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S Conley

Publications and source records attributed to S Conley.

12 recordsLinked to original sources
PubMed1991

The inability of human immunodeficiency virus to infect chimpanzee monocytes can be overcome by serial viral passage in vivo.

Studies of lentivirus infection in ruminants, nonhuman primates, and humans suggest that virus infection of macrophages plays a central role in the disease process. To investigate whether human immunodeficiency virus type 1 (HIV-1) can infect chimpanzee macrophages, we recovered monocytes from peripheral blood mononuclear cells of HIV-1-negative animals and inoculated these and control human monocytes with a panel of four human-passaged monocytotropic virus strains and one chimpanzee-passaged isolate. HIV-1 infected human monocytes synthesized proviral DNA, viral mRNA, p24 antigen, and progeny virions. In contrast, except for the chimpanzee-passaged HIV-1 isolate, chimpanzee monocytes failed to support HIV-1 replication when cultured under both identical and a variety of other conditions. Proviral DNA was demonstrated only at background levels in these cell cultures by polymerase chain reaction for gag- and env-related sequences. Interestingly, the chimpanzee-passaged HIV-1 isolate did not replicate in human monocytes; viral p24 antigens and progeny virions were not detected. The same monocytotropic panel of HIV-1 strains replicated in both human and chimpanzee CD4+ T lymphoblasts treated with phytohemagglutinin and interleukin-2. The failure of HIV-1 to infect chimpanzee monocytes, which can be overcome by serial in vivo viral passage, occurs through a block early in the viral life cycle.

Animals↗
PubMed1991

Decrease in cytokine production by HIV-infected macrophages in response to LPS-mediated activation.

The capacity of human monocytes/macrophages (M/M) infected with a human immunodeficiency virus-1 (HIV-1) isolate to produce several immunomodulating cytokines including interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage chemoattractant and activating factor (MCAF) was examined. Although HIV infection itself induced significant increases in the level of mRNAs for IL-1 beta, TNF-alpha, IL-6, and IL-8, the levels of lipopolysaccharide (LPS)-induced mRNAs for IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, IL-8, and MCAF were decreased over those of uninfected LPS-stimulated cells. In addition, HIV-infected M/M produced lower amounts of IL-8 protein, as measured by radioimmunoassay over an 18-day culture period. These results suggest that HIV infection generally suppresses the LPS-inducible cytokine production in human M/M. The impact of the role of these cytokines in the immunity and pathogenesis of HIV-1 infection is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study.

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1-5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6-12 and 12-17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.

Adolescent↗
PubMed1990

Antibody-mediated in vitro neutralization of human immunodeficiency virus type 1 abolishes infectivity for chimpanzees.

This study was undertaken to establish whether antibody directed against the human immunodeficiency virus type 1 (HIV-1) principal gp120 type-specific neutralization determinant can abolish the infectivity of HIV-1 in chimpanzees. Challenge inocula of the IIIb virus isolate were mixed in vitro with either immunoglobulin G (IgG) from an uninfected chimpanzee, nonneutralizing IgG from an HIV-seropositive human, a virus-neutralizing murine monoclonal antibody directed against the HIV-1 IIIb isolate, or virus-neutralizing IgG from a chimpanzee infected with the IIIb isolate. Both neutralizing antibodies were directed against the principal neutralization determinant of the challenge isolate. Establishment of infection following inoculation of each virus-antibody mixture into chimpanzees was assessed by virus-specific antibody development and by virus isolation. No protective effect was noted either with the control IgG or with the nonneutralizing anti-HIV IgG. By contrast, the polyclonal chimpanzee virus-neutralizing IgG prevented HIV-1 in vivo infection, while the neutralizing monoclonal antibody notably decreased the infectivity of the challenge virus. Hence, antibody to the gp120 principal neutralization determinant is able both to prevent HIV-1 infection in vitro and to inhibit infection in vivo.

Animals↗
PubMed1990

Evaluation of neonatal subglottic stenosis: a 3-year prospective study.

Subglottic stenosis is the most common cause of chronic airway obstruction. It results in prolonged tracheal cannulation of infants and children. Following the widespread adoption over the past 20 years of prolonged intubation for respiratory support in neonates, the incidence of acquired subglottic stenosis increased dramatically. On January 1, 1987, we began a 3-year prospective study to delineate potential etiologic factors involved in the development of subglottic stenosis in neonates. The present study analyzes data from 289 infants. Relationships between birth weight, gestational age, endotracheal tube size, duration of intubation and ventilation, number and difficulty of intubations, and the subsequent need for medical and surgical therapy are discussed. Whole organ larynges from autopsy specimens provide histological correlation.

Apgar Score↗
PubMed1989

Peripheral T-cell lymphoma.

