A genome-wide scan for quantitative trait loci affecting respiratory disease and immune capacity in Landrace pigs.

Respiratory disease is the most important health concern for the swine industry. Genetic improvement for disease resistance is challenging because of the difficulty in obtaining good phenotypes related with disease resistance; however, identification of genes or markers associated with disease resistance can help in the genetic improvement of pig health. The purpose of our study was to investigate whether quantitative trait loci (QTL) associated with disease resistance were segregated in a purebred population of Landrace pigs that had been selected for meat production traits and mycoplasmal pneumonia of swine (MPS) scores over five generations. We analysed 1395 pigs from the base to the fifth generation of this population. Two respiratory disease traits [MPS scores and atrophic rhinitis (AR) scores] and 11 immune-capacity traits were measured in 630-1332 animals at 7 weeks of age and when the animal's body weight reached 105 kg. Each of the pigs, except sires in the base population, was genotyped using 109 microsatellite markers, and then, QTL analysis of the full-sib family population with a multi-generational pedigree structure was performed. Variance component analysis was used to detect QTL associated with MPS or AR scores, and the logarithm of odds (LOD) score and genotypic heritability of the QTL were estimated. Five significant (LOD > 2.51) and 18 suggestive (LOD > 1.35) QTL for respiratory disease traits and immune-capacity traits were detected. The significant QTL for Log-MPS score, located on S. scrofa chromosome 2, could explain 87% of the genetic variance of this score in this analysis. This is the first report of QTL associated with respiratory disease lesions.

Elucidation of correspondence between swine chromosome 4 and human chromosome 1 by assigning 27 genes to the ImpRH map, and development of microsatellites in the proximity of 14 genes.

Loci affecting swine intramuscular fat content, backfat thickness, carcass weight, and daily weight gain were assigned to regions of swine chromosome (SSC) 4, which were shown to correspond to human chromosome (HSA) 1p22--> q25 by ZOO-FISH, bidirectional chromosome painting, as well as by the linkage map of genes. In order to select candidate genes responsible for the above traits from the human genome database, precise correspondence between SSC4 and HSA1 is a prerequisite. In the present study, 27 genes, PTGFR, GBP1, GBP2, GFI1, GCLM, ABCD3, EXTL2, KCNA3, ADORA3, KCND3, WNT2B, NRAS, SYCP1, PTGFRN, IGSF2, NOTCH2, S100A10, SHC1, SSR2, LMNA, CCT3, CD5L, PEA15, FCER1G, EAT2, DDR2, and LAMB3, located in the HSA1 region corresponding to SSC4 or possibly SSC4, were assigned to the IMpRH map. The alignment of genes from centromere to telomere in the SSC4 q arm is basically conserved in HSA1p22-->q25 with the direction from the q arm to the p arm, which is in good agreement with results from linkage mapping. In addition, the present study first demonstrated that WNT2B residing in the middle of the HSA1 region was assigned to SSC18 with a high lod score (> 5), and that at least three intrachromosomal rearrangements occurred in the region in the process of swine and human evolution. PTGFR, and LAMB3 localized at both ends of the HSA1 region were assigned to SSC6 and SSC9, respectively, which is consistent with regional correspondence reported earlier. In the course of the above analysis, microsatellite markers were developed in the proximity of eleven genes localized on SSC4, and three genes on other swine chromosomes.

Thromboxane A2 synthetase inhibitors. 2. Syntheses and activities of tetrahydronaphthalene and indan derivatives.

A series of 1-imidazolylalkyl-substituted or 5-thiazolylalkyl-substituted tetrahydronaphthalenecarboxylic acid and indancarboxylic acid derivatives were prepared and tested for the inhibitory activities of thromboxane A2 (TXA2) production in vitro and ex vivo. Most of the compounds showed potent TXA2 synthetase inhibitory activities in vitro and had long duration of inhibition of TXA2 production in rats when orally or intravenously administrated. The imidazole analogues had slightly less potency in vitro than the thiazole analogues, but the activities of the imidazole analogues in ex vivo models were equal or superior to the activities of the thiazole analogues. 6-(1-Imidazolyl-methyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride hemihydrate (47a, DP-1904) was chosen for clinical studies.

