NHI address coding--is it a threat to the potential of population health surveillance?
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Databases, Factual↗
Biomedical subjects
T Regan
Publications and source records attributed to T Regan.
Psychometric analysis of the Visual Form Discrimination Test.
The Visual Form Discrimination Test is a matching-to-sample test involving visual discrimination. Although normative information has been presented, limited psychometric data have been available. The current study estimated the internal consistency and additional psychometric properties of the test in a sample of 66 persons with acute traumatic brain injury. Internal consistency as measured by alpha was .66. A homogeneous sample and a restricted range of scores likely attenuated this estimate. Using the standard cutoff score, only 32% of the sample showed impaired performance. Visual form discrimination as measured by this test may be affected less by traumatic brain injury than other cognitive processes such as attention and memory.
Adolescent↗
Identification of transcription activators that regulate gonococcal adaptation from aerobic to anaerobic or oxygen-limited growth.
Analysis of the Neisseria gonorrhoeae DNA sequence database revealed the presence of two genes, one encoding a protein predicted to be 37. 5% identical (50% similar) in amino acid sequence to the Escherichia coli FNR protein and the other encoding a protein 41% and 42% identical (54 and 51% sequence similarity) to the E. coli NarL and NarP proteins respectively. Both genes have been cloned into E. coli and insertionally inactivated in vitro. The mutated genes have been transformed into gonococci and recombined into the chromosome. The fnr mutation totally abolished and the narP mutation severely diminished the ability of gonococci to: (i) grow anaerobically; (ii) adapt to oxygen-limited growth; (iii) initiate transcription from the aniA promoter (which directs the expression of a copper-containing nitrite reductase, AniA, in response to the presence of nitrite); and (iv) reduce nitrite during growth in oxygen-limited media. The product of nitrite reduction was identified to be nitrous oxide. Immediately upstream of the narL/narP gene is an open reading frame that, if translated, would encode a homologue of the E. coli nitrate- and nitrite-sensing proteins NarX and NarQ. As transcription from the aniA promoter was not activated during oxygen-limited growth in the presence of nitrate, the gonococcal two-component regulatory system is designated NarQ-NarP rather than NarX-NarL. As far as we are aware, this is the first well-documented example of a two-component regulatory system working in partnership with a transcription activator in pathogenic neisseria. A 45 kDa c-type cytochrome that was synthesized during oxygen-limited, but not during oxygen sufficient, growth was identified as a homologue of cytochrome c peroxidases (CCP) of other bacteria. The gene for this cytochrome, designated ccp, was located, and its regulatory region was cloned into the promoter probe vector pLES94. Transcription from the ccp promoter was repressed during aerobic growth and induced during oxygen-limited growth and was totally FNR dependent, suggesting that the gonococcal FNR protein is a transcription activator of at least two genes. However, unlike AniA, synthesis of the CCP homologue was insensitive to the presence of nitrite during oxygen-limited growth.
Adaptation, Physiological↗
Regulation of the lipopolysaccharide-specific sialyltransferase activity of gonococci by the growth state of the bacteria, but not by carbon source, catabolite repression or oxygen supply.
The enzyme sialyltransferase (STase) of Neisseria gonorrhoeae is a major pathogenicitiy determinant. Using a refined method for assaying the STase activity, the Km for CMP-NANA was shown to be 14 +/- 2 microM, higher than that reported previously. Rates of sialylation by Nonidet extracts, prepared under conditions that optimise solubilisation of the membrane-bound enzyme, were 6 to 20 nmol of NANA transferred from CMP-14C-NANA onto isolated lipopolysaccharide/min./mg of extracted protein, far higher than the previously reported rates of less than 1 nmol of NANA transferred/min./mg of extracted protein. Gonococci grew more slowly with lactate or pyruvate than with glucose as the carbon source. Although growth with a mixture of limiting concentrations of both glucose and lactate was biphasic, diauxic growth was also found in the control culture supplied with glucose alone. The growth rate in the presence of lactate alone was slower than with glucose. The growth rate increased slightly relative to the glucose culture when both substrates were available; lactate was consumed more rapidly than glucose. Higher STase activities were found in bacteria harvested in the exponential than in the stationary phase of aerobic growth: the activity in aerated cultures was higher than those of oxygen-limited or anaerobic cultures. Similar STase activities were found in bacteria that had been grown with glucose, lactate or pyruvate as the carbon and energy source. Sialyltransferase synthesis is essentially constitutive: it is not regulated by glucose repression or by induction by lactate or anaerobiosis.
