Delayed low density lipoprotein (LDL) catabolism despite a functional intact LDL-apolipoprotein B particle and LDL-receptor in a subject with clinical homozygous familial hypercholesterolemia

We identified a 38-yr-old male patient with the clinical expression of homozygous familial hypercholesterolemia presenting as severe coronary artery disease, tendon and skin xanthomas, arcus lipoides, and joint pain. The genetic trait seems to be autosomal recessive. Interestingly, serum concentrations of cholesterol responded well to diet and statins. We had no evidence of an abnormal low density lipoprotein (LDL)-apolipoprotein B (apoB) particle, which was isolated from the patient using the U937 proliferation assay as a functional test of the LDL-binding capacity. The apoB 3500 and apoB 3531 defects were ruled out by PCR. In addition, we found no evidence for a defect within the LDL-receptor by skin fibroblast analysis, linkage analysis, single-strand conformational polymorphism and Southern blot screening across the entire LDL-receptor gene. The in vivo kinetics of radioiodinated LDL-apoB were evaluated in the proband and three normal controls, subsequently. The LDL-apoB isolated from the patient showed a normal catabolism, confirming an intact LDL particle. In contrast the fractional catabolic rate (d-1) of autologous LDL in the subject and the normal controls revealed a remarkable delayed catabolism of the patient's LDL (0.15 vs. 0.33-0.43 d-1). In addition, the elevation of LDL-cholesterol in the patient resulted from an increased production rate with 22.8 mg/kg per day vs. 12.7-15.7 mg/kg per day. These data indicate that there is another catabolic defect beyond the apoB and LDL-receptor gene causing familial hypercholesterolemia.     

Thin-film inductive heads for perpendicular recording

A modified thin-film magnetic head for perpendicular recording in rigid disk drives with improved read/write characteristics, especially at high areal bit densities, is presented. The head on which the modified design is based is described. It combines the advantages of single-pole heads and thin-film heads, writing with the sharp field edge of the leading pole and reading like a thin-film head. To increase the writing efficiency and improve the yield, the sequence of magnetic layers in the head is changed; the second layer of the four-layer head is embedded in the substrate, where it can be placed much closer to the pole tip of the first layer. The improved write capability depends mainly on the position of the embedded layer. In addition, there results an improved magnetic flux guidance from the embedded layer into the pole tip layer, providing the potential for a significant improvement in fabrication yield. The embedded-layer approach also allows a further increase in areal density. The results of read/write tests and the write-wide and read-narrow characteristics are presented     

Inhibitory effects of sulfonated shale oils (ammonium bituminosulphonates, Ichthyols) on enzymes of polyenoic fatty acid metabolism

The two commercial pharmaceutical preparations of ammonium bituminosulphonates, Leukichthol and Dark Ichthyol, were shown to inhibit the formation of 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE) from external arachidonic acid by human polymorphonuclear leukocytes stimulated by ionophore A-23187 in a dose-dependent manner. Pure arachidonate 15-lipoxygenases from rabbit reticulocytes and soya beans, and the particulate prostaglandin endoperoxide synthase from sheep vesicular glands, were also inhibited. With the reticulocyte lipoxygenase, the Ichthyols suppressed the enzyme activity by two different mechanisms: (1) a prolongation of the lag period typical of lipoxygenase catalysis, and (2) by a lowering of the maximal enzymatic activity after the end of lag period. As expected, the first effect was reversed by the addition of the lipoxygenase product 13S-hydroperoxy-9Z,11E-octadecadienoic acid (13-HpODE). Ammonium bituminosulphonates are thus universal inhibitors of lipoxygenase activities, and the latter are of potential importance in inflammatory dermatoses.     

Production of 3R-hydroxy-polyenoic fatty acids by the yeast Dipodascopsis uninucleata

Various fatty acids were fed to the yeast Dipodascopsis uninucleata UOFS Y 128, and the extracted samples were analyzed for the accumulation of 3-hydroxy metabolites with the help of electron impact gas chromatography-mass spectrometry. Fatty acids containing a 5Z,8Z-diene system (5Z,8Z,11Z-eicosatrienoic, 5Z,8Z,11Z,14Z-eicosatetraenoic, and 5Z,8Z,11Z,14Z,17Z-eicosapentaenoic acids) yielded the corresponding 3-hydroxy-all-Z-eicosapolyenoic acids. Moreover, linoleic acid (9Z,12Z-octadecadienoic acid) and 11Z,14Z,17Z-eicosatrienoic acid were converted to the 3-hydroxylated metabolites of shorter chain length, e.g., 3-hydroxy-5Z,8Z-tetradecadienoic acid and 3-hydroxy-5Z,8Z,11Z-tetradecatrienoic acid, respectively. In contrast, no accumulation of a 3-hydroxy metabolite was observed with oleic acid (9Z-octadecenoic acid), linolelaidic acid (9E,12E-octadecadienoic acid), γ-linolenic acid (6Z,9Z,12Z-octadecatrienoic acid), and eicosanoic acid as substrate. These findings pinpoint that the 3-hydroxylation of a fatty acid in Dipodascopsis uninucleata requires a 5Z,8Z-diene system either directly or following initial incomplete β-oxidation. Following analysis of the enantiomer composition, the arachidonic acid metabolite was identified as 3R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid, which rules out a normal β-oxidation as biosynthetic route to this new class of oxylipins.     

