Search PubMed⌕ Search

Biomedical subjects

S Jacobson

Publications and source records attributed to S Jacobson.

At least 145 records · Page 8Linked to original sources

Gd HP-DO3A--experimental evaluation in brain and renal MR.

GD HP-DO3A, a neutral (nonionic) IV MR contrast agent presently in clinical trials, was evaluated with respect to imaging characteristics in rats. Following administration of 0.25 mmol/kg I.V., 58 +/- 19%, i.e. (n = 6) enhancement was noted in a brain gliosarcoma model. Meningeal spread of neoplasia could be identified due to its enhancement (69 +/- 26%) in nine animals. The time course of renal enhancement was quantitated at two dosages, 0.05 (n = 4) and 0.25 mmol/kg (n = 8). At the higher dose, enhancement of both cortex and medulla plateaued between 9 and 23 min postinjection. At the lower dose, enhancement of renal medulla was maximum at 2 min postinjection. These enhancement characteristics (both brain and kidney), at equivalent contrast dosages, are comparable to that previously published for Gd-DTPA. However, Gd HP-DO3A has the potential to be utilized clinically at higher doses than Gd-DTPA, with no reported adverse effects in initial trials employing up to 0.3 mmol/kg.

Animals↗

Tissue plasminogen activator for the treatment of thromboembolism in infants and children.

We report our experience with the use of tissue plasminogen activator to treat 12 infants and children with various thromboembolic states after conventional thrombolytic agents had failed. The dosage range was between 0.1 to 0.5 mg/kg per hour. Complete clot dissolution occurred in seven cases after 2 hours to 3 days of therapy. Partial clot dissolution and clinical improvement were noted in another four patients. Bleeding complications were noted in 6 of the 12 patients and included bruising, oozing from various venipuncture sites, and bleeding; these complications were controlled by clinically available means. In all cases with bleeding the dose rate was in the higher range (0.46 to 0.50 mg/kg per hour). In one patient, restlessness, agitation, and screaming were noted during administration of tissue plasminogen activator and when it was reinstituted. We conclude that tissue plasminogen activator is effective in inducing clot lysis in children. Because the effective dose appears to overlap with those causing bleeding, we recommend that a dose of 0.1 mg/kg per hour be started and increased gradually if clot dissolution does not occur, with close monitoring for bleeding.

Adolescent↗

Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease.

The human T-lymphotropic virus type I (HTLV-I), the first human retrovirus to be characterized, is associated with adult T-cell leukaemia and a chronic progressive disease of the central nervous system termed tropical spastic paraparesis, or HTLV-I-associated myelopathy. Only 1% of individuals infected with HTLV-I develop clinical disease however. The various manifestations of an HTLV-I infection may be related to differences in the genetic backgrounds of individuals, infection with variant strains of HTLV-I, differences in viral tropism or host immune response to the virus. Whereas the humoral response to HTLV-I is well characterized, little is known about the human cellular immune response, such as the production of cytotoxic T lymphocytes. Here we report the presence of high levels of circulating HTLV-I-specific cytotoxic T lymphocytes in patients with HTLV-I associated neurological disease but not in HTLV-I seropositive individuals without neurological involvement. These cytotoxic T lymphocytes are CD8+, HLA class I- restricted and predominantly recognize the HTLV-I gene products encoded in the regulatory region pX. These findings suggest that HTLV-I-specific cytotoxic T lymphocytes may contribute to the pathogenesis of associated neurological disorders associated with HTLV-I.

Adult↗

Immunological studies in tropical spastic paraparesis.

Tropical spastic paraparesis (TSP) and other chronic-progressive myelopathies have been clearly associated with increased serum and cerebrospinal fluid antibody titers to human T-lymphotropic virus type I (HTLV-I). However, little is known about the cellular immune function in TSP. In the present study, activated T lymphocytes were found in the peripheral blood of patients with TSP. Specifically, there were increased numbers of large CD3+ cells that also expressed HLA-DR and interleukin-2-receptor molecules. A significantly elevated spontaneous lymphoproliferative response was demonstrated in all patients tested. Generation of measles virus-specific cytotoxic T-cell response was reduced in 4 of 4 patients. This was similar to previous findings in patients with multiple sclerosis. However, unlike multiple sclerosis, reduced generation of cytotoxic T-cell response to influenza and mumps viruses was observed in 2 of 4 patients. These observations confirm further the strong association between TSP and an HTLV-I-like virus and suggest that the observed abnormalities of the cellular immune response in TSP are related to infection of lymphocytes by the retrovirus.

