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Biomedical subjects

A M Lee

Publications and source records attributed to A M Lee.

At least 55 records · Page 3Linked to original sources

Inter-individual variation of selenium in maternal plasma, cord plasma and placenta.

Selenium (Se) in high doses has been known to cause injury to the fetus and newborn. The major difficulty in assessing the effects of selenium on human reproduction stems from the need for a suitable means of estimating maternal and fetal exposure. The present investigation, therefore, examines the respective reliability of maternal plasma, cord plasma and placenta as epidemiological indicators as well as inter-individual variation of this trace element. An unselected population of 128 pregnancies was studied. Obstetrical characteristics were noted. Selenium concentrations were determined for maternal plasma, cord plasma, and placental tissue by fluorometric analysis. Maternal plasma selenium concentrations (Se-Bm) were significantly greater than fetal concentrations (Se-Bc). Placental selenium (Se-Pl) levels were four times that of fetal levels. Variability of Se-Bc is best explained by placental concentrations. Maternal weight and ethnic origin are significantly correlated with Se-Bc. Female newborn have higher selenium levels than male newborn. The present study demonstrates the significance of the placenta as an indicator of fetal selenium exposure.

Adult↗

Metabolic changes associated with ingestion of different macronutrients and different meal sizes in rats.

Indirect calorimetry was used to investigate whole-body metabolic changes occurring during and after feeding in the rat. Measurement of respiratory exchange allowed the derivation of respiratory quotient (RQ = CO2 produced/O2 consumed) and energy expenditure [EE = O2 consumed (364 + 113RQ)], giving an estimate of the energy substrate (fat, carbohydrate, or protein) being utilised and the total substrate oxidation occurring, respectively. Concurrent measurement of locomotor activity (ACT) allowed the changes in EE attributable to feeding (postprandial thermogenesis) to be generally dissociated from those attributable to activity. Experiment 1 examined alterations in RQ, EE, and ACT following brief (< 5 min) calorically matched meals of Froot Loops (86% carbohydrate), casein (protein), lard (fat) and lab chow (mixed macronutrient) and following the ingestion of 0.1% saccharin (which is calorically inert). Rapid (< 5 mins) and sustained increases in RQ occurred following Froot Loop and lab chow meals indicating increased utilization of carbohydrates as an energy substrate. Casein caused little change in RQ, while lard caused a drop in RQ approximately 30 min following ingestion, indicating increased fat utilization following absorption of the lard meal. Saccharin caused little change in RQ, suggesting that a sweet taste is not sufficient to alter substrate utilization. Increased EE was seen following the Froot Loops and lab chow meals in the absence of corresponding increases in ACT, suggesting a postprandial thermogenic effect of these meals. In Experiment 2, the metabolic changes accompanying a large (5 g) and small (0.5 g) Froot Loops meal were compared. The large meal resulting in a larger, more rapid and more sustained increase in RQ than the small meal. In addition, there was an increase in EE in the absence of corresponding increases in ACT following the large meal suggesting the presence of postprandial thermogenesis. It is concluded that both meal macronutrient content and meal size are important determinants of postprandial substrate utilization and thermogenesis in rats.

Animals↗

Use of the teleost saccule to identify genes involved in inner ear function.

The vertebrate inner ear sensory epithelia contain different types of hair cells and supporting cells. The teleost saccule is anatomically similar to the mammalian saccule and is primarily involved in the detection of translational acceleration and orientation with respect to gravity. To facilitate molecular studies of the teleost saccule cDNA libraries were constructed from microdissected Lepomis macrochirus (bluegill sunfish) saccular maculae. To our knowledge, this is the first report of cDNA libraries constructed from the saccule. In one instance, a non-polymerase chain reaction-based method of amplifying a mRNA population from limited amounts of starting tissue was employed that allowed construction of cDNA libraries from nanogram amounts of tissue mRNA. Conventional cDNA libraries were constructed from the sunfish saccular maculae as well. These cDNA libraries enriched in hair cell and supporting cell transcripts should facilitate molecular biological studies of inner ear sensory epithelia. As an example of their utility, efforts to identify tyrosine kinases expressed in the saccular endorgan using low-stringency hybridization screening of these cDNA libraries and the partial sequence of a cDNA found to encode an erbB-2-related tyrosine kinase are also reported.

Amino Acid Sequence↗

Biologicals: test procedures available to assess components and products, with limitations.

