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Biomedical subjects

S Jacobson

Publications and source records attributed to S Jacobson.

At least 127 records · Page 7Linked to original sources
PubMed1993

High human T cell lymphotropic virus type 1 (HTLV-1)-specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-1-associated neurological disease.

The frequencies of human T cell lymphotropic virus type 1 (HTLV-1)-specific CD8+ precursor cytotoxic T lymphocytes (pCTL) were quantitated from lymphocytes obtained from the peripheral blood and cerebrospinal fluid (CSF) of infected individuals with and without HTLV-1-associated neurological disease. An estimate of the pCTL was obtained by separating CD8+ cells, plating these cells in limiting dilution, and testing wells for HTLV-1 specific lysis. Targets consisted of autologous lymphoblastoid cell lines (LCL) infected with vaccinia constructs expressing HTLV-1 gene products or LCL pulsed with HTLV-1 synthetic peptides. In patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the frequency of HTLV-1 p40X-specific pCTL was at least 40-280-fold higher than in asymptomatic HTLV-1-infected individuals. All HAM/TSP patients (five of five) predominantly recognized HTLV-1 products encoded within the pX region. Lower pCTL to env were demonstrated in three patients, and only one of five HAM/TSP patients had pCTL to gag. A synthetic peptide corresponding to the tax region of HTLV-1 (peptide 11-19, amino acid sequence LLFGYPVYV) was recognized in association with human histocompatibility leukocyte antigen (HLA)-A2 in two HLA-A2 HAM/TSP patients with a high CD8+ pCTL frequency of 1/325 and 1/265, respectively. A second immunodominant region of HTLV-1 tax (peptide 90-55, amino acid sequence VPYKRIEEL) was identified to be restricted by HLA-B14 in two HLA-B14 HAM/TSP patients with a CD8+ pCTL frequency of 1/640 and 1/1,125, respectively. Lymphocytes from the CSF of a patient with HAM/TSP also showed a pCTL frequency against p40X of similar magnitude to that demonstrated from peripheral blood lymphocytes (PBL). The HLA-A2-mediated CSF pCTL activity to the immunodominant tax-specific peptide 11-19 was also comparable to pCTL from PBL. These results indicate that an extremely high pCTL frequency to HTLV-1 tax-encoded peptides may be related to pathogenesis of myeloneuropathy associated with HTLV-1.

Adult↗
PubMed1993

Isolation of HTLV-II from a patient with chronic, progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis.

An increasing spectrum of diseases has been shown to be associated with the human T-cell lymphotropic virus type I (HTLV-I), most notably a chronic, progressive myelopathy termed HTLV-I--associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia. HTLV-II is a close relative of HTLV-I and is structurally similar but molecularly distinct. This virus is endemic in Amerindian populations and a high seroprevalence rate has been observed in intravenous drug abusers. Here, for the first time, we have identified a patient with a chronic, progressive neurological disease clinically indistinguishable from HTLV-I--associated myelopathy/tropical spastic paraparesis from whom we have isolated and characterized HTLV-II in the absence of any other detectable human retrovirus. Antibodies to HTLV were detected in both serum and cerebrospinal fluid, with typical HTLV-II banding patterns on Western blots. HTLV-II viral sequences were detected in high copy number from peripheral lymphocytes by polymerase chain reaction techniques, and cloning and sequencing of this virus revealed a 99.5% homology with prototype HTLV-II. These results serve to alert the medical community to the possibility that in addition to HTLV-I, HTLV-II may be associated with a neurological disorder.

Brain↗
PubMed1993

Demonstration of human T-cell lymphotropic virus type I (HTLV-I) from an HTLV-I seronegative south Indian patient with chronic, progressive spastic paraparesis.

