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Biomedical subjects

J B Peter

Publications and source records attributed to J B Peter.

At least 19 recordsLinked to original sources

Laboratory diagnosis of parvovirus B19 infection.

The sensitivity and application of the polymerase chain reaction (PCR) for the diagnosis of parvovirus B19 (B19) infection was investigated by simultaneously assaying a collection of 279 consecutively received samples for presence of anti-B19 IgM and IgG antibodies by Western blot and for B19 DNA by PCR and dot-blot hybridization (dot-blot); samples were sera from patients with suspected B19 infection. PCR and dot-blot detected B19 DNA in 9% (16/179) and 1% (2/179), respectively of Ab-positive samples (IgM+/IgG-, IgM+IgG+, IgM-IgG+), and in 28% (15/54) and 2% (1/54), respectively, of IgM+ samples. PCR also detected B19 DNA in 2% (2/100) of IgM-/IgG- samples, both of which had normal total IgG and IgM levels. PCR is of unique value because it permits diagnosis of B19 infection even in the absence of specific acute phase (IgM) and in the presence or absence of convalescent-phase (IgG) Ab.

Antibodies, Viral

Assessment of different methods to detect increased autochthonous production of immunoglobulin G and oligoclonal immunoglobulins in multiple sclerosis.

The formulae for immunoglobulin G (IgG) synthesis rate, IgG(loc), IgG index, and IgG extended index in determining increased autochthonous production (intra-blood-brain barrier synthesis) of IgG was assessed in 50 chronic progressive multiple sclerosis patients. The results of all four formulae clearly show elevated intra-blood-brain barrier IgG synthesis in 35 patients, 94% of whom had oligoclonal immunoglobulins detected by the method of isoelectric focusing with immunofixation and silver staining (IEF-IS). The results from the four formulae are all normal in seven patients (none have oligoclonal immunoglobulins by IEF-IS) and are discordant in eight patients (five have oligoclonal immunoglobulins by IEF-IS). Whenever intra-blood-brain barrier synthesis of IgG is suspected, IEF-IS should be used to assay for oligoclonal immunoglobulins because this method is more sensitive than agarose electrophoresis with either Coomassie blue dye or silver stain (94% vs. 74% vs. 54%).

Blood-Brain Barrier

Intra-blood-brain barrier synthesis of IgG: comparison of IgG synthesis formulas in a computer model and in 1,629 consecutive specimens.

We evaluated four formulas for estimating the intra-blood-brain barrier (IBBB) synthesis of IgG in a computer model of two types of BBB damage and in 1,629 consecutively received pairs of CSF and serum. These four formulas were the IgG synthesis rate (SR), IgG(loc) (ie, local), IgG index, and IgG extended index. Results from the 1,629 specimens and the computer model of type 2 BBB damage (partial or total loss of selective filtration) accurately predicted problems encountered with the IgG SR in clinical practice. In both the model and with the results from the 1,629 specimens, the combination of the IgG(loc) and IgG index formulas minimized the possibility of false-positive and false-negative results and yielded the most reliable results for IBBB synthesis of IgG in the presence or absence of increased permeability of the BBB. Additional studies with detailed clinical correlations will allow an accurate assessment of how effectively this combination of formulas can help to rule in or out the diagnosis of a particular disease or inflammatory condition of the CNS.

Albumins

Hypogammaglobulinemia in asthmatic patients.

