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Objective: To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis. Methods: In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed. Results: The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 28.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome. Conclusions: Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

Background: Primary localized cutaneous amyloidosis (PLCA) is a chronic pruritic skin disorder. The genetic basis of familial (f)PLCA involves mutations in the oncostatin M receptor (OSMR) and interleukin-31 receptor A (IL31RA) genes, but the disease pathophysiology is not fully understood., Aim: To investigate the OSMR mutation spectrum in patients with sporadic (s)PLCA/fPLCA, lichen/macular PLCA in mainland China., Methods: This study was carried out on 64 patients with sPLCA, along with 36 with fPLCA and 10 unaffected individuals collected from 23 unrelated Chinese families. Genomic DNA was extracted from peripheral blood samples. Mutation screening of 17 OSMR exons was performed by Sanger sequencing., Results: PLCA lesions are typically localized to the shins, forearm and back. Sequence analysis of OSMR exons demonstrated that the OSMR missense mutation rate in patients with fPLCA (63.89%) was significantly higher than that in patients with sPLCA (34.38%). The male/female ratio of patients carrying a homozygous OSMR mutation (0.29) was significantly lower than that of patients carrying a heterozygous OSMR mutation (1.08; P < 0.05) and of patients with wildtype OSMR (1.75; P < 0.01). Age of onset of PLCA with OSMR homozygous mutation (median age 20 years) was earlier than that of PLCA with OSMR heterozygous mutation (median age 32 years; P < 0.01) or PLCA with wildtype genotype (median age 32 years; P < 0.01)., Conclusion: The present data indicate OSMR mutations as not only the main cause of fPLCA, but also the potential source of the pathogenesis of sPLCA, although the exact molecular mechanism remains unknown., (© 2019 British Association of Dermatologists.)

The tensile plastic deformation of dendrite-reinforced Ti-based metallic glass composites (MGCs) was investigated. It was found that there is a critical normalized strain-hardening rate (NSHR) that determines the plastic stability of MGCs: if the NSHR is larger than the critical value, the plastic deformation of the MGCs will be stable, i.e. the necking and strain localization can be effectively suppressed, resulting in homogeneous plastic elongation. In addition, dendrite-reinforce MGCs are verified as being intrinsically ductile, and can be used as good coatings for improving the surface properties of pure titanium or titanium alloys. These findings are helpful in designing, producing, and using MGCs with improved performance properties., Competing Interests: The authors declare no competing financial interests.

Objective: To analyze the clinical characteristics and treatment outcome of children with multi-system Langerhans cell histiocytosis (MS-LCH)., Method: From January 2007 to December 2013, newly diagnosed patients with histopathologically-confirmed MS-LCH were enrolled in this retrospective study. All patients were treated on the Shanghai Children's Medical Center LCH protocol (LCH-Ⅱ modified protocol). Survival was determined using the Kaplan-Meier method with differences between different groups compared using the Log-Rank test. Prognostic relevance of different parameters were analyzed by Cox proportional hazard model., Result: Of the 131 patients (86 boys and 45 girls), the median age was 3 years (range 3 months to 14 years). Rapid response at week 6 was achieved in 79% (104/131) evaluable patients and 74% patients (48/65) with risk organ involvement. The 3-year event free survival (EFS) and 3-year overall survival (OS) for all cases were (62±5)% and (82±4)%. The 3-year OS was significantly different between age at diagnosis ≤2 years and >2 years group.The 3-year OS was also significantly different between patients with and without risk organ involvement.The 3-year OS of patients who had rapid response at week 6 was significantly higher than that of those without rapid response (χ(2) =12.600, 11.583, 38.711; P=0.000, 0.001, 0.000). Cox regression analysis showed that risk organ involvement and poor response at week 6 were the most important prognostic factors for patients with MS-LCH (OR=12.352, 14.356; P=0.001, 0.000). However, age was not the independent prognostic risk factor (OR=1.013, P=0.207). There were 36 patients (28%, 36/131) who experienced disease progression or relapse. The time to disease progression or relapse ranged from 1 to 25 months from the initial diagnosis (median 11 months). Significantly lower OS (18±3)% was observed in 20 patients with risk organ involvement at progression or relapse. Patients with poor response at week 6, younger age or risk organ involvement at diagnosis was associated with disease progression/relapse (χ(2)=15.747, 7.289, Z=3.865; P=0.000, 0.007, 0.000)., Conclusion: Risk organ involvement and poor response at week 6 are the strongest prognostic factors for patients with MS-LCH. Second initial treatment for patients with poor response at week 6 and effective salvage therapy need to be taken into account in our future studies.