Carbon↗
Characterization of a sialyltransferase-deficient mutant of Neisseria gonorrhoeae strain F62: instability of transposon Tn1545 delta3 in gonococci and evidence that multiple genetic loci are essential for lipooligosaccharide sialylation.
Neisseria gonorrhoeae strain JB1 was previously shown to be defective in the sialylation of lipoologosaccharide (LOS) by exogenous CMP-NANA. The LOS components synthesized by the mutant now have been shown by mass spectrometry to be similar to those in the parental strain, F62, and to include the 4.5 kDa widely conserved lacto-N-neotetraose component that can be sialylated. The same two LOS components could be sialylated on the surface of the mutant and parental strains. One major component was sialylatable after chemical extraction of the LOS from either strain. These data confirm that the mutant, JB1, retains the ability to synthesize the LOS target required for the conversion by sialylation of serum-sensitive gonococci to serum resistance. A single base frame-shift mutation was found in the lst gene from the mutant, resulting in the replacement of the final 61 amino acids at the C-terminus of the sialyltransferase by four residues. Seventeen independent clones of the lst gene were isolated from the parental strain, but none of them complemented the sialyltransferase defect of the mutant and no sialyltransferase activity expressed from the clones could be detected in Escherichia coli. Although the data suggest that the mutant might be defective in genes at more than one chromosomal locus and that multiple loci are essential for sialyltransferase synthesis and activity, the alternative possibility, that DNA adjacent to the lst gene encodes a product which is toxic to E. coli, cannot be excluded. The site of insertion of the transposon Tn1545-Delta3 in strain JB1 was cloned and sequenced. The transposon is located in an intergenic region adjacent to genes for a putative ATP-dependent transport protein, but encoding no recognizable function relevant to LOS sialylation. Evidence that transposon Tn1545-Delta3 is unstable in gonococci is presented.
Blotting, Southern↗
Evolution of collaborative ambulatory anticoagulation consultation services in a family practice residency.
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Anticoagulants↗
Loss of low-affinity nerve growth factor receptor during malignant transformation of the human prostate.
BACKGROUND: The low-affinity nerve growth factor receptor (LNGFR) exhibits an inverse association of epithelial expression with the degree of differentiation of prostate adenocarcinoma tissue. However, the stage at which loss of LNGFR expression is first manifested in the malignant prostate has not been determined. METHODS: In order to characterize loss of LNGFR expression in the clinically localized malignant prostate of untreated patients, the pattern of expression of the LNGFR was examined in nonmalignant tissues, consisting of normal and prostatic intraepithelial neoplastic tissues, and in malignant tissues that had been graded by Gleason's scores and categorized into well, moderately, and poorly differentiated adenocarcinomas. In order to determine whether there was an inverse correlation between LNGFR expression and prostate-specific antigen (PSA) secretion, preoperative concentrations of PSA in the serum were also analyzed in relation to the differentiative state of the adenocarcinomas. RESULTS: Premalignant prostate tissues exhibited expression of the LNGFR on all epithelia, whereas in malignant prostate tissues a proportion of epithelia exhibited loss of expression of the LNGFR. An increase in Gleason score of the adenocarcinoma tissue was associated with an increase in the proportion of epithelia that exhibited loss of expression of the LNGFR. Moreover, the proportion of epithelia expressing the LNGFR was inversely correlated with an increase in the concentration of serum PSA. The loss of LNGFR expression was first manifested in epithelia that occurred toward the center of adenocarcinoma tissue. Furthermore, extensive loss of expression of the LNGFR of approximately 63% occurred in well-differentiated adenocarcinomas. CONCLUSIONS: These observations demonstrate that loss of LNGFR expression is first observed in well-differentiated malignant epithelia. Hence, loss of the LNGFR may be indicative of the initial stages of malignant transformation of prostate epithelia, as well as all subsequent stages of prostate adenocarcinomas.
Adenocarcinoma↗
Left ventricular diastolic function in hypertension and role of plasma glucose and insulin. Comparison with diabetic heart.
