First laser cooling of relativistic ions in a storage ring.
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Journal Article↗
Biomedical subjects
R Klein
Publications and source records attributed to R Klein.
Prevention of creatine kinase-MB release in coronary artery disease and pacing-induced myocardial ischemia by isosorbide dinitrate spray.
The effect of isosorbide dinitrate (ISDN) spray on release of the isoenzyme creatine kinase-MB (CK-MB) after myocardial ischemia induced by atrial pacing was evaluated in 8 patients with coronary artery disease. Atrial pacing to ischemia (ST-segment depression of greater than or equal to 1.5 mm for greater than or equal to 80 ms) resulted in elevation of CK-MB levels in plasma drawn from the coronary sinus, from 1.8 +/- 1.5 to 6.8 +/- 7.0 ng/ml (p less than 0.001) at 30 minutes after onset of ischemia. When atrial pacing was repeated at the same rate after 1 squirt of ISDN spray, 1.25 mg, the CK-MB levels were not altered despite significant ischemic ST-segment depression. It is concluded that ISDN prevents the process responsible for myocardial release of CK-MB, being either micronecroses or a reversible consequence of ischemia.
Administration, Oral↗
A dose-finding study of the hemodynamic effect of isosorbide dinitrate spray in congestive heart failure.
A dose-finding study of the hemodynamic effect of a new formulation of isosorbide dinitrate (ISDN) spray was performed in 12 patients with chronic congestive heart failure. Doses of 1.25, 2.5, 5.0 mg and placebo, as 1 squirt, were randomly given to all patients. Hemodynamic measurements were performed by a Swan-Ganz catheter before and at 30 seconds and 1, 5, 10, 20 and 30 minutes after drug administration and every 30 minutes thereafter, until return of hemodynamic variables to baseline. Hemodynamic improvement evident as decreases in right-sided pressures and an increase in cardiac output was observed within 1 minute from administration of ISDN spray, and peaked at 5 minutes. Near maximal effect was achieved by the 2.5-mg dose. Thus, 2.5 mg of ISDN spray (new formulation) dose. Thus, 2.5 mg of ISDN spray (new formulation) produces rapid, near-maximal hemodynamic improvement in patients with congestive heart failure.
Administration, Oral↗
Looking after consumers in the new NHS.
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Community-Institutional Relations↗
The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain.
We previously identified two tyrosine protein kinase genes, designated trk and trkB, that code for putative neurogenic cell surface receptors. In this study, we report that the mouse trkB locus codes for at least two classes of receptor-like molecules. These trkB proteins, designated gp145trkB and gp95trkB, have identical extracellular and transmembrane domains, suggesting that they might recognize the same ligand(s). However, only gp145trkB contains a long cytoplasmic region, which includes a catalytic tyrosine protein kinase domain. trkB transcripts coding for this protein were observed in the cerebral cortex and the pyramidal cell layer of the hippocampus. In contrast, transcripts coding for the noncatalytic gp95trkB molecule were found in the ependymal linings of the cerebral ventricles and in the choroid plexus. These results illustrate that a tyrosine protein kinase locus can code for two structurally and functionally distinct cellular receptors.
Amino Acid Sequence↗
Universal reaction-limited colloid aggregation.
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Journal Article↗
Dictyopterin, 6-(D-threo-1,2-dihydroxypropyl)-pterin, a new natural isomer of L-biopterin. Isolation from vegetative cells of Dictyostelium discoideum and identification.
A major pterin was isolated by reverse-phase high-performance liquid chromatography from cellular extract of vegetative cells of Dictyostelium discoideum after perchloric deproteinization and oxidation with acidic iodine. This compound was characterized by its chromatographic behavior, its absorption and fluorescence properties, by its oxidation product with alkaline permanganate, by secondary ion mass spectrometry and by circular dichroism. The final identification was obtained by comparison with authentic materials. It is concluded that the major pterin of D. discoideum is the compound 6-(D-threo-1,2-dihydroxypropyl)-pterin. The name dictyopterin is proposed for this new natural isomer of L-biopterin.
Biopterins↗
Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck.
STUDY OBJECTIVE: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. DESIGN: Nonrandomized, prospective trial. SETTING: A comprehensive cancer center. PATIENTS: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity. INTERVENTIONS: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy. RESULTS: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L. CONCLUSIONS: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.
Adult↗
Demonstration of "naturally occurring mitochondrial antibodies" in family members of patients with primary biliary cirrhosis.
