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Biomedical subjects

T Tong

Publications and source records attributed to T Tong.

At least 19 recordsLinked to original sources

Dot-immunogold filtration assay as a screening test for syphilis.

A dot-immunogold filtration assay (DIGFA) for the rapid detection of reaginic antibody in the serum of syphilitic patients was developed. The assay was simple, rapid, and reproducible. The test completion time was 2 min, and the assay required no equipment. The positive dot was very obvious, and the results could easily be determined with the naked eye. A total of 350 serum samples were examined by DIGFA, the rapid plasma reagin test, and the fluorescent treponemal antibody-absorption test. The levels of agreement between DIGFA and the rapid reagin test and between DIGFA and the fluorescent treponemal antibody-absorption test were 100 and 98%, respectively. The results of clinical application indicated that DIGFA could be used as a routine screening test for syphilis.

Antibodies, Bacterial

Familial cardiomyopathy with cataracts and lactic acidosis: a defect in complex I (NADH-dehydrogenase) of the mitochondria respiratory chain.

Four patients in one generation of a multiply consanguineous pedigree died with cardiomyopathy, cataracts, and lactic acidemia. Postmortem heart and skeletal muscle tissues from one patient were analyzed. A low (12% control) activity of NADH-CoQ reductase (complex I) in heart and normal activity in skeletal muscle mitochondria was found. Cultured skin fibroblasts obtained from two individuals in the pedigree showed elevated lactate to pyruvate ratios in the range of 2 to 3.5 times normal and decreased complex I + III activity (42 and 54% of control activities) in isolated mitochondria. Western blot analysis and enzymatic assay showed normal levels of CuZn-superoxide dismutase, but grossly elevated levels of the mitochondrial Mn-superoxide dismutase. Southern blot analysis in heart muscle cells from the patient tested revealed multiple mitochondrial DNA deletions which indicate free oxygen radical damage. We hypothesize that a nuclear-encoded defect in the respiratory chain is responsible for excessive free oxygen radical production in these infants which contributes to the prenatal onset of cardiomyopathy and cataracts.

Acidosis, Lactic

The proliferative response and anti-oncogene expression in old 2BS cells after growth factor stimulation.

The limited replicative lifespan of diploid human cells in vitro (cellular senescence) serves as a cellular model of aging. We examined the proliferative response of 2BS cells of different population doubling levels to fibroblast growth factor (FGF). DNA synthesis was measured by thymidine incorporation. As the cells aged, there was a significant decrease in the stimulation of DNA synthesis by FGF addition (P < 0.01). The effective concentration of FGF and the latent period prior to DNA synthesis did not change. Expression of Rb and p53 mRNA after growth factor stimulation was also examined. Young and old cells had similar Rb mRNA levels, whereas the p53 mRNA level was significantly reduced in old cells. After both cells were treated by FGF or epidermal growth factor (EGF), Rb expression increased 210-275% in young cells and 50-60% in old ones. However, no significant change was found in p53 gene transcriptions after FGF addition. The results further suggest that cell aging is associated with a progressive loss of the ability of cells to respond to growth factors.

Cell Division

Cell aging of human diploid fibroblasts is associated with changes in responsiveness to epidermal growth factor and changes in HER-2 expression.

The limited replicative life span of diploid human cells in vitro (cellular senescence) serves as a cellular model of aging. We examined the proliferative response of 2BS cells of different population doubling levels to epidermal growth factor (EGF). DNA synthesis was measured by thymidine incorporation. As the cells aged, there was a significant decrease both in the baseline level of DNA synthesis and in the stimulation of DNA synthesis by EGF addition. The effective concentration of EGF and the latent period prior to DNA synthesis did not change. EGF receptor mRNA expression also remained unchanged as the cells aged, in the absence or presence of EGF, suggesting that the defect in old cells lies downstream in the EGF signaling pathway. As the cells reached 100% of their life span, however, there was a 70% decrease in EGF receptor mRNA. Expression of the EGF receptor homologue HER-2 was also examined. The HER-2 mRNA level was significantly reduced in old cells. Moreover, HER-2 expression was stimulated by EGF addition in young cells but not in old cells. The results suggest that cell aging is associated with a progressive loss in the ability of cells to respond to growth factors.

Cell Division

TGF-beta 1 gene expression in cultured human keratinocytes does not decrease with biologic age.

