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Biomedical subjects

K A Williams

Publications and source records attributed to K A Williams.

At least 91 records · Page 5Linked to original sources
PubMed1992

Minimum energy conformations of proline-containing helices.

Proline occurs frequently in transmembrane alpha-helices of transport and receptor proteins even though statistical surveys demonstrate the overwhelming preference of this residue for a non-alpha-helical, hydrophilic environment. As a result, membrane-buried proline has been proposed to be functionally important, with function arising from structural discontinuity or destabilization of the helix. Destabilization may occur by Pro-mediated conformational transitions between discrete states, and may be manifested in membrane protein systems through reversible processes such as channel opening and closing or signal transduction. In this study, computer modeling of a model transmembrane alpha-helix, (Ala)8-Leu-Pro-Phe-(Ala)8, in a medium of low polarity (dielectric = 2), is used to examine the occurrence and energetic accessibility of Pro-mediated conformational interconversions. Leu psi and chi 1, Pro psi, and Phe phi and chi 1 torsion angles were assigned random values so that a data base of 200 conformations for each of the cis and trans states was generated. The conformations were minimized and low-energy structures organized into families. This analysis demonstrated that the most populated lowest energy family is the Trans-I conformation, corresponding to proline in a kinked alpha-helix. Two additional trans structures, Trans-II and Trans-III, as well as a cis conformation, Cis-I, are also energetically competitive. Interconversions between the trans states could thus be mediated by changes at a single torsion angle, accompanied by minor local hydrogen-bonding rearrangements. This work substantiates that membrane-buried proline can provide the basis for conformational transitions between discrete alpha-helix-based structures in a nonpolar environment.

Amino Acid Sequence↗
PubMed1992

Differential growth of brain and retinal bovine pericytes.

Within the central nervous system, pericyte degeneration in diabetes mellitus occurs only in the retinal microcirculation and is not seen in the brain. This study sought to elucidate differences between bovine retinal and brain pericytes. When pairs of retinal and brain pericytes from individual calves were cultured in vitro, the morphological organisation of early post-confluent retinal pericyte cultures was consistently different from that of brain pericyte cultures. When retinal and brain pericyte cultures were grown to second passage in high or normal glucose medium supplemented with fetal calf serum, brain pericyte cultures grew significantly faster than retinal pericytes in either medium (p less than 0.0001). Brain pericytes thus appeared to grow intrinsically faster than retinal pericytes and this effect was largely independent of glucose concentration. Brain pericytes also grew faster than retinal pericytes in high glucose medium containing human diabetic or control serum (p less than 0.002). The proliferative effect of serum from diabetic patients with non-proliferative diabetic retinopathy on pericytes grown in high glucose medium was not significantly different from that of control serum. Both brain and retinal pericytes showed variation in their ability to replicate in high concentrations of glucose. The selectivity of pericyte degeneration to the retinal circulation does not appear to be due to changes in the mitogenic activity of diabetic serum for retinal pericytes, but may relate to the intrinsic relative inability of the retinal pericyte to reproliferate in response to the metabolic injury of diabetes mellitus.

Analysis of Variance↗
PubMed1992

Quantitative planar imaging of glucose metabolic activity in myocardial segments with exercise thallium-201 perfusion defects in patients with myocardial infarction: comparison with late (24-hour) redistribution thallium imaging for detection of reversible ischemia.