We measured quantitative immunoglobulins (IgG, IgA, IgM, and IgG subclasses) in 101 unselected asthmatic patients. We identified hypogammaglobulinemia in 12 patients primarily involving IgG (dose-related) without a strong prediction for any IgG subclass. IgA and IgM were also suppressed but to a lesser extent. This prevalence of hypogammaglobulinemia (.12 +/- standard error of .03) is significantly greater than that seen in the normal population (approximately .025 +/- .017, P = .01). Hypogammaglobulinemia was strongly associated with use of systemic corticosteroids (P = .0001). A cumulative steroid dose of greater than or equal to 5 mg/day for at least 2 years was found in 10/12 patients with hypogammaglobulinemia compared with 37/89 patients without hypogammaglobulinemia (P = .024). No significant increase in the number of infectious episodes was seen in the hypogammaglobulinemic patients. To assess the significance of hypogammaglobulinemia in asthmatics, we assessed responses to tetanus and pneumococcal vaccine in three groups of asthmatics: (1) those with total IgG less than 400 mg/dL who had been on chronic oral steroids, (2) those with total IgG between 855 and 1199 mg/dL who were currently receiving oral steroids, and (3) those with total IgG between 855 and 1199 mg/dL who were not receiving oral steroids. All patients responded normally to tetanus vaccine, but three of eight patients in the hypogammaglobulinemic group showed impaired responses to pneumococcal vaccine. Patients with impaired pneumococcal responses were not clearly distinguishable on the basis of sinus disease or pneumonia. We conclude that although many patients with severe, steroid-dependent asthma experience repeated episodes of bronchitis or exacerbations of sinusitis, these problems are rarely associated with an impairment in specific antibody production. IgG subclass deficiencies are not common in this patient population. A very small subgroup of patients manifest a more severe hypogammaglobulinemia (IgG less than 400 mg/dL) or an inordinate frequency of infectious episodes. Given that bronchitis or sinusitis can be attributed to factors other than hypogammaglobulinemia in these patients, an assessment of specific antibody production in response to pneumococcal vaccination is warranted. A small but significant percentage of such patients will demonstrate impaired responses. These patients should be considered at increased risk for bacterial infections and should, therefore, be monitored closely for infectious episodes.

Adolescent

The new HLA.

The application of molecular genetics and biochemical techniques to the study of the HLA system over the past few years has resulted in tremendous advances in our knowledge of this area of the human genome. In this article, we describe the "new HLA" that has been pieced together recently through the combined efforts of molecular geneticists, biochemists, and HLA serologists, as well as developments in attempts to elucidate the associations of HLA antigens and disease.

Biochemical Phenomena

Neopterin and beta 2-microglobulin and the assessment of intra-blood-brain-barrier synthesis of HIV-specific and total IgG.

In HIV-seropositive patients, we evaluated the clinical utility of measuring combinations of serum and CSF levels of neopterin and beta 2-microglobulin (beta 2-M) (by RIA), as well as the intra-blood-brain-barrier (IBBB) IgG synthesis rate, IgG index, and HIV antibody index (by rate nephelometry, EIA, and formulae) for the assessment of HIV infection of the CNS. We studied paired sera and CSF from 31 HIV-seropositive patients: asymptomatic (16), ARC (12), and AIDS (3). A normal serum neopterin level predicts normal levels of serum beta 2-M, CSF neopterin, or CSF beta 2-M in 90%, 100%, and 100%, respectively, of our patients. An elevated serum neopterin level predicts an elevated level of serum beta 2-M or CSF neopterin in 81% and 62%, respectively, of cases. The HIV antibody index and IBBB IgG synthesis rate or IgG index must be determined separately because they do not predict each other and are not predicted by levels of neopterin or beta 2-M.

Antibodies, Viral

DNA ploidy and cell-cycle analysis: tools for assessment of cancer prognosis.

DNA ploidy and cell cycle analysis as measured by flow cytometry (FC) and image analysis (IA) have moved out of the realm of the research laboratory to become valid clinical tests used in the assessment of prognosis of the cancer patient. Although much information on the relationship of DNA ploidy/%S-phase analysis to patient prognosis is available in the literature, the data are not presented in such a way as to be helpful in clinical decision making. Because predictive values and confidence intervals, which measure the likelihood that a given clinical test will rule in or rule out a clinical outcome, were not calculated in previous reviews, conclusions about the clinical utility of these analyses were not possible. Using the available raw data on DNA ploidy and %S-phase analysis from previously published papers, predictive values and confidence limits were calculated for specific clinical presentations. In several such clinical situations (tumor type, stage, etc.), predictive value of greater than 90% was derived. We conclude that in these situations DNA ploidy and %S-phase analysis can be used to predict clinical outcome, to design treatment, and to guide patient management. The evaluation of the clinical utility of these tests must ultimately rest on prospective trials which show that randomized arms respond to treatment regimens dependent upon the DNA ploidy and %S-phase status.

Cell Cycle

Selective IgA deficiency, IgG subclass deficiency, and the major histocompatibility complex.

