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Biomedical subjects

A Parkes

Publications and source records attributed to A Parkes.

At least 19 recordsLinked to original sources
PubMed2000

Altered expression of estrogen receptor coregulators during human breast tumorigenesis.

The hypothesis that altered expression of specific coactivators/repressors of the estrogen receptor occurs during human breast tumorigenesis in vivo is examined in this study. Using in situ hybridization and reverse transcription-PCR assays, the expression of two coactivators (SRA and AIB1) and one repressor (REA) of the estrogen receptor was compared between matched breast tumors and adjacent normal human breast tissue. The levels of SRA and AIB1 mRNA were increased in tumors compared with normal tissues (n = 19; Wilcoxon matched pairs test; P < 0.01). In contrast, the expression of REA mRNA was not different between tumors and normal tissues (n = 19; Wilcoxon; P = 0.110). The ratios of AIB1:REA and SRA:REA were higher (Wilcoxon; P < 0.05) in tumors compared with normal tissues. Furthermore, SRA:AIB1 was higher (Wilcoxon; P = 0.0058) in tumors compared with normal tissues. Although our study is small, these data are consistent with the above hypothesis and suggest that such alterations may have a role in the altered estrogen action occurring during breast tumorigenesis.

Breast↗
PubMed2000

Expression of a repressor of estrogen receptor activity in human breast tumors: relationship to some known prognostic markers.

The expression of a specific repressor of estrogen receptor activity (REA) was investigated by a semiquantitative reverse transcription-PCR assay in 40 human breast tumor biopsy samples with respect to steroid hormone receptor status and other known prognostic variables. The data showed that REA expression was positively correlated with estrogen receptor (ER) levels as defined by ligand-binding assays (Spearman r = 03231; P = 0.042) and that the median level of REA mRNA was significantly (Mann-Whitney two-tailed test, P = 0.0424) higher in ER+ tumors (median = 94.5; n = 30) compared with ER- tumors (median = 645; n = 10), with no significant differences (P = 0.4988) associated with progesterone receptor status alone. In addition, REA expression was inversely correlated with tumor grade (Spearman r = -0.4375; P = 0.0054). When the tumors were divided into two groups based on grade, REA expression was significantly (Mann-Whitney two-tailed test, P = 0.0024) higher in low-grade (median = 97; n = 16) compared with high-grade (median = 76; n = 23) tumors. These results provide preliminary data suggesting that the expression of REA varies among breast tumors and is correlated with known treatment response markers and inversely correlated with a marker of breast cancer progression. REA together with ER status may be an improved marker of endocrine therapy responsiveness in human breast cancer.

Biomarkers, Tumor↗
PubMed1998

Interleukin-6 levels are not increased in women with postpartum thyroid dysfunction.

Postpartum thyroid dysfunction (PPTD) is an autoimmune-mediated thyroid destructive process. Human interleukin-6 (IL-6) is a cytokine found to be increased in subacute thyroiditis, amiodarone-induced thyrotoxicosis, Graves' disease, and other thyroid destructive processes. We report serum IL-6 levels in PPTD in two independent studies. New York Study: In a previous prospective study we demonstrated that PPTD occurred in 25% (7/28) of women with type 1 diabetes mellitus. IL-6 determinations were made on the frozen serum samples of these 28 women during each trimester of their pregnancy and at 1.5, 3, 6, 9, and 12 months postpartum. IL-6 levels were found to be similar in women with PPTD compared with women without PPTD (mean 3.06+/-2.25 vs. 2.51+/-2.21 pg/mL; p = 0.15). No difference in IL-6 levels was found between the pre- and the postpartum periods (mean 2.67+/-1.82 vs. 3.04+/-2.44 pg/mL; p = 0.30) in all 28 women. Cardiff Study: Serum IL-6 levels were measured on frozen serum samples of 30 women with PPTD. IL-6 levels were below the detection limit (25 fmol/L or 0.65 pg/mL) in 94 (67%) of these samples. No significant difference in the mean serum IL-6 levels were found between any time points in the study. There was no correlation between serum IL-6 levels, thyroid peroxidase (TPO)- antibodies and serum thyrotropin (TSH) levels at any time point. IL-6 levels during pregnancy or postpartum were not found to be significantly different in women with PPTD compared with women without PPTD.

Adult↗
PubMed1997

Novel measurement for automated interference pattern analysis of the diaphragm.

The automated interference pattern analysis for limb muscles was modified to take into account the unique features of the needle EMG of the diaphragm. The modification was successful in recording more accurately the number of small and large segments and the activity levels with inspiratory effort. "Clouds" were generated in ten healthy subjects. The techniques may prove useful in electrophysiological investigations.