Exercise thallium-201 24-hour redistribution imaging and myocardial glucose metabolism with F-18-deoxyglucose were used to identify reversible ischemia in 30 patients with previous myocardial infarction. Metabolic images were obtained using a planar gamma camera fitted with a rotating tungsten collimator. Of 184 exercise thallium perfusion defects, late redistribution occurred in 88. Metabolic evidence for reversibility (metabolism-perfusion mismatch) was identified in 91% of these 24-hour reversible segments. However, 72% of the segments with fixed perfusion defects also had residual ischemia by F-18-deoxyglucose. Out of 26 fixed severe thallium defects, 69% had F-18-deoxyglucose evidence for residual ischemia. A subset of 14 patients underwent serial exercise thallium scintigraphy or gated equilibrium radionuclide angiography after revascularization or medical therapy. Out of 46 fixed thallium defects in these patients, 30 demonstrated serial scintigraphic improvement. F-18-deoxyglucose-thallium mismatch was present in 81% of these segments, but was absent in the majority of the unimproved segments. Thus quantitative planar imaging of myocardial glucose metabolism with F-18-deoxyglucose using a well-collimated gamma camera can detect clinically important reversible ischemia in segments with fixed thallium defects at late redistribution imaging.

Coronary Disease↗
PubMed1992

Factors predictive of corneal graft survival. Report from the Australian Corneal Graft Registry.

Risk factors for graft failure after penetrating keratoplasty were investigated in 961 patients from records collected prospectively by the Australian Corneal Graft Registry. The most common cause of graft failure was irreversible rejection. A multivariate proportional hazards regression analysis indicated that the key predictors of graft failure were: an indication for graft other than keratoconus or corneal dystrophy; a failed previous graft (ipsilateral eye); aphakia; inflammation at the time of graft; presence of an anterior chamber or iris-clip intraocular lens; graft size outside the range of 7.0 to 7.9 mm diameter; and corneal vascularization occurring in the postoperative period.

Adolescent↗
PubMed1992

Voice-recognition/knowledgebase reporting systems for ambulatory care patient records.

Speech recognition technology coupled with knowledgebase templates for the evaluation of specific patient complaints together constitute a technology that is currently available for patient reporting in the ambulatory care center. A system based on this technology offers advantages in legibility, speed of record creation, risk management, and reimbursement. It has both direct and indirect educational benefits for the clinician. While training requirements and system costs are reasonable, they continue to be the major stumbling block to widespread use of such systems.

Ambulatory Care Information Systems↗
PubMed1992

Patterns of corneal graft rejection in the rabbit and reversal of rejection with monoclonal antibodies.

The purpose of this study was to determine whether the local administration of monoclonal antibodies could reverse rabbit corneal graft rejection. To provide a rational basis for the choice of monoclonal antibodies as potential immunosuppressive agents, the phenotypes of cells infiltrating rejecting rabbit corneal allografts were examined by immunohistochemistry. About half the leukocytes accumulating in these grafts bore an immunodominant T cell marker, over two-thirds carried MHC class II antigens, and about one-fifth carried myeloid cell markers. A kinetic study of the cell population appearing in rabbit aqueous during corneal graft rejection was performed by examination of repetitive anterior chamber taps taken over a ten-day period; again, the major components were T cells, MHC class II antigen-positive cells and myeloid cells. Monoclonal antibodies L11/135 (directed against a peripheral T cell determinant), 2C4 (directed against a monomorphic MHC class II antigen), and LION 2 (directed against a myeloid antigen) were chosen for intracameral injection into rabbits with rejecting corneal grafts. Each animal received a total of 50-100 micrograms of antibody in two injections at 3-4-day intervals. L11/135 and LION 2 reversed rejection in 5/9 and 8/12 animals, respectively, in the absence of any other immunosuppression; 2C4 was without effect. We suggest that monoclonal antibody therapy in corneal transplantation deserves further attention.

Animals↗
PubMed1992

Clinical nuclear imaging techniques for the diagnosis and evaluation of acute myocardial infarction.

