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Biomedical subjects

F J Liu

Publications and source records attributed to F J Liu.

32 records · Page 2Linked to original sources

The in vivo biologic effect of interleukin 2 and interferon alfa on natural immunity in patients with head and neck cancer.

Given the association of deficient natural immunity with the risk of metastatic disease, the ability to activate natural killer cell function may have a therapeutic significance. The effect of continuous infusion of interleukin 2 plus intramuscular interferon alfa on natural immune status was, therefore, analyzed in eight patients with head and neck cancer. Also evaluated was the effect of interleukin 2-interferon alfa therapy on lymphokine-activated killer cell activity as well as total lymphocyte count, percent of lymphocyte subsets, and levels of both circulating immune complexes and antibody classes. Both the percent and absolute number of natural killer cells (ie, CD56+ CD3- lymphocytes) within peripheral blood as well as natural killer cell activity against K562 targets increased significantly with treatment. The remaining immune parameters were not significantly altered. The demonstrated capacity to modulate natural immune function supports the potential use of interleukin 2-containing regimens as a preventive measure against metastatic disease in patients with head and neck cancer.

Adult↗

Serologic determinants of survival in patients with squamous cell carcinoma of the head and neck.

Specific circulating serum proteins may reflect unique properties governing the growth and progression of head and neck cancers. One hundred three previously untreated patients with squamous cell carcinoma of the head and neck were prospectively evaluated for serum IgA, IgG, and IgM and C1q-binding macromolecules. Immunoglobulins were assessed by the immunoturbidimetric technique. C1q-binding macromolecules (C1qBM) were measured utilizing the iodine-125 assay of Zubler et al (J Immunol 1976; 116: 232-5). Neither the level of serum immunoglobulins nor C1qBM values were correlated with the primary site, AJC (American Joint Committee on Cancer) stage of disease, or size of primary lesion. Likewise, comparison of serum IgA with C1qBM values demonstrated that these laboratory parameters were independent variables (r = 0.15 by Pearson linear regression). Univariate statistical analysis, utilizing the Cox proportional hazard model, showed serum IgA and C1qBM values to each contribute significantly to the ability to predict survival in patients with advanced squamous cell carcinoma of the head and neck (p = 0.01 and 0.003, respectively). Furthermore, multivariate analysis reveals that both C1qBM and serum IgA levels contribute significantly to the hazards model beyond staging in predicting survival (p less than 0.001). Predictive results were most apparent in patients with stage IV disease and related to the probability of both regional and distant metastatic recurrences. Conversely, serologic analysis provided no information in patients who were staged early. These results support pretreatment multiparametric serologic analysis of patients with squamous cell carcinoma of the head and neck.

Adult↗

An immunologic profile of young adults with head and neck cancer.

Numerous reports have suggested, although never demonstrated, a suppressed immune defense mechanism as a contributing factor in the development of head and neck cancer in the young adult. Twenty-four previously untreated adults less than or equal to 40 years of age with squamous cell carcinoma were examined for lymphocyte function (natural killer cell activity and in vitro lymphocyte blastogenesis response to mitogens), total lymphocyte number and percentage of lymphocyte subsets, and humoral immune status (circulating IgA, IgG, and IgM). As compared with 33 healthy young adults, no significant immunologic deficit could be identified. On the contrary, the young adult cancer population had significantly increased lymphocyte numbers (P less than 0.05) and serum IgA, IgG, and IgM levels (P less than 0.001, respectively). These young cancer patients cannot be considered to be immunosuppressed. Alternative biologic mechanisms must be defined to account for the increasing incidence of head and neck cancer over the last decade among young adults in the United States.

Adult↗

Immunologic determinants of head and neck cancer response to induction chemotherapy.

Various measures of immune response were assessed prior to induction chemotherapy (intravenous [IV] cisplatin, fluorouracil [5-FU], and bleomycin) in 43 previously untreated head and neck cancer patients to derive a clinical response prediction model. These were parameters of functional cellular immunity (natural killer [NK] cell activity, lymphocyte blastogenesis response to mitogens), total lymphocyte and lymphocyte subset numbers and percentages, and circulating humoral immunity (total immunoglobulin, immunoglobulin classes, and C1q binding activity [C1q BA]). The C1q BA may reflect levels of circulating immune complexes within peripheral blood. The objective primary tumor response rate was 65% (16 complete responses and 12 partial responses). Univariate logistic regression analysis showed that failure to respond to therapy was significantly related to higher value (vis-à-vis response) of humoral immune parameters total immunoglobulin (Ig), P less than .01; IgG, P less than .01; and C1q BA, P less than .001. No association between cellular immune response measurements and response to chemotherapy was identified. By multivariate logistic regression analysis, only C1q BA levels were predictive of drug therapy responsiveness (P less than .001). Results extend our previous investigations regarding C1q BA measurement in head and neck cancer patients, and show that C1q BA levels add accuracy of prediction of subsequent chemotherapy response to that based solely on standard staging criteria and other parameters of immune status.