BACKGROUND: Experimental production of glucose intolerance has been associated with increased diastolic stiffness of the left ventricle, accompanied by interstitial fibrosis. Because carbohydrate metabolism is altered in hypertension, we undertook the present study to assess the relation of diastolic dysfunction in hypertension to plasma glucose and insulin concentrations. The latter are also affected by obesity. To facilitate this analysis, we studied moderately obese hypertensives. Elucidation of these relations was then sought in diabetic subjects. METHODS AND RESULTS: Subjects undergoing catheterization for chest pain were included in the study when significant coronary disease was not present. In groups 1 (lean), 2 (obese), 3 (lean hypertensive), and 4 (obese hypertensives), intraventricular pressures and volumes were determined. Fasting plasma glucose, insulin, hemoglobinAIC, and glucose tolerance were assessed. Basal ejection fraction and end-systolic wall stress were normal in the four groups. Chamber stiffness was significantly elevated in the hypertensives and was higher in group 4 than in group 3 (P < .05). Diastolic dysfunction was correlated with fasting blood glucose (r = .69, P < .006) but not with plasma insulin or left ventricular mass. Chamber stiffness was also increased in diabetics, with a larger effect in the obese. CONCLUSIONS: Hypertension is associated with increased diastolic stiffness of the left ventricle, which is enhanced by moderate obesity, and abnormal carbohydrate metabolism. Experimentally and in humans, hypertension is associated with interstitial fibrosis of mycardium, the presumed basis for the diastolic dysfunction. Chamber stiffness in group 4 hypertensives was similar to that in the lean diabetics but less than that in the obese diabetics. Although the latter exhibited a correlation with plasma hemoglobinAIC, the large rise in stiffness suggests a potential role for growth factors in further alteration of myocardial composition.
Blood Glucose↗
Emergence of CD52-, glycosylphosphatidylinositol-anchor-deficient lymphocytes in rheumatoid arthritis patients following Campath-1H treatment.
CD52 is a glycosylphosphatidyl-inositol (GPI)-linked glycoprotein expressed at high levels on normal T and B lymphocytes and at lower levels on monocytes, while being absent on granulocytes and bone marrow stem cell precursors. The emergence of CD52- lymphocytes of both T and B cell lineages was observed in three out of 25 rheumatoid arthritis patients treated with teh humanized antibody Campath-1H in phase II clinical trial. Whereas the majority of CD52- B cells had disappeared from the peripheral blood by 3 months post-treatment, both CD52- CD4+ and CD8+ T cells persisted in the circulation for at least 20 months. In the two patients that were tested, the GPI-anchored surface molecules CD55 and CD59 were also absent on the CD52- cells, although expression of other cell surface transmembrane, proteins (CD3, CD4 and CD2) was unaffected. The CD52- cells maintained a stable phenotype in vitro despite repeated re-stimulation in culture. Both CD52- and C52+ clones, established from one of the patients, responded to a similar extent to several T cell mitogens, as assessed by proliferation, suggesting that a general defect in expression of GPI-linked molecules does not impair T cell activation. These data show that an immune attack against a GPI-anchored surface molecule can result in the selection of a GPI-anchor-deficient cell population. Despite the persistence of CD52- T cells in the peripheral blood, no adverse reactions associated with the presence of these cells were noted in any of the patients; in fact they responded with longer remission times after Campath-1H treatment than the other patients in the trial.
Adult↗
Is justification of animal research necessary?
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Animal Rights↗
Influence of dietary myoinositol on myocardial vulnerability and norepinephrine release in a diabetic animal model.
In a canine model of diabetes enhanced ventricular vulnerability (VFT) has been associated with reduced myocardial myoinositol and increased release of norepinephrine (NE). To assess the role of the polyol, a dietary supplement of myoinositol was fed for 1 year to a diabetic group. Diabetes was induced with alloxan, 30 mg/kg. Controls (Group 1) were compared with diabetics without (Group 2) and with the inositol supplement (Group 3). After 1 year the animals were anesthetized to assess VFT. Basal heart rate and arterial pressure were comparable. The VFT in Group 1 was 43 +/- 2.6 ma, 26.7 +/- 2.8 ma in Group 2 (P < 0.02) and 39 +/- 3.5 ma in Group 3 (P < 0.02 vs. Group 2). Since the cardiac sympathetic system may promote arrhythmogenesis, the release of NE into the coronary sinus (CS) has been determined. To assess basal NE release serial arterial (A) and (CS) samples were taken at 5 min intervals for 20 min during infusion of 3H-NE. There was no significant difference between the diabetic groups in the level of arterial NE (HPLC). The mean for NEA-CS was higher in Group 2 (-228 +/- 33 pg/ml) compared to normals (-75 +/- 19 P < 0.02). In Group 3 the mean NE in the coronary venous effluent was -33 +/- 9 pg/ml, significantly less than Group 2. Infusion of 3H-NE was attended by significantly higher 3H-NEcs levels in Group 2. While dihydroxyphenylglycol (DHPG) was increased, 3H DHPG was not, suggesting that an impaired uptake mechanism contributed to the increased NEcs.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Evaluation of CNBr, FMP and hydrazide resins for immunoaffinity purification of factor IX.
