Novel strategies for genomic prediction of untested single-cross maize hybrids using unbalanced historical data.

KEY MESSAGE: Weighted outperformed unweighted genomic prediction using an unbalanced dataset representative of a commercial breeding program. Moreover, the use of the two cycles preceding predictions as training set achieved optimal prediction ability. Predicting the performance of untested single-cross hybrids through genomic prediction (GP) is highly desirable to increase genetic gain. Here, we evaluate the predictive ability (PA) of novel genomic strategies to predict single-cross maize hybrids using an unbalanced historical dataset of a tropical breeding program. Field data comprised 949 single-cross hybrids evaluated from 2006 to 2013, representing eight breeding cycles. Hybrid genotypes were inferred based on their parents' genotypes (inbred lines) using single-nucleotide polymorphism markers obtained via genotyping-by-sequencing. GP analyses were fitted using genomic best linear unbiased prediction via a stage-wise approach, considering two distinct cross-validation schemes. Results highlight the importance of taking into account the uncertainty regarding the adjusted means at each step of a stage-wise analysis, due to the highly unbalanced data structure and the expected heterogeneity of variances across years and locations of a commercial breeding program. Further, an increase in the size of the training set was not always advantageous even in the same breeding program. The use of the two cycles preceding predictions achieved optimal PA of untested single-cross hybrids in a forward prediction scenario, which could be used to replace the first step of field screening. Finally, in addition to the practical and theoretical results applied to maize hybrid breeding programs, the stage-wise analysis performed in this study may be applied to any crop historical unbalanced data.

A laparoscopic approach to allograft nephrectomy and bilateral native nephrectomy: a case report.

INTRODUCTION: Laparoscopic surgery is rapidly emerging as the standard of care for a variety of urological conditions, even among patients who have undergone prior renal transplantation. We describe the technique of bilateral native nephrectomy and allograft nephrectomy by laparoscopy. CASE REPORT: A 32-year-old man with end-stage renal disease who had undergone a cadaveric renal transplant presented with chronic graft dysfunction. He had received a living donor kidney transplant with a postoperative course complicated by persistent proteinuria and refractory hypertension. Our nephrology service indicated the need for bilateral native nephrectomy and allograft nephrectomy for better blood pressure control following a second transplant. Bilateral native nephrectomy was performed following the previous reported techniques for pure laparoscopic nephrectomy. Allograft nephrectomy started by dissection of the iliac vessels to identify the vascular anastomosis. The hilum of the transplanted kidney was accessed. The renal vessels were clipped and transected. The ureter was identified and clipped. All three kidneys were removed from the abdominal cavity through a 3-cm skin incision. RESULTS: The left nephrectomy took 25 minutes and the right nephrectomy, 40 minutes. The estimated blood loss was 300 mL and the total operative time was 210 minutes. The patient had an uneventful postoperative course and was discharged on the third postoperative day. CONCLUSIONS: We demonstrate the feasibility of laparoscopic allograft nephrectomy and bilateral native nephrectomy in a transplant recipient.

Effects of musicokinetic therapy and spinal cord stimulation on patients in a persistent vegetative state.

We developed a method of musicokinetic therapy (MKT), employing a trampoline with live music performance (saxophone or electric piano), in an attempt to improve the clinical condition of patients in a persistent vegetative state (PVS). As an initial step for assessing the effect of MKT on PVS. we analyzed the changes in PVS score (range: 0-30) after MKT, which was continued for 3 months, in a consecutive series of 26 patients. These patients fulfilled the definition of PVS adopted by the Multi-Society Task Force on PVS. In this series, 7 patients were being treated by spinal cord stimulation at the same time. We, therefore, also had an opportunity to examine the effect of spinal cord stimulation on PVS. A greater or lesser improvement in PVS score (post-MKT score - pre-MKT score, mean +/- SD: 8.27 +/- 5.52) was observed in all patients except one. Among 12 patients who had been in PVS for 1 year or more before the initiation of MKT, 7 patients (56.3%) demonstrated improvement of their PVS score by 5 or more, and 4 patients (33.3%) reached a post-MKT score of greater than 20. The condition defined as PVS can never be scored better than 20. Since it is commonly felt that spontaneous improvement rarely occurs if PVS has continued for more than 6 months, the improvement after MKT appears to be better than that which could be observed spontaneously. The improvement in PVS score was often noted in patients with brain damage caused by trauma or SAH. There was no significant difference in improvement of the PVS score between patients who were treated by spinal cord stimulation and those who were not. Although the present study did not directly prove an effect of MKT on PVS, because no controls were involved, the results were consistent with the hypothesis that MKT is useful for improving the clinical condition of patients in PVS, especially those with severe brain damage caused by trauma or SAH.

