Considering dominance in reduced single-step genomic evaluations.

Single-step models including dominance can be an enormous computational task and can even be prohibitive for practical application. In this study, we try to answer the question whether a reduced single-step model is able to estimate breeding values of bulls and breeding values, dominance deviations and total genetic values of cows with acceptable quality. Genetic values and phenotypes were simulated (500 repetitions) for a small Fleckvieh pedigree consisting of 371 bulls (180 thereof genotyped) and 553 cows (40 thereof genotyped). This pedigree was virtually extended for 2,407 non-genotyped daughters. Genetic values were estimated with the single-step model and with different reduced single-step models. Including more relatives of genotyped cows in the reduced single-step model resulted in a better agreement of results with the single-step model. Accuracies of genetic values were largest with single-step and smallest with reduced single-step when only the cows genotyped were modelled. The results indicate that a reduced single-step model is suitable to estimate breeding values of bulls and breeding values, dominance deviations and total genetic values of cows with acceptable quality.

On the limited increase in validation reliability using high-density genotypes in genomic best linear unbiased prediction: observations from Fleckvieh cattle.

This study investigated reliability of genomic predictions using medium-density (40,089; 50K) or high-density (HD; 388,951) marker sets. We developed an approximate method to test differences in validation reliability for significance. Model-based reliability and the effect of HD genotypes on inflation of predictions were analyzed additionally. Genomic breeding values were predicted for at least 1,321 validation bulls based on phenotypes and genotypes of at least 5,324 calibration bulls by means of a linear model in milk, fat, and protein yield; somatic cell score; milkability; muscling; udder, feet, and legs score as well as stature. In total, 1,485 bulls were actually HD genotyped and HD genotypes of the other animals were imputed from 50K genotypes using FImpute software. Validation reliability was measured as the coefficient of determination of the weighted regression of daughter yield deviations on predicted breeding values divided by the reliability of daughter yield deviations and inflation was evaluated by the slope of this regression. Model-based reliability was calculated from the model. Distributions for validation reliability of 50K markers were derived by repeated sampling of 50,000-marker samples from HD to test differences in validation reliability statistically. Additionally, the benefit of HD genotypes in validation reliability was tested by repeated sampling of validation groups and calculation of the difference in validation reliability between HD and 50K genotypes for the sampled groups of bulls. The mean benefit in validation reliability of HD genotypes was 0.015 compared with real 50K genotypes and 0.028 compared with 50K samples from HD affected by imputation error and was significant for all traits. The model-based reliability was, on average, 0.036 lower and the regression coefficient was 0.036 closer to the expected value with HD genotypes. The observed gain in validation reliability with HD genotypes was similar to expectations based on the number of markers and the effective number of segregating chromosome segments. Sampling error in the marker-based relationship coefficients causing overestimation of the model-based reliability was smaller with HD genotypes. Inflation of the genomic predictions was reduced with HD genotypes, accordingly. Similar effects on model-based reliability and inflation, but not on the validation reliability, were obtained by shrinkage estimation of the realized relationship matrix from 50K genotypes.

The effect of coronal plane angulation on patient reported outcome measures of operatively treated distal femur fractures: A multi-center prospective evaluation.

OBJECTIVES: The goal of this trial was to determine whether coronal plane angulation affects functional and clinical outcomes after the fixation of distal femur fractures. DESIGN: Multicenter, randomized controlled trial SETTING: 20 academic trauma centers PATIENTS/PARTICIPANTS: 156 patients with distal femur fractures were enrolled. 123 patients were followed 12 months. There was clinical outcome data available for 105 patients at 3 months, 95 patients at 6 months and 81 patients at one year. INTERVENTION: Lateral locked plating or retrograde intramedullary nailing MAIN OUTCOME MEASUREMENTS: Radiographic alignment, functional scoring including SMFA, Bother Index, and EQ-5D. Clinical scoring of walking ability, need for ambulatory support and ability to manage stairs. RESULTS: At 3 months, there was no difference between groups (varus, neutral or valgus) with respect to any of the clinical functional outcome scores measured. At 6 months, compared to those with neutral alignment, patients with varus angulation had a worse Stair Climbing score (4.33 vs. 2.91, p = 0.05). At 12 months, the average patient with neutral or valgus alignment needed less ambulatory support than the average patient in varus. Walking distance ability was no different between the groups at any time point. With respect to the validated patient-based outcome scores, we found no statistical difference in in the SMFA, Bother, or EQ-5D between patients with valgus or varus mal-alignment and those with neutral alignment at any time point (p > 0.05). Regardless of coronal angulation, the SMFA trended towards lower (improved) scores over time, while EQ-5D scores for patients with varus angulation did not improve over time. CONCLUSIONS: Valgus angulation and neutral angulation may be better tolerated in terms of clinical outcomes like stair climbing and need for ambulatory support than varus angulation, though patient reported outcome measures like the SMFA, Bother Index and EQ-5D show no statistical significance. Most patients with distal femur fractures tend to improve during the first year after injury but many remain significantly affected at 12 months post injury.

