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PubMed2000

Bowman's layer structure and function: critical or dispensable to corneal function? A hypothesis.

PURPOSE: The purpose of this article is to review available information regarding development, structure, and function of Bowman's layer in the cornea. Disease-related abnormalities of Bowman's layer are described. A hypothesis is advanced to explain the development and maintenance of Bowman's layer. METHODS: Literature review and hypothesis formulation based on previous studies. RESULTS: Information is presented that supports the hypothesis that Bowman's layer forms as a result of cytokine-mediated interactions occurring between corneal epithelial cells and keratocytes that include chemotactic and apoptotic effects on the keratocytes. This hypothesis suggests that Bowman's layer results from such interactions beginning in early development and continuing into adulthood in humans and other animals, such as chickens. CONCLUSIONS: Bowman's layer may be a visible indicator of ongoing stromal-epithelial interactions in the human and have no critical function in corneal physiology. Bowman's layer is commonly destroyed in diseases such as advanced bullous keratopathy where stromal-epithelial interactions may be interrupted. Bowman's-like layers often form in response to epithelium, for example when epithelial plugs extend into the stroma in corneas with radial keratotomy incisions.

Animals↗

PubMedDate not supplied

Auditory brain stem response wave V latency-intensity function and three audiologic measures of cochlear function.

The purpose of this study was to compare the sensitivity of the ABR wave V latency-intensity (L-I) function to that of Alternate Binaural Loudness Balance, Loudness Discomfort Level, and Acoustic Reflex Threshold tests in identifying sensory hearing losses. Five audiometric groups were tested by each procedure. The groups included subjects with normal hearing, and with conductive, high-frequency sensory, flat sensory, and retrocochlear hearing losses. The ability of each test to separate sensory from retrocochlear impairments was investigated. A positive discriminator for cochlear impairments was of particular interest. A combination of wave V L-I slope at lower intensities and the dB HL value that separates steep and shallow slopes of the L-I function appears to meet this objective.

Adolescent↗

PubMed2005

Sexual function in females with severe cervical spinal cord injuries: a controlled study with the Female Sexual Function Index.

The objective of this study was to identify the sexual adjustment of females with severe cervical spinal cord injuries (SCI) using the Female Sexual Function Index (FSFI). The 19-item questionnaire of the FSFI concerns sexual function and satisfaction in sex life. This study, conducted by the Orthopaedic and Psychiatry Departments of Patras University, used a sample of a series of 39 consecutive female patients with severe traumatic SCI. We compared these female patients with an age-economic-educational level- and marital status-matched control group of the general population. Sexual activity was lower among females with SCI, but the desire, the emotional quality of sex life and overall sexual satisfaction did not differ from the controls. These results demonstrate that sexual life in females with SCI remains almost unaffected.

Adult↗

PubMed2001

Comparative effects of ionic and nonionic iodinated low-osmolar contrast media on platelet function with the PFA-100 (platelet function analyzer).

