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Biomedical subjects

R Oswald

Publications and source records attributed to R Oswald.

At least 19 recordsLinked to original sources

Antimycobacterial 3-aryl-2H-1,3-benzoxazine-2,4(3H)-diones.

A series of 153 derivatives of 3-phenyl-2H-benzoxazine-2,4(3H)-dione substituted in position 6 or 7 on benzoxazine and on the phenyl ring was synthesized. The compounds were evaluated in vitro for antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium. The activity of the compounds increases with increasing hydrophobicity and electron-withdrawing properties of the substituents on the phenyl ring, whereas the effect of the substituents on the benzoxazine ring seems to be more complex.

Algorithms↗

Theoretical investigations of proton-bound cluster ions.

Several proton-bound cluster ions have been studied by means of coupled cluster calculations with large basis sets. Among these are complexes of a krypton or xenon atom with the cations HCO+, HN2+ and HNCH+. Various spectroscopic properties have been calculated in all cases. Effects of vibrational anharmonicity are particularly pronounced for the intramolecular stretching vibrations of Kr...HN2+ and Xe...HN2+. The proton stretching vibration of (N2)H+(N2) is predicted around 800 cm-1, with a large transition dipole moment of 1.15 D. Both (N2)H+(N2) and (HCN)H+(NCH) have linear centrosymmetric equilibrium structures. Those of (OC)H+(CO) and (HCC-)H+(CCH-) are asymmetric with barrier heights to the centrosymmetric saddle points of 382 and 2323 cm-1, respectively. The dissociation energy of the anionic complex Cl-...HCCH is calculated to be Do = 3665 cm-1, 650 cm-1 larger than the corresponding value for Br-...HCCH. The complex between a fluoride ion and acetylene is more strongly bound and shows strongly anharmonic behaviour, similar to the bihalides FHF- or ClHCl-. Strong Fermi resonance interaction is predicted between nu 3 (approximately proton stretch) and 2 nu 4 (first overtone of intermolecular stretch).

Journal Article↗

Transport, catabolism and release of histamine in the ruminal epithelium of sheep.

Whereas intraruminal histamine does not affect healthy ruminants, histaminosis is apparent during ruminal acidosis. We therefore investigated the factors that, under physiological circumstances, prevent intoxication by intraruminal histamine and the disturbances occurring during acidotic or hypoxic epithelial damage. After mucosal (m) or serosal (s) application of 80 microM histamine, its flux across the isolated epithelia of the sheep rumen was determined radioactively (hist-rad flux) in Ussing chambers. The non-catabolized component of the hist-rad fluxes was determined by high-pressure liquid chromatography (HPLC) (histamine flux). The difference between hist-rad and histamine fluxes indicated efficient intraepithelial catabolism of histamine at pH 7.4 (m-s direction, 98.7%; s-m direction, 93.3%). Both 0.1 mM 2,4-dinitrophenol (DNP) and mucosal acidification to pH 5.1 increased hist-rad fluxes and decreased catabolic efficiency. pH-dependent secretion of histamine was indicated by differences between m-s and s-m fluxes of histamine and/or hist-rad. Epithelial permeability to hist-rad and mannitol was similar and their fluxes correlated partly. Epithelial release of endogenous histamine was 1.5 pmol x cm(-2) x h(-1) and was not increased by the mast cell stimulator, compound 48/80 (10 ng x ml(-1)). We conclude that histamine absorption across the intact epithelium is efficiently restricted by a low permeability to histamine in combination with catabolic and secretory processes. Especially increases in paracellular permeability and/or inhibition of catabolism enhance histamine absorption.

2,4-Dinitrophenol↗

An integrated logistics support system for training crew medical officers in advanced cardiac life support management.

The purpose of this paper is to present an approach for the development of an integrated logistics support system for training space flight crew medical officers in advanced cardiac life support (ACLS). The most practical approach to deal with this problem has been determined to be the training of one or more of the crew members on the mission as crew medical officers (CMO's). If this approach is taken, there are a number of problems that must be addressed. The basic approach presented in this paper is to develop a performance quality index for ACLS tasks and use this index to monitor and control the performance of crew members throughout their tenure as CMO's. The control tool of the system is based on an integrated learning and forgetting model used to forecast CMO performance level at a given point during flight training. The model represents an aid for trainers in determining a training regime and maintaining the performance standards. A performance evaluator and trainer is also developed to help in the establishment of trainee performance level during training or retraining. All of these tools were evaluated using either expert opinion questionnaires or experimental results. In conclusion, the results presented provide the tools required for an integrated logistics support system for training ACLS personnel.

