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Biomedical subjects

T Hoff

Publications and source records attributed to T Hoff.

At least 19 recordsLinked to original sources

The response of endocrine system to stress loads during space flight in human subject.

The responses of endocrine system to the exposure to stress-work load and hormonal changes during oral glucose tolerance tests were studied in the Slovak astronaut before (three weeks before flight), during (on the 4th and the 6th days of space flight), and after space flight (1-3 days and 15-17 days after space flight) on board of space station MIR. Blood samples during the tests were collected via cannula inserted into cubital vein, centrifuged in the special appliance Plasma-03, frozen in Kryogem-03, and at the end of the 8-day space flight transferred to Earth in special container for hormonal analysis. Preflight workload produced an increase of plasma norepinephrine and a moderate elevation of epinephrine levels. Plasma levels of insulin, growth hormone, prolactin and cortisol were not markedly changed immediately or 10 min after the end of work load. The higher increases of plasma growth hormone, prolactin and catecholamine levels were noted after workload during space flight as compared to preflight response. The higher plasma glucose and insulin levels were noted during the oral glucose tolerance test in space flight and also in the post flight period. Plasma epinephrine levels were slightly decreasing during glucose tolerance test; however, plasma norepinephrine levels were not changed. The similar patterns of catecholamine levels during glucose tolerance test were found when compared the preflight, in-flight and post flight values. These data demonstrate the changes of the dynamic responses of endocrine system to stress-work and metabolic loads during space flight in human subject.

Adaptation, Physiological↗

A recombinase-mediated transcriptional induction system in transgenic plants.

We constructed and tested a Cre-loxP recombination-mediated vector system termed pCrox for use in transgenic plants. In this system, treatment of Arabidopsis under inducing conditions mediates an excision event that removes an intervening piece of DNA between a promoter and the gene to be expressed. The system developed here uses a heat-shock-inducible Cre to excise a DNA fragment flanked by lox sites, thereby generating a constitutive GUS reporter gene under control of the CaMV 35S promoter. Heat-shock-mediated excision of several, independent lines resulted in varying degrees of recombination-mediated GUS activation. Induction was shown to be possible at essentially any stage of plant growth. This single vector system circumvents the need for genetic crosses required by other, dual recombinase vector systems. The pCrox system may prove particularly useful in instances where transgene over-expression, or under-expression by antisense, would otherwise affect embryo, seed or seedling viability.

Acetyltransferases↗

Detection limit, cut-off and specificity of an improved rapid assay for cardiac troponin T.

The performance of an improved version of the troponin T rapid test TROPT Sensitive was investigated in a multicentre evaluation at twelve centres. The detection limit and the cut-off were determined in a method comparison with Elecsys Troponin T using a total of 365 samples from patients with suspected acute coronary syndromes and 91 samples from healthy blood donors or non-cardiological patients. The analytical specificity was determined by measuring 1271 blood samples from blood donors without any myocardial injury. The test cut-off (90% of results positive) is 0.08 microg/L, and the detection limit is about 0.05 microg/L. The analytical specificity of the test is between 99.7 and 99.9%. With its small area of undefined significance between positive and negative results and its high sensitivity and specificity, TROPT Sensitive is very well suited to the reliable detection of troponin T positive patients with acute coronary syndromes.

Biomarkers↗

Effect of microgravity on plasma catecholamine responses to stressors during space flight.

The effect of microgravity on the sympathicoadrenal system (SAS) activity in humans and animals has not yet been clarified. Our previous studies suggested that the SAS activity, evaluated by circulating and/or urinary catecholamine (CA) levels in astronauts during space flights, was found to be rather unchanged. However, CA levels were measured in astronauts only at rest conditions. The aim of the present study was to investigate effect of microgravity during space flight and post-flight readaptation on responsiveness of the SAS to somatic and psychic stressors evaluated by levels of catecholamines and their metabolite in the blood of the Slovak cosmonaut during his stay on board the space station Mir.

Adaptation, Physiological↗

Are US health professionals likely to prescribe mifepristone or methotrexate?