Adult↗

IgG heavy-chain subclass typing of myeloma paraproteins by isoelectric focusing immunoblot analysis.

The objective of this study was to develop a clinical laboratory method for subclass typing of human immunoglobulin G (IgG) paraproteins. Serum proteins were isoelectrically focused (IEF) in a mini-gel and passively blotted by capillary diffusion onto untreated nitrocellulose. Unreacted sites on the nitrocellulose were blocked with bovine serum albumin and the bound IgG was detected with peroxidase-conjugated anti-human IgG1-4 monoclonal antibodies from WHO/IUIS clones. The IEF immunoblot specificity was demonstrated by analysis of documented IgG, IgA, and IgM myeloma proteins of known subclass and light-chain composition. IEF immunoblots of sera from 18 myeloma patients who had an above-normal total IgG concentration produced IEF immunoblot patterns composed of five to 10 discrete bands (pI range 6.0 to 8.4). In contrast, no detectable IgG bands were observed with sera containing IgA and IgM paraproteins. The observed subclass frequencies of IgG paraproteins were 56% IgG1 (10/18), 28% IgG2 (5/18), 11% IgG3 (2/18), and 5% IgG4 (1/18). IEF immunoblot analysis permits the monitoring of changes in the pI and subclass of an IgG paraprotein over the course of a myeloma patient's therapy program.

Adult↗

Positive direct antiglobulin test and high serum immunoglobulin G values.

To investigate the association between the positive direct antiglobulin test (DAT) and hypergammaglobulinemia, the authors prospectively studied 154 patients, classified into three groups: Group 1, 52 patients with a positive DAT result in pretransfusion samples; Group 2, 52 patients with a negative DAT result; and Group 3, 50 patients initially found to have an elevated serum immunoglobulin G (IgG) level. Serum protein electrophoreses and IgG quantifications were performed for all three groups. Serum haptoglobin and lactate dehydrogenase (LD) isoenzyme electrophoreses were also assayed for Group 1. Of 52 patients in Group 1, 17 (33%) had an elevated serum IgG level and nonreactive eluates. Clinical history, haptoglobin, and LD isoenzyme studies did not suggest increased red blood cell destruction. Only 2 (4%) of 52 patients in Group 2 had an elevated serum IgG level. Of 50 in Group 3, 25 (50%) had a positive DAT result with nonreactive eluates and did not have hemolytic diseases. Two of 10 patients (20%) with serum IgG levels ranging from 18 to 20 g/L (1.8-2.0 g/dL), 13 of 29 (45%) with serum IgG levels from 20 to 40 g/L (2.0-4.0 g/dL), 4 of 6 (67%) with serum IgG levels from 40 to 60 g/L (4.0-6.0 g/dL), and 6 of 6 (100%) with serum IgG levels from 60 to 80 g/L (6.0-8.0 g/dL) had a positive DAT result. The authors concluded there is a significant correlation between a positive DAT result and serum IgG concentrations and that the higher the elevated serum IgG, the more frequently the positive DAT result is observed. Elevated serum IgG levels may explain many positive DAT results in pretransfusion blood samples.

Acquired Immunodeficiency Syndrome↗

Plasma fibronectin values in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex.

The authors studied the circulating fibronectin concentrations in the plasma of 24 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) and of 74 age- and sex-matched healthy blood donors. They adapted a commercially available turbidimetric immunoassay for use with a centrifugal analyzer. The assay showed within-run precision of 2.1%, 2.3%, 1.8%, and 1.1%, and an accuracy of 90%, 99%, 98%, and 98% at fibronectin concentrations of 126 mg/L, 200 mg/L, 293 mg/L, and 317 mg/L, respectively. Between-run precision was 5%, 3%, and 2% for 66 mg/L, 218 mg/L, and 283 mg/L concentrations, respectively. Plasma fibronectin values obtained from the healthy blood donors were in good agreement with those values reported by other investigators using various methods. No significant differences between the plasma fibronectin values of the patient population (mean +/- 2 SD = 294 mg/L +/- 110 mg/L) and of the control group (mean +/- 2 SD = 311 mg/L +/- 130 mg/L) were noted. The authors conclude that the measurement of fibronectin concentrations in patients with AIDS or ARC does not contribute significantly to the diagnosis and therapeutic management of these patients.

