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Biomedical subjects

C C Hsieh

Publications and source records attributed to C C Hsieh.

At least 109 records · Page 6Linked to original sources

Bone marrow transplantation for therapy-related myelodysplasia: comparison with primary myelodysplasia.

Therapy-related myelodysplasia (MDS) is a fatal marrow disorder distinct from primary MDS. We examined the efficacy of bone marrow transplantation (BMT) as a treatment for patients with therapy-related MDS. Eighteen patients with therapy-related MDS and twenty-five patients with primary MDS received an allogeneic, syngeneic, or unrelated donor BMT. Graft-versus-host disease prophylaxis included methotrexate, methotrexate plus cyclosporine, FK-506, or T cell depletion. Conditioning regimens consisted of cyclophosphamide/total body irradiation, with and without cytosine arabinoside, busulfan/cyclophosphamide, and cyclophosphamide/etoposide/carmustine. For patients with therapy-related MDS, the median age was 32 years and the actuarial disease-free survival was 24% (95% confidence interval 6, 42%) with a median follow-up of 3 years. For patients with primary MDS, the median age was 36 years and the actuarial disease-free survival at 3 years was 43% (95% confidence interval 22, 64%). Four of the therapy-related patients and two of the primary patients have relapsed. Three patients experienced graft failure; all three had received T cell-depleted marrow and two had marrow fibrosis. Our results suggest that patients with therapy-related MDS can be successfully transplanted. Transplantation should be considered early in the disease, since long-term disease-free survival is achievable.

Adolescent↗

Immunolocalization of interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in radicular cysts.

To investigate the mechanisms involved in expansion of radicular cysts, monoclonal antibodies against interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were used to localize the sites of MMP-1 and TIMP-1 expression in 30 radicular cysts. Positive MMP-1 staining was detected in the lining epithelium and subepithelial fibroblasts, macrophages, endothelial cells and osteoblasts/osteocytes in all specimens. Positive TIMP-1 staining was identified in osteoblasts/osteocytes and endothelial cells of all specimens, and in the lining epithelium and subepithelial fibrous connective tissue wall of five radicular cysts with an intense inflammatory cell infiltrate. The number and distribution of positive cells for MMP-1 or TIMP-1 varied widely among individual specimens, but strong immunostaining was constantly detected at sites with prominent subepithelial inflammation. Results here support the hypothesis that MMP-1 may play an important role in the expansion of radicular cysts. The absence of TIMP-1 expression in lining epithelium and subepithelial fibroblasts and macrophages in most cases studied indicated that an imbalance between MMP-1 and TIMP-1 production may lead to radicular cyst expansion.

Antibodies, Monoclonal↗

Prenatal diagnosis of tetralogy of Fallot with absent pulmonary valve accompanied by hydrops fetalis.

Tetralogy of Fallot with absent pulmonary valve is a rare congenital cardiac anomaly. We report on the echocardiographic features of a fetus with such an anomaly and aneurysm of the pulmonary artery associated with hydrops fetalis and polyhydramnios. The prognosis of tetralogy of Fallot with absent pulmonary valve and pulmonary aneurysm is grave, especially in a fetus with intrauterine heart failure. Serial sonographic follow-up is mandatory to detect the signs of hydrops fetalis. Early intervention and intensive treatment should be given to improve the perinatal outcome once the prenatal diagnosis is made.

Adult↗

Sexually transmitted diseases and risk of HIV infection in men attending a sexually transmitted diseases clinic in Dakar, Senegal.

This cross-sectional study was carried out among male outpatients with symptoms of STDs at the STD reference centre at the Institute of Social Hygiene (IHS), Dakar, Senegal, from March 1989 through May 1991. This study was used to determine the prevalence of STDs and HIV among male patients attending an STD clinic and to identify their socio-demographic characteristics and risk factors. A total of 975 patients were enrolled in the study. The most common syndromes were urethritis (76%) and genital ulcers (22%). Considering single infections, the major STD agents were Neisseria gonorrheae (N.gonorrheae, 30%), Chlamydia trachomatis (C.trachomatis, 15%), Treponema pallidum (T.pallidum, 12%), and Haemophilus ducreyi (H.ducreyi, 7%). HIV prevalence was 2.6 percent (25/975). After multivariate analysis, the risk factors associated with HIV infection were a history of sex with prostitutes (odds ratio [OR] = 8.6, 95% confidence interval [CI] = 2.0-37.8), unprotected sexual contact (OR = 5.6, 95% CI = 1.2-25.0), a history of urethritis (OR = 3.4, 95% CI = 1.3-8.9), current STDs due to H.ducreyi or T.pallidum (OR = 6.1, 95% CI = 2-18.8), and mixed STD infection (OR = 5.3, 95% CI = 1.3-21.8). HIV prevalence was quite low in this population compared to similar studies of STD patients from other sub-Saharan African countries. Neisseria gonorrheae and Chlamydia trachomatis were the leading causes of STDs. A history of risky sexual behaviour, previous STDs, current genital ulcers, and mixed STD infections were associated with HIV infection. Further studies are necessary to determine changes in the relationship of STDs and HIV infection in this population.