Contamination with a pathogen, residual live organisms in inactivated products, and a lack of safety of live products may be considered to constitute the greatest risks associated with the use and the international movement of biological products. Although tests are conducted to monitor the risks, the limitations of such tests must be recognised and steps should always be taken to minimise and, as far as possible, avoid the risk. Tests must be suitably sensitive and specific for their function, but they must also be practical and reproducible. Studies on the sensitivity of tests provide a measure of their limitations. The author describes points to consider for the assessment of the suitability of different test methods. Emphasis is placed on tests for parameters associated with risk, such as extraneous agent testing. Examples of such analyses are discussed. There is a need for an exchange of information and a scientific debate on such issues if international acceptance of test methods and harmonization of requirements are to be achieved.

Animals↗

Stress-induced changes in respiratory quotient, energy expenditure and locomotor activity in rats: effects of midazolam.

Changes in O2 consumption, CO2 production and locomotor activity were examined in rats exposed to (1) brief footshock, (2) an aversive conditioned stimulus (CS) predicting footshock, or (3) the anxiogenic drug FG-7142. Respiratory quotient (RQ = CO2 produced/O2 consumed) and energy expenditure [EE = O2 consumed (364 + 113RQ)] were derived to give an estimate of the energy substrate (fat, carbohydrate or protein) being utilised and total substrate oxidation respectively. In experiment 1, footshock (4 x 5 s 0.6 mA shocks over 2 min) produced an immediate increase in RQ, EE and activity. The RQ and EE effects were attenuated by the benzodiazepine midazolam (1 mg/kg). In experiment 2, an aversive CS, consisting of flashing light and buzzer that had 24 h earlier been repeatedly paired with foot-shock (20 x 5 s 0.6 mA shocks) caused a pronounced drop in RQ, an increase in EE and locomotor activity suppression. The effects of the aversive CS on RQ and EE were reversed by midazolam (1 mg/kg). In experiment 3, FG-7142 (10 mg/kg) produced a steep drop in RQ that persisted for at least 2 h and which was reversed by midazolam (1 mg/kg) and delayed by the benzodiazepine antagonist RO 15-1788 (10 mg/kg). FG-7142 also tended to inhibit EE and locomotor activity, but these effects did not reach statistical significance. Overall, these data show that stress causes profound alterations in RQ, EE and activity and that the pattern of change in these parameters differs with the nature of the stressor involved.

Animals↗

Predicting pure tone thresholds in normal and hearing-impaired ears with distortion product emission and age.

Distortion product emission (DPE) growth functions, demographic data, and pure tone thresholds were recorded in 229 normal-hearing and hearing-impaired ears. Half of the data set (115 ears) was used by a discriminant analysis routine to classify DPE and demographic features into either a normal pure tone threshold (PTT) group or an impaired PTT group (PTT greater than 30 dB SPL) at six frequencies in the audiometric range. The six discriminant functions developed from this classification process were then used to predict pure tone threshold group membership in the remaining 114-ear data set. Frequency-specific prediction accuracy varied from 71% (correct classification of hearing impairment at 1025 Hz) to 92% (correct classification of normal hearing at 2050 Hz). Of the 45 DPE and demographic variables evaluated, the DPE amplitude associated with an f2 of moderate level (50 dB SPL) and a frequency corresponding to pure tone threshold was generally most predictive. DPE level was found to be weakly correlated with subject age and perhaps for this reason age was frequently included in discriminant functions. For our data, discriminant functions with one variable, two variables, or 5-10 variables showed no differences in predictive performance. This research suggests that DPE measures can reliably categorize pure tone thresholds as normal or impaired in large populations with varied cochlear hearing status.

Acoustic Stimulation↗

The in vivo effects of rhIL-1 alpha therapy on human monocyte activity.

Pleiotropic cytokines such as interleukin-1 alpha (IL-1 alpha) have multiple effects on peripheral blood monocytes (PBMs). This study examined the ability of in vivo recombinant human IL-1 alpha (rhIL-1 alpha) therapy to enhance clinically important monocyte functions in ovarian cancer patients prior to chemotherapy. After 4 days of continuous infusion, in vivo rhIL-1 alpha therapy amplified both the number and activity of PBMs. Therapy with rhIL-1 alpha increased the number of PBMs sixfold. These monocytes had a significantly increased ability to produce superoxide anion in response to phorbol 12,13-dibutyrate stimulation. Their ability to secrete spontaneously the immunomodulatory cytokines IL-1 alpha and IL-1 beta was significantly increased, but their ability to secrete tumor necrosis factor alpha (TNF-alpha) was not significantly elevated. These effects of rhIL-1 alpha infusion on cytokine secretion by PBMs appear to be related to rhIL-1 alpha-induced increases in the mRNA levels for these cytokines. In contrast, rhIL-1 alpha therapy did not significantly alter PBM response to lipopolysaccharide (10 micrograms/ml). In summary, infused rhIL-1 alpha, in addition to its use as a myeloprotective agent, has enhancing effects on the number and activity of PBMs. The effects of rhIL-1 alpha infusion on PBM function demonstrated here should at least transiently increase the ability of monocytes to combat infection and enhance host immune response.

