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Biomedical subjects

S Shu

Publications and source records attributed to S Shu.

At least 127 records · Page 7Linked to original sources
PubMed1982

Mechanisms of immunologic eradication of a syngeneic guinea pig tumor. I. Quantitative analysis of adoptive immunity.

Adoptive immunity against a syngeneic hepatoma (line-10) of Sewall-Wright inbred strain 2 guinea pigs was analyzed by a two-dimensional titration of iv transferred immune lymphoid cells versus intradermal tumor challenges. Tumor resistance increased exponentially as a function of the number of immune lymphoid cells transferred. Within the tumor challenge doses analyzed, suppression of tumor growth mediated by the transferred immune lymphoid cells appeared to be independent of the primary immune response in the recipient. Quantitatively, rejection of a given number of tumor cells reflected the number of transferred immune cells and was independent of the presence of the same tumor at other skin sites. There was no evidence indicating that transferred immune cells were attracted specifically to the tumor inoculation site. The number of tumor cells that could be rejected at a skin site by adoptive immunity was greater than the estimated number of immune lymphoid cells present at the challenge site.

Animals↗
PubMed1981

Adoptive immunity to the guinea pig line 10 hepatoma and the nature of in vitro lymphoid-tumor cell interactions.

Adoptive transfer of spleen cells from specifically immunized donors to nonimmunized recipients was used to study tumor immunity in vivo to the syngeneic line 10 guinea pig hepatoma. Hepatoma cells cultured as monolayers on fibronectin-coated surfaces served as targets for immune splenocytes in a 3H release cytotoxicity assay in vitro. An antigenically distinct syngeneic guinea pig hepatoma (line 1) was used to study the specificity of adoptive systemic immunity and of the cytotoxicity in vitro. The protection afforded by adoptive immunization against challenge with hepatoma cells was tumor line specific, while in most cases cytotoxicity in vitro was not. The in vitro cytotoxic effect was abolished after absorption of the immune spleen cells with monolayers of either line 10 or line 1. In contrast, the in vivo tumor-specific rejection activity of line 10 immune spleen cells was depleted after absorption with line 10 but not with line 1 or other control monolayers. These studies revealed that the immune cells mediating cytotoxicity in vitro were functionally distinct from those conveying adoptive protection in vivo. Immune cells possessed receptors for tumor-specific rejection antigens on hepatoma cells, and their interaction did not lead to destruction of the neoplastic cells in vitro.

Animals↗
PubMed1978

Light transmission analysis of lymphocyte activation by mitogens: a new technique.

In vitro lymphocyte transformation was evaluated by laser light transmission cytometry. Criteria are given for optimal application of this system to assessment of total cells and proportion of lymphoblasts in cultures. The light transmission studies revealed that cell numbers in mitogen stimulated cultures increase steadily, reaching a plateau. The percentage of lymphoblasts reached a peak after 4 days culture. The kinetics of [3H]-thymidine incorporation are similar. The increase in total cell number concomitant with decrease in [3H]thymidine incorporation at the fifth and sixth days indicates discordance between the cell proliferation and utilization of exogenous thymidine. The kinetics of total cell numbers and percentage of lymphoblasts suggest that in vitro reversion of lymphoblasts to small lymphocytes occurred. In addition to examining directly the cellular events during blastogenesis with ease, the current method appeared to be more reproducible than the [3H]thymidine incorporation assay.

Absorption↗
PubMed1977

Pemphigus antibody action on skin explants: kinetics of acantholytic changes and stability of antigens in tissue cultures of normal monkey skin explants.

The pathogenic effect of the intercellular antibodies of pemphigus was studied by using organ culture of monkey skin. Skin explants that were grown on sera with intercellular antibody titers of 320 or greater fixed these antibodies within one day as demonstrated by direct immunofluorescence for IgG. None of the control sera gave such staining patterns. Following the binding of intercellular antibodies, characteristic histologic changes appeared, notably separation of individual epidermal cells and acantholysis. These histologic changes became more marked in two to five days. During this period, the bound antibodies and the intercellular antigens decreased and disappeared. These temporal relationships of immunofluorescence and histologic findings suggest that pemphigus antibodies play a role in the induction of acantholysis.

Acantholysis↗
PubMed1977

Nuclear deposits of immunoglobulins in skin of patients with systemic lupus erythematosus.

Skin nuclear speckled IgG deposition was noted in seven patients. The patients' clinical courses satisfied at least four of the preliminary criteria of the American Rheumatism Association for the diagnosis of systemic lupus erthematosus (SLE). Examination of approximately 700 additional biopsies from patiets with SLE, connective tissue and various skin diseases as well as normal individuals, failed to demonstrate similar nuclear immunoglobulin deposition. Sera from these seven patients had higher titre, complement fixing anti-nuclear antibodies (ANA) of IgG class which produced a speckled nuclear fluorescent pattern. In addition, the sera of all seven patients demonstrated by gel double diffusion precipitating antibodies against nuclear ribonucleoprotein (RNP) or Sm antigens.

