Insulin-like growth factor-binding protein-1 and prostate cancer.
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Case-Control Studies↗
Biomedical subjects
R Bergstrom
Publications and source records attributed to R Bergstrom.
Thermoprotective mechanisms of irrigation during bipolar cautery.
Bipolar cautery is routinely used in operations of the head and neck, as well as in other specialties, both for dissection and for achieving hemostasis. Whereas simultaneous irrigation is frequently used to minimize neuronal injury, its effectiveness has not been tested under controlled conditions. Our objectives in this study were to test the hypothesis that including irrigation during bipolar cautery is thermoprotective and to identify the mechanisms underlying the thermoprotective effect. The thermoprotective role of irrigation with bipolar cautery was tested in a rat model in which the sciatic nerve was exposed and a 1-second stimulus at 40 or 20 watts was applied with bipolar cautery forceps placed directly on the nerve in the presence or absence of simultaneous irrigation. We used the Sciatic Functional Index as used to quantitate the degree of paresis induced. The results showed that simultaneous irrigation reduced the percentage of animals showing paresis. This effect was significant for animals exposed to 40- and 20-watt cautery. The mechanism for the reduction in the degree of paresis by irrigation could not be attributed to a lowering of the maximal temperature achieved after bipolar cautery. Instead, the thermoprotective mechanism of the irrigation involved an enhanced recovery to basal temperatures when measured at 15 seconds after nerve stimulation with 40 or 20 watts. Reducing the power from 40 watts to 20 watts did not significantly lessen the tissue temperature. The results of this study suggest that irrigation done simultaneously with bipolar cautery enhances temperature recovery to basal levels and plays a role in thermoprotection against the effects of cautery.
Animals↗
A case illustrating the continued dilemmas in treating abdominal pregnancy and a potential explanation for the high rate of postsurgical febrile morbidity.
BACKGROUND: Abdominal pregnancy is potentially highly morbid and often complicated by postoperative fever. CASE: A 29-year-old gravida 2 para 0 presented with a 17-week size-demised abdominal pregnancy. We describe the continued difficulty in determining the timing and type of intervention. In addition, we found that the gestational sac was colonized by group B streptococcus at the time of surgery. CONCLUSION: This case illustrates that preoperative colonization of the intra-abdominal gestational sac may contribute to postoperative febrile morbidity. We suggest treating patients with prophylactic antibiotics and avoiding spill of gestational sac contents into the peritoneal cavity. Placement of a sterile Foley bulb into the uterine cavity can confirm the extrauterine position of the pregnancy prior to undertaking surgery.
Adult↗
Hormone replacement therapy and the risk of breast cancer. Nested case-control study in a cohort of Swedish women attending mammography screening.
There is concern that hormone replacement therapy (HRT) increases the risk of breast cancer. We undertook a case-control study of this risk relationship within a cohort of 40- to 74-year-old women in Uppsala County, Sweden, who participated in mammography screening. Incident cases of breast cancer were ascertained during 5 years of follow-up. In all, 435 cases (87% invasive, 13% in situ cancers) were detected, 313 through screening and 122 through clinical diagnosis. As controls, 1,740 women were selected randomly. Information on risk factors and use of HRT was obtained through interviews before the start of follow-up. Multivariate analyses revealed an increased risk among users of any type of HRT for more than 10 years, the odds ratio (OR) being 2.1 (95% confidence interval [CI] 1.1-4.0), as well as when restricting analyses to cases diagnosed through mammography screening. After stratification for compound type, risk estimates were apparently higher among women reporting estradiol-progestin combined treatment vs. estradiol or conjugated estrogens alone, with ORs for more than 10 years of intake being 2.4 (95% CI 0.7-8.6) and 1.3 (95% CI 0.5-3.7), respectively. Analyses through a model including both compound type and length of hormone intake confirmed a significant excess risk linked to treatment for more than 10 years, OR = 2.6 (95% CI 1.3-5.1). Our results indicate a moderately increased risk of breast cancer after many years of HRT and, hypothetically, a further enhancement of the risk with added progestins.
Adult↗
Protein phosphatase-2A association with microtubules and its role in restricting the invasiveness of human head and neck squamous cell carcinoma cells.
