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Biomedical subjects

A Young

Publications and source records attributed to A Young.

At least 109 records · Page 6Linked to original sources
PubMed1999

Expression of intercellular adhesion molecules ICAM-1 and ICAM-2 in human endometrium: regulation by interferon-gamma.

The purpose of this study was to localize intercellular adhesion molecule (ICAM)-1 and ICAM-2 in human endometrium and myometrium throughout the menstrual cycle, and to determine whether the expression of these molecules is regulated by interferon (IFN)-gamma. ICAM-1 and ICAM-2 distribution was examined in endometrial biopsies by immunocytochemistry, and Northern blotting was used to quantify ICAM-1 and ICAM-2 mRNA expression in isolated endometrial glands. Stromal fibroblast cultures were exposed to IFN-gamma and the effect on expression of ICAM-1 and ICAM-2 was determined by immunocytochemistry and Northern blotting. ICAM-1 was localized in vivo to the apical surface of the glandular epithelium, the vascular endothelium and endometrial stromal cells throughout the menstrual cycle. Stromal expression of ICAM-1 was up-regulated in menstrual specimens. Northern blotting confirmed the presence of ICAM-1 mRNA in isolated endometrial glands. The expression of ICAM-1 antigen and message was increased in stromal cell culture after incubation with IFN-gamma in a time-dependent manner, suggesting that this cytokine stimulates the expression of ICAM-1 in the endometrial stroma. ICAM-2 antigen expression was restricted to the vascular endothelium. ICAM-2 mRNA was absent in endometrial glands. The widespread distribution of ICAM-1 in human endometrium suggests that this molecule is involved in the process of menstruation, the functioning of glands, blood vessels and stroma, and in regulating leukocyte trafficking into the tissue. ICAM-2 is restricted to the vascular endothelium where it might modulate leukocyte invasion of the stroma and myometrial connective tissue.

Antigens, CD↗
PubMed1999

Nitric oxide donors stimulate prostaglandin F(2alpha) and inhibit thromboxane B(2) production in the human cervix during the first trimester of pregnancy.

Nitric oxide (NO) donors are capable of ripening the human cervix during pregnancy. The purpose of this study was to examine how NO donors may be involved in this process. Cervical biopsies were obtained from pregnant women randomized to receive isosorbide mononitrate (n = 10) or no treatment (n = 10) prior to suction termination. Enzyme-linked immunosorbent assays (ELISA) were performed on culture supernatant for interleukin (IL)-1, IL-6, IL-8, IL-10, IL-15, tumour necrosis factor-alpha, monocyte chemoattractant protein-1 and prostaglandin metabolites. Immunohistochemistry was performed to localize these cytokines, cyclooxygenase (COX)-1, COX-2 and prostaglandin dehydrogenase in cervical tissue and reverse transcription-polymerase chain reaction (RT-PCR) to identify COX-1 and COX-2 expression. Biopsies treated with the NO donor isosorbide mononitrate (IMN) produced significantly greater amounts of prostaglandin F(2alpha) in culture and lower amounts of thromboxane B(2) than controls (572.8 versus 34.9 pg/ml, P < 0.05; 53.3 pg/ml versus 530.9 pg/ml, P < 0.01 respectively). The release of other prostaglandins and of cytokines was not affected by treatment with NO. Inflammatory mediators were localized to cervical tissue and COX-1 and COX-2 expression was confirmed by RT-PCR. In conclusion, the mechanism of NO donor-induced cervical ripening during pregnancy may be mediated in part via increased prostaglandin F(2alpha) synthesis.

Base Sequence↗
PubMed1999

Myometrial constitutive nitric oxide synthase expression is increased during human pregnancy.

