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Biomedical subjects

E W Johnson

Publications and source records attributed to E W Johnson.

At least 19 recordsLinked to original sources

Effects of dietary supplementation with L-carnitine and fat on blood acid-base responses to handling in slaughter weight pigs.

Blood acid-base responses to handling were evaluated in slaughter weight pigs fed diets supplemented with l-carnitine and fat. The study was carried out as a randomized block design with a 2 x 2 factorial arrangement of treatments: 1) dietary L-carnitine supplementation (0 vs. 150 ppm, as-fed basis); and 2) dietary fat supplementation (0 vs. 5%, as-fed basis). Sixty pigs (91.1 +/- 5.14 kg BW) were housed in mixed-gender groups of five and had ad libitum access to test diets (0.68% true ileal digestible lysine, 3,340 kcal of ME/kg, as-fed basis) for 3 wk. At the end of the feeding period (110.3 +/- 7.52 kg BW), pigs were subjected to a standard handling procedure, which consisted of moving individual animals through a facility (12.2 m long x 0.91 m wide) for eight laps (up and down the facility), using electric prods (two times per lap). There was no interaction between dietary L-carnitine and fat supplementation for any measurement. Pigs fed 150 ppm of supplemental L-carnitine had lower baseline blood glucose (P < 0.05) and higher baseline blood lactate (P < 0.05) concentrations than the nonsupplemented pigs. After handling, pigs fed L-carnitine-supplemented diets had a higher (P < 0.05) blood pH and showed a smaller (P < 0.05) decrease in blood pH and base excess than those fed the nonsupplemental diets. Baseline plasma FFA concentrations were higher (P < 0.01) in pigs fed the 5% fat diet. After the handling procedure, blood glucose, lactate, and plasma FFA were higher (P < 0.05) in pigs fed the 5 vs. 0% fat diets, but blood pH, bicarbonate, and base excess were not affected by dietary fat. The handling procedure decreased (P < 0.01) blood pH, bicarbonate, base excess, and total carbon dioxide and increased (P < 0.01) blood lactate, partial pressure of oxygen, and glucose, and also increased (P < 0.01) rectal temperature. Free fatty acid concentrations were increased by handling in pigs fed both 0 and 5% fat and 150 ppm L-carnitine. In conclusion, dietary L-carnitine supplementation at the level and for the feeding period evaluated in the current study had a relatively small but positive effect on decreasing blood pH changes in finishing pigs submitted to handling stress; however, dietary fat supplementation had little effect on blood acid-base balance.

Acid-Base Equilibrium↗

Effects of stachyose on performance, diarrhoea incidence and intestinal bacteria in weanling pigs.

A three-week trial was conducted to evaluate the effects of the oligosaccharide stachyose on performance, diarrhoea incidence and intestinal bacterial populations in weaned pigs (7.96 +/- 0.2kg). A total of 144 crossbred (Landrace x Large White x Duroc) pigs weaned at 28 days were allotted to one of four treatments with six pens per treatment and six pigs per pen. The experimental diets were based on maize, dried whey and whole-fat milk and were supplemented with 0, 1 or 2% stachyose. A fourth diet contained no milk but instead contained 20% soybean meal to provide 0.78% stachyose and 0.21% raffinose. Inclusion of 1 or 2% stachyose in the diet depressed growth compared with pigs fed the control diet. Pigs fed the soybean meal diet gained weight at a rate similar to pigs fed the diet containing 1% added stachyose. Diarrhoea incidence was highest for pigs fed the soybean meal diet and lowest for pigs fed the control diet, with pigs fed the diets containing stachyose being intermediate. Pigs fed 1% stachyose had more lactobacilli in the ileum as well as more bifidobacteria in the caecum and colon than control pigs. They also had fewer enterobacteria in the colon. In contrast, pigs fed the diet containing 2% stachyose had fewer lactobacilli and bifidobacteria in the jejunum, ileum and caecum than did control pigs. Volatile fatty acids in the ileum, caecum and colon were highest for pigs fed 1% stachyose and lowest for pigs fed 2% stachyose. Volatile fatty acid concentrations were not significantly different between pigs fed the soybean meal diet and those fed the control. The overall results of this experiment indicate that the oligosaccharide stachyose had a negative effect on pig performance and its presence may partially explain the poorer performance observed when soybean meal is used as the sole source of supplemental protein in cereal-based diets fed to weaned pigs.

