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Biomedical subjects

L Taylor

Publications and source records attributed to L Taylor.

At least 19 recordsLinked to original sources

Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity.

Interleukin-8 (IL-8) is a key mediator in the migration of neutrophils from the circulation to the site of inflammation in the tissue. IL-8 is secreted by many cell types in response to proinflammatory stimuli such as interleukin 1, tumor necrosis factor, and lipopolysaccharide and is a potent chemoattractant and activator of neutrophils. Neutrophil activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity (MGSA/GRO) are structurally and functionally related to IL-8 and, like IL-8, bind to specific G protein-coupled receptors on neutrophils. In the present study two closely related cloned IL-8 receptor subtypes are characterized by expression of the cDNA clones in monkey kidney cells (COS-7) or chinese hamster ovary cells and analysis of their ligand binding profiles. Both receptor subtypes bind 125I-labeled IL-8 with similar high affinity, however, the F3R receptor binds IL-8 exclusively, while the 4Ab receptor binds both IL-8 and MGSA/GRO with high affinity and NAP-2 with lesser affinity. Furthermore, we demonstrate with the use of intersubtype chimeric receptors that the specificity of ligand binding to both IL-8 receptor subtypes is dictated by the heterogeneous NH2-terminal domain. The F3R receptor is representative of a restricted IL-8 receptor subtype, and 4Ab represents a nonrestricted receptor subtype. It is proposed that these subtypes be named IL-8 receptors alpha and beta, respectively.

Amino Acid Sequence

Functional expression of the bradykinin-B2 receptor cDNA in Chinese hamster lung CCL39 fibroblasts.

The bradykinin (BK) B2 receptor cDNA was synthesized by rt-PCR and transfected into the Chinese hamster lung fibroblasts, CCL39. The CCL39 do not contain the mRNA for this receptor and do not bind BK. Clones of transfected cells were screened for BK receptor mRNA, binding of BK, and for [Ca2+]i response to BK. The clones showed various levels of receptor mRNA. Scatchard analysis of three clones, B6, B5 and B1, each gave a Kd of approximately 1.0nM while the Bmax for each clone differed at 320, 38.7, and 5.39 fmoles per 10(6) cells respectively. The [Ca2+]i response of the three clones to BK decreased with the receptor number/cell. Thus, levels of mRNA, BK binding and [Ca2+]i response proved proportionally related in the transfected clones. The actions of BK and alpha-thrombin, which has an endogenous receptor in these cells, were assessed in clone B6. BK proved active but also distinct from thrombin. BK at 10nM and thrombin at 2units/ml both effectively increased cytosolic [Ca2+]i. BK at 10nM stimulated PGE2 production three fold over basal, while thrombin only marginally elevated PGE2 levels. Alone, BK stimulated a small increase in 3H-thymidine incorporation into DNA. However, in combination with insulin, BK stimulated DNA synthesis to 76% of thrombin, a potent mitogen in these cells. These results illustrate that the BK-B2 receptor cDNA can be stably transfected into a mammalian cell and can activate transmembrane signalling pathways.

Animals

Theoretical and therapeutic considerations for the anxiety disorders.

Everyone is familiar with that paralyzing state of dread known as anxiety. Although it is unpleasant, the experience of anxiety has adaptive aspects: it can serve as an impetus to effect beneficial life change and can facilitate psychological development. Anxiety becomes of clinical concern, however, when it interferes with intellectual function, or arrests normal social or vocational pursuits. Anxiety disorders are chronic illnesses. Treatment can eliminate many of the disease's debilitating features, but the underlying disorder is not usually cured. Discontinuation of treatment-pharmacological, behavioral, or both-often results in the recurrence of symptoms. The focus of treatment, therefore, generally centers on striking a balance between the goal of alleviating the patient's symptoms, and the need to avoid the deleterious effects which result from long-term treatment (1). The intention of this paper is to review theoretical and therapeutic considerations for four types of anxiety disorder: panic disorder, generalized anxiety disorder, social phobia, and obsessive-compulsive disorder. In doing this, emphasis will be placed on the physiological concomitants and, when possible, neuropsychological bases of these illnesses. Furthermore, pharmacological treatment will be related to the underlying substrata of the disorder whenever possible.

Anti-Anxiety Agents

SK HEP-1: a human cell line of endothelial origin.

SK-HEP-1 is an immortal, human cell line derived from the ascitic fluid of a patient with adenocarcinoma of the liver. We have determined that these cells are of endothelial origin. Despite the location of the tumor from which SK HEP-1 was derived, the cell line does not have properties of hepatocytes. Northern blot analysis of total cellular RNA shows no messenger RNA for the hepatic-specific proteins albumin, alpha-fibrinogen, or gamma-fibrinogen. Endothelial characteristics are seen by transmission electron microscopy. These features include numerous pinocytotic vesicles, electron dense granules consistent with Weibel-Palade bodies, and abundant intermediate filaments, identified immunocytochemically as vimentin. Cultures grown on plastic dishes grow in bundles of polygonal to spindle-shaped cells. Proteins characteristic for endothelial cells are identified by immunocytochemistry. Addition of basement membrane material (Matrigel) or type I collagen to the cultures induces these cells to organize into a tubular network.

