Breast cancer incidence and mortality in Milwaukee's North Shore communities.
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Breast Neoplasms↗
Biomedical subjects
S Park
Publications and source records attributed to S Park.
Optical activity of a nucleotide-sensitive tryptophan in myosin subfragment 1 during ATP hydrolysis.
The xanthene probes 5'-iodoacetamido-fluorescein and -tetramethylrhodamine specifically modify skeletal muscle myosin subfragment 1 (S1) at the reactive thiol residue (SH1) and fully quench the fluorescence emission from tryptophan residue 510 (Trp510) in S1 (T.P. Burghardt and K. Ajtai, Biophys. Chem., 60 (1996) 119; K. Ajtai and T.P. Burghardt, Biochemistry, 34 (1995) 15943). The difference between the fluorescence intensity obtained from S1 and probe-modified S1 comes solely from Trp510 in chymotryptic S1, a protein fragment that contains five tryptophan residues. The rotary strength and quantum efficiency of Trp510 were measured using difference signals from fluorescence detected circular dichroism (FDCD) and fluorescence emission spectroscopy. These structure-sensitive signals indicate that the binding of nucleotide or nucleotide analogs to the active site of S1 causes structural changes in S1 at Trp510 and that a one-to-one correspondence exists between Trp510 conformation and transient states of myosin during contraction. The Trp510 rotary strength and quantum efficiency were interpreted structurally in terms of the indole side-chain conformation using model structures and established computational methods.
Adenosine Triphosphate↗
Fatty acid oxidation enzyme gene expression is downregulated in the failing heart.
BACKGROUND: During the development of heart failure (HF), the chief myocardial energy substrate switches from fatty acids to glucose. This metabolic switch, which recapitulates fetal cardiac energy substrate preferences, is thought to maintain aerobic energetic balance. The regulatory mechanisms involved in this metabolic response are unknown. METHODS AND RESULTS: To characterize the expression of genes involved in mitochondrial fatty acid beta-oxidation (FAO) in the failing heart, levels of mRNA encoding enzymes that catalyze the first and third steps of the FAO cycle were delineated in the left ventricles (LVs) of human cardiac transplant recipients. FAO enzyme and mRNA levels were coordinately downregulated (> 40%) in failing human LVs compared with controls. The temporal pattern of this alteration in FAO enzyme gene expression was characterized in a rat model of progressive LV hypertrophy (LVH) and HF [SHHF/Mcc-facp (SHHF) rat]. FAO enzyme mRNA levels were coordinately downregulated (> 70%) during both the LVH and HF stages in the SHHF rats compared with controls. In contrast, the activity and steady-state levels of medium-chain acyl-CoA dehydrogenase, which catalyzes a rate-limiting step in FAO, were not significantly reduced until the HF stage, indicating additional control at the translational or post-translational levels in the hypertrophied but nonfailing ventricle. CONCLUSIONS: These findings identify a gene regulatory pathway involved in the control of cardiac energy production during the development of HF.
Adult↗
Cleft containing reactive thiol of myosin closes during ATP hydrolysis.
The probe binding cleft of myosin subfragment 1 (S1) contains the reactive thiol, SH1, and tryptophan 510 (Trp-510). Solvent accessibility to Trp-510, measured using the acrylamide quenching of its fluorescence, is highest in rigor and decreases during the ATPase cycle prior to force generation. These data suggest the probe binding cleft closes during ATP hydrolysis and opens during force generation. The closing of the probe binding cleft may be the origin of the shape change of S1 during ATP hydrolysis.
Adenosine Triphosphate↗
Optimization of the separation and detection of the enantiomers of isoproterenol in microdialysis samples by cyclodextrin-modified capillary electrophoresis using electrochemical detection.
Isoproterenol is a chiral catecholamine with a half-life of elimination of less than 10 min. In order to study the pharmacokinetics of this compound using microdialysis sampling, an analytical method was needed which could resolve the individual enantiomers of isoproterenol and required less than 1 microliter of sample. A capillary electrophoretic method using a run buffer containing methyl-O-beta-cyclodextrin as a chiral recognition agent was developed which could resolve the enantiomers of isoproterenol. The detection limits using UV absorbance detection were found to be too high to determine the concentration of isoproterenol in plasma for a sufficient time following administration to establish the pharmacokinetics. The detection limits were decreased three orders of magnitude to 3 ng/ml by using an amperometric detector. The detection limits were decreased to 0.6 ng/ml using an on-column concentration technique in which peak stacking was accomplished by following the sample injection with a plug of acid.
