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Biomedical subjects

A Shaw

Publications and source records attributed to A Shaw.

At least 109 records · Page 6Linked to original sources

Prediction of temperature rise in layered media from measured ultrasonic intensity data.

It is now widely recognized that under some circumstances exposure to ultrasound at current diagnostic levels may result in undesirable heating in tissue. The National Council on Radiation Protection and Measurements (NCRP) and the American Institute of Ultrasound in Medicine (AIUM) in conjunction with the National Electrical Manufacturers Association (NEMA) have suggested relatively simple methods for estimating the in situ temperature rise based on simplified ultrasonic intensity profiles. In this paper, the measured spatial intensity distribution from three unscanned ultrasonic transducers is used in an integral solution to the bioheat equation to calculate the temperature increase in layered media, and these calculations are compared with the simple predictions under similar conditions. The transducers included weak and strong focusing devices and one device with a non-cylindrical beam. The ratio between the NCRP and AIUM/NEMA predictions varied from 0.5 to 2.3 in equivalent situations. The ratio between the simple predictions and the more detailed calculations varied from 0.7 to 3.2 for NCRP, and from 0.3 and 3.5 for AIUM/NEMA. These results highlight the need, firstly, to establish simple 'standard' methods for estimating likely temperature increase during clinical examination, and secondly to be clear about whether these methods are intended to give 'worst case' or 'typical' estimates.

Algorithms↗

p59fyn tyrosine kinase regulates p56lck tyrosine kinase activity and early TCR-mediated signaling.

To study the role of p59fyn in T cell activation, we used antisense RNA to inhibit p59fyn expression in a T cell clone. Transfectants with reduced levels of p59fyn were functionally impaired in their responses to antigen, Con A+recombinant IL-1 and cross-linking with anti-TCR mAb. Induction of tyrosine phosphorylation on most intracellular substrates was greatly reduced. We also noted that the lck kinase activity was greatly reduced even though the amount of lck protein was equivalent to that present in parental D10 cells. Our results suggest that the protein tyrosine kinase p59fyn is critical in TCR-mediated signaling and also suggests that p59fyn may regulate p56lck tyrosine kinase activity.

Animals↗

Patients' experiences of emergency admission: how relevant is the British government's Patients Charter?

This paper evaluates the British government's Patients Charter from the perspective of patients admitted via accident and emergency departments. It uses qualitative data obtained about issues of concern to these patients to judge whether the standards set out in the Charter are appropriate to their priorities and, conversely, if there are issues of importance to these patients which the Charter overlooks. Semi-structured interviews were conducted with 83 patients admitted to two London hospitals. It is concluded that the rights and standards outlined in the Patients Charter are generally appropriate to these patients' experiences, although some are defined too narrowly. The study identified a number of issues of importance to patients which are not mentioned in the Patients Charter: pain relief, giving information, receiving information, reception staff, examinations and investigations, physical environment, and other people in casualty. The patient wants rather more than recent British government documents suggest.

Adolescent↗

Nuclear localization of the PEP protein tyrosine phosphatase.

PEP is an intracellular protein tyrosine phosphatase expressed primarily by cells of hematopoietic origin that can be divided structurally into a catalytic domain and a large carboxy-terminal domain. The carboxy-terminal domain is enriched in proline, glutamic acid, serine, and threonine residues (PEST sequences) and contains a nonperfect tandem repeat sequence enriched in proline residues and a carboxy terminus enriched in basic amino acids. Here we show that PEP is diffusely expressed in lymphoid tissues, consistent with expression by many different cell types. Analysis of the PEP protein identifies a nuclear localization sequence within the extreme carboxy terminus. Transfer of 18 amino acids from the carboxy terminus of PEP to beta-galactosidase conferred nuclear localization, indicating that this sequence was sufficient for nuclear localization. Proteins enriched in PEST sequences are often rapidly degraded. However, pulse-chase analysis indicates that PEP has a half-life of greater than 5 h.

Amino Acid Sequence↗

Caring for gravely ill children.