OBJECTIVE: To determine US health professionals' knowledge, attitudes, and practices regarding mifepristone and methotrexate as abortifacients. METHODS: In 1997, we conducted a nationally representative telephone survey of US obstetrician/gynecologists (OBs), family practice physicians (FPs), nurse practitioners (NPs), and physician assistants (PAs). RESULTS: Most health professionals surveyed considered themselves at least "somewhat familiar" with mifepristone or methotrexate, but few reported being "very familiar" with the methods. OBs were most likely to report being familiar with mifepristone (79%), followed by NPs/PAs (73%), and FPs (62%). FPs and NPs/PAs reported being less familiar with methotrexate than with mifepristone. If mifepristone were approved by the Food Drug Administration (FDA), 54% of OBs said they would be "very" or "somewhat" likely to prescribe the drug for abortion, including 35% of OBs who do not perform surgical abortions currently. About half of FPs and NPs/PAs were interested in offering mifepristone if approved by the FDA. Few health professionals reported ever having prescribed methotrexate for abortion. CONCLUSION: The providers most likely to express interest in offering medical alternatives were OBs who reported they "ever perform surgical abortions." Many health professionals who said they do not perform surgical abortions also said they would be interested in prescribing mifepristone, indicating a potential expansion of the number of health professionals who will provide abortion services. Medical protocol and legal issues may inhibit or slow expansion of the pool of providers offering medical abortion.

Abortifacient Agents, Nonsteroidal↗

Using quality function deployment to capture the voice of the customer and translate it into the voice of the provider.

BACKGROUND: Health care has a number of historical barriers to capturing the voice of the customer and to incorporating customer wants into health care services, whether the customer is a patient, an insurer, or a community. Quality function deployment (QFD) is a set of tools and practices that can help overcome these barriers to form a process for the planning and design or redesign of products and services. The goal of the project was to increase referral volume and to improve a rehabilitation hospital's capacity to provide comprehensive medical and/or legal evaluations for people with complex and catastrophic injuries or illnesses. HIGH-LEVEL VIEW OF QFD AS A PROCESS: The steps in QFD are as follows: capture of the voice of the customer, quality deployment, functions deployment, failure mode deployment, new process deployment, and task deployment. The output of each step becomes the input to a matrix tool or table of the next step of the process. CASE STUDY EXAMPLE: In 3 1/2 months a nine-person project team at Continental Rehabilitation Hospital (San Diego) used QFD tools to capture the voice of the customer, use these data as the basis for a questionnaire on important qualities of service from the customer's perspective, obtain competitive data on how the organization was perceived to be meeting the demanded qualities, identify measurable dimensions and targets of these qualities, and incorporate the functions and tasks into the delivery of service which are necessary to meet the demanded qualities. DISCUSSION: The future of providing health care services will belong to organizations that can adapt to a rapidly changing environment and to demands for new products and services that are produced and delivered in new ways.

Arizona↗

Biochemical and genetic characterization of three molybdenum cofactor hydroxylases in Arabidopsis thaliana.

Aldehyde oxidases and xanthine dehydrogenases/oxidases belong to the molybdenum cofactor dependent hydroxylase class of enzymes. Zymograms show that Arabidopsis thaliana has at least three different aldehyde oxidases and one xanthine oxidase. Three different cDNA clones encoding putative aldehyde oxidases (AtAO1, 2, 3) were isolated. An aldehyde oxidase is the last step in abscisic acid (ABA) biosynthesis. AtAO1 is mainly expressed in seeds and roots which might reflect that it is involved in ABA biosynthesis.

Aldehyde Oxidase↗

Missed opportunities: teenagers and emergency contraception.