The biologic activity of cultured epithelial grafts is believed to diminish with increasing cellular age. Therefore, keratinocytes from young donors are used preferentially in the production of cultured allografts for wound treatment. However, the impact of biologic age on cytokine gene expression by human keratinocytes has not been previously investigated. In this study, transforming growth factor-beta 1 (TGF-beta 1) gene expression in human keratinocytes derived from normal foreskins of males ranging in age from 7 months to 82 years was analyzed. Keratinocytes were harvested from fresh specimens and cultivated in vitro on 3T3 fibroblast feeder layers through second passage. The cells were analyzed both qualitatively and semiquantitatively for TGF-beta 1 gene expression using three separate techniques: in situ hybridization, Northern hybridization, and competitive polymerase chain reaction. By in situ hybridization, the signal representing TGF-beta 1 transcript was detected in cells in all layers of the stratified cultures, and immunohistochemical staining for TGF-beta 1 protein was equally intense in all layers. Northern blots of total RNA extracted from the cultivated cells showed no decrease in band density with increasing biologic age. Likewise, no decrease in TGF-beta 1 mRNA levels with biologic age was observed using a semiquantitative polymerase chain reaction assay. These results indicate that the potential for TGF-beta 1 gene expression in cultured foreskin keratinocytes does not decline with increasing cellular age. The findings imply that the clinical performance of cultured grafts, at least as it relates to the elaboration of this growth factor, may not be significantly altered by the biologic age of the keratinocyte donor.

Adult

The lifetime risk of developing breast cancer.

BACKGROUND: The lifetime risk of developing breast cancer in U.S. women, often quoted as one in nine, is a commonly cited cancer statistic. However, many estimates have used cancer rates derived from total rather than the cancer-free population and have not properly accounted for multiple cancers in the same individual. PURPOSE: Our purpose was to provide a revised method for calculating estimates of the lifetime risk of developing breast cancer and to aid in interpretation of the estimates. METHODS: A multiple decrement life table was derived by applying age-specific incidence and mortality rates from cross-sectional data to a hypothetical cohort of women. Incidence, mortality, and population data from 1975-1988 were used, representing the geographic areas of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. The incidence rates reflected only the first breast primary cancer; mortality rates reflected causes other than breast cancer. The population denominator used in calculating incidence rates was adjusted to reflect only those women without previously diagnosed breast cancers in the hypothetical cohort. RESULTS: Our calculations showed an overall lifetime risk for developing invasive breast cancer of approximately one in eight with use of 1987-1988 SEER data, although up to age 85, it was still the commonly quoted one in nine. CONCLUSION: Our estimate was calculated assuming constant age-specific rates derived from 1987-1988 SEER data. Because incidence and mortality rates change over time, conditional risk estimates over the short term (10 or 20 years) may be more reliable. A large portion of the rise in the lifetime risk of breast cancer estimated using 1975-1977 data (one in 10.6) to an estimate using 1987-1988 data (one in eight) may be attributed to 1) early detection of prevalent cases due to increased use of mammographic screening and 2) lower mortality due to causes other than breast cancer. A common misperception is that the lifetime risk estimate assumes that all women live to a particular age (e.g., 85 or 95). In fact, the calculation assumes that women can die from causes other than breast cancer at any possible age. Cutting off the lifetime risk calculation at age 85 assumes that no women develop breast cancer after that age. While the lifetime risk of developing breast cancer rose over the period 1976-1977 to 1987-1988, the lifetime risk of dying of breast cancer increased from one in 30 to one in 28, reflecting generally flat mortality trends.

Adolescent

Cutaneous malignant melanoma. II. The natural history and prognostic factors influencing the development of stage II disease.

The survival history of 259 patients with Stage I cutaneous malignant melanoma who were at risk for developing regional nodal metastases (Stage II) were studied. Eighty-seven of 377 Stage I patients (23%) developed regional nodal metastases (Stage IIB) with 40% 5-year survival. Fifty patients had regional nodal metastases at presentation, with or without a known primary (Stages IIA or IIC, respectively), with a 42% 5-year survival. A step-down multivariate analysis using the Cox regression model revealed four risk factors as being highly significant for predicting a more favorable survival outcome: (1) thinner Breslow thickness (P = 0.0001), (2) pathologic Stage I disease (P = 0.004), (3) no clinical ulceration (P = 0.0004), and (4) being a woman younger than 50 years of age (P = 0.029). These results are discussed in reference to other series.

Age Factors

Cutaneous malignant melanoma (Arizona Cancer Center experience). I. Natural history and prognostic factors influencing survival in patients with stage I disease.

The authors have studied the natural history of 377 patients with Stage I cutaneous malignant melanoma followed at the Arizona Cancer Center, Tucson. Two hundred eight patients, or 55%, remained free of metastatic disease after a median follow-up of 30 months. The survival at 5, 8, and 10 years was 69, 65, and 63%, respectively. Natural breakpoints in Breslow thickness for survival occurred at 0.85, 1.95, and 4.00 mm. These are not significantly different from those found by other investigators. A step-down multivariate analysis using the Cox regression model yielded four factors as highly significant in predicting survival: Breslow thickness (P less than 0.001), an age/sex interaction (P = 0.0012), clinical ulceration (P = 0.0039), and a prophylactic node dissection (P = 0.019). No predictive value for a BANS or non-BANS location was detected. These results are discussed in reference to other large series which describe the natural history of cutaneous melanoma.