Peripheral T-cell lymphoma is the most common type of T-cell lymphoma seen in adults in the United States. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 years), 59% were male, and 36 patients (27%) had a history of a preceding disorder of the immune system. The tumors were grouped histologically into large cell (43%), mixed large and small cell (40%), and small cell (17%). The stage at diagnosis was I (7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkin's lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (nine patients), or no treatment (nine patients). Fifty percent of the intensively treated patients achieved complete remission and the actuarial 4-year survival was 45%. However, the 4-year, disease-free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterparts, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook.

Adolescent↗
PubMed1988

Ranulas--mucoceles of the oral cavity: experience in 26 children.

Ranulas or mucoceles of the floor of the mouth are uncommon but do occur in approximately 5% of patients undergoing submandibular duct relocation for the management of uncontrollable sialorrhea. Review of our experience with 26 patients over 12 years ending in 1986 substantiated a concept previously advocated by other authors that ranulas are usually extravasation pseudocysts developing after disruption of sublingual gland elements, and that excision of the ipsilateral sublingual gland is the management approach of choice.

Child↗
PubMed1987

Parent-to-child transplantation with cyclosporine immunosuppression.

The use of cyclosporine, a fungal endecapeptide immunosuppressive agent, has greatly improved the outcome of haploidentical transplantation in adults, but less impressively improved the result of parent to child transplantation. The incidence of allograft loss and treated rejection episodes was much greater in pediatric than in adult recipients, and the evidences of nephrotoxicity lessened. Although resistance of the child's immune system to the effects of the drug cannot be excluded, it appears more likely that this relates to the rapid clearance of the agent in the pediatric age group (39.6 mL/min/kg) versus in adults (12.3 mL/min/kg), thereby reducing the area under the serum concentration curve from 765 +/- 593 to 386 +/- 277 ng/mL/hr per mg/kg (mean +/- SD). This effect caused trough serum levels measured by radioimmunoassay to be below the putative threshold. These findings demonstrate the need for higher cyclosporine doses and frequency in pediatric compared with adult patients.

Adolescent↗
PubMed1987

Complications of cyclosporine-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center for from one to five years.

The therapeutic efficacy of cyclosporine (CsA) as an immunosuppressive agent was complemented by a modest, long-term incidence of toxic complications in 402 renal allograft recipients engrafted one to five years prior to analysis. The overall patient and graft survivals at one year were 97% and 84% (actual), and at five years 92% and 67% (actuarial). The immunosuppressive therapeutic index was excellent: only 12% of allografts were lost from rejection, with 5% of patients succumbing to infection. While infections were common, tending to emanate in the urinary tract or to be viral in etiology, they were generally mild and readily controlled. Only four patients displayed malignancies; none succumbed to this cause. The most common toxic complication was hypertrichosis, which was accentuated in pediatric patients. While tremors occurred in 20% of patients, primarily during the first three months, other neuroectodermal complications of parethesias, depression, somnolence, and seizures were rare. Hepatotoxicity, which was noted in 50% of patients, particularly recipients of cadaveric grafts, generally was first seen as a transaminase elevation, at least partially reversible by dose-reduction and abating by the third year. Associated disturbances of cholelithiasis and pancreatitis were occasionally observed. Nephrotoxicity was the only persistent, long-term complication. Hypertension occurred in 72% of patients during the first month, 36% in the second year, and about 15% thereafter. Hyperuricemia, which occurred in about 30% of recipients during the first two years, was occasionally associated with symptomatic gout. The mean serum creatinine level remained elevated throughout the follow-up period at 1.8-1.9 mg/dl, suggesting persistent, but nonprogressive, drug-induced renal injury. The present analysis documents the relative safety of CsA for long-term therapy, and highlights the need for new approaches to ameliorate drug-induced nephrotoxicity.

Adolescent↗
PubMed1987

Myelopathy in neonatal and infantile lupus erythematosus.

Two children with lupus erythematosus and myelopathy were studied. The first child developed the neonatal lupus erythematosus syndrome associated with transplacentally acquired anti-Ro/SSA antibodies. The cutaneous manifestations of neonatal lupus erythematosus disappeared but a residual myelopathy was confirmed at 16 months of age. The second child developed cutaneous lupus erythematosus at 3 months of age associated with a total deficiency of the Clr component of complement. A myelopathy and mesangial glomerulonephritis developed at 2 years of age which required treatment with corticosteroids. These two children with CNS lupus erythematosus, one associated with transplacentally acquired antibodies and the other associated with a complement deficiency, may suggest an immune-mediated mechanism for the pathogenesis of myelopathy in childhood lupus erythematosus.

Antibodies, Antinuclear↗