The role of protein phosphatase-2A (PP-2A) in regulating the motility and adhesion of human head and neck squamous cell carcinomas (HNSCC) was investigated. Immunofluorescent staining of these HNSCC cells showed PP-2A can co-localize with microtubules. That the PP-2A influences motility was shown by the increase in HNSCC cell migration through laminin and vitronectin when PP-2A was selectively inhibited with low dose okadaic acid, and by the reduction in invasion through these same matrix components by elevators of PP-2A activity. Motility of HNSCC cells through collagen I or fibronectin was not modulated by PP-2A. The reduction in HNSCC migration through vitronectin or laminin that resulted from treatment with PP-2A elevators was associated with an increase in cellular adhesiveness to these same ECM components. These studies show the association of PP-2A with the cellular cytoskeleton and its role in restricting the invasiveness of tumor cells through select extracellular matrix components.
Calcitriol↗
Chromosomal deletion complexes in mice by radiation of embryonic stem cells.
Chromosomal deletions ("deficiencies') are powerful tools in the genetic analysis of complex genomes. They have been exploited extensively in Drosophila melanogaster, an organism in which deficiencies can be efficiently induced and selected. Spontaneous deletions in humans have facilitated the dissection of phenotypes in contiguous gene syndromes and led to the positional cloning of critical genes. In mice, deletion complexes created by whole animal irradiation experiments have enabled a systematic characterization of functional units along defined chromosomal regions. However, classical mutagenesis in mice is logistically impractical for generating deletion sets on a genome-wide scale. Here, we report a high-throughput method for generating radiation-induced deletion complexes at defined regions in the genome using ES cells. Dozens of deletions of up to several centiMorgans, encompassing a specific locus, can be created in a single experiment and transmitted through the germline. The ability to rapidly create deletion complexes along chromosomes will facilitate systematic functional analyses of the mammalian genome.
Animals↗
A search for recall bias in a case-control study of diet and breast cancer.
BACKGROUND: In retrospective studies of dietary habits and breast cancer risk, recall bias is a concern since diet has been publicized as a cause of breast cancer. METHODS: In a case-control study of diet and breast cancer risk nested within a cohort of women screened with mammography, we contrasted answers to a retrospective dietary interview with answers to a dietary questionnaire which was filled out before any diagnostic procedures for breast cancer were undertaken. The source population was all women aged 40-74 in two counties in Sweden invited to mammographic screening and asked to fill out a questionnaire before the screening. Cases and controls were subsequently defined -- matched on age, county of residence, and time of mammography -- and approached for an interview. RESULTS: In all, 265 cases and 431 controls participated in the study. Means of frequencies differed between the agreement in the questionnaire's and the interview's classifications of study subjects into quartiles of monthly intake varied between 31 percent and 57 percent. Kappa statistics in all food groups were below 0.41. In a regression analysis, case subjects with low responses on the questionnaire about intake of meat, snacks, and coffee and tea gave higher responses on interview than did controls who had low questionnaire responses for these food groups. The reverse was also true: cases' responses that were high on the questionnaire were lower on interview for these food groups than were controls' responses. CONCLUSIONS: We found few signs of recall bias, and the few indications of a differential misclassification that we found were not in food groups that have been publicly discussed as causes of breast cancer.
Adult↗
Hypertension in Japanese Americans: the Seattle Japanese-American Community Diabetes Study.
AMONG SEATTLE'S JAPANESE AMERICANS, hypertension is associated with older age, male gender (in the younger age groups), glucose intolerance (impaired glucose tolerance and diabetes), and visceral obesity (measured by computed tomography). The gender difference in prevalence of hypertension is absent in those ages 65 to 74 and in those with diabetes. In the absence of diabetes, hypertension is not associated with fasting plasma insulin levels in the older second generation, but it is in the younger third generation. The association of hypertension with plasma insulin in the third generation may be due to the association between diabetes and plasma insulin and the presence of many prediabetic individuals in this generation. About three-fourths of Japanese Americans are aware of their hypertension, slightly more than half of hypertensive Japanese Americans are being treated with anti-hypertensive medication, and of those receiving anti-hypertensive medication, less than half have their hypertension controlled. Women tend to be less aware of hypertension, to receive anti-hypertensive medication less often, and to have their hypertension less well-controlled than men.
