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J L Bussiere

Publications and source records attributed to J L Bussiere.

At least 19 recordsLinked to original sources
PubMed2003

Animal models as indicators of immunogenicity of therapeutic proteins in humans.

Animal models have not been able to predict the immunogenicity of therapeutic proteins in humans reliably. The main issue is that administration of a human protein in an animal species is likely to be immunogenic. In non-human primate studies, we have seen a variety of responses; from little to no antibody response, to a strong neutralizing response, or even a cross-reactive antibody response. These have generally not correlated well with the immune response seen in humans. The route of administration, duration and schedule of dosing, the cumulative dosage of the protein, the pharmacological (i.e., immune altering) properties of the protein, as well as the purity of the clinical material can influence the immunogenicity. The animal studies should mimic these factors to the best extent possible for the animal model to be at all relevant to humans. Models do exist which provide valuable information to compare the immunogenicity of various compounds or routes of administration. Presumably, this 'relative' immunogenicity would be similar in humans. Additional characterization of transgenic mice, or use of homologous proteins, may help to establish better models to predict immunogenicity.

Animals↗
PubMed1999

Lack of developmental neurotoxicity of MN rgp 120/HIV-1 administered subcutaneously to neonatal rats.

The potential for neurotoxic effects was evaluated in rat off-spring after exposure in utero and/or during the neonatal period to a recombinant subunit vaccine of gp120 prepared from the MN strain of HIV-1 (MN rgp 120/HIV-1). Thirty pregnant female rats were given MN rgp120/HIV-1 with alum adjuvant, and 30 rats were given vehicle, once every 3 days from Day 1 of presumed gestation until parturition. One pup/sex/litter from treated and control group dams were given a daily subcutaneous injection, from Day 1 through Day 22 postpartum (PP) of vehicle, MN rgp120/HIV-1, MN rgp120/HIV-1 with alum, or MN rgp120/HIV-1 with QS-21 adjuvant. Neurobehavioral and physical development were evaluated (preweaning reflex and development, sexual maturation, motor activity, acoustic startle, passive avoidance, functional observational battery, and water M-maze testing), and tissues were processed for anatomical examination (whole and regional brain weights, and neuropathology). Administration of MN rgp120/HIV-1, with or without adjuvant, to pups did not cause any persistent effect on any parameter evaluated. Neurohistological examination did not reveal any pathological effects related to treatment. Thus, MN rgp120/HIV-1 alone or formulated as a vaccine does not cause neurotoxicity or developmental toxicity in neonatal rats after exposure in utero and/or during the neonatal period.

AIDS Vaccines↗
PubMed1997

Vasculitis confined to the calves. Report of a case.

Polyarteritis nodosa is a systemic disease of which limited forms have been reported, with the most common involving the skin. Only 13 cases with lesions confined to the calves have been reported to date. We report a new case.

Female↗
PubMed1996

Subchondral insufficiency fracture of the femoral head.

We report two cases of subchondral insufficiency fractures of the femoral head. Clinical manifestations of this lesion are nonspecific. Radionuclide bone scanning demonstrates early hyperactivity. Initial roentgenograms are usually normal. Magnetic resonance imaging establishes the diagnosis and rules out other conditions.

Aged↗
PubMed1995

Atrial septal aneurysm. Morphological characteristics in a large population: pathological associations. A French multicenter study on 259 patients investigated by transoesophageal echocardiography.

UNLABELLED: A strong association between interatrial septal aneurysm (IASA) and stroke has recently led many authors to consider IASA as a potential cardiac source of embolism. We studied the morphological characteristics and main associations of IASA in a large cooperative study based on transoesophageal echocardiographic examinations; 259 IASA were studied in 134 men and 125 women with a mean age of 59 +/- 15 years. Fifty-five percent of IASA were found to overlap the commonly described fossa ovalis region. IASA protruded into the right atrium in 90% of the cases. They appeared thin in 81% of the patients and highly mobile in 79%. Fifty-eight percent of patients had a history of systemic embolic events, while an atrial septal shunt was detected in 61% of the patients. In patients with an embolic event, only the mobility of IASA was significantly higher than in those with no embolic event. In nine cases a pulmonary embolism was associated with arterial embolism. Furthermore, we reported three cases of paradoxical embolism. However, the true demonstration of a thrombus within the IASA was quite rare. CONCLUSION: IASA is probably an important risk factor for stroke. In patients with IASA and a history of embolic events, IASA may enhance migration of a thrombus constituted in situ or transiting through it. Marked mobility of IASA may also increase the risk of peripheral embolus.

Adult↗
PubMed1995

Cervical epidural infection. Four case-reports.