Objective: To implore the effect of continuous positive airway pressure (CPAP) therapy on dizziness patients and its mechanism. Method: Seventy-five dizziness patients were enrolled. All patients accepted polysomnographic test, dizziness handicap inventory, Pitsburgh sleep quality index and Epworth sleepiness scale before and after CPAP therapy. Patients were divided into two groups according to a polysomnographic test: OSAHS group (AHI≥15) and without OSAHS group (AHI<15); divided into three groups according to dizziness handicap inventory score: mild dizziness group (00.05), but CPAP therapy could ameliorate sleep disorder of the OSAHS group. ③Different levels of dizziness had no impact on improving DHI during CPAP therapy. However, the effect on sleep improvement decreased when patients had heavier dizziness. ④Treating by CPAP after three months could significantly improve patients dizziness ( P <0.01). ⑤The dizziness of the patients in younger old group and old group have significant improvement after CPAP therapy ( P <0.01). However, only younger old group has better sleep. Conclusion: CPAP therapy could dramatically improve dizziness in patients with sleep disorders., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

The plastic flow of bulk metallic glasses (BMGs) is characterized by intermittent bursts of avalanches, and this trend results in disastrous failures of BMGs. In the present work, a double-side-notched BMG specimen is designed, which exhibits chaotic plastic flows consisting of several catastrophic avalanches under the applied loading. The disastrous shear avalanches have, then, been delayed by forming a stable plastic-flow stage in the specimens with tailored distances between the bottoms of the notches, where the distribution of a complex stress field is acquired. Differing from the conventional compressive testing results, such a delaying process is independent of loading rate. The statistical analysis shows that in the specimens with delayed catastrophic failures, the plastic flow can evolve to a critical dynamics, making the catastrophic failure more predictable than the ones with chaotic plastic flows. The findings are of significance in understanding the plastic-flow mechanisms in BMGs and controlling the avalanches in relating solids.

Cellular bulk metallic glasses (BMGs) have exhibited excellent energy-absorption performance by inheriting superior strength from the parent BMGs. However, how to achieve high energy absorption capacity in cellular BMGs is vital but mysterious. In this work, using step-by-step observations of the deformation evolution of a series of cellular BMGs, the underlying mechanisms for the remarkable energy absorption capacity have been investigated by studying two influencing key factors: the peak stress and the decay of the peak stress during the plastic-flow plateau stages. An analytical model of the peak stress has been proposed, and the predicted results agree well with the experimental data. The decay of the peak stress has been attributed to the geometry change of the macroscopic cells, the formation of shear bands in the middle of the struts, and the "work-softening" nature of BMGs. The influencing factors such as the effect of the strut thickness and the number of unit cells have also been investigated and discussed. Strategies for achieving higher energy absorption capacity in cellular BMGs have been proposed.

Buffalo grass [Buchloe dactyloides (Nutt.) Engelm.] plants can be either male, female, or hermaphrodite (monoecious). As there is no morphological difference in the early vegetative growth of these three classes of plants, it is worthwhile to use molecular biological methods to attempt to identify the sex of a plant at this early growth period. In this study, we identified 23 plants that had a stable sex for over at least 3 years. Of these, 9 were male plants, 10 were female plants, and 4 were hermaphrodites. Screening of 300 RAPD primers identified a primer, namely S211 (5'-ttccccgcga-3'), which is capable of identifying male plants. The specific fragment was cloned, sequenced, and submitted to the GenBank database (accession No. JN982469). When used to identify the sex of 188 plants during their first growing season, the S211 primer correctly identified 85.8% of all male plants. Our results showed that the S211 primer can identify the male, and in doing so, it facilitates buffalo grass breeding work.

The Daya Bay Reactor Neutrino Experiment has measured a nonzero value for the neutrino mixing angle θ(13) with a significance of 5.2 standard deviations. Antineutrinos from six 2.9 GWth reactors were detected in six antineutrino detectors deployed in two near (flux-weighted baseline 470 m and 576 m) and one far (1648 m) underground experimental halls. With a 43,000 ton-GWth-day live-time exposure in 55 days, 10,416 (80,376) electron-antineutrino candidates were detected at the far hall (near halls). The ratio of the observed to expected number of antineutrinos at the far hall is R=0.940±0.011(stat.)±0.004(syst.). A rate-only analysis finds sin(2)2θ(13)=0.092±0.016(stat.)±0.005(syst.) in a three-neutrino framework.