Animals↗
Frequent loss of heterozygosity in region of the KIP1 locus in non-small cell lung cancer: evidence for a new tumor suppressor gene on the short arm of chromosome 12.
To refine the chromosomal localization of a putative tumor suppressor gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 36 primary non-small cell lung cancer (NSCLC) samples with matched normal DNA using 22 highly informative polymorphic markers. Twelve cases showed LOH at one or more loci on chromosome 12. LOH of chromosome arm 12p was more frequent in large cell carcinoma than squamous cell carcinoma, indicating molecular genetic heterozygosity within the major NSCLC subtypes. We identified the smallest commonly deleted region on chromosome 12p13. This region is flanked by D12S269 and D12S308, including the KIP1 gene. Mutational analysis of KIP1 using PCR-single strand conformation polymorphism and Southern Blot analysis showed no homozygous deletions, rearrangements, or point mutations, suggesting that the altered gene in this region is not the KIP1 gene. These data suggest that a new tumor suppressor gene which is involved in tumorigenesis of NSCLC is in the region of KIP1.
Carcinoma, Non-Small-Cell Lung↗
The multicomponent nature of equilibrium in persons with parkinsonism: a regression approach.
Lower extremity strength and joint range of motion, body sway, and electromyography responses have all been determined to be factors in balance control of healthy older individuals. The purpose of this study was to identify variables which effect balance control (equilibrium scores) of persons with Parkinsonism, and examine their relationships and predictive abilities. The composite equilibrium score from the sensory organization protocol of the Equitest was used as the dependent variable for the regression analysis. The independent variables included: 1) strategy score; 2) path sway during voluntary body displacement; 3) percent peak torque of knee flexion relative to that of knee extension (%PTKFKE); 4) peak torque of inversion of the ankle at (PTINV); 5) dorsiflexion ROM; and 6) medium loop latency (EMG). The model produced a significant overall relationship accounting for 88% of the variability in equilibrium scores. Positive and significant coefficients indicated a predicted increase in the equilibrium composite score with increases in the strategy score, PTINV and %PTKFKE. These results suggest that postural control of persons with Parkinsonism can be strongly predicted by these three variables.
Aged↗
Photoperturbation of the heme a3-CuB binuclear center of cytochrome c oxidase CO complex observed by Fourier transform infrared spectroscopy.
Purified cytochrome c oxidase CO complex from beef heart has been studied by Fourier transform infrared absorbance difference spectroscopy. Photolysis at 10-20 Kelvin results in dissociation of a3FeCO, formation of CuBCO, and perturbation of the a3-heme and CuB complex. The vibrational perturbation spectrum between 900 and 1700 cm-1 contains a wealth of information about the binuclear center. Appearance in infrared photoperturbation difference spectra of virtually all bands previously reported from resonance Raman spectra indicate the importance of polarization along the 4-vinyl:8-formyl axis, which results in the reduction of heme symmetry to C2v. Frequency-shifted bands due to the 8-formyl and 4-vinyl groups of the a3-heme have been identified and quantitated. The frequency shifts have been interpreted as being due to a change in porphyrin polarization with change in spin state of the iron by photodissociation of CO or perturbation of the CuB coordination complex.
Animals↗
Relative effects of high saturated fatty acid levels in meat, dairy products, and tropical oils on serum lipoprotein and low-density lipoprotein degradation by mononuclear cells in healthy males.
