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Biomedical subjects

C Nathan

Publications and source records attributed to C Nathan.

At least 145 records · Page 8Linked to original sources
PubMed1980

Role of oxygen-dependent mechanisms in antibody-induced lysis of tumor cells by activated macrophages.

The alloantiserum-dependent lysis of TLX9 lymphoma cells by peritoneal cells from Bacille Calmette-Guerin (BCG)-treated mice was inhibited 62 percent by depletion of oxygen. This effect did not appear to be a result of interference with mitochondrial respiration because cyanide, azide, and dinitrophenol did not inhibit cytotoxicity. Preincubating the effector cells for 2 h without glucose, which markedly reduces their ability to release hydrogen peroxide, likewise suppressed antibody-dependent cytolysis by 62 percent. Lysis of sensitized lymphoma cells was virtually abolished by 6 mg/ml of thioglycollate broth, a concentration that also abrogated the detectable release of hydrogen peroxide and the lysis of lymphoma cells by BCG-activated macrophages in response to phorbol myristate acetate (PMA). This concentration of thioglycollate broth was not toxic to the effector cells, as judged by adherence to plastic, binding of opsonized erythrocytes, and phagocytosis of radiolabeled starch granules. Catalase, superoxide dismutase, horseradish peroxidase, mannitol, ethanol, benzoate, and diazabicyclooctane were without consistent effects. Cytochalasin B and dihydrocytochalasin B both markedly suppressed cytolysis, whether induced by antibody or by PMA (ID(50), 0.5 mug/ml). Cytoehalasin B was an equally potent suppressor of glucose uptake and PMA-induced hydrogen peroxide release by BCG-activated macrophages (ID(50), 0.5 mug/ml). However, dihydrocytochalasin B lacked these latter effects, which suggests that cytotoxicity required intact contractile elements. The extracellular lysis of antibody-coated lymphoma cells by BCG-activated macrophages appears to have a predominantly oxidative basis.

Animals↗
PubMed1980

Endemic aminoglycoside resistance in gram-negative bacilli: epidemiology and mechanisms.

Isolates of gentamicin-resistant gram-negative bacilli from clinical specimens peaked at nine to 10 per month in 1973-1974. Instituting barrier-type precautions during 1974-1977 was associated with a sustained 87% reduction in resistant Enterobacteriaceae. The number of resistant Pseudomonadaceae fell temporarily by 28%, paralleling gentamicin usage. During an endemic 15-month period in 1976-1977 nonenzymatically mediated resistant Pseudomonas aeruginosa often emerged after aminoglycoside therapy in patients who had prior carriage of sensitive strains of the same serotype (P = 0.002); this resistance was associated with wound or sputum isolates (P = 0.003). Resistant Enterobacteriaceae more often demonstrated the converse, that is, spread of urinary tract isolates with enzymatically mediated resistance from patients not on aminoglycoside therapy. These findings suggest that control measures to minimize occurrence of resistant bacilli include barrier-type precautions for patients with resistant Enterobacteriaceae, evaluation of transfers and readmissions as a source of resistant organisms, and reduction of aminoglycoside use to decrease the selection of nonenzymatic resistance.

Amikacin↗
PubMed1980

Identity and interspecific transfer of gentamicin-resistance plasmids in Staphylococcus aureus and Staphylococcus epidermidis.

The hypothesis that emergence of gentamicin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis in a neonatal special care nursery was the result of transfer of a single plasmid between these two species was examined. In experiments with mixtures of staphylococci, either in mixed cultures or on human skin, isolates of S. aureus and S. epidermidis transferred their gentamicin-resistance plasmids both intra- and interspecifically. By electron microscopy, the molecular masses of the plasmids from S. aureus and S. epidermidis were the same, 12.2 +/- 0.36 (standard deviation) and 12.3 +/- 0.56 megadaltons, respectively. Restriction endonuclease analysis of the plasmids from five isolates of S. aureus and two isolates of S. epidermidis, with use of the enzymes HaeIII, EcoRI, XbaI, and HindIII, showed no differences in the digestion patterns of the seven gentamicin-resistance plasmids. The results supported the hypothesis that plasmid transfer between S. aureus and S. epidermidis occurs in nature.

Conjugation, Genetic↗
PubMed1979

Activation of macrophages in vivo and in vitro. Correlation between hydrogen peroxide release and killing of Trypanosoma cruzi.

