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Biomedical subjects

S Jacobson

Publications and source records attributed to S Jacobson.

At least 163 records · Page 9Linked to original sources
PubMed1989

HLA class II-restricted presentation of cytoplasmic measles virus antigens to cytotoxic T cells.

To analyze the nature of the HLA class II-restricted cytotoxic T-lymphocyte (CTL) response to measles virus, murine fibroblasts were transfected with expressible cDNA clones for human HLA-DR antigen and for measles virus matrix or nucleocapsid proteins. DR-positive murine fibroblasts transfected with measles virus matrix or nucleocapsid genes were lysed by class II-restricted measles virus-specific CTL lines. Lysis was as efficient as with infected autologous B-cell lines, even though the measles virus cytoplasmic proteins were undetectable by antibodies in the transfected target cells. These results demonstrate that cytoplasmic viral antigens can be presented to CTL in the context of HLA class II antigens and that measles virus matrix and nucleocapsid proteins contribute to class II-restricted measles virus-specific CTL responses. These results also show that endogenously synthesized measles virus proteins can be efficiently presented by class II antigens. The implications of these findings for measles virus pathogenesis and for antigen processing are discussed.

Animals↗
PubMed1989

Upper airway obstruction.

Upper airway obstruction is an uncommon but obviously serious management issue that will present to the Emergency Department from time to time. This article covers upper airway obstruction in the adult patient and concentrates on the acute and subacute presentations.

Airway Obstruction↗
PubMed1988

Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis.

Tropical spastic paraparesis (TSP) is a slowly progressive myelopathy associated with increased serum and cerebrospinal fluid antibodies to the human T-lymphotropic retrovirus type I (HTLV-I) (ref. 1), and has been observed in many regions of the world. A similar condition known as HTLV-I-associated myelopathy occurs in the Kagoshima prefecture of Japan. Recent but controversial reports suggest involvement of virus related to HTLV-I in multiple sclerosis. Magnetic resonance imaging and electrophysiological studies indicate that TSP lesions are like multiple sclerosis in that they are disseminated throughout the nervous system. Complete virus from patients with TSP has proved difficult to isolate using techniques successful in adult T-cell leukaemia cases associated with HTLV-I. Here we report the isolation of an HTLV-I-like virus from T-cell lines derived from the peripheral blood and cerebrospinal fluid of TSP patients. The monoclonal antibody OKT3 was used to generate non-transformed T-cell lines that express HTLV-I antigens. Infectious virus was demonstrated by co-cultivation and complete, replicating virions were visualized ultrastructurally.

Antigens, Viral↗
PubMed1988

Immunological findings in neurological diseases associated with antibodies to HTLV-I: activated lymphocytes in tropical spastic paraparesis.

A retrovirus involvement in the etiology of certain neurological diseases is currently an area of intense interest. Tropical spastic paraparesis and other chronic progressive myelopathies have been clearly associated with increased serum and cerebrospinal fluid antibody titers to human T-lymphotropic virus type I; however, little is known about the cellular immune response. In the present study, activated T-lymphocytes were found in the peripheral blood of patients with this disorder. There were increased numbers of large CD3-positive cells that also expressed histocompatibility leukocyte Class II (DR) and interleukin 2-receptor molecules. In addition, a significantly elevated spontaneous lymphoproliferative response was demonstrated in all patients. This is consistent with the known in vitro effects of human T-lymphotropic virus type I. In one patient, a defect in the generation of measles virus-specific cytotoxic T cells was identified. These observations indicate abnormalities of the cellular immune response in tropical spastic paraparesis.

Antibodies, Viral↗
PubMed1988

Multichannel intracranial recording device using a color imaging brain mapping system.

A procedure is described for the manufacture and use of a multichannel (up to 20) intracranial recording device. Electrodes are arranged in a horizontal plane, and can be controlled by a conventional microdrive. Data from multiple channels are visualized and analyzed utilizing a commercially available color imaging brain mapping system. Potential research applications include studies of neural generators of evoked responses through the simultaneous recording of intracranial and scalp potentials.

Animals↗
PubMed1988

In situ analysis of microvascular pericytes in hypertensive rat brains.

We used immunofluorescence microscopy and isoactin-specific antibodies to characterize the pattern and prevalence of pericytes within the brain microcirculation. Blood pressures of normotensive, Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were measured prior to sacrifice and pressure-perfusion fixation. WKY and SHR brains were subdivided into ten major regions prior to ultracryomicrotomy. Sections 0.3-0.5 micron wide were treated with 10-40 micrograms/ml affinity-purified antibodies to the muscle and non-muscle actin isoforms. These localization studies show that there are four times the number of pericyte-rich capillaries in the SHR motor cortex compared to WKY counterparts (59.9 vs. 15.3%). In contrast, the sensory cortex of both rat strains is deficient in muscle actin staining surrounding the capillaries. The most striking difference in pericyte presence and muscle actin antibody staining between the SHR and WKY was observed in the tegmentum of the brainstem. There is nearly a one-to-one coincidence observed in pericyte and capillary profiles present within thin, frozen sections of the SHR midbrain. SHR pons capillaries were also pericyte-enriched. WKY analyses of plastic embedded thin sections confirmed the presence of pericytes and their filament-enriched processes encircling the capillaries of the hypertensive brains. These results suggest that pericytes may play important roles in hypertension and cerebrovascular disease processes.