Adenocarcinoma

Infections in severely traumatized children.

To study the incidence and types of infection among severely traumatized children, we reviewed the medical charts of 212 children, hospitalized following traumatic injury, who received antibiotics at sometime during their hospitalization. Infection occurred in 19%. Eleven children had trauma-related infections, whereas 29 (71% of those infected) had 36 nosocomial infections. Tracheitis, sepsis, and urinary tract infections were the most common nosocomial infections and were diagnosed in the second week (10 +/- 3 days) following injury. Nosocomial infections were more likely to develop in children who were more severely injured and who had a greater number of invasive procedures. Severe head injury (cerebral edema or subarachnoid hemorrhage) was more common in those with nosocomial infection (P < .0002, odds ratio 6.8, 95% confidence interval 2.2 to 21.3). Those without these injuries were much less likely to develop nosocomial infections (specificity 97% and negative predictive value 86%). Finally, the development of any nosocomial infection prolonged the hospitalization by a mean of 16 +/- 6 days when comparing children with the same degree of traumatic injury. Prevention of nosocomial infection in children with severe trauma will significantly reduce length of hospitalization.

Accidents, Traffic

Developmental changes in the recognition and comprehension of facial expression: implications for frontal lobe function.

Children aged 6-15 years old and adults (over 18) were given three tests designed to test perception and comprehension of facial expression. In the first test subjects were given two composite symmetrical faces made from the left or right half of a normal face, the subjects' task being to indicate which composite more closely resembled the original face. In the second test the subjects matched a series of photographs from Life magazine with key photographs of one of six distinct emotions (sad, fear, happy, anger, disgust, surprise). In the third test the subjects chose a key photograph that was appropriate for the face of a faceless character in a cartoon. On the composite faces test the subjects in all groups exhibited a preference for the left visual field composite, implying that all age groups were processing the faces in a similar manner. The results of the other two tests showed that there was an improvement in the perception of facial expression between the ages of 6 and 8 years, little change until about 13 years, and then a second improvement to adult performance at about 14 years. The performance of the 8- to 13-year-old children was similar to that of adult patients with frontal lobe injuries, which could be taken as evidence that the regions of the frontal lobe involved in the performance of these tasks may not be mature until about 14 years of age.

Adult

Relationship between affect and memory: motivation-based selective generation.

Two experiments examined the influence of anger and retaliatory motivation on memory for negative material. In the 1st study, 60 male undergraduates memorized words with positive, negative, and neutral semantic connotations. It was found that angered men who expected to retaliate against their provocateur recalled more negative words than other words, and more than Ss in all other affect and evaluation conditions. Angered men in the nonretaliation condition displayed no differences in negative word recall. The 2nd experiment investigated memory for details of a provoking experience. Angered men who expected to retaliate more accurately recalled the details of their provocation, but whether they were given the retaliation information before or after provocation had no bearing on memory for these details. Results are discussed in terms of a motivation-based selective generation hypothesis for the relationship between anger and memory.

Adult

Clinical efficacy of spinal instrumentation in lumbar degenerative disc disease.

In review of 871 lumbar fusion procedures performed during the last 8 years, the theoretical advantages of lumbar spinal instrumentation are not borne out in simple discogenic disease. Four groups of 30-35 patients without previous surgery who underwent fusion by different techniques were matched for age, sex, length of follow-up, surgeons, number of levels fused, duration of preoperative symptoms, diagnosis, and type of third party payer. At least for the diagnoses of herniated disc with segmental instability and the instrumentation systems used in this study, results were superior with no internal fixation. This is in keeping with the higher complication rates and frequent need for implant removal reported by many authors.

Adult

A skills programme for preclinical medical students.

An education programme in which preclinical medical students are introduced to common procedural skills is described. This programme is presented by a multidisciplinary health care team using short lectures, demonstrations, mannequin practice, and, in selected instances, practice on class-mate volunteers. The programme was evaluated by the students immediately following the presentation and for one class during their clinical activities one year later. The students' support for this programme was generally enthusiastic and remained undiminished upon reflection 12 months later.

Attitude of Health Personnel

Ability of surrogates to represent satisfaction of nursing home residents with quality of care.

OBJECTIVE: To measure the ability of surrogates to accurately represent nursing home residents' satisfaction with the nursing home care. DESIGN: Comparison by correlation analysis of questionnaire answers by nursing-home residents and their designated surrogates. SETTING: Four non-profit community nursing homes. PARTICIPANTS: One-hundred fifty-two resident-surrogate pairs were included, based on the following criteria: (1) the resident was able to respond to questions verbally and in English, had cognitive abilities sufficient to understand the questions, and had a responsible party who had a telephone number in the medical record; (2) both the resident and the surrogate agreed to be interviewed. OUTCOME MEASURES: A 26-item instrument (21 specific and 5 global items) was developed to measure surrogates' perceptions of residents' satisfaction with the quality of the physician services, nursing care, and the nursing home environment. The instrument was scored on a 4-point Likert scale in which higher scores indicated greater satisfaction and paralleled a similar instrument designed for nursing home residents. Correlation of residents' with surrogates' scores on the satisfaction instruments was examined. RESULTS: The mean score for most items was greater than 3.0, indicating overall satisfaction with the care. Correlations between surrogates and residents on specific items ranged from 0.1 to 0.55. Correlations were highest for global items and items addressing satisfaction with the environment. CONCLUSION: We conclude that nursing home residents' surrogates cannot accurately express the residents' satisfaction with all areas of nursing home care and that their evaluations should not be taken in lieu of the residents' opinions.