Animal Feed↗

A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum.

To better understand the pathogenetics of pseudoxanthoma elasticum (PXE), we performed a mutational analysis of ATP-binding cassette subfamily C member 6 (ABCC6) in 122 unrelated patients with PXE, the largest cohort of patients yet studied. Thirty-six mutations were characterized, and, among these, 28 were novel variants (for a total of 43 PXE mutations known to date). Twenty-one alleles were missense variants, six were small insertions or deletions, five were nonsense, two were alleles likely to result in aberrant mRNA splicing, and two were large deletions involving ABCC6. Although most mutations appeared to be unique variants, two disease-causing alleles occurred frequently in apparently unrelated individuals. R1141X was found in our patient cohort at a frequency of 18.8% and was preponderant in European patients. ABCC6del23-29 occurred at a frequency of 12.9% and was prevalent in patients from the United States. These results suggested that R1141X and ABCC6del23-29 might have been derived regionally from founder alleles. Putative disease-causing mutations were identified in approximately 64% of the 244 chromosomes studied, and 85.2% of the 122 patients were found to have at least one disease-causing allele. Our results suggest that a fraction of the undetected mutant alleles could be either genomic rearrangements or mutations occurring in noncoding regions of the ABCC6 gene. The distribution pattern of ABCC6 mutations revealed a cluster of disease-causing variants within exons encoding a large C-terminal cytoplasmic loop and in the C-terminal nucleotide-binding domain (NBD2). We discuss the potential structural and functional significance of this mutation pattern within the context of the complex relationship between the PXE phenotype and the function of ABCC6.

ATP-Binding Cassette Transporters↗

Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene.

A notable difficulty in annotating genomic sequence is identifying the correct start codon in a gene. An important such case has been found with KRIT1, the cerebral cavernous malformation type 1 (CCM1) gene. Analysis of human and mouse genomic sequence encompassing the region containing KRIT1/Krit1 using exon/gene-prediction and comparative alignment programs revealed putative exons upstream of the previously described first exon. These additional candidate exons show significant matches to mouse and human ESTs that are contiguous with and extend upstream from the previously designated 5' end of the KRIT1 cDNA sequence. RT-PCR and 5'RACE experiments confirm the presence of four additional upstream coding exons that encode an additional 207 amino acids. Importantly, a novel frameshift mutation in one of these newly identified KRIT1 exons has been found in a CCM1 family. These data establish the authentic KRIT1 amino acid sequence and suggest that the additional KRIT1 exons may harbor mutations in other CCM1 families. In addition, these results provide another example of the utility of rigorous computational and comparative sequence analysis for refining gene structure.

Alternative Splicing↗

The "stinger".

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Brachial Plexus Neuropathies↗

Bulging disks.

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Aging↗

H reflex and F wave latencies to soleus normal values and side-to-side differences.

OBJECTIVE: Electromyographers must reliably differentiate between H reflexes and F waves when recording from the soleus muscle in the evaluation of S1 radiculopathy. The use of F waves in root-level injuries is questioned, whereas H reflexes have shown value in the evaluation of S1 radiculopathy. We studied the relationship between the tibial H reflex and F wave latencies in the limbs of 40 subjects. DESIGN: After recording the H wave latency, we changed the gain to 200 microV/cm and increased the stimulation to supramaximal for ten additional responses without moving the recording or stimulating electrodes. We also calculated the predicted H wave latency with the standard formula. Forty subjects, mean age 32 yr, consented and participated. RESULTS: The mean of the average F wave was 1.76 ms longer than the ipsilateral H reflex latency. The mean side-to-side difference of the average F wave was 0.56 ms. The H reflex latency side-to-side difference was 0.36 ms. CONCLUSION: The findings suggest that the average F wave latencies have a predictive value in the clinical context similar to the H reflex.