Adult↗

Total failure energy of a composite resin bonded to human enamel.

Total failure energy is defined as the energy required to stress a bond to the point of fracture. This study was designed to assess and compare the total failure energy of a resin-enamel bond with conventional tensile and shear bond strengths. A commercially available composite resin was bonded to human enamel surface. During testing, the applied load versus displacement of the load fixture was recorded and analyzed by a data acquisition system. The tensile and shear bond strengths as well as the total failure energies were calculated. The mean tensile bond strength (21.2 MPa) was higher than the mean shear bond strength (11.6 MPa). The mean total energy applied for tensile failure of the bond (2.1 kg.mm) was also higher than that for the shear failure (1.5 kg.mm). There were statistically significant correlations between bond strength and total failure energy. The failure modes of the shear bond test revealed a higher frequency of adhesive failures compared to the tensile bond test. Further, a dramatic difference existed in the cohesive failure mode between tensile (cohesive composite failure) and shear (cohesive enamel failure) tests. The total failure energy, which represents the fracture strength as well as the failure process of a bond, may be considered an appropriate criterion for characterizing the failure of a bond.

Composite Resins↗

Effects of glucose on placental hormones in the human term placenta in vitro.

Glucose intake during pregnancy results in a decrease in endogenous insulin-like growth factor binding protein-1 (IGFBP-1). However, the exact role of glucose on placental secretion of IGFBP-1 is unclear. This study was designed to investigate the direct effects of glucose on the production of IGFBP-1 and other placental hormones, using an isolated placental preparation. Using the dual recirculating perfusion system for an isolated human placenta lobule, a total of 43 experiments were performed over a duration of 6 hours. Twenty placentae were perfused with a medium containing 141 +/- 10 mg/dL (7.83 +/- 0.56 mmol/L) glucose (group I) and 23 placentae with 242 +/- 12 mg/dL (13.43 +/- 0.67 mmol/L) glucose (group II). Levels of insulin, glucose, lactate, insulin-like growth factor (IGF-I), IGFBP-1, human placental lactogen (hPL) and beta-human chorionic gonadotropin (beta-hCG) were measured at 30 minute intervals during perfusion. Insulin and IGF-I were barely detectable in the perfusates and their levels were not modulated by glucose. IGFBP-1 was predominantly detected in the maternal rather than the fetal compartment of the placental circulation. Glucose increased the levels of IGFBP-1 in the maternal circulation in groups I and II during the first two hours of perfusion (188 +/- 58% and 193 +/- 31%, respectively). However, during the subsequent 4 hour period, the increase in IGFBP-1 concentration was significantly higher in group II (926 +/- 427%) than in group I (428 +/- 216%) (p < 0.05). There was no difference in the levels of hPL or beta-hCG between the two groups in the maternal circulation. Thus, glucose stimulates the production of IGFBP-1 in the maternal circulation of a placenta in vitro. This increase in IGFBP-1 by glucose in vitro, as opposed to the decrease of IGFBP-1 in vivo, may be due to a lack of circulatory maternal insulin in the isolated placental preparation. These results also suggest that there may be a functional barrier within the placenta that prevents an increase in the level of IGFBP-1 in the fetal circulation.

Chorionic Gonadotropin, beta Subunit, Human↗

Perinatal characteristics in relation to incidence of and mortality from prostate cancer.

OBJECTIVE: To test the hypothesis that factors causing morbidity and mortality from prostate cancer may operate in utero. DESIGN: Matched case-control study of singleton men born between 1874 and 1946 at one hospital. SETTING: Uppsala University Hospital. SUBJECTS: 250 patients with prostate cancer and 691 controls, including 80 patients who died from prostate cancer and their 196 matched controls. MAIN OUTCOME MEASURES: Mother's age at menarche, parity, pre-eclampsia or eclampsia before delivery, age at delivery and socioeconomic status; case or control's birth length and weight, placental weight, prematurity derived from gestational age, and presence of jaundice. RESULTS: Both pre-eclampsia (odds ratio 0, 95% confidence interval 0 to 0.71) and prematurity (0.31, 0.09 to 1.04) were inversely associated with incidence of prostate cancer. Among subjects born full term, placental weight, birth weight, and ponderal index (weight/height 3) showed non-significant positive associations with prostate cancer incidence, and stronger associations with mortality. CONCLUSION: Prenatal exposures that are likely correlates of pregnancy hormones and other growth factors are important in prostate carcinogenesis and influence the natural course as well as the occurrence of this cancer.

