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PubMed1992

Glycerylphosphorylcholine (GPC) diesterase related alterations in the oxygen consumption profile of rat spermatozoa in differing functional states.

The functional interaction of the estrogen-induced uterine enzyme glycerylphosphorylcholine (GPC) diesterase with epididymal rat sperm before and after incubation under capacitating conditions was investigated indirectly, by measuring the glycerol phosphate (GP) released on enzymatic hydrolysis of GPC and using oxygen consumption as a measure of oxidative phosphorylation by the sperm. Freshly released, washed sperm metabolized GP but not GPC. Utilization of GP was found to be inhibited by 2 microM oligomycin but was enhanced dose-dependently in the presence of the uncoupling agent, 2,4-dinitrophenol, indicating that the process was essentially similar to that occurring in somatic mitochondria in that it involved electron transport via ubiquinone and the cytochrome system and was coupled to ATP synthesis. However, on incubation of sperm under conditions supporting capacitation, which led to a striking increase in oxygen consumption, the presence of GP decreased oxygen uptake significantly, in a manner similar to that occurring in the presence of the glycolysable substrate, glucose. The implications of these GPC diesterase-induced metabolic alterations in sperm function are discussed.

Animals↗
PubMed2004

Impact of lung volume reduction surgery versus rehabilitation on quality of life.

This study aims at evaluating the effects of lung volume reduction versus respiratory rehabilitation on quality of life, assessed by three different questionnaires. Sixty emphysematous patients were randomised by computer to receive either surgery (n = 30) or rehabilitation (n = 30). Life quality was evaluated by the Nottingham Health Profile, the Short Form (SF)-36 item and the St George's questionnaires. As reported previously, dyspnoea index, forced expiratory volume in one second, residual volume, 6-min walk test and arterial oxygen tension improved after surgery more than after rehabilitation. Quality of life was significantly improved after surgery as follows Nottingham Health Profile physical mobility; SF-36 physical and social functioning, mental and general health, emotional role; St George's general, activity. At multivariate analysis 6- and 12-month changes after surgery of Short Form-36 physical functioning, general health, and St George's activity domains were significantly correlated with forced expiratory volume in one second, while Short Form-36 social functioning and Nottingham Health Profile isolation correlated with residual volume. Functional and especially symptomatic improvements persisted: dyspnoea index, residual volume, and Short Form-36 and St Georges's physical scores were still significant at 4 yrs. Surgery produces greater and longer effects than rehabilitation on quality of life by improving both physical and psychosocial domains. Symptomatic improvements persisted at 4 yrs.

Activities of Daily Living↗
PubMed2002

Quantitative analysis of varying profiles of hypoxia in relation to functional vessels in different human glioma xenograft lines.

Tissue oxygenation influences the radiation response of tumors. To further investigate the underlying mechanisms of tumor hypoxia, the spatial distribution of hypoxic cells in relation to the vasculature was studied. In a panel of three human glioma xenograft lines (E2, E102, E106) with different growth characteristics, tumor line-specific patterns of hypoxia (pimonidazole) and (functional) vasculature (Hoechst 33342) were observed. Two of the three glioma lines showed a more homogeneous distribution of perfused vessels (E102 and E106) than the third glioma line (E2). Although all tumors showed hypoxia, the distance at which the steepest part of the gradient of the hypoxia marker was found varied significantly among the different glioma lines. The faster-growing E102 tumors had the longest distance (>300 microm). These results indicate that tumor line-specific factors, rather than vascular geometry alone, may determine the oxygenation status of a tumor. As a consequence, vascular density cannot be used as a surrogate parameter for tumor hypoxia when comparing different tumors. Additional hypoxia and perfusion markers will further improve our understanding of changes in tumor physiology at the microregional level explaining the relationship between the low oxygen levels and the response of tumors to treatment.

Animals↗
PubMed2002

The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses.