Bulk metallic glasses are brittle and fail with no plastic strain at room temperature once shear bands propagate. How do metallic glasses deform when the size is less than that of shear bands? Here we show that Al90Fe5Ce5 metallic glass with a size <20  nm can be extremely elongated to ∼200%. Remarkably, even an atomic chain was formed after sample necking, which was never observed in metallic glasses. The unexpected ductility may originate from the fast surface diffusion and the absence of shear band formation, and may guide the development of ductile metallic glasses for engineering applications.

Objective: To identify the molecular and physiologic abnormality in familial myotonia with cold sensitivity, hypertrophy, and no weakness., Background: Sodium channel mutations were previously identified as the cause of several allelic disorders with varying combinations of myotonia and periodic paralysis. A three-generation family with dominant myotonia aggravated by cooling, but no weakness, was screened for mutations in the skeletal muscle sodium channel alpha-subunit gene (SCN4A)., Methods: Single-strand conformation polymorphism was used to screen all 24 exons of SCN4A and abnormal conformers were sequenced to confirm the presence of mutations. The functional consequence of a SCN4A mutation was explored by recording sodium currents from human embryonic kidney cells transiently transfected with an expression construct that was mutated to reproduce the genetic defect., Results: A three-generation Italian family with myotonia is presented, in which a novel SCN4A mutation (leucine 266 substituted by valine, L266V) is identified. This change removes only a single methylene group from the 1,836-amino-acid protein, and is present in a region of the protein previously not known to be critical for channel function (domain I transmembrane segment 5). Electrophysiologic studies of the L266V mutation showed defects in fast inactivation, consistent with other disease-causing SCN4A mutations studied to date. Slow inactivation was not impaired., Conclusions: This novel mutation of the sodium channel indicates that a single carbon change in a transmembrane alpha-helix of domain I can alter channel inactivation and cause cold-sensitive myotonia.

The most common neurologic complication in patients with acquired immunodeficiency syndrome (AIDS) is cerebral toxoplasmosis. Patients with cerebral toxoplasmosis have characteristic findings on clinical examination and neuroimaging. They require prolonged treatment and have a considerable mortality rate. We report a case of cerebral toxoplasmosis in a foreign laborer with AIDS, in whom a human immunodeficiency virus (HIV) screening test failed to detect-HIV infection. The patient, a 23-year-old man from Thailand, presented in a confused state 2 weeks after his arrival in Taiwan. Computed tomography showed a mass effect, and magnetic resonance imaging showed multiple ring-enhanced lesions in the cerebrum. Serologic tests were positive for anti-HIV antibody and also showed high anti-Toxoplasma immunoglobulin G titers. Although symptomatic treatment was initiated, the patient's condition deteriorated rapidly and he died of multiple organ failure due to brain stem herniation a few days after admission. As the number of foreign laborers working in Taiwan has increased dramatically in recent years, the issues raised by this case are the efficacy of our screening protocols for foreign laborers and the increased occupational hazards encountered by medical personnel in Taiwan.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is a protein expressed consistently in EBV-infected cells and EBV-associated malignant tissues. A panel of monoclonal antibodies (MAbs) was generated against the C terminus of EBNA-1 and evaluated for the detection of EBNA-1 in different cell lines. The epitopes recognized were mapped. Since sequence variations of EBNA-1 have been reported in nasopharyngeal carcinoma (NPC) tissues and in infected healthy individuals, the ability of these MAbs to recognize a recombinant protein derived from an NPC biopsy was also analysed. MAb 4H11 appeared to react with EBNA-1 sequences from different sources, whereas MAbs 5C11, 5F12 and 8F6 failed to recognize a recombinant EBNA-1 protein cloned from an NPC patient. Using different recombinant EBNA-1 fragments in an immunoblot format, this study demonstrates that the domain bounded by amino acids 408 and 498 is very immunogenic in mice in that epitopes in this region are recognized by various MAbs. Amino acid sequences of EBNA-1 were also deduced from nucleotide sequences amplified from three Burkitt's lymphoma cell lines, two spontaneous lymphoblastoid cell lines, two NPC biopsies and one NPC hybrid cell line, NPC-KT, and compared to the sequence from B95-8. The amino acid sequence of EBNA-1 in Akata is almost identical to that in an NPC biopsy, except for amino acid 585. The results of this study indicate that the immunogenic epitopes of EBNA-1 are highly variable.

