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Biomedical subjects

F E Ward

Publications and source records attributed to F E Ward.

At least 55 records · Page 3Linked to original sources
PubMed1985

Comparison of multiple HLA-A alleles at the DNA level by using Southern blotting and HLA-A-specific probes.

Numerous alleles of the HLA-A gene have been serologically identified. In this report we present a rapid and straightforward means to assess HLA-A polymorphism at the genomic level. Using 5' and 3' HLA-A-specific DNA probes and Southern blotting, we have placed the recognition sequences for five endonucleases relative to the coding regions of 15 HLA-A alleles. These data permit two interesting conclusions: four of the HLA-A alleles studied are associated with unique restriction fragments, and HLA-A alleles of a cross-reactive group are more closely related at the DNA level than are noncross-reactive alleles.

Alleles↗
PubMed1985

Color discrimination as a function of saturation, field size, and adaptation level.

The purpose of our research was to investigate color discrimination under conditions of ambient illumination that may reduce CRT display saturation and contrast. Our research measured both the variability of color matching and the offsets from a match necessary for a 100% discrimination difference. We did this for four dominant wavelengths each at five saturation levels. Our subjects were tested at low, medium, and high adaptation levels for both large and small test stimulus sizes. In general, our results for the low luminance color matching conditions are in agreement with the published literature. For the high luminance and small field conditions, our data suggest that color discrimination should not be predicted from the 1960 CIE Uniform Chromaticity Space data. Color discrimination varies dramatically with dominant wavelength; reds and greens are more difficult to discriminate than yellows and yellow-greens.

Adaptation, Physiological↗
PubMed1984

Severe combined immunodeficiency with natural killer-cell predominance: abrogation of graft-versus-host disease and immunologic reconstitution with HLA-identical bone marrow cells.

A 3 1/2-month-old infant with severe combined immunodeficiency was found to have an unusual blood lymphocyte phenotype. Thirty percent of her cells formed rosettes with sheep erythrocytes, but only 7.9% reacted with the pan T monoclonal antibody OKT3, and 5% reacted with an antibody (OKT4)-recognizing T-helper cells. Surprisingly 19.4% of her cells reacted with an antibody (OKT8)-recognizing T-suppressor cells and 94% reacted with OKT10 . Few reacted with other monoclonal antibodies detecting cellular activation antigens. Despite absence of T or B cell function, her monocyte-depleted blood lymphocytes caused a high degree of specific lysis of 51Cr-labeled K562 erythromyeloid cells in a natural killer-cell assay. Most of her lymphocytes were large and had azurophilic granules and a monocytoid nucleus. Because she had received a nonirradiated, unrelated red-cell transfusion 3 days earlier, 4.8 X 10(9) nucleated bone-marrow cells from her HLA-identical brother were given shortly after admission. Two days later a graft-versus-host reaction began but subsided completely within 3 days. On day 15 posttransplantation, a profuse secretory diarrhea began, accompanied by a rise in her serum IgE from 4 to 3000 IU. With engraftment, the number of T10+ cells and natural killer-cell function fell to normal, and full immunologic reconstitution was achieved.

Antibodies, Monoclonal↗
PubMed1984

Monocyte suppression of antigen-specific lymphocyte responses in diffuse cutaneous leishmaniasis patients from the Dominican Republic.

Patients from the Dominican Republic with diffuse cutaneous leishmaniasis showed in vivo and in vitro anergy to leishmanial antigen. Relatives of these DCL patients living in the same endemic area frequently showed skin test and lymphocyte reactivity to leishmanial antigens. This further supports the concept of specific anergy in patients with diffuse cutaneous leishmaniasis. Adherent suppressor cells modulate the antigen-specific lymphocyte proliferative response. Suppressor cells could also be isolated by Percoll gradient centrifugation. Co-culturing of lymphocytes and monocytes from HLA-identical leishmanin responders and nonresponders also identified the suppressor cell as a monocyte. In one patient, this suppression disappeared when clinical cure had been accomplished.

Adolescent↗
PubMed1983

Isolation of heavy chain class switch variants of a monoclonal anti-DC1 hybridoma cell line: effective conversion of noncytotoxic IgG1 antibodies to cytotoxic IgG2 antibodies.

Spontaneously arising class switch variants of the Genox 3.53 hybridoma cell line were isolated. They secrete IgG2a or IgG2b monoclonal antibodies of anti-DC1 specificity identical to that of the IgG1 secreting parental cell. In contrast to the parental monoclonal antibody, those secreted by the variants are cytotoxic to peripheral blood B lymphocytes of DC1 positive individuals and are thus compatible with existing HLA typing techniques. This provides a general method for converting noncytotoxic anti-HLA antibodies into cytotoxic typing reagents.

Animals↗
PubMed1983

SFR3-DR5, a monoclonal antibody with HLA-DR5 specificity.