Sera from 81 healthy family members (including husbands) of 13 patients with primary biliary cirrhosis were tested by Western blotting against the antigen fractions M9 and M2 derived respectively from rat liver and beef heart mitochondria. Fifty-eight (70%) were positive and recognized four major (molecular weights 98 kD, 65 kD, 61 kD, 58 kD) and eight minor determinants (85 kD, 81 kD, 78 kD, 54 kD, 48 kD, 45 kD, 40 kD, 30 kD) labeled alpha-my. Each of the 58 sera recognized at least one of the four major polypeptides. In contrast, only 6% of 80 primary biliary cirrhosis patients had antibodies against one of these epitopes. Sera from 25 patients with different infectious disorders previously shown to react with submitochondrial particles by enzyme-linked immunosorbent assay also recognized at least one of the four major determinants. From these findings it was concluded that these antibodies may belong to the family of natural autoantibodies. Since they reacted with submitochondrial fractions, they were defined as "naturally occurring mitochondrial antibodies". The high incidence of "naturally occurring mitochondrial antibodies" in primary biliary cirrhosis-contact persons may be taken as indirect evidence for a contagious immunogenic agent circulating in the blood of primary biliary cirrhosis-patients. In contrast, the absence of "naturally occurring mitochondrial antibodies" in primary biliary cirrhosis-patients themselves implies that an underlying B-cell defect is responsible for this lack of antibody production. Considering the protective role of naturally occurring antibodies in general, this postulated B-cell defect could be a major factor in the etiopathogenesis of primary biliary cirrhosis.
Antibodies↗
Autoantibodies in primary biliary cirrhosis.
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Antibodies, Antinuclear↗
The spatial distribution of attention during covert visual orienting.
Many studies of covert orienting of visual attention in response to informative pre-cues have focused on the spatial distribution of improved or impaired performance. One can find at least four different models in the literature, each describing a different distribution: the fixed gradient spotlight; the zoom lens spotlight; the hemifield activation hypothesis; and the flexible allocation of resources model. In previous work examining procedural details that might have led to the formulation of the hemifield activation hypothesis, it was postulated (Klein and McCormick 1989) that under conditions of uncertainty about which of two locations to attend, an observer may focus attention on a visual channel (i.e., midlocation placement of a fixed gradient spotlight) that is spatially intermediate. The present experiment was designed to distinguish among the four models of attentional distribution, and to test the midlocation placement strategy. Our findings show support for midlocation placement, demonstrate evidence against flexible allocation and hemifield activation, but could not differentiate between fixed gradient and zoom lens variants of the spotlight model.
Attention↗
Britain's new market model of general practice: do consumers know enough to make it work?
In 1989 the British Government announced radical plans, now in the process of implementation, for the reform of the National Health Service. The proposals for primary health care imply a market model, insofar as they assume that patients will be active consumers searching out those general practices which best meet their needs. This paper tests one key assumption of this strategy, i.e., that patients have the information required to make such choices. It does so by analysing the data generated by a survey of the health beliefs and practices of 4266 people. The results suggest that British consumers lack the knowledge needed to make market-style choices and that, more generally, policy makers applying the market model to health care should explicitly address the problem of how to create a better informed public.
Adolescent↗
Assessment of cataracts from photographs in the Beaver Dam Eye Study.
Presence and severity of age-related cataract was determined in adults 43 to 84 years of age in Beaver Dam, Wisconsin. Duplicate photograph gradings for nuclear sclerosis (n = 1160), cortical opacities (n = 1159), and posterior subcapsular cataract (n = 1137) were performed. There are five levels of nuclear sclerosis. Exact agreement occurred in 64.7% of the cases; agreement within one category in 99.8%. For cortical opacities, graders estimate involved area in nine segments of the lens. When the continuous scale is divided into 12 categories of severity, exact agreement varied between 73.5 and 82.4%; for agreement within one category, rates varied between 84.6 and 89.9%. For posterior subcapsular cataracts, exact agreement for involvement of the central circle occurred in 95.0% and agreement within one category occurred in 97.7%. Intraobserver comparisons disclosed similar concordance. These grading schemes are semiquantitative, reproducible, and can be performed for the large numbers of photographs from population-based studies.
Adult↗
Increased testosterone in type I diabetic subjects with severe retinopathy.
Diabetic retinopathy rarely occurs before puberty, suggesting that changes in sex hormones may influence the development of this condition. The authors measured serum testosterone, estradiol, DHEA-S, and sex hormone binding globulin levels in 26 men and 22 women with type I diabetes from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population-based study of diabetic complications. The mean age was 23 years and the mean duration of diabetes was 14 years. Subjects with proliferative or preproliferative retinopathy (greater than or equal to retinopathy level 51-80) were matched by duration of diabetes (+/- 2 years) and sex to subjects with minimal or no retinopathy (less than or equal to retinopathy level 21). Seven stereoscopic retinal photographs of each eye were obtained and photographs were read by the University of Wisconsin Reading Center. Serum testosterone concentrations were significantly higher in male diabetic subjects with proliferative retinopathy (648 +/- 36 ng/dl) than in male diabetic subjects with minimal or no retinopathy (512 +/- 43 ng/dl) (P = 0.017). No other statistically significant differences in sex hormones between subjects with and without proliferative retinopathy were observed. Although these results should be regarded as preliminary because of the small number of subjects, they support the hypothesis that testosterone concentrations may be associated with the development of retinopathy in type I diabetic patients.
