PubMed Health⌕ Search

Biomedical subjects

S Jacobson

Publications and source records attributed to S Jacobson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Refractory priapism of unknown etiology in a pediatric patient.

Priapism is a urologic emergency that can occur in any age group and every patient should receive prompt urologic consultation. Management of priapism is based on the recognition of underlying pathophysiology; ready differentiation between high-flow and low-flow priapism; reversal of any potential precipitating factors; the use of corporal aspiration irrigation combined with intracavernosal alpha adrenergic therapy; and when necessary, a shunting procedure. Delay in recognition or treatment can be crucial as the incidence of long-term complication rises substantially with the duration of the priapism.

Adolescent↗
PubMed2000

Characterization and sequencing of prototypic human T-lymphotropic virus type 1 (HTLV-1) from an HTLV-1/2 seroindeterminate patient.

Serological screening for human T-lymphotropic virus type 1 (HTLV-1) parallels the standard screening process for human immunodeficiency virus (HIV), in which samples found positive by enzyme-linked immunosorbent assay (ELISA) are confirmed with a modified Western blot procedure. There are a significant number of cases in which HTLV-1/2 ELISA-positive specimens demonstrate an incomplete banding pattern on this Western blot. Individuals providing these atypical antibody responses are categorized as seroindeterminate for HTLV-1/2. Although HTLV-1 genomic sequences are readily detectable in the peripheral blood lymphocytes (PBL) of seropositive individuals, previous studies have repeatedly demonstrated that PBL from the vast majority of HTLV-1/2 seroindeterminate individuals are PCR negative for HTLV-1. As a result, identification of the agent responsible for this indeterminate reactivity has been of interest. We have generated an HTLV-1-positive B-cell line (SI-1 B) from one of these seroindeterminate individuals. Previous screening for HTLV-1 in PBL from this patient had been routinely negative by primary PCR; however, HTLV-1 tax had been periodically detected by nested PCR. DNA sequence data generated with genomic DNA from the SI-1 B cell line and HTLV-1-specific primers demonstrated the presence of a full-length viral genome with >97% homology to the Cosmopolitan form of HTLV-1. A 12-bp deletion was identified in the 3'-gag/5'-prot region, which would predict translation of altered or nonfunctional proteins from these genes. We propose that this HTLV-1/2-seroindeterminate patient is infected with a prototypic form of HTLV-1 at an extremely low viral load and that this finding may explain HTLV-1/2 seroindeterminate reactivity in at least a subset of these individuals.

Antibodies, Viral↗
PubMed2000

EEG in delirium.

Electroencephalography (EEG) is an inexpensive and noninvasive probe of functional brain activity that is one of the few clinically accessible measures capable of detecting changes in delirium. In EEG characteristics of delirium include slowing or dropout of the posterior dominant rhythm, generalized theta or delta slow-wave activity, poor organization of the background rhythm, and loss of reactivity of the EEG to eye opening and closing. These are paralleled by the quantitative EEG (QEEG) findings of increased absolute and relative slow-wave (theta and delta) power, reduced ratio of fast-to-slow band power, reduced mean frequency, and reduced occipital peak frequency. In alcohol and sedative withdrawal, EEG findings may include attenuation of voltage and prominence of beta activity. Specificity of EEG and QEEG findings in delirium has been questioned, particularly vis-'a-vis EEG changes in normal aging and in dementia. As noted in the text, however, specificity can be increased by the use of careful data acquisition and skillful interpretation. In the future, it is expected that QEEG methods will largely replace EEG in application to delirium.

Brain↗
PubMed2000

Increased lymphoproliferative response to human herpesvirus type 6A variant in multiple sclerosis patients.

Several reports have suggested an association of human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) based on immunohistochemical demonstration of HHV-6 antigens in inflammatory lesions, detection of increased HHV-6 specific serum antibody titers, and amplification of HHV-6 DNA from sera and cerebrospinal fluid of MS patients but not in controls. Characterization of the cellular immune response of MS patients to HHV-6 may further clarify the role of HHV-6 in MS and provide insight into the pathogenesis of this immune-mediated disease. We have compared lymphoproliferative responses to HHV-6A (U1102)-, HHV-6B (Z29)-, and HHV-7 (H7SB)-infected cell lysates in healthy controls and patients with MS. Most healthy controls (71%) proliferated to HHV-6B lysate, and fewer (33%) responded to the HHV-6A lysate. In contrast, 67% of MS patients had a lymphoproliferative response to HHV-6A, which is a significant increase in comparison with healthy controls. A similar frequency of lymphoproliferative response (78%) to HHV-6B was demonstrated in MS patients. Lymphoproliferation to HHV-7 lysate was demonstrated in 23% of healthy controls and 28% of MS patients. These results indicate that the lymphoproliferative response to the HHV-6A variant, which was recently reported to have greater neurotropism, is increased in MS patients.

