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Biomedical subjects

S K Krueger

Publications and source records attributed to S K Krueger.

At least 19 recordsLinked to original sources
PubMed1997

Pulmonary flavin-containing monooxygenase (FMO) in rhesus macaque: expression of FMO2 protein, mRNA and analysis of the cDNA.

Pulmonary microsomes from Rhesus macaque express a flavin-containing monooxygenase (FMO) resembling the FMO2 ortholog from rabbit with respect to immunochemical cross-reactivity and expression in lung, but not liver. A full-length cDNA was cloned following screening of a Rhesus macaque lung cDNA library. The nucleotide sequence contained an open reading frame encoding 535 amino acids with 85 and 84% identity to FMO2 from rabbit and guinea pig, respectively, and an identical location of the putative FAD- and NADP-binding sites. Northern blots of monkey lung mRNA revealed multiple size FMO2 transcripts. These mRNA transcripts are expressed in lung, but not in liver or kidney.

Amino Acid Sequence↗
PubMed1997

Safety and efficacy of carvedilol in severe heart failure. The U.S. Carvedilol Heart Failure Study Group.

BACKGROUND: Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function. METHODS AND RESULTS: One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P < .05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004). CONCLUSION: The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.

Adrenergic beta-Antagonists↗
PubMed1996

Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. US Carvedilol Heart Failure Study Group.

BACKGROUND: We tested the hypothesis that carvedilol inhibits clinical progression in patients with mildly symptomatic heart failure due to left ventricular (LV) systolic dysfunction. METHODS AND RESULTS: Patients (n = 366) who had mildly symptomatic heart failure with an LV ejection fraction (LVEF) < or = 0.35, had minimal functional impairment (defined as the ability to walk 450 to 550 m on a 6-minute walk test), and were receiving optimal standard therapy, including ACE inhibitors, were randomized double-blind to carvedilol (n = 232) or placebo (n = 134) and followed up for 12 months. The primary end point was clinical progression, defined as death due to heart failure, hospitalization for heart failure, or a sustained increase in heart failure medications. Clinical progression of heart failure occurred in 21% of placebo patients and 11% of carvedilol patients, reflecting a 48% (P = .008) reduction in the primary end point of heart failure progression (relative risk, 0.52; CI, 0.32 to 0.85). This effect of carvedilol was not influenced by sex, age, race, cause of heart failure, or baseline LVEF. Carvedilol also significantly improved several secondary end points, including LVEF, heart failure score, NYHA functional class, and the physician and patient global assessments. Carvedilol reduced all-cause mortality but had no effects on the Minnesota Living With Heart Failure scale, the distance walked in 9 minutes on a self-powered treadmill, or cardiothoracic index. The drug was well tolerated. CONCLUSIONS: Carvedilol, when added to standard therapy, including an ACE inhibitor, reduces clinical progression in patients who are only mildly symptomatic with well-compensated heart failure.

Adolescent↗
PubMed1996

A Feldmannia algal virus has two genome size-classes.

Persistent viruses occur intracellularly in brown algae, specifically the Ectocarpales, and as reported here in the genus Feldmannia. Feldmannia species are small (1 mm-several cm), filamentous forms with single-celled meiotic sporangia that normally produce haploid zoospores. In the isolate reported here, spores were not observed in the sporangia but rather numerous (approximately 10(6) per cell) polyhedral viruses are formed in their place. Two dsDNA genome classes of 158 and 178 kbp, with two restriction site variants of each, are described. The individual abundance of each genome in viral preparations is affected by culture temperature. A cosmid library was used to generate circular restriction enzyme (BamHi, Noti, and Psti) site maps.

DNA, Circular↗
PubMed1996

A brown algal virus genome contains a "RING" zinc finger motif.