The role of LL-37, a human cationic antimicrobial peptide, in the immune system is not yet clearly understood. It is a widely expressed peptide that can be up-regulated during an immune response. In this report, we demonstrate that LL-37 is a potent antisepsis agent with the ability to inhibit macrophage stimulation by bacterial components such as LPS, lipoteichoic acid, and noncapped lipoarabinomannan. We also demonstrate that LL-37 protects mice against lethal endotoxemia. In addition to preventing macrophage activation by bacterial components, we hypothesized the LL-37 may also have direct effects on macrophage function. We therefore used gene expression profiling to identify macrophage functions that might be modulated by LL-37. These studies revealed that LL-37 directly up-regulates 29 genes and down-regulated another 20 genes. Among the genes predicted to be up-regulated by LL-37 were those encoding chemokines and chemokine receptors. Consistent with this, LL-37 up-regulated the expression of chemokines in macrophages and the mouse lung (monocyte chemoattractant protein 1), human A549 epithelial cells (IL-8), and whole human blood (monocyte chemoattractant protein 1 and IL-8), without stimulating the proinflammatory cytokine, TNFalpha. LL-37 also up-regulated the chemokine receptors CXCR-4, CCR2, and IL-8RB. These findings indicate that LL-37 may contribute to the immune response by limiting the damage caused by bacterial products and by recruiting immune cells to the site of infection so that they can clear the infection.

Adjuvants, Immunologic↗
PubMed2002

The eicosanoid factor: a determinant of individuality of nephron segments.

BACKGROUND: Nephron function is segmented, each segment has characteristic transport mechanisms and individual eicosanoid profiles. The transport function of the medullary thick ascending limb of Henle's loop (mTAL) establishes the osmolar gradient upon which extra cellular fluid volume (ECFV) conservation depends. The overriding importance of the mTAL to regulation of ECFV is evident in the diuretic-natriuretic potency of furosemide-like agents which target the mTAL. RESULTS: The mTAL has been shown to be heavily invested with cytochrome P450 monooxygenases (CYP), chiefly omega/omega-1 hydroxylase activity, that generate 19- and 20-hydroxyeicosatetraenoic acid (HETEs). However, displacement of omega hydroxylase by an inducible cyclooxygenase mechanism (COX-2) can be effected by several interventions: long-term infusion of angiotensin II (ANG II), adrenalectomy and elevated extracellular Ca2+ concentrations. This switching mechanism (CYP > COX-2) has been shown to be dependent on activation of tumor necrosis factor alpha (TNFalpha) by ANG II. It represents a long-term adaptive mechanism of the mTAL with production of PGE2 whereas in the short-term, ANG 11 increases 20-HETE synthesis by the mTAL. The effect of Ca2+ on mTAL eicosanoid-related mechanisms provides an explanation for the natriuretic response to hypercalcemia and diminished ability to concentrate urine. CONCLUSION: The expression of COX-2 in the TAL has been linked to activation of the renin-angiotensin system, glucocorticoid deficiency and hypercalcemia, all of which operate through a mechanism in which production of TNFalpha by the TAL is pivotal.

Animals↗
PubMed1985

Comparison between antibiotic irrigation and mobilization of pectoral muscle flaps in treatment of deep sternal infections.

Between January of 1978 and December of 1983, 41 patients developed deep sternal infections with mediastinitis after cardiac operations. Between January of 1978 and December of 1981, 19 of these patients were treated with débridement, primary wound closure, and mediastinal antibiotic irrigation (Group I). Between January of 1982 and December of 1983, 22 patients were treated with débridement, open "clean" packing, and delayed wound closure by the technique of pectoral muscle flap mobilization, which preserves the thoracoacromial pedicles and the pectoral humeral attachments (Group II). The purpose of this study was to compare the results of the treatment of deep sternal infections after cardiac operations with these two techniques. The perioperative hemodynamic, operation, functional, and pathological profiles of both groups of patients were the same. The cosmetic and functional results were the same in both groups as were shoulder girdle and torso mobility. We conclude that either technique is equally effective in the management of patients in whom the serious complication of deep sternal infection with mediastinitis develops after cardiac operation, and we now recommend débridement and pectoral muscle flap closure in one stage.

Anti-Bacterial Agents↗
PubMed1997

[The use of regression functions for reconstruction of the cutaneous profile, from facial bone elements].

Based on a sample of 51 living subjects, aged 21 years, whose sex was known and who has a teleradiographic tracing of the head (including soft tissues) in vestibular orientation, statistical mean types were established using the rectangular coordinates of 9 skeletal points and 10 cutaneous points. Spatial variability was demonstrated. The position of the skin points was placed relative to the homologue skeletal points and was used for simple and multiple "regression" equations for each of the coordinates. This study demonstrated that, despite application of sophisticated statistical procedures, there is a great degree of incertainty in the validity of facial "reconstruction" for a given subject.

Adult↗
PubMed1999

Selectivity profile of muscarinic toxin 3 in functional assays of cloned and native receptors.