Cardiac imaging in a patient with anomalous origin of the left coronary artery from the pulmonary artery--a case report.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is an uncommon congenital heart disease and has a high mortality rate in infancy. However, myocardial ischemia does not develop until adolescence or adulthood in about 10% of patients. Moreover, the diagnosis of ALCAPA is often difficult in cases without heart murmur or cardiac symptoms. The authors report the case of a 31-year-old man with ALCAPA. He was admitted to the hospital for evaluation of mild shortness of breath at exercise, but he had no typical chest symptoms due to myocardial ischemia or heart failure until age 31 and he had no heart murmur. Moreover, electrocardiogram did not show an old myocardial infarction or myocardial ischemia. Therefore, the authors did not suspect ALCAPA until they performed transthoracic echocardiography and exercise-stress single photon emission computed tomography (SPECT) with Tc-99m-tetrofosmin. The final diagnosis was established from the results of coronary arteriography. In the present case, a transthoracic echocardiogram showed abnormal coronary circulation, and exercise-stress SPECT revealed reversible myocardial ischemia. Transthoracic echocardiography and myocardial SPECT imaging could be a useful noninvasive tools for diagnosing the ALCAPA.

Suppression of experimental membranous glomerulonephritis in rats by an anti-MHC class II antibody.

BACKGROUND: We previously reported that idiopathic membranous nephropathy (IMN) strongly correlated with HLA-DRB1*1501-DRB5*0101-DQAI*0102-DQB1* 0602, a specific haplotype of human major histocompatibility complex (MHC), in Japanese patients. To investigate the role of MHC in the development of rat Heymann nephritis (HN), an animal model of membranous nephropathy, a monoclonal antibody (mAb) specific to rat MHC class II antigen (RT1B) was administered, and its effectiveness in inhibiting HN was assessed. METHODS: Active HN was induced in HN-sensitive Lewis rats by administering brush border proteins of rat proximal uriniferous tubules (FX1A). Rats were divided into four groups: rats treated with 1,000 micorg anti-rat MHC class II mAb, rats treated with 100 microg anti-rat MHC class II mAb, rats treated with murine myeloma IgG, and rats that did not receive either FX1A or any other mAb. We examined the differences in 24-hour urinary protein excretion and serum alloantibody titers against FX1A between groups at different time intervals, and the histologic features of kidneys at the end of the study. RESULTS: HN was induced in Lewis rats by inoculation with FX1A antigen. Administration of anti-MHC class II mAb successfully lowered urinary proteins, production of anti-FX1A alloantibodies, and the development of glomerular lesions in a dose-dependent manner. CONCLUSION: The present results demonstrated that the MHC class II molecule itself is directly involved in the pathogenesis of HN, and suggest that this therapy would be any better (or less toxic) than nonselective immunosuppressants in the treatment of IMN.

Relationship between fluctuation pattern of blood pressure during hemodialysis treatment and cardiovascular morphology: an autopsy study of 53 cases.

BACKGROUND: Cardiovascular morphological changes are often conspicuous in autopsy examination of chronic hemodialysis (HD) patients. On the other hand, the fluctuation pattern in blood pressure (BP) during HD treatment varies from one patient to another. Cardiovascular changes may correlate with clinical findings including BP fluctuation patterns during HD, although no autopsy studies have previously examined this issue. METHODS: In this study, 53 autopsies of patients who had been on chronic HD were reviewed. We determined the relationship between BP fluctuation during HD treatment along with stable and cardiovascular morphology, including heart weight, ventricular wall thickness, circumferences of the valves and the severity of aortic arteriosclerosis and coronary stenosis. Patients were divided into 4 groups according to the pattern of BP fluctuation during HD treatment at about 6 months before death: group 1 (n = 13), symptomatic hypotension and/or decline pattern during HD; group 2 (n = 11), continuously high BP during HD treatment; group 3 (n = 17), continuous normal BP during HD treatment, and group 4 (n = 12), continuously low BP without symptomatic hypotension during HD treatment. RESULTS: Heart weight and ventricular wall thickness were greatest in group 2. The scores for aortic arteriosclerosis in groups 1 and 2 were higher than in groups 3 and 4. The coronary stenosis index was significantly higher in group 1 than in the other groups, and that in group 2 was higher than in group 4. Multiple regression analysis showed that age, HD duration and pulse pressure were independent variables for the score of arteriosclerosis, and the decline pattern of BP fluctuation during HD and pulse pressure were independent variables for coronary stenosis index. CONCLUSIONS: Our results suggest that certain clinical parameters including BP during HD may reflect cardiovascular morphological changes in stable HD patients, although further examination, such as 24-hour blood pressure measurement is recommended to elucidate the pathophysiology of cardiovascular diseases in HD patients.