Diaphragm↗
PubMed1997

Pre-TCR signaling components trigger transcriptional activation of a rearranged TCR alpha gene locus and silencing of the pre-TCR alpha locus: implications for intrathymic differentiation.

A rearranged TCR alpha transgene remains transcriptionally inactive in rag-2-/- thymocytes but can be induced by CD3-mediated signals with concomitant maturation of double-negative (DN) thymocytes to the CD4+CD8+ double-positive (DP) stage. Reciprocally, the same signals silence pre-TCR alpha (pT alpha) expression. In normal C57BL/6 thymocytes, TCR alpha expression is not detected in DN thymocytes while, in contrast, TCR beta expression is initiated at the most immature c-kit+CD44+CD25- stage and continues throughout thymocyte development. pT alpha expression is first detected at the intermediate c-kit +/- CD44+CD25+ DN stage, increases during transition to the more mature c-kit-CD44-CD25+ stage and is lost at the DP stage. Thus, although TCR beta and pT alpha expression are independent, the pre-TCR complex mediates signals controlling the appearance of alpha beta TCR through selective regulation of TCR alpha and pT alpha genes.

Animals↗
PubMed1996

Development of CD4-CD8- alpha beta TCR+NK1.1+ T lymphocytes: thymic selection by self antigen.

Development of CD4-CD8- double negative (DN) alpha beta TCR+ cells were examined by cell transfer experiments using an Ly-5 congenic mouse system. Purified DN alpha beta TCR+ thymocytes injected intrathymically emigrated from the thymus to the spleen. The same cells did not return to the thymus when injected i.v. Similarly, peripheral DN alpha beta TCR+ cells from spleen and liver did not go to the thymus when injected i.v. but migrated to the spleen. These results indicate that DN alpha beta TCR+ thymocytes develop within the thymus and emigrate to peripheral organs. It is thus likely that peripheral DN alpha beta TCR+ cells are at least partly of thymic origin. DN alpha beta TCR+ thymocytes are unique in that they express a natural killer cell marker, NK1.1, which is not found on conventional T cells. We further examined the thymic selection of DN alpha beta TCR+NK1.1+ thymocytes by using an anti-HY TCR-transgenic (tg)/Rag-2(-/-) mouse system with H-2 backgrounds that were negative, positive, or nonselecting for conventional T cells. The number of DNtg TCR alpha beta+NK1.1+ cells was m prominent in male H-2b animals in which conventional T cells are deleted by HY/H-2Db recognition. Fewer DNtg TCR alpha beta+NK1.1+ cells were found in H-2b females (positive selecting background), and almost no DNtg TCR alpha beta+NK1.1+ cells were detected in H-2d animals (nonselecting background). Unlike conventional T cells, DNtg TCR alpha beta+NK1.1+ cells from anti-HY/Rag-2(-/-) H-2b mice express Fc(epsilon)RI(gamma) and CD3zeta as DN alpha beta TCR+NK1.1+ cells from normal C57BL/6 mice. Our results indicate that DNtg TCR alpha beta+NK1.1+ cells are positively selected by self Ag/MHC and emigrate to the peripheral organs.

Adoptive Transfer↗
PubMed1996

Needle EMG of the human diaphragm: power spectral analysis in normal subjects.

Needle EMG of the diaphragm was performed in 43 diaphragms in 23 healthy volunteers. The mean +/- standard deviation for the median frequency (MF) of the power spectrum was 233.3 +/- 58.1 Hz. The MF increased with age and showed a negative correlation with the forced vital capacity (FVC), but there was no correlation with other anthropometric measures or the results of phrenic nerve conduction study. The higher MF in older subjects may be due to early recruitment of larger units. The negative correlation between MF and FVC is likely secondary to a lower level of contraction required for normal breathing in subjects with high FVC. The integrated EMG (iEMG) of each inspiration strongly correlated with the tidal volume and the duration of inspiration. Power spectral analysis of diaphragmatic EMG is feasible and reliable. It can be used to assess respiratory muscle fatigue and may help in the diagnosis of neuromuscular disorders affecting the diaphragm.

Adult↗
PubMed1995

Phrenic nerve conduction study in normal subjects.