The utility of MRI in acute stage of carbon monoxide poisoning.

Intracranial abnormalities by magnetic resonance imaging (MRI) in acute carbon monoxide (CO) poisoning have been described in two cases. Edematous bilateral lesions have been demonstrated in the globus pallidus. Findings correspond with the pathological changes described in literature. In our experience MIR is a more sensitive examination compared to serial computed tomography (CT) in acute CO poisoning.

An infant with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation.

Here we report a case with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation. A 7-month-old Japanese boy was diagnosed to have NK cell leukemia based on the existence of abnormal cells in the bone marrow with the phenotype of CD3(-) /CD4(+) /CD7(-) /CD8(-) /CD16(-) /CD33(+) /CD34(-) /CD56(+) /HLA-DR(+) /NKB1(+) / CD94(+). The leukemic cells showed few azurophilic granules in the cytoplasm and weak cytotoxic activity. Although he presented with a huge mass occupying the bilateral paranasal sinuses and hepatosplenomegaly, he achieved complete remission by the conventional chemotherapeutic regimen for acute myelogenous leukemia, followed by an unrelated cord blood transplantation. He has remained in complete remission for 14 months posttransplant. To our knowledge, this is the youngest reported case with precursor NK cell leukemia; cord blood transplantation may thus be the treatment of choice for this disease.

Activation of aniline by extracts from plants and induction of chromosomal damages in Chinese hamster ovary cells.

Activation of aniline by plant extracts was studied by a chromosomal damage induction assay in Chinese hamster ovary (CHO) cells in vitro. Extracts from roots of Vicia faba activated aniline and the activation caused increases in chromosomal aberrations (CAs) and endoreduplicated cells (ERCs), but did not cause sister-chromatid exchanges (SCEs). Extracts from Pisum sativum and Lactuca sativa, however, did not activate aniline. All C-hydroxylated metabolites of aniline, o-aminophenol, m-aminophenol and p-aminophenol, induced not only CAs but also SCEs in CHO cells. These results show that the pathway for aniline activation by Vicia extracts is by means other than the C-hydroxylation.

Role of alpha 1-adrenoceptor subtypes which mediate positive chronotropy in neonatal rat cardiac myocytes.

We investigated the involvement of alpha 1-adrenoceptor subtypes in the positive chronotropic response to norepinephrine (NE) in neonatal rat cardiac myocytes at day 3 of culture. The cardiac myocytes at day 3 of culture exhibited a dose-dependent positive chronotropic response to NE in the presence of propranolol, a beta-adrenoceptor antagonist. The positive chronotropic responses to NE were completely antagonized by the alpha 1-adrenoceptor antagonist prazosin. The NE-induced positive chronotropic response was inhibited 68% by the alpha 1B-adrenoceptor antagonist, chloroethylclonidine (CEC), but partially (41%) so by the alpha 1A-adrenoceptor antagonist, WB4101. In the membrane fraction derived from cardiac myocytes at day 3 of culture, pretreatment with CEC decreased the Bmax of the alpha 1-adrenoceptor to 22% of the control value. The NE-induced positive chronotropic response was inhibited 62 and 77% by the voltage-gated Ca2+ channel blocker such as nifedipine and verapamil, respectively. These findings indicate (1) that cultured neonatal rat cardiac myocytes possess both alpha 1-adrenoceptor subtypes, i.e., alpha 1A and alpha 1B, (2) that the predominant alpha 1-adrenoceptor subtypes mediating NE-induced positive chronotropy in neonatal rat cardiac myocytes at day 3 of culture are alpha 1B-subtypes, and (3) that NE-induced positive chronotropy may be caused via voltage-gated Ca2+ channel activation.

Induction of chromosome damage by aniline and its C-hydroxylated metabolites in the root cells of Vicia faba.