Aerospace Medicine↗

NHS ombudsman. A job for strife.

The commissioner's office investigates only about 4 per cent of the complaints received. The average time taken for an investigation is 45 weeks. The impact of the commissioner's work on the NHS is difficult to establish.

Administrative Personnel↗

A cautionary tale.

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Emergency Service, Hospital↗

Serum cytidine deaminase as a measure of disease activity in rheumatoid arthritis and systemic lupus erythematosus.

Serum cytidine deaminase (CD) as a marker of disease activity was assessed in 100 patients with rheumatoid arthritis (RA) and in 102 assessments of 85 patients with systemic lupus erythematosus (SLE). In RA CD levels correlated well with clinical assessment of disease activity, but were not influenced by varying dosages of ibuprofen as therapy. In SLE significant correlations were found between CD and anti-DNA antibody titers, as well as C3 complement levels. A subset of clinically active patients with SLE with elevated CD levels but normal anti-DNA titers was identified. Serum CD levels may be a clinically useful marker in RA and in certain subgroups of patients with SLE.

Adult↗

Unbounded health.

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Health Services Needs and Demand↗

Interaction of a benzomorphan opiate with acetylcholinesterase and the nicotinic acetylcholine receptor.

The benzomorphan opiate, (-)N-allynormetazocine [(-)ANMC, (-)SKF10047], has been shown previously to bind two distinct sites on acetylcholine receptor (AChR)-rich membranes from Torpedo electroplaque. The low affinity site seems to correspond to the site for noncompetitive blockers on the AChR. The high affinity site, which can be photoaffinity labeled using UV irradiation, was distinct from this site. We show here, using a variety of techniques, that the high affinity binding site for (-)ANMC is on the acetylcholinesterase (AChE) associated with these membranes. The Triton X-100-solubilized peptide photolabeled with (-)[3H]ANMC co-migrates with acetylcholinesterase activity on velocity sucrose gradient centrifugation and fast protein liquid chromatography. In addition, the labeled peptide cannot be precipitated with monoclonal or polyclonal antibodies raised against the nicotinic AChR but can be precipitated with anti-AChE antibodies. Localization of the binding site on AChE was confirmed by photolabeling of and reversible binding to the 11 S AChE purified from Torpedo californica. The binding and photolabeling had characteristics and affinity similar to those for the high affinity binding site in Torpedo electroplaque membranes. Competition studies with specific AChE inhibitors suggest that the binding site may be the catalytic site of the enzyme, which exists on the 66-kDa globular protein. The effect of (-) and (+)ANMC on AChE activity was also investigated. ANMC inhibited AChE activity at micromolar concentrations in a stereoselective fashion, with the (-)isomer exhibiting a 2-fold higher affinity than the (+) isomer. The inhibition was consistent with a competitive blockade of AChE activity.

Acetylcholinesterase↗

Ankylosed teeth as abutments for maxillary protraction: a case report.

It has been recognized that using the maxillary teeth to deliver extraoral force to the maxilla not only results in sutural remodeling but also periodontal remodeling and tooth movement. In patients with severe maxillomandibular malrelationships, the potential for tooth movement often limits the amount and duration of extraoral force and, consequently, affects the success of treatment. This case report describes a technique to intentionally ankylose deciduous teeth in a patient with severe maxillary retrusion. The ankylosed teeth were used as abutments to deliver an anteriorly directed intermittent extraoral force. After 12 months of treatment, the anterior crossbite was nearly corrected. At that point the ankylosed teeth loosened because of root resorption and the treatment was terminated. Cephalometric superimposition demonstrated that the occlusal correction was the result of anterior maxillary movement with little mandibular growth and no movement of the ankylosed teeth. The results suggest that intentionally ankylosed teeth may be used as abutments for extraoral traction in patients with a severe disturbance in maxillary growth.