Action Potentials↗

Auto hypocrisy.

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Attitude to Health↗

Coronary artery bypass performed without the use of cardiopulmonary bypass is associated with reduced cerebral microemboli and improved clinical results.

STUDY OBJECTIVES: Strokes and neurocognitive dysfunction have been correlated with cerebral microemboli produced during cardiopulmonary bypass (CPB). The purpose of this study was to determine whether, and to what extent, off-pump coronary artery bypass (OPCAB) reduces the occurrence of cerebral microemboli compared with traditional coronary artery bypass grafting (CABG) with CPB and to compare clinical results. DESIGN AND PATIENTS: A retrospective review of 137 patients undergoing elective CABG was performed, 70 of whom underwent traditional CABG and 67 of whom underwent OPCAB. Using transcranial Doppler ultrasonography, 40 patients (20 CABG, 20 OPCAB) were continuously monitored intraoperatively for the occurrence and pattern of cerebral microemboli. SETTING: Private, university-affiliated tertiary care hospitals. RESULTS: There was no statistical difference in the age, sex, or underlying comorbidities between those patients undergoing CABG and OPCAB. CABG patients did have a slightly lower preoperative ejection fraction (50.9% vs 55.5%, p = 0.03). Despite these similar preoperative characteristics, the OPCAB group experienced significant reductions in cerebral microemboli (27 vs 1,766, p = 0.003), transfusion requirements (29.9% vs 47.1%, p = 0.04), intubation time (3.3 vs 9.5 h, p < 0.001), ICU length of stay (1.5 vs 2.8 days, p = 0.02), and overall hospitalization (4.9 vs 6.6 days, p = 0.01) without an increase in mortality. Fewer strokes and deaths were observed in the OPCAB group, but these trends failed to reach statistical significance. CONCLUSIONS: In similar patient populations, OPCAB was associated with significantly fewer cerebral microemboli and improved clinical results without an increase in mortality. We believe that these early results support OPCAB as a viable and potentially safer alternative to traditional CABG.

Aged↗

Out-patient parenteral antibiotic therapy (OPAT): clinical outcomes and adverse events.

A chart review was conducted of patients in a program featuring self directed, home infusion of antibiotics for serious infections utilizing an out-patient medical office for teaching, mixing of drugs, and monitoring of patients. 302 courses of out-patient parenteral antibiotic therapy (OPAT) were administered to 221 patients. Therapy was successful in 94% of the episodes. Objective adverse events were noted in 25% of patients. To maximize the chance for a successful outcome, treatment plans should be individualized and structured to include systematic monitoring for adverse effects.

Ambulatory Care↗

Immunocytochemical characteristics of cells and fibers in the nasal mucosa of young and adult macaques.

The mammalian nasal cavity is lined by an olfactory mucosa (OM) and a respiratory mucosa (RM). The principal OM cell type is the olfactory receptor neuron (ORN). However, little is known about ORNs in the life histories of primates. The RM, similar to the RM in the tracheobronchial tract (TBT), is dominated by ciliated columnar cells. Neuroendocrine cells (NECs) are essential in the TBT; little is known about nasal NECs. This study examined the immunolabeling characteristics of primate OM and RM for three important proteins-calretinin (CR), olfactory marker protein (OMP), and protein gene product 9.5 (PGP). Tissues from newborn to 15-year-old macaques were analyzed to determine the expression of these proteins during various stages of development. Standard immunocytochemistry on aldehyde-fixed tissues was applied, utilizing the avidin-biotin peroxidase (ABC) method. Immuno-electron microscopy confirmed the immunoreactive cell types. ORNs were immunoreactive for CR, OMP, and PGP at all ages studied. Immunoreactivity for PGP also was displayed in a subset of ciliated, columnar epithelial cells in the RM and in an extensive network of subepithelial fibers spread throughout both mucosae. The results suggest that macaque ORNs express three important proteins over a wide life history, and that the macaque may be a reliable model for studying primate/human olfaction during aging. The PGP-labeling results also suggest that the macaque nasal peptidergic fibers express PGP and that the respiratory epithelium contains NECs with labeling characteristics similar to those in the TBT.