BACKGROUND: Much has been written about the care of the hopelessly ill adult, but there is little guidance for pediatric health care professionals in the management of children who are critically or terminally ill. METHODS: Through a 3-day meeting in Tarrytown, NY, attended by a group of pediatricians and others directly involved in these issues, a principled approach was developed for the treatment of, and health care decision-making for, children who are gravely ill. RESULTS: The group agreed that the needs and interests of the child must be the central focus of any treatment plan and that the child should be involved to as great extent possible, consistent with developmental maturity, in the decision-making process. Quality of future life should be viewed as being relevant in all decisions. Parents are believed to be the natural guardians of children and ought to have great latitude in making decisions for them. However, parental discretion is not absolute and professionals must maintain an independent obligation to protect the child's interests. CONCLUSIONS: Decision-making should be collaborative among patient, parents, and professionals. When conflict arises, consultation and ethics committees may assist in resolution. When cure or restoration of function is no longer possible, or reasonable, promotion of comfort becomes the primary goal of management. Optimal use of pain medication and compassionate concern for the physical, psychological, and spiritual well-being of the child and family should be the primary focus of the professionals caring for the dying child.

Adolescent↗

An unwanted inheritance? Family studies into the genetics of asthma.

1. Atopy underlies allergic asthma, rhinitis and eczema. 2. Atopy can be defined as a general state of excessive IgE responsiveness. 3. The aim of these genetic studies is the development of more effective preventions and treatments for asthma and other atopic disorders.

Adult↗

The crystal structure of lysin, a fertilization protein.

Lysin, a protein from abalone sperm, creates a hole in the envelope of the egg, permitting the sperm to pass through the envelope and fuse with the egg. The structure of lysin, refined at 1.9 angstroms resolution, reveals an alpha-helical, amphipathic molecule. The surface of the protein exhibits three features: two tracks of basic residues that span the length of the molecule, a solvent-exposed cluster of aromatic and aliphatic amino acids, and an extended amino-terminal hypervariable domain that is species-specific. The structure suggests possible mechanisms of action.

Amino Acid Sequence↗

Histidine 52 is a critical residue for rapid formation of cytochrome c peroxidase compound I.

The crystal structure and reactivity with hydrogen peroxide are reported for a mutant of a cloned cytochrome c peroxidase [CcP(MI)], in which the conserved distal His (His-52) is replaced with Leu. The reaction of the H52L enzyme with peroxide was examined as a function of pH in 0.1 M phosphate buffers and buffers in which nitrate was used to adjust the ionic strength. The pH-independent bimolecular rate constant for the reaction of H52L with peroxide was 731 +/- 44 and 236 +/- 14 M-1 s-1 in phosphate and nitrate-containing buffers, respectively. This represents a 10(5)-fold decrease in rate relative to the CcP(MI) parent under comparable conditions. Single-crystal diffraction studies showed that no dramatic changes in the structure or in the accessibility of the heme binding site were caused by the mutation. Rather, the mutation caused significant structural changes only at residue 52 and the nearby active-site water molecules. The residual reactivity of the H52L enzyme with peroxide was pH- and buffer-dependent. In nitrate-containing buffer, the apparent bimolecular rate constant for the reaction with peroxide decreased with decreasing pH; the loss of reactivity correlated with protonation of a group with an apparent pKA = 4.5. Protonation of the group caused a loss of reactivity with peroxide. This is in contrast to the CcP(MI) parent enzyme, as well as all other mutants that have been examined, where the loss of reactivity correlates with protonation of an enzyme group with an apparent pKA = 5.4.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystallography↗

Novel T cell antigen 4-1BB associates with the protein tyrosine kinase p56lck1.

4-1BB is a 30-kDa inducible T cell Ag, and is expressed predominantly as a 55-kDa dimer on both CD4+ and CD8+ T lymphocytes. The cytoplasmic tail of 4-1BB contains the sequence Cys-Arg-Cys-Pro, which is similar to the sequence Cys-X-Cys-Pro, which mediates the binding of the CD4 and CD8 molecules to the protein tyrosine kinase p56lck. An anti-4-1BB mAb, 53A2, was used to determine whether 4-1BB may associate with p56lck. The 53A2 mAb specifically recognized 4-1BB on a CD8+ T cell line, CTLL-2, and coimmunoprecipitated a 56-kDa protein along with 4-1BB. Peptide mapping indicated that the 56-kDa phosphoprotein was identical to p56lck. The coimmunoprecipitation of p56lck with 4-1BB also occurred in nonlymphoid cells such as insect (Sf-21) and HeLa cells when the two recombinant proteins were coexpressed. Analysis of mutant p56lck recombinant proteins showed that two cysteine residues critical for p56lck-CD4 (or -CD8) complex formation are also required for the p56lck-4-1BB interaction. These studies establish that 4-1BB physically associates with p56lck.