By using acetylcholine-induced stimulation of [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding to membrane G proteins as a functional assay of the cloned human m1-m4 muscarinic receptor subtypes stably expressed in Chinese hamster ovary cells, muscarinic toxin 3 (MT3) was found to block the m4 receptor with a potency (pA2 = 8.33) much higher than those displayed at the m1 (pA2 = 6.78), m3 (pA2 = 6.3), and m2 (pA2 < 6.3) subtypes. In N1E-115 cells, which have been reported to express m4 receptors coupled to inhibition of cAMP, MT3 potently antagonized the carbachol-induced inhibition of adenylyl cyclase with a pA2 of 8. 81 and displayed monophasic inhibitory curves. Unexpectedly, in NG108-15 cells, known to express only m4 receptors, MT3 counteracted the carbachol inhibition of adenylyl cyclase with a lower potency (pA2 = 7.60) and showed a biphasic inhibitory curve, suggesting the participation of both m4 and m2 receptors. This possibility was supported by radioligand binding data showing that MT3 failed to completely displace the binding of [3H]N-methylscopolamine to NG108-15 cell membranes and by reverse transcription-polymerase chain reaction analysis, revealing the presence of mRNAs for both m4 and m2 receptor subtypes. These data demonstrate that MT3 possesses a high functional receptor selectivity for both the cloned and native m4 receptors and that in cell systems containing m4 and m2 receptors coupled to a common response, the toxin constitutes a powerful tool to resolve the relative contribution by each receptor subtype.

Adenylyl Cyclases↗
PubMed1996

A cross-national study of quality of life factors associated with patterns of elderly disablement.

This study examines individual-level data of non-institutionalized elderly from Bahrain, Burma, DPR Korea, Egypt, Indonesia, Jordan, Sri Lanka, Thailand and Tunisia. The Grade of Membership multivariate procedure is used to determine profiles of disablement, based upon functional disability and depression items, and to examine socio-demographic and quality of life covariates associated with such profiles. The analysis yielded six profiles or types of disablement: functionally and emotionally healthy, functionally healthy with some depressive symptoms, some strength problems, severely depressed, mobility problems and functionally frail. The healthy profile had higher probabilities associated with males, whereas the very depressed, and those with physical strength limitations, and mobility problems were more likely to be female. There is a strong positive association between age and functional disabilities. The more depressed profiles, however, tended to be among the younger age categories, and the depressed had higher probabilities associated with being not married. The examination of quality of life covariates indicates that the functional and emotional limitations generally are correlated with a lower quality of life. The more functionally disabled and the depressed profiles had more negative self-assessments of health and lower morale scores. The very depressed had less instrumental social support in terms of available kin. Also, the functionally and emotionally disabled profiles expressed less satisfaction of visits with family and friends. Country-specific patterns of elderly disablement indicate a possible disability transition such that as countries become more developed there may be an increase in the prevalence of disabled elderly. However, there are exceptions to this trend, and these may be due to both cultural factors and data limitations.

Activities of Daily Living↗
PubMed2005

Repetitive behavior profiles in Asperger syndrome and high-functioning autism.

Although repetitive behaviors are a core diagnostic domain for autism spectrum disorders, research in this area has been neglected. This study had two major aims: (1) to provide a detailed characterization of repetitive behaviors in individuals with Asperger Syndrome (AS), high-functioning autism (HFA), and typically developing controls (TD); and (2) to examine whether differences in repetitive behavior profiles could provide evidence for the external validity of AS separate from HFA. Specifically, it was hypothesized that circumscribed interests would be more prevalent and cause more impairment in the AS group than the HFA group, while the reverse would be true for other categories of repetitive behavior. The parent(s) of 61 children and adolescents (19 with AS, 21 with HFA, and 21 TD) completed two interviews focused specifically on lifetime and current repetitive behavior symptoms. No reliable differences in repetitive behavior between AS and HFA children were found. Results suggested that circumscribed interests differ in developmental course from the three other DSM-IV-TR categories of repetitive behavior. Internal consistency among the four DSM-IV-TR categories of repetitive behavior was high, alpha = .84, providing evidence for a unitary repetitive behaviors factor. The importance of expanding research in the repetitive behavior domain is highlighted as part of the necessary integration of behavioral and neurobiological approaches to understanding the etiology of autism.

Adolescent↗
PubMed1994

Subcortical aphasia: the core profile of capsulostriatal infarction.