Here we describe a human T-cell lymphotropic virus type I (HTLV-I) seronegative patient from South India with a chronic, progressive spastic paraparesis from which HTLV-I has been isolated from peripheral blood lymphocytes. HTLV-I pol and tax viral sequences were detected in DNA from fresh peripheral blood lymphocytes (PBL) by polymerase chain reaction (PCR) and liquid hybridization techniques. Southern blot analysis of the PCR products demonstrated a low copy number of HTLV-I at the level of one viral copy per 10,000 fresh PBL. A long-term CD4+ T-cell line was established from PBL of this patient using recombinant interleukin-2, OKT3, and feeder cells. DNA from these cultured lines was amplified and portions of the HTLV-I long terminal repeat (U3), pol, env, and tax regions were sequenced (a total of 1,115 bp). The sequence data showed that the HTLV-I associated with this patient was 98.8% homologous to prototype HTLV-I. Southern blot analysis also confirmed the presence of full-length HTLV-I. These results indicate that HTLV-I can be demonstrated in an HTLV-I seronegative patient from South India with a chronic progressive neurological disorder.

Base Sequence↗
PubMed1993

Neuroaxonal dystrophy in HTLV-1-associated myelopathy/tropical spastic paraparesis: neuropathologic and neuroimmunologic correlations.

Detailed neuropathologic and immunohistologic analysis of a case of serologically and polymerase chain reaction-confirmed human immunodeficiency virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is reported in a 73-year-old North American black woman. In addition to the usual neuropathologic features of HAM/TSP, including tractal degeneration of the spinal cord, leptomeningeal and perivascular fibrosis, perivascular demyelination and chronic inflammation, neuroaxonal spheroids were prominent in the spinal cord. Neuroaxonal dystrophy was characterized by neurofilamentous masses that were immunoreactive for phosphorylated neurofilament epitopes, but not ubiquitin. Neuroimmunologic analysis of the inflammatory reaction revealed a prevalence of CD8+ T cells and class I major histocompatibility molecules (MHC) (HLA-ABC and beta 2-microglobulin), but very few CD4+ T cells. Microglia were highly reactive for class II MHC (HLA-DR alpha) and this was attributed to activation, rather than CD4 interaction, since CD4 presence was minimal. Inflammatory cytokine immunoreactivity was also detected in glia. It is concluded that the cumulative effects of cytotoxic T cell (CD8) infiltration and the possible involvement of cytokines were responsible for the unusual degree of neuroaxonal dystrophy and vascular fibrosis, as well as the observed demyelination in this case.

Aged↗
PubMed1993

Oral labetalol versus oral nifedipine in hypertensive urgencies in the ED.

Therapy in hypertensive urgencies is debated and complicated by the side effects of available agents. In a prospective, randomized, open labeled study, the use of oral labetalol, an alpha- and beta-adrenergic blocker, with oral nifedipine in hypertensive urgencies in the emergency department was compared. Patients with diastolic blood pressures (DBP) of more than 120 mm Hg without criteria for a hypertensive emergency were eligible. The drugs were given in a loading manner with doses and timing based on their respective pharmacokinetics until a DBP of 110 mm Hg or lower was obtained or 4 hours had passed. Either an initial labetalol dose of 200 mg and a repeat dose of 100 to 200 mg at 2 hours, depending on the DBP or nifedipine, 10-mg bite and swallow every hour up to a total dose of 20 mg were given. Ten patients were enrolled into each study group. A 100% response rate was defined as a DBP of 110 mm Hg or less was observed for nifedipine and an 80% response rate for labetalol (P > .2) was observed. The mean time to control was 67.5 minutes for labetalol and 60.0 minutes for nifedipine (P > .2). The pretreatment pressure for labetalol was 195/127 mm Hg and for nifedipine was 198/128 mm Hg (P > .2), which decreased to a posttreatment pressure for labetalol of 154/100 mm Hg and for nifedipine of 163/100 mm Hg (P > .2). The mean decrease in systolic (SBP)/DBP was 42.6/26.5 mm Hg with labetalol and 34.9/28.4 mm Hg for nifedipine (P > .2). No significant side effects occurred with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

HTLV-II infection in Florida Indians.