Amino Acid Sequence↗

Correlation between Src family member regulation by the protein-tyrosine-phosphatase CD45 and transmembrane signaling through the T-cell receptor.

Stimulation of tyrosine phosphorylation is an early and important event in antigen-induced T-cell activation. T-cell clones deficient in expression of CD45, a transmembrane protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48), are impaired in their ability to respond to either antigen or T-cell receptor cross-linking. Analysis of the CD45-deficient CD8+ T-cell clone L3M-93 demonstrates that the Src family members p56lck and p59fyn show increased immunoreactivity with anti-phosphotyrosine antibody and exhibit decreased kinase activity. The site of increased tyrosine phosphorylation in Src family members was identified by comparison of cyanogen bromide peptide maps. Phosphorylation of the C-terminal phosphopeptide, containing the negative regulatory site of tyrosine phosphorylation, from the CD45-deficient cells was increased 8-fold for p56lck and 2-fold for p59fyn. These data suggest that CD45 dephosphorylates the negative regulatory site of multiple Src family members in the cytotoxic T-lymphocyte clone L3 and show a correlation between the ability to respond efficiently to antigen and the dephosphorylation of Src family members by CD45.

Animals↗

Experimental validation of predicted temperature rises in tissue-mimicking materials.

Increasingly, it is recognised that diagnostic ultrasound is capable of causing temperature rises sufficient to damage tissue. Predictions of this heating are often based on simplified models of both the in vivo conditions and the relevant physical effects. Few measurements have been made to verify these predictions, however, particularly for the tightly focused beams often employed in diagnosis. Furthermore, non-linear effects in both the acoustic field and the surrounding medium have largely been ignored in calculations. To provide an alternative way to estimate the heating, NPL has developed a measurement system to determine directly the temperature rise in tissue-mimicking materials. If necessary, the measurement results can be processed to model the effects of blood perfusion. The temperature is measured using thin-film thermocouples, which have essentially no interaction with the ultrasound or thermal fields. Measurements were made on transducers operating in the frequency range 2-10 MHz and with focal beam-widths from 1 to 3 mm. The measurements agree with theoretical predictions that use either the measured beam-profile or a simplified (Gaussian) model. The results are also compared with the standard soft-tissue models developed by the National Council on Radiation Protection and Measurements (NCRP) and jointly between the American Institute of Ultrasound in Medicine and the National Electrical Manufacturers Association (AIUM/NEMA). On average, the predictions of the NCRP formula are 15% higher than the measurements, confirming its validity as a worst-case model. The predictions based on the AIUM/NEMA formula, however, are typically 30% lower than the measured values.

Body Temperature↗

Selective management of gastroschisis according to the degree of visceroabdominal disproportion.

OBJECTIVE: This study analyzed the factors influencing the postoperative results after the repair of gastroschisis defects during the past 27 years. SUMMARY BACKGROUND DATA: The clinical results after the repair of gastroschisis abdominal defects have improved appreciably during the past 25 years, with the long-term survival rate in most large children's centers currently being approximately 90%. The improvement in survival has been largely attributed to advances in perioperative care, frequent use of parenteral nutrition, and better techniques of surgical repair. METHODS: Between 1965 and 1992, 84 infants with gastroschisis underwent surgical repair. The management of 52 infants after 1979 was compared with that of 32 during the previous 14 years. Associated anomalies were present in 29%. The average birth weight was 2412 g. In 31%, primary fascial closure was performed. In another 31% with moderate visceroabdominal disproportion (VAD), a silastic chimney was used initially, and complete repair was performed at a second operation. For 25% who had severe VAD, more than two operative reconstructions were necessary. Seven of 52 infants with moderate VAD underwent initial skin-flap closure and secondary repair within 12 days. RESULTS: Almost all complications (27%) and deaths (4%) occurred in infants with severe VAD and were largely unrelated to associated malformations or birth weight. The length of postoperative mechanical ventilation, need for parenteral nutrition, need for multiple operations, and length of hospitalization were all directly related to the severity of the VAD. CONCLUSIONS: Complete repair of gastroschisis at the initial operation is the optimal goal; however, the severity of VAD has permitted this approach in only one third of patients in this study. Delayed repair with a silastic chimney and one or more reconstructive procedures has provided excellent long-term survival with low morbidity and mortality rates. Although skin-flap closure is no longer used initially, this technique has been helpful for the residual defect in infants with severe VAD who have had multiple silon chimney repairs (Applied Biomaterial, Silverdale, WA).

