Biomedical subjects
Publications and source records attributed to L Lee.
An unusual presentation of non-Hodgkins lymphoma is presented in an immunocompromised patient. The importance of having a high index of suspicion for malignancy in transplant patients is stressed.
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The thermosensing ability of the Trg and Tap chemoreceptors in Escherichia coli was investigated after amplifying these receptors in a host strain lacking all four known chemoreceptors (Tar, Tsr, Trg, and Tap). Cells with an increased amount of either Trg or Tap showed mostly smooth swimming and no response to thermal stimuli. However, when the smooth-swimming bias of the cells was reduced by adding Trg- or Tap-mediated repellents, the cells showed clear changes in the swimming pattern upon temperature changes; Trg-containing cells showed tumbling at 23 degrees C but mostly smooth swimming at 32 degrees C, while Tap-containing cells showed smooth swimming at 20 degrees C but tumbling at 32 degrees C. These results indicate that although both Trg and Tap have the ability to sense thermal stimuli, Trg functions as a warm receptor, as reported previously for Tar and Tsr, while Tap functions as a cold receptor.
With the advent of pediatric biomedical technology research in the past few decades, concern for the rights of children as research subjects is increasing. This article offers an orientation for pediatric nurses regarding the historical background of protection of children's rights, ethical principles, ethical issues of consent and risk versus benefit, and nursing implications relating to research involving children.
We examined the role of N-linked glycosylation of the insulin-like growth factor-II (IGF-II)/mannose 6-phosphate (Man-6-P) receptor in binding of [125I]IGF-II to the receptor. First we studied the synthesis and posttranslational processing of this receptor in rat C6 glial cells, which have abundant IGF-II/Man-6-P receptors. Cells were pulse labeled with [35S]methionine and lysed, and the IGF-II/Man-6-P receptor was immunoprecipitated using a specific IGF-II/Man-6-P receptor antibody (no. 3637). Analysis of the immunoprecipitate by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with reduction of disulfide bonds showed a 235-kDa receptor precursor that was processed into the mature 245-kDa IGF-II/Man-6-P receptor within 2 h of chase. Digestion of the 235-kDa precursor with endoglycosidase-H (Endo H) produced a 220-kDa form, whereas the mature 245-kDa receptor was relatively resistant to cleavage by Endo H. When cells were cultured in the presence of 2 microM monensin, the 235-kDa receptor was not further processed into the mature Endo H-resistant receptor form. In addition, the presence of swainsonine in C6 glial cell cultures led to the formation of a 240-kDa receptor hybrid molecule, which was cleaved by Endo H into a 225-kDa species. When tunicamycin was present during the pulse-chase labeling experiment, a 220-kDa receptor species accumulated. This species was 205 kDa by immunoblotting when SDS-PAGE was performed under nonreducing conditions. Pure IGF-II/Man-6-P receptor was digested with N-glycosidase-F, and the digest was immunoblotted with antiserum 3637 after SDS-PAGE under nonreducing conditions. Whereas undigested receptor was a single band of 215 kDa under nonreducing conditions, digested receptor was 205 kDa. The binding affinity of IGF-II for the digested receptor was the same as the binding affinity of IGF-II for the undigested receptor. In addition, affinity cross-linking experiments showed that [125I]IGF-II also bound to the unglycosylated receptor precursor that accumulated in the tunicamycin-treated cells, and the binding affinity of IGF-II for this species was indistinguishable from the binding affinity of IGF-II for the mature receptor. We conclude that IGF-II can bind to an IGF-II/Man-6-P receptor that lacks N-linked oligosaccharides.
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A review of the incidence of heat disorders in the Singapore Armed Forces was done in relation to the preventive and corrective measures applied. Data was compiled and analysed from records kept by the SAF Medical Services. A thorough review was made into all the preventive measures carried out thus far and the effectiveness was evaluated. There was a rise in the incidence of heat strokes from eight cases in 1984 to a peak of 46 cases in 1986. Subsequently, aggressive measures were adopted and the incidence fell significantly in 1988 and 1989. The main strategy involved a comprehensive health education programme, regulations, active surveillance and aggressive treatment. However, the incidence has not fallen to the pre-1984 levels. Therefore, a strict vigilance must be constantly maintained to prevent further mortality and morbidity.