Adult↗
PubMed2000

Extended observations on the association of HHV-6 and multiple sclerosis.

Throughout the years, a long list of viruses has been associated with multiple sclerosis (MS), however no virus to date has been definitively identified as the etiologic agent of this disease. Recently, human herpesvirus 6 (HHV-6), a newly described herpesvirus, has been suggested to play a role in MS based on: immunohistochemical demonstration of HHV-6 in MS plaques, increased antibodies response to HHV-6 in sera and CSF of MS patients, and the demonstration of HHV-6 DNA in the serum of MS patients but not in normal individuals. To extend these observations we have focused our research in multiple directions. We have increased the number of MS patients tested for HHV-6 serum DNA providing confirmation of our previous study. Additionally we have investigated a possible correlation between HHV-6 viremia and clinical activity. Finally to provide insight into the pathogenesis of this disease, we have begun to characterize the cellular immune response of MS patients to HHV-6. Collectively these studies will help to define the role that HHV-6 may play in the pathogenesis of MS.

Herpesviridae Infections↗
PubMed2000

Trauma in cirrhotics: survival and hospital sequelae in patients requiring abdominal exploration.

Hepatic cirrhosis significantly increases the mortality and morbidity of elective surgery; therefore we hypothesized that cirrhosis would adversely impact outcome after abdominal trauma. We used the trauma registry to identify 17 patients with cirrhosis who sustained trauma injuries requiring emergent exploratory laparotomy. Patients were characterized with respect to age, sex, hospital days, intensive care unit days, and trauma scores. A control group (n = 73) was constructed from the registry by matching age, sex, Injury Severity Score (ISS) and Abbreviated Injury score. Mortality rates were compared by Fisher's exact test and age, ISS, Revised Trauma Score 2, and hospital and intensive care unit days were compared by Student's t test. Despite similar ISS between cirrhotic patients and controls, patients with cirrhosis had a fourfold increase in mortality (mortality odds ratio = 7.2; 95% confidence interval = 2.2-24.0). Cirrhotic trauma patients had a complication rate of 71 per cent and a mortality of 44 per cent. We conclude that cirrhosis is a major independent risk factor for mortality in trauma patients with injuries that require emergent abdominal surgery.

APACHE↗
PubMed1999

Involvement of IL-15 in the pathogenesis of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis: implications for therapy with a monoclonal antibody directed to the IL-2/15R beta receptor.

Human T lymphotropic virus type I (HTLV-I) is the causative agent of an inflammatory neurological disease termed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). An ongoing lymphocyte activation exists in patients with HAM/TSP, which was demonstrated by the spontaneous proliferation of their PBMC ex vivo. It was shown that spontaneous proliferation present in HAM/TSP is due, in part, to an IL-2/IL-2R autocrine loop. However, addition of Abs against IL-2 or IL-2R alpha only partially inhibited the spontaneous proliferation. Since IL-15 is a cytokine with similar functional characteristics to those of IL-2, we reasoned that IL-15 might be an additional growth factor that contributes to the spontaneous proliferation observed in HAM/TSP. In this study, we demonstrated that IL-15 mRNA expression was elevated in PBMC obtained from HAM/TSP patients when compared with those of the normal donors. Furthermore, we showed that the addition of blocking Abs against IL-15 or its receptor inhibited the spontaneous proliferation of HAM/TSP PBMC. Addition of Abs directed toward both IL-15 and IL-2, or their receptors, inhibited the proliferation almost completely. These data suggest the existence of two autocrine loops involving IL-15/IL-15R and IL-2/IL-2R, both contributing to the spontaneous proliferation of HAM/TSP PBMC.

Antibodies, Monoclonal↗
PubMed1999

Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy.

Human T cell lymphotropic virus-I (HTLV-I)-associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetramers loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR Vbeta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.

Adult↗
PubMed1999

Reduced anterior tibial translation associated with adaptive changes in the anterior cruciate ligament-deficient joint: goat model.