Nitric oxide (NO), derived from L-arginine by the action of nitric oxide synthase (NOS), is a mediator of many diverse biological activities, including vasodilation, neurotransmission and inhibition of platelet adhesion. A role for NO in the maintenance of rat and rabbit pregnancy is supported by a variety of studies. A recent study in women demonstrated that myometrial inducible NOS (iNOS) expression was greater in the early third trimester than either the late third trimester or in the non-pregnant condition, suggesting that increased iNOS expression is involved in the maintenance of human pregnancy. Constitutive NOS (cNOS) expression was not determined. The aim of this study was to compare constitutive NOS (both eNOS and bNOS) expression in the human non-pregnant uterus, preterm pregnant uterus (25-34 weeks gestation) and term pregnant uterus (>37 weeks gestation) using immunohistochemistry and Western blotting. Preterm pregnant samples were taken from women with a variety of pathologies necessitating early delivery. We found that eNOS and bNOS protein concentrations were greater in the preterm pregnant myometrium than non-pregnant myometrium. eNOS, but not bNOS, protein concentration was lower in myometrial samples obtained at term compared with those obtained preterm. We conclude that the constitutive isoforms of NOS are also up-regulated in human pregnancy and may play a role in the maintenance of myometrial quiescence.

Blotting, Western↗
PubMed1999

Larsen scoring of digitized X-ray images.

OBJECTIVE: To determine how Larsen scores from digitized X-rays compare to those from film originals. METHODS: A hundred sets of radiographs of patients recruited with early rheumatoid arthritis (RA) were assessed using the Larsen scoring system. Digitized copies of these sets were then viewed on a computer screen and scored according to Larsen in a random order. The quality of the digitized image was also recorded. For each set of X-rays, the signed difference between the score from film and the score from the digitized images was calculated. RESULTS: A total of 95% of the digitized X-ray sets were scored successfully; 5% were not scored due to the images being unreadable. The mean difference between the two sets of scores was -1.2 (95% CI [-2.06, -0.37]). There was no trend in the difference with respect to the mean of the two scores (P>0.1). CONCLUSION: The Larsen scoring of digitized X-ray images has been validated.

Analog-Digital Conversion↗
PubMed1999

Effect of ketorolac and low-molecular-weight heparin individually and in combination on haemostasis.

Low-molecular-weight heparins, when used in surgical patients for thromboprophylaxis, may be used concurrently with ketorolac, a non-steroidal anti-inflammatory drug that is used for analgesia. Because these two agents can influence the haemostatic system, it is important to identify any such effect. The haemostatic interaction between dalteparin and ketorolac was assessed in a double-blind, placebo-controlled, randomized, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo and dalteparin/placebo. The effect of ketorolac and dalteparin on haemostasis was assessed by measuring in-vitro platelet aggregation, anti-factor-Xa, activated partial thromboplastin times and skin bleeding time. The results were analysed for evidence of an interaction between ketorolac and dalteparin. Ketorolac inhibited platelet aggregation in whole blood and platelet-rich plasma. The administration of dalteparin led to a significant increase in levels of anti-factor-Xa and a significant prolongation in the activated partial thromboplastin time, although it remained within the range of the normal population. There was no evidence of any interaction between ketorolac and dalteparin with regard to platelet aggregation, anti-factor-Xa activity or activated partial thromboplastin time. The administration of ketorolac significantly prolonged the skin bleeding time. There was a significant interaction between ketorolac and dalteparin to prolong the bleeding time, although dalteparin alone had no effect on bleeding time. There was an interaction between ketorolac and dalteparin, which affected bleeding times. Such an interaction raises the possibility of haemorrhagic complications developing perioperatively when these agents are used concomitantly. Further studies are required to examine the clinical importance of this interaction.

Adolescent↗
PubMed1999

Axonal transport of N-terminal huntingtin suggests early pathology of corticostriatal projections in Huntington disease.

Aggregation of N-terminal mutant huntingtin within nuclear inclusions and dystrophic neurites occurs in the cortex and striatum of Huntington disease (HD) patients and may be involved in neurodegeneration. We examined the prevalence of inclusions and dystrophic neurites in the cortex and striatum of 15 adult onset HD patients who had mild to severe striatal cell loss (grades 1, 2 or 3) using an antibody that detects the N-terminal region of huntingtin. Nuclear inclusions were more frequent in the cortex than the striatum and were sparse or absent in the striatum of patients with low-grade striatal pathology. Dystrophic neurites occurred in both regions. Patients with low-grade striatal pathology had numerous fibers with immunoreactive puncta and large swellings within the striatal neuropil, the subcortical white matter, and the internal and external capsules. In the globus pallidus of 3 grade 1 cases, N-terminal huntingtin markedly accumulated in the perinuclear cytoplasm and in some axons but not in the nucleus. Findings suggest that in the earlier stages of HD, accumulation of N-terminal mutant huntingtin occurs in the cytoplasm and is associated with degeneration of the corticostriatal pathway.