As part of stereotactic surgery, microelectrode recordings of somatosensory neurons in thalamus were obtained in 5 patients. Neurons with receptive fields on the lips and tongue were consistently activated when these structures were involved in production of speech sounds. The magnitudes of these responses were similar to those elicited by experimentally applied mechanical stimuli, suggesting that speech-induced somatosensory inputs are not suppressed at the thalamic level.
The crystal structure of carp parvalbumin (pI = 4.25) has been refined by restrained least-squares analysis employing X-ray diffractometer data to 1.5-A resolution. The final residual for 12,653 reflections between 10 and 1.5 A with I(hkl) greater than 2 sigma(I) is 0.215. A total of 74 solvent molecules were included in the least-squares analysis. The root mean square deviation from ideality of bond lengths is 0.024 A. The model has a root mean square difference of 0.59 A from the positions of the main-chain atoms in a previously reported structure [Moews, P. C., & Kretsinger, R. H. (1975) J. Mol. Biol. 91, 201-228], which was refined by difference Fourier syntheses using data collected by film to 1.9 A. Although the overall features of the two models are very similar, there are significant differences in the amino-terminal region, which was extensively refit, and in the number of oxygen atoms liganding calcium in the CD and EF sites, which increased from six to seven in the CD site and decreased from eight to seven in the EF site.
A case of maxillary ameloblastic carcinoma metastatic to the mandible is presented. Of 33 cases of ameloblastic carcinoma reported in the English literature 10 have occurred in the maxilla. Of these, none produced mandibular metastases. The authors review the literature, describing clinical presentation, histological appearance, and treatment of this rare lesion.
This study investigated the ability of aphasic patients with mild auditory comprehension problems to respond to synthetic speech produced by an inexpensive speech synthesizer attached to a personal computer. Subjects were given four practice sessions with synthetic speech; testing of synthetic speech comprehension was performed during Sessions 1 and 4. During testing, aphasic subjects' comprehension of synthetic speech was compared with their comprehension of natural speech on four tasks: (a) picture identification, (b) following commands, (c) yes/no questions, and (d) paragraph comprehension with yes/no questions. Aphasic subjects comprehended natural speech better than synthetic speech in Session 1 but not in Session 4. Their synthetic speech scores improved between Sessions 1 and 4. There was also a significant difference among scores on the four tasks for both sessions. The means for picture identification were highest, followed by yes/no questions, commands, and finally paragraph comprehension for both sessions. Although performance by some subjects on some tasks was accurate enough to indicate that an inexpensive speech synthesizer could be a useful tool for working with mild aphasic patients, considerable caution in selecting both tasks and patients is warranted.
The purpose of this investigation was to describe the occurrence of laryngeal pathologies and their distribution across age, sex, and race in a pediatric sample. Data were collected on 731 patients seeking evaluation or treatment at a children's hospital otolaryngology clinic. The most frequent laryngeal pathologies were subglottic stenosis, vocal nodules, laryngomalacia, and vocal fold paralysis. For the total sample, laryngeal pathologies were significantly more common to males than females. Laryngeal pathologies were most common in the youngest patients. The distribution of pathologies within each race was similar to that found throughout the total sample. Comparisons with similar investigations are made. Implications for management are discussed.
The Tar chemoreceptor of Escherichia coli mediates attractant responses to aspartate, maltose, and phenol, repellent responses to Ni2+ and Co2+, and thermoresponses. To understand the role of threonine residue 154, which is located in the ligand-binding domain of Tar, we replaced the residue with serine, isoleucine, and proline by site-directed mutagenesis. The replacements caused reductions in aspartate sensing but had only a small effect on maltose sensing and almost no effect on phenol sensing, repellent sensing, and thermosensing. These results indicate that Thr-154 of Tar is rather specifically involved in aspartate sensing. The reductions in the response threshold for aspartate by the replacements with serine, isoleucine, and proline were less than 1, about 2, and more than 5 orders of magnitude, respectively. When the corresponding threonine residue in the Tsr chemoreceptor was replaced with the same amino acids, roughly similar reductions in the response threshold for serine resulted. Thus, these threonine residues seem to have a common role in detecting the aspartate and serine attractant families. A mechanism by which these chemoreceptors detect the amino acid attractants is discussed.