Random amplified polymorphic DNA (RAPD) bands that distinguish Meloidogyne hapla and M. chitwoodi from each other, and from other root-knot nematode species, were identified using a series of random octamer primers. The species-specific amplified DNA fragments were cloned and sequenced, and then the sequences were used to design 20-mer primer pairs that specifically amplified a DNA fragment from each species. Using the primer pairs, successful amplifications from single juveniles were readily attained. A mixture of four primers in a single PCR reaction mixture was shown to identify single juveniles of M. hapla and M. chitwoodi. To confirm specificity, the primers were used to amplify DNA from several isolates of M. hapla that originated from different crops and locations in North America and also from isolates of M. chitwoodi that differed in host range. In characterizing the M. hapla isolates, it was noted that there was a mitochondrial DNA polymorphism among isolates for cleavage by the restriction endonuclease DraI.

Study Objectives: To describe four patients having total anomalous pulmonary venous connection with an intrapulmonary vertical vein, rendering difficulty in diagnosis and surgery., Setting: a tertiary referral center., Patients and Methods: By reviewing medical records, 4 of 25 patients with right atrial isomerism and total anomalous pulmonary venous connection were identified to have an intrapulmonary vertical vein. All four patients underwent echocardiography, catheterization, and angiography. One underwent MRI. Two underwent open-heart surgery and one received a modified Blalock-Taussig shunt., Results: Right atrial isomerism was present in all four patients. On chest x-ray films, an abnormal shadow resembling scimitar syndrome was seen in two patients. Imaging the vertical vein was unsuccessful with an echocardiogram in all four patients. The intrapulmonary course of the vertical vein was depicted with a pulmonary venogram in two patients and with magnetic resonance in one patient. The intrapulmonary segment remained undetected until autopsy in one patient. All four patients died. At autopsy, the pulmonary venous confluence was hypoplastic in all four hearts. The vertical vein was buried in pulmonary parenchyma and drained to superior vena cava with significant obstruction., Conclusion: In the presence of right atrial isomerism and total anomalous pulmonary venous connection, there may be an intrapulmonary pulmonary venous connection that may be obstructed. Anastomosing the pulmonary venous confluence to the atrium may be difficult because of hypoplasia of the pulmonary venous confluence.

Objective: To investigate the effects of 3-week versus 4-week administration of benzathine penicillin G (BPG) on the incidence of Group A streptococcal infections and the recurrences of rheumatic fever (RF)., Study Design: We started, in 1979, randomly allocating all patients with RF to a 3-week or 4-week BPG prophylaxis program. They were examined at the RF clinic, every 3 to 6 months, and at any time they did not feel well. During 1979 to 1989, throat cultures and sera for antistreptolysin O and streptozyme titers were obtained at each clinic visit. Chest radiographs, electrocardiogram, color Doppler echocardiograms, and acute phase reactants were obtained., Subjects: Two hundred forty-nine patients fulfilled the revised Jones criteria and were followed until December 1991: 124 in the 3-week and 125 in the 4-week program. Their age, sex, weight, percentage with history of RF, severity of cardiac involvement, follow-up duration, and compliance to program were comparable. Eight hundred eighty throat cultures were collected in the 3-week program and 770 were collected in the 4-week program. Six hundred sixteen and 627 sera were determined in each program for antistreptolysin O, and 582 and 592 sera for streptozyme titers., Results: True streptococcal infections occurred in both programs: 39 infections in the 3-week program, and 59 infections in the 4-week program (7.5 vs 12.7 per 100 patient-years). Four infections with no antibody response occurred in the 3-week program, and three such infections in the 4-week program. Nine RF recurrences occurred in 8 patients in the 3-week program, and 16 recurrences in 16 patients in the 4-week program. Prophylaxis failure occurred in 2 of 124 patients in the 3-week program, and in 10 of 125 patients in the 4-week program (0.25 vs 1.29 per 100 patient-years). The overall recurrences/infections rate in each program was comparable, 13.6% vs 15.5%, but the recurrences/ infections rate due to prophylaxis failure was higher in the 4-week program than in the 3-week program, 3.0% versus 9.7%., Conclusions: This 12-year prospective and controlled study documented that streptococcal infections and RF recurrences occurred more often in the 4-week program than in the 3-week program. The risk of prophylaxis failure was fivefold greater in the 4-week program than in the 3-week program.