OBJECTIVE: To determine American teenagers' awareness of and knowledge about emergency contraceptive pills and their likelihood to use them. METHODS: We conducted a nationally representative telephone survey between March 28, 1996, and May 5, 1996, of 1510 teenagers (757 girls and 753 boys), aged 12 to 18 years, living in the continental United States in households with telephones. The sample overrepresented African American, Latino, and low-income teenagers. The error attributable to sampling and other random effects for the total sample is +/-3 percentage points at the 95% confidence level. RESULTS: Of the 1510 teenagers, only about one quarter (23%) were aware that "anything" could be done after unprotected sex to prevent pregnancy. Slightly more (28%) had heard of "morning-after pills" or emergency contraceptive pills. Of the 423 teenagers who had heard of emergency contraceptive pills, one third (32%) did not know that a prescription is necessary to obtain them, and three quarters (78%) underestimated how long after unprotected intercourse the emergency contraceptive pill regimen could be initiated. Only 9% knew that emergency contraceptive pills are effective as long as 72 hours after unprotected sex. After being told about the option of emergency contraceptive pills, two thirds (67%) of teenaged girls said that they would be likely to use emergency contraceptive pills. Among the 66% of teenaged girls who had not previously heard of emergency contraceptive pills, 64% said that they would be likely to use them. CONCLUSIONS: Emergency contraceptive pills have great potential as a tool for reducing unplanned pregnancies among teenaged girls in the United States. Few teenaged girls were aware that this option exists. Once informed, teenaged girls reported being very interested in taking emergency contraceptive pills if needed.

Adolescent↗

Are we making progress with emergency contraception? Recent findings on American adults and health professionals.

OBJECTIVES: To determine how awareness of and practices and attitudes toward emergency contraceptive pills (ECPs) have progressed among the American public and US health professionals. METHODS: In 1997, we conducted two nationally representative telephone surveys of Americans and health professionals of their knowledge, attitudes, and practices on ECPs and compared the findings to previous surveys. RESULTS: 66% of women and 51% of men 18 to 44 years old had heard of ECPs, up from 61% of women and 45% of men the same age in 1994. Only 1% of women surveyed reported having ever used this method, reflecting no change from 1994. Only 11% of women knew enough about ECPs to be able to use them. Americans named media as the primary source of information about ECPs. The proportion of physicians who had prescribed ECPs at least once in the preceding year increased significantly in 1997: 85% of obstetrician/gynecologists and 50% of family physicians compared to 69% and 34% in 1995. Almost all health professionals considered ECPs to be safe (99%) and effective (100%), yet relatively few discussed this option with their patients, and even fewer commonly prescribed it. CONCLUSION: Ongoing efforts are needed to improve awareness among the general public and to encourage health professionals to discuss and offer ECPs more widely.

Adolescent↗

Isolation of two Arabidopsis cDNAs involved in early steps of molybdenum cofactor biosynthesis by functional complementation of Escherichia coli mutants.

Most organisms appear to have a molybdenum cofactor consisting of a complex of molybdenum and a pterin derivative. Very little is known about molybdenum cofactor biosynthesis in plants or other eukaryotes, because the instability of the cofactor and its precursors makes it difficult to analyze this pathway. We have isolated two cDNA clones from the higher plant Arabidopsis thaliana encoding genes involved in early steps of molybdenum cofactor biosynthesis. The cDNAs were obtained by functional complementation of two Escherichia coli mutants deficient in single steps of molybdenum cofactor biosynthesis. The two cDNAs, designated Cnx2 and Cnx3, encode proteins of 43 and 30 kDa, respectively. They have significant identity to the E. coli genes, moaA and moaC, involved in molybdenum cofactor biosynthesis. Both genes have N-terminal extensions that resemble targeting signals for the chloroplasts or the mitochondria. Import studies with the translated proteins and purified mitochondria and chloroplasts did not show import of these proteins to either of these organelles. Northern analysis show that Cnx2 is expressed in all organs and strongest in roots. Cnx3 is not expressed in abundant levels in any tissue but roots. For both genes there is no detectable difference in the expression level from plants grown with nitrate or with ammonium. The Cnx2 gene has been mapped to chromosome II. Southern analysis suggests that both genes exist as single copies in the genome.

Amino Acid Sequence↗

Transient expression of prostaglandin endoperoxide synthase-2 during mouse macrophage activation.