Carboplatin↗

Multiple supernumerary premolars: their occurrence in three patients.

The occurrence of supernumerary teeth in the premolar regions of three patients is reported. Of the 20 supernumerary teeth identified, 16 had crowns which resembled premolars and may thus be considered to be supplemental premolars, while the remainder were conical in shape. The delayed development of the supernumerary teeth in the premolar region supports the hypothesis that these teeth were part of a post-permanent dentition. The eruption of six of the eight supernumerary teeth in the 30-year-old patient demonstrated that given time some of these teeth can erupt into the dental arch.

Adolescent↗

Control of product batches (before and after registration). The British approach.

In the United Kingdom, some pre-registration testing of immunological products is carried out. However, this is normally not extensive. Usually the tests are laboratory tests undertaken to verify results obtained by the manufacturer or quality controller. For many years, routine post-registration testing of batches of immunological products has been carried out. However, this has ceased and had been replaced by a new system known as the Quality Assurance/Quality Control (QA/QC) scheme. The new scheme is designed to provide the Veterinary Medicines Directorate (VMD) with assurance of the continuing quality of batches of immunological products. The basis of the scheme is a system of inspection of companies' quality control facilities and procedures, every eight months, by staff with appropriate microbiological qualifications and experience. Before an inspection is carried out, the company must provide detailed documentation on the facilities and the quality control procedures used for each product. This provides the inspector with the background information for the inspection and discussions with the company.

Animals↗

Presentation of the EEC directive (81/852)--quality.

The EC directive 81/852 has been revised to include a number of parts setting out the information to be included in applications for marketing authorizations for veterinary immunological products. Part 6 contains the details of the quality aspects which must be addressed by the applicant. It is divided into sections and provides the applicant with the structure and layout to be used for the presentation of the information in the dossier. The applicant must provide sufficient detail to allow the competent authority to assess the quality of the product, including aspects such as batch-to-batch consistency and the risk of contamination of batches with extraneous agents. Thus the dossier must contain details of the starting materials, the method of manufacture, and the controls and tests on the starting materials and intermediate and finished products. The details of the blending and composition must be included. Limits of acceptance should be provided. Procedures used such as inactivation and purification steps and quality control tests should have been shown to be appropriate and the results of the validation studies must be presented. The information supplied must be accompanied by results obtained from batches manufactured by the method described. A justification of the proposed shelf-life of the product must be made with supporting evidence from real-time stability studies.

Animals↗

Chitin utilization by marine bacteria. A physiological function for bacterial adhesion to immobilized carbohydrates.

Chitin turnover is essential for recycling carbon and nitrogen in marine ecosystems. A key step in this process is the adhesion of marine bacteria to chitin-containing particulates. Vibrio species were therefore surveyed for their ability to bind to immobilized carbohydrates, and one, Vibrio furnissii, adhered to glycosides of three sugars, N-acetylglucosamine (the preferred ligand), D-mannose, and D-glucose. A single Ca(2+)-requiring lectin is responsible for binding to the three sugars. Cells adhering to the chitin analogue divided at the same rate as cells in liquid culture. The first progeny of adherent cells continued to bind to the beads, but the population gradually shifted to a large fraction of free swimming cells, a process that may be necessary for colonization. Metabolic energy is required for cell adhesion to the glycosides, and transient (or no) adhesion occurred in incomplete growth media. The results were explained by studying met and pro mutants. Both the initiation and maintenance of lectin-mediated adhesion requires continuous protein synthesis; expression of lectin activity is a major priority of these cells and functions under conditions adequate for minimal protein synthesis, but insufficient to support cell growth. The adhesion/deadhesion apparatus is apparently used to continuously monitor the nutrient status of the environment, i.e. as a nutrient sensorium. In incomplete medium, cells deadhere, presumably to migrate to a more favorable environment.

Bacterial Adhesion↗

Chimeric BCR-abl messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia.