Aged

Measurement of cold challenge responses in primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis.

Using computed thermography continuous temperature recordings were made before and after cold challenge of the fingers of control subjects and patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis. Basal skin temperature measurements (Tpre) were significantly lower in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in the controls. Temperatures immediately after cold challenge (T0) were significantly lower in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in controls. The lag phase before the start of temperature recovery (Tlag) was significantly greater in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in control subjects. The maximum recovery index (R%) was significantly less in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in controls. The maximum rate of change of temperature during the rapid phase of rewarming (Gmax) was significantly greater in controls than in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis. Discriminant analysis showed that the dynamic parameters of rewarming (Tlag, Gmax, and R%) showed greater variation between the patients with primary Raynaud's phenomenon and those with Raynaud's phenomenon associated with systemic sclerosis than did Tpre or T0. This method of analysis of cold challenge will be used in studies of the effects of treatment of Raynaud's phenomenon.

Adult

Isolation of monochromosomal hybrids following fusion of human diploid fibroblast-derived microcells with mouse A9 cells.

Rodent x human hybrids containing single human chromosomes are valuable tools in the study of human genetics. Using a retrovirus carrying the neomycin gene, we generated a neomycin-resistant (neor) pool of human diploid fibroblasts. Following fusion of microcells prepared from this pool to mouse A9 cells, we obtained four neor hybrids containing a single human chromosome 2, 3, 5, or 15.

Animals

Does aging affect liver microtubules?

Microtubules are essential for many cell processes, e.g., ligand-receptor endocytosis and the vectorial movement of endosomes. The cytoskeleton, particularly microtubules, may undergo age-related changes that are reflected in cell dysfunctions. For example, the translocation of 125I-IgA-containing vesicles from the sinusoidal surface to the pericanalicular cytoplasm is reduced (greater than 40%) in old versus young rats. Electron microscopic analysis demonstrated that the concentration of microtubule profiles in young animals is within 10-20% of that in old rats. The relative concentration of polymerized tubulin declines greater than 70% by 12 months of age, but the total tubulin content remains unchanged until later, i.e., declining 50% by 24 months. Concomitant increases occur in the free fractions of microtubule-associated proteins (MAP), i.e., MAP1 and heat-stable MAPS. These fractions are not associated with polymerized tubulin. The declines in total and polymerized tubulin, together with the increases in the MAPS' free fractions, may be indicative of fewer and/or shorter microtubules. These data lend credence to the supposition that aging is accompanied by perturbations of microtubule functions that ultimately are expressed as biomarkers characteristic of aging.

Aging

Syphilis in the 'unbooked' pregnant woman.

To determine the prevalence of syphilis in the 'unbooked' pregnant woman attending King Edward VIII Hospital, Durban, mothers who had no previous history or record of antenatal care were studied over a 3-month period. One hundred and fourteen mothers were recruited, 35 (30.7%) of whom had reactive syphilis serology. None had clinical evidence of primary or secondary syphilis. Clinical evidence of congenital syphilis was found in 4 of the 35 (11.5%) babies born to mothers with reactive syphilis serology. While the fluorescent treponemal antibody absorption (FTA-ABS) IgG test was positive in umbilical cord and neonatal venous blood of all 35 babies, the FTA-ABS IgM test was negative in all specimens, including the sera from the 4 babies with clinical signs of syphilis. The FTA-ABS IgM test is therefore of little value for the laboratory confirmation of congenital syphilis. It also has limitations when it comes to screening asymptomatic neonates born to mothers with reactive syphilis serology.

Adult

Silent ischemia in rehabilitation patients: limited clinical utility of electrocardiographic monitoring.

In a prospective blinded trial, 24-hour continuous electrocardiographic monitoring for silent ischemia was used to try to identify rehabilitation patients at risk for cardiac complications. Five of 42 patients had episodes of silent ischemia, none of which occurred during physical therapy sessions. One of these patients had syncope while wearing the Holter; none of the other four patients had significant cardiac complications during their rehabilitation, and all were discharged home. None of the patients without ischemia on the monitor had complications, but two patients of 14 whose ECGs precluded monitoring for ischemia had complications. In addition, six patients had episodes of nonsustained asymptomatic ventricular tachycardia, 12 had episodes of supraventricular tachycardia, and four had significant ventricular ectopy, all without clinical significance. Despite the apparent high sensitivity and specificity of the technique, the positive predictive value of monitoring eligible patients for silent ischemia was 20%. We conclude that ambulatory electrocardiographic monitoring for silent ischemia or ectopy has limited clinical utility in the rehabilitation population.

Aged