The induction of sister-chromatid exchanges (SCEs) and chromosome aberrations (CAs) by aniline hydrochloride (AH) and its C-hydroxylated metabolites, o-, m- and p-aminophenol, in the root cells of Vicia faba was examined. AH induced CAs, but not SCEs. All the C-hydroxylated metabolites of aniline induced both SCEs and CAs. However, the treatment of cells with these metabolites at concentrations that did not cause significant increases in CAs resulted in significant increases in SCEs. These results seem to suggest that the substance that induced CAs in root cells treated with AH was not the C-hydroxylated metabolites of aniline.

Induction of chromosome damage by benzo[a]pyrene, 2-aminofluorene and cyclophosphamide in the root cells of Vicia faba.

The induction of sister-chromatid exchanges (SCEs) and chromosome aberrations (CAs) by benzo[a]pyrene (BP), 2-aminofluorene (2-AF) and cyclophosphamide (CP) in the root cells of Vicia faba was examined. BP and 2-AF induced CAs, but not SCEs. CP induced both SCEs and CAs.

A comparison of Vicia-faba-root S10 and rat-liver S9 activation of ethanol, maleic hydrazide and cyclophosphamide as measured by sister-chromatid exchange induction in Chinese hamster ovary cells.

A comparison of Vicia-faba-root S10 with rat-liver S9 was made in their capacity to bring about, in vitro, the metabolic activation of ethanol, maleic hydrazide (MH) and cyclophosphamide (CP) that can lead to the induction of sister-chromatid exchanges (SCEs) in CHO cells. When NADP was a cofactor in the S9 mix, ethanol, MH and CP all induced an increase of SCEs with rat-liver S9. With Vicia-root S10, however, ethanol induction of SCEs was very weak and no effect at all was observed with MH and CP. When NAD was a cofactor in the S9 mix, Vicia-root S10 activated ethanol and produced an increase in SCEs.

SCE induction in human lymphocytes by combined treatment with aniline and norharman.

In human lymphocytes, aniline was unable to induce an increase of SCEs in vitro with or without metabolic activation by S9 mix. p-Aminophenol, one of the C-hydroxylation metabolites of aniline in the body, however, increased the SCE frequencies of lymphocytes at a concentration of 10-4 M. The addition of norharman to aniline plus S9 mix increased the SCE frequencies. The increase, however, was due to the SCE-inducing activity of norharman. These data show that the addition of norharman, which enhances the sensitivity of the Salmonella/microsome test, does not produce an enhancement of the sensitivity of the SCE test.

Promutagen activation by Vicia faba: an assay based on the induction of sister-chromatid exchanges in Chinese hamster ovary cells.

Plant activation of promutagens was studied using Vicia faba S10 (in vitro activation) and the extracts prepared from promutagen-treated roots of Vicia faba (in vivo activation). The induction of sister-chromatid exchanges in Chinese hamster ovary cells was used as an endpoint to evaluate the cytogenetic effects of promutagens activated by Vicia faba. Cyclophosphamide and ethyl alcohol were activated both by Vicia S10 and by the Vicia extracts, and their activation resulted in an increase in SCEs. Benzo[a]pyrene, 2-aminofluorene, and maleic hydrazide were not activated. Aniline was activated, but without effect on the induction of SCEs. The activation capacity in vitro and in vivo of Vicia faba was not very pronounced, except for the activation of ethyl alcohol, when compared with that of rat-liver S9, and showed differences in activation for the 6 chemical agents tested.

Plant extracts induce chromosome aberrations and sister-chromatid exchanges in Chinese hamster ovary cells and human lymphocytes.

Effects of extracts from Vicia faba were compared with those of Zea mays for the induction of sister-chromatid exchanges (SCEs) and of chromosome aberrations (CAs) in Chinese hamster ovary (CHO) cells. CA induction by the maize extract was also tested in human lymphocytes. The extracts from roots and leaves of Vicia faba induced CAs and SCEs in CHO cells. The extracts from maize leaves also induced SCEs and CAs in CHO cells, and CAs in human lymphocytes. Maize extracts were more potent in inducing SCEs than Vicia extracts and the SCE- and CA-inducing capacity of maize extracts decreased during preincubation before addition to cells.