Abdominal Muscles↗

The use of propofol in a child with hepatitis A.

Propofol was used for the induction and maintenance of anaesthesia in a 4-year-old girl with hepatitis A and haematemesis. The anaesthetic was uneventful with no postoperative sequelae.

Anesthesia, Intravenous↗

Signet ring variant of lobular carcinoma of the breast: a clinicopathologic and immunohistochemical study.

Signet ring carcinoma of the breast often metastasizes to gastrointestinal tract and female genital tract. We report clinicopathologic features of 10 breast carcinomas with signet ring features, five of which had unusual metastatic patterns. The primary breast tumor in all these cases was lobular carcinoma. Although signet ring cells were prominent in metastatic sites, the primary tumor lacked signet ring cells in two cases. A linitis plastica-like presentation and presence of signet ring cells in gastric metastases raised a strong possibility of primary gastric carcinoma in three cases. The monoclonal antibody to gross cystic disease fluid protein (GCDFP-15) was positive in signet ring cell-rich areas in the primary breast tumor (8/10) and/or in the metastases in all cases. For comparison we studied GCDFP-15 immunoreactivity in 10 infiltrating lobular and 10 infiltrating ductal breast carcinomas with no obvious signet ring cells, and in 14 signet ring carcinomas from other sites (10 gastric, 2 prostatic, 2 colonic). The gastric, colonic, and one prostatic signet ring carcinoma were nonreactive. One prostatic signet ring carcinoma exhibited focal but unequivocal positivity with GCDFP-15. The cases of this report reinforce the concept that signet ring carcinoma of the breast is usually a variant of lobular carcinoma and not a distinct entity. Signet ring cell predominance in metastases, even in the absence of signet ring cells in the primary tumor, attest to the morpho-functional heterogeneity of lobular carcinoma. GCDFP-15 is a sensitive marker for signet ring breast carcinoma and a very useful adjunct tool in the diagnosis of metastatic signet ring carcinoma of mammary origin.

Adult↗

Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues.

Advanced glycation end products (AGEs), the final products of nonenzymatic glycation and oxidation of proteins, are found in the plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes. A novel integral membrane protein, termed receptor for AGE (RAGE), forms a central part of the cell surface binding site for AGEs. Using monospecific, polyclonal antibody raised to human recombinant and bovine RAGE, immunostaining of bovine tissues showed RAGE in the vasculature, endothelium, and smooth muscle cells and in mononuclear cells in the tissues. Consistent with these data, RAGE antigen and mRNA were identified in cultured bovine endothelium, vascular smooth muscle, and monocyte-derived macrophages. RAGE antigen was also visualized in bovine cardiac myocytes as well as in cultures of neonatal rat cardiac myocytes and in neural tissue where motor neurons, peripheral nerves, and a population of cortical neurons were positive. In situ hybridization confirmed the presence of RAGE mRNA in the tissues, and studies with rat PC12 pheochromocytes indicated that they provide a neuronal-related cell culture model for examining RAGE expression. Pathological studies of human atherosclerotic plaques showed infiltration of RAGE-expressing cells in the expanded intima. These results indicate that RAGE is present in multiple tissues and suggest the potential relevance of AGE-RAGE interactions for modulating properties of the vasculature as well as neural and cardiac function, prominent areas of involvement in diabetes and in the normal aging process.

Animals↗