We have developed a monoclonal antibody with HLA-DR5 serologic specificity. The antibody, SFR3-DR5, binds specifically to DR5-positive lymphoblastoid cell lines, and immunoprecipitates alpha- and beta-chains characteristic of DR antigens from them. Cytotoxic activity of the antibody segregates with the DR5-bearing haplotype in a family. The antibody reacted with the cells of 16 of 17 DR5 individuals and was negative on all DR5-negative cells tested. SFR3-DR5 reacted weakly with PWM-activated cells of the single DR5 individual whose B lymphocytes were unreactive with the monoclonal antibody by cytotoxicity. Possible interpretations of these results are discussed.

Animals↗
PubMed1982

DR antigens on melanoma cells: analysis with monoclonal antibodies.

Two monoclonal antibodies (691-13-17 and 37-7) can precipitate DR antigens from radioiodinated, detergent solubilized melanoma cells. However, after complete depletion of lysates with one antibody (691-13-17) alpha-like chains can be still be precipitated from some melanoma cells by the other antibody (37-7). Antibody 37-7 also precipitates an additional distinct antigen from SK-MEL 37 but not from any five other melanoma cell lines.

Animals↗
PubMed1982

Homogeneous substrate-labeled fluorescent immunoassay for carbamazepine.

Carbamazepine is an anticonvulsant drug useful in the management of epilepsy. Because of the narrow therapeutic range, serum carbamazepine monitoring is useful for ensuring adequate drug therapy without toxicity. We report the development of a homogeneous substrate-labeled fluorescent immunoassay for carbamazepine in human serum. A carbamazepine fluorogenic reagent (FR) has been synthesized. Upon hydrolysis by beta-galactosidase, the nonfluorescent FR produces a fluorescent product. This enzymic hydrolysis sin inhibited when the FR binds with antibody against carbamazepine. The inhibition is relieved when carbamazepine competes with FR for available antibody binding sites. Thus, increasing levels of carbamazepine result in increasing levels of fluorescence that can be conveniently monitored with any conventional fluorometer. For low, medium, and high control sera (4, 12, and 16 micrograms carbamazepine/ml), the within-run coefficient of variation for the assay is 5.5%, 1.6%, and 2.9%, respectively, while the respective between-run coefficients of variation are 3.5%, 1.9%, and 2.3%. Fifty-three clinical serum samples were assayed by the SLFIA, gas chromatography (GC), high pressure liquid chromatography (HPLC), and an enzyme immunoassay method. The SLFIA method compares favorably with the HPLC technique (r - 0.97, slope = 1.10, y-intercept = 1.21), the enzyme immunoassay (r = 0.98, slope = 1.07, y-intercept = 0.82), and the GC method (r = 0.95, slope = 1.01, y-intercept = -0.03).

Antibodies↗
PubMed1981

Lymphocyte suppressor activity in patients with polyglandular failure.

The Con-A--activated suppressor function of lymphocytes from polyglandular failure (PGF) patients in human mixed lymphocyte culture was compared to a normal population. As a group, PGF patients were found to have decreased suppressor activity: 67% of normal for autologous suppression, 45% of normal for heterologous. However, lymphocytes from most PGF patients have neither an absolute lack of suppressor activity nor an absolute inability to respond to suppression. The marked variability of assayed suppression, depending on the combination of stimulators and responder cells tested, limit the utility of this assay in defining individuals with abnormal suppressor function. One patient's lymphocytes were unique in that although suppression of heterologous cells was normal, suppression of her own cells was defective. Defective suppressor function may be related to the susceptibility of these patients to multiple autoimmune diseases.

Adult↗
PubMed1981

Statistical methods for studying homozygous typing cells of unknown specificity.

A situation can arise in D typing in which the HLA (A,B,C,D, or DR) specificities of the responders are known and the specificities of the HTC's are unknown. The most powerful and direct method of detecting association between the unknown stimulator (HTC) and any given HLA specificity is by comparing the observed double normalized values (DNV's) of individuals known to be positive for the specificity with the DNV's of negative individuals. This can be done by comparing the two groups with a Kolmogorov-Smirnov test (K-S test), an established statistical procedure for evaluating correlation between continuous variables, such as the DNV, and discrete variables (such as presence of D type). The application of the K-S test will generate as a "cutoff" value of point that maximizes the average of the frequencies of correct assignments in D positives and D negatives. We also propose an alternative method of computing the "r" value. We have analyzed 49 HTC's from the 8th International Workshop and present the association observed with the D and DR specificities.

Alleles↗
PubMed1981

Antimicrobial 3-methyleneflavanones.

The antimicrobial activity previously attributed to flavanone Mannich bases was found to be due to their breakdown products, 3-methyleneflavanones. Among the latter compounds, highest potency was observed when the flavanone phenyl ring contained bromine or chlorine substituents. 3-Methylene-2-phenylflavanone (8) was synthesized and shown to be equal to hexachlorophene in tests against representative Gram-positive microorganisms.

Anti-Bacterial Agents↗
PubMed1981

Familial predisposition to filarial infection--not linked to HLA-A or-B locus specificities.