Adult↗
Vitamin D3 and ceramide reduce the invasion of tumor cells through extracellular matrix components by elevating protein phosphatase-2A.
Increasing phosphorylation reactions by protein kinase A (PKA) or reducing dephosphorylation reactions of protein phosphatase-2A (PP-2A) increases the invasiveness of Lewis lung carcinoma (LLC) cells, as measured by their capacity to traverse extracellular matrix (ECM)-coated filters. Metastatic LLC-LN7 variants have reduced PP-2A activity when compared to nonmetastatic LLC-C8 variants. Immunoblotting showed that this reduced level of PP-2A activity was not due to reduced levels of the PP-2A catalytic (C) subunit. The cellular PP-2A activity could be stimulated by addition of C2-ceramide to LLC-LN7 lysates, or by incubating cells with either C2-ceramide or with a noncalcemic analog of vitamin D3, which has previously been shown to stimulate the release of ceramide. These treatments to elevate PP-2A activity in metastatic LLC-LN7 cells resulted in a decline in their capacity to invade through select (ECM) components, particularly through vitronectin and laminin. Underscoring the importance of PP-2A in limiting the invasiveness of tumor cells was the demonstration that LLC-LN7 cell transfectants overexpressing the PP-2A C alpha subunit were less invasive through ECM components than the wild-type cells. Invasion by these cells was further reduced by additionally increasing PP-2A activity by incubation with C2-ceramide or the vitamin D3 analog. These results suggest a role of a vitamin D3/ceramide/PP-2A pathway in limiting the invasiveness of tumor cells through select ECM components.
Animals↗
Clostridium perfringens invasiveness is enhanced by effects of theta toxin upon PMNL structure and function: the roles of leukocytotoxicity and expression of CD11/CD18 adherence glycoprotein.
Clostridium perfringens infections are characterized by the lack of an inflammatory response at the site of infection and rapidly progressive margins of tissue necrosis. Studies presented here investigated the role of theta toxin from C. perfringens in the pathophysiology of these events. Mice passively immunized with neutralizing monoclonal antibody against theta toxin and challenged with an LD100 of log phase C. perfringens had significantly less mortality than untreated controls. Intramuscular injection of killed, washed C. perfringens in mice induced a massive time-dependent influx of polymorphonuclear leukocytes (PMNL) into tissue; injection of either viable, washed C. perfringens or killed organisms plus theta toxin dramatically attenuated PMNL influx although PMNL accumulated in adjacent vessels. The anti-inflammatory effects could not be attributed to an absence of chemoattractants since C. perfringens proteins had chemotactic factor activity, and killed bacilli generated serum-derived chemotactic factors. Scanning and transmission electron microscopy demonstrated the dramatic leukocidal effects of high doses of theta toxin on PMNL. In contrast, sublethal concentrations of theta toxin primed PMNL chemiluminescence, disrupted PMNL cytoskeletal actin polymerization/disassembly, and stimulated functional upregulation of CD11b/CD18 adherence glycoprotein. In summary, these results demonstrate that theta toxin is an important virulence factor in C. perfringens infection. In a concentration-dependent fashion, theta toxin contributes to the pathogenesis of clostridial gangrene by direct destruction of host inflammatory cells and tissues, and by promoting dysregulated PMNL/endothelial cell adhesive interactions.
Actins↗
Frequently nebulized beta-agonists for asthma: effects on serum electrolytes.
