Biomedical subjects
Publications and source records attributed to R Oswald.
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.
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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.
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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.
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.
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.
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.
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.
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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.
A double blind study was conducted to establish the possible correspondence between some motor points and acupuncture loci. The protocol calls for the acupuncturist marking the first group of volunteers with invisible ink at the acupuncture loci. Then the motor points in the same volunteer are found by electrodiagnosis. The error is made visible by UV illumination. In the second group, the procedure is reversed. A statistical analysis of the error yields the following classes of correspondences: (a) Excellent: 1st Dorsal Interosseus (hand) = LI-4; Abductor Pollicis Brevis = Lu-10; Abductor Minimi Digiti = SI-4; 1st Dorsal Interosseus (foot) = LI-3; Tibialis Anterior = Curious Locus; Orbicularis Oculi = GB-1; Frontalis = GB-14; Splenius Capitis = GB-20; Sternocleidomastoid = LI-18; Semi Spinalis Capitis = BI-10. (b) Good: Opponens Pollicis = Curious Locus; Peroneus Longus = Curious Locus; Flexor Digitorum Longus = Ki-3 (Ki-6); Trapezius (upper) = GB-21; Rectus Abdominis = Ki-15; Vastus Medialis = Sp-10.
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