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Biomedical subjects

S Jacobson

Publications and source records attributed to S Jacobson.

At least 181 records · Page 10Linked to original sources

DNA restriction fragment length polymorphism of HLA-DR2: correlation with HLA-DR2-associated functions.

HLA-DR2 can be divided into at least 3 distinct HLA-D clusters which correlate with structural differences within the HLA-D region. Further, a functional counterpart of this subdivision has been previously identified. The presence of a particular DR beta 2 polypeptide chain correlated precisely with the susceptibility of measles virus-infected HLA-DR2 homozygous typing cell lines to lysis by measles virus-specific, HLA class II-restricted CTL clones. To determine if a genetic basis for these functional differences could be detected, the degree of polymorphism at the DNA level within the serologically defined HLA-DR2 haplotype has been examined. By using DNA probes for DR beta and DQ beta 4 of the 5 HLA-D clusters of HLA-DR2 could be distinguished and a RFLP pattern was identified which correlates with known immunological functions associated with these various D types. In addition, this technique of 'molecular genotyping' was used to investigate a limited panel of patients with multiple sclerosis (MS) who were HLA typed as either HLA-DR2,2 or HLA-DR2,blank. The RFLP profile of the HLA-DR2 Dw2 D type was found in all of these MS patients.

Cell Line↗

Serum concentrations of meperidine in patients with sickle cell crisis.

We compared mean serum concentrations of meperidine in sickle cell patients in crisis and control patients receiving meperidine prior to incision and drainage of abscesses. Eight sickle cell and five control patients without confounding illnesses consented to participate and received 100 mg meperidine in the deltoid or gluteal muscle for pain. Blood samples were drawn at baseline, 0.25, 0.50, 0.75, 1.0, 1.5, and 2.0 hours postinjection. In the sickle cell group, mean peak concentration of meperidine was 0.32 +/- 0.08 micrograms/mL at an average of 0.5 +/- 0.07 hours postinjection. Among controls mean peak concentration was 0.72 +/- 0.37 micrograms/mL at an average of 0.6 +/- 0.11 hours. The difference in peak concentrations was significant at all time intervals (P less than .01); the difference in times to peak was not significant. We conclude that, given a standard dose, serum concentrations of meperidine differ between sickle cell and control patients, which may suggest reasons for the relatively poor pain control often noted in sickle cell patients.

Absorption↗

Impaired measles virus-specific cytotoxic T cell responses in multiple sclerosis.

To assess whether an virus-specific immune defect may be associated with multiple sclerosis (MS), we have examined the ability to generate measles virus-and influenza virus-specific cytotoxic T cells (CTL) in patients with MS, normal individuals, and other disease controls (ODC). The mean (+/- SEM) measles virus-specific CTL response for normal individuals and ODC was 26.9 +/- 2.9% (N = 17) and 26.7 +/- 2.8% (N = 13) specific lysis, respectively. In contrast, the capacity of MS patients to generate measles virus-specific CTL was markedly diminished. Peripheral blood lymphocytes from MS patients stimulated with measles virus lysed their measles virus-infected autologous B cell line at a group mean level of 6.0 +/- 1.4% (N = 16) specific lysis. MS patients had significantly lower measles virus-specific CTL responses than normal individuals (p less than 0.00001) or ODC (p less than 0.0001). Importantly, this lowered response did not reflect a generalized depressed cytolytic activity of MS patients, since influenza virus-specific CTL and NK activity from these patients were comparable to normals and ODC. Thus, in MS there is a significant depression of measles virus-specific CTL which suggests that this virus-specific immune dysfunction may play a role in the pathogenesis of this disorder.

Adolescent↗

Identification of a specific HLA DR2 Ia molecule as a restriction element for measles virus-specific HLA class II-restricted cytotoxic T cell clones.

By using a panel of HLA-D-defined subtypes of HLA-DR2 HCL with known beta chain structural variabilities, we have demonstrated that HLA-DR2, OKT4+ cytotoxic T lymphocyte (CTL) clones specific for measles virus are apparently restricted to a distinct DR beta chain. The presence of this DR beta 2 molecule correlated precisely with the susceptibility of measles virus-infected HLA-DR2 HCL to lysis by these CTL clones. These studies demonstrate that delineation of HLA-DR2 into various subgroups can have a functional significance that parallels the structural differences within the HLA-D region. These results are discussed in the context of the possible association of HLA class II-restricted, measles virus-specific CTL and multiple sclerosis.

B-Lymphocytes↗

Comparison of the performance of serum and urine hCG immunoassays in the evaluation of gynecologic patients.

We conducted a study to compare the performance of serum and urine pregnancy tests in the evaluation of gynecologic patients presenting to our ED. The overall efficiency of the two tests was very similar: 99.5% for the serum test, and 97.6% for the urine test. In patients proven to have ectopic pregnancies, however, the serum test was positive in 100%; the urine test was positive in only 60%. The serum test misclassified (gave false-negative or false-positive results) in three of 607 patients (0.5%). The urine test misclassified 14 of 607 patients (2.3%). Moreover there were 18 inconclusive or invalid urine test results. Thus the urine test provided misinformation or no information in 32 of 607, or 5.3%, of the total study population.