STUDY OBJECTIVE: To determine the magnitude of the changes in serum potassium, magnesium, and phosphate during the treatment of acute bronchospasm with repeated doses of beta-adrenergic agonists. DESIGN: Prospective study of a convenience sample of asthmatic patients. SETTING: University teaching hospital emergency department. TYPE OF PARTICIPANTS: Twenty-three patients met the inclusion criteria of age of more than 16 years; a history of asthma or chronic obstructive pulmonary disease; and an acute exacerbation. INTERVENTIONS: Baseline peak expiratory flow rate and serum potassium, magnesium, and phosphate levels were measured. Nebulized albuterol (2.5 mg) was administered every 30 minutes until the patient was discharged from the ED. Before each albuterol treatment, repeat serum levels of potassium, magnesium, and phosphate were determined. MEASUREMENTS AND MAIN RESULTS: Baseline peak expiratory flow rate averaged 188 +/- 119 L/min. Serum potassium levels decreased significantly (P = .0001 by repeated-measures analysis of variance) from 4.10 +/- 0.468 (baseline) to 3.55 +/- 0.580 mmol/L (90 minutes) and 3.45 +/- 0.683 mmol/L (180 minutes). Potassium decreased to less than 3.0 mmol/L in 22% of patients at some point during the study. Magnesium decreased from 1.64 +/- 0.133 mmol/L (baseline) to 1.48 +/- 0.184 mmol/L (90 minutes) and 1.40 +/- 0.219 mmol/L (180 minutes) (P = .0001). Phosphate levels also decreased, from 3.74 +/- 1.029 (baseline) to 2.84 +/- 0.957 mmol/L (90 minutes) and 2.55 +/- 0.715 mmol/L (180 minutes) (P = .0001). CONCLUSION: Aggressive administration of nebulized albuterol during the emergency treatment of acute bronchospasm is associated with statistically significant decreases in serum potassium, magnesium, and phosphate. The mechanism and clinical significance of these findings are unknown and warrant further study.
Adolescent↗
Effects of different designs and extension of a food frequency questionnaire on response rate, completeness of data and food frequency responses.
The authors studied how the introduction of several modifications to a basic food frequency questionnaire can influence the results of dietary surveys. Modifications covered eight combinations based on three levels: increasing versus decreasing order of frequency categories; questionnaires without versus with questions about portion sizes, and questionnaires without versus with extra non-dietary questions. The sample included 6783 women between the ages of 40 and 70 years who took part in mammography screening. The women were randomly assigned to one of the eight study groups. All of the women in each group received one of the eight differently modified questionnaires. The forms extended in length by extra non-dietary questions and portion size categories resulted in a 20% higher total non-response compared to the shorter basic form. Partial non-response was significantly lower for all four questionnaire types that included portion sizes. When portion sizes were included in the questionnaire, the reported mean frequency of consumption was significantly reduced for fat (-10 times per month), milk (-6), bread (-5), vegetables (-2) and fish (-0.4). The decreasing order of responses to the frequency categories was associated with a statistically significant increase in the frequency responses for bread (2.6 times per month), vegetables (2) and fish (0.6). These data provide evidence that the design and extension of food frequency questionnaires influence the results of dietary studies.
Adult↗
Homology among Escherichia coli K1 and K92 polysialytransferases.
The neuS-encoded polysialytransferase (polyST) in Escherichia coli K1 catalyzes synthesis of polysialic acid homopolymers composed of unbranched sialyl alpha 2,8 linkages. Subcloning and complementation experiments showed that the K1 neuS was functionally interchangeable with the neuS from E. coli K92 (S. M. Steenbergen, T. J. Wrona, and E. R. Vimr, J. Bacteriol. 174:1099-1108, 1992), which synthesizes polysialic acid capsules with alternating sialyl alpha 2,8-2,9 linkages. To better understand the relationship between these polySTs, the complete K92 neuS sequence was determined. The results demonstrated that K1 and K92 neuS genes are homologous and indicated that the K92 copy may have evolved from its K1 homolog. Both K1 and K92 structural genes comprised 1,227 bp. There were 156 (12.7%) differences between the two sequences; among these mutations, 55 did not affect the derived primary structure of K92 polyST and hence were synonymous with the K1 sequence. Assuming maximum parsimony, another estimated 17 synonymous mutations plus 84 nonsynonymous mutations could account for the 70 amino acid replacements in K92 polyST; 36 of these replacements were judged to be conservative when compared with those of K1 polyST. There were no changes detected in the first 146 5' or last 129 3' bp of either gene, suggesting, in addition to the observed mutational differences, the possibility of a past recombination event between neuS loci of two different kps clusters. The results indicate that relatively few amino acid changes can account for the evolution of a glycosyltransferase with novel linkage specificity.
Amino Acid Sequence↗
Chemical and enzymatic degradation of ganciclovir prodrugs: enhanced stability of the diadamantoate prodrug under acid conditions.