A significantly increased prevalence of antibodies to human T-cell leukemia virus (HTLV) has been described in several native American populations in the United States and Latin America. Initial virologic studies indicate that HTLV-II is the predominant virus responsible for this antibody pattern. We obtained blood samples from 106 Seminole Indians living on four reservations in Southern Florida. Seropositivity to HTLV-I/II was found in 14 (13.2%) of these individuals. Polymerase chain reaction (PCR) documented HTLV-II and the absence of HTLV-I in 7 of the 9 donors available for follow-up testing of white blood cells. Evaluation of various risk factors excluded blood transfusion or intravenous drug use as an important contributing factor to the HTLV-II seroprevalence rate. These studies support the hypothesis that HTLV-II is endemic in many native American tribes in the Western hemisphere.

Florida↗
PubMed1993

Comparison of gamma interferon, tumor necrosis factor, and direct cell contact in activation of antimycobacterial defense in murine macrophages.

We compared the abilities of gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and sensitized murine lymph node lymphocytes to activate syngeneic murine peritoneal macrophages to inhibit the growth of intracellular Mycobacterium bovis BCG in vitro. IFN-gamma could activate antimycobacterial defense only when added to macrophage cultures prior to their infection with BCG. TNF-alpha was without any effect. In contrast, BCG-sensitized lymphocytes could induce antimycobacterial defenses when added after macrophages had been infected with BCG. The cell-mediated effect required direct contact between effector lymphocytes and the targets (BCG-infected macrophages), as revealed in studies in which these cell populations were separated by a semipermeable membrane. Cyclosporin A, which inhibits the production of relevant macrophage-activating lymphokines, did not abrogate the ability of sensitized lymphocytes to activate antimycobacterial effects in infected macrophages. Furthermore, only BCG-sensitized lymphocytes, and not Listeria-sensitized lymphocytes, could activate the antimycobacterial effects. These lymphocytes were not cytotoxic to the infected macrophages. The presence of anti-TNF-alpha antibody in cocultures reduced the antimicrobial effects. We propose that the activation of antimycobacterial defense in macrophages can occur by direct physical contact with sensitized lymphocytes. This process may be due to lymphocyte membrane-associated TNF-alpha, as we previously demonstrated in our studies of antileishmanial defense.

Animals↗
PubMed1993

Sequence comparisons of HTLV-I from HAM/TSP patients and their asymptomatic spouses.

We amplified and sequenced portions of the human T-lymphotropic virus type I (HTLV-I) (U3), pol, env, and pX provirus regions (1212 bp per person) from peripheral blood lymphocytes (PBL) of two married couples (case 1 and case 2). Both husbands are patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and the wives are asymptomatic HTLV-I carriers. We selected these regions because the LTR and env regions of murine retrovirus models have been involved in determining tissue tropism. In addition, the predominant immunogenic epitope for HTLV-I-specific cytotoxic T cells obtained from circulating PBL of HAM/TSP patients was localized in the HTLV-I pX region. Our aim was to examine variations in these HTLV-I regions between affected and asymptomatic spouses. In the HTLV-I regions studied, we detected no sequence variation between each couple. These data do not favor the hypothesis that neurotropic mutants of HTLV-I are involved in the pathogenesis of HAM/TSP.

Base Sequence↗
PubMed1993

Acute epiglottitis in the adult: experience with a seasonal presentation.

Acute epiglottitis in adults may follow an unpredictable clinical course, complicated by acute airway obstruction. Our experience with this disease was evaluated by looking at yearly incidence, seasonal occurrence, and clinical variables of both intubated and conservatively managed patients. In our series of 17 cases from 1987 through 1990, 16 occurred in 1988 and 1989. Ten of 17 cases occurred during the summer months. The two patients who developed stridor went on to require intubation and tracheotomy. Statistical analysis of our data revealed that, in adult acute epiglottitis, stridor is a strong predictor of airway obstruction. A significant summer seasonal predominance was seen, as well as a suggestion of an epidemic in 1988 and 1989.

Acute Disease↗
PubMed1992

HTLV-I-specific cytotoxic T lymphocytes in the cerebrospinal fluid of patients with HTLV-I-associated neurological disease.