Lymphangioma confined exclusively to the mediastinum occurs rarely in patients under 2 years of age. A 17-month-old girl presented with recurrent respiratory symptoms and signs. Chest radiographs taken at 9 and 17 months of age showed a large mediastinal mass, which had increased in size during the interval. Sonography revealed the mass to be cystic and multiloculated. Magnetic resonance imaging demonstrated a heterogeneous mass lying in the anterior and superior mediastinum and enveloping the great vessels. The child underwent a left thoracotomy and the tumor was almost completely removed. The pathologic diagnosis was cavernous lymphangioma. The postoperative course was uneventful. Lymphangioma, though rare, should be considered in the differential list of mediastinal tumors and cysts in infants.

Objective: To compare the efficacy of injections of 1.2 million units of benzathine penicillin G given every 3 weeks versus every 4 weeks for secondary prevention of rheumatic fever, based on the long-term outcome of patients receiving such prophylaxis., Methods: A total of 249 consecutive patients with rheumatic fever, randomly assigned to either a 3-week or a 4-week regimen, were examined every 3 to 6 months, and followed for 794 and 775 patient-years, respectively., Results: Compliance with each regimen was comparable: 83 (66.9%) of 124 patients in the 3-week group versus 92 (73.6%) of 125 patients in the 4-week group stayed in the program (p > 0.05). Streptococcal infections occurred less frequently in those receiving the 3-week regimen: 7.5 versus 12.6 per 100 patient-years (p < 0.01). Prophylaxis failed in 2 patients receiving the 3-week regimen and in 10 receiving the 4-week regimen (0.25 and 1.29 per 100 patient-years respectively; p = 0.015). Serum penicillin levels were adequate (> or = 0.02 micrograms/ml) in 100 (56%) of 179 samples obtained 21 days after penicillin injection in the 3-week regimen, and in 51 (33%) of 155 samples obtained 28 days after injection in the 4-week regimen (p < 0.01). Of 71 patients with mitral regurgitation in the 3-week regimen, 47 (66%) no longer had the murmur; of 87 patients in the 4-week regimen, 40 (46%) no longer had the murmur (p < 0.05)., Conclusions: This 12-year controlled study indicates that the outcome of patients with rheumatic fever is better with a 3-week than with a 4-week penicillin prophylaxis regimen. Greater emphasis and more widespread use of the 3-week regimen should be recommended.

A PCR-based codominant marker has been developed which is tightly linked to Mi, a dominant genetic locus in tomato that confers resistance to several species of root-knot nematode. DNA from tomato lines differing in nematode resistance was screened for random amplified polymorphic DNA markers linked to Mi using decamer primers. Several markers were identified. One amplified product, REX-1, obtained using a pair of decamer primers, was present as a dominant marker in all nematode-resistant tomato lines tested. REX-1 was cloned and the DNA sequences of its ends were determined and used to develop 20-mer primers. PCR amplification with the 20-mer primers produced a single amplified band in both susceptible and resistant tomato lines. The amplified bands from susceptible and resistant lines were distinguishable after cleavage with the restriction enzyme Taq I. The linkage of REX-1 to Mi was verified in an F2 population. This marker is more tightly linked to Mi than is Aps-1, the currently-used isozyme marker, and allows screening of germplasm where the linkage between Mi and Aps-1 has been lost. Homozygous and heterozygous individuals can be distinguished and the procedure can be used for rapid, routine screening. The strategy used to obtain REX-1 is applicable to obtaining tightly-linked markers to other genetic loci. Such markers would allow rapid, concurrent screening for the segregation of several loci of interest.