We report the chemical and enzymatic hydrolysis of two hydrophobic prodrugs of ganciclovir (3 = dipropionate ester; 4 = diadamantoate ester). Both prodrugs undergo hydrolysis showing a pH dependence of kobs = kH+aH+ + ko + kHO-aHO- and a pH of maximum stability near pH 5. Only 4 exhibited a shelf life (t90) greater than 2 years. Compound 4 reacts significantly slower than ganciclovir in acidic media, even though the adamantyl esters provide additional reaction sites (which would be expected to increase the rate of degradation) that are distally removed from the guanine ring system, offering negligible steric or electronic substituent effects. Both 3 and 4 hydrolyzed in tissue homogenate, where kobs followed liver greater than intestine much greater than skin. Based on these findings of chemical stability, lipophilicity, and acceptable rate of enzymatic cleavage by skin esterases, 4 meets several of the criteria required for the topical sustained delivery of ganciclovir.
Animals↗
The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis.
We investigated the relative efficacies of penicillin, clindamycin, and erythromycin in a mouse model of myositis due to Streptococcus pyogenes. Penicillin was ineffective unless given at the time of bacterial injection, and treatment delays of 2 h reduced its efficacy such that survival was no better than that of untreated control animals (P less than .05). Survival of erythromycin-treated mice was greater than that of both penicillin-treated mice and untreated controls, but only if treatment was begun within 2 h. Mice receiving clindamycin, however, had survival rates of 100%, 100%, 80%, and 70% even if treatment was delayed 0, 2, 6, and 16.5 h, respectively. Thus, clindamycin demonstrated superior efficacy to penicillin among all the various treatment groups (P less than .05). Our results corroborate the failure of penicillin in this model of streptococcal infection and suggest that, unlike penicillin, the efficacy of clindamycin is not adversely altered by the "Eagle effect."
Animals↗
Selection of a derivative of the antiviral agent 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) with improved oral absorption.
Various diesters of 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) were screened in order to identify a derivative with improved oral absorption. The solubilities and dissolution rates decreased with increasing chain length and branching of the ester group. However, the dipropionate ester showed an anomalously faster dissolution rate. The rates of hydrolysis to DHPG in the presence of intestinal homogenates were found to increase with increasing carbon number for the straight-chain alkyl esters and decreased with branching. The shorter-chain alkyl esters were relatively more stable in intestinal homogenates than in liver homogenates. Therefore they may have a better membrane permeability than DHPG due to their intact ester group. The hydrolysis rates in human blood increased with increasing carbon number for the straight-chain alkyl esters. The dipropionate ester appeared to be the most promising derivative because of its rapid dissolution rate, slower hydrolysis in the intestine, and rapid conversion to DHPG in liver and blood.
Acyclovir↗
The use of an infusion pump in arthroscopy.
The use of an infusion pump is an effective method of irrigating the joint in arthroscopy. A Sarns roller blood pump is used to pump fluid into the joint through the arthroscope with outflow by gravity drainage through a plastic cannula. Flow and pressure can be adjusted independently. Measurements were made of calf, knee, and thigh swelling after arthroscopy in 42 patients; the average swelling of each was less than 1 cm. In 45 patients, the average rate of flow through the joint was 45 mm/min, with a measured outflow of 40 mm/min. Intraarticular pressure greater than 200 mm Hg can be obtained with the pump, compared with maximum pressures only slightly greater than 100 mm Hg with gravity inflow alone. The operator must carefully monitor the system; retention of excessive fluid can lead to postoperative swelling and morbidity.
Adolescent↗
Molecular structure of troponin C from chicken skeletal muscle at 3-angstrom resolution.
The x-ray structure of chicken skeletal muscle troponin C (TnC), the Ca2+-binding subunit of the troponin complex, shows that the protein is about 70 angstroms long with an unusual dumbbell shape. The carboxyl and amino domains are separated by a single long alpha helix of about nine turns. Only the two high-affinity Ca2+-Mg2+ sites of the COOH-domain are occupied by metal ions resulting in conformational differences between the COOH- and NH2-domains. These differences are probably important in the triggering of muscle contraction by TnC. Also the structure of TnC is relevant in understanding the function of other calcium-regulated proteins, in particular that of calmodulin because of its strong similarity in amino acid sequence.
Animals↗