Adult↗
PubMed1999

EMG responses to free fall in elderly subjects and akinetic rigid patients.

OBJECTIVES: The EMG startle response to free fall was studied in young and old normal subjects, patients with absent vestibular function, and patients with akinetic-rigid syndromes. The aim was to detect any derangement in this early phase of the "landing response" in patient groups with a tendency to fall. In normal subjects the characteristics of a voluntary muscle contraction (tibialis anterior) was also compared when evoked by a non-startling sound and by the free fall startle. METHODS: Subjects lay supine on a couch which was unexpectedly released into free fall. Latencies of multiple surface EMG recordings to the onset of free fall, detected by a head mounted linear accelerometer, were measured. RESULTS AND CONCLUSIONS: (1) EMG responses in younger normal subjects occurred at: sternomastoid 54 ms, abdominals 69 ms, quadriceps 78 ms, deltoid 80 ms, and tibialis anterior 85 ms. This pattern of muscle activation, which is not a simple rostrocaudal progression, may be temporally/spatially organised in the startle brainstem centres. (2) Voluntary tibialis EMG activation was earlier and stronger in response to a startling stimulus (fall) than in response to a non-startling stimulus (sound). This suggests that the startle response can be regarded as a reticular mechanism enhancing motor responsiveness. (3) Elderly subjects showed similar activation sequences but delayed by about 20 ms. This delay is more than can be accounted for by slowing of central and peripheral motor conduction, therefore suggesting age dependent delay in central processing. (4) Avestibular patients had normal latencies indicating that the free fall startle can be elicited by non-vestibular inputs. (5) Latencies in patients with idiopathic Parkinson's disease were normal whereas responses were earlier in patients with multiple system atrophy (MSA) and delayed or absent in patients with Steele-Richardson-Olszewski (SRO) syndrome. The findings in this patient group suggest: (1) lack of dopaminergic influence on the timing of the startle response, (2) concurrent cerebellar involvement in MSA may cause startle disinhibition, and (3) extensive reticular damage in SRO severely interferes with the response to free fall.

Accidental Falls↗
PubMed1999

Adolescent substance use disorders: findings from a 14-year follow-up of speech/language-impaired and control children.

Intervening on the development of adolescent addiction requires an understanding of the role of precursors. In a community sample of youth with and without early childhood speech/language (S/L) impairments, 12.7% of participants had a substance use disorder (SUD). Among these participants, 42.0% met criteria for more than 1 SUD. Interestingly, rates of SUDs did not differ by S/L status. However, S/L-impaired participants did show greater psychiatric comorbidity and poorer functioning. A total of 80% of S/L participants with SUDs had a concurrent diagnosis of antisocial personality disorder, compared with 43.8% of SUDs controls. In a logistic regression analysis, we found age 5 mother-rated problem behavior scores and an interaction between S/L status and teacher-rated conduct problem scores were predictive of SUDs. High conduct scores were predictive of SUDs development among control participants but not among S/L-impaired participants. First substance use and initial SUDs symptoms suggest that a window of opportunity exists to reach these troubled young people before they spiral into addiction.

Adolescent↗
PubMed1999

The physiology of physical performance and training in old age.

Maximal aerobic power, muscular strength and explosive power decline even with healthy ageing. Their values are lower in women than in men of the same age. Women are therefore at risk of crossing functionally important thresholds much earlier. Physical training can increase maximal aerobic power, muscular strength and explosive power in older men and women. These increases may help to delay the crossing of thresholds, and may therefore help the older individual to maintain their independence. For the older patient there may be an additive effect of age and disease. Rehabilitation-induced improvements in exercise performance can therefore offer the potential for even greater gains in the everyday functional ability of the older cardiac patient. When performing tests of physiological responses to exercise or when designing exercise programmes for older people, adaptations need to be made to ensure they are suitable for use with the intended age group.

Activities of Daily Living↗
PubMed1999

Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process.

