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Biomedical subjects

C Chuang

Publications and source records attributed to C Chuang.

34 records · Page 2Linked to original sources

Relation between recurrence of cancer of the colon and blood transfusion.

Data suggest that blood transfusion can cause immunosuppression. The incidence of recurrence of tumours was examined retrospectively in patients who had undergone potentially curative operations for cancer of the colon during 1970-81. Tumours recurred in six of 68 patients (9%) who had not been given transfusions and in 56 of 129 patients (43%) who had (p much less than 0.0001). Transfusion was also found to be significantly associated with the time to recurrence after adjustment for other baseline prognostic factors (p less than 0.05). Perioperative transfusion may be a significant risk factor in the prognosis of cancer of the colon. Whether this association is causal is unknown.

Adult↗

A technique for quantitating airway size from bronchial casts.

To develop a technique for quantitating the size of airways at various positions in the bronchial tree, we analyzed casts of formalin-fixed excised lungs of five mature male ferrets. The left lower lobe of each cast was dissected, the diameter and position of each terminal bronchiole were entered into a computer programmed to reconstruct the airway system, and the cross-sectional areas of 120 conducting airways were measured. The fraction of the lobe served by each measured airway was estimated by dividing the sum of the squared diameters of the terminal bronchioles subtended by that airway by the summed squared diameters of all terminal bronchioles in the lobe. In each cast the relationship between an airway's cross-sectional area (Y) and the fraction of the lobe it was estimated to subtend (X) was described (0.91 less than R2 less than 0.95) by the expression ln(Y) = A + B ln(X) + C [ln(X)]2. Linear regression of ln(Y) on ln(X) for 30-50 airways estimated to serve fractions of the lobe around each of three arbitrarily selected levels (airways serving 0.7, 2.2, and 9.5% of the lobe) was adequate to characterize the area of airways at each level in each of the five animals with 95% confidence intervals narrower than 8% of the estimated area. Variability of airway size at each level among the five casts was modest, suggesting that this technique identified analagous airways in the various animals. Interindividual variability did not increase when the data were reanalyzed with terminal units defined on the basis of airway diameters rather than on the morphological identification of terminal bronchioles.

Animals↗

Antitumor immunity induced by hybrid tumor cells: comparison between hybrids and the parental tumor.

The ability of hybrid tumor cells to induce antitumor immunity has been evaluated in the line 1 alveolar cell carcinoma (L1) model of BALB/c mice. Hybrid tumor cells were produced by fusing freshly dissociated L1 cells isolated from in vivo tumors with the hypoxanthine:aminopterin:thymidine-sensitive cell line, GM 347, derived from C3H mice. Each hybrid was characterized by DNA content and expression of H-2 antigens using a fluorescence-activated cell sorter. Irradiated L1 cells in the presence or absence of Corynebacterium parvum were capable of immunizing BALB/c mice against a challenge of live L1 cells, provided the challenge dose was small (50% lethal dose was between 6 X 10(4) and 1.2 X 10(5) L1 cells). Testing of five hybrid clones and 1 uncloned hybrid line for their immunizing ability demonstrated a range in immunizing ability with none showing a statistically significant improvement in survival (p less than 0.0018) when compared to untreated controls. However, one hybrid clone, MoHb-L1-C2, was selected in which the survival of mice immunized with it compared to controls had a p value of 0.0255. A tumor (labeled L1/A) which grew in one of the mice immunized with this clone was removed and hybridized with GM 347 to yield a second set of hybrids. Both this variant of L1 cells and a hybrid clone made from it (MoHb-L1A-C18) were capable of immunizing mice against a challenge of live L1/A (p values of 0.0000 and 0.0028, respectively, when compared to controls). However, L1 cells were not able to immunize effectively against L1/A, and MoHb-L1A-C18 did not immunize against L1. This suggests that L1/A is a subpopulation of L1 cells with a different antigenic composition. The limited success of MoHb-L1A-C18 against L1/A is thought to be due to the narrower range of antigenic specificities in L1/A and the ability of MoHb-L1A-C18 to represent an important antigenic subpopulation of L1/A.