Two hundred and twenty-five Polynesians were selected from a larger study population for the evaluation of potential genetic influences on the susceptibility to bancroftian filariasis. Analysis showed that there was significantly familial clustering of patients with filariasis and that this clustering was most compatible with genetic transmission of disease susceptibility. The data best fit a model in which the hypothetical gene for filariasis was recessive with a frequency of 0.82 +/- 0.15 in the population and a penetrance of 0.62 +/- 0.14. The alternative hypothesis that susceptibility was environmentally (i.e., not genetically) determined was also compatible with the data but was estimated to be 1.9 times less likely to account for the observed findings than the genetic hypothesis. Extensive evaluation of HLA-A and -B locus specificities failed to detect significant linkage either between particular antigen specificities and the clinical manifestations of filariasis or between individual haplotypes (indicated by HLA markers in studies of large families) and the predisposition to filarial infection or disease.

Adolescent↗
PubMed1981

A homogeneous fluorescent immunoassay for human immunoglobulin M.

We describe a homogeneous substrate-labeled fluorescent immunoassay for human IgM. In this competitive-binding method we use a fluorogenic substrate for Escherichia coli beta-galactosidase, N-(6-aminohexyl)-7-beta-galactosyl-coumarin-3-carboxamide, which is covalently coupled to IgM. The fluorescence emission intensity of the labeled IgM at 450 nm (with excitation at 400 nm) is negligible, but when beta-galactosidase is added, the acetal linkage of the galactosyl moiety is hydrolyzed and the product has a greatly enhanced fluorescence. Formation of this fluorescent product is inhibited when antibody specific for IgM is bound to the labeled protein. In competitive-binding reactions, IgM from the serum competes with the labeled IgM for antibody binding sites and consequently the fluorescence produced by the enzymic reaction is related to the IgM concentration. The working range of the assay is between 0.5 and 5.0 g of IgM per liter when a 50-fold predilution of the sera is used. The assay does not cross react significantly with immunoglobulins G or A.

Fluorescent Antibody Technique↗
PubMed1980

Virus-immune cytotoxic T cells recognize structural differences between serologically indistinguishable HLA-A2 molecules.

The self-specificity of human influenza virus-immune cytotoxic T cells has been analyzed in order to identify the relationship between the self-determinants which they recognize and the serologically defined HLA-A and -B antigenic determinants. Virus-immune T cells were generated in vitro by culture of normal adult peripheral blood lymphocytes with A/HK influenza virus. Virus-immune effectors from HLA-A2 positive donors were tested on panels of virus-infected target cells from donors who were either HLA-mismatched or matched only for the HLA-A2 specificity. Virus-immune T cells from 11/11 A2-positive donors lysed all A2-matched virus-infected target cells (and no HLA-mismatched targets), except that each of these effector cell populations consistently failed to lyse the virus-infected target cells from one A2-positive donor (designated M7). Although the A2 antigen of donor M7 could also be distinguished from the A2 antigen of other donors by alloimmune cytotoxic T cells, no differences in the A2 antigen of donor M7 could be defined by extensive serological analyses. Results of isoelectric focusing of A2 molecules from three individuals plus M7 demonstrated that the M7 A2 heavy-polypeptide chain is structurally distinct. These results indicate that: 1) there is a strong but incomplete association between a self antigen recognized by virus-immune T cells and the serologically defined HLA-A2 specificity; and 2) there may be at least two structurally and functionally distinct epitopes on the same A2 molecule: one is the serologically defined HLA-A2 antigenic determinant; the other is the self determinant recognized by T cells on HLA-A2 molecules.

Cell Line↗
PubMed1980

The self determinants recognized by human virus-immune T cells can be distinguished from the serologically defined HLA antigens.

The self specificity of human influenza virus-immune cytotoxic T cells has been analyzed in order to clarify the relationship between the self antigens that they recognize and the serologically defined HLA-A and -B antigens. Virus-immune effectors from HLA-A2-positive donors were tested on panels of virus-infected target cells from donors who were either HLA-mismatched or matched only for HLA-A2. Virus-immune T cells from 11 out of 11 A2-positive donors lysed all A2-matched virus-infected target cells (and no HLA-mismatched targets), except that each of these effector cells consistently failed to lyse virus-infected target cells from one A2-positive donor (designated M7). Although the A2 specificity of donor M7 could also be distinguished from the A2 antigen of other donors by alloimmune cytotoxic T cells, no differences in the A2 antigen of donor M7 could be defined by extensive serologic analyses. These results indicate that there is a strong but incomplete association between a self antigen recognized by virus-immune T cells and the serologically defined HLA-A2 specificity.

Absorption↗
PubMed1979

Human eye tracking as a sequential input adaptive process.

Sequential input adaptive system theory is applied to human eye tracking of targets with one-dimensional motion defined by since functions, sums of sine functions and triangle functions. The sequential theory describes the mean eye tracking movements of two subjects for these inputs. The theory is predictive for irregular inputs in that when its parameters for a subject are identified and adjusted for a reference input, it then predicts mean eye tracking behavior for that subject for inputs of comparable complexity.

Eye Movements↗