Previous work from our laboratory has shown that the intestine of the suckling rat, unlike adult rat intestine, contains abundant quantities of at least two soluble neutral maltase-glucoamylases. These enzymes are related antigenically to membrane-bound maltase-glucoamylase, which predominates in adult intestine, but are either more easily solubilized or occupy a different cellular locus. To study the soluble enzymes further, we attempted their isolation from the intestine of 11-day-old suckling rats. Initial attempts were complicated by proteolytic degradation, despite the addition of phenylmethylsulfonyl fluoride, N-ethylmaleimide, leupeptin, pepstatin, and EDTA to buffers used for homogenization and column chromatography. Addition of aprotinin, amastatin, bestatin, and phosphoramidone resulted, however, in the isolation of two stable, high molecular weight maltases (HM1 and HM2). Both enzymes eluted before a papain-solubilized membrane-derived maltase-glucoamylase on Sepharose 4B and were separable by DE-52 and Sepharose 6B - Tris affinity columns. They were further purified on a lentil lectin - Sepharose 4B column. Substrate specificities were almost the same and characteristic of maltase-glucoamylases. Hydrophobic binding properties and pH optima of HM1 and HM2 were also similar. HM1 was resolved by sodium dodecyl sulfate - polyacrylamide gel electrophoresis into approximately equal portions of an endo-beta-N-acetylglucosaminidase H sensitive enzyme of molecular weight (MW) 200,000 and an endo-beta-N-acetylglucosaminidase H resistant but endo-beta-acetylglucosaminidase F sensitive enzyme of MW 400,000. In contrast, most of HM2 consisted of a doublet of MW 200,000 - 210,000 that was endo-beta-N-acetylglucosaminidase H sensitive. The intestine of the suckling rat, therefore, contains two soluble maltase-glucoamylase fractions, with a major portion of high mannose rather than complex oligosaccharides.(ABSTRACT TRUNCATED AT 250 WORDS)
This study characterizes the contribution of prostanoids to endothelium-dependent responses in two vascular regions of the guinea pig. We compared the mechanisms of relaxation responses to acetylcholine and adenosine triphosphate (ATP) in the coronary vasculature and in the abdominal aorta of the guinea pig. Endothelium-dependent responses were examined in an isolated, potassium-arrested guinea pig heart utilizing a modified Langendorff preparation. Coronary vessels were constricted with prostaglandin F2 alpha and dilated with acetylcholine (10(-9)-10(-6) mol) or ATP (10(-10)-10(-7) mol) before and after exposure to indomethacin (14 microM, n = 6) or ibuprofen (150 microM, n = 5). Helically cut strips of abdominal aorta (n = 6) were suspended in isolated tissue baths for measurement of isometric force. Relaxation to acetylcholine (5.5 x 10(-7) M) and ATP (10(-5) M) was quantified in strips contracted with norepinephrine before and after exposure to indomethacin (14 microM). In addition, the endothelium was damaged by exposing vessels to free radicals generated by electrolysis of the buffer (4 Hz, 9 V, 1 ms, 5 min). Following electrolysis of the buffer, relaxation responses to acetylcholine and ATP were significantly attenuated in both preparations. In the perfused heart, endothelium-dependent dilatation to acetylcholine, but not ATP were significantly inhibited in the presence of indomethacin or ibuprofen. In contrast, acetylcholine- and ATP-induced relaxation responses in the aorta were not altered by indomethacin. We conclude that prostaglandins contribute to acetylcholine-induced dilatation in the coronary bed but not in the abdominal aorta of the guinea pig. Furthermore, in the coronary bed, different endothelial factors mediate relaxation to acetylcholine and ATP.
Nasal allergen challenges in allergic rhinitis subjects provoke characteristic alterations in nasal and eustachian tube (ET) function. The purpose of this study was to examine the effect of natural pollen exposure on nasal physiology and inflammatory mediators. Grass pollen counts, ET function (sonotubometry), nasal resistance (rhinomanometry), symptoms, mediator levels (saline wash), and skin test reactivity in nine adults with grass allergy were monitored weekly before (week 1), during (weeks 2 to 9) and after (weeks 10 and 11) grass pollen season. Pollen counts peaked at week 3, and then decreased gradually. Mean nasal resistance (cm H2O/L/sec) increased from a baseline of 2.4 +/- 0.5 to 3.7 +/- 1.1 at week 3, peaked at week 4 (5.3 +/- 1.2), remained elevated (weeks 5-8), peaked again at week 9 (6.6 +/- 1.4), and then decreased, Bilateral ET obstruction was not present in any of the subjects at baseline, but was present in five of the nine subjects at week 4. Symptom severity paralleled grass pollen counts. Peak mediator levels were observed at weeks 2 and 9 for histamine and at weeks 3 and 10 for leukotriene C4. Seasonal increases in grass and histamine-induced wheal sizes were also observed. These data show that measurable changes in the function of the nose and ET and the levels of nasal mediators and dermal reactivity accompany and track pollen counts during seasonal exposure and suggest that therapy for seasonal allergic rhinitis should be (1) directed at reducing airway inflammation and (2) continued well beyond the time of peak pollen exposure.