Adenocarcinoma, Bronchiolo-Alveolar↗

The pathology of superficially invasive, thin vulvar squamous cell carcinoma.

Thirty-six cases of vulvar squamous cell carcinoma 5 mm or less in thickness were studied, and potential predictors of lymph node metastases were evaluated. Tumor thickness and depth of stromal invasion were measured. Inguinal lymph node metastases were present in six (17%) cases, all of which had primary neoplasms more than 3 mm thick. The most superficial lesion to have lymph node metastasis was 3.2 mm thick and had 1.6 mm of stromal invasion. Nonetheless, depth of stromal invasion of less than 3 mm was associated with statistically fewer lymph node metastases (7%) than that of neoplasms with 3 mm or more of stromal invasion (50%). Although lymphatic or blood capillary invasion was present in four (11%) cases, this feature had no statistically significant association with lymph node metastasis. There was no relationship between clinical stage, surface diameter, or histological grade of the lesion and lymph node metastasis. A significant percentage of cases had either carcinoma in situ (31%) or atypical hypertrophic dystrophy (19%) in the epithelium adjacent to the infiltrating carcinoma. Koilocytotic atypia suggestive of human papilloma virus infection was present in the adjacent epithelium in 47% of the cases. This study suggests that thickness of the neoplasm is a valid predictor for the presence or absence of lymph node metastasis in vulvar squamous cell carcinoma; it may be more useful than neoplastic depth of invasion in this regard.

Carcinoma in Situ↗

Site-specific pausing of deoxyribonucleic acid synthesis catalyzed by four forms of Escherichia coli DNA polymerase III.

Sites on an fd DNA template which terminate synthesis catalyzed by each of four forms of Escherichia coli DNA polymerase III have been identified at single nucleotide resolution. Results were obtained by comparing the products made by forms of DNA polymerase III with products generated from the same 3'-terminus by using the dideoxynucleotide sequencing method, on high-resolution polyacrylamide gel electrophoresis. Each form of DNA polymerase III generates products of distinct lengths ending at a limited number of preferred sites of synthesis termination. The addition of auxiliary subunits to the DNA polymerase III core form of the enzyme has a distinct functional effect on primer elongation and specificity of polymerase pausing. Most sites (65%) can be correlated to positions of potential secondary structure in the template arising via local hydrogen-bonding interactions. The proximity of polymerase pausing to sites adjacent to hairpin stems was related to the size of the enzyme since the smaller core form of DNA polymerase III generally paused at sites which were closer to the base of these structures than the larger holoenzyme. The occurrence of termination sites is markedly affected by the inclusion of spermidine or Escherichia coli single-stranded DNA binding protein in the reaction mixtures. Additionally, a nucleotide composition specificity of pause sites has been observed.

Base Composition↗

Antitumor immunity induced by hybrid murine tumor cells: requirements for optimal immunization.

Hybrid tumor cells have been evaluated for their ability to induce specific antitumor immunity in inbred female C3H/He mice challenged with the syngeneic BA tumor. Hybrid cells were produced by fusion of BA cells with a BALB/c renal adenocarcinoma, which is hypoxanthine phosphoribosyl transferase-deficient and grows well in culture. Corynebacterium parvum was evaluated as an adjuvant for BA and hybrid cells. The BA tumor was shown to be poorly immunogenic, and four weekly injections of BA cells alone or C. parvum alone did not confer significant immunity. When BA cells and C. parvum were mixed, survival time was prolonged and most mice remained tumor-free. Hybrid cell lines derived from the BA tumor were produced in culture in unlimited quantities and were successfully used as immunogens. The addition of C. parvum to hybrids gave a significant incremental increase in survival when compared to the survival resulting from immunization by hybrids without adjuvant. When hybrids without adjuvant were used, several weekly injections were required for effective immunization. Irradiated and unirradiated hybrids were compared, and it was found that irradiation did not diminish hybrid immunogenicity. The potential problems and advantages of this concept of therapy are discussed.