Age Factors↗

Assessment of postpartum time-dependent disease risk in case-control studies: an application for examining age-specific effect estimates.

Among subjects who have experienced a biological event, such as menarche, menopause or a delivery, one cannot distinguish the effects of time since the event from age at the event due to the linear dependency among these time variables and age at study ('current age'). This is a well-known problem that also exists in the determination of the short- and long-term influence of childbirth on subsequent disease risk, since one must take into account in the analysis both current age and age at delivery. We describe an approach to assess in case-control studies the effect of a full-term pregnancy on time-dependent disease risk by including nulliparous women in the analysis and considering current age as a modifier of the effect of age at delivery. One then uses current age-specific odds ratio estimates that compare uniparous to nulliparous women to examine whether the relative rate of disease varies over time after a delivery. Analytic options include stratified analysis and modelling with interaction terms for unconditional or conditional logistic regression analysis. As an example, we have applied this analysis to a large case-control study that utilized record linkage between the Cancer Registry and the Fertility Registry of Sweden and that documented a transient increase in breast cancer risk after a childbirth, followed by a long-term reduction in this risk.

Adult↗

Cigarette smoking and pancreas cancer: a case control study of the search programme of the IARC.

A multi-centre case-control study of pancreas cancer, designed to be population-based, to use a random sample of local populations as controls and to use a common protocol and core questionnaire, was conducted as the first study of the SEARCH programme of the International Agency for Research on Cancer. "Ever-smokers" were found to be at increased risk for pancreas cancer compared with "never-smokers" consistently in all strata of gender, response status and centre. Risk of pancreas cancer was found to increase with increasing lifetime consumption of cigarettes, the relative risk rising to 2.70 (95% C.I. 1.95 to 3.74) in the highest intake category. The overall trend in risk was highly significant and the association was found consistently in each stratum of gender, response status and centre. Fifteen years had to pass from quitting cigarette smoking until the risk fell to a level compatible with that in never-smokers among the heaviest group of smokers; among the 2 lowest tertiles this happened within 5 years. Further, reported smoking habits more than 15 years before diagnosis appeared to have no influence on pancreas-cancer risk, irrespective of amount smoked. The results are consistent with a causal role for cigarette smoking in the aetiology of pancreas cancer and illustrate that ceasing to smoke cigarettes can lead to reductions in the elevated risk of pancreas cancer produced by this habit.

Case-Control Studies↗

Testicular nonseminoma and seminoma in relation to perinatal characteristics.

BACKGROUND: Testicular cancer incidence peaks during the third decade of life, and an increasing trend in the occurrence of this disease has been seen in many countries. Few risk factors have been established for testicular cancer, but evidence suggests that causal factors operate early in life, perhaps even in utero. PURPOSE: We performed a case-control study to evaluate specific perinatal characteristics as risk factors for the two main histopathologic types of testicular cancer: seminomas and nonseminomas. METHODS: Two hundred thirty-two case patients with invasive testicular cancer and 904 individually matched control subjects (all singleton births), nested in a cohort of men born at 10 hospitals in Sweden from 1920 through 1978, were included in the study. Perinatal information about the study subjects and their parents was obtained from birth records. For the mothers, information was recorded concerning age at menarche, marital status, parity, age at delivery, maternal weight at delivery and at first visit to a maternal-care center, education and/or profession, and any medical problems encountered during pregnancy or after delivery. For the fathers, information was obtained concerning age at delivery and education and/or profession. For the study subjects, information was recorded about the following: gestational age, birth length and weight, placental weight, method of delivery (normal, cesarean section, or with forceps or vacuum extractor), medical problems during hospital stay, presence of jaundice, method of feeding at discharge, and duration of hospital stay after birth. Individuals diagnosed with testicular cancer were identified through the Swedish National Cancer Registry and the Uppsala Regional Cancer Registry. The data were analyzed by use of conditional logistic regression modeling. RESULTS: When testicular cancer was modeled as a single entity, significantly elevated risks were associated with neonatal jaundice (adjusted odds ratio [OR] = 2.30; 95% confidence interval [CI] = 1.07-4.94) and with either low (< 2500 g) or high (> or = 4000 g) birth weight (OR = 2.59; 95% CI = 1.05-6.38 and OR = 1.58; 95% CI = 1.10-2.29, respectively). When seminomas and nonseminomas were analyzed separately, high maternal socioeconomic status (OR = 2.54; 95% CI = 1.05-6.12), neonatal jaundice (OR = 3.96; 95% CI = 1.47-10.69), and low birth weight (OR = 7.62; 95% CI = 1.59-36.60) were associated with nonseminomas, whereas high placental weight (OR = 3.50; 95% CI = 0.97-12.62) suggested increased risk for seminomas. CONCLUSIONS AND IMPLICATIONS: Perinatal exposures appear to influence the risk of testicular cancer, and seminomas and nonseminomas may have somewhat different risk profiles. Future epidemiologic studies should consider the possibility of etiologic heterogeneity in the development of seminomas and nonseminomas.

