An improved method for the screening of YAC libraries.
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Biomedical subjects
Publications and source records attributed to B Davies.
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Salicylhydroxamic acid inhibited the luminol-dependent chemiluminescence of human neutrophils stimulated by phorbol 12-myristate 13-acetate or the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). This compound had no inhibitory effect on the kinetics of O2.- generation or O2 uptake during the respiratory burst, but inhibited both the peroxidative activity of purified myeloperoxidase and the chemiluminescence generated by a cell-free myeloperoxidase/H2O2 system. The concentration of salicylhydroxamic acid necessary for complete inhibition of myeloperoxidase activity was 30-50 microM (I50 values of 3-5 microM) compared with the non-specific inhibitor NaN3, which exhibited maximal inhibition at 100-200 microM (I50 values of 30-50 microM). Whereas taurine inhibited the luminol chemiluminescence of an H2O2/HOC1 system by HOC1 scavenging, this compound had little effect on myeloperoxidase/H2O2-dependent luminol chemiluminescence; in contrast, 10 microM-salicylhydroxamic acid did not quench HOC1 significantly but greatly diminished myeloperoxidase/H2O2-dependent luminol chemiluminescence, indicating that its effects on myeloperoxidase chemiluminescence were largely due to peroxidase inhibition rather than non-specific HOC1 scavenging. Salicylhydroxamic acid prevented the formation of myeloperoxidase Compound II, but only at low H2O2 concentrations, suggesting that it may compete for the H2O2-binding site on the enzyme. These data suggest that salicylhydroxamic acid may be used as a potent inhibitor to delineate the function of myeloperoxidase in neutrophil-mediated inflammatory events.
Partial lipodystrophy continues to be a baffling disorder. Procedures used for facial contour restoration have varied. Dermal-fat grafts, fat injections, microvascular free-flap grafts, and occasional injections of medical-grade liquid silicone are currently the most common methods of facial contour restoration, and although these techniques have resulted in good cosmetic results, there are drawbacks to each. We present a review of the medical literature concerning facial lipodystrophy and its cosmetic correction along with case reports of contour restoration in two facial lipodystrophic patients.
We have devised a strategy that utilizes the polymerase chain reaction (PCR) for the detection and isolation of intron-containing genes in the presence of an abundance of processed pseudogenes. The method depends on the genomic DNA sequence between the PCR primers spanning at least one intron in the gene of interest, resulting in the generation of a larger intron-containing PCR product in addition to the smaller PCR product amplified from the intronless pseudogenes. A unique intron probe isolated from the larger PCR product is used for the detection of intron-containing clones from recombinant DNA libraries that also contain pseudogene clones. This method has been used successfully for the selective isolation of an intron-containing rat L19 ribosomal protein gene in the presence of multiple pseudogenes. Analysis of a number of mammalian ribosomal protein multigene families by PCR indicates that they all contain only a single gene with introns.
We have used salicylhydroxamic acid (SHAM) to inhibit intraphagosomal myeloperoxidase activity in order to evaluate the role of this enzyme in the killing of Staphylococcus aureus by human neutrophils. 50 microM-SHAM reduced the luminol-dependent chemiluminescence response stimulated during phagocytosis of unopsonized latex beads and opsonized S. aureus by over 80% and 60%, respectively. When opsonized S. aureus were incubated with neutrophils, 45% were killed within 15 min incubation and 60% by 1 h. However, in neutrophil suspensions incubated with 50 microM-SHAM, only 13% were killed by 15 min whilst 71% still remained viable after 1 h. This inhibitor had no effect upon the number of bacteria phagocytosed or upon degranulation. In a cell-free system, 2.5 microM-H2O2 alone killed 55% of the bacteria, whereas in the presence of myeloperoxidase (i.e. 10 mU myeloperoxidase and 2.5 microM-H2O2) virtually all of the bacteria were killed: the addition of 50 microM-SHAM abolished this myeloperoxidase-enhanced killing but did not affect the H2O2-dependent killing. We therefore conclude that in normal neutrophils whilst H2O2 is required for killing of this pathogen, both myeloperoxidase-dependent and -independent pathways exist.