To determine the effects of three saturated fatty acid combinations on lipoprotein metabolism, we fed 18 21- to 32-year-old men three diets in a crossover design for 28-day periods separated by washout periods of 4 to 6 weeks. The men self-selected a prescribed diet at home emphasizing saturated fat as the visible fat for 1 week. Then, they ate experimental diets providing 40%, 15%, 17%, and 7% of food energy, respectively, as total, saturated, monounsaturated, and polyunsaturated fatty acids, levels representing amounts available in the US diet. Different test fatty acid combinations, given at 4 to 6 energy% (en%) each, were incorporated into food products: 12:0 + 14:0, 14:0 + 16:0, and 16:0 + 18:0. Test fatty acids were equalized by giving free myristic acid (14:0) with palm kernel oil or butter and sheanut butter (high in 18:0) with lard. The diet highest in 12:0 + 14:0 also provided 4.2 en% 16:0, the most common saturated fatty acid in the US diet. Mean apparent absorption of all fatty acids was at least 90%. The three diets produced similar concentrations of serum total and low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B-100 regardless of the apo E phenotype of the subjects. Compared with baseline, the experimental diets affected serum high-density lipoprotein (HDL) concentrations (P < .06), with the highest values occurring on diet 12:0 + 14:0. When the change from baseline in receptor-mediated degradation of 125I-LDL in freshly isolated mononuclear cells (MNC) was stratified by apo E phenotype, diet 16:0 + 18:0 produced a 30% increase, compared with a 9% decrease on diet 12:0 + 14:0 and a 6% increase on diet 14:0 + 16:0 in subjects with the apo E3/3 phenotype. These results suggested that different saturated fatty acid combinations, consumed at levels typical of availability in the United States and with diets providing ample unsaturated fat, had similar cholesterolemic properties in healthy males despite some subtly different effects on lipoprotein metabolism.
Adult↗
Protective effect of ginseng on radiation-induced DNA double strand breaks and repair in murine lymphocytes.
We have examined the effects of ginseng on the induction and repair of gamma-ray-induced DNA double strand breaks (dsb) using neutral filter elution technique at pH 9.6 in cultured murine spleen lymphocytes. Ginseng water extract 500 micrograms/ml was added to the culture medium either for 48 hours prior to irradiation. Ginseng extract showed protective effect against the formation of dsb when it was treated for 48 hours before 100 Gy gamma-ray-irradiation. While repair was almost completed until 220.2 minutes after irradiation, DNA repair of irradiated cells in the presence of ginseng extract was did not return to the corresponding control levels even after 621.8 minutes. From these data, it could be calculated that ginseng reduced the relative strand scission factor (RSSF) by about 2. Therefore, it could be concluded that ginseng has radioprotective effect against gamma-ray induced DNA dsb and repair in cultured mouse lymphocytes.
Animals↗
Reconstruction of incomplete syndactyly of the toes using both dorsal and plantar flaps.
A new modified method for surgical correction of simple incomplete syndactyly of the toes has been devised. This procedure involves both a dorsal and a plantar skin flap and does not require a skin graft. Reconstruction of syndactyly using only skin flaps situated near the toes almost always results in skin deficiency. Use of a plantar flap from the sole provides sufficient skin for one toe and can be closed primarily. Fourteen cases involving 11 patients have been treated by this method, which is described herein.
Child, Preschool↗
Temporal changes in chromatin, intracellular calcium, and poly(ADP-ribose) polymerase during Sindbis virus-induced apoptosis of neuroblastoma cells.
Sindbis virus (SV) induces apoptosis in many vertebrate cells, but the mechanism is unknown. To gain insight into this mechanism, the nature and time course of intracellular changes related to programmed cell death were studied in SV-infected mouse neuroblastoma cells. New virus production began at 5 h after infection and reach a peak at 12 h. Hoechst 33342 staining of DNA analyzed by flow cytometry demonstrated changes in chromatin beginning 6 h after infection. These chromatin changes were cell cycle dependent, affecting cells in G0/G1 but not S phase. Apoptosis was not dependent on increases in intracellular Ca2+ and occurred more rapidly in the absence of extracellular Ca2+. Nuclear changes were accompanied by activation of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), resulting in increased consumption of NAD which was apparent by 10 h after infection. SV-induced apoptosis also involved the proteolytic cleavage of PARP. This cleavage was detectable at 16 h after infection approximately the same time that DNA fragmentation was apparent by agarose gel electrophoresis. We conclude that SV-induced apoptosis of neuroblastoma cells is dependent on viral replication, is not dependent on a rise in intracellular Ca2+, and is accompanied by activation of PARP and of a protease that cleaves PARP.
Animals↗
Lacrimal canaliculus obstruction: nonsurgical treatment with a newly designed polyurethane stent.