Birth Weight↗

Pattern of gp120 sequence divergence linked to a lack of clinical progression in human immunodeficiency virus type 1 infection.

Differential rates of AIDS development and/or T4 lymphocyte depletion in HIV-1-infected individuals remain unexplained. The hypothesis that qualitative differences in selection pressure in vivo may account for different rates of disease progression was addressed in nine eligible study participants from a cohort of 315 homosexual men who have been followed since 1985. Disproportionately fewer changes in variable regions and more in C3 of gp12O were found to be significantly associated with slower disease progression. Our finding provides the first example to demonstrate that differential selection pressure related to the emergence of HIV-1 variants is associated with long term nonprogression. Candidate vaccines that elicit strong selection pressure on C3 of gp120 are likely to provide better protection than those targeting variable regions.

Base Sequence↗

Parity, age at first and last birth, and risk of breast cancer: a population-based study in Sweden.

Associations between parity and the risk of breast cancer, and the relative importance of age at first and age at last birth on breast cancer risk, were estimated in a case-control study nested in a nation-wide cohort of Swedish women born between 1925 and 1960. A total of 12,782 women with breast cancer and five times as many individually age-matched controls, aged less than 60 years with concomitant fertility information, were included in the analysis. Increasing parity was associated with a pronounced decrease in the risk of breast cancer with each additional birth conferring a 10 percent risk reduction (odds ratio 0.90 [95% CI 0.88-0.91]). In an analysis limited to women with two or more parities, and after adjustment for the effects of ages at interim births, the risk of breast cancer increased by about 13 percent for each five-year increment in age at first birth (odds ratio 1.13 [1.08-1.19]). For every five year-increase in age at last birth there was a small risk increase of marginal statistical significance (odds ratio 1.05 [1.01-1.09]). The present findings contradict recent claims that age at last birth has a stronger effect than age at first birth on breast cancer risk. The dominance of age at first birth as risk modulator is likely to reflect the protection afforded by the terminal differentiation of breast cells induced by a first pregnancy.

Age Factors↗

Characterization of somatic cell hybrids exhibiting extinction of AFP, albumin and an AFP-HPRT transgene.

We utilized an AFP-HPRT transgene, i.e. the HPRT coding sequences under the regulation of AFP enhancer and promoter sequences, to localize the AFP extinguisher locus in intertypic somatic cell hybrids (hepatoma X fibroblast). This hybrid gene construct, which directly links AFP regulation to a reversibly selective gene, enabled the selection of stably transfected cells which express AFP, as well as cells showing extinction of AFP. Mouse hepatoma cells stably transfected with and expressing the transgene were fused to human fibroblasts, and the resulting somatic cell hybrids were characterized using Southern, Northern and karyotypic analyses. That several hybrids exhibited the proper extinction of AFP, AFP-HPRT and albumin suggests coregulation of these genes by an extinguisher. Segregant lines derived from these hybrids were selected for the loss of extinguisher activity and for reexpression of the transgene. Karyotypic analysis of hybrid and segregant lines, exhibiting proper AFP, albumin and AFP-HPRT phenotypes, revealed that the presence of human chromosome 7 was most closely associated with the AFP-extinguished state. The hybrids generated in these studies now make it possible to isolate the sequences responsible for AFP and albumin extinction.

Albumins↗

Does age at the last birth affect breast cancer risk?