The American Red Cross has developed an immunoaffinity chromatography method to purify human coagulation Factor IX to high levels of purity for therapeutic treatment of hemophilia B. The resin currently used in this process is Sepharose CL2B, a cross-linked 2% agarose, which is activated with cyanogen bromide to immobilize an anti-Factor IX monoclonal antibody. This study evaluated two alternative resins and coupling chemistries, a synthetic polymer bead activated by 2-fluoro-1-methyl-pyridinium toluene 4-sulfonate (FMP) and a cross-linked 2% agarose bead with free hydrazide groups for site-specific coupling. The cyanogen bromide and FMP chemistries immobilize the monoclonal antibody in a random orientation. In hydrazide coupling, the monoclonal antibody is immobilized by the non-antigen-binding part of the molecule which, theoretically, should increase the amount of immobilized monoclonal antibody able to bind antigen. To examine this, the capacity of the resins to bind Factor IX and the purity and recovery of Factor IX eluted from the resins were measured. The FMP-activated resin exhibited the lowest capacity, binding only 2% of the Factor IX feed. Sepharose CL2B bound 87% of the loaded protein, while the hydrazide resin bound 43%. These results suggest that (a) hydrazide activation may be insufficient to orient monoclonal antibody and (b) other factors such as steric hindrances and diffusional resistances during immobilization may be important. Neither of the other resins tested demonstrated improved performance compared with cyanogen bromide-activated Sepharose CL2B for the immunoaffinity purification of Factor IX.
Antibodies, Monoclonal↗
Effectiveness of multiple bolus administration of tissue-type plasminogen activator in acute myocardial infarction.
The feasibility and possible advantages of intravenous bolus administration of recombinant tissue-type plasminogen activator (rt-PA) were investigated in 26 consecutive patients with early (less than 6 hours) evolving acute myocardial infarction. Either an intravenous infusion of 40 clot-lysis megaunits (cIMU) double-chain rt-PA over 1.5 hours followed by 20 cIMU over 5 hours (infusion group, n = 12) or 4 intravenous bolus injections of 10 cIMU at 20 minute intervals (bolus group, n = 14) were randomly administered. Coronary arteriography was performed before and at regular predefined intervals up to 90 minutes from the start of rt-PA administration, and at 24 hours. Acute recanalization of the infarct-related coronary artery was demonstrated in 7 of 12 patients (58%; 95% confidence interval 28 to 85%) in the infusion group and 11 of 14 patients (79%; 95% confidence interval 49 to 95%) in the bolus group (difference not significant). Two patients in the bolus group had reoccluded by 24 hours. Mean time from the start of rt-PA to patency of the infarct-related coronary artery was 39 +/- 6 (standard error of the mean) minutes in the infusion group and 28 +/- 6 minutes in the bolus group (p = 0.2). There were no significant differences in the minimum infarct-related coronary artery luminal diameter measured by computerized quantitative arteriography between the infusion group and the bolus group at 90 minutes or at 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Early coronary reperfusion blunts the procoagulant response of plasminogen activator inhibitor-1 and von Willebrand factor in acute myocardial infarction.
The effects of early coronary recanalization on the plasma levels of two procoagulant acute phase proteins, the fastacting plasminogen activator inhibitor and von Willebrand factor, were investigated in 24 patients with myocardial infarction receiving intravenous recombinant tissue-type plasminogen activator (rt-PA) within 6 h of the onset of symptoms. Coronary angiography was performed before and 90 min after the start of rt-PA infusion. Continuous electrocardiographic recordings and 4 h plasma creatine kinase MB isoenzyme (CK MB) were performed over the first 24 h. Plasma plasminogen activator inhibitor activity, von Willebrand factor and C-reactive protein were measured before rt-PA infusion, daily for the first 3 days and after 90 days. In the entire group, plasminogen activator inhibitor activity peaked at 24 h (day 1), representing a significant increase over values at all other times (p = 0.03). von Willebrand factor was higher in the first 2 days of infarction compared with after 90 days (p = 0.001). C-reactive protein peaked on day 2, with an eightfold increase over values on admission (p = 0.001). In the 16 patients with a patent infarct-related artery at 90 min, infarct size estimated by integrated 24 h CK MB, time for ST segment elevation to decrease to half-maximum and peak C-reactive protein were reduced significantly by more than twofold compared with values in the 8 patients with an occluded artery at 90 min. The patients with early recanalization also had lower plasminogen activator inhibitor activity on day 2 (p = 0.05) and day 3 (p = 0.02) and lower 0 to 72 h averaged von Willebrand factor (p = 0.01). Thus, early coronary recanalization curtails the response of plasminogen activator inhibitor activity and von Willebrand factor to myocardial infarction, most likely by reducing the extent of ischemia and necrosis and the consequent acute phase reaction. By blunting the early postinfarction procoagulant state, prompt recanalization may reduce the risk of thromboembolic complications in the first days after myocardial infarction.