AIDS-Related Complex↗

The relationship of circulating IgA to cellular immunity in head and neck cancer patients.

The relationship of circulating IgA titers and multiple parameters of cell-mediated immunity was examined in 97 patients with head and neck cancer. In 26% of the patients, IgA titers were above one standard deviation of controls, with highest levels noted in patients with advanced disease. In 40 patients for whom multiple immune parameters were tested in vitro, increasing concentrations of IgA were associated with an enhanced immunologic helper state defined by a generalized hypergammaglobulinemia, increased percentage of T4+ lymphocytes, higher T4/T8 ratio, and an increased lymphocyte blastogenesis response to mitogens. IgA concentrations were inversely related to percentages and absolute number of Leu 11+ natural killer cell subsets, and also to disease-free survival (p less than 0.005 by Cox proportional hazards model). The immune correlations identified here are similar to those noted in many autoimmune diseases. Head and neck cancer patients are an immunologically heterogeneous population, among whom elevated IgA blood levels may reflect the autoimmune nature of cancer, an immunologic state defined by its tumor-promoting capacity.

Adult↗

Treatment of the thalassemia syndrome with splenectomy.

Splenectomy was performed on 152 patients with thalassemia (thal), including 90 cases with Hb H disease, 48 cases with homozygous beta-thal, and 14 cases with Hb E-beta-thal. The therapeutic effect in Hb H disease was 83.3%, and 32.3% in Hb E-beta-thal and beta-thal. In Hb H disease, the hemoglobin (Hb) level increased 30 g/l in 14 of 29 cases. After splenectomy, the life-span (T1/2) of 51Cr RBC in Hb H and Hb E-beta-thal increased to 18.2 +/- 2.6 and 18.2 days, respectively. The number of inclusion (Heinz) bodies attached to the RBC membrane increased after surgery. The interdermal delayed supersensitivity reaction became negative in seven of 26 cases of Hb H disease; the IgG also decreased after surgery. The number of PAS positive foam cells in the spleen correlated to Hb level after surgery. Infection is a common complication.

China↗

Underestimation of monoclonal proteins by serum protein electrophoresis on cellulose acetate.

Our study of 95 serum samples from 37 patients with monoclonal gammopathy revealed distorted irregular monoclonal (M) protein bands after serum protein electrophoresis (SPE) on cellulose acetate membrane. In 71 (75%) of the 95 sera, the M-protein was underestimated and the albumin concentration overestimated. Dilution of the serum sample before SPE eliminated the abnormality of the M-protein bands. By SPE, the mean albumin concentration in these 71 undiluted sera was 45.8 (SD 7.4) g/L vs 37.9 (SD 5.8) g/L for the diluted sera; moreover, this was true of individual samples: measured albumin concentration in each diluted serum sample was always less than in the undiluted serum. As measured by the bromcresol green dye-binding method, the albumin concentration was 32.8 (SD 5.9) g/L. Similarly, the M-protein concentration in SPE was 49.5 (SD 12.3) g/L for the undiluted sera vs 61.8 (SD 15.1) g/L for the diluted sera, and the M-protein concentration in each diluted serum sample always exceeded that in the undiluted serum. Underestimation of M-protein limits the usefulness of M-protein measurement in evaluating the patient's response to therapy and for early detection of disease progression. SPE strips should be carefully inspected visually, and sera with M-protein band abnormalities should be diluted and re-assayed if SPE is to quantify concentrations of M-protein and albumin accurately.

Blood Protein Electrophoresis↗

Acute injury to differentiating Clara cells in neonatal rabbits results in age-related failure of bronchiolar epithelial repair.