RATIONALE AND OBJECTIVES: This study was designed to (1) compare the effects of ionic (ioxaglate) and nonionic (iodixanol and iohexol) iodinated low-osmolar contrast media (CM) on platelet function in human whole blood by using the new PFA-100trade mark, a "platelet function analyzer"; (2) determine the animal species closest to human with regard to platelet reactivity to CM; and (3) evaluate which element of the ioxaglate solution supports this activity. METHODS: For all studies, platelet adhesion and aggregation were measured using the PFA-100trade mark system with adenosine diphosphate-primed collagen membrane cartridges. Results are shown as the membrane closure time (MCT; the longer the MCT, the greater the antiaggregatory effect) and given as medians. Citrated whole-blood samples from six healthy volunteers were mixed for 1 minute with a 10% (vol/vol) solution of ioxaglate, iodixanol, or iohexol or their respective ionic and nonionic controls (isotonic saline and mannitol). The test solution/control solution ratio for the MCT was calculated for the blood of humans, guinea pigs, rabbits, dogs, and rats. Isotonic saline and iso-osmolar (280 mOsm/kg) and hyperosmolar (560 mOsm/kg) solutions of meglumine hydrochloride, meglumine ioxaglate (560 mOsm/kg), and sodium ioxaglate (600 mOsm/kg) were tested under similar conditions. RESULTS: All three CM caused significant prolongation of MCT when compared with their respective controls (ioxaglate: 300 seconds, ie, "no closure" on the PFA-100trade mark system; iodixanol: 179 seconds; iohexol: 171 seconds; saline: 115 seconds; mannitol: 118 seconds). The antiplatelet effect of ioxaglate was higher than that of iodixanol and iohexol (P < 0.05). The animal species tested did not differ significantly from the human species with regard to an effect of their blood on MCT. Both ioxaglic acid salts caused a higher prolongation of MCT when compared with saline (sodium salt: 259 seconds; meglumine salt: 212 seconds; P < 0.05 vs. saline) but not versus the ioxaglate commercial solution. Conversely, both iso- and hyperosmolar solutions of meglumine hydrochloride (108 and 128 seconds, respectively) did not lengthen MCT versus saline, but their MCTs were shorter than that of the commercial solution of ioxaglate (P < 0.05). CONCLUSIONS: The ionic CM ioxaglate displayed a greater antiaggregatory effect on human platelets than did both iso-osmolar (iodixanol) and hyperosmolar (iohexol) nonionic CM. This effect seems to be linked to the ioxaglic moiety, because neither osmolality nor sodium or meglumine appeared to play a significant role.

Adult↗

PubMed1998

Application of functional independence measure-function related groups and resource utilization groups-version III systems across post acute settings.

OBJECTIVES: The present study evaluated alternative patient classification systems for skilled nursing facility and rehabilitation facility patients. METHODS: Medicare patients were selected from a random sample of 27 rehabilitation facilities and 65 skilled nursing facilities participating in a national longitudinal study of subacute care. Detailed casemix and resource use data was obtained on 513 patients with hip fracture and 483 stroke patients. The Functional Independence Measure-Function Related Groups (FIM-FRGs) classification system for rehabilitation facilities was replicated on length of stay and tested on resource use for rehabilitation facility patients as well as for skilled nursing facility patients. Modifications to the FIM-FRGs also were tested. The Resource Utilization Groups-Version III classification was tested on rehabilitation facility patients. RESULTS: The FIM-FRGs explained the same amount of variance in length of stay as in the original FIM-FRGs development sample (R2 hip fracture = 0.14, R2 stroke = 0.28), and similar variance in resource use. A modified version of the FIM-FRGs explained more variance in length of stay (R2 hip fracture = 0.19, R2 stroke = 0.39) and resource use (R2 hip fracture = 0.20, R2 stroke = 0.41). Neither model adequately predicted length of stay or resource use in skilled nursing facility patients. The Resource Utilization Groups-Version III rehabilitation groups accounted for little variance in rehabilitation facility patients' per-diem resource use (R2 = 0.11). CONCLUSIONS: The FIM-FRGs are valid for resource use as well as length of stay for rehabilitation facility patients, but are not valid for skilled nursing facility patients. Similarly, the Resource Utilization Groups-Version III system does not apply to rehabilitation facility patients. Related work, however, suggests that development of a single episode-based patient classification system for skilled nursing facility and rehabilitation facility patients is possible and should be pursued.

Activities of Daily Living↗

PubMed1997

Risk factors for delayed graft function in cadaveric kidney transplantation: a prospective study of renal function and graft survival after preservation with University of Wisconsin solution in multi-organ donors. European Multicenter Study Group.