In an attempt to understand which amino acids in the membrane anchor of cytochrome b5 might be determinants of its ability to support the cytochrome P450-catalyzed oxidation of selected substrates, the synthetic rat cytochrome b5 gene has been mutated by site-directed mutagenesis. The mutant proteins have been expressed in Saccharomyces cerevisiae, purified and assayed for their ability to support the cytochrome P450-catalyzed metabolism of the cytochrome b5 requiring substrate methoxyflurane (G. Vergères and L. Waskell, 1992, J. Biol. Chem. 267, 12583-12591). The rate of reduction of the cytochromes b5 by cytochrome P450 reductase has been examined by stopped-flow spectrophotometry to determine whether an altered rate of reduction of cytochrome b5 could explain the observed activity of cytochrome b5 in the purified reconstituted mixed-function oxidase system. A mutant in which the 22-amino-acid membrane anchor was replaced by a sequence of 22 leucines was unable to support methoxyflurane metabolism in the reconstituted system and was reduced by cytochrome P450 reductase at a rate (k = 4.5 x 10(-3) s-1) slow enough to explain this finding. Comparison of the rate of reduction of this mutant cytochrome b5 in 0.025% Tergitol and 40 microM dilauroylphosphatidylcholine suggests that this slow rate of reduction may be explained partially by aggregation of the polyleucine protein. The Pro115Stop mutant protein, which has been truncated by 19 amino acids in its COOH terminus resulting in a protein with one-half of the putative membrane anchor, supports methoxyflurane oxidation at 12-20% of the rate of the wild type protein. In addition it is reduced by cytochrome P450 reductase at a rate which should be capable of supporting a normal rate of production formation. The fact that the Pro115Stop mutant can be reduced at a rate capable of supporting a normal rate of methoxyflurane oxidation but in fact only supports methoxyflurane oxidation at 30% of the normal rate suggests that the mutant protein is deficient in its interactions with cytochrome P450. The mutant proteins, Pro115Ala and Ala116Pro, behaved essentially as did the wild type protein demonstrating that the presence (Pro115Ala) or absence (Ala116Pro) of an alpha helix in the middle of the putative membrane-binding domain of cytochrome b5 was not a determinant of the interaction of cytochrome b5 with cytochrome P450 reductase and cytochrome P450.(ABSTRACT TRUNCATED AT 400 WORDS)

Tyrosine 74, which is part of a hydrophobic patch on the surface of rat cytochrome b5, also forms van der Waals contacts with the heme prosthetic group of the protein. In addition it is a member of an aromatic network of amino acids which includes Phe-35 and the axial ligand, His-39. Because of its strategic location in the protein, the Tyr-74 residue was mutated to a lysine in order to investigate how it affected the interaction of heme with the protein and whether it might be an alternative binding site and an electron transfer path which cytochrome b5 would use with its amphipathic electron transfer partners cytochrome P450 and its corresponding NADPH cytochrome P450 reductase. The mutant protein receives electrons from NADPH cytochrome P450 reductase and provides the second electron to cytochrome P450 to catalyze the metabolism of methoxyflurane, a substrate which requires cytochrome b5 for its metabolism, at the same rate as the wild type protein. The Tyr74Lys mutant exhibits a normal redox potential and spectroscopic properties identical to those of the wild type protein. Under equilibrium conditions in the presence of urea, heme dissociation and denaturation occur simultaneously with a free energy of 3.4 kcal/mol. The free energy of activation of heme dissociation from the wild type protein is 22.7 kcal/mol. The free energy and free energy of activation of the Tyr74Lys mutant are 1.4 kcal/mol less than the wild type values, indicating that the mutant binds heme 10-fold less tightly and dissociates heme 10 times faster than the wild type protein. Heme transfer experiments demonstrate that heme spontaneously dissociates 6 times faster from the mutant than the wild type protein (t1/2 = 1.9 and 11.5 h, respectively). The most likely conformation of Lys-74 in the mutant protein was determined by calculating the Lys-74 rotamer with the minimal energy using an energy-based conformation search method. This conformation was subsequently modeled on the computer graphics. Not unexpectedly, the side chain of Lys-74 is shifted toward the surface of the protein to allow solvation of the positive charge on the epsilon amino group of lysine. This movement of the lysine residue results in the formation of a cavity on the surface of the cytochrome b5 molecule, which exposes a heme methyl and vinyl group to aqueous solvent thereby destabilizing the binding between the protein and its hydrophobic prosthetic heme group.

In order to elucidate the effects of corticosteroids on fetal hearts during midtrimester, pregnant rats were injected with a daily dose of betamethasone (1 mg/kg) from the 12th day through the 17th day of pregnancy. The fetal cardiovascular and pulmonary systems were studied on the 21st day of pregnancy (term). The treated fetuses showed the following signs of hydrops fetalis: retarded growth, pale, edematous skin, and decreased movement. The thymus and lung displayed prominent hypoplasia. The morphometry of the treated fetuses revealed: decreased right ventricle mass by 37% and decreased left ventricle mass by 29%. We concluded betamethasone had a significant effect on the developing fetal cardiovascular system, inducing hydrops fetalis. Additionally, beta-methasone caused hypoplasia of the thymus and lung.