Low-noise, interference-resistant amplifier suitable for biological signals.

Minor changes in conventional low-noise amplifier circuits decrease circuit noise and attenuate the unwanted effects of varying impedances and potentials which exist between commonly employed electrodes and the tissues of biological subjects. The resulting reduction of intrinsic amplifier noise and reduced susceptibility to external interference is helpful in the study of low-frequency signals of microvolt level.

Liver transplantation for hepatocellular carcinoma after yttrium therapy: a case report.

Yttrium-90 microspheres constitute one of the most recent treatment options for hepatocellular carcinoma (HCC) in the setting of cirrhosis. As such, their spectrum of indication is not yet fully established. Herein, we have reported the case of a patient with HCC beyond the listing criteria for liver transplantation (OLT) who was treated preoperatively with selective transarterial chemoembolization and yttrium-90 microspheres. He was subsequently transplanted with a liver from an 81-year-old donor allocated through Eurotransplant as a "rescue offer." The posttransplant course was uneventful. Pathologic examination revealed a multifocal, well-differentiated pT2 tumor with no vascular invasion. The patient is currently alive and in good condition at 14 months posttransplant, with no evidence of tumor recurrence by a current computed tomography scan. This report provided encouraging information on the potential of yttrium-90 microspheres as a bridging option before OLT for multifocal HCC.

Magnetic resonance imaging of the shoulder in the primary care setting.

MRI is an excellent noninvasive method of diagnosing difficult shoulder problems. Although usually not needed for classic primary impingement syndrome or clinically obvious rotator cuff tears, MRI may be helpful in diagnosing secondary causes of impingement or in some cases involving partial rotator cuff tears. Some surgeons may use MRI preoperatively to define the extent of the rotator cuff tear, as this may alter their surgical approaches.

Triplane fracture of the distal tibial epiphysis. Long-term follow-up.

The cases of twenty-three patients in whom a triplane fracture had been treated at the Naval Hospital, Oakland, California, between 1974 and 1985, were reviewed. The anatomical configuration of the fracture was confirmed in fifteen patients. Eleven of the fifteen patients had a three-fragment fracture. Plain radiographs alone did not accurately demonstrate the configuration of the fracture. Twenty patients were asymptomatic when they were evaluated eighteen to thirty-six months after the injury, but only eight of fifteen patients were asymptomatic when they were evaluated thirty-eight months to thirteen years after the fracture. Residual displacement of two millimeters or more after reduction was associated with a less than optimum result unless the epiphyseal fracture was outside the primary weight-bearing area of the ankle.

Arthroscopic treatment of transchondral talar dome fractures.

Fifteen cases of transchondral talar dome fractures treated arthroscopically at the Naval Hospital in Oakland, California, were reviewed. Roentgenograms and results from clinical examination were assessed preoperatively and at regular intervals postoperatively. Clinical followup of 18 months was obtained in all cases (range, 18 to 36 months; mean, 26 months). All lesions were treated with arthroscopic excision of fragments with abrasion and/or drilling of the remaining crater. There were nine excellent results, four good, one fair, and one poor. There were no complications. Results of arthroscopic treatment compare favorably to those of open arthrotomy.