Adaptive changes in the menisci and adjacent posterior capsule were documented within anterior cruciate ligament-deficient knee (stifle) joints in the goat model. These physical changes in the menisci and capsule developed over time and were associated with reduction in the initial (time zero) abnormal anterior tibial translation following transection of the anterior cruciate ligament. At 50 N of applied force, the normal goat knee joint has a total anterior-posterior translation of 0.6+/-0.1 mm (+/- SEM) at 45 degrees of flexion and 0.3+/-0.1 mm at 90 degrees. The translation immediately after transection (time zero) with 50 N of force was 8.2+/-0.5 mm at 45 degrees and 4.9+/-0.9 mm at 90 degrees. Within 8 months after transection and at 50 N of force, the treated knees had reduced translation values of 5.3+/-0.6 mm at 45 degrees of flexion and 2.9+/-0.5 mm at 90 degrees, or 35 (p<0.001) and 40% reductions, respectively, compared with the values at time zero. Magnetic resonance images of the ligament-deficient stifle joints, as well as gross measurements and image analysis after dissection, consistently demonstrated increases in cross-sectional area and volume of the menisci compared with the contralateral controls. These secondary changes were most pronounced in the posterior portion of the medial menisci, and histologic evaluation demonstrated hypercellularity with the accumulation of poorly organized collagen, reduced safranin O staining (proteoglycan matrix synthesis), a thickened capsule and capsule attachment, and increased vascularity at the meniscal capsule interface.

Adaptation, Physiological↗
PubMed1999

Modifying chromatin and concepts of cancer.

A wave of biochemical and genetic progress has identified proteins that influence transcription by modifying chromatin. Many such factors are broadly conserved and, strikingly, occur in human diseases as partners in chromosomal translocations. Understanding the function of these factors will be key to defining mechanisms of transcriptional regulation and understanding cancers linked to aberrant chromatin modification.

Acetyltransferases↗
PubMed1999

HTLV-I/II seroindeterminate Western blot reactivity in a cohort of patients with neurological disease.

The human T-cell lymphotropic virus type I (HTLV-I) is associated with a chronic, progressive neurological disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis. Screening for HTLV-I involves the detection of virus-specific serum antibodies by EIA and confirmation by Western blot. HTLV-I/II seroindeterminate Western blot patterns have been described worldwide. However, the significance of this blot pattern is unclear. We identified 8 patients with neurological disease and an HTLV-I/II seroindeterminate Western blot pattern, none of whom demonstrated increased spontaneous proliferation and HTLV-I-specific cytotoxic T lymphocyte activity. However, HTLV-I tax sequence was amplified from the peripheral blood lymphocytes of 4 of them. These data suggest that patients with chronic progressive neurological disease and HTLV-I/II Western blot seroindeterminate reactivity may harbor either defective HTLV-I, novel retrovirus with partial homology to HTLV-I, or HTLV-I in low copy number.

Adult↗
PubMed1999

Chemokines in chronic progressive neurological diseases: HTLV-1 associated myelopathy and multiple sclerosis.

It is hypothesized that in MS and HTLV-1, chemokine and chemokine receptor expression are important mechanisms by which T cells migrate to sites of inflammation. Preliminary evidence supports the roles of several chemokines, including MIP 1beta, in mediating the enhanced migration capacity of MS derived PBLs. In addition, the ligand CCR-5 seems to be up regulated on PBLs from some MS patients. Analysis of T cell clones does not reveal a definite correlation between cytokine phenotype and chemokine receptor profile. The chemokines and chemokine receptor family are likely to be important molecules in chronic progressive neurological diseases, in which immune cells invade the central nervous system.

Autoimmune Diseases↗
PubMed1998

The effect of human beta2-microglobulin on major histocompatibility complex I peptide loading and the engineering of a high affinity variant. Implications for peptide-based vaccines.

The ability to directly load cell surface major histocompatibility complex (MHC) class I molecules with peptides provides a potentially powerful approach toward the development of vaccines to generate cell-mediated immunity. We demonstrate that exogenous beta2-microglobulin (beta2m) stabilizes human cell surface MHC I molecules and facilitates their loading with exogenous peptides. Additionally, using three-dimensional crystal structures and known interaction sites between MHC I heavy chains and beta2m, we engineered variants of human beta2m (hbeta2m) with a single serine substitution at residue 55. This alteration was predicted to promote hydrophobic interactions at the MHC I heavy chain/beta2m interface and displace an ordered water molecule. Compared with hbeta2m, the serine to valine substitution at residue 55 had improved ability to bind to cell surface HLA-A1, HLA-A2, and HLA-A3 molecules, facilitate exogenous peptide loading, and promote recognition by peptide-specific T cells. The inclusion of hbeta2m or higher affinity variants when pulsing cells with MHC-restricted peptides increases the efficiency of peptide loading 50-80-fold. Therefore, the inclusion of hbeta2m in peptide-based vaccines may increase cell surface antigen densities above thresholds that allow recognition of peptide antigens by the immune system, particularly for cryptic, subdominant, or marginally antigenic peptides.

Antigen Presentation↗
PubMed1998

A comparison of nebulized budesonide, intramuscular dexamethasone, and placebo for moderately severe croup.