Chorionic Gonadotropin↗

Concentration of selenium in plasma and erythrocytes during total parenteral nutrition in Crohn's disease.

Plasma- and erythrocyte-selenium concentrations were determined in five consecutive patients with Crohn's disease given preoperative total parenteral nutrition - nil per os - for a mean period of 34 days per patient. No blood components were administered during the total parenteral nutrition. Before the total parenteral nutrition the plasma-selenium level and, to a less extent, the erythrocyte-selenium levels were below the reference values. After three weeks of total parenteral nutrition both concentrations had fallen. There were, however, clinical and biochemical signs of improvement during the total parenteral nutrition, as indicated by an increase in body weight, P-albumin and P-transferrin. In one female patient given 39 days of preoperative total parenteral nutrition containing 0.06 mumol (5 micrograms) selenium per 24 h the decreasing levels of plasma-selenium and erythrocyte-selenium were both correlated to the duration of the total parenteral nutrition (r = 0.87 and 0.96, respectively). The results suggest that total parenteral nutrition patients may be at risk for selenium deficiency, and that a supplementary administration of selenium via total parenteral nutrition may be required.

Adult↗

Distinct proliferative T cell clonotypes are generated in response to a murine retrovirus-induced syngeneic T cell leukemia: viral gp70 antigen-specific MT4+ clones and Lyt-2+ cytolytic clones which recognize a tumor-specific cell surface antigen.

After immunization of B6 mice with the syngeneic retrovirus-induced T cell leukemia/lymphoma FBL-3, two major tumor-specific proliferative T cell clonotypes were derived. T cell clones derived from long-term lines propagated by in vitro culture with irradiated tumor cells and syngeneic spleen cells were exclusively of the Lyt-2+ phenotype. Such clones were cytolytic, retained their proliferative phenotype indefinitely when expanded by repeated cycles of reactivation and rest, and recognized a tumor-specific cell surface antigen in association with class I MHC molecules. This tumor cell antigen was not present on nontransformed virus-infected cells. Class II MHC-restricted MT4+ clones specific for the viral antigen gp70 were derived from lymph node T cells of FBL-3 tumor-immune mice only by in vitro culture with purified Friend virus in the presence of syngeneic splenic APC. Once derived, however, such clones could be stimulated in the presence of FBL-3 tumor cells and syngeneic spleen cells, demonstrating the reprocessing of tumor-derived gp70 antigen by APC in the spleen cell population. In contrast, no reprocessing of the tumor cell surface antigen by splenic APC for presentation to the class I MHC-restricted T cell clones could be demonstrated. Evidence is presented that FBL-3 T leukemia/lymphoma cells function as APC for Lyt-2+ class I MHC-restricted clones, and that no concomitant recognition of Ia molecules is required to activate these clones. Both Lyt-2+ and MT4+ clones were induced to proliferate in the presence of exogenous IL2 alone, but this stimulus failed to result in significant release of immune interferon. In contrast, antigen stimulation of both clones resulted in proliferation as well as significant immune interferon release. Immune interferon production is not required for the generation of MHC-restricted cell-mediated cytolytic function.

Animals↗

Distribution of immunoreactive growth hormone releasing factor(1-44)NH2 in the tuberoinfundibular system of the rhesus monkey.

Using an antiserum which reacts with the carboxyl terminus of GRF(1-44)NH2, the distribution of immunoreactive growth hormone releasing factor (GRF) in the rhesus monkey hypothalamus was delineated by peroxidase immunocytochemistry. Immunoreactive material was present in dense terminal fields in the median eminence closely associated with portal capillaries but in a location distinct from that noted for immunoreactive thyrotropin-releasing hormone (TRH) or somatostatin. GRF-immunoreactive cell bodies were identified in the arcuate nucleus and ventromedial nucleus. These studies provide evidence for the presence of GRF(1-44)NH2 in the primate brain and demonstrate that in the hypothalamus it is localized exclusively in cells and fibers corresponding to the tuberoinfundibular system.

Animals↗

Urinary excretion and blood concentrations of trace elements and electrolytes during total parenteral nutrition in Crohn's disease.