The use of nuclear imaging techniques allows the accurate detection of myocardial infarction, determination of the impact of infarction on ventricular performance, assessment of the myocardial salvage with thrombolysis, identification of preserved regional metabolism in jeopardized myocardial segments, and the elucidation of inducible reversible ischemia requiring aggressive therapeutic intervention. Assessment of myocardial salvage after thrombolysis or revascularization can be accomplished with serial perfusion imaging. Infarct-avid imaging with Tc-99m-PYP can be used to rapidly determine the size and location of the acute transmural myocardial infarction. In the future, however, the improved image quality and diagnostic accuracy of immunoscintigraphy with antimyosin antibodies may supplant PYP imaging. Studies of global ventricular function can be performed at rest, or with multiple interventions using portable scintigraphic devices. The measurement of the dynamic response of left ventricular ejection fraction over time shows promise for risk stratification. As yet, there has been no comprehensive comparison of the relative predictive value of metabolic imaging parameters, perfusion/antibody uptake mismatch, Tl-201 redistribution, or ejection fraction response data. Such a comparison could optimize the diagnostic algorithm for post-infarction damage assessment and risk stratification.

Coronary Disease↗
PubMed1992

Cryopreservation of rabbit and cat corneas at -18 to -24 degrees C.

A simple method of corneal cryopreservation, in which corneas were frozen at -18 to -24 degrees C, was examined. Rabbit and cat corneas were placed successively in solutions of 50% fetal calf serum in McCarey-Kaufman medium with an increasing glycerol and glucose content. They were then frozen and stored in a -20 degrees C domestic freezer. Rabbit corneas stored in this way were examined in vitro by light and scanning electron microscopy, and both rabbit and cat corneas were also assessed after orthotopic allotransplantation into adult recipient animals. Functional corneal grafts were obtained with rabbit and cat tissue that had been cryopreserved for 3-4 weeks and 1 week, respectively. Endpoint analysis (by light and scanning electron microscopy) of grafts that had survived for 50 days indicated the presence of an intact corneal endothelial monolayer. The corneal endothelium slowly degenerated as the storage time was increased. Importantly, however, the endothelium appeared to withstand the freezing and thawing processes and we conclude that it may be possible to store corneas at temperatures above -196 degrees C, without the need for complex, low-temperature cryopreservation systems.

Animals↗
PubMed1992

Computer applications in quality assurance.

The computer is rapidly becoming an essential tool for the physician. Proper use of computers in practice will help physicians achieve both higher levels of quality and greater consistency in patient care. Only with computers can physicians rapidly access and process all the data now needed to best address the needs of their patients. As computer use in practice becomes the standard, the inability to use these tools will be incompatible with quality care. The computer is rapidly becoming essential to modern medical management strategies that demand efficiency, accuracy, and cost effectiveness in response to patient demands for assurance that quality care is being delivered.

Computer Systems↗
PubMed1992

The frequency of asymptomatic and electrically silent exercise-induced regional myocardial ischemia during first-pass radionuclide angiography with upright bicycle ergometry.

The presence of asymptomatic (silent) myocardial ischemia during provocative testing may limit the detection of ischemic heart disease, unless sensitive indicators of ischemia are utilized. Exercise ventricular function studies are well suited for ischemia detection since segmental dysfunction is an early pathophysiologic event in the ischemic cascade. In this study, we examined the rest and stress first-pass radionuclide angiographic studies of 104 patients with coronary artery disease and exercise-induced regional wall motion abnormalities. Asymptomatic ischemia was observed in 83 patients, while only 21 patients were symptomatic. Clinical variables were not different between the two groups, except for a higher frequency of a prior anginal history in the symptomatic group. The peak heart rate and pressure-rate product were significantly higher in the silent ischemia group, as these patients are not limited by symptoms. Wall motion scores, resting and exercise ejection fractions were similar in the two groups. The frequency of an ischemic electrocardiographic ST-segment response was low, and was not significantly different between groups. These data indicate that electrically and symptomatically silent myocardial ischemia are frequent occurrences with upright bicycle ergometry. Without adjunctive cardiac imaging, this mode of exercise may not be appropriate for the evaluation of ischemic heart disease.

Aged↗
PubMed1991

Long-term outcome after corneal transplantation. Visual result and patient perception of success.

