclonal antibody directed against the trypsin-resistant macrophage Fc receptor (FcR II). Thus, tumor cells coated with homologous immunoglobulin interact with FcR II on activated macrophages to trigger an extra-cellular cytolytic response.

Animals↗