Vicia faba chromosomal aberration assay.

A collaborative study involving laboratories in six countries was initiated under the sponsorship of the International Programme on Chemical Safety (IPCS) to determine the sensitivity, efficiency and reliability of the Vicia faba root tip meristem chromosomal aberration assay using a standardized protocol. The six laboratories that participated in this study were located in the Slovak Republic, India, Japan, Poland, Sweden and the USA. All laboratories adhered to a standardized protocol for the Vicia faba chromosomal aberration assay. Four coded chemicals, azidoglycerol (AG), N-methyl-N-nitrosourea (MNU), sodium azide (NaN3) and maleic hydrazide (MH) were tested with the Vicia faba chromosomal aberration assay. Of the four chemicals, three (MH, AG and MNU) were found to be clastogenic and gave a concentration related response. However, the results of NaN3 were equivocal which might be explained by the stability of NaN3. The conclusions from this study suggest that the Vicia faba chromosomal aberration bioassay is an efficient and reliable short-term bioassay for the rapid screening of chemicals for clastogenicity.

Effects of epidural anesthesia on the cardiovascular response to a rapid increase in isoflurane concentration.

STUDY OBJECTIVE: To compare circulatory variables to an abrupt increase in isoflurance concentration via mask in patients who received either upper thoracic or lumbar epidural anesthesia, or neither. DESIGN: Prospective study. SETTING: Operating room at a university hospital. PATIENTS: 45 ASA physical status I female patients scheduled for elective surgeries with general anesthesia. INTERVENTIONS: Patients received thoracic (TEA group) or lumbar (LEA group) epidural anesthesia, or neither (control group) (n = 15 per group). An epidural catheter was inserted through the T1-T2 intervertebral space in the TEA group or L2-L3 in the LEA group, and 10 mL of 2% lidocaine without epinephrine was injected. Two minutes after induction of anesthesia with thiamylal, the inspired isoflurane concentration was rapidly increased from 0.5% to 5% and maintained for 5 minutes. MEASUREMENTS AND MAIN RESULTS: Heart rate and mean arterial pressure (MAP) were measured every minute. Mean analgesic levels obtained by epidural block were C4-T6 and T10-S1 in the TEA and LEA groups, respectively. Heart rate increased after the increase in isoflurane concentration in all groups, but increased significantly less in the TEA group than in the control or LEA groups (p < 0.05). Isoflurane also increased MAP in the control group throughout the 5-minute period, but only at the first minute of inhalation in the TEA and LEA groups. The increases in MAP in the TEA and LEA groups were significantly less than that in the control group (p < 0.05). CONCLUSION: Epidural anesthesia can blunt circulatory responses to a sudden increase in isoflurane concentration.

The effect of propofol and thiamylal on hypertensive responses to a rapid increase in isoflurane concentration.

STUDY OBJECTIVE: To compare the effects of propofol and thiamylal on the hyperdynamic circulatory response caused by a rapid increase in isoflurane concentration. DESIGN: Prospective, randomized, double-blind study. SETTING: Operating rooms of a university hospital. PATIENTS: 30 ASA physical status I adult patients scheduled for elective surgery with general anesthesia. INTERVENTIONS: Patients were anesthetized with either propofol 2 mg/kg (propofol group, n = 15) or thiamylal 4 mg/kg (thiamylal group, n = 15). Two minutes after anesthesia induction, the inspired isoflurane concentration was rapidly increased from 0.5% to 5% and maintained for 5 minutes. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure significantly increased after the increase in isoflurane concentration in the thiamylal group, but it did not change in the propofol group. The isoflurane-induced increase in rate-pressure product was significantly greater in the thiamylal group than in the propofol group. CONCLUSION: Propofol induction of anesthesia more effectively attenuates the circulatory responses to a sudden increase in isoflurane concentration than does thiamylal.

[Usefulness of electroencephalogram and transcranial Doppler sonography for brain function monitoring during selective cerebral perfusion].