The authors report four cases of cervical epidural infection, in two females (aged 58 and 82 years) and two males (aged 41 and 51 years). Risk factors were noninsulindependent diabetes mellitus in one patient and multiple myeloma treated by chemotherapy in another. Duration of cervical pain at evaluation was five to 15 days. Three patients had a fever and a neurologic deficit: one had brachial diplegia; the myeloma patient developed brachial diplegia after a lumbar puncture and the diabetic patient developed quadriplegia with respiratory disorders also after a lumbar puncture. Cerebrospinal fluid studies showed elevated protein levels with approximately 20 cells per mm3 and no pathogens in smears or cultures. Roentgenograms were normal at admission. The diagnosis was established by myelography (n = 2) and/or computed tomography (n = 2) and/or magnetic resonance imaging (n = 2). The infected area was anterior in three cases and posterolateral in one. Two to seven vertebral levels were affected. A Staphylococcus aureus was recovered from the blood cultures in all four cases and from a local specimen in one of the two patients who had a laminectomy. Of the two patients who did not have surgery, one had a normal neurologic evaluation and the other was an elderly patient with myeloma. In both, antimicrobial and corticosteroid therapy ensured complete resolution of the infection, and the myeloma patient recovered normal neurologic function. Residual neurologic loss was seen in one of the two surgically-treated patients. Two patients developed discitis.

Adult↗
PubMed1995

Aortic occlusion in a patient with antiphospholipid antibody syndrome in systemic lupus erythematosus.

A 41-year-old woman with systemic lupus erythematosus and lupus anticoagulant developed aortic thrombosis. The patient was receiving low dose aspirin. Aortography showed a complete obliteration of the infrarenal aorta. Computed tomography and magnetic resonance imaging showed no evidence of aortitis. The patient improved with medical treatment. Six other published cases are reviewed.

Adult↗
PubMed1993

Immunosuppressive effects of morphine on immune responses in mice.

Implantation of a 75-mg morphine sulfate pellet subcutaneously into mice of different strains and sexes caused profound immunosuppression of their spleen cell primary in vitro antibody responses to sheep red blood cells. No sex differences were observed. In mice of the C3H lineage, naltrexone blocked the immunosuppression. In mice in the C57BL/6J lineage, naltrexone was ineffective in blocking the effects of morphine and was itself suppressive. In beige C57BL/6J bgJ/bgJ mice, placebo pellets were also suppressive. The mechanism of the morphine-induced immunosuppression was investigated in C3HeB/FeJ mice. Addition of normal splenic macrophages to in vitro cultures restored immune responses, as did IL-1, IL-6 and IFN-gamma, suggesting that morphine-induced immunosuppression is due to a deficit in macrophage function. Morphine pellet implantation induced splenic atrophy. Whether suppression is attributable to decreased macrophage numbers or to decreased functional capacity of individual macrophages is currently under investigation.

Animals↗
PubMed1993

Morphine treatment in vitro or in vivo decreases phagocytic functions of murine macrophages.

Studies were performed to compare in vitro and in vivo effects of morphine on the phagocytic function of murine peritoneal macrophages. Macrophage monolayers were incubated with Candida albicans for 30 min in the absence of autologous serum. Morphine added in vitro was found to decrease both the phagocytic activity (percent of phagocytic cells) and the phagocytic index (average number of ingested yeasts per cell) in a concentration-dependent manner, with maximal effects of 26% and 41%, respectively, at 10(-6) M. When morphine was administered in vivo via an implanted 75-mg pellet, there was a 22% decrease in phagocytic activity and a 40% decrease in the phagocytic index. Naltrexone completely blocked the effects of morphine both in vitro and in vivo. The results suggest that morphine is capable of interacting directly with opioid receptors on macrophages, resulting in a decrease in phagocytic function.

Animals↗
PubMed1993

Effects of in vivo morphine treatment on antibody responses in C57BL/6 bgJ/bgJ (beige) mice.

C57BL/6J bgJ/bgJ (beige) mice are less sensitive than other strains to the analgesic effects of morphine, although they have normal numbers of mu receptors. In the present study, beige mice and their normal littermates (beige+) were treated in vivo with morphine or the opioid antagonist, naltrexone and their primary in vitro antibody responses were assessed. Morphine treatment caused splenic atrophy and suppressed the primary in vitro antibody response in beige and beige+ mice. However, these effects were not blocked by naltrexone co-treatment. In these mouse strains, naltrexone decreased spleen size and antibody responses by itself, which may mask its ability to antagonize morphine. In beige mice, placebo pellet implantation suppressed the primary in vitro antibody response. Morphine did not cause a further suppression of the antibody response in beige mice compared to placebo. Because of this anomalous response to placebo treatment, the immunosuppressive effects of morphine on the antibody response/10(7) cells can not be attributed to a specific drug effect in this strain. However, when antibody responses were expressed on a per spleen basis, the overall capacity to respond to antigenic challenge was suppressed by morphine treatment.