The brown filamentous alga Feldmannia sp. contains a large icosahedral dsDNA virus, FsV, of which there are multiple variants. A 4.5-kb SstI-HindIII fragment (SH4.5) that is conserved among all genome variants was sequenced. Three open reading frames (ORF-1, -2, and -3, containing 555, 2022, and 411 bp, respectively) were shown to be transcriptionally active by ribonuclease protection assay. A "RING" zinc finger motif and a nucleotide binding site motif were identified in ORF-2.

Amino Acid Sequence↗
PubMed1996

Percutaneous extraction of a fractured, exposed atrial "J" lead retention wire.

The recent identification of fracturing of the retention wire in the Telectronics atrial lead, models 329-701 and 330-801, and the report of death due to cardiac tamponade caused by aortic puncture resulting from protrusion of the retention wire, necessitates fluoroscopic screening of these patients and the explantation of all leads identified to have the component failure. We present in this paper a percutaneous alternative to lead explantation in patients with protrusion of the retention wire through the polyurethane insulation and with an otherwise properly functioning atrial lead.

Electrodes, Implanted↗
PubMed1995

Quantitation of digoxigenin-labeled DNA hybridized to DNA and RNA slot blots.

Quantitation of message from low-abundance mRNAs and limited availability of tissues requires sensitive methods for probe detection, accurate methods for quantitation of signal, and the ability to strip and reprobe membranes. A random-primed, digoxigenin-labeled probe from cDNA of FMO1, an isoform of the flavin-containing monooxygenase gene family, from rabbit was used in the evaluation and optimization of the Genius system for quantitation of signal from DNA and RNA slot blots. Criteria for optimization were a low signal to noise ratio, a linear increase in density of signal vs nuclei acid concentration of bands on X-ray film, complete stripping of membranes, and reproduction of the initial banding pattern upon rehybridization. A low signal-to-noise ratio was obtained with an aqueous prehybridization/hybridization solution. DNA slot blots were successfully quantitated before and after alkaline stripping from positively charged membranes. RNA slot blots were subject to excessive and uneven loss of RNA from the membranes during stripping procedures. Reliable quantitation for more than one cycle of detection required highly charged nylon membranes, and careful tailoring of RNA fixation methods and alkaline stripping conditions.

Animals↗
PubMed1993

Heart transplantation in Lincoln, Nebraska: the Nebraska Heart Transplant Program experience.

The results of the Nebraska Heart Transplant Program are presented. Survival at one and four years, cost, waiting time and return to work rates are reported and compared to known standards. Survival is 91 percent at one year and 76 percent at four years after transplant. These data as well as costs, waiting time and return to work compare favorably with published and reported data. We conclude the results of the Nebraska Heart Transplant Program by all parameters evaluated are excellent. Referral of patients to distant programs causes needles inconvenience and higher patient costs, and is not justified.

Adolescent↗
PubMed1992

Effects of combined pre- and postnatal ethanol exposure (three trimester equivalency) on glial cell development in rat optic nerve.

This study evaluated the effects of a combined gestational and 10 day postnatal alcohol exposure (human three trimester equivalency) on the development of glial cells in the rat optic nerve. Pregnant rats were exposed to alcohol via a liquid diet, then their pups were artificially reared and further exposed to alcohol for 10 postnatal days via a gastrostomy fed liquid diet. Control animals, born of pair fed dams, were artificially reared on pair fed isocaloric diets. Optic nerve tissues were prepared for light and electron microscopic studies from animals on gestational days (G) 15 and 20 and postnatal days (P) 5, 10, 15, 20 and 90. There were fewer glial cells per cross-section on day 15 and the cross-sectional areas of optic nerves were smaller on days G20, P15 and P90 in the ethanol exposed animals. There was an alcohol-induced delay in the appearance of immature cells within the oligodendroglia lineage and a decrease in the number of oligodendroglia present at 15 and 20 days, indicating a delay in the maturation of oligodendroglial cells. These effects were compensated for by 90 days. Maturation of the astrocytic cell lineage was generally unaffected by the alcohol although there was evidence of increased numbers of cells in the lineage. There was no consistent indication of alcohol-induced degeneration of glial cells or their organelles. Thus, alcohol exposure for all of gestation and 10 postnatal days in the rat causes a delay in oligodendrocyte maturation but appears to have no long-term effects on the glial cell population of the optic nerve. Such a delay, by contributing to delays in myelin development, could help to explain some of the neurological dysfunctions associated with developmental alcohol exposures.