Adenocarcinoma↗

Modifications in the classification of primary myelodysplastic syndromes: the addition of a scoring system.

A retrospective series of patients with the primary myelodysplastic syndrome has been reviewed and the survival updated. A scoring system is proposed that has advantages in predicting survival outcome. The importance of either dysmegakaryocytopoiesis or dysgranulocytopoiesis is emphasized because of its prognostic impact on leukaemic progression. Over 50 per cent of the patients die from either acute leukaemia or consequences of defective marrow production of granulocytes and platelets. Although only a few cases were included, the RAEB-T group has a very poor outcome and appears much closer to FAB M2 in biologic behaviour than RAEB. Both the criteria for the FAB subtypes and the scoring system can be applied easily in each case of myelodysplasia. Of the 56 patients only 9 were still alive as of April, 1984. Eight of these were in the RA-S and RA categories (or using the scoring system grouping 7 were group 1). All of the 16 patients who progressed to overt AML died within 4 weeks, and none was treated with chemotherapy. Of the remaining 31 patients, half died as a result of infection and/or haemorrhage and the remainder from apparently unrelated causes (cardiovascular, carcinoma, renal failure). These latter deaths are not surprising in light of the median age of 72 years.

Anemia↗

A comparison of chi-square partitioning and two logit analyses of ordinal pain data from a pharmaceutical study.

We study three approaches for the analysis of ordinal pain data. The first is essentially non-parametric, based on partitioning the goodness-of-fit statistic for testing the homogeneity model. The other two involve the modelling of quite different logit functions of the multinomial probabilities. We discuss and compare the characteristics of these three approaches using actual data from an analgesic trial.

Analgesics↗

A new model for ordinal pain data from a pharmaceutical study.

For the pain data analysed previously by Cox and Chuang, this paper proposes a new model that assumes monotone scores for ordered response categories. This proposed model possesses several attractive features and allows a stochastic ordering of the drugs under comparison. Such a model also provides insight regarding the ordinal scale used to classify response. Estimation of the parameters in the model is obtained by use of BMDP3R.

Analgesics↗

The analysis of a titration study.

For analysis of data from a titration study, this paper adopts the idea of a life table analysis and utilizes a logistic linear dose-response model. The procedure uses iterated reweighted least-squares to provide parameter estimates. Computation of the asymptotic covariance of the life-table estimates of the response rates involves Greenwood's formula and a conditioning argument. A special case consists of examination of the covariance structure when no dropouts took place. Data from a titration study that investigated the efficacy of an anti-hypertensive compound illustrate the procedure.

Antihypertensive Agents↗

A possible association between survival time and transfusion in cervical cancer.

Some studies suggest that transfusion may be associated with an increased risk of recurrence of and death due to malignant human neoplasms. We examined retrospective data from patients with cervical cancer to see if any association between transfusion of blood at the time of initial treatment and the time interval to recurrence and death could be detected in this cancer. In 130 patients with cervical cancer, seen over a ten-year period at our institution, there was a trend toward earlier recurrence in transfused patients, but this trend did not achieve statistical significance. Death due to cervical cancer recurrence occurred after a median of Death due to cervical cancer recurrence occurred after a median of 12 months in the transfused patients and a median of 68 months in the non-transfused individuals, which was statistically significant. Transfused patients had, on average, more favorable prognostic factors than those not transfused, such as less advanced clinical stage of disease. Analysis using a proportional hazards risk model failed to demonstrate a significant association between transfusion and time to recurrence when other prognostic factors were considered, but a significant association between transfusion and time to cancer-related death (p less than 0.05) was found. While these results cannot be viewed as conclusive due to the small number and heterogeneity of the patients analyzed, our data support the possibility of an association between transfusion and cervical cancer survival. Further studies are warranted to confirm or refute this relationship.

Blood Transfusion↗