It has been reported that catecholamine release is associated with stressful events and that adrenaline administration induces hyperfibrinolysis. To examine the possible involvement of the adrenoreceptor mechanism in the regulation of fibrinolytic activity at rest and to maximum exercise, 12 healthy volunteers (six males and six females, age range 19-21 yr) were orally medicated with two formulations of a beta blocker. The drug treatments consisted of 1) a single dose of OM756 alpha 10 mg propranolol "Inderal" tablet, 2) a single dose of a generic 10 mg propranolol tablet, and 3) a single dose of generic placebo. The drug administrations were assigned to the subjects using a complete Latin square design and double-blind procedure and were separated by 7 d. Two hours after the administration of the respective drug treatment, subjects exercised to maximal capacity using a graded exercise protocol on a bicycle ergometer. Prior to and 2 h after the drug administration and immediately after maximum exercise, heart rate, blood pressure, and oxygen consumption were measured and venous blood was removed and analyzed for fibrinolytic activity using a standard fibrin plate method. ANOVA showed that the resting and maximum heart rates were significantly reduced (P less than 0.05) following oral premedication with either of the two formulations of beta blocker, while blood pressure and oxygen consumption were unaffected. ANOVA also showed no difference in the resting fibrinolytic activity 2 h post-administration of the drug treatments but a significant decrease (P less than 0.05) in the normal fibrinolytic response to maximum exercise. It was concluded, therefore, that the resting level of fibrinolytic activity is not mediated via an adrenergic pathway but that the enhanced fibrinolytic activity to maximum exercise is partially regulated via an adrenoreceptor mechanism.
A double-blind controlled study of moclobemide and diazepam in patients with atypical depression showed both to be effective antidepressants and anxiolytics. Statistical comparison showed diazepam to be significantly better than moclobemide at week 4. However, by week 8 there was no significant difference between the two drugs for depression scores although diazepam was a significantly better anxiolytic. Side-effects were minimal, and the most common side-effects emerging for both drugs were sleep disturbance and physical tiredness.
The purpose of this study was to determine whether the development of receptive language lags behind nonverbal cognitive development in school age persons with mental retardation. The relation between receptive language and nonverbal MA was examined as a function of MA level and the linguistic form to be understood. Individual differences in the receptive language-MA relation were also investigated. Results indicated that the relation between receptive language and MA varied across MA levels, linguistic forms, and individuals at the same MA for listeners with mental retardation.
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An anterior hairline incision with subcutaneous (superficial to the frontalis muscle) dissection is recommended for certain categories of rhytidectomy patients. Patient selection is a very important preoperative procedure. The technique and results are described and illustrated. Advantages and disadvantages are discussed.
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Results using our modification of the Putterman procedure are reported in 43 eyelids. The procedure is very effective in cases of minimal to moderate eyelid ptosis (3 mm or less) and in the presence of normal levator function. The patients, following a thorough clinical evaluation, are tested using 2.5% phenylephrine eyedrop solution, which acts as an extremely useful prognostic indicator. Depending on the degree of ptosis and the response to phenylephrine, 6 to 9 mm of combined Müller's muscle and conjunctiva is resected using a specially designed clamp under local or attended local anesthesia (no tarsal plate is resected). The incision is repaired using a running 6-0 Prolene horizontal mattress technique, and the ends are brought up through the skin and tied over the tarsal plate. In the treatment of 43 eyelids, with the exception of one slight overcorrection, there were no complications encountered with this simple procedure. Excellent results can be expected in properly selected patients, and recovery time is minimal. Our success in the last 4 years with this modified procedure allows us to strongly recommend it for the correction of mild to moderate ptosis when there is an acceptable response to phenylephrine.
A 50-yr-old woman had a right upper lobectomy that revealed the pathologic changes of eosinophilic pneumonia and mucoid impaction. In the mucus plug within the segmental bronchus, aspergillus was demonstrated by direct staining. A diagnosis of allergic bronchopulmonary aspergillosis was made. After a latent period of 17 yr, she presented with the clinicopathologic features of the Churg-Strauss Syndrome. The putative role of aspergillus in the etiology of this syndrome is discussed.
This paper reports a study of hearing and middle-ear function in 100 Down's Syndrome individuals, and the findings are compared with those of previous studies. The high incidence of middle-ear dysfunction and the associated conductive hearing loss, and the progressive sensorineural loss frequently found in Down's Syndrome are discussed. The role of surgical treatment and the use of hearing aids in the management of deafness in Down's Syndrome are reviewed.
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Understanding the speech act(s) a sentence conveys requires that a listener follow conversational rules and use clues provided by the sentence and the context in which it is spoken. To trace the development of speech act comprehension in mentally retarded and nonretarded school age children, we examined their responses to sentences such as Would you open the telephone book? and Could you roll the shoebox? These sentences can be intended as questions or as directives. Nonretarded adults follow the "answer obviousness" rule and interpret a sentence of this type as a question if the answer to the question is nonobvious to the speaker, but as a directive if the question has an obvious answer. We manipulated answer obviousness by varying both the context and linguistic properties of the interrogative. Retarded and nonretarded individuals at the nonverbal MAs of 5, 7, and 9 years were studied. Retarded and nonretarded individuals at all MAs followed the answer obviousness rule and used the contextual and linguistic clues available. There were only minor differences between MA-matched retarded and nonretarded subjects despite the fact that the retarded subjects had serious deficits in receptive linguistic competence. The implications for understanding the development of comprehension in retarded persons and for understanding the relations among language, cognition, and communication in general are considered.