Recently, it has been shown that in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated neurological disease, high levels of HTLV-I-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood. These CTLs predominantly recognized products of the pX region of HTLV-I, had a CD8+ phenotype, and were human leukocyte class I restricted. Moreover, these responses were not detected in asymptomatic, HTLV-I-seropositive individuals. This implied a role for these CTLs in the pathogenesis of the neurological disorder associated with HTLV-I. We have extended these observations by demonstrating HTLV-I-specific CTLs directly from lymphocytes obtained from the cerebrospinal fluid of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. Uncultured cerebrospinal fluid lymphocytes were used directly as effectors on a variety of targets expressing HTLV-I. These cells were lysed in a virus-specific and HLA class I-restricted manner. Moreover, the cerebrospinal fluid lymphocytes were sorted into purified CD8+ populations, cloned by limiting dilution, and assayed for CTL activity. An exceedingly high proportion of these resultant lines were shown to be cytolytic and precursor frequency analysis indicated that as many as 1 in 500 cells were HTLV-I-specific CTLs. The majority of these CTL lines recognized HTLV-I gene products encoded within the pX region of HTLV-I. The significance of these HTLV-I-specific CTLs in the central nervous system of patients with HTLV-I-associated neurological disease is discussed with regard to the potential role of CTLs in the pathogenesis of this disease.

Adult↗
PubMed1992

Preformatted charts improve documentation in the emergency department.

STUDY OBJECTIVES: To determine if the use of programmed charts with complaint-specific entry criteria results in improved documentation of patient encounters and better clinical outcome. DESIGN: Prospective study. SETTING: Emergency department of an urban university hospital. TYPE OF PARTICIPANTS: Female patients presenting to the emergency department with gynecologic complaints of abdominal pain, bleeding, or vaginal discharge. INTERVENTIONS: Programmed and blank charts were provided randomly for physicians in the ED. MEASUREMENTS: Chart scores based on documentation criteria for patient history, physical examination, laboratory studies, diagnosis, and discharge instructions and patient outcome scores of 0% to 100% based on the persistence of their complaints at the time of the follow-up interview. MAIN RESULTS: Overall documentation of history, physical examination, and laboratory studies was more complete on programmed charts than on blank charts (81.1% vs 71%, P less than .0001). The patient history portion of the charts was found to benefit the most from the use of programmed charts (74.8% vs 60.1%, P less than .0001). Although programmed charts demonstrated better documentation, there was no statistically significant correlation with patient outcome parameters or with patient satisfaction with the quality of medical care. However, more patients whose physicians used programmed charts were satisfied with their physicians' explanations of their problem (chi 2 = 5.2, P less than .02). CONCLUSION: Programmed charts improve documentation by facilitation of the documentation process and allow more time for patient-physician interaction. Quality of documentation alone, however, is not a reliable indicator of patient outcome or of the quality of care received.

Abdominal Pain↗
PubMed1992

Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome.

BACKGROUND: The purpose of this study is to provide a case definition of chronic fatigue syndrome in an outbreak occurring in the Nevada-California region to evaluate candidate etiologic agents and observe the natural history of the illness. METHODS: Patients diagnosed as having chronic fatigue syndrome were studied by repeated interviews, questionnaires, and blood collection over a 3-year period. Serum samples were tested for antibodies to Epstein-Barr virus, human herpesvirus-6, and human T-lymphotropic viruses I and II. Leukocytes from typical cases were also assayed for human T-lymphotropic viruses I and II. RESULTS: Cases were defined as persons who had: (1) severe persistent fatigue following an acute illness appearing in an individual with no previous physical or psychological symptoms; (2) presenting signs and symptoms of an acute infection; (3) severe and persistent headache and/or myalgias; and (4) abrupt change in cognitive function or the appearance of a new mood disorder. After 3 years of follow-up, almost all study subjects were able to return to pre-illness activity. None of the viruses evaluated--human T-lymphotropic viruses I and II, Epstein-Barr virus, or human herpesvirus-6--could be etiologically linked to these outbreaks. CONCLUSION: Clinical features of outbreaks of chronic fatigue syndrome differ sufficiently to suggest different etiologic agents. Giardiasis appears to have precipitated one of the four clusters in this study but the cause(s) of the other three outbreaks is as yet uncertain. The overall prognosis of chronic fatigue syndrome is usually favorable.