Phrenic nerve conduction studies were performed in 50 phrenic nerves from 25 normal subjects using a technique modified from previously described methods. The normal ranges for latency, amplitude, negative peak area, and duration were established. The latency correlates with age and the amplitude increases with chest circumference. With our method, the amplitude increases and the duration decreases with lung volume. We found good right-left agreement and reproducibility. Therefore, the unaffected side can be used as a reference in unilateral phrenic nerve lesions and previous studies can be used for comparison in serial studies. We recommend that phrenic nerve conduction studies be used routinely to diagnose and monitor patients with respiratory involvement from neuromuscular diseases.

Action Potentials↗
PubMed1995

Neuromuscular disorders associated with failure to wean from the ventilator.

OBJECTIVE: To determine, by retrospective chart analysis, the frequency, type and significance of neuromuscular disorders in patients whose clinical features suggested a neuromuscular cause of failure to wean. BACKGROUND: Failure to wean is a common and difficult problem in critical care units. While a neuromuscular cause may be suspected in some patients, the frequency and type has not been determined utilizing comprehensive electrophysiological studies of limbs and the respiratory system. Such knowledge may aid in patient management and prognosis. METHODS: The clinical setting was a critical care/trauma centre that admits 1500 patients per year, approximately 500 being on ventilators for longer than five days. We analyzed the hospital charts of 40 patients admitted to the unit during three years, whose respiratory assessment suggested a neuromuscular cause for failure to wean from the ventilator. To investigate this possibility, we performed electrophysiological studies of the limbs and also of the respiratory system by phrenic nerve conduction and needle electromyography of the chest wall and diaphragm. The results were compared to 25 healthy controls. RESULTS: 38 of 40 patients (95%) had a neuromuscular disorder: 25--critical illness polyneuropathy, 2--Guillain-Barré syndrome, 4--diabetic and critical illness polyneuropathy, 2--uremic and critical illness polyneuropathy, 10--an abnormality of central drive, 5--unilateral phrenic nerve palsy, 3--a neuromuscular transmission defect, and 5--a primary myopathy. Fifteen (38%) had a combination of disorders. Patients with more severe polyneuropathy took longer to wean, a mean of 136 versus 52 days (p = 0.007). The severity of the polyneuropathy had no effect on mortality. CONCLUSIONS: Electrophysiological studies of limbs and the respiratory system are together valuable in confirming the presence, and identifying the specific type of neuromuscular cause for difficulty in weaning from the ventilator. This information is important in patient management and prognosis.

Adolescent↗
PubMed1995

Effect of background scene complexity and field dependence on the legibility of head-up displays for automotive applications.

This study examined the legibility of information presented on head-up displays (HUDs) for automotive application as a function of background scene complexity, the position of the HUD within field of view relative to the background scene, and the perceptual capacity of the perceiver. Groups of field-dependent and field-independent subjects viewed video footage from the perspective of following a lead car on an open road with low, moderate, and high scene complexity. Subjects were required to track the lead vehicle and identify HUD-presented targets of a specified orientation and specified changes in a HUD-presented speedometer. The results indicate that (a) HUD legibility deteriorated with increased visual complexity of the background scene; (b) positioning the HUD on the roadway reduced the effect of background scene complexity on HUD legibility; and (c) field-dependent subjects made fewer correct and more false positive target identifications than did field-independent subjects.

Adolescent↗
PubMed1994

Head-up displays and their automotive application: an overview of human factors issues affecting safety.

In response to the recent innovations to use head-up displays (HUDs) in vehicles, this paper discusses the relevant human factors issues arising from this display format and the potential safety implications. A review is made of the relevant HUD literature, primarily from the aviation field. The primary issues for automotive HUDs relevant to system performance and safety in the driving task involve interference from background scene complexity, system novelty, user perceptual style, cognitive disruption, and perceptual tunnelling. Basic research is necessary to investigate the extent of these issues as well as to resolve fundamental design specifications (e.g. HUD size, shape, placement, information content). It is suggested that the introduction of HUDs into vehicles be carefully considered. This will necessitate not only the reconsideration what constitutes an in-vehicle display, but also what constitutes the information to be conveyed.

Accidents, Traffic↗
PubMed1992

Needle electromyography of the diaphragm.

A method is described for performing needle electromyography of the diaphragm which is safe and causes little discomfort. It provides valuable information concerning neuropathies and myopathies which may affect the diaphragm, and complements information derived from phrenic nerve conduction studies. Firing patterns of motor unit potentials during spontaneous respiration identify upper motor neurone disorders causing respiratory insufficiency.

Action Potentials↗
PubMed1991

Increased urinary transferrin excretion in exercising normoalbuminuric insulin-dependent diabetic patients.