Adolescent↗
PubMed1977

Bullous disease of childhood: report of a case demonstrating antibasal cell antibody.

This report describes a child with protracted bullous disease responsive only to high doses of steroids, who on immunofluorescent testing, consistently displays antibasal cell antibody. The child had been treated with penicillin a week prior to the development of the bullous disease. The etiologic possibility of this drug history in the evolution of the bullous disease is raised, with particular respect to recent reports of similar circulating antibody in drug reactions.

Antibodies↗
PubMed1976

Quantitative studies of peroxidase labeled antibody. I. Indirect staining system analyzed by chessboard titraions.

The sensitivity and specificity of immunohistological staining procedures employing horseadish peroxidase labeled antibody were evaluated with the aid of chessboard titrations. Two indirect staining systems, detecting antinuclear antibody and pemphigus intercellular antibody, were examined with reference to indirect immunofluorescence. In both systems, chessboard titration results showed that plateau titers of serum antibodies appeared to be a function of label content. The plateau endpoints reflected the anti-immunoglobulin concentrations of conjgates. With a conjugate of molar enzyme to protein ratio (E/P) of 1.1, the sensitivity of indirect staining appeared to be equivalent to that of immunofluorescent staining performed with a conjugate with molar fluorescein to protein ratio of 4.8. Sensitivity decreased sharply with conjugates of low E/P rations. Three methods of assaying the peroxidase content of conjugates were evaluated for reproducibility and sensitivity in relation to staining properties.

Animals↗
PubMed1975

Studies on defined immunofluorescence in clinical immunopathology. II. Relationship of F/P ratios pf conjugates and staining properties in indirect immunofluorescence.

The effect of conjugate F/P ratios on titers of patient antibodies was evaluated with two model systems in IIF chessboard titrations, notably, antinuclear antibodies and the intercellular antibodies of pemphigus. The plateau titers of both antibodies and F/P conjugate ratios were analyzed and proved to have a high degree of linear relationship statistically. Single titrations of other tissue antibodies, including skin basement membrane antibodies of bullous pemphigoid, MTA, GPA, SMA, and ThA with the same group of conjugates yielded similar information. A quantitative relationship between the two parameters was established.

Animals↗
PubMed1975

Studies on defined immunofluorescence in clinical immunopathology. III. Past progress, some new methods, and prospects for the future.

Experience with chessboard titrations over the past 9 years has shown that essentially all indirect IF staining systems that employ anti-IgG conjugates can be defined with the aid of assays for F/P ratios and/or antibody concentrations. Some improvements in the radial diffusion assays for antibody protein have been effected by refinements in methodology. Studies with a form of the Dass system showed that over a 16-fold range of light intensities, relatively little change occurred in "titers" of IgG (comparably to titers of patient sera) or in PEP conjugates as seen in DASS chessborad titrations. An analysis of 233 PEP values included in 12 literature reports on indirect IF tests indicate that 88% fall within one doubling dilution of 1/16 unit/ml or about 12.5 mug labeled Ab/ml. The DASS reactions also are within this range. Factors responsible for variation beyond these limits in indirect IF tests were analyzed. The most important factor appears to be experimental errors. Other factors include low titers of primary antibodies, some aberrant conjugates, and a recent shift toward greater sensitivity of chessboard titrations. The latter appears to be due primarily to modes of reading and should be controlled by the constant use of reference sera. It now seems possibe that future IF studies may be defined with the aid of this DASS system. To achieve this goal, it will be necessary to not only elaborate microanalytic techniques of the type that have been considered at this Conference but also to generate macroanalytic methods that can be used in parallel with them as a basis for interpreting microscopic observations both in the DASS system and in IF studies of sera and tissues.

Animals↗
PubMed1975

Diagnostic importance of immunofluorescence in oral bullous diseases and lupus erythematosus.

Immunofluorescent tests have proved to be of diagnostic importance for pemphigus, bullous pemphigoid, cicatricial pemphigoid, systemic lupus erythematosus, and discoid lupus erythematosus. Immunofluorescence test procedures, necessary specimens, and test findings have been reviewed as aids to dentists in the utilization and interpretation of these tests for the study of oral lesions.

Antibodies, Antinuclear↗
PubMed1975

Incidence and titers of antinuclear, antismooth muscle, and other autoantibodies in blood donors.

Sera from 107 blood donors ranging in age from 18 to 66 years were tested by indirect immunofluorescence for titers of various autoantibodies. These were matched for sex in diffferent age brackets. Antinuclear antibody (ANA) titiers of 10 or more appeared in 45 per cent of the sera examined. However, only 5.6 per cent had ANA titers of 80 or more, and only one subject had a titer of 160. ANA titers of 80 or greater were only found in the oldest age group (51 years or older). In those subjects with detectable ANA, 57.7 per cent were female and 32.8 per cent were male. The prevalence of thyroid cytoplasm and gastric parietal cell antibodies also appeared both age and sex related, while smooth muscle antibodies did not. Anti-DNA antibody, pemphigus antibody, bullous pemphigoid antibody, and mitochondrial antibody were detected in none of the sera tested. No relationships were seen in pairs of autoantibodies.