Antibodies, Viral↗
PubMed1992

Design: a voice activated thermostat.

The voice activated thermostat was designed so the temperature in a house could be set without having to touch the thermostat. This is especially useful for a quadriplegic who would like to change the temperature of the room he is in. For simplicity, it was designed using VCP200 speaker-independent word recognizer chip. This chip comes pre-programmed with a limited number of words, so programming of words was not necessary. Every time the activation word is said the digital thermostat changes by one degree.

Electronics↗
PubMed1991

Induction of CD4+, human T lymphotropic virus type-1-specific cytotoxic T lymphocytes from patients with HAM/TSP. Recognition of an immunogenic region of the gp46 envelope glycoprotein of human T lymphotropic virus type-1.

Although the humoral response to human T lymphotropic virus type-1 (HTLV-I) has been well characterized in patients with HTLV-I-associated neurologic disease (HAM/TSP), little is known about a functional HTLV-I-specific human T cell response, such as CTL, in these patients. To define both the phenotype of the responding CTL and the fine specificity of this response, long term T cell lines were generated from two HAM/TSP patients who were from two different countries. Patient's peripheral blood lymphocytes were repeatedly stimulated in vitro with an HTLV-I expressing autologous T cell line. The resultant long term T cell culture was shown to be CD4+ and cytotoxic for targets expressing HTLV-I Ag. Using a panel of synthetic peptides that span hydrophilic regions of the HTLV-I gp46 envelope glycoprotein, the CTL lines generated from both patients were shown to recognize the same region of the HTLV-I envelope between amino acids 196-209 as defined by the synthetic peptide sp4a1. Interestingly, this sequence overlaps a region of HTLV-I envelope that had also been shown to elicit a strong B cell response in HAM/TSP patients (amino acids 190-203). One CTL line recognized this HTLV-I epitope in the context of HLA DQ5 whereas the other CTL line was restricted by HLA DRw16. The generation of two independent CTL lines from two HAM/TSP patients from different geographic areas that recognize the same region of the HTLV-I envelope glycoprotein highlights the immunogenic nature of this envelope region.

Amino Acid Sequence↗
PubMed1991

Spontaneous lymphocyte proliferation in HTLV-II infection.

We measured lymphocyte proliferation in the absence of antigenic stimulation in 45 HTLV-II infected, 9 HTLV-I infected, and 19 HTLV-I seronegative intravenous drug users (IVDU). Lymphocyte proliferation was higher in IVDUs infected with HTLV-II than in seronegative IVDUs but lower than among those infected with HTLV-I. Higher rates of proliferation were also associated with needle sharing, CD4+ and IL2R+ lymphocyte counts, and HTLV-I antibody titres.

Adult↗
PubMed1991

Changes in leukocyte recirculation, NK cell activity, and HLA-DR expression in peripheral blood mononuclear cells of MS patients treated with Poly ICLC.

To investigate the cellular immune effects of the interferon inducer, Poly ICLC, in humans, peripheral blood mononuclear cells from patients with multiple sclerosis receiving Poly ICLC as part of a preliminary clinical trial were studied. Peripheral blood mononuclear cell phenotype analysis using fluoresceinated monoclonal antibodies and flow microfluorometry showed decreases in the percentages and absolute numbers of all lymphocyte subsets 24 h after infusion. These changes returned toward baseline at 48 h except the percentage of CD-4 positive cell which increased above baseline levels. The percentage of HLA-DR antigen positive cells and CD-16 (Leu 11a) positive cells were increased 24 h after infusion but returned to baseline at 48 h. NK activity as determined by chromium release from K562 target cells was decreased at 24 h but increased 48 h after drug infusion. The increases in percentages of HLA-DR antigen and CD-16 positive cells at 24 h and NK activity at 48 h are consistent with the in vitro effects of IFN while the decreases in peripheral blood mononuclear cells are suggestive of changes in cell recirculation.

Antigens, CD↗