Murine equivalent of the human histo-blood group ABO gene is a cis-AB gene and encodes a glycosyltransferase with both A and B transferase activity.

We have cloned murine genomic and complementary DNA that is equivalent to the human ABO gene. The murine gene consists of at least six coding exons and spans at least 11 kilobase pairs. Exon-intron boundaries are similar to those of the human gene. Unlike human A and B genes that encode two distinct glycosyltransferases with different donor nucleotide-sugar specificities, the murine gene is a cis-AB gene that encodes an enzyme with both A and B transferase activities, and this cis-AB gene prevails in the mouse population. Cloning of the murine AB gene may be helpful in establishing a mouse model system to assess the functionality of the ABO genes in the future.

Mitochondrial 16S rRNA sequence diversity of hominoids.

We determined nucleotide sequences of the 16S rRNA gene of mitochondrial DNA (mtDNA) (about 1.6 kb) for 35 chimpanzee, 13 bonobo, 10 gorilla, 16 orangutan, and 23 gibbon individuals. We compared those data with published sequences and estimated nucleotide diversity for each species. All the ape species showed higher diversity than human. We also constructed phylogenetic trees and networks. The two orangutan subspecies were clearly separated from each other, and Sumatran orangutans showed much higher nucleotide diversity than Bornean orangutans. Some gibbon species did not form monophyletic clusters, and variation within species was not much different from that among species in the subgenus Hylobates.

Evolution of the ABO blood group gene in Japanese macaque.

We determined 5 sequences of Japanese macaque ABO blood group gene exon 7 (ca. 0.5 kb) and 2 sequences for exon 5 and intron 6 (ca. 1.7 kb). We compared those data with published sequences of other Old World monkey species, and the results suggest that alleles A and B were polymorphic in the ancestral species of macaques, and that B type allele evolved independently in macaque and baboon lineages.

Gene diversity of chimpanzee ABO blood group genes elucidated from intron 6 sequences.

The human and nonhuman primate ABO blood group gene shows relatively large numbers of nucleotide differences around the exon 7 region. In this study we determined intron 6 sequences for 9 alleles of common chimpanzee and for 3 alleles of bonobo to estimate nucleotide diversities among them. Sequence length polymorphisms are observed in this region as a repeat appears one to five times. From a phylogenetic network of intron 6 sequences of ABO blood group genes for humans, common chimpanzee, and bonobo, parallel substitutions and/or some kinds of convergent events are predicted in the chimpanzee lineage. We also estimated nucleotide diversities for common chimpanzee and bonobo ABO blood group genes; these values were 0.219% and 0.208%, respectively.

Gene diversity of chimpanzee ABO blood group genes elucidated from exon 7 sequences.

Human and non-human primate ABO blood group genes show relatively large numbers of nucleotide differences. In this study, we determined exon 7 sequences for 10 individuals of common chimpanzee and for four individuals of bonobo to estimate nucleotide diversities among them. Sequence data showed the existence of chimpanzee specific 9-base deletion in the beginning of the exon 7 coding region. From a phylogenetic network of exon 7 sequences of ABO blood group genes for human, common chimpanzee, bonobo and gorilla, effects of parallel substitutions and/or some kinds of convergent events are inferred in the chimpanzee lineage. We also estimated nucleotide diversities for common chimpanzee and bonobo ABO blood group genes, and these values were 0.4% and 0.2%, respectively. These values are higher than that of most human genes.

Association between HLA-DRB1*15 and Japanese patients with rheumatoid arthritis complicated by renal involvement.