Actins↗
PubMed1988

Antigen presentation to HLA class II-restricted measles virus-specific T-cell clones can occur in the absence of the invariant chain.

A human fibroblast line expressing HLA-DR1 antigen on its surface was generated by transfection with DR alpha and DR beta cDNAs. Expression of the invariant chain gene was not detectable in the transfected fibroblasts and was not induced by infection with measles virus. Lysis of measles virus-infected cells occurred with DR1- but not with DR4-restricted measles virus-specific cytotoxic T-lymphocyte (CTL) clones and was inhibited by a monoclonal antibody specific for DR antigen. Therefore, the invariant chain is not required for DR-restricted presentation of measles virus antigens by this fibroblast line. Transfected fibroblasts were lysed as efficiently as an autologous B-cell line even though they expressed much less surface DR antigen. Lysis of both the transfected fibroblasts and the B-cell line was insensitive to treatment with chloroquine. These results demonstrate that expression of a DR alpha beta heterodimer at the surface of this fibroblast line is necessary and sufficient for presentation of measles virus antigens to specific CTL clones.

Antigen-Presenting Cells↗
PubMed1988

MR imaging of rat brain glioma: Gd-DTPA versus Gd-DOTA.

The enhancement properties of gadolinium diethylenetriaminepentaacetic acid (DTPA) and gadolinium tetraazacyclododecanetetraacetic acid (DOTA) were compared using a rat glioma model. In vitro analysis included the calculation of T1 relaxivity and determination of characteristic curves. Enhancement of the intracerebral glioma was studied in 23 rats approximately 2 weeks after glioma implantation with Gd-DTPA in 12 rats and Gd-DOTA in 11 rats. Six rats were also studied 1 week after implantation. Gd-DTPA exhibited a slightly greater T1 relaxivity in vitro than Gd-DOTA. Enhancement of the glioma was also greater with Gd-DTPA than with Gd-DOTA (P less than .05).

Animals↗
PubMed1988

Lumbar percutaneous diskectomy.

The lumbar percutaneous diskectomy is a new procedure for the treatment of herniated lumbar intervertebral disks that have not advanced to sequestration, fibrosis, or osteophyte formation. The procedure is done under local anesthesia, and there is no entrance into the spinal canal.

Adult↗
PubMed1987

Characterization of microvascular cell cultures from normotensive and hypertensive rat brains: pericyte-endothelial cell interactions in vitro.

We used specific markers and fluorescence microscopy to identify and characterize cerebrovascular cells. Cultures were derived from brain microvessels isolated from normotensive (Wistar Kyoto, WKY) and spontaneously hypertensive (SHR) rat brains prior to, coincident with and following the onset of chronic hypertension. Endothelial cells were characterized using di-acyl LDL and non-muscle isoactin-specific antibodies. Cerebrovascular pericytes were identified with the anti-muscle and non-muscle actin antibody staining. Using this combination of cell culture and fluorescence localization, we have been able to demonstrate that brain pericytes are tightly associated with the endothelial cells of the hypertensive-prone and hypertensive cell cultures, but not with the normotensive endothelial cultures. While the endothelial-pericyte ratio in the hypertensive-prone microvascular cultures was between 5:1 and 10:1, the number of pericytes associated with the hypertensive rat brain cultures increased two to five times (2:1-1:1). Muscle and non-muscle actin antibody staining localized the spindle-shaped pericytes of the hypertensive microvascular colonies. Pericytes were found overlaying and encircling the endothelial cells. Normotensive pericytes were not endothelial-associated. Whereas the hypertensive pericyte is devoid of stress fibers, the normotensive pericyte is a larger, spread-out cell possessing numerous stress fibers rich in muscle and non-muscle actin. These results provide the first evidence that the etiology and inception of cerebrovascular disease may be pericyte-related and suggest that pericyte contraction could play a pivotal role in regulating the flow of blood within the brain microcirculation.

Actins↗
PubMed1987

Satisfaction with practices: emergency physicians versus internists.