Adolescent↗

Total body potassium, fat and water during total parenteral nutrition in Crohn's disease.

The body composition was studied by measurement of body weight (BW) and total body potassium (TBK), fat and water in 13 patients with Crohn's disease (CD), who were given altogether 18 courses of total parenteral nutrition (TPN) with nil by mouth each lasting at least 3 weeks. At the start of TPN, one group of steroid-free patients displayed intracellular potassium depletion, as reflected by the ratio TBK/lean body mass (LBM) (group 1). Another group of steroid-free patients showed no depletion of intracellular potassium (group 2). The patients given prednisolone all showed intracellular potassium depletion and were assigned to a separate group (group 3). During the initial 19-44 days of TPN, TBK, LBM and BW increased in group 1. All patients with intracellular potassium depletion (groups 1 + 3) showed an increase in TBK and TBK/LBM during the initial 19-51 days of TPN. For steroid-free patients (groups 1 + 2) there were linear relationships between the rate of energy supply per kg LBM and the 24 h change in BW during the third and fourth weeks of TPN (r = 0.79) and between the 24 h change in BW and LBM during the first 19-44 days of TPN (r = 0.59). A steady state in BW was found on administering 53 kcal/kg LBM/24 h. It is concluded that CD patients with intracellular potassium depletion are likely to be improved in terms of TBK and TBK/LBM by at least 3 weeks of TPN as given in the present study. Steroid-free CD patients with intracellular potassium depletion are, moreover, likely to show an improvement in LBM by at least 3 weeks of TPN, and an increase in their BW during the initial 3-6 weeks of TPN will probably reflect an increase in LBM. The pre-TPN TBK/LBM ratio may be a predictor of the repletion rate of the LBM compartment during TPN of steroid-free wasted CD patients.

Journal Article↗

Nucleotide sequence analysis of a provirus derived from an individual with tropical spastic paraparesis.

Human T-cell lymphotropic virus type 1 (HTLV-1), the cause of inapparent infections and T-cell leukemias and lymphomas, has also been implicated in two chronic neurological diseases, tropical spastic paraparesis (TSP) and HTLV-1 associated myelopathy (HAM). We initiated a search for a neurotropic variant of HTLV-1 that might be responsible for these chronic progressive myelopathies by cloning and sequencing a provirus from a T-cell line from an individual with TSP. The LTRs and genes of the TSP provirus differ from HTLV-1 by 20-30 nucleotides in each region, but none of the substitutions ostensibly affect functional sites with the exception of the env gene. We document one substitution in the region encoding gp46 common to TSP and HAM proviruses and a mutation that introduces two stop codons in the region encoding gp21. The latter should delete about 100 amino acids from the transmembrane anchor, and, for this reason, the progeny of the sequenced provirus are likely to be defective viruses, maintained in the culture through coinfection of cells with wild-type non-defective HTLV-1. While defective viruses could be responsible for persistent infection of the nervous system in TSP, this cannot be generally the case as we show that HTLV-1 DNA amplified from cell lines from two other individuals with TSP lacked the stop codons. Similarly, comparisons of DNA amplified from HTLV-1 DNA in cases of ATL, HAM, and TSP did not establish a correlation between the mutation in gp46 and neurological disease. The issue of neurotropic variants in HTLV-1 associated neurological disease thus remains an open one which may be resolved in the future by examining proviruses in cells in the lesions in the nervous system; or proviruses in ATL and HAM/TSP which differ in their ability to replicate in glial or neuronal cells.

Amino Acid Sequence↗

AIDS education in the emergency department.