Adolescent↗
PubMedDate not supplied

Role of juvenile hormone-esterase in mating-stimulated egg development in the moth Heliothis virescens.

Juvenile hormone (JH) titer in virgin females of Heliothis virescens is significantly lower than that in mated females of the same age. The JH titer in virgin females follows a diel pattern in which it begins to increase towards the end of photophase, remains high around the onset of scotophase, and declines during scotophase. The titer reaches its lowest levels at the onset of photophase, and remains low during the first half of photophase. In mated females, the diel pattern of JH titers is not as pronounced. JH-esterase (JHE) activity in mated females is significantly lower than that of virgin females during photophase; JHE levels in the former are similar to levels seen in newly emerged females. JHE activity in mated females also exhibits a diel pattern, in which activity is low during photophase and high at the onset of scotophase. Evidence for the indirect involvement of JHE in the mating-stimulated egg development is provided by the effect of selected JHE inhibitors in inhibiting JHE activity and stimulating egg production in virgin females.

Animals↗
PubMedDate not supplied

Choristoneura fumiferana entomopoxvirus prevents metamorphosis and modulates juvenile hormone and ecdysteroid titers.

Larvae of the spruce budworm, Choristoneura fumiferana, infected with C. fumiferana entomopoxvirus (CfEPV) continue to feed and grow without undergoing metamorphosis and die as moribund larvae. The lethal dose (LD(50)) and lethal time (LT(50)) values for fourth instar larvae are 2.4 spheroids and 25.2 days, respectively. One hundred percent of the control fourth instar larvae, which were fed water instead of virus, pupated by 18 days post feeding (PF). Only 30% of the larvae that were fed the LD(50) dose and none of the larvae that were fed the LD(95) dose pupated by 18 days PF. Of the control larvae, 95% became adults by 24 days PF, whereas in the treated group only 2% of larvae that were fed the LD(50) dose and none of the larvae that were fed the LD(95) dose became adults by 24 days PF. Some of the virus-treated larvae died as either larval/pupal or pupal/adult intermediates. These phenotypic effects were similar to the larval/pupal and pupal/adult intermediates, resulting from treating larvae with juvenile hormone (JH) or its analogs, which suggests that EPV may cause such abnormalities by modulating JH and/or ecdysteroid titers. In untreated sixth instar larvae the JH titer decreased to low levels by 24 h after ecdysis and remained low throughout larval life. EPV-fed sixth instar larvae had 2112 pg/ml on day 0, 477 pg/ml on day 1 and 875 pg/ml on day 8 of the sixth instar. Control larvae contained 860 ng of ecdysteroids per ml hemolymph on day 8 of the sixth instar, whereas EPV-treated larvae of the same age (30 days PF) had only 107 ng of ecdysteroids per ml of hemolymph. Thus, EPV infection results in increased JH titer and decreased ecdysteroid titer. Northern hybridization analysis was performed using RNA isolated from control and EPV-fed larvae and cDNA probes for (i) juvenile hormone esterase (JHE), which is JH inducible, (ii) Choristoneura hormone receptor 3 (CHR3), which is ecdysteroid inducible, and (iii) larval specific diapause associated protein 1 (DAP1), whose expression is larval specific. EPV-treated larvae showed higher levels of JHE and DAP1 mRNA and lower levels of CHR3 mRNA, indicating that they had higher levels of JH and lower levels of ecdysteroids. Thus, our data show that EPV prevents metamorphosis by modulating ecdysteroid and JH levels.

Animals↗
PubMedDate not supplied

Enhanced therapeutic potential of adoptive immunotherapy by in vitro CD28/4-1BB costimulation of tumor-reactive T cells against a poorly immunogenic, major histocompatibility complex class I-negative A9P melanoma.

Costimulation plays a critical role in T-cell activation and amplification of anti-tumor immunity. Although CD28 engagement triggers an early activation signal, activation-induced 4-1BB molecule on T cells transmits a crucial signal for further expansion and maturation of effector cells. In this report, the authors show that costimulation through CD28 and 4-1BB pathways synergistically enhances the therapeutic efficacy of T cells from tumor-draining lymph nodes. Intravenous adoptive transfer of costimulated T cells into mice bearing disseminated micrometastasis of a poorly immunogenic, major histocompatibility complex class I-negative A9P melanoma results in a 60% cure rate. Autopsy of mice that died after unsuccessful treatment revealed tumor growth in the liver, spleen, and skin with minimal or no evidence of pulmonary disease. In contrast, mice that received no treatment or noncostimulated T cells had massive pulmonary tumors, suggesting that adoptively transferred T cells are less effective against growth of extrapulmonary tumors. These results show that costimulation of tumor-draining lymph node T cells through CD28 and 4-1BB increases their potential for cancer immunotherapy and suggests that improper trafficking of tumor-reactive T cells to extrapulmonary sites must be improved to enhance clinical efficacy.

4-1BB Ligand↗