Endoscopic instrumentation, correction, and fusion of idiopathic scoliosis.

BACKGROUND CONTEXT: Endoscopic techniques have been used since 1993 to treat thoracic disk disease. Thorascopic techniques evolved into means of treating not only disk disease but also correcting thoracic spinal deformity with instrumentation and fusion. PURPOSE: To evaluate the efficacy of endoscopic instrumentation, correction, and fusion of thoracic idiopathic scoliosis. STUDY DESIGN: A retrospective review of 50 patients who have undergone endoscopic instrumentation, correction, and fusion for scoliosis. PATIENT SAMPLE: Fifty consecutive patients undergoing treatment for primary thoracic idiopathic scoliosis. OUTCOME MEASURES: Evaluation of operative time, curve correction, and fusion rates were evaluated. METHODS: Fifty patients with the diagnosis of primary thoracic scoliosis underwent thoracoscopic techniques of instrumentation, correction, and fusion. On follow-up, the patients were evaluated for spinal alignment restoration, axial derotation, postoperative pain, rehabilitative time, and complications. RESULTS: The initial curve correction averaged 50%, improving to over 68% in the last 10 cases. Hypokyphosis correction averaged 21 degrees. Additionally, there has been a decrease in rehabilitation time, less time off work or school, and decreased blood loss and postoperative pain. There were 14 complications and no deaths recorded. The factors involved in a successful fusion include total diskectomy, complete cartilaginous end plate removal, and autogenous bone graft. CONCLUSIONS: The initial results of the thoracoscopic-assisted techniques for primary thoracic scoliosis are promising. As with most evolving techniques, surgical times are decreasing and rates of correction are improving.

[The care of amputation stumps by osteo-myeloplastic according to v. Ertl]. / Die Versorgung von Amputationsstümpfen durch Osteo-Myoplastik nach v. Ertl.

The osteo-myoplastic operation of stumps induces the formation of an osseous bridge between the tibia and fibula. The surgical procedure consists of using flexible cortico-periosteal flaps after subcortico-periosteal resection of the osseous stumps. At the same time a myoplastic operation is performed connecting the adductors with the abductors, the flexors with the extensors respectively. The operation technique is described in details. With this treatment a stump is formed that permits exposure to pressure. The stump can be used like a heel. Besides further advantages by this operation the neuro-vascular system becomes normalized. This always causes the preoperative pains to be passed.

Transcriptional regulation of nitrate reductase mRNA levels by cytokinin-abscisic Acid interactions in etiolated barley leaves.

To investigate the mechanisms by which the expression of a specific gene may be modulated by multiple hormones, the regulation of nitrate reductase (NR) mRNA levels by cytokinin and abscisic acid (ABA) was studied in etiolated barley (Hordeum vulgare L. cv Robust) leaves using a barley NR cDNA as a probe. Northern blot analyses of the levels of NR mRNA indicate that accumulation of the mRNA was enhanced by the cytokinin, benzyladenine (BA), and suppressed by ABA and that the hormonal effects on NR gene expression were responsive to dose concentrations (10(-7) to 10(-4) molar). The NR mRNA levels were influenced by the BA/ABA concentration ratios, and the inhibition of the NR transcript levels by ABA was not totally reversed by addition of equal concentrations (10(-7) to 10(-4) molar) of BA. Nuclear runoff transcription studies showed that the level of transcription was suppressed by ABA, and addition of an equal concentration of BA partially reversed the ABA action. Thus, the interaction of cytokinin and ABA on NR gene expression is, at least in part, at the level of transcription.

Cytokinin enhancement of the light induction of nitrate reductase transcript levels in etiolated barley leaves.

To investigate the molecular mechanism of cytokinin regulation of nitrate reductase (NR) activity, the influence of benzyladenine (BA) on the level of NR transcript was studied in etiolated barley leaves using a barley NR cDNA as a probe. Northern blot analyses of the levels of NR poly (A)+ RNA indicate that the amount present is proportional to the concentration of BA (2 x 10(-8) to 2 x 10(-4) M) applied to the leaves. Enhancement of NR mRNA by 2 x 10(-5) M BA was clearly detected after 15 minutes of exposure of the leaves to light. The enhancement is cytokinin-specific and adenine is ineffective. Brief treatment with the protein synthesis inhibitor, cycloheximide, inhibited BA-enhanced NR activity but did not inhibit BA-enhanced NR transcript level, thus the enhancement was independent of concurrent protein synthesis. Nuclear runoff transcription studies showed that the enhancement of NR mRNA was at least partially due to increased transcription rates.

