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Nonvertebral infections of the musculoskeletal system by mycobacerium tuberculosis

Chapter by: Kramer SB; Lee HSS; Abramson SB
in: Tuberculosis by Ron WN; Garay SM [Eds]
Philadelphia : Lippincott Williams & Wilkins, 2004
pp. 577-586
ISBN: 0781736781
CID: 3979

Occupancy of adenosine receptors raises cyclic AMP alone and in synergy with occupancy of chemoattractant receptors and inhibits membrane depolarization

Cronstein BN; Kramer SB; Rosenstein ED; Korchak HM; Weissmann G; Hirschhorn R
We have recently demonstrated that adenosine, acting via adenosine A2 receptors, inhibits generation of superoxide anions (O2-) by stimulated neutrophils. To determine the mechanism(s) by which adenosine inhibits O2- generation stimulated by the chemoattractant N-formylmethionylleucylphenylalanine (FMLP), we examined cyclic AMP (cAMP) concentrations, stimulated membrane depolarization and Ca2+ movements. Neither adenosine nor 5'-N-ethylcarboxamidoadenosine (NECA), the most potent agonist at adenosine A2 receptors, increases neutrophil cAMP content. However in the presence of the non-methylxanthine phosphodiesterase inhibitor, Ro-20-1724, both adenosine and NECA elicit a reversible increase in intracellular cAMP concentration. The chemoattractant FMLP also elicits an increment in the neutrophil cAMP content. NECA, in the presence of Ro-20-1724, synergistically enhances the increment in cAMP following stimulation by FMLP. However Ro-20-1724 does not potentiate the inhibition of O2- generation by NECA. Unlike other agents which increase neutrophil cAMP concentrations, NECA, even in the presence of a phosphodiesterase inhibitor, only trivially inhibits degranulation. We also found that adenosine markedly inhibits stimulated membrane depolarization but does not affect the stimulated increment in free ionized intracellular calcium. Moreover, inhibition by adenosine of O2- generation does not vary with the concentration of extracellular calcium. These results fulfil the last criterion for the demonstration of an A2 receptor on human neutrophils, and indicate that adenosine occupies an A2 receptor on neutrophils to raise intracellular cAMP in synergy with occupancy of the FMLP receptor. The results reported here also indicate that cAMP is not the second messenger for inhibition of O2- generation by adenosine and its analogues
PMID: 2844154
ISSN: 0264-6021
CID: 9838

Adenosine; a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils

Cronstein BN; Rosenstein ED; Kramer SB; Weissmann G; Hirschhorn R
Adenosine specifically inhibits superoxide anion generation by N-formyl-methionyl-leucyl-phenylalanine-stimulated neutrophils without affecting either degranulation or 'aggregation.' We present data that also supports the hypothesis that adenosine engages a specific cell surface receptor to mediate inhibition of stimulated neutrophils. Theophylline (10 and 100 mu M), a competitive antagonist at adenosine receptors, reversed the effects of adenosine (0.1 mu M) on superoxide anion generation by stimulated neutrophils. The adenosine analogue 5'N-ethylcarboxamidoadenosine (NECA) was a more potent inhibitor of superoxide anion generation than either N6-phenylisopropyladenosine (PIA) or adenosine, an order of potency consistent with that previously demonstrated for adenosine A2 receptors. 2-Chloroadenosine inhibited superoxide anion generation at concentrations similar to NECA. [3H]-NECA and [3H]-2-chloroadenosine bound to a single receptor on intact neutrophils. The characteristics of the receptors for [3H]-NECA and [3H]-2-chloroadenosine were similar (Kd = 0.22 and 0.23 mu M, respectively; number of binding sites = 9.31 and 11.1 X 10(3) sites/cell, respectively). NECA, 2-chloroadenosine, adenosine, and PIA inhibited binding of [3H]-NECA with a rank order similar to that for inhibition of superoxide anion generation (NECA = 2-chloroadenosine greater than adenosine greater than PIA). There was 50% inhibition of superoxide anion generation by NECA at approximately 20% receptor occupancy. Adenosine, derived from damaged tissues, may serve as a specific, endogenous modulator of superoxide anion generation by activated neutrophils through interaction at this newly described receptor on human neutrophils
PMID: 2989364
ISSN: 0022-1767
CID: 9843

Combined preoperative and postoperative radiation for bladder cancer. Results of RTOG/Jefferson Study