The prevention of the spread of acquired immunodeficiency syndrome (AIDS) depends on an educated public reducing their risk of infection. To test the hypothesis that effective community AIDS education can be based in an emergency department, we designed and evaluated two educational interventions in a high-volume urban ED. A pretest/post-test design was used in which subjects were assigned to receive either an active education program, a passive education program, or no education program. Knowledge gains and self-reported risk-reduction behavior were evaluated by follow-up testing within a five-week period. The active and passive groups had significantly greater knowledge gains than the control group (P less than .001). Significantly greater reported reductions in high-risk behavior were found in both the active and passive groups compared with the control group (P less than .01). This study demonstrates that an ED-based AIDS education program can have a significant impact on improving knowledge and reducing self-reported risk behaviors.

Acquired Immunodeficiency Syndrome↗

Psychological predictors of young adults' drinking behaviors.

Path analyses using data from 72 men and 78 women between 22 and 32 years of age compared two models linking personality (conflict resolution styles, intimacy maturity, and occupational identity status) and social roles (family and work status) to young adults' alcohol use. Poor conflict resolution skills and less adult work statuses best accounted for men's excessive drinking, and problems with intimacy best accounted for women's use of alcohol to alleviate emotional distress. In addition, poor conflict resolution skills partly mediated the effects of parent's drinking on son's alcohol consumption. Occupational identity status and intimacy maturity correlated with men's use of drugs rather than men's alcohol use.

Adolescent↗

Isolation of human T-cell lymphotropic virus type 2 from Guaymi Indians in Panama.

Human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma and with a chronic degenerative myelopathy. However, another major type of HTLV, HTLV-II, has been isolated only sporadically, and little is known of disease associations, transmission routes, and risk factors for HTLV-II infection. Recent studies indicate that a high percentage of certain groups of i.v. drug users and blood donors are infected with HTLV-II. Seroepidemiologic studies have found an elevated rate of seroreactivity to HTLV among Guaymi Indians from Bocas del Toro Province, Panama. To identify the cause of seroreactivity among this unique population we used HTLV-II-specific polymerase chain reaction techniques to detect HTLV genetic sequences from blood leukocytes of three seropositive Guaymi Indians. The HTLV-II primer-amplified polymerase chain reaction products from two of these subjects were partially sequenced and matched published HTLV-II nucleotide sequences in both p24 gag (94% of 107 bases) and pol (98% of 112 bases) regions. A CD4+ T-lymphocyte line established from one of these same subjects produced HTLV-II-specific proteins when tested in antigen-capture and immunoblot assays, as well as mature HTLV particles. The demonstration of HTLV-II infection in this geographically and culturally isolated Central American Indian population without typical risk factors for HTLV infection suggests that HTLV-II infection is endemic in this population and provides an important clue to potential natural reservoir for this virus.

Base Sequence↗

Informed consent for neuroleptics with elderly patients in two settings.

This paper presents the results of four studies that evaluated the use of neuroleptics in an aging population both in nursing homes and in a psychiatric teaching hospital. The purpose was to determine the degree to which prescribing practices were in compliance with recent court rulings respecting the right of patients to informed consent to "exceptional" medication. The results indicate that physicians in nursing homes do not inform their patients of the risks of neuroleptics, do not seek consent, and do not consider competency to be even an issue. Elderly patients in the acute academic setting were informed of risks and benefits. However, both consent to medication and the competency to give this consent were presumed until or unless the patient failed to acquiesce. The degree to which these practices might be in potential conflict with state law, ignore the benefits of a negotiated doctor/patient partnership, and demonstrate one aspect of poor quality of care are discussed, and policy recommendations are made.

Aged↗

The effect of prolonged aspirin therapy on experimental balloon-catheter arterial wall injury.

Indications for aspirin following percutaneous transluminal angioplasty are not well defined. Although aspirin's early antithrombotic effect is believed to be beneficial, the long-term influence of aspirin on myointimal proliferative response following balloon-catheter angioplasty is still being investigated. This study quantitates arterial wall thickening, including intimal hyperplasia, at 4 months following balloon-catheter aortic injury in New Zealand white rabbits (n = 12), comparing aspirin treatment (30 mg/kg) with controls. Aspirin was administered daily for 1 month prior and 4 months following aortic injury. Myointimal proliferation was noted in both groups. The mean area of the intima and media as well as the maximum thickness of the intima were similar (p greater than .05) in both the aspirin treatment and control groups. Cellular hyperplasia was evaluated by media smooth muscle cell counts using an ocular reticle. There was a trend toward higher cell counts with aspirin treatment, although there was no significant difference between the two groups. Prolonged aspirin therapy did not alter the degree of myointimal hyperplasia at 4 months postinjury in our model.