Aging↗

Breakpoint sequences of an 1;8 translocation in a family with Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is a common, heritable neurological disorder manifested by chronic motor and vocal tics with childhood onset. Previous extensive linkage analysis failed to identify a GTS gene based on an autosomal dominant pattern of inheritance. Recently, a family was reported with a balanced chromosomal translocation t(1;8)(q21.1;q22.1) in family members with GTS or tics. Chromosome 8q22.1 was previously implicated in GTS by both association and linkage results. We therefore cloned and sequenced both translocation breakpoints from this family. The CBFA2T1 gene was identified 11 kb distal to the 8q22.1 breakpoint. Sequencing of CBFA2TI exons within 37 unrelated GTS patients failed to identify any mutations. However, it is possible that the translocation altered the expression of this gene or another nearby gene. Examination of the breakpoint sequences revealed a duplication of six nucleotides from chromosome 8 but no change in the chromosome 1 sequence. The sequences immediately flanking the breakpoints on the two chromosomes were modestly similar, but the breakpoints did not occur within known interspersed repeats. Our results add to our knowledge of the genetics of GTS and the mechanisms of balanced chromosomal translocations.

Bacteriophages↗

Coronary artery bypass grafting performed with or without a bypass pump: early results.

INTRODUCTION: Traditionally, heart bypass surgery has required stopping of the heart and the use of cardiopulmonary bypass. Numerous complications have been associated with exposure to this extracorporeal circuit. Newer techniques of local cardiac wall stabilization now enable this operation to be performed safely "Off Pump". The early clinical results of Off Pump Coronary Artery Bypass (OPCAB) will be compared to a similar group of traditional Coronary Artery Bypass Grafting (CABG) patients. METHODS: A retrospective review of 137 consecutive patients undergoing elective coronary artery bypass grafting was performed, 68 of who underwent traditional CABG and 69 of who underwent OPCAB. Inclusion criteria consisted of first time cardiac surgical procedures with an ejection fraction > or = 20%, without significant renal failure (creatinine < 2.0). RESULTS: There was no statistical difference in the age, sex, cardiac function or underlying co-morbidities between those undergoing CABG and OPCAB. CABG patients had slightly more vessels bypassed than those in the OPCAB group (3.0 vs 2.6, p = 0.010). Despite similar preoperative characteristics, the OPCAB group experienced a reduction in morbidity without an increase in mortality. CONCLUSION: In similar patient populations, OPCAB was associated with significantly reduced transfusion requirements, intubation time, ICU and overall hospital lengths of stay, with no increase in mortality. Further investigation is warranted to ascertain the role of the OPCAB in the general cardiac surgical community.

Aged↗

Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1).

Cerebral cavernous malformations (CCM) are congenital vascular anomalies of the brain that can cause significant neurological disabilities, including intractable seizures and hemorrhagic stroke. One locus for autosomal dominant CCM ( CCM1 ) maps to chromosome 7q21-q22. Recombination events in linked family members define a critical region of approximately 2 Mb and a shared disease haplotype associated with a presumed founder effect in families of Mexican-American descent points to a potentially smaller region of interest. Using a genomic sequence-based positional cloning strategy, we have identified KRIT1, encoding a protein that interacts with the Krev-1/rap1a tumor suppressor, as the CCM1 gene. Seven different KRIT1 mutations have been identified in 23 distinct CCM1 families. The identical mutation is present in 16 of 21 Mexican-American families analyzed, substantiating a founder effect in this population. Other Mexican-American and non-Hispanic Caucasian CCM1 kindreds harbor other KRIT1 mutations. Identification of a common Mexican-American mutation has potential clinical significance for presymptomatic diagnosis of CCM in this population. In addition, these data point to a key role for the Krev-1/rap1a signaling pathway in angiogenesis and cerebrovascular disease.

Blood Vessels↗