We investigated regulation of macrophage prostaglandin production during activation by interferon gamma (IFN-gamma) and lipopolysaccharide (LPS). An in vitro model was established using the mouse macrophage-like cell line RAW 264.7. Cells were cultivated in the presence of IFN-gamma and LPS for up to 48 h and changes in the secretion of nitric oxide (NO.) and tumor necrosis factor alpha (TNF-alpha) were observed as activation markers. Under these conditions a prompt and strong increase in PGE2 production was found in the first 8 h followed by nearly constant generation of PGE2 during the next 40 h. In contrast, the activity of prostaglandin endoperoxide synthase (PGHS), measured as PGE2 production of microsomal protein fractions, was also increased, but reached a clear maximum at 24 h. Recently a second form of PGHS was cloned (PGHS-2) and specific antibodies and mRNA probes for both isoforms are available. PGHS-2 enzyme was expressed maximally after 24 h of activation whereas PGHS-1 was not influenced. In the presence of IFN-gamma and LPS, PGHS-2 mRNA expression reached a maximum at 8 h but PGHS-1 mRNA was not induced during the whole time period. These data indicate that changes in PG synthesis following macrophage activation are due to regulation of PGHS-2 expression.

Animals↗

Interleukin-1-induced cyclooxygenase 2 expression is suppressed by cyclosporin A in rat mesangial cells.

The immunosuppressive drug cyclosporin A (CsA) has considerable nephrotoxic side effects which seem to be related to its interference with the synthesis of vasoactive prostanoids. Therefore, the molecular mechanism of the effect of CsA on the synthesis of prostaglandin E2 (PGE2) was investigated in rat renal mesangial cells (RMC). CsA effectively inhibited the PGE2 synthesis induced by inflammatory cytokines such as interleukin 1 (IL-1) or tumor necrosis alpha (TNF alpha). The induction by IL-1 and the inhibition by CsA were reflected in the enzyme activity of the cyclooxygenase. The changes in activity could be correlated with the expression of the inducible cyclooxygenase isoform (COX2), which is characterized by its 4.4 kb mRNA: the expression of this enzyme was enhanced by IL-1 and suppressed by CsA on the mRNA and protein level as determined by Northern and Western blot analyses. Suppression of COX2 mRNA was also observed when the message was induced by LPS or ionophore A23187. The expression of the basal cyclooxygenase isoform (COX1), which was constitutively expressed in proliferating mesangial cells, was not affected by IL-1 or CsA. Interferon gamma, which did not induce prostaglandin synthesis or influence COX mRNA expression, augmented the expression of MHC antigens in RMC. This induction was insensitive to CsA treatment. We could thus show that the inducible cyclooxygenase isoform in mesangial cells is a molecular target for CsA providing a possible mechanism for the interference of the drug with the balance of vasoactive prostanoids.

Animals↗

Differentiation-associated expression of prostaglandin G/H synthase in monocytic cells.

Significant progress in the investigation of the regulation of prostanoid formation has recently been made by cloning a second gene coding for prostaglandin G/H synthase (PGHS; EC 1.14.99.1). In this study we examined the expression of the two PGHS isoforms during phorbol ester induced monocytic differentiation of human myeloid leukemia cells (U937). Murine and ovine PGHS-1 probes hybridized to 2.8- and 5.5-kb mRNA species, whereas the murine PGHS-2 probe hybridized to a 5.3-kb species. Western blot analysis using antisera to mouse PGHS-1 and to a synthetic peptide derived from a mouse PGHS-2-specific region revealed a band of 70 kDa for PGHS-1 and a doublet of about 85 kDa for PGHS-2. Unlike PGHS-2, which was not expressed in U937 control cells, both PGHS-1 protein and mRNA were detected in untreated U937 cells. TPA strongly induced PGHS-2 protein and also increased the amount of PGHS-1 protein. Correspondingly, a marked induction of PGHS-2 mRNA was found, but virtually no change in the expression of the PGHS-1 2.8-kb mRNA occurred. The induction of both PGHS isoforms turned out to be dexamethasone-sensitive. The suppression of PGHS-2 induction was more pronounced. These results suggest that both PGHS-1 and to a larger extent PGHS-2 contribute to the upregulation of prostanoid synthesis during monocytic differentiation.

Animals↗

Effects of glucocorticoids on the TPA-induced monocytic differentiation.