Animals↗

Impaired human leukocyte antigen-restricted measles virus-specific cytotoxic T-cell response in subacute sclerosing panencephalitis.

The capacity of peripheral blood lymphocytes to proliferate in response to measles virus and to generate measles virus-specific cytotoxic T lymphocytes (CTL) was examined in 4 patients with subacute sclerosing panencephalitis (SSPE). The lymphoproliferative response to measles virus was obtainable in the 4 SSPE patients. In contrast, the CTL response to measles virus was reduced in 3 of the 4 SSPE patients. This defect appeared to be in the generation of the measles virus-specific CTLs, since measles virus-infected target cells from the patients could be lysed by human leukocyte antigen-matched peripheral blood lymphocytes from healthy individuals. The SSPE patients with reduced measles virus CTL response had a normal ability to generate mumps virus, influenza virus, or alloantigen-specific CTLs. The lysis of measles virus-infected targets that was observed with these SSPE patients could be reduced by depleting the effectors of natural killer cells or by performing cold target blocking with K562 cells, indicating that the lysis of the measles virus-infected targets was probably mediated by natural killer cells. These results demonstrate a reduction in the cell-mediated immune response to measles virus as measured by the generation of measles virus-specific CTLs in 3 of the 4 SSPE patients studied. This defect could relate to the persistence of measles virus in these patients.

Adolescent↗

Virus-specific cytotoxic T lymphocytes in multiple sclerosis: a normal mumps virus response adds support for a distinct impairment in the measles virus response.

An impairment of the measles virus-specific cytotoxic T lymphocyte response in multiple sclerosis was previously reported. This response is predominantly mediated by HLA class II-restricted CD4+ cells. In the present report, virus-specific cytotoxic T lymphocyte responses in multiple sclerosis were further studied by examining the response to mumps virus. No significant difference was detected in the generation of mumps virus-specific cytotoxic T lymphocyte responses between normal individuals and multiple sclerosis patients with impaired measles virus-specific cytotoxicity. A portion of the mumps virus-specific cytotoxic T lymphocyte response could be mediated by HLA class II-restricted CD4+ cells generated from both normal controls and MS patients. This CD4+ cell-mediated portion of the response was similar in both groups. These findings support the view that there is a distinct measles virus-specific impairment in cell-mediated cytotoxicity in multiple sclerosis.

Antigens, Differentiation, T-Lymphocyte↗

Pathways of viral antigen processing and presentation to CTL: defined by the mode of virus entry?

Processing requirements for antigen presentation to cytotoxic T lymphocytes (CTL) vary among viruses and between major histocompatibility complex (MHC) class I- and class II-restricted responses to the same virus. In this article, Eric Long and Steven Jacobson argue that the mode of virus entry may define processing pathways and that the invariant chain associated with MHC class II molecules may account for the distinct processing requirements for MHC class I- and class II-restricted CTL.

Animals↗

Experimental trials with Gd(DO3A)--a nonionic magnetic resonance contrast agent.

Gd(DO3A), a member of a new family of nonionic MRI contrast agents, was evaluated in vivo in a rat model. In 10 animals, enhancement of an intracerebral glioma was studied following Gd(DO3A) injection. Correlation with tissue pathology was obtained in all cases. Comparative studies of renal enhancement were performed in 15 animals, utilizing disodium Gd(DTPA)2-, sodium-Gd(DOTA)-, and Gd(DO3A). With the glioma model, Gd(DO3A) administration provided enhancement of tissue with an altered blood brain barrier, thus permitting identification of the bulk of the neoplastic lesion. Comparative studies revealed that enhancement of normal renal medulla was equal or superior with Gd(DO3A).

Animals↗