Animals↗
PubMed1993

Pyrogenic doses of intracerebroventricular interleukin-1 did not induce analgesia in the rat hot-plate or cold-water tail-flick tests.

There are a few reports in the literature that cytokines can induce analgesia (5, 6, 18). The present study sought to characterize the analgesic effects of intracerebroventricularly (icv) administered interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) in rats. In the cold-water tail-flick test (CWT), latency to tail withdrawal from a -3 degrees C liquid was timed; in the hot-plate test (HP), latency to a rear paw lick or a jump from a 55 degrees C surface was measured. In some experiments, core body temperature was also monitored with a rectal thermistor. In the CWT, human recombinant (hr) IFN-alpha induced a small, statistically significant effect at just one dose (15,000 U icv), but no dose of hr-IL-1 alpha (250-1000 U icv) or hr-IL-1 beta (125-2000 U icv) induced a significant effect at any time point. On the other hand, dose-related increases in body temperature were observed after icv injection of both IL-1 alpha and IL-1 beta. The largest hyperthermic effect was a 1.7 (+/- 0.15) degrees C rise 120 min after administration of 1000 U IL-1 beta. In a second analgesic assay, the HP, IL-1 beta was ineffective as well. Since IL-1 alone did not induce analgesia, we tested its capacity to potentiate morphine analgesia. Morphine (5.0 and 10 micrograms, icv) induced analgesia in the CWT (32.7 and 61.8% maximum analgesia, respectively); however, there was no significant effect of IL-1 beta on morphine-induced analgesia. In summary, we failed to find an analgesic effect of IL-1, alone or in combination with morphine, at doses which clearly had a physiological effect; this is in contrast to the reports cited above.

Analgesia↗
PubMed1993

Polyarticular septic arthritis.

Twenty-five cases of polyarticular septic arthritis (PASA) were observed in our department over a 13-year period. They accounted for 16.6% of all septic arthritis (15% on average in the literature). A male predominance was noted in our patients, as well as in the literature. The knee was the most frequent location followed by the elbow, shoulder, and hip, in varying order depending on the series. An average of 4 joints was involved. The causative microorganism was Staphylococcus aureus in 20/25 of our patients and in about 50% of published cases. Other frequently causative organisms were streptococci and gram-negative bacteria. Blood cultures and joint aspirations were positive in 19/22 and 23/25 of our cases, respectively. Other septic lesions were noted in 10/25 of our cases. Fever and severe leukocytosis were absent at admission in 5/25 (literature, 37%) and 10/25 of our 25 patients, respectively. The underlying disease was rheumatoid arthritis in 13/25, while 9 of the other patients had immunodepression caused by drugs or by concurrent illness. Typically, rheumatoid arthritis was long-standing and erosive, patients having ulcerated calluses on the feet. This skin source was also noted in 23/36 published cases of PASA in rheumatoid arthritis. Systemic lupus erythematosus was an uncommon disease in PASA, but its presence promoted gram-negative infection. Despite effective therapy with 2 antibiotics, 8/25 patients died, a prognosis that is equally severe in cases reported in the literature (30%) and one that has remained surprisingly stable over the last 40 years. For comparison, the death rate was only 4% in our patients with MASA. Factors contributing to a poor prognosis were age greater than 50 years, rheumatoid arthritis as an underlying disease, and disease of staphylococcal origin. Septic polyarthritis should be considered even when the clinical picture is not florid--when patients have low fever and normal white blood cell counts. Nor should the simultaneous involvement of distant joints rule out infection. Indeed, the frequency of underlying rheumatic disease and its treatment may further confuse the clinical presentation. Joints suspected of harboring infection should be aspirated, including those previously affected by the concurrent rheumatism.

Aged↗
PubMed1993

Suppression of peritoneal macrophage phagocytosis of Candida albicans by opioids.

Receptor-selective opioid agonists have been found to suppress the capacity of macrophages to ingest opsonized sheep erythrocytes. In an effort to characterize the immunomodulatory activity of opioids further, experiments were done to examine the uptake of Candida albicans by opioid-treated murine peritoneal macrophages. It was found that treatment with morphine and selective mu, i.e., DAMGO, delta, i.e., DPDPE, and kappa, i.e., trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzene-acetamide methanesulfonate, receptor agonists resulted a concentration-dependent suppression of both the percentage of phagocytic cells and the average number of ingested yeasts. Antagonists selective for mu, i.e., H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, delta, i.e., naltrindole, and kappa, i.e., norbinaltorphimine, opioid receptors completely blocked the respective receptor-selective agonist-induced suppression. These results suggest that the mu, delta and kappa opioid receptors can modulate macrophage function.

Amino Acid Sequence↗