BACKGROUND: Delayed graft function (DGF) remains an important complication in renal transplantation. In this multicenter study, we investigated the influence of donor and recipient factors on the occurrence of DGF and DGF's effect on long-term graft survival. METHODS: A total of 547 transplanted kidney allografts, retrieved from multi-organ donors, were analyzed, and results were compared with literature on kidney-only donors. RESULTS: Median follow-up of patients without graft failure was 3.4 years. Twenty-four percent of the recipients developed DGF. In univariate analysis, the following factors significantly increased the incidence of DGF: (a) among the donor factors, mean creatinine level >120 micromol/L and prolonged cold ischemia time (CIT); and (b) among the recipient factors, previous transplant(s), no intraoperative use of mannitol, poor quality of reperfusion, absence of intraoperative diuresis, and pretransplant anuria or oliguria. After stepwise logistic regression, donor age, CIT, recipient's number of previous transplants, and intraoperative diuresis proved to be of independent prognostic value for the occurrence of DGF. Overall graft survival was 91%, 87%, and 72% at 3 months, 1 year, and 4 years after transplantation, respectively. In case of DGF, graft survival was approximately 10% lower when compared with cases with immediate graft function (P<0.001). No difference in incidence of DGF was found between grafts of multi-organ donors and kidney-only donors. CONCLUSIONS: DGF results in an approximately 10% higher rate of graft failure. DGF incidence can be reduced by the administration of mannitol during transplantation, which minimizes CIT and optimizes donor management. Grafts from multi-organ donors and kidney-only donors appear to be of equal quality.

Cadaver↗

PubMed2000

Long-term functional islet mass and metabolic function after xenoislet transplantation in primates.

BACKGROUND: Pancreatic islet transplantation (PIT) is an attractive alternative for patients with type I diabetes mellitus. PIT is not yet an effective clinical reality due in part to the high incidence of rejection and early loss of functional islet mass. In addition, current immunosuppressive drugs have toxic effects on islets and increase the risk of morbidity and mortality. In the present study, the effects of PIT on glycemic parameters were assessed in spontaneously diabetic primates. METHODS: Five insulinopenic nonhuman primates (three Macacca fascicularis, one Ceropithecus aethiops, and one Macacca mulatta) were studied. All required twice-daily treatment with 4-10 U of insulin. For immunosuppression, the animals received anti-CD3-immunotoxin (100 microg/kg(initially infused 2 hr before transplantation and again on day +1), cyclosporine (CsA) (20 mg/kg(i.v./2 hr before transplantation), cyclosporine microemulsion (Neoral) 60 mg/kg/b.i.d. on days +1 to +3 with dose adjusted by blood levels, and methylprednisolone (15 mg/kg day 0 to +3). Three recipients were given islets from a single donor (M mulatta). The islets were prepared by a semiautomated technique using Liberase. A mean of 13,136 islet equivalents/kg was infused into the portal vein. Two animals (M fascicularis and M mulatta) were used as a diabetic, nontransplanted control. Several metabolic parameters were evaluated. RESULTS: All monkeys that underwent transplantation experienced reversal of diabetes mellitus with normalization of all diabetic glycemic parameters. In the nontransplanted primates given the same immunosuppression but no PIT, diabetic metabolic parameters were unchanged after 9 months of follow-up. In contrast, all three PIT recipients established fasting and nonfasting euglycemia within 1-2 weeks, and none required exogenous insulin after day 10. Normal intravenous glucose tolerance tests were observed at day 15, and no significant differences in the glucose disappearance rate (Kg) were observed at days 15, 45, 190, and 365 days after transplantation. The acute insulin response to glucose indicated no significant reduction of functional islet mass. CONCLUSIONS: PIT in severely insulinopenic type I diabetes mellitus primates resulted in restoration of normal glycemic parameters and durable islet mass. Operational tolerance was achieved with only 4 days of drug administration, sparing the animals from chronic exposure to potentially diabetogenic immunosuppressive drugs. These results offer an exciting new potential for type I diabetes mellitus treatment.

Animals↗

PubMed2004

Effects of functional electrostimulation on pain, muscular strength, and functional capacity in patients with osteoarthritis of the knee.