Arizona

Treatments for Centruroides exilicauda envenomation.

We treated two cases of severe envenomation by the scorpion Centruroides exilicauda. The first infant was treated with a species-specific scorpion antivenom, which produced a delayed but dramatic return of all vital signs to normal. A second infant was treated with two doses of intravenous propranolol hydrochloride and had a rapid, dramatic decrease in heart rate but only gradual resolution of neurologic symptoms. These cases demonstrate the severe symptoms of envenomation by this scorpion in the infant and show two possible treatments.

Antivenins

Evaluation of an automated image analysis system for counting human tumor colonies.

The Omnicon FAS II image analysis system was applied to counting tumor colonies grown in a soft agar human tumor clonogenic assay with a detailed protocol designed to assess the instrument's sensitivity, specificity, precision, and accuracy. Comparisons of technician and instrument counts were done on a blinded basis. Sensitivity studies (which used metal microspheres) yielded a correlation coefficient (r) of 0.999 between technicians and the counter. A field-by-field analysis of the instrument's specificity for identifying individual objects correctly as tumor colonies rather than artifacts (as identified by the technician) was excellent (r = 0.95). In the precision studies (determined with repeated automated counting of the same samples for five days), the median coefficient of variation was less than 7%. Accuracy was evaluated on cultures of fresh biopsies from 30 human cancers obtained for drug sensitivity testing as well as on a series of tumor cell lines. The correlation between the mean number of colonies counted by the technicians and by the colony counter was greater than 0.91. Similar comparisons of mean percent survival of tumor colony-forming cells after drug exposure between technician and machine were also quite acceptable (r = 0.85). We conclude that the colony counter provided sufficient reliability to be applied to counting human tumor colonies grown in vitro. In addition, the colony counter performed the Petri dish counts ten times faster than experienced technicians and without associated operator fatigue.

Animals

Use of survival analysis to determine the clinical significance of new Q waves after coronary bypass surgery.

There are few data on the long-term effects of new Q waves on survival and morbidity after coronary bypass graft surgery (CABG). We followed 1340 patients who underwent CABG in 1978 at 10 hospitals participating in the Coronary Artery Surgery Study (CASS). The incidence of perioperative Q-wave infarction was 4.76% (range 0.0-10.3% by hospital). The rate of infarction was higher in patients who had an increased left ventricular end-diastolic pressure or cardiomegaly on the preoperative chest radiograph. Patients who received more grafts or who had longer cardiopulmonary bypass time were also at higher risk of infarction. In a stepwise discriminant analysis of 44 clinical, angiographic and surgical variables, cardiopulmonary bypass time, topical cardiac hypothermia and cardiomegaly entered the stepwise selection of variables. Long-term survival was adversely affected by the appearance of new postoperative Q waves. The hospital mortality was 9.7% in the 62 patients who had new postoperative Q waves and 1.0% in the 1278 patients who did not (p less than 0.001); the 3-year cumulative survival rates were 85% and 95%, respectively (p less than 0.001). In patients who survived to hospital discharge, the presence of new postoperative Q waves did not adversely affect 3-year survival (94% and 96%, respectively). The survival rates were worse in patients who had a history of infarction or who had impaired left ventricular function preoperatively. The number of readmissions to hospital after CABG among the patients who had a transmural perioperative infarction was similar to to that among patients who did not. We conclude that the appearance of new Q waves after CABG adversely affects survival. The major impact on mortality occurs before hospital discharge. Patients who are destined to have a perioperative infarct cannot be predicted from commonly measured preoperative and angiographic variables.

Adult

Impaired metabolism of methylphenobarbital after a combined drug overdose: treatment by resin hemoperfusion.

A 38-yr-old woman who by history ingested 13 g methylphenobarbital, alcohol, and 6 g acetaminophen became comatose slowly over 4 d. Acute hepatic injury appeared to impair the oxidative N-demethylation of methylphenobarbital to its product, phenobarbital. On the eighth day after ingestion she was treated because of protracted coma with Amberlite XAD-4 resin hemoperfusion. Hemoperfusion, which removed 0.83 g methylphenobarbital and 2.10 g phenobarbital, led to transient clinical improvement. When supportive patient management fails to produce a satisfactory clinical course in a methylphenobarbital-intoxicated patient, hemoperfusion could be a useful adjunct to therapy.

Acetaminophen