The median rate of urinary transferrin excretion is greatly increased by exercise in subjects with uncomplicated type 1 (insulin-dependent) diabetes. This increase is proportionally far greater than that seen in urinary albumin excretion rate after the same exercise. Non-diabetic control subjects showed no rise in urinary transferrin excretion rate following exercise. N-acetyl-beta-D-glucosaminidase excretion rate was higher in diabetic than control groups but did not rise with exercise. Our results suggest that patients with apparently uncomplicated diabetes have abnormal renal function. In this group an elevated urinary transferrin excretion rate appears to be a more sensitive indicator of altered renal function than is elevated albumin excretion rate. The mechanism underlying exercise-induced urinary loss of transferrin remains to be elucidated.

Acetylglucosaminidase↗
PubMed1991

Abnormal blood pressure response to exercise in normoalbuminuric insulin dependent diabetic patients.

Eight male normoproteinuric Type I (insulin dependent) diabetic patients and eight age- and sex-matched non-diabetic control subjects were studied for their response to exercise. Systolic blood pressure showed an exaggerated response to exercise in the diabetic group (median 123, range 98-151 mmHg, pre-exercise vs. 187, 163-217 mmHg, immediately post exercise P less than 0.01) compared to the control group (median 112 (100-145) pre-exercise, 153 (138-178) post exercise). Resting noradrenaline levels were lower in the diabetic (D) compared with the control (C) group (D: 1.66, 0.55-3.92 nmol/l vs. C: 2.96, 2.04-4.49 nmol/l, P less than 0.02). Levels rose during exercise by 79% (25-307%) and 43% (4-90%) respectively (NS). Resting urinary sodium was raised in the diabetic group and fell during exercise (P less than 0.05) (D: 146, 74-244 mumol/min, C: 108.5 (83.4-151.0) pre-exercise vs. D: 73, 48-264 mumol/min, C: 81.7 (23.0-92.0) post exercise). Resting atrial natriuretic peptide levels were lower in the diabetic group (D: 10.1, 4.3-16.9 pmol/l vs. C: 16.0, 9.5-22.9 pmol/l, P less than 0.02) and levels rose significantly in both groups during exercise (D: 25.9, 5.2-38.9 pmol/l vs. C: 28.6, 17.3-47.2 pmol/l, P less than 0.05). We conclude that exercise provokes an exaggerated rise in systolic blood pressure and decrease in urinary sodium excretion in normoalbuminuric diabetic patients. These findings may reflect increased sensitivity to the renin-angiotensin-aldosterone system. Reduced atrial natriuretic peptide levels may stimulate sodium retention and increased blood pressure in early diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1989

Recording sound from human skeletal muscle: technical and physiological aspects.

In order to examine technical factors that influence muscle sound recording, single twitches of muscle were utilized since their waveforms were likely to be reproducible. We observed that satisfactory recordings could be made with either Archer air interface, or Hewlett-Packard direct contact sensor, microphones. Firm contact and stability between the microphone and the skin surface were particularly important. Frequencies below 20 Hz, the lower limit of the human auditory range, must be recorded, since they account for at least 90% of the power of the muscle sound wave. The chief frequencies were below 4 Hz. The sound wave produced by a maximal twitch of human thenar muscle induced by median nerve stimulation at the wrist is maximal in amplitude over the center and recedes to near zero at the margins of the muscle. It is preceded by the muscle compound action potential and is followed by the force curve, recorded with a strain gauge attached to the thumb. The sound resembles force in total time course, and it increases with increasing strengths of nerve stimulation. However, it differs in its latency, phase relationships, and response to nerve stimulation at different frequencies. Some of the features of muscle sound suggest it relates to both the active contractile and the parallel elastic components of muscle during a twitch contraction, but not the series elastic component.

Adult↗
PubMed1983

The IgG subclass distribution of thyroglobulin antibody synthesized in culture.

Thyroglobulin autoantibodies synthesized by Hashimoto lymphocytes in culture and present in serum have been analysed in terms of their IgG subclass distribution. The autoantibodies produced in vitro were frequently IgG4 or IgG1, whether pokeweed mitogen or Epstein-Barr virus was used to stimulate the cultures, and the subclass distribution of these thyroglobulin antibodies was similar to that observed in the patients' serum. It appears therefore that the antibodies synthesized in vitro in response to polyclonal B-cell activators resemble those produced in vivo, and it seems likely that both pokeweed mitogen and Epstein-Barr virus influence the same B-cell precursors of autoantibody-synthesizing cells, albeit by different mechanisms.

Adolescent↗