Adolescent↗
Chronometric analysis of apparent spotlight failure in endogenous visual orienting.
Subjects made speeded responses to peripheral luminance increments or decrements preceded by informative central precues. In 4 experiments one of these stimuli was much more likely to occur than the other. In a simple detection task, the likely and unlikely stimuli showed equivalent cuing effects. In a discrimination task (bright/dim), the likely stimuli showed cuing but the unlikely one did not (spotlight failure), and there was a tendency to make the likely response when the unlikely stimulus occurred at the cued location. In Experiment 5, the 2 stimuli were equally likely, and a choice was required. Large cuing effects were observed for both stimuli with no evidence of a speed-accuracy trade-off. A logogen-activation framework is described within which criterion and sensitivity adjustments are needed to accommodate the full pattern of results. Endogenous orienting appears to enhance processing of all stimuli at attended (relative to unattended) locations, an effect that may be masked by specific stimulus or response expectancies.
Adult↗
The validity of estimating the incidence of diabetic retinopathy from prevalence.
A method for estimating incidence rates of a disease from prevalence proportions with differential mortality was validated for diabetic retinopathy in a large population of diabetic persons followed for 4 years, 1980-1982 to 1984-1986, in southern Wisconsin. Four-year age- or duration-specific incidence rates of retinopathy were calculated from prevalence and mortality in persons with and those without retinopathy. These rates were lower than the actual rates obtained at the 4-year follow-up examination by 50% or more in most age intervals in both younger and older onset persons. Estimated duration-specific rates were up to 29 and 57% lower than the actual rates in younger and older onset persons, respectively. These discrepancies could not be accounted for by violations of the assumptions underlying the method. In applying the method to diabetic retinopathy, age- and duration-specific incidence may be more appropriate. Such estimated rates agree well with actual rates except in older onset persons with diabetes of short duration.
Adolescent↗
Liver membrane antibodies (LMA) recognize a 26-kD protein on the hepatocellular surface.
Sera from 82 patients with chronic inflammatory liver diseases and from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Hashimoto's thyroiditis were studied by immunoblotting against purified liver plasma membranes (LPM) and soluble liver protein (SLP) fractions from different species after previous separation by SDS-PAGE. Eighteen of 19 sera with LMA of IgG type in immunofluorescence assay and six LMA-negative sera (three sera from patients with RA) showed antibodies of the IgG or IgM classes against a protein with a molecular weight of 26 kD which was present in LPM and SLP fractions from rats, rabbits, pigs and humans. The reaction with 26-kD liver protein did not correlate with other known autoantibody-antigen systems. All sera were negative in the 26-kD region with liver mitochondria, liver microsomes and soluble proteins of kidney (with one exception), heart and gut from the rat. The 26-kD protein was purified by affinity chromatography on immobilized anti-26-kD protein antibodies from patients, eluted from the 26-kD band of immunoblots. Studies with purified 26-kD liver protein and with SLP as antigens after separation in two-dimensional electrophoresis confirmed that patient serum and experimental rabbit antiserum react with the same protein. Eluted patient antibodies and rabbit antisera showed a linear fluorescence pattern on isolated hepatocytes from rat and rabbit. The data indicate that one of the target antigens of LMA is a species-nonspecific 26-kD protein located on the hepatocellular surface.
Adolescent↗
Anti-M9 antibodies in sera from patients with primary biliary cirrhosis recognize an epitope of glycogen phosphorylase.
Anti-M9 antibodies in sera from patients with primary biliary cirrhosis (PBC) were previously found to recognize two antigenic determinants at 98 and 59 kD, using a purified antigen fraction derived from rat liver mitochondria in the Western blot. Here we show that these antibodies are directed against an epitope of the enzyme glycogen phosphorylase. By Western blotting, a determinant at 98 kD was obtained testing anti-M9 positive sera against phosphorylase from skeletal muscle, and after plasmin treatment a degradation product appeared at 59 kD. Both determinants were identical to the M9-specific determinants 98 and 59 kD as shown by absorption studies. When these antibodies were eluted from the 98 and 59 kD determinants of the M9 antigen after immunoblotting, they again recognized the same epitopes on plasmin-treated phosphorylase. Furthermore, phosphorylase enzyme activity could be also demonstrated in the purified M9 fraction, and anti-M9-positive/anti-M2-negative but not anti-M9-negative/anti-M2-positive sera could be shown to stimulate phosphorylase activity. Testing sera from 1189 patients with different hepatic and non-hepatic disorders against M9 and phosphorylase from skeletal muscle by ELISA, 20% were positive with phosphorylase and only 2% with the M9 fraction. These data indicate that the commercially available phosphorylase from skeletal muscle cannot be recommended as M9 source. It may still contain non-PBC-specific epitopes which are probably recognized by naturally occurring antibodies directed against this highly conserved protein.
Autoantibodies↗