We performed serological phenotyping of HLA antigens in 175 patients with rheumatoid arthritis (RA) with (n = 41) and without (n = 134) renal involvement (RI), and DNA typing of HLA class II alleles in 75 patients. Among the patients with RA, the frequency of serologically determined HLA-DR4 was found to be significantly increased (odds ratio: 1.8, confidence interval: 1.3-2.5, p = 2.4x10(-4)). In the patients without RI, the frequency of serological DR4 significantly increased (odds ratio: 2.2, confidence interval: 1.6-3.3, p = 2. 6x10(-5)). On the other hand, among the patients with RI, a serological determinant, DR15, did significantly increase (odds ratio: 2.7, confidence interval: 0.9-8.4, p = 1.2x10(-3)) in comparison to the controls. At the DNA level, we found that the association of Japanese RA patients with serological HLA-DR4 was based on that with a genotype of HLA-DRB1*0405 (odds ratio: 2.4, confidence interval: 1.5-4.0, p = 4.4x10(-4)) and also found an association of HLA-DRB1*1501 (odds ratio: 2.8, confidence interval: 1.2-6.6, p = 0.017) with RA patients having RI. Our results confirmed the association of HLA-DRB1*04 with RA over the ethnic barrier at the DNA level. Our results also suggested a distinct genetic effect of HLA-DRB1*1501 in the aspect of the susceptibility of RI in RA.

Phototaxic behavior and the retinotectal transport of horseradish peroxidase (HRP) in surgically created cyclopean salamander larvae (Ambystoma).

UNLABELLED: Negative phototaxis (NP) was used to evaluate the recovery of vision in albino axolotl larvae with one eye discarded and the other transplanted either to the orbit (orthoclops) or to the top of the head (cyclops). NP was assessed at approximately 1, 2 and 3 months postoperatively, using an automated, infrared monitor. Some 88% of the orthoclopes and 64% of the cyclopes recovered NP. However, among the cyclopes that did recover, the quantitative aspects of NP were virtually the same as those of the orthoclopes. That the cyclopean eye can regenerate retinotectal pathways was established by anterograde tracing of horseradish peroxidase (HRP). But where previously uninjured animals transported HRP to the contralateral tectum, both the cyclopes and the orthoclopes distributed the enzyme to the left and right tectal halves. Heavy deposits of HRP were found in the tecta of some animals that lacked NP. To find out if an optic tectum is actually required for NP, a series of ablation experiments were performed, using Ambystoma punctatum larvae. Tectectomy had the same effect on NP as bilaterally extirpating the eyes or intracranially severing both optic nerves, i.e. removing the tectum abolished NP. THE RESULTS: (1) confirm the efficacy of the ectopic eye in the cyclops preparation; (2) show that the ectopic eye can regenerate retinotectal pathways; (3) indicate that retinotectal contact is a necessary but insufficient condition for NP.

[Laboratory studies of the molluscacidal action of the maguey (Agave legrelliana) on Biomphalaria havanensis]. / Estudios de la acción molusquicida en el laboratorio del maguey (Agave legrelliana), sobre Biomphalaria havanensis.

A study was carried out on the molluscacidal action of agave (Agave legrelliana) on the mollusk Biomphalaria havanensis, host of Schistosoma. Different concentrations of the plant's juice extract were tested to determine lethal doses. 3 experimental series were carried out using 144 mollusks in each. LD50 = 0.14 mL/L and LD90 = 0.47 mL/L were determined using the "probilog" computerized program. The regression equation was Y = 5.29 + 2.53 in X. Density, pH, liquid content and absorbance of the juice were determined. The stability of the A. legrelliana juice extract was compared using LD90 and it was observed that its effectiveness was reduced after long storage periods. The results attained were very encouraging since large volumes of water abounding in intermediate host mollusks can be treated with small quantities of juice at the same time that the toxicity which might be introduced by products of chemical origin is reduced.

Efficacy of ivermectin against live mites and eggs of Sarcoptes scabiei in pigs.

Sows infested with Sarcoptes scabiei var. suis (ssvs) were treated with 75, 150 and 300 micrograms/kg of ivermectin by a single subcutaneous injection at the neck region. Compared to the numbers of mites and eggs just before injection, those on post treatment weeks (PTW) 1, 2 and 4 showed significant decreases. Especially at 300 micrograms/kg, the counts showed almost all mites and eggs were eradicated on PTW 1, manifesting ivermectin to possess potential effect on ssve without apparent abnormal side effect. Potential mitocide effect of ivermectin on ssvs was revealed.

Long-term survival of a free split-thickness skin graft on a large seroma.

A free skin graft about 12 cm in diameter transplanted after excision of a Bowen's carcinoma on the back totally survived for a long period on seroma and was confirmed to have revascularization from the host skin margin. Repeated evacuations of the fluid and subsequent pressure dressings failed to cause adherence of the graft to the bed, even on the thirty-ninth postoperative day. Histologic examination of the graft and the bed revealed partial epithelialization on the face-to-face surfaces, to which no adherence was attributed. The incomprehensible phenomenon in this unusual clinical case evokes a new interest in the mechanism of free skin graft survival, particularly in the phase of serum imbibition.