BACKGROUND: Osteoarthritis (OA) of the knee is a common cause of chronic disability in patients with quadriceps muscle weakness. Beneficial effects have been proposed for functional electrostimulation (FES) and exercise at the muscle level. OBJECTIVES: The objective of the study was to begin to compare the effects of both therapeutic modalities on quadriceps muscle strength, pain, and functional capacity in patients with OA of the knee and to prove whether the combination of these modalities provides greater benefits than the use of each therapeutic modality alone. METHODS: This pilot study included 37 patients with OA of the knee who were assessed at baseline and at 8 weeks, accounting for the following variables: body mass index, knee pain (measured using a VAS), WOMAC, quadriceps strength (measured using a dynamometer) and 6-minute walk test. Patients were randomized into 3 groups: (A) 8 patients who received FES 3 times per week; (B) 10 patients recruited into a twice-a-week physical training program; and (C) 8 patients under combined therapy; 29.7% of patients were lost to follow-up due to noncompliance with the treatment plan, leaving a total of 26 patients at 8 weeks. RESULTS: Pain and WOMAC improved in all 3 groups; strength improved significantly in the exercise-only group; the FES + exercise combination improved strength significantly when compared with the individual therapeutic procedures. CONCLUSIONS: FES merits a larger placebo-controlled study as it may prove to be useful patients with OA of the knee; the combination with exercise was helpful in improving muscle strength. This technique may be considered in patients who are unable to carry out physical activity due to health problems or in those who are not interested in physical activity.

Journal Article↗

PubMed1998

Critical residues for histone acetylation by Gcn5, functioning in Ada and SAGA complexes, are also required for transcriptional function in vivo.

Several previously known transcription cofactors have been demonstrated in vitro recently to be histone acetyltransferases and deacetyltransferases, suggesting that remodeling of chromatin through histone acetylation plays a fundamental role in gene regulation. Clear evidence has not yet been obtained, however, to demonstrate that histone acetylation is required for gene activation in vivo. In this study we performed an alanine-scan mutagenesis through the HAT (histone acetyltransferase) domain identified previously by deletion mapping in recombinant yeast Gcn5. We identified multiple substitution mutations that eliminated completely Gcn5's ability to potentiate transcriptional activation in vivo. Strikingly, each of these mutations was also critical for free and nucleosomal histone acetylation by Gcn5 functioning within the native yeast HAT complexes, Ada, and SAGA. Moreover, the growth phenotypes of these mutations as measured by colony size and liquid growth assay closely tracked transcription and HAT activities. In contrast, mutations that did not affect in vivo function of Gcn5 were able to acetylate histones. These data argue strongly that acetylation is required for gene regulation by Gcn5 in vivo, and support previous arguments that nucleosomal histones are among the physiological substrates of acetylation by Gcn5.

Acetylation↗

PubMed2001

Probability density function and "plus" and "minus" structure functions in a turbulent channel flow.

We consider the statistical properties of the longitudinal velocity increments in a turbulent channel flow at different distances from the wall. The probability density function (PDF) of the velocity difference of the streamwise component near the wall are found to be, especially at small scales, strongly skewed, showing a very long left tail. We consider "plus" and "minus" structure functions and compute separately the statistics for the right and left part of the PDF. It is found that the relative scaling exponents for the right tail are less affected by the presence of the wall and their values are consistent with the ones found in experiments in homogeneous and isotropic turbulence. A simple phenomenological model that explains the results obtained is also given.

Journal Article↗

PubMed2001

Partition function for a one-dimensional delta-function Bose gas.

The N-particle partition function of a one-dimensional delta-function Bose gas is calculated explicitly using only the periodic boundary condition (the Bethe ansatz equation). The N-particles cluster integrals are shown to be the same as those by the thermal Bethe ansatz method.

Journal Article↗

PubMed2002

Local approximation of the correlation energy functional in the density matrix functional theory.

A local approximation formula of the correlation energy functional E(c) in terms of the first-order reduced density matrix (1-RDM) is presented. With the contracted Schrödinger equation the principal dependence of E(c) on the natural occupation numbers n(i) is identified. Using the effective mass theory, E(c) is expressed as a functional of the local density and the local variable, J = SUM (i)[square root of (n(i)(1-n(i))] /phi(i)/(2), where phi(i) are the natural spin orbitals. This local approximation satisfies the homogeneous coordinate scaling relation, gives the exact result for a one-electron system, and is almost free from the exchange energy error. It reproduced about 90% of the correlation energies of atoms and molecules.