The insulin-like growth factor-II/mannose 6-phosphate receptor which targets acid hydrolases to lysosomes, has two different binding sites, one for the mannose 6-phosphate (Man-6-P) recognition marker on lysosomal enzymes and the other for insulin-like growth factor-II (IGF-II). We have asked whether IGF-II can regulate the cellular uptake of the lysosomal enzyme 125I-beta-galactosidase by modulating the binding of 125I-beta-galactosidase to the IGF-II/Man-6-P receptor. We first isolated high affinity 125I-beta-galactosidase by affinity chromatography on an IGF-II/Man-6-P receptor-Sepharose column. Specific uptake (mannose 6-phosphate-inhibitable) of 125I-beta-galactosidase in BRL 3A2 rat liver cells and in rat C6 glial cells was 3.7-4.8 and 4.0-8.0% of added tracer, respectively. The cell-associated 125I-beta-galactosidase in the uptake experiments largely represented internalized radioligand as measured by acid or mannose 6-phosphate washing. The uptake of 125I-beta-galactosidase was inhibited by an antiserum (No. 3637) specific for the IGF-II/Man-6-P receptor. Low concentrations of IGF-II also inhibited the uptake of 125I-beta-galactosidase. Maximal concentrations of IGF-II inhibited uptake by 73 +/- 8% (mean +/- S.D.) in C6 cells and by 77 +/- 6% in BRL 3A2 cells compared to the level of inhibition by mannose 6-phosphate. The relative potency of IGF-II, IGF-I, and insulin (IGF-II much greater than IGF-I; insulin, inactive) were characteristic of the relative affinities of the ligands for the IGF-II/Man-6-P receptor. IGF-II also partially inhibited the binding of 125I-beta-galactosidase to C6 and BRL 3A2 cells at 4 degrees C and inhibited the binding to highly purified IGF-II/Man-6-P receptor by 58 +/- 14%. We conclude that IGF-II inhibits the cellular uptake of 125I-beta-galactosidase and that this inhibition is partly explained by the ability of IGF-II to inhibit binding of 125I-beta-galactosidase to the IGF-II/Man-6-P receptor.
Cultures of dissociated retinal neurons and photoreceptors from homozygous wild-type, heterozygous rd/+ and homozygous rd/rd retinas have been used to investigate the capacity of isolated photoreceptor cells to synthesize and secrete the interphotoreceptor retinoid-binding protein (IRBP). Retinal cells were dissociated on postnatal day 2 and grown in chemically defined medium in the absence of glial and pigmented epithelial cells. Expression of IRBP immunoreactive materials in these cultures was cell type-specific and developmentally regulated. Thus increasing numbers of rod photoreceptor cells showed immunoreactivity during the first week in culture, whereas nonphotoreceptor cell types remained consistently negative. Photoreceptor immunoreactivity could be detected in permeated (detergent-treated) as well as in unpermeated preparations, the latter suggesting that some IRBP is associated with the photoreceptor cell surface. These materials appeared to be loosely bound to the photoreceptors, since they disappeared when the cultures were exposed for 6 hr to IRBP-free medium but not when they were exposed to IRBP-containing medium. IRBP synthesis and secretion could be demonstrated by analyzing either cell extracts or conditioned medium by "slot blot" and Western blot techniques using affinity purified antibodies against bovine IRBP as well as by fluorographic analysis after metabolic labeling of the cultures with 35S-methionine. Comparisons of cultures from the different genotypes showed many similarities, including the abundance of IRBP-immunoreactive photoreceptors in 7 day cultures. However, immunochemical analysis showed lower conditioned medium/cell extract IRBP ratios in rd/rd cultures, an observation consistent with previous reports suggesting that IRBP secretion may be deficient in rd/rd photoreceptor cells.