With the advent of echocardiography, total anomalous pulmonary venous connection (TAPVC) can be readily diagnosed without much difficulty. However, noninvasive detection of the presence of pulmonary venous obstruction in TAPVC remains a difficult issue. During a 5.5-year period, 42 patients were found to have TAPVC by catheterization, surgery, and/or autopsy: 17 had supracardiac drainage, 13 paracardiac drainage, nine infracardiac drainage, and three mixed drainage. Obstruction to pulmonary venous drainage was found in 24 patients (57%). Patients with right isomerism tended to have a higher incidence of pulmonary venous obstruction than those with the usual atrial arrangement (80% vs. 44%, p < 0.05). Color Doppler combined with cross-sectional echocardiography provided accurate delineation of drainage sites in 93% cases (39 of 42). Among the 39 cases with correct echocardiographic delineation of the drainage site, obstruction was detected by echocardiography in 22 cases with a sensitivity of 100% (22 of 22) and a specificity of 85% (17 of 20). Therefore, complete echocardiography, including cross-sectional images and color Doppler proved to be a reliable tool in the detection of drainage sites and pulmonary venous obstruction in TAPVC.

Heterodera schachtii and H. cruciferae are sympatric in California and frequently occur in the same field upon the same host. We have investigated the use of polymerase chain reaction (PCR) amplification of nematode DNA sequences to differentiate H. schachtii and H. cruciferae and to assess genetic variability within each species. Single, random oligodeoxyribonucleotide primers were used to generate PCR-amplified fragments, termed RAPD (random amplified polymorphic DNA) markers, from genomic DNA of each species. Each of 19 different random primers yielded from 2 to 12 fragments whose size ranged from 200 to 1,500 bp. Reproducible differences in fragment patterns allowed differentiation of the two species with each primer. Similarities and differences among six different geographic populations of H. schachtii were detected. The potential application of RAPD analysis to relationships among nematode populations was assessed through cluster analysis of these six different populations, with 78 scorable markers from 10 different random primers. DNA from single cysts was successfully amplified, and genetic variability was revealed within geographic populations. The use of RAPD markers to assess genetic variability is a simple, reproducible technique that does not require radioisotopes. This powerful new technique can be used as a diagnostic tool and should have broad application in nematology.

This is a case of neonatal tuberous sclerosis associated with cardiac rhabdomyoma and manifested by fetal cardiac arrhythmia-bradycardia. The prenatal echocardiography showed multiple cardiac tumors which occupied the left and right ventricles. The largest one measured 5.2 cm in diameter. It was found to be 4.5 x 4.1 x 3.5 cm in size at autopsy. A postnatal cranial echogram showed multiple subependymal nodules. The patient expired after 7 hours of life. The autopsy findings confirmed the diagnosis. The mother of the patient had adenoma seb'aceum on the face and an ungual fibroma on the left little finger. Cranial computerized tomography revealed a small calcified tubercle.

We studied the surgical anatomy of 14 hearts with isolated ventricular septal defects and the precise relationship of the atrioventricular conduction axis to their rims. Ten of these hearts were investigated by serial sectioning of their atrioventricular conduction systems. All defects were divided into perimembranous or muscular types as previously suggested by Soto et al. The distinguishing feature of the perimembranous defect was that the central fibrous body formed part of its rim, this fact indicated that the conduction tissue was always to the right of the surgeon's hand when the defect was approached through the right atrium. The precise relationship of the ventricular conduction tissues varied depending upon whether the perimembranous defect extended into the inlet, trabecular or outlet components of the muscular septum. The nonbranching bundle was closest to the septal rim in the inlet and trabecular defects, frequently being buried in a remnant of the interventricular membranous septum. However, in these defects the nonbranching and branching bundles were also found in other specimens remote from the septal crest, yet were carried on the left ventricular aspect of the septum. In perimembranous inlet defects, the penetrating bundle detoured deep into the central fibrous body. In perimembranous outlet defects, the conduction tissues were remote from the septal crest. In contrast to these findings, the conduction tissues were away from the edges of the defects in trabecular and outlet muscular defects. In conclusion, in the perimembranous inlet defect, the placement of the sutures on the annulus of tricuspid valve should be avoided in view of its abnormal long penetrating bundle.