There has been disagreement about the precise characteristics of "subcortical aphasia." We evaluated 14 patients with aphasia after subcortical lesions and controlled for duration, general anatomic site of lesions (capsulostriatal only), and etiology. The clinical profiles of the patients were quite similar, varying in severity in rough proportion to lesion size and varying in quality in proportion to anterior paraventricular extent. Large lesions were associated with impaired "executive" and "generative" language functions. Similar aphasia profiles in patients with deep frontal and paraventricular white matter lesions suggest that damage to a frontal-caudate functional system underlies a "core" aphasia profile in these patients.

Aged↗
PubMed2007

Ambulatory blood pressure monitoring and renal functions in children with a solitary kidney.

The aim of this study is to investigate the blood pressure (BP) profile, microalbuminuria, renal functions, and relations with remaining normal kidney size in children with unilateral functioning solitary kidney (UFSK). Sixty-six children with UFSK were equally divided into three groups: unilateral renal agenesis (URA), unilateral atrophic kidney (UAK), and unilateral nephrectomy (UNP). Twenty-two age-, weight-, and height-matched healthy children were considered as a control group. The serum creatinine level and first-morning urine microalbumin and creatinine concentrations were determined by the standard methods. Also, the BP profile was determined by ambulatory blood pressure monitoring (ABPM). We found that the serum creatinine level was higher and creatinine clearance was lower in each patient groups compared to those of the control group (p < 0.05). Compared with the controls, each group of patients had mean office, 24-h, daytime, and night-time systolic and diastolic BP values similar to those of the controls (p > 0.05). An inverse correlation was found between the renal size standard deviation scores (SDS) of normal kidneys and 24-h systolic and diastolic BP load SDS in all of the patients (p < 0.05; r = -0.372, r = -0.295, respectively). The observed relationship between renal size SDS and 24-h mean arterial pressure (MAP), systolic and diastolic BP load SDS suggests that children with UFSK should be evaluated by using ABPM for the risk of hypertension.

Adolescent↗
PubMed2002

Characteristics and functional outcomes of 130 patients with keratoconus attending a specialist contact lens clinic.

AIMS: To evaluate the demographic profile, management and functional outcomes of patients with keratoconus attending the contact lens clinic of a tertiary ophthalmic referral centre over a one year period. METHODS: A retrospective cohort analysis was conducted by reviewing the computerised hospital records of 130 patients attending The Western Eye Hospital contact lens department over the period 1st Jan 1999 to 31st Dec 1999. Data on age, gender, referral pattern, visual acuity, contact lens fitting, degree of visual success, and some information on penetrating keratoplasty were obtained. RESULTS: 16.4% of all patients attending the Contact Lens clinic had keratoconus. The mean age at referral was 28.6 years and the mean age of keratoconus during the study period was 34.9 years. There was a predominance of male patients. Optometrists formed 72.2% of the referrals, and had prescribed some form of refractive correction in 70% of patients (two-thirds contact lenses) prior to hospital assessment. Of the 130 patients seen in the department during the study period, the post-referral management included bilateral contact lens fitting for 102 patients (78.5%), monocular contact lens fitting for 24 patients (18.5%) and no intervention in four patients (3%). The types of contact lenses used included PMMA lenses (2.7%), rigid gas permeable lenses (96.1%) of the spherical, elliptical and special cone lens designs, Keratosoft or Softperm lenses (0.8%) and scleral lenses (0.4%). Eleven eyes of eight patients had received penetrating keratoplasty (PK) prior to hospital assessment, of whom seven eyes needed post-surgical contact lens fitting. The main reasons for PK were contact lens intolerance (83%), frequent contact lens displacement (8.5%) and unsatisfactory visual acuity despite good contact lens fit (8.5%). Sixty-five per cent of patients were able to wear their contact lenses for more than 12 hours a day. With contact lens wear, 87% of patients had a visual acuity of 6/9 or better and 59% of eyes had improved visual acuity of 0.6 logMAR or more. CONCLUSION: Optometrists were the main source of referral for keratoconus patients to the Hospital Eye Service (HES). The mean age at referral was 28.6 years, with a predominance of male patients. Blurred vision formed the main presenting visual symptom on initial hospital assessment; subsequently, more than two-thirds of patients required bilateral contact lenses. Rigid gas permeable contact lenses remain the mainstay treatment for advanced keratoconus, with various designs enabling a large proportion of patients to attain improved visual acuity.

Adolescent↗