Here we have examined the connection between IgA deficiency, IgG subclass deficiency, and the absence of alleles of complement C4, and show that IgA deficient subjects who have IgG subclass deficiencies may also have an increased frequency of C4 null alleles. In our group, we found an increased incidence of HLA B38 which might reflect the ethnic composition of the patients tested. While family studies are of primary importance to assess the relationships between histocompatibility antigens and immune deficiency, these studies are complicated by the observation that C4 null alleles are not always inherited with the humoral defect.

Adult

Serum and CSF levels of IL-2, sIL-2R, TNF-alpha, and IL-1 beta in chronic progressive multiple sclerosis: expected lack of clinical utility.

We measured interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) by ELISA in paired sera and CSF from 50 chronic progressive multiple sclerosis (CPMS) patients during worsening disability, 19 patients with other neurologic diseases (OND), and in sera from 40 healthy volunteers. In the CPMS patients, 28% (14/50), 10% (5/50), 16% (8/50), and 6% (3/50) had elevated serum levels of IL-2, sIL-2R, TNF-alpha and IL-1 beta, respectively, compared with healthy controls. The only analyte we detected in the CSF was IL-2 in 1 CPMS patient (1/50, 2%). We also saw elevated serum sIL-2R in 16% (3/19) of OND patients. We found no significant difference in mean levels of serum sIL-2R between the 3 groups. Our study, the largest to date of CPMS patients, shows that serum and CSF levels of IL-2, sIL-2R, TNF-alpha, or IL-1 beta are not sensitive for, and the serum sIL-2R level is not specific for, CPMS. Therefore, measurement of these analytes will not be clinically useful for therapeutic or prognostic purposes in the majority of CPMS patients.

Chronic Disease

B-cell surface phenotypes of proliferating myeloma cells: target antigens for immunotherapy.

Dual-parameter flow cytometric analysis of B-cell antigens and DNA content was used to determine the phenotypes of proliferating tumor cells (S-phase cells) from 30 patients with multiple myeloma. B4 (CD19), J5 (CALLA, CD10), B1 (CD20), and monotypic surface immunoglobulin (Slg) were expressed heterogeneously in 24 patients. J5 and monotypic Slg were found most frequently but were always expressed on a significantly lower percentage of cells than the antigens typically associated with plasma cells, cytoplasmic immunoglobulin (Clg) and T10 (CD38). S-phase cells were found in each antigen(+) subset. B antigen(+) cycling cells were demonstrated in 16 patients whose marrow or blood cells expressed B antigens exclusively in the hyperdiploid fraction and therefore were certainly part of the myeloma clone. Similar to the low level of proliferative activity of the T10(+), Clg(+), and PCA1(+) subsets, the percentages of cycling cells of the preplasma cell B-antigen-bearing myeloma subsets ranged from less than 1% to 12%. The tumor cells of four patients were also studied with dual-color surface antigen analysis and demonstrated independent expression of B antigens, with only rare coexpression of T10 and monotypic Slg, J5, or B4. These findings are consistent with the presence of distinct myeloma subsets bearing differing B phenotypes in the same tumor and provide evidence that the proliferation in myeloma is occurring at various developmental stages in the malignant B lineage. These antigens may be important targets for immunologic therapy aimed at eliminating the entire proliferating compartment of this B-cell tumor.

Antigens, Differentiation, B-Lymphocyte

Dietary regulation of fibrinolytic factors.

W examined the short-term effects of a high-complex carbohydrate, low fat diet on the plasmin-dependent fibrinolytic pathway. A population of 27 adult American Caucasians exposed to the diet for 3 weeks showed highly significant reductions in the levels of plasminogen (P = 0.0001), tissue plasminogen activator (tPA) (P = 0.0001) and plasminogen activator inhibitor (tPAI) (P = 0.0017). Fibrinogen levels also decreased, but the changes did not reach statistical significance (P = 0.07). In contrast, the levels of the Lpa(a) lipoprotein, a potential inhibitor of fibrinolysis, remained remarkably constant despite a marked decrease in the levels of apolipoprotein B, a major constituent of Lp(a). Correlations between the levels of tPA, tPAI and plasma triglyceride were observed among the individuals both before and after the dietary challenge. Although the mechanisms responsible for the effects are unknown, the dramatic responsiveness of the thrombolytic pathway to dietary challenge is likely to be of importance in understanding the etiology of coronary artery disease and other vascular disorders.

Apolipoproteins