A newly designed polyurethane stent was used to successfully treat 30 eyes (in 28 patients) with epiphora resulting from obstruction of the lacrimal canaliculus. After stent placement, epiphora resolved in all eyes. During follow-up, epiphora recurred in 20 eyes, but epiphora did not recur and the lacrimal canaliculus was patent in 12 eyes after the stent was removed. The stent appears to be valuable for nonsurgical treatment of obstruction of the lacrimal canaliculus.
Equipment Design↗
Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients.
A subset of human growth hormone (GH)-secreting pituitary tumors contains the gsp oncogene that encodes an activation mutation of the alpha-subunit of the stimulatory GTP-binding protein (G(S) alpha). This study was undertaken to investigate the frequency of the gsp oncogene in GH-secreting pituitary tumors in Korean acromegalic patients and to elucidate the clinical characteristics of these patients to endocrine testing. Direct polymerase chain reaction sequencing revealed the gsp oncogene mutation in 9 out of 21 tumors (43%) at amino acid 201 of the G(S) alpha protein. A single nucleotide mutation in the tumors carrying the gsp oncogene was observed, which replaced an arginine (CGT) in the normal protein with cysteine (TGT) in eight tumors and serine (AGT) in one tumor. The patients with the gsp oncogene mutation (group 1) were older (54 +/- 10 vs 41 +/- 11 years, p = 0.0085) than those without the mutation (group 2). Sex, tumor size and grade, basal GH and prolactin levels, the GH response to oral glucose loading, the GH fluctuation and the paradoxical response to thyrotropin-releasing hormone or gonadotropin-releasing hormone did not differ between the groups. The gsp oncogene was found mostly in somatotroph adenomas. The octreotide-induced GH suppression was significantly higher in group 1 than in group 2 (95 +/- 5% vs 81 +/- 17%, p = 0.0335). The GH response to bromocriptine did not differ between the groups. These results suggest that the G(S) alpha mutations of GH-secreting tumor are observed in Korean acromegalic patients with similar frequency to those of western countries. The patients with gsp oncogene are likely to be older than those without the oncogene, and show excellent response of GH suppression to octreotide.
Acromegaly↗
GHb is a better predictor of cardiovascular disease than fasting or postchallenge plasma glucose in women without diabetes. The Rancho Bernardo Study.
OBJECTIVE: To examine the relation between GHb, fasting plasma glucose (FPG), postchallenge plasma glucose (PCPG), and mortality from cardiovascular disease (CVD) and ischemic heart disease (IHD) in older adults. RESEARCH DESIGN AND METHODS: A community-based study of 1,239 nondiabetic older adults followed for an average of 8 years, from baseline (1984-1987) to 1993. RESULTS: GHb, but not FPG or PCPG, was significantly related to CVD and IHD mortality in women but not men. The age-adjusted relative hazard for those in the highest quintile of GHb (> or = 6.7%) compared with women with lower levels was 2.37 for fatal CVD (95% CI = 1.30-4.31, P = 0.005) and 2.43 for IHD (95% CI = 1.12-5.25, P = 0.024). This association persisted after adjustment for all covariates (age, systolic blood pressure, BMI, LDL, HDL, triglycerides, cigarette smoking, antihypertensive medication use, and estrogen use). GHb was significantly associated with LDL and HDL levels in women, but the association between GHb and CVD or IHD persisted after adjustment for these lipoproteins. CONCLUSIONS: We concluded that GHb is a better predictor of CVD and IHD mortality than FPG or PCPG in women without diabetes; no single measure of glycemia was predictive in men. The reason for the sex difference is unexplained.
Adult↗
Efficacy of in vitro treatment of chronic myelogenous leukemia cell line, K562 cells, using 4-hydroperoxycyclophosphamide, alpha-interferon and gamma-interferon.