Antimicrobial treatment of clinical mastitis in the eastern United States: The influence of dairy farmers' mastitis management and treatment behavior and attitudes

To assess both the behaviors and social variables related to antimicrobial therapy for clinical mastitis, we sent a survey to 1,700 dairy farms in Michigan, Pennsylvania, and Florida in January and February 2013. The survey included questions related to 7 major areas: sociodemographic and farm characteristics, milking proficiency, milking systems, cow environment, infected cow monitoring and treatment, farm labor, and attitudes toward mastitis and related antimicrobial use. The overall response rate was 41% (21% in Florida, 39% in Michigan, and 45% in Pennsylvania). Herd size ranged from 9 to 5,800 cows. Only a small proportion of herds frequently or always cultured milk samples for bacteriology from cows with a high somatic cell count (17%), cows with clinical mastitis (18%), or bulk tank milk (13%). Likewise, only 56% of herds frequently or always maintained records of all treated cows and 49% reviewed records before administering mastitis treatments. Multivariate analysis determined that use of treatment records was associated with increased likelihood of frequent use for both intramammary (IMA) and systemic (SYA) administration of antimicrobial drugs for therapy of clinical mastitis. As would be expected, use of natural (organic) therapies was associated with decreased use of IMA, as was the respondent being a member of an Amish community. Lower levels of education and the use of bacterins to control Staphylococcus aureus mastitis were also associated with decreased IMA, whereas increased use of IMA at dry off and the belief that “bad luck” plays a role in mastitis problems were associated with increased IMA. Use of an internal teat sealant, the respondent being the sole proprietor, being from Michigan, use of conductivity to measure subclinical mastitis, the respondent placing increasing importance on decreasing antibiotic residues in cull cows, and having financial incentives for employees linked to somatic cell count were associated with increased use of SYA for the treatment of clinical mastitis. Use of sand or mattresses for bedding were associated with decreased SYA. These findings highlight the need to improve the acceptance of practices that are consistent with prudent antimicrobial use for the treatment of clinical mastitis on dairy farms. Additionally, the willingness of dairy farmers to administer antimicrobial drugs for the treatment of clinical mastitis is associated with other mastitis-related practices and attitudes.     

Oxylipin formation in fungi: biotransformation of arachidonic acid to 3-hydroxy-5,8-tetradecadienoic acid by Mucor genevensis

STUDY OBJECTIVE: The objectives of the present study were to evaluate the importance of intrapulmonary lymph nodes (IPLNs) in the differential diagnosis of small pulmonary nodules and to review the CT findings of IPLNs. DESIGN: Retrospective analysis of patient records. SETTING: Chest Disease Research Institute Hospital, Kyoto University. PATIENTS: Between January 1991 and May 1996, we examined 26 patients with pulmonary nodular shadows smaller than 1 cm in diameter that could not be diagnosed before surgery. All patients (19 men, 7 women) underwent chest CT (28 to 72 years old; mean, 52.3 years). RESULTS: The pathologic diagnoses were IPLNs in 46.2% (12/26), pulmonary hamartoma in 23.1% (6/26), lung cancer in 11.5% (3/26), pulmonary tuberculoma in 11.5% (3/26), and metastatic lung tumor in 7.7% (2/26). IPLNs were located in the lower lobe in 72%. The characteristic CT findings of IPLNs were a clear border and location close to the pleura. Two of them resembled lung cancer. The CT features in these two IPLNs and in three small lung cancers overlapped. CONCLUSIONS: In the present study, we investigated small nodular shadows <1 cm in diameter and found that IPLNs located underneath the pleura are important to consider in the differential diagnosis of lung cancer. The CT scan findings of IPLNs were not necessarily specific and sometimes resembled those of lung cancer. Because of their location, video-assisted thoracic surgery is useful in making a definite diagnosis.     

Functional and multivalued dependencies in nested databases generated by record and list constructor

The impact of the list constructor on two important classes of relational dependencies is investigated. Lists represent an inevitable data structure whenever order matters and data is allowed to occur repeatedly. The list constructor is therefore supported by many advanced data models such as genomic sequence, deductive and object-oriented data models including XML. The article proposes finite axiomatisations of functional, multivalued and both functional and multivalued dependencies in nested databases supporting record and list constructor. In order to capture different data models at a time, an abstract algebraic approach based on nested attributes is taken. The presence of the list constructor calls for a new inference rule which allows to infer non-trivial functional dependencies from multivalued dependencies. Further differences to the relational theory become apparent when the independence of the inference rules is investigated. The extension of the relational theory to nested databases allows to specify more real-world constraints and increases therefore the number of application domains. * Results of this article were partly presented at the 3rd International Symposium on Foundations of Information and Knowledge Systems (FoIKS), Vienna, Austria, 2004 [58], and the 23rd International Symposium on Principles of Database Systems (PODS), Paris, France, 2004 [54]. ** Sebastian Link was supported by Marsden Funding, Royal Society of New Zealand.     

Short communication: Herd-level variables associated with overmilking in Michigan dairy herds

The objective of this study was to determine the herd-level variables that are associated with overmilking in 64 Michigan dairy herds with a mean herd size of 451 cows (range: 59–2,771 cows). Participating producers completed surveys to indicate their mastitis management practices and attitudes. Additionally, milking protocols were observed and milk flow dynamics for 3,824 cows were estimated using digital vacuum recorders. The median duration of overmilking was 47 s (95% confidence interval, CI: 38.6 to 55.9 s), with a mean of 55% (95% CI: 49.5 to 61.1%) of cows within each herd overmilked by at least 30 s. Median milking time for all herds was 324 s (95% CI: 302 to 346 s) and was found to be positively correlated with median duration of overmilking (r = 0.670). Backward multivariate analysis was used to determine which of 45 herd-level milking and management variables were associated with median duration of overmilking. Median duration of overmilking was negatively associated with the duration of time needed to complete 1 milking for the entire herd (adjusted R² = 0.13). Herds that operate milking facilities below maximum daily capacity may be prone to overmilking. Given the low coefficient of determination, variables unaccounted for in this study, such as equipment function or manual detachment by milking operators, are likely the most important risk factors for overmilking.