C-Reactive Protein↗
Ventricular vulnerability in diabetes and myocardial norepinephrine release.
Previously the authors have observed a reduction of the ventricular fibrillation threshold (VFT) in a mild diabetic model. This investigation examines the role of more severe hyperglycemia in altering the ventricular fibrillation threshold and how the sympathetic nervous system modulates the response. Alloxan diabetes was induced in eight male mongrel dogs 3-5 years of age (Group 2), for comparison with matched controls (Group 1). Hemoglobin A1c rose from 2.9 +/- .4-7.8 +/- .3% and body weight was maintained with daily insulin. After 1 year, anesthesia was induced with chloralose and an electrode catheter placed at the right ventricular apex. VFT was 41.7 +/- 1.8 ma in Group 1 and 27.8 +/- 2.1 ma in the diabetics of Group 2 (p less than .001). There was significantly greater decline of VFT in response to epinephrine infusion in Group 2. The threshold in diabetics rose to normal levels after infusion of the beta-blocking agent, esmolol. Subsequently, the response of the cardiac sympathetic system was assessed during ventricular pacing at 200 beats/minute. Serial paired blood samples were taken from catheters in the aorta and coronary sinus for catecholamine assay by HPLC. Both groups had similar coronary blood flow responses by the thermal method, as well as changes in arterial pressure. While no change occurred in Group 1, a progressive rise of norepinephrine (NE) concentration was observed in coronary venous effluent of Group 2 (p less than .01). The basal arterial-coronary sinus difference was-123 +/- 52 pg/ml, which rose during pacing in Group 2 to a peak of -376 +/- 9.3 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of diabetes on myocardial perfusion in the atherosclerotic monkey.
We examined the influence of diabetes on the severity of coronary atherosclerosis, as judged by coronary morphometric and blood flow studies. Cynomolgus monkeys were fed a coconut-peanut oil mixture plus cholesterol to induce the plaque lesions of atherosclerosis in nondiabetic (group 2) and diabetic monkeys (group 3). Group 1 consisted of chow-fed controls. After 18 months of hypercholesterolemia, the animals were anesthetized to assess myocardial blood flow, by use of radioactive microspheres. Transmural and inner/outer wall flow ratios were normal in the two lipid-fed groups in the basal state. Vasodilation after adenosine (0.45 mg/kg/min IV) elicited a more than threefold rise of transmural blood flow in group 1, and a significantly reduced increment in groups 2 and 3. The blood flow ratio was not different from unity in group 1 but declined to 0.69 +/- 0.03 in group 2 and 0.69 +/- 0.06 in group 3, with similar decrements of heart rate and aortic pressure. In contrast to results in group 1, left ventricular filling pressure rose and velocity of contractile elements declined to a similar extent in groups 2 and 3 after adenosine, consistent with myocardial ischemia. Morphometric measurements as well as chemical analyses were performed on the three major coronary arteries. The degree of intimal thickening and increase of cholesterol and collagen content were comparable in groups 2 and 3. Thus, in this model the plaque lesions of atherosclerosis did not appear to be intensified by diabetes. Moreover, the responses to adenosine in terms of myocardial underperfusion and mechanical dysfunction were comparable in the two experimental groups.
Adenosine↗
The question is not, "can they talk"?
An argument for denying moral rights to nonhuman species is that beliefs, desires, and interests are inherent in the normal human capacity for speech and, since only humans are linguistically capable, only humans can have rights. We argue that linguistics and many conceptual abilities are ontogenetically independent in humans and that various morally relevant mental capacities can exist independently. We also then argue that phylogenetic independence is also possible and hence, that the concept of an inherent dependence of moral standing on having linguistic capabilities is insufficient for denying rights to nonhumans.
Animal Experimentation↗
The rights of humans and other animals.
Animals have occupied a precarious, often changing position in the major moral traditions of Western thought. Viewed as reincarnations of human souls in Eastern thought, they have been denied not only souls but awareness in others. And while some theories argue that we have duties directly to sentient animals, others maintain that all our duties involving these animals are indirect duties to humanity. The implications of these approaches for animal experimentation will be explained, as will the fundamental difference between the philosophy of animal rights, on the one hand, and these traditional approaches, on the other. That philosophy is categorically abolitionist in its implications concerning the harmful use of animals in science, whereas the traditional approaches are reformist at best.
Animal Testing Alternatives↗