Alpha-interferon (alpha-IFN) and gamma-interferon (gamma-IFN) are highly effective biologic agents in the treatment of chronic myelogenous leukemia (CML). 4-hydroperoxycyclophosphamide (4-HC) is the most commonly used chemotherapeutic drug when purging bone marrow contaminated with malignant cells. To investigate the efficacy of alpha-IFN, gamma-IFN and 4-HC as purging agents in CML patients, K562 cells, a human CML cell line, were treated in vitro with these drugs singly or in combination. The cytotoxic effect was evaluated by MTT assay. Data were analyzed for synergism by the median effect principle of Chou and Talalay. Using Southern blot analysis, the effect of purging on the suppression of bcr gene rearrangement was also evaluated. Alpha-IFN, gamma-IFN and 4-HC all showed good concentration-dependent cytotoxic effect. Median cytotoxic doses of alpha-IFN gamma-IFN and 4-HC were 0.03 microM 0.20 microM and 1.97 microM respectively, and molar ratios of median doses of alpha-IFN to 4-HC, gamma-IFN to 4-HC and alpha-IFN to gamma-IFN were 1:80, 1:10 and 1:8, respectively. The combination treatment of alpha-IFN and 4-HC, and gamma-IFN and 4-HC showed significant synergistic cytotoxic activities, but combination of alpha-IFN and gamma-IFN was antagonistic. Status of bcr gene rearrangements in K562 cells was not changed after the treatments. Our results appear to provide an efficient method for removing CML cells from the bone marrow of CML patients.
Antineoplastic Agents↗
Hematopoietic and reproductive hazards of Korean electronic workers exposed to solvents containing 2-bromopropane.
OBJECTIVES: The purpose of this study was to describe hematopoietic and reproductive hazards of Korean electronic workers exposed to solvents containing 2-bromopropane. METHODS: Detailed medical and occupational histories were taken and thorough physical examinations with clinical laboratory tests were done for 33 workers (8 men and 25 women). Previous and present exposure was investigated in detail by industrial hygienists. RESULTS: Of the 25 female workers, 16 were shown to have secondary amenorrhea with high follicle-stimulating hormone levels, normal prolactin levels, and hot flashes. A total of eight workers with amenorrhea concurrently showed findings of pancytopenia. Among eight male workers, two showed azoospermia and another four showed some degree of oligospermia (normal > 20 million. ml-1) or reduced sperm motility (normal > 50%). The bone marrow effects and the testis or ovarian failure was shown to be the main health hazards in this workplace. Except for the cleaning solution containing 97.4% 2-bromopropane, no other known physical or chemical agents could be identified as responsible for the gonadal and bone marrow effects, including ionizing radiation, lead, ethylene glycol ether and its acetates, benzene, and dibromochloropropane. CONCLUSIONS: No previous studies have reported human toxicity for 2-bromopropane, but the results of this study lead to the tentative conclusion that the causal agent for the gonadal and bone marrow effects among the workers might be 2-bromopropane.
Adult↗
Bone marrow scintigraphy using technetium-99m-antigranulocyte antibody in hematologic disorders.
UNLABELLED: Bone marrow is the primary site for many hematologic disorders. To date, however, no suitable bone marrow imaging method has been found. The present study investigates the usefulness of bone marrow immunoscintigraphy using 99mTc-labeled antigranulocyte antibody (anti-NCA-95) in 31 patients with hematologic disorders. METHODS: One milligram of antibody labeled with 259-370 MBq 99mTc was injected intravenously, and bone marrow images were taken 4 hr later. We also calculated the uptake ratios of lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B). RESULTS: Of 15 patients with aplastic anemia, 7 showed diffusely decreased antibody uptake (L/B = 2.3 +/- 0.8, I/B = 3.0 +/- 0.8) compared to control patients (n = 21, L/B = 8.2 +/- 2.5, I/B = 10.3 +/- 3.1) Six patients had both decreased and increased uptake areas and two had normal to slightly increased uptake. Of those patients receiving various types of therapy for aplastic anemia, all but one showed increased or irregular uptake. The degree of antibody uptake in the bone marrow correlated with peripheral blood analyses (hemoglobin, white blood cells, platelets). Of six patients with myelodysplastic syndrome, four had irregular uptake and two diffusely decreased uptake. Four patients with myelogenous leukemia showed normal uptake, whereas two with lymphocytic leukemia had decreased uptake. Patients with iron deficiency anemia, pure red cell aplasia or thalassemia minor exhibited normal uptake with bone marrow expansion. CONCLUSION: Immunoscintigraphy with antigranulocyte antibody is a useful method for evaluating the bone marrow status of patients with various hematologic disorders.
Adolescent↗