It is well known that neurologic complications greatly affect the postoperative mortality of patients with aortic arch aneurysm. Selective cerebral perfusion (SCP) has been reported to be useful in maintaining cerebral circulation during aortic arch surgery. However, there has been no appropriate method to evaluate brain function during SCP. The purpose of this study was to introduce two new devices, the Lifescan electroencephalogram (EEG) monitor (Neurometrics) and the TC2-64 (EME) transcranial Doppler sonography (TCD), both used for monitoring brain function during SCP in patients undergoing aortic arch surgery. The Lifescan performs aperiodic analysis, and maps each waveform in relation to its frequency, amplitude, and time of occurrence rather than averaging a large number of waveforms over a given period. The Lifescan shows 80% of the whole amplitude of each wave as the activity edge (AE). The flow velocity of the middle cerebral artery was measured by TCD during SCP. With a decrease in body temperature, the EEG and AE gradually showed a trend toward a slower wave and lower amplitude. When circulatory arrest occurred prior to SCP, EEG and AE rapidly showed burst suppression, which was restored after the introduction of SCP. TCD could measure the flow velocity of the left middle cerebral artery even during cardiopulmonary bypass. The flow velocity disappeared during circulatory arrest and was restored after the induction of SCP. It is concluded that the adoption of EEG and TCD is useful in determining the intraoperative cerebral function during SCP.

[A case of acute exacerbation of idiopathic interstitial pneumonia after pneumonectomy].

A 52-year-old male was scheduled for right upper lobectomy due to lung cancer. The patient was diagnosed as having stable idiopathic interstitial pneumonia (IIP) based on preoperative lung biopsy, physical examination and laboratory data. He received prophylactic steroids to prevent an acute exacerbation of IIP. However, he fell into severe hypoxia 5 days after operation, and died of respiratory failure 43 days after operation. It must be born in mind that the patients with IIP may suffer exacerbation even if their lungs have been diagnosed as in stable stage. Prophylactic use of steroids may cause a deterioration in IIP due to delayed healing and infection.

[The effects of spinal anesthesia on liver blood flow measured by the ICG clearance meter].

ICG (indocyanine green) clearance meter is a new equipment that can measure the plasma disappearance of ICG through a photopiece attached to the tip of the finger. In this study we evaluated the effects of spinal anesthesia on liver blood flow using this method in 12 adult patients who were scheduled for elective surgery under spinal anesthesia. ICG clearance was read from an ICG clearance meter RK-1000 (Sumitomo Electric) following intravenous administration of ICG (0.5 mg.kg-1). The data are shown as the plasma disappearance rate (K) and the 15-minute retention rate (R15). The measurements were performed prior to spinal anesthesia and when the sensory level of anesthesia reached Th5. Spinal anesthesia was performed with tetracaine (12-15 mg). Heart rate, arterial blood pressure, and cardiac output (measured by NCCOM) were recorded simultaneously. Mean arterial pressure, heart rate and ICG clearance decreased significantly but cardiac index was unchanged. Our results suggest that high spinal anesthesia causes circulatory disturbance of the liver, and that this is probably followed by a drop in arterial blood pressure.

[Cardiopulmonary resuscitation with cardiopulmonary bypass for intraoperative cardiac arrest].

A 67-year-old man was scheduled for left upper lobectomy under epidural and general anesthesia. About 1 hour after the beginning of operation, he developed cardiac arrest due to sudden massive bleeding from the pulmonary artery. In spite of open chest cardiac massage and intravenous administration of epinephrine, we could not resuscitate him successfully. More than 30 minutes after the cardiac arrest, cardiopulmonary bypass (CPB) was started and mean arterial blood pressure was maintained at 50-60 mmHg. His pulmonary artery was repaired under CPB. One hour after CPB, the weaning from artificial circulation was attempted and the spontaneous beating was observed. However, he developed low cardiac output syndrome due to long time ischemia resulting in hemorrhagic infarction. Therefore, the intra-aortic balloon pumping was started and his hemodynamics was immediately restored. We presume that CPB is useful for intraoperative resuscitation and this gives us new application of advanced life support for the patient in whom the conventional technique is ineffective.