Inflammatory mediators in the cervix, placenta and fetal membranes play a crucial role in human parturition. The aim of this study was to determine whether the upper and lower segments of the myometrium are infiltrated by inflammatory cells during pregnancy and parturition. Myometrial biopsies were obtained from non-pregnant women, and pregnant women at term before and after the onset of spontaneous labour. Subpopulations of inflammatory cells were identified using immunocytochemistry. The intercellular adhesion molecules, 1 and 2, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule and E-selectin were immunolocalized to investigate their involvement in leukocyte accumulation. Histological analysis demonstrated that inflammatory cells, predominantly neutrophils and macrophages, infiltrate human myometrium during spontaneous labour at term. The infiltrate is predominant in the lower uterine segment but is also present in the upper segment. Increased expression of E-selectin was found on the vascular endothelium of biopsies obtained during labour, suggesting a role for this molecule in the accumulation of leukocytes. These results suggest that inflammatory cell infiltration is part of the physiological mechanisms that occur in the myometrium during parturition. Further understanding of this process may suggest new strategies aimed at preventing preterm delivery.

Cell Adhesion Molecules↗
PubMed1998

Synergy between amylin and cholecystokinin for inhibition of food intake in mice.

Several gastrointestinal peptides which are secreted in response to nutrients have been reported to suppress food intake. Amylin is a peptide hormone co-secreted with insulin from pancreatic beta-cells in response to nutrient stimuli. Cholesystokinin (CCK) is secreted from duodenal and jejunal mucosal cells in response to fat and protein. Amylin and CCK-8 have been reported to reduce food intake in rodents when given centrally as well as peripherally. Amylin injected intraperitoneally (i.p.) reduced food intake over the subsequent 30 min in overnight fasted mice by a maximum of 57 +/- 6% with an ED50 of 0.93 nmol/kg (3.63 microg/kg) +/- 0.34 log units. On a molar basis, this potency was similar to that of CCK-8 (ED50 0.85 nmol/kg (0.97 microg/kg) +/- 0.28 log units; p = 0.93) which inhibited food intake by a maximum of 71 +/- 7%. When amylin and CCK-8 were injected i.p. as an amylin:CCK-8 mixture, immediately before presentation of food in overnight fasted mice, food intake in the subsequent 30 min was reduced by a maximum of 91%, an amount that was greater than that producable by i.p. injection of amylin or CCK-8 alone. Isobolar analysis revealed a marked synergy between amylin and CCK-8 in reducing food intake, such that statistically ineffective doses of amylin and CCK, when combined, evoked near-maximal inhibition of food intake. Because the typical physiological event is for amylin and CCK both to be secreted in response to mixed meals, the synergy between them could indicate a shared role in physiological appetite control.

Amyloid↗
PubMed1998

Pericentrin and gamma-tubulin form a protein complex and are organized into a novel lattice at the centrosome.

Pericentrin and gamma-tubulin are integral centrosome proteins that play a role in microtubule nucleation and organization. In this study, we examined the relationship between these proteins in the cytoplasm and at the centrosome. In extracts prepared from Xenopus eggs, the proteins were part of a large complex as demonstrated by sucrose gradient sedimentation, gel filtration and coimmunoprecipitation analysis. The pericentrin-gamma-tubulin complex was distinct from the previously described gamma-tubulin ring complex (gamma-TuRC) as purified gamma-TuRC fractions did not contain detectable pericentrin. When assembled at the centrosome, the two proteins remained in close proximity as shown by fluorescence resonance energy transfer. The three- dimensional organization of the centrosome-associated fraction of these proteins was determined using an improved immunofluorescence method. This analysis revealed a novel reticular lattice that was conserved from mammals to amphibians, and was organized independent of centrioles. The lattice changed dramatically during the cell cycle, enlarging from G1 until mitosis, then rapidly disassembling as cells exited mitosis. In cells colabeled to detect centrosomes and nucleated microtubules, lattice elements appeared to contact the minus ends of nucleated microtubules. Our results indicate that pericentrin and gamma-tubulin assemble into a unique centrosome lattice that represents the higher-order organization of microtubule nucleating sites at the centrosome.

Animals↗