Aging↗
PubMed1991

Short- and long-term effects of combined pre- and postnatal ethanol exposure (three trimester equivalency) on the development of myelin and axons in rat optic nerve.

This study evaluated the effects of a combined gestational and 10 day postnatal alcohol exposure (human three trimester equivalency) on the development of myelin and axons in rat optic nerve. Rats were exposed during gestation via liquid diet, then their artificially reared pups were further exposed for 10 postnatal days via an ethanol-containing diet fed by gastrostomy. Control animals from pair-fed dams were artificially reared for 10 days on pair-fed isocaloric diets. Anesthetized animals were perfused with fixative on gestational days (G) 15 and 20 and postnatal days (P) 5, 10, 15, 20, and 90, then optic nerve tissues prepared for electron microscopy. Optic nerve cross-sectional areas were generally less from G20 through P90 in ethanol exposed animals. Counts of the number of myelinated nerve fibers per unit area and of the numbers of fibers in different stages of myelin development revealed that alcohol exposure caused a delay in myelin acquisition at 10 and 15 days that was compensated for at 20 and 90 days. Myelin thickness as a function of axon diameter was decreased in the alcohol exposed animals from 10 through 90 days, indicating a permanent reduction in the relative thickness of myelin. These results show that alcohol exposure for all of gestation and 10 postnatal days in the rat (human three trimester equivalency) causes a permanent reduction in myelin thickness along with a delay in myelin acquisition in the optic nerve. Such alterations in developing and adult myelin could help to explain some of the neurological and visual dysfunctions associated with developmental alcohol exposures.

Animals↗
PubMed1991

Phenobarbital increases rat hepatic prostaglandin F2 alpha, glutathione S-transferase activity and oxidative stress.

Eight-week-old female F344/N rats were fed 3.0 or 6.0% of calories (kcal%) as linoleate with or without 0.05% phenobarbital (PB) for 35 days. PB treatment increased glutathione S-transferase (GST) activity by 80% and prostaglandin (PG) F2 alpha levels 4-fold (p less than 0.05). PB decreased hepatic alpha-tocopherol significantly. Hepatic linoleate was decreased by PB in rats fed 6 kcal% but not 3 kcal% linoleate. Increased dietary linoleate had no significant effect on hepatic PGF2 alpha or alpha-tocopherol levels or GST activity. This study suggests that PB hepatotoxicity and tumor-promoting ability may be mediated, at least in part, by PGF2 alpha. PB's effect on PGF2 alpha could be a result of both GST-mediated prostaglandin synthesis and oxidative stress. The removal of significant amounts of hepatic alpha-tocopherol during oxidative stress induced by PB might diminish endogenous inhibition of hepatic PG synthesis by a-tocopherol.

Animals↗
PubMed1991

Effects of alpha-tocopherol, phenobarbital, and butylated hydroxyanisole during promotion of diethylnitrosamine-initiated rat hepatocarcinogenesis.