As reported previously, mouse peritoneal macrophages could be activated to kill intracellular trypomastigotes of Trypanosoma cruzi, the agent of Chagas' disease, in either of two ways: by immunizing and boosting the mice (3), or by culturing resident or inflammatory macrophages in spleen cell factor(s) (SCF) in vitro (2). Macrophages activated in vivo became less trypanocidal with time in culture, and cells activated in vitro lost trypanocidal capacity when CSF was removed (2). In the present study, the ability of macrophages to release H2O2 in response to phorbol myristate acetate (PMA) could be induced in vivo and in vitro, and reversed in vitro, in a manner correlating closely with changes in trypanocidal activity. Macrophages could be activated in vitro with SCF in a time-dependent and dose-dependent fashion, so that they released as much H2O2 as macrophages activated in vivo. The sensitivity of epimastigotes and trypomastigotes to enzymatically generated H2O2 suggested that the generation of H2O2 by activated macrophages could be plausible explanation for their trypanocidal activity. Of the biochemical correlates of macrophage activation reported to date, increased ability to release H2O2 seems most closely allied to enhanced capacity to kill an intracellular pathogen.

Animals↗
PubMed1978

Infections due to gentamicin-resistant Staphylococcus aureus strain in a nursery for neonatal infants.

An apparently homogeneous strain of Staphylococcus aureus resistant to gentamicin (Gmr), kanamycin, tobramycin, and sisomicin, but susceptible to amikacin and netilmicin, caused multiple infections in neonatal infants in a special care nursery. Nasal cultures revealed a high rate of carriage of the Gmr staphylococcus in infants without clinical infection. Segregating patients according to a modified cohort system and use of careful aseptic techniques led to apparent elimination of the Gmr strain. The resistance to aminoglycosides in this strain was mediated by an aminoglycoside 6'-N-acetyltransferase and a gentamicin phosphotransferase. Genetic determinants for these enzymes were borne on a circular covalently closed plasmid of approximately 11 megadaltons. These resistance determinants closely resemble those found in isolates of S. aureus that have caused nosocomial infections in patients in Europe.

Gentamicins↗
PubMed1978

In vitro activity of 5-episisomicin in bacteria resistant to other aminoglycoside antibiotics.

Eighty-seven isolates of Pseudomonas, Enterobacteriaceae, and Staphylococcus, chosen because of their resistance to other aminoglycosides, were tested for susceptibility to 5-episisomicin. Tests were performed in Mueller-Hinton agar and also, with 38 of these isolates, in Mueller-Hinton broth. Of Enterobacteriaceae, 85 and 95.5% were inhibited by 5 and 10 mug of 5-episisomicin per ml, respectively. Amikacin inhibited 74 and 91% of the strains at 10 and 20 mug/ml, respectively. Fifty-four percent of P. aeruginosa were inhibited by 5-episisomicin and amikacin. Eighty-three percent of S. aureus were inhibited by netilmicin and amikacin, whereas only 50% were inhibited by 5-episisomicin. Isolates resistant to 5-episisomicin were most often resistant to the other aminoglycosides and occurred in gram-negative bacilli that did not carry aminoglycoside-modifying enzymes. Five of 23 isolates that carried a 6'-N-acetyltransferase (AAC-6') and one of two that carried an aminoglycoside 3-acetyltransferase were resistant to and acetylate 5-episisomicin. Strains carrying other aminoglycoside-modifying enzymes were inhibited by 5-episisomicin. Thus, 5-episisomicin is a promising aminoglycoside not attacked by most aminoglycoside-modifying enzymes. Resistance will probably most often be based upon nonenzymatic mechanisms which will also affect other aminoglycosides.

Drug Resistance, Microbial↗
PubMed1978

In vitro activity of Sch 21420, derivative of gentamicin B, compared to that of amikacin.

The minimal inhibitory concentration of Sch-21420 closely paralleled amikacin for 125 strains of aerobic gram-negative bacilli and Staphylococcus aureus primarily selected for testing because of resistance to other aminoglycoside antibiotics. Fifteen of 26 strains requiring 20 mug or more of amikacin per ml for inhibition were inhibited by two- to fourfold less Sch 21420. The majority of organisms resistant to both agents owed their resistance to mechanisms other than the carriage of aminoglycoside-modifying enzymes. Most strains carrying aminoglycoside 6'-acetyltransferase, capable of modifying amikacin, were susceptible to 10 mug or less of Sch 21420 per ml.

Acetyltransferases↗
PubMed1976

In vitro comparison of netilmicin, a semisynthetic derivative of sisomicin, and four other aminoglycoside antibiotics.