BACKGROUND: In children with croup, treatment with nebulized budesonide decreases symptoms, but it is uncertain how budesonide compares with dexamethasone, the conventional therapy for croup, and whether either reduces the rate of hospitalization. METHODS: We performed a double-blind, randomized trial involving 144 children with moderately severe croup. The children were treated with racepinephrine and a single dose of 4 mg of nebulized budesonide (48 children), 0.6 mg of intramuscular dexamethasone per kilogram of body weight (47 children), or placebo (49 children). The children were assessed before treatment and then hourly for five hours after treatment. Physicians who were unaware of the treatment assignments determined the children's need for further treatment and hospitalization. RESULTS: The characteristics of the groups were similar at base line, including the types of viruses identified, the types of croup, and the clinical severity of the illness. The overall rates of hospitalization were 71 percent in the placebo group (35 of 49 children), 38 percent in the budesonide group (18 of 48 children), and 23 percent in the dexamethasone group (11 of 47 children) (unadjusted P=0.001 for the comparison of budesonide with placebo, P<0.001 for the comparison of dexamethasone with placebo, and P=0.18 for the comparison of budesonide with dexamethasone). Children treated with budesonide or dexamethasone had a greater improvement in croup scores than those given placebo (P=0.03 and P<0.001, respectively), and those treated with dexamethasone had a greater improvement than those treated with budesonide (P=0.003). CONCLUSIONS: In children with moderately severe croup, treatment with intramuscular dexamethasone or nebulized budesonide resulted in more rapid clinical improvement than did the administration of placebo, with dexamethasone offering the greatest improvement. Treatment with either glucocorticoid resulted in fewer hospitalizations.

Administration, Inhalation↗
PubMed1998

Demonstration of human T lymphotropic virus type I (HTLV-I) tax-specific CD8+ lymphocytes directly in peripheral blood of HTLV-I-associated myelopathy/tropical spastic paraparesis patients by intracellular cytokine detection.

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurologic disease caused by HTLV-I infection and has been associated with elevated levels of several proinflammatory cytokines in both serum and cerebrospinal fluid. It is unknown what kind of cells secrete these cytokines and if HTLV-I Ags are associated with this phenomenon. Here, we investigated the expression of cytokines in PBL from eight HAM/TSP patients, nine HTLV-I-infected asymptomatic carriers, and seven healthy controls by flow cytometry combined with intracellular cytokine staining. PBL were cultured with brefeldin A without mitogen and IL-2 for 14 h. Under these conditions, CD8+ cells produced proinflammatory cytokines including IFN-gamma, TNF-alpha, and IL-2, which were significantly elevated in HAM/TSP patients. The proportion of CD8+ cells producing IFN-gamma in HAM/TSP patients, asymptomatic carriers, and healthy controls were, on average, 4.9, 0.4, and 0.3%, respectively. IFN-gamma production by these CD8+ cells was suppressed by anti-HLA-class I Ab. Purified CD8+ cells from an HLA-A2 HAM/TSP patient produced IFN-gamma by cocultivation with autologous CD4 cells, the main reservoir of HTLV-I in vivo, or allogenic HLA-A2+ B cells pulsed with a known immunodominant HTLV-I tax peptide. These data suggest that high levels of circulating HTLV-I-specific CD8+ T lymphocytes have the potential to produce proinflammatory cytokines and may promote inflammatory responses to HTLV-I in HAM/TSP patients.

CD8-Positive T-Lymphocytes↗
PubMed1998

Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19- specific CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients.

Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic paraparesis is a demyelinating inflammatory neurologic disease associated with HTLV-1 infection. HTLV-1 Tax11-19-specific cytotoxic T cells have been isolated from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2-Ig complex to directly visualize HTLV-1 Tax11-19-specific T cells from peripheral blood and cerebrospinal fluid without in vitro stimulation. Five of six HTLV-1-associated myelopathy/tropic spastic paraparesis patients carried a significant number (up to 13.87%) of CD8(+) lymphocytes specific for the HTLV-1 Tax11-19 peptide in their peripheral blood, which were not found in healthy controls. Simultaneous comparison of peripheral blood and cerebrospinal fluid from one patient revealed 2.5-fold more Tax11-19-specific T cells in the cerebrospinal fluid (23.7% vs. 9.4% in peripheral blood lymphocyte). Tax11-19-specific T cells were seen consistently over a 9-yr time course in one patient as far as 19 yrs after the onset of clinical symptoms. Further analysis of HTLV-1 Tax11-19-specific CD8(+) T lymphocytes in HAM/TSP patients showed different expression patterns of activation markers, intracellular TNF-alpha and gamma-interferon depending on the severity of the disease. Thus, visualization of antigen-specific T cells demonstrates that HTLV-1 Tax11-19-specific CD8(+) T cells are activated, persist during the chronic phase of the disease, and accumulate in cerebrospinal fluid, showing their pivotal role in the pathogenesis of this neurologic disease.

Flow Cytometry↗