Mohiuddin, M; Kramer, S; Newall, J; Parsons, J; Wiley, A; Strong, G; Mulholland, S G
Ninety-two patients with bladder cancer have been treated with combined pre- and postoperative radiation in a Radiation Oncology Study Group (RTOG) Phase I-II study and at Thomas Jefferson University Hospital. Patients with invasive bladder cancer were entered into the study and given low-dose preoperative radiation (500 rad) to the whole pelvis, either on the day of or the day before cystectomy. Following surgery, patients were pathologically staged. Patients with stage B1 (T2) (grade 3 or 4), stage B2 and C (T3) tumors were given 4500 rad in 5 weeks postoperative radiation. Follow-up in the study ranges from a minimum of 24 months to 5 years, with a median of 36 months. Incidence of complications was 15% (14/92). The 4-year actuarial survival (Kaplan-Meier) by stage of disease is 68% for stage B1 (T2) (grade 3 or 4), 78% for stage B2, and 57% for stage C. These survival results appear to be better than those obtained with other approaches of adjuvant therapy and/or surgery in comparable histopathologically staged patients
PMID: 3967204
ISSN: 0008-543x
CID: 125864


Kramer, SB; Hirschhorn, R
ISSN: 0009-9279
CID: 30922

Salmonella bacteremia in systemic lupus erythematosus. Eight-year experience at a municipal hospital

Abramson, S; Kramer, S B; Radin, A; Holzman, R
Non-endemic Salmonella bacteremia tends to occur in patients with chronic disease. We reviewed all cases of Salmonella infection documented in adults at Bellevue Hospital during the years 1975-1982. Unexpectedly, the most frequent underlying disease found among bacteremic patients was systemic lupus erythematosus (SLE). Patients with SLE accounted for 6 of 30 Salmonella bacteremias as compared with 13 of 2,388 non-Salmonella gram-negative bacteremias. Salmonella was the single most frequent gram-negative isolate from the blood of SLE patients. All lupus patients with Salmonella infection were bacteremic. In contrast, isolates from blood represented only 23% of all Salmonella infections documented in the non-lupus population. Presentation was characterized by fever (greater than 103 degrees F) and abdominal pain. Four of the 6 patients were hypocomplementemic. All were receiving immunosuppressive therapy. We conclude that SLE patients in a municipal hospital setting are at increased risk for Salmonella sepsis. This should be considered when empiric antibiotic therapy is initiated.
PMID: 3881103
ISSN: 0004-3591
CID: 691762

Adenosine modulates the generation of superoxide anion by stimulated human neutrophils via interaction with a specific cell surface receptor

Cronstein BN; Kramer SB; Rosenstein ED; Weissmann G; Hirschhorn R
PMID: 3000259
ISSN: 0077-8923
CID: 9844

Adenosine deaminase is not required for the generation of superoxide anion

Cronstein BN; Kramer SB; Weissmann G; Hirschhorn R
Neutrophils and macrophages generate superoxide anion during the respiratory burst in response to various stimuli, including microorganisms. It has recently been proposed that an important source of superoxide anion during the respiratory burst that stimulates murine macrophages is the sequential metabolism of adenosine via adenosine deaminase and xanthine oxidase to uric acid. Thus, the immunodeficiency state associated with adenosine deaminase deficiency may be caused at least in part by a defect in superoxide anion generation. The ability to generate superoxide anion of stimulated neutrophils isolated from three children with adenosine deaminase deficiency and associated severe combined immunodeficiency was tested. Neutrophils from all three patients were able to generate superoxide anion. One of these generated 19.1 nmol cytochrome c reduced/10(6) cells (normals = 5.3-33.0, mean 18.4 +/- 7.1) while the other two generated low normal levels. Neutrophils from all three children also generated more superoxide anion after addition of exogenous adenosine deaminase. Thus, no evidence to support a role for cellular adenosine deaminase in the release of superoxide anion by stimulated neutrophils was found. Although neutrophils from patients deficient in adenosine deaminase appear to have no inherent defect in the generation of superoxide anion, the abnormally high concentrations of adenosine found in the plasma of these patients could, in vivo, secondarily, inhibit superoxide anion release.
PMID: 6321074
ISSN: 0090-1229
CID: 9845


ISSN: 0009-9279
CID: 40980

Systemic lupus erythematosus in a patient with Reiter's syndrome [Case Report]

Aisen PS; Cronstein BN; Kramer SB
PMID: 6639698
ISSN: 0004-3591
CID: 9846