The promotion-suppressing ability of two antioxidants was measured to determine the role of oxidative stress in hepatocarcinogenesis. Four-day-old female F344/N rats were dosed with diethylnitrosamine (10 mg/kg). After weaning, they were fed semipurified diets with and without 500 ppm alpha-tocopherol, or the same two diets containing 500 ppm phenobarbital, or 5,000 ppm butylated hydroxyanisole (BHA) for 3 or 11 months. By 11 months, phenobarbital-fed groups had eaten 30% more than other groups did (p less than 0.05), suggesting a role for increased caloric intake in phenobarbital promotion. Phenobarbital and BHA significantly reduced body weights and increased liver weights compared with control rats. After three months, alpha-tocopherol significantly suppressed mean volume of placental glutathione S-transferase (PGST)-positive altered hepatic foci (AHF), regardless of xenobiotic treatment. Phenobarbital increased and BHA decreased the numbers of AHF compared with those of the control group. After 11 months, mean focal volume was significantly suppressed by BHA compared with that of the control group, and phenobarbital increased the total volume of AHF [PGST-positive plus gamma-glutamyltransferase (GGT)-positive AHF] compared with rats fed either control or BHA diets. BHA treatment also increased hepatic glutathione levels by 40% compared with control and rats fed phenobarbital. In conclusion, alpha-tocopherol had only a slight, early effect to suppress promotion of hepatocarcinogenesis. BHA suppressed some indices of promotion at both times and increased hepatic glutathione; however, BHA's toxicity (which suppressed body weight) may also be a factor in its supposable promotion-inhibitory effects.

Analysis of Variance↗
PubMed1990

Effects of postnatal ethanol exposure on glial cell development in rat optic nerve.

This study morphologically evaluated the effects of limited postnatal alcohol exposure on the development of glial cells in the rat optic nerve. Rat pups were artificially reared on Days 5-18 with a supplemented milk diet fed via a chronic gastrostomy tube. Experimental animals received 4% ethanol in their diet on Days 5-9, otherwise the experimental and control animals received identical diets. Optic nerve tissues were prepared for electron microscopy on Days 10, 16, 22, 29, and 90. There were fewer glial cells per cross section and the cross-sectional areas of optic nerves were smaller on Days 10 and 16 in the ethanol-exposed animals. The alcohol caused a delay in the maturation of oligodendroglial cells at 10 days as evidenced by decreases in the total number of oligodendroglia present and by a delay in the appearance of immature cells within the oligodendroglial lineage. All of these effects were compensated for at later ages. There was no evidence of alcohol-induced degeneration of glial cells or their organelles. Thus, postnatal alcohol exposure causes a delay in oligodendrocyte maturation but appears to have no long-term effects on the glial cell population of rat optic nerve.

Animals↗
PubMed1989

Accurate determination of the transaortic valve gradient using simultaneous left ventricular and femoral artery pressures.

Accurate determination of the transaortic valve gradient has required two catheters, one in the left ventricle and one in the ascending aorta. We now report a new technique for measurement of the transaortic valve gradient from the simultaneous left ventricular (LV) and femoral artery (FA) pressure tracings. This technique was compared with the "true" gradient obtained by measurement of the simultaneous LV and central aortic pressures, and is accurate (R = 0.999) and relatively simple. Other approaches used to determine the mean transaortic valve gradient were less accurate: simultaneous LV-FA (R = 0.991); aligned LV-FA (R = 0.974); averaged simultaneous and aligned LV-FA (R = 0.981); and nonsimultaneous LV-aorta pullback (R = 0.953). Thus, this new technique provides an accurate transaortic valve gradient without requiring the use of two central catheters.

Aorta↗
PubMed1989

Comparison of three techniques for percutaneous balloon aortic valvuloplasty of aortic stenosis in adults.

Three different techniques for percutaneous balloon aortic valvuloplasty h have been described: retrograde single balloon, retrograde double balloon, and antegrade techniques. This report describes our experience using the three techniques in twenty-five consecutive procedures. All techniques resulted in a significant decrease in transvalvular pressure gradient and an increase in calculated aortic valve area, without significant difference among the three. There was no increase in the degree of aortic regurgitation after valvuloplasty by any of the techniques. Vascular complications occurred only with the retrograde double balloon technique. Cardiac tamponade during balloon inflation occurred with both the retrograde single and double balloon techniques. Three deaths occurred; two during the antegrade technique and one after the retrograde double balloon technique. Thus, balloon aortic valvuloplasty can be effectively performed using any of the three techniques. However, the differing techniques have inherent advantages in specific situations, as well as potential complications.

Aged↗