A program to modify the prescribing of antilipemic agents by promoting the use of extended-release niacin tablets is described. Between December 1987 and August 1988, pharmacists at a 1188-bed Veterans Affairs medical center observed a large increase in the number of outpatient prescriptions for antilipemic agents. In an attempt to control costs, a program to promote the use of extended-release niacin tablets for treating hyperlipemia was conducted during August and September 1988. Various educational materials on niacin were distributed to physicians. A display on therapy of hyperlipemia was featured at the monthly drug fair, and articles on niacin were presented during a journal club meeting of ambulatory-care clinicians. Pharmacists succeeded in having extended-release niacin tablets placed on the formulary in September. Data on the number of prescriptions filled for antilipemic agents were collected before and after the niacin promotional program. The number of prescriptions filled for extended-release niacin 500-mg tablets increased steadily during a six-month study period after the program ended; the number of prescriptions filled for regular niacin decreased by 50%. As prescribing of extended-release niacin increased, prescribing of colestipol, gemfibrozil, and probucol declined. The promotional program was well received by most of the medical staff. A program of education and formulary management successfully changed physician prescribing habits for antilipemic agents.

To determine the most suitable vaccination schedule in developing countries, a study was conducted to reevaluate the immunogenicity of monovalent measles vaccine and trivalent measles-mumps-rubella vaccine at different ages. The success rate of measles vaccination was 84% at 9 months, 88% at 12 months and 100% at 15 months of age. Vaccination with measles vaccines at 9 and 15 months of age was also 96% immunogenic. Most vaccinees (16 of 17) not responding to the first measles vaccine before 1 year of age developed measles antibody with another shot of vaccine after 15 months of age. Trivalent measles-mumps-rubella vaccine worked well in children ages 14 to 18 months. Administering trivalent vaccine and hepatitis B vaccine concurrently at 1 year of age, rubella and mumps antibodies developed in more than 95% of vaccinees, while measles antibody was detected in 88%. Responses to hepatitis B vaccine in this situation were good; 89% of vaccinees developed antibody against hepatitis B surface antigen (greater than or equal to 10 mIU/ml) and the geometric mean titer was 362.49 mIU/ml. In summary vaccination twice at 9 and 15 months is effective and is a useful regimen in developing countries where measles is still endemic. Trivalent vaccine and hepatitis B vaccine will not interfere with each other when given together at 1 year of age.

A newborn with ambiguous external genitalia and the stigmata of Turner syndrome presented with the following features: short stature, hypertelorism, bilateral epicanthal folds, ptosis, low-set ears with prominent auricles, high-arched palate, low posterior hairline, webbed neck, broad and short chest, widely-spaced and hypoplastic nipples and clitoris-like phallus with hypospasdias. He also had patent ductus arteriosus, the secundum type of atrial septal defect and mitral stenosis. Chromosomes of peripheral blood showed mosaicism of cells with 45,XO/46,XY. An exploratory laparotomy was performed at five months of age. The right side ovotestis-like gonad was removed. The left side gonad in the scrotum was normal. No pathological gonadoblastoma was found.

In order to clarify cross-sectional morphology of tetralogy of Fallot in the fetus, 202 rat fetuses with tetralogy of Fallot induced by maternal administration of bis-diamine were studied using cesarean section, the whole body freezing method and by photographing cross sections of the fetal heart on a freezing microtome. Some characteristic features such as large subaortic ventricular septal defects, aortic overriding over the ventricular septum, aortomitral fibrous continuity, and narrow infundibulum and pulmonary valve were found. Moreover, three subtypes were noticed. In classic tetralogy of Fallot with stenotic infundibulum, the size of the pulmonary arteries was smaller in proportion to the infundibular stenosis. In the second type with absent infundibular septum and severe valvular pulmonary stenosis, the pulmonary arteries were most hypoplastic. In the third type with absent pulmonary valve, the pulmonary arteries were dilated forming aneurysms. In the last type only, ventricles were dilated and grossly hypertrophic.

A method is described for the quantitative analysis of thebaine from Papaver bracteatum, using a single high-pressure liquid chromatographic column. The procedure gives base-line separation of thebaine without the need for gradient elution equipment, and can be completed within 12 min. Thebaine isolated by this technique was shown to be pure, regardless of the age of plant or plant part from which it was obtained.

The fungicides benlate, maneb, and captan depressed plant growth, thebaine concentration, and thebaine yield per plant when administered chronically to Papaver bracteatum. The chronic administration of dicofol inhibited plant growth and thebaine yield per plant, but did not affect thebaine concentration. Malathion and pyrethrins had no adverse effects on either plant growth or thebaine content.