Urinary excretion of trace elements (Cr, Co, Cu, Fe, Mn, Se, Zn, Sb, Cs, Rb), electrolytes (Na, K, Ca, Mg, phosphate), and nitrogen were determined during days 1-5 and 54-79 of total parenteral nutrition (TPN, nil per os) given to six patients with Crohn's disease. Whole-blood concentrations of Cr, Fe, Zn, Cs, and Rb and serum concentrations of electrolytes were determined before the TPN and on days 54-79 of TPN. The 24-hr urinary excretion of zinc was lower on days 54-79 than on days 1-5, but the rates of excretion of the other essential trace elements during TPN displayed no significant change. The urinary excretion of Cu, Fe, and Mn was numerically lower than the intravenous administration of these elements during days 1-5 and 54-79 of TPN, whereas the urinary excretion of zinc was lower than the supply only during days 54-79. The whole-blood concentration of zinc was low but constant during TPN, whereas the initially low levels of Cr and Fe were normalized on days 54-79. The results suggest that the supply of the essential trace elements Cr, Co, Cu, Fe, Mn, and Zn was largely adequate during two to three months of TPN and that the human body may adapt to a somewhat low supply of zinc, 20-30 mumol/24 hr.

Adolescent↗

The distribution of thyrotropin-releasing hormone (TRH) in the rhesus monkey spinal cord.

The distribution of thyrotropin-releasing hormone (TRH) in the Rhesus monkey spinal cord was studied using a highly specific antibody to TRH and the indirect peroxidase-antiperoxidase technique. TRH-positive fibers were found at all levels of the spinal cord and were in greatest concentration in the ventral gray, intermediolateral column and central gray. All motor nuclear groups in lamina IX of the ventral gray were innervated by TRH, frequently in close association with perikarya of alpha-motoneurons. The motor nuclei in the lumbar cord were the most heavily stained and contrasted to the minimal staining in the retrodorsolateral nuclear groups of the cervical, thoracic and sacral cord. Within the intermediolateral column, which contains the majority of preganglionic sympathetic neurons, TRH terminal fields reached their highest density between T2-T4 and T12-L2. Other preganglionic neurons including the nucleus intercalatus spinalis and the dorsal commissural nucleus were also densely innervated. These studies demonstrate the preferential distribution of TRH in the monkey spinal cord to regions containing alpha-motoneurons and preganglionic neurons and indicate that TRH may play an important role in the regulation of motor function and in the autonomic nervous system.

Animals↗

Psychiatry in the emergency department: factors associated with treatment and disposition.

Patients with psychiatric problems present difficult treatment and dispositional decisions to physicians in general hospital emergency departments (ED). We studied the relationships between the psychosocial characteristics of patients given psychiatric diagnoses and clinical decisions made by nonpsychiatrists and psychiatrists in our ED. Decisions concerning psychiatric consultation in the ED, dispositional decisions (admission, discharge), and referral for psychiatric outpatient care for patients discharged were reviewed for 246 patients. The relationships between decisions and 13 indicators of patients' psychosocial characteristics were evaluated by use of stepwise logistic regression techniques. Psychiatric-related variables (severity of symptoms, history of psychiatric hospitalization or outpatient treatment, and psychotropic medications at entry to the ED) were associated with decisions made by both psychiatrists and nonpsychiatrists. However, nonpsychiatric variables including patient's age, "rudeness," diffuseness of medical complaints, time of day, and month of presentation also were related to decisions. Practitioners should be sensitive to social factors that affect their decisions about psychiatric patients.

Adolescent↗

Assessing the quality of emergency care: the medical record versus patient outcome.

The relationship between the quality of medical records and patients' health status outcomes remains unclear. For a group of patients treated and discharged with diagnoses of acute bronchial asthma, we asked: Is the quality of medical records directly and positively related to the quality of patients' health status outcomes once factors not completely within physicians' control are taken into account? Record quality was assessed by comparing information recorded with a set of criteria considered to constitute effective care. Data reflecting health status were based on telephone interviews with patients one to three and 10 to 12 days following visits. Correlation and multiple regression analyses showed the quality of records to be negatively, although not significantly, related to patients' health statuses. The results of the analyses are used to assess the adequacy of quality assurance programs concerned only with the quality of medical records, and to evaluate the advantages and disadvantages of including assessments of patients' health statuses in regular quality assurance reviews. We conclude that quality assurance programs periodically should include reviews of patients' health status outcomes.

Adolescent↗

Measles virus-specific T4+ human cytotoxic T cell clones are restricted by class II HLA antigens.

We have generated measles virus-specific T cell clones from a patient with multiple sclerosis who has been described previously as a strong responder to measles virus. T cell clones were screened on the basis of their capacity to proliferate to measles virus. The cell surface phenotype of each clone was OKT3+, OKT4+, OKT8-. The majority of these clones (11 of 14) were cytotoxic for their autologous measles virus-infected lymphoblastoid B cell target. This cytotoxicity was specific for measles virus inasmuch as these T cell clones could not lyse influenza or mumps virus-infected B cell targets. By using a panel of HLA-defined measles virus-infected B cell lines, these clones were shown to recognize measles virus in the context of HLA class II determinants. A monoclonal antibody that recognizes HLA class II monomorphic determinants (L243), but not a monoclonal antibody that recognizes HLA class I antigens (W6/32), inhibited the lysis of the autologous measles virus-infected B cell target by these T cell clones. These results demonstrate that these cytotoxic T cell clones specific for measles virus are HLA class II restricted.

Clone Cells↗