We studied the relative importance of age at first and age at last full-term pregnancy (FTP) in a large data set of 3950 cases and 11,510 controls, of whom 2263 cases and 7359 controls had two or more FTPs. We found that a 5-year delay in age at first FTP is associated with an odds ratio of 1.17 (95% confidence interval of 1.05-1.29), whereas a 5-year delay in the age of last FTP is associated with an odds ratio of 1.05 (95% confidence interval 0.96-1.14). Misleading results concerning the relative importance of age at first and last FTP may be obtained when parity is only adjusted in broad categories, uniparous women whose FTP is, simultaneously, both the first and the last are not excluded from the analysis, and age at any FTP between the first and last is not controlled for.

Adult↗

Regulation of the acute phase response genes alpha 1-acid glycoprotein and alpha 1-antitrypsin correlates with sensitivity to thermal injury.

BACKGROUND: The response to thermal injury is a complex physiologic process requiring communication between sites of injury and distal target organs. The liver, one of these target organs, synthesizes a family of secretory proteins, the acute phase reactants (APRs), that carries out specific protective functions. This study investigates the response of positively regulated (alpha 1-acid glycoprotein and alpha 1-antitrypsin) and negatively regulated (albumin) APR genes to severe thermal injury in three rat strains with differing abilities to survive thermal stress. METHODS: Age and weight matched male Buffalo, Sprague-Dawley, and Fischer 344, 12- to 16-week-old rats (275 to 325 gm) received a 40% total body surface area scald burn. Total RNA was isolated from livers at 0, 2, 5, 12, 24, and 48 hours. Northern blot hybridization was performed with 32P-labeled rat alpha 1-glycoprotein, rat albumin, and mouse alpha 1-antitrypsin cDNAs. Relative amounts of alpha 1-glycoprotein, alpha 1-antitrypsin, and albumin mRNAs were determined by means of densitometric analyses. RESULTS: All three strains elicit both a positive and negative acute phase (AP) response. Significant differences were observed in the degree and kinetics between strains. Those more sensitive to thermal injury exhibited a more intense positive AP response and possibly a delayed recovery. The AP response between these strains correlates with the variation in ability to survive severe trauma. CONCLUSIONS: The differences in the kinetics and intensity of induction of APR genes between Buffalo, Sprague-Dawley, and Fischer rat strains suggest that the least intense AP response and its timely recovery correlated with the ability to survive a severe thermal injury and that, conversely, the more intense and prolonged response correlated with sensitivity to severe thermal injury. We propose that this may be a basis for variation in survival to thermal injury.

Animals↗

Effect of thermal injury on the expression of transcription factors that regulate acute phase response genes: the response of C/EBP alpha, C/EBP beta, and C/EBP delta to thermal injury.

BACKGROUND: Eukaryotic organisms possess natural defense mechanisms that protect against stress stimuli. One such mechanism is the activation of families of stress response genes (e.g., the acute phase response). Transcription of many of these genes is regulated by the leucine zipper or bZIP proteins (CCAAT binding/enhancer binding proteins [C/EBPs]). The aim of this study was to show that the C/EBP transcription factor genes respond to thermal injury. METHODS: Age- and weight-matched male Buffalo, Sprague-Dawley, and Fischer 344 12- to 16-week-old rats (275 to 325 gm) received a 40% total body surface area scald burn. Total RNA was isolated from livers at 0, 2, 5, 12, 24, and 48 hours. Northern blot hybridization was performed with 32P-labeled C/EBP alpha, C/EBP beta, and C/EBP delta cDNAs. Relative amounts of each mRNA were determined by densitometric analyses. For Western analyses liver nuclear and cytoplasmic protein extracts were prepared from burned and control rats. Nuclear protein extracts were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted onto a PVDF membrane, and detected by using an enhanced chemiluminescence detection kit. RESULTS: Expression of C/EBP genes is regulated in response to 40% total body surface area scald burn. A simultaneous decrease in C/EBP alpha and an increase in C/EBP beta and C/EBP delta mRNA levels occur in response to thermal injury. Western analyses detect changes in C/EBP alpha and C/EBP beta pool levels that suggest a differential regulation of these genes in response to thermal injury. CONCLUSIONS: The responses of C/EBP alpha, C/EBP beta, and C/EBP delta are similar in Buffalo, Sprague-Dawley, and Fischer rats. The induced level, however, of C/EBP beta mRNA was highest in the Sprague-Dawley strain and lowest in the Buffalo strain and correlates well with the mortality of these strains. Because C/EBP beta is associated with the transactivation of stress response genes, this may explain the intensity of the response in the susceptible strains. This agrees with our hypothesis that the higher degree of sensitivity of the Sprague-Dawley rat to stress relative to the Buffalo strain may be due to inherently higher levels of factors such as C/EBP whose functions are associated with activation of stress response genes.

Acute-Phase Reaction↗