Nonciliated bronchiolar (Clara) cells are progenitor cells during lung development. During differentiation, they have a heightened injury susceptibility to environmental toxicants bioactivated by cytochrome P450 monooxygenase. When neonatal rabbits are treated with the P450-mediated cytotoxicant 4-ipomeanol (IPO), abnormal bronchiolar epithelium results. This study establishes the impact of IPO cytotoxicity on 3 stages of rabbit Clara cell differentiation, early (2.5 and 5 days postnatal [DPN]), intermediate (7 and 9 DPN), and late (15 and 21 DPN), and relates the cytotoxicity to the extent of bronchiolar repair. Neonates received a single dose of IPO (5 mg/kg) and were assessed by qualitative pathology 48 hours later for injury or at 4 weeks for repair. IPO injured the 3 stages of Clara cell differentiation to the same degree; epithelium was swollen, exfoliated, and squamated. Epithelial repair differed among the 3 stages. Bronchioles of animals treated during early and intermediate stages had simple squamous and irregularly shaped cuboidal cells. Animals treated during late stages were similar to controls. Thus, differentiating Clara cells are susceptible to injury by the P450-mediated cytotoxicant IPO, but the extent of repair varies based on when the initial injury occurs.

Acute Disease↗

Serum calcitonin in small cell carcinoma of the prostate.

Small cell carcinoma (SCC) of the prostate is a rare and recently recognized subtype of prostate cancer. The neuroendocrine component of the prostate carcinoma is becoming more frequently detected in classic adenocarcinoma of the prostate. Clinically, these tumors represent a considerable portion of so called androgen independent prostatic carcinomas. It has been hypothesized that the neuroendocrine cells being admixed with adenocarcinoma is selected and emerges as a hormone refractory carcinoma after the androgen blockade. The SCC shows a spectrum from a mixed adenocarcinoma with SCC component to the extreme case of pure SCC. Characteristically, prostatic SCC shows low measurable serum level of traditional prostate tumor marker, prostatic specific antigen (PSA). Instead, SCC secretes several neural peptides and calcitonin (CT) is one of them. The usefulness of serum CT as a neuroendocrine marker was evaluated retrospectively in 16 patients with SCC of the prostate (5 pure SCCs and II combined adenocarcinoma and SCCs). The serum CT was measured by radioimmunoassay. In all the patients, serum CT level was measured after SCC was diagnosed histologically. All 16 patients presented with advanced tumor with extensive metastasis. Nine (56 percent) out of 16 cases showed elevated serum CT (range 42 approximately 2,654 pg/ml) and chemically supported the diagnosis of SCC. Owing to the retrospective nature of the study, the serum CT was measured only once in most of the cases, and the value of monitoring the disease progress or the responsiveness to the chemotherapy could not be evaluated. Survival analysis by logrank test did not show statistically significant prognostic value of serum CT in SCCs of the prostate. However, patients with extremely high serum CT level tend to have poor survival. Future studies are needed for further evaluation of serum CT as a disease monitor and prognostic marker in SCC of the prostate. Serum CT may have a role as a tumor marker in the early diagnosis of SCC of the prostate, which often is not diagnosed until the advanced stage.

Adenocarcinoma↗

Underestimation of monoclonal proteins by agarose serum protein electrophoresis.

The effect of serum dilution on monoclonal protein quantitation by serum protein electrophoresis (SPE) on the agarose gel Paragon system was investigated in 388 serum samples from 106 patients with Ig G monoclonal gammopathy. It was found that the pre-electrophoretic 1:5 serum dilution recommended by the manufacturer was adequate for some but not all sera, especially those with the highest M-protein concentrations. As a result of the inadequate dilution, 232 (60 percent) of the 388 samples had M-protein concentrations that were significantly underestimated and the corresponding albumin concentrations overestimated. By Paragon SPE, the mean albumin concentration in these 232 sera was 41.8 (SD 6.7) g/L. After further dilution of these sera, the mean albumin concentration was 36.7 (SD 6.8) g/L and was, in each case, always less than that in the corresponding 1:5 diluted serum. By the bromcresol green (BCG) dye-binding method, the albumin concentration was 34.9 (SD 4.3) g/L. Similarly, the M-protein concentration for 1:5 diluted sera was 51.9 (SD 12.9) g/L vs. 59.1 (SD 16.1) g/L for the further diluted sera, with the M-protein concentration in each further diluted sample always exceeding that in the corresponding 1:5 diluted serum. Underestimation of the M-protein concentration limits its clinical utilization in evaluating the patient's response to therapy and for early detection of disease progression. A recommendation was made of a 1:10 dilution of sera that contain total protein from 91 g/L to 114 g/L and a 1:20 dilution of sera in which the protein content is in the range of 115 g/L to 152 g/L to insure accurate estimation of protein fractions by Paragon SPE.

Antibodies, Monoclonal↗