No comparison has been made of satisfaction with practices of emergency physicians versus other specialists. We used a previously tested questionnaire that measures differences between current and preferred practice conditions, and with items regarding training and practice, and intention to change positions. It was sent to 250 physicians practicing emergency medicine and 250 practicing internal medicine in a metropolitan area. Both specialty types were defined by type of practice, rather than by specialty training or board certification. Ninety-five (38%) emergency physicians and 79 (32%) internists responded. Factor and correlation analyses identified six satisfaction indexes: resources, professional autonomy, administrative autonomy, patient relationships, professional relationships, and status. Physicians practicing emergency medicine were less satisfied, that is, reported more difference between current and preferred conditions, than physicians practicing internal medicine with professional autonomy, patient relations, and status (by t tests, P less than .01 for each). Emergency physicians were more satisfied with professional relationships (P less than .01). Only 40% of emergency physicians, versus 60% of internists, reported no intention to leave their present position within the next two years (P less than .02). Expectation of position change by physicians practicing emergency medicine was predicted by dissatisfaction with professional autonomy, lack of board certification, recency of graduation from medical school, and belief that monetary compensation would be higher elsewhere (R square, 0.35; P less than .01), while variables such as patient load, hours worked per week, and hospital size proved unimportant. We identified areas of dissatisfaction among emergency physicians that differed from those among internists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Distinct signals are required for proliferation and lymphokine gene expression in murine T cell clones.

Experiments were performed to assess the capacity of lectin (Con A), ionomycin, phorbol ester (PMA), and recombinant IL 2 to mediate proliferation as well as the expression of cell surface IL 2 receptors, two lymphokine genes, IL 2 and IFN-gamma, and the c-myc proto-oncogene in cloned T cell populations. Stimulation of T cell clones with recombinant IL 2 resulted in proliferation and sustained expression of the c-myc cellular proto-oncogene, but did not induce the expression of mRNA for the lymphokines IFN-gamma and IL 2. In contrast, stimulation of cloned T cells with lectin alone induced significant IFN-gamma and IL 2 mRNA expression, up-regulation of the number of cell surface IL 2 receptors, and transient c-myc expression. Ionomycin alone was not a sufficient signal for lymphokine mRNA induction. The phorbol ester PMA alone induced neither proliferation nor lymphokine gene expression but potentiated lectin and ionomycin-mediated signals. We also performed experiments to examine whether the T cell response to extracellular stimuli was a function of the activation state of the cell. Reexposure of 48-hr antigen-activated cloned cells to identical stimuli revealed several differences. Low but significant levels of IFN-gamma mRNA were now also reinduced in activated clones cells in response to IL 2 or PMA alone. Activated cells were refractory to reinduction of IL 2 mRNA by any stimulus, which may reflect a physiologic mechanism to limit clonal expansion after antigenic stimulation. This could be partially reversed by restimulation with lectin in the presence of cycloheximide, suggesting a role for a labile protein repressor in the down-regulation of IL 2 mRNA expression. PMA alone induced an IL 2-independent proliferative response. We demonstrate that distinct signals are required for lymphokine gene expression vs cellular proliferation in cloned T lymphocyte populations, and that the capacity of extracellular stimuli to reinduce expression of lymphokine genes or to mediate cell proliferation is altered by prior activation.

Animals↗
PubMed1986

Polypeptide specificities of measles virus-reactive T cell lines and clones derived from a patient with multiple sclerosis.

Eleven cloned and uncloned measles virus-specific T cell lines were generated from peripheral blood lymphocytes obtained from a patient with multiple sclerosis and were assayed for measles polypeptide specificity. Three clones reacted specifically with the fusion (F) protein and one recognized the hemagglutinin (HA). Two reacted with whole virus but not with any of the purified proteins. Five cell lines proliferated in response to multiple measles polypeptides. The addition of anti-HA or anti-F monoclonal antibodies to two of the multispecific cell lines each resulted in partial suppression of the proliferative response to whole virus by the cell lines. Two of the three F-reactive clones recognized antigen in association with a subgroup of HLA-DR4; the third responded to F only in the presence of autologous antigen-presenting cells. Of the two clones that reacted only with whole virus, one was restricted to DP3 and one to autologous cells. The HA-specific clone was DP3 restricted. Several cell lines recognized multiple measles polypeptides in association with a single HLA antigen. Recognition of individual measles polypeptides does not segregate with specific genetic restriction elements.

Antigens, Viral↗
PubMed1986

Fluorescence-activated cell analysis of P-fimbriae receptor accessibility on uroepithelial cells of patients with renal scarring.

Pyelonephritogenic Escherichia coli possess P-fimbriae that bind to uroepithelial cells by recognizing a receptor containing the alpha-D-Galp-(1-4)-beta-D-Galp carbohydrate structure. The accessibility of P-fimbriae receptors was determined using uroepithelial cells from 19 female patients with verified renal scarring and a history of febrile urinary tract infection, and 13 healthy controls. The binding of fluorescein isothiocyanate labeled P-fimbriated Escherichia coli to a large number of uroepithelial cells from each individual was studied using the method of fluorescence-activated cell sorting analysis, which allows examination of a large number of cells and selection of cells of a given size. The uroepithelial cells from the patients exhibited a significantly higher binding capacity to P-fimbriated Escherichia coli than did uroepithelial cells from healthy controls (p less than 0.01). The determination of P-fimbriae receptor accessibility on uroepithelial cells may be useful for detecting risk groups among patients with recurrent urinary tract infections.

Adult↗