Journal Article↗

PubMed2003

Parameter-free calculation of response functions in time-dependent density-functional theory.

We have established and implemented a fully ab initio method which allows one to calculate optical absorption spectra, including excitonic effects, without solving the cumbersome Bethe-Salpeter equation, but obtaining results of the same precision. This breakthrough has been achieved in the framework of time-dependent density-functional theory, using new exchange-correlation kernels f(xc) that are free of any empirical parameter. We show that the same excitonic effects in the optical spectra can be reproduced through different f(xc)'s, ranging from frequency-dependent ones to a static one, by varying the kernel's spatial degrees of freedom. This indicates that the key quantity is not f(xc), but f(xc) combined with a response function. We present results for the optical absorption of bulk Si and SiC in good agreement with experiment, almost indistinguishable from those of the Bethe-Salpeter approach.

Journal Article↗

PubMed1982

Anaesthesia and cognitive functioning. Mental function in postoperative day patients at the time of their release.

Day care patients at Law Hospital, who had received either a general or a local anaesthetic in conjunction with minor surgery, were assessed by five tests of mental function before surgery and before discharge from hospital some hours after surgery. These patients did not perform differently from control patients, who were subjected to the same two testing sessions, without intervening surgery or anaesthesia. It was concluded that the day cases were quite capable of normal cognitive functioning at the time of their discharge and that the procedures followed by the hospital for the discharge of day cases are generally adequate.

Adult↗

PubMed1990

The effect of hypoxia on capillary endothelial cell function: modulation of barrier and coagulant function.

As the cells forming the luminal vascular surface, endothelium is exposed to alterations in the vascular microenvironment, such as hypoxaemia. In this report we demonstrate that hypoxia, with pO2 as low as 12-14 mmHg, was not toxic to endothelium, but reversibly modulated central cellular functions essential for maintenance of homeostasis: permeability of monolayers to solutes increased in a dose-dependent manner, and cell surface coagulant properties were shifted to promote activation of coagulation. The anticoagulant cofactor thrombomodulin was suppressed and an apparently novel activator of factor X, distinct from the classical extrinsic and intrinsic systems, was induced. The hypoxia-induced factor X activator was cell surface-associated, had properties of a cysteine protease, had Mr corresponding to approximately 100 kDa, based on sodium dodecyl sulphate-polyacrylamide electrophoresis (SDS-PAGE), and isoelectric point (pI) approximately 5.0. These findings indicate that hypoxia dynamically modulates endothelial function providing insights into the contribution of microvascular endothelial dysfunction in the pathogenesis of vascular lesions.

Animals↗

PubMed2006

Genetic and functional interaction between Ryh1 and Ypt3: two Rab GTPases that function in S. pombe secretory pathway.

We have previously isolated ypt3-i5 mutant and showed that Ypt3 GTPase functions in the fission yeast secretory pathway. Here, the same genetic screen led to the isolation of ryh1-i6, a mutant allele of the ryh1+ gene encoding a homolog of Rab6. The ryh1-i6 mutant showed phenotypes that support its role in retrograde traffic from endosome to the Golgi. Interestingly, ryh1+ gene deletion was synthetically lethal with ypt3-i5 mutation. Consistently, the over-expression of the GDP-conformational mutant, Ryh1T25 N, inhibited the growth of ypt3-i5 mutant but had no effect on that of wild-type cells. Furthermore, the over-expression of the Ryh1T25N mutant inhibited the acid phosphatase glycosylation and exacerbated the cell wall integrity of ypt3-i5 mutant, but had no effect on those of wild-type cells. GFP-Ryh1 and GFP-Ypt3 both localized at the Golgi/endosome, but showed distinct subcellular localizations. The localization of GFP-Ryh1 in ypt3-i5 mutant and that of GFP-Ypt3 in ryh1-i6 mutant were distinct from those in wild-type cells. In addition, Ryh1 as well as Ypt3 were shown to be involved in acid phosphatase secretion. These results suggest that Ryh1 is involved in the secretory pathway and