The human monocytic cell line U937 was used as a model system to investigate the effects of glucocorticoids on monocytic differentiation. Upon incubation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 x 10(-9) M) for 48 to 72 h, the immature U937 cells ceased to proliferate and became morphologically and functionally macrophage-like. Preincubation of the cells with glucocorticoids (dexamethasone and prednisolone, 10(-7) and 10(-6) M) but not progesterone (10(-6) M) had marked effects: The cells remained in suspension and developed very little cell-cell interaction. This correlated with decreased expression of the surface molecules ICAM-1 and CD18 as determined by fluorescence-activated cell sorter analysis. The TPA-induced ability of the cells to release lysozyme or to generate reactive oxygen radicals (determined as reduction of nitroblue tetrazolium) was markedly reduced. The induction of cyclooxygenase activity and thus the ability to release prostanoids was almost completely abolished. Inhibition of prostanoid synthesis was also observed when the glucocorticoids were administered 24 or 48 h after TPA. The primary step of TPA induction, the activation and translocation of protein kinase C, however, was not affected by glucocorticoids as determined by activity measurements and Western blot analysis. There was no change in the subsequent TPA-induced induction of c-fos. The down-regulation of the differentiation-related oncogenes c-myc and c-myb was the same in cells treated with TPA in the presence or absence of glucocorticoids. Furthermore, no significant effect of glucocorticoids on the TPA-induced growth arrest was observed. Glucocorticoids thus interfere with TPA-induced functions, which are typical for activated macrophages; however, they do not impair the differentiation process and concomitant growth inhibition.

Cell Adhesion↗

Transformation of Halogen-, Alkyl-, and Alkoxy-Substituted Anilines by a Laccase of Trametes versicolor.

The laccase of the fungus Trametes versicolor was able to polymerize various halogen-, alkyl-, and alkoxy-substituted anilines, showing substrate specificity similar to that of horseradish peroxidase, whereas the laccase of Rhizoctonia praticola was active only with p-methoxyaniline. The substrate specificities of the enzymes were determined by using gas chromatography to measure the decrease in substrate concentration during incubation. With p-chloroaniline as the substrate, the peroxidase and the Trametes laccase showed maximum activity near pH 4.2. The transformation of this substrate gave rise to a number of oligomers, ranging from dimers to pentamers, as determined by mass spectrometry. The product profiles obtained by high-pressure liquid chromatography were similar for the two enzymes. A chemical reaction was observed between p-chloroaniline and an enzymatically formed dimer, resulting in the formation of a trimer. All three enzymes oxidized p-methoxyaniline to 2-amino-5-p-anisidinobenzoquinone di-p-methoxyphenylimine, but only the T. versicolor laccase and the peroxidase caused the formation of a pentamer (2,5-di-p-anisidinobenzoquinone di-p-methoxyphenylimine). Our results demonstrate that in addition to horseradish peroxidase, a T. versicolor laccase can also polymerize aniline derivatives.

Journal Article↗

Cold agglutinins in infectious mononucleosis and heterophil-antibody-negative mononucleosis-like syndromes.

Cold agglutinins (CA) were evaluated prospectively in patients with various mononucleosis syndromes and in a large control group. Cold agglutinins with anti-i specificity were seen mainly in heterophil-positive or -negative Epstein-Barr virus (EBV)-induced infectious mononucleosis (31.8% of cases). Unclassified CA with equal reactivity against cord and adult erythrocytes were seen in 56 of 150 (37.3%) cases of heterophil-antibody-positive infectious mononucleosis (IM), in 1 of 7 (14.3%) cases of heterophil-negative EBV-induced IM, and in 12 of 31 (38.7%) cases of the heterophil-negative mononucleosis-like syndrome due to cytomegalovirus or other unspecified agents. One patient with heterophil-positive IM had a persistent, partially papain sensitive CA with anti-Pr-like activity. Anti-i CA were seen in less than 1.0% of healthy young adults (500) or patients without mononucleosis (500) submitted for heterophil studies. Unclassified CA were noted in 3.2% of the latter 1000 samples.

Agglutinins↗

Understanding the managed care backlash.

This paper examines the depth and breadth of the public backlash against managed care and the reasons for it. We conclude that the backlash is real and influenced by at least two principal factors: (1) A significant proportion of Americans report problems with managed care plans; and (2) the public perceives threatening and dramatic events in managed care that have been experienced by just a few. In addition, public concern is driven by fear that regardless of how well their plans perform today, care might not be available or paid for when they are very sick.

Adult↗