Snellen acuity, reading line, and keratometry were measured in a cohort of 60 patients at 2 or more years after penetrating keratoplasty was performed. Patients were asked to complete a questionnaire to elicit information on their perceptions of visual function and the success of the procedure. Using preferred correction, a Snellen acuity of 6/18 or better was achieved by 65%, and a reading line of N8 or better was achieved by 57% of index grafts. Thirty-eight percent had more than 5 diopters (D) of astigmatism in the graft. Approximately 75% of patients reported satisfaction with their graft (satisfaction being associated with better acuity in the grafted eye than the other eye), graft clarity, and a perceived improvement in lifestyle. Dissatisfaction appeared to be associated with graft failure and problems with contact lens wear. The findings have implications for patient selection for corneal transplantation and for the measurement of outcome.

Adolescent↗
PubMed1991

Cross-modal speech perception in adults and infants using nonspeech auditory stimuli.

Adults and infants were tested for the capacity to detect correspondences between nonspeech sounds and real vowels. The /i/ and /a/ vowels were presented in 3 different ways: auditory speech, silent visual faces articulating the vowels, or mentally imagined vowels. The nonspeech sounds were either pure tones or 3-tone complexes that isolated a single feature of the vowel without allowing the vowel to be identified. Adults perceived an orderly relation between the nonspeech sounds and vowels. They matched high-pitched nonspeech sounds to /i/ vowels and low-pitched nonspeech sounds to /a/ vowels. In contrast, infants could not match nonspeech sounds to the visually presented vowels. Infants' detection of correspondence between auditory and visual speech appears to require the whole speech signal; with development, an isolated feature of the vowel is sufficient for detection of the cross-modal correspondence.

Adult↗
PubMed1991

A monoclonal antibody exhibiting reactivity with both X-hapten- and lactose-bearing glycolipids.

The tissue reactivity of a monoclonal antibody raised against human granulocytes, FMC 34, was shown to overlap with antibodies including FMC 10, which is directed against the X-hapten, and with T5A7, which is directed against lactose-bearing antigens. Reactivity of FMC 34 on sections of human cornea was more widespread than that of either FMC 10 or T5A7. High sensitivity fluorescence testing revealed that both FMC 34 and T5A7 reacted weakly with the T-lymphocyte cell line JM, unlike the CD15 antibody FMC 10. Competitive binding experiments showed that binding of FMC 34 to granulocytes was inhibited by preincubation with T5A7, while FMC 34 itself was able to inhibit the binding of both FMC 10 and T5A7. The binding of FMC 10 was not inhibited by preincubation of cells with T5A7. Saturation-binding analyses revealed that each human granulocyte could bind 17.5 x 10(5) molecyles of FMC 34, which was more than three times the number of molecules of FMC 10 which could be bound to each cell. The additional reactivity of FMC 34 appears to be due to its capacity to bind fucosylated and non-fucosylated lactose-bearing structures.

Antibodies, Monoclonal↗
PubMed1991

Nuclear imaging analysis of human low-density lipoprotein biodistribution in rabbits and monkeys.

We have evaluated the biodistribution of human low-density lipoprotein (LDL) radiolabeled with 99mTc or with 123I-tyramine cellobiose in rabbits and in rhesus monkeys. Biodistribution was assessed after intravenous injection of radiolabeled LDL by quantitative analysis of scintigrams, counting of excreta, and counting of tissues at necropsy. Both rabbits and monkeys showed lower renal uptake (123I:99mTc approximately 1:3, as regional percent injected activity corrected for physical decay) and excretion (1:2 to 1:4), but higher hepatic (1.5:1 to 2:1) and cardiac (1.7:1 to 4:1) uptake of 123I than of 99mTc. Adrenals were visualized in normolipemic animals with 123I-tyramine cellobiose-LDL but not with 99mTc-LDL. Hyperlipemic animals showed increased cardiac (up to six-fold) and decreased hepatic activity (by 50%-60%) of both radionuclides. We conclude that 123I-tyramine cellobiose-LDL is better suited than 99mTc-LDL for dynamic studies of LDL metabolism in vivo.

Animals↗