Acrocephalosyndactylia↗

[The high affinity binding site for chlorpromazine is present only as a single copy per cholinergic receptor molecule and is shared by four polypeptide chains].

3H chlorpromazine binds to acetylcholine receptor-rich membrane fragments prepared from Torpedo marmorata electric organ in three different manners: (1) at the level of high affinity sites from which it is displaced by perhydrohistrionicotoxin, (2) at the level of low affinity sites insensitive to this toxin, and (3) in a non saturable manner to a presumably lipidic phase. Binding of chlorpromazine to the first two categories of sites independently stabilizes the "desensitized" high affinity state of the receptor for cholinergic agonists. There exists one high affinity site per two snake alpha-toxin sites, thus per 250,000 daltons light form of the receptor. Under the conditions of 3H chlorpromazine high affinity binding, ultraviolet irradiation results in the covalent incorporation of this ligand to the four chains of the receptor.

Animals↗

Dissection of the 66 000-dalton subunit of the acetylcholine receptor.

The 66 000-dalton or delta subunit of the acetylcholine receptor from Torpedo marmorata was covalently labeled in the presence of carbamoylcholine by 5-azido [3H]trimethisoquin (5-A[3H]T), a photoaffinity derivative of the local anesthetic trimethisoquin. After the attack of purified receptor with increasing concentrations of trypsin, the delta chain successively yielded fragments with apparent molecular weights of 50 000 (distinct from the beta subunit and referred to as the 50 000-bis (fragment), 49 000, and 47 000. With nondenatured (sodium cholate solubilized or membrane-bound) receptor, the 47 000-dalton fragment was not sensitive to trypsin and contained all of the covalent 5-A[3H]T label. This fragment was still glycosylated and had the same amino acid N terminus, valine, as the intact delta chain. A specific in vitro phosphorylation site of the delta subunit was located between the 49 000- and 50 000-dalton trypsin cleavage fragment and most likely is exposed to the cytoplasmic side of the membrane. A 16 000-dalton fragment of the delta chain was identified, which carriers a disulfide bond (or bonds) capable of cross-linking nonreduced receptor 9S monomerse into 12S dimers. The fragment did not remain associated with the receptor molecule after trypsin treatment.

Animals↗

Ultraviolet light-induced labeling by noncompetitive blockers of the acetylcholine receptor from Torpedo marmorata.

Reversible ligands were attached covalently to membrane-bound acetylcholine receptor from Torpedo marmorata by a method which is generally applicable and does not require the synthesis of specially designed molecules. UV irradiation of the receptor in the presence of [3H]trimethisoquin, [3H]phencyclidine, or [3H]perhydrohistrionicotoxin resulted in the labeling of the binding site(s) for these noncompetitive blockers of the permeability response. The labeling of the delta chain was enhanced by carbamoylcholine, and this increase was blocked by snake alpha-toxins. The effect of carbamoylcholine on [3H]trimethisoquin binding was more pronounced than with the other two noncompetitive blockers; in all instances, the labeling was abolished by unlabeled histrionicotoxin. These three compounds therefore interact with the high-affinity site for noncompetitive blockers. Incorporation of radioactivity also occurred into the alpha chain but either was insensitive to cholinergic effectors or decreased in the presence of carbamoylcholine (or snake alpha-toxin), probably as a result of an interaction with the acetylcholine-binding site. In contrast to the other noncompetitive blockers tested, [3H]chlorpromazine heavily labeled the four receptor polypeptides (alpha, beta, gamma, delta), and this labeling also was enhanced by carbamoylcholine and decreased by histrionicotoxin. These data indicate a contribution of the delta chain to the binding site(s) of several well-characterized noncompetitive blockers and suggest that other receptor polypeptides may also contribute to this binding.

Affinity Labels↗

Inflation: tracing the causes.

In the first half of 1979, the U.S. inflation rate was running higher than the alarming pace of most of the previous 10 years. Because the current price increases are led by the necessities--food, energy, medical care, housing and interest rates--inflation was having a particularly devastating impact on lower income families whose incomes go almost exclusively for those necessities. Workers remain on a treadmill--losing ground in real spendable earnings despite new wage increases.

Economics↗