One hundred isolates of Pseudomonas and Enterobacteriaceae, of which 85 were chosen because of their resistance to gentamicin or amikacin, were tested for susceptibility to netilmicin (SCH 20569), a new semisynthetic derivative of sisomicin, and to four other aminoglycosides. Tests were performed in Mueller-Hinton agar and, with 43 of these isolates, also in Mueller-Hinton broth. Most isolates of Escherichia coli, Klebsiella, Enterobacter, Citrobacter, and Serratia that were gentamicin resistant proved to be susceptible to netilmicin and amikacin. Tests of representative isolates of this group showed that they owed their resistance to the production of aminoglycoside-adenylylating enzymes. Four isolates of Serratia, detected by their resistance to amikacin, were also highly resistant to netilmicin but were susceptible to gentamicin. These isolates produced aminoglycoside-acetylating enzymes. Gentamicin-resistant Proteus and Providencia were, in general, highly resistant to netilmicin but were susceptible to amikacin. These isolates also produced aminoglycoside-acetylating enzymes. Most gentamicin-resistant strains of Pseudomonas were resistant to netilmicin, either by enzymatic aminoglycoside modification or by other undefined mechanisms. Thus, like amikacin, netilmicin extends the aminoglycoside susceptibility pattern of Enterobacteriaceae to include gentamicin-resistant isolates that produce aminoglycoside-adenylylating enzymes. It is ineffective against strains, some of them susceptible to amikacin, gentamicin, or tobramycin, that produce aminoglycoside-acetylating enzymes.

Amikacin↗
PubMed1975

[ Study of prolactin and blood gonadotropins in amenorrheas-galactorrhea. Dynamic exploation in 13 cases].

A study of the secretion of prolactin and plasma gonadotrophins was carried out comparatively in 3 groups of patients: histologically confirmed prolactin adenoma (group 1), idiopathic or iatrogenic amenorrhoea/galactorrhoea syndrome (group 2), empty sella turcica syndrome (group 3). The last group differs fundamentally from the two previous by the presence of a normal basal LH and FSH levels and normal LH-RH stimulation. Prolactin is not increased. It may be suppressed by L-dopa and stimulated by TRH. There exist no differences, apart from neuroradiological criteria, between the other two groups. The level of LH is slightly decreased but the response to LRH is positive, this effect often being more clear on FSH. Prolactin levels are raised, this no doubt explaining the negative response to TRH and chlorpromazine stimulation. Suppression by L-dopa is positiive, reflecting the absence of autonomy of prolactin adenomata. The water load test is unsatisfactory. There exists at the present time no method sufficiently discriminating to exclude the presence of a tumour at the origin of an amenorrhoea-galactorrhoea syndrome.

Adenoma↗
PubMed1974

Gentamicin-adenylyltransferase activity as a cause of gentamicin resistance in clinical isolates of Pseudomonas aeruginosa.

Gentamicin adenylyltransferase activity was found in extracts of clinical isolates of gentamicin-resistant Pseudomonas aeruginosa. Extracts of one of these isolates, P. aeruginosa POW, inactivated gentamicin in the presence of adenosine 5'-triphosphate. Extracts of strain POW catalyzed the binding of radioactivity from [(14)C]adenine adenosine 5'-triphosphate to gentamicin components, tobramycin, sisomicin, kanamycin A and B and, to a variable degree, streptomycin and spectinomycin. The substrate profile with these agents and other aminocyclitols was similar to that obtained with R factor-mediated gentamicin adenylyltransferase found in Enterobacteriaceae. Adenylylating activity was absent in gentamicin-susceptible mutants of strain POW. Adenylylation may be added to acetylation as an enzymatic mechanism responsible for gentamicin resistance among strains of P. aeruginosa.

Adenosine Triphosphate↗
PubMedDate not supplied

The comparative in vitro activity of clinafloxacin and other antimicrobials against vancomycin-susceptible and vancomycin-resistant enterococci.

The susceptibilities of 50 unique vancomycin-susceptible (n = 15) and vancomycin-resistant (n = 35) enterococci to 6 antimicrobials were compared. Teicoplanin was consistently the most active agent for all strains. Ampicillin and imipenem were active primarily for vancomycin-sensitive Enterococcus faecalis. Clinafloxacin and ciprofloxacin showed poorer activity compared to prior studies, suggesting that the emergence of quinolone resistance is now occurring in enterococci.

Ampicillin↗
PubMedDate not supplied

Group counseling for children adopted at older ages.

Children adopted at older ages have special emotional needs and problems that can complicate their development. Counseling groups specifically designed for this population provide these children with opportunities to share with others who have had similar experiences.

Adolescent↗