We correlated polymerase chain reaction (PCR)-detectable BCR-abl fusion transcripts with cytogenetic status in 24 patients with acute lymphocytic leukemia (ALL). Of 10 Philadelphia chromosome negative (Ph-) patients, only one was found to exhibit a BCR-abl fusion transcript. Fourteen patients with Ph+ ALL, including eight in clinical remission, exhibited PCR-detectable BCR-abl rearrangements. A detectable Ph chromosome was present in only five of the eight patients in clinical remission. Of the three cytogenetically negative, BCR-abl-positive patients, two eventually succumbed to post-bone marrow transplantation (BMT) relapse. The third died of early transplant complications. Serial PCR analyses were performed on four Ph+ ALL patients in clinical remission who underwent allogeneic BMT. One patient who was PCR negative on post-BMT days 21 and 75 became PCR-positive on day 116 and died in relapse on day 154. One patient was weakly positive for BCR-abl on day 23, negative on day 56, but died of transplant complications on day 124. Two patients exhibited no post-BMT BCR-abl rearrangements and remain well on days 279 and 371. Our findings suggest that PCR analysis may be useful in the early identification of relapse in patients transplanted for Ph+ ALL.

Adult↗

Epikeratoplasty with nonlyophilized tissue in children with aphakia.

We studied 75 epikeratoplasty procedures using nonlyophilized tissue performed by eight ophthalmic surgeons in 70 eyes (47 patients) to correct for aphakia in children less than 8 years of age (mean age, 3.4 +/- 2.1 years). Of the 47 patients in the study, 24 were girls and 23 were boys; 23 patients had bilateral surgery. Seven of the epigrafts required removal; two were not replaced, and five underwent successful repeat epikeratoplasty. Overall, the success rate (that is, the percentage of epigrafts that remained optically and functionally clear throughout the course of this study) for the epikeratoplasty procedure was 89% (62 of 70 eyes) for initial surgery and 96% (67 of 70 eyes) for repeat surgery. The average spherical equivalent was +14.4 +/- 3.7 diopters preoperatively and +0.3 +/- 2.9 diopters one year after the operation. One year after the final surgical procedure, 42 of 56 eyes (75%) were within 3 diopters of emmetropia. In the 29 verbal patients, best-corrected visual acuity was 20/100 or better in 25 (86.2%) one year after the operation.

Aphakia↗

Monoclonal IgMs with anti-Gal(beta 1-3) GalNAc activity in lower motor neuron disease; identification of glycoprotein antigens in neural tissue and cross-reactivity with serum immunoglobulins.

IgM monoclonal antibodies (M-proteins) with anti-Gal(beta 1-3)GalNAc and anti-Gal(beta 1-3)GlcNAc activity that bind to gangliosides GD1b and GM1, from two patients with lower motor neuron disease were tested for binding to neural glycoproteins. The M-proteins bound to several glycoproteins in the central and peripheral nervous system including to some in the non-myelin or axonal fraction only. Peanut agglutinin (PNA) which is specific for Gal(beta 1-3)GalNAc, bound to the same protein bands. Since serological studies revealed that the M-proteins were complexed to IgG, serum immunoglobulins were tested for presence of Gal(beta 1-3)GalNAc epitopes. Both PNA and the M-proteins bound to immunoglobulin heavy and light chains, suggesting that the circulating M-proteins bind to Gal(beta 1-3)GalNAc on other immunoglobulins. These studies indicate that in addition to gangliosides the M-proteins might bind to Gal(beta 1-3)GalNAc bearing glycoproteins in vivo and that carbohydrate epitopes on immunoglobulins might have a role in the development and regulation of autoantibodies which cross-react with neural antigens and may cause neurological disease.

Antibodies, Monoclonal↗

Preactive planning and conceptions of success in elementary health education.

Prospective classroom teachers' thoughts and understanding about teaching health were examined in this study. The study described the preactive thought processes of classroom teachers as they planned a lesson on health and teachers' conceptions of success and failure during the lesson. Before teaching a 30-minute lesson in health, participants were asked to "think aloud" during a planning session. Content of the thoughts was audiotaped, transcribed, and analyzed. After the lesson, participants listed critical events they described as related to success and lack of success during the lesson. Content of the written accounts was organized into clusters with common elements. Findings indicated teachers' concerns during planning were related to identifying and arranging content for maximum involvement and enjoyment. Most teachers defined success in terms of student affective rather than cognitive behaviors.

Attitude↗