Leptin impairs metabolic actions of insulin in isolated rat adipocytes.

Leptin is an adipocyte hormone involved in the regulation of energy homeostasis. Generally accepted biological effects of leptin are inhibition of food intake and stimulation of metabolic rate in ob/ob mice that are defective in the leptin gene. In contrast to these centrally mediated effects of leptin, we are reporting here on leptin effects on isolated rat adipocytes. Leptin impairs several metabolic actions of insulin, i.e. stimulation of glucose transport, glycogen synthase, lipogenesis, inhibition of isoproterenol-induced lipolysis, and protein kinase A activation, as well as stimulation of protein synthesis. Insulin effects were reduced by leptin (2 nM) with a half-life of about 8 h. At low leptin concentrations (<1 nM), the insulin sensitivity was reduced leading to a shift to the right in the dose-response curve. At higher concentrations the responsiveness was diminished, resulting in nearly complete inhibition of insulin effects at >30 nM leptin. The IC50 value of leptin was 3.1 +/- 1 nM after 15 h of preincubation of adipocytes in primary culture. The natural splice variant des-Gln49-leptin exhibited a significantly lower potency. Adipocytes regained full insulin sensitivity within a few hours after leptin removal. The stimulation of glucose transport by vanadate was not affected by leptin. These data show specific and potent impairment of insulin action by leptin in the physiological concentration range of both leptin and insulin, which may be related to the pathophysiology of insulin resistance in both non-insulin-dependent diabetes mellitus and obesity.

Localization of cytokinin biosynthetic sites in pea plants and carrot roots.

The biosynthesis of cytokinins was examined in pea (Pisum sativum L.) plant organs and carrot (Daucus carota L.) root tissues. When pea roots, stems, and leaves were grown separately for three weeks on a culture medium containing [8-(14)C]adenine without an exogenous supply of cytokinin and auxin, radioactive cytokinins were synthesized by each of these organs. Incubation of carrot root cambium and noncambium tissues for three days in a liquid culture medium containing [8-(14)C]adenine without cytokinin demonstrates that radioactive cytokinins were synthesized in the cambium but not in the noncambium tissue preparation. The radioactive cytokinins extracted from each of these tissues were analyzed by Sephadex LH-20 columns, reverse phase high pressure liquid chromatography, paper chromatography in various solvent systems, and paper electrophoresis. The main species of cytokinins detectable by these methods are N(6)-(Delta(2)-isopentyl_adenine-5'-monophosphate, 6-(4-hydroxy-3-methyl-2-butenyl-amino)-9-beta-ribofuranosylpurine-5'- monophosphate, N(6)-(Delta(2)-isopentenyl)adenosine, 6-(4-hydroxy-3-methyl-2-butenylamino)-9-beta-ribofuranosylpurine, N(6)-(Delta(2)-isopentenyl)adenine, and 6-(4-hydroxy-3-methyl-2-butenylamino)purine. On the basis of the amounts of cytokinin synthesized per gram fresh tissues, these results indicate that the root is the major site, but not the only site, of cytokinin biosynthesis. Furthermore, cambium and possibly all actively dividing tissues are responsible for the synthesis of this group of plant hormones.

Chronic leptin treatment does not prevent the development of obesity in transgenic mice with brown fat deficiency.

With the exception of ob/ob mice, circulating plasma leptin is elevated in all other obese rodents as well as in obese humans, suggesting that leptin resistance rather than leptin deficiency is a characteristic feature of obesity. The exact molecular mechanisms leading to leptin resistance and the applicability of exogenous leptin to overcome resistance to the anorectic effect of the hormone, are insufficiently characterized. The aim of this study was to investigate whether chronic leptin administration could prevent the development of obesity and its associated disorders in transgenic mice with toxigene mediated ablation of brown adipose tissue (BAT). Daily injections of leptin were started at the age of 6 weeks, when body weight, food intake and plasma leptin levels of transgenics were not different from control mice. Over the next 6 weeks, leptin treated transgenics showed the same excessive body weight gain as transgenic mice injected with saline. Leptin treatment was furthermore not able to prevent the development of hyperphagia, hyperglycaemia, hyperinsulinaemia and hyperlipidaemia in transgenic mice. In contrast, control mice injected with leptin had significantly lower body weight, food intake and plasma triglycerides than those treated with saline. In summary, leptin treatment was not able to prevent the development of obesity and its associated abnormalities in transgenic mice with BAT deficiency. This data suggests that intact BAT function is of critical importance for leptin's effect on food intake and energy expenditure, and that primary dysfunction of BAT is associated with leptin resistance, even when hyperleptinaemia is not yet present.

Leptin reduces juvenile fat stores by altering the circadian cycle of energy expenditure.

The recently identified hormone leptin (ob protein) secreted by white adipose tissue is widely thought to provide a feedback signal limiting fat storage by decreasing food intake. By artificially rearing leptin-treated and control littermates fed identical amounts of milk, however, we show here that lean suckling-age rats treated with recombinant murine leptin can reduce fat storage solely by increasing energy expenditure. Continuous measurements of core temperature and metabolic rate show that this increase is not uniform throughout the day but is especially prominent in the morning when rat pups usually conserve energy by entering a torpor-like state. Leptin's alleviation of hypometabolic, torpor-like states is thus not restricted to cases of impaired hormone production but seems instead to be a normal biological function independent of its effects on food intake.

Open tibia fractures in the splenectomized trauma patient: results of treatment with locking, intramedullary fixation.

OBJECTIVE: To confirm our clinical impression that patients with traumatic splenectomy had more complications in the treatment of open tibia fractures, we retrospectively reviewed the records of patients with open tibia fractures treated between 1989 and 1992. MATERIALS AND METHODS: Eight patients with open tibia fractures and traumatic splenectomies were compared to 43 patients with open tibia fractures and intact spleens. The latter group typically underwent either exploratory laparotomy or peritoneal lavage. The two groups were similar with respect to age, mechanism of injury, fracture wound classification, and injury severity score (22.4 in the splenectomized patients, 18.6 in the control). All tibia fractures were treated with a nonreamed, cross-locked, titanium intramedullary nail, and all patients were treated according to the same protocol of antibiotic therapy. Patients were followed for two years or until roentgenographic and clinical union. RESULTS: The splenectomized patients had a significantly higher incidence of chronic osteomyelitis (25% vs. 4.6%), and the need for additional tibial surgeries to achieve union (75% vs. 16%). Time to union averaged 11.3 months in the splenectomized group and 7.6 months in the patients with intact spleens. CONCLUSIONS: The increased risk for chronic osteomyelitis and other complications of tibial fracture in the splenectomized patients should be taken as an argument favoring splenic, repair, when possible, rather than splenectomy in victims of blunt multiple trauma.

Transcriptional regulation of hydroxypyruvate reductase gene expression by cytokinin in etiolated pumpkin cotyledons.

To understand the mechanisms by which the expression of a specific gene is modulated by cytokinin, the regulation of hydroxypyruvate reductase (HPR) transcript levels by N6-benzyladenine (BA) in etiolated pumpkin (Cucurbita pepo L. cv. Halloween) cotyledons was investigated. A pumpkin HPR cDNA was generated by reverse transcriptase-polymerase chain reaction and its nucleotide sequence was determined. An antisense HPR RNA was prepared for RNase protection analysis of HPR-mRNA expression patterns in the cotyledons of dark-grown pumpkin seedlings. Treatment of the cotyledons with BA was shown to modulate HPR mRNA levels in a dose- and time-dependent manner. Similarly, nuclear run-on studies showed that the rate of transcription was also enhanced by BA treatment of the cotyledons. These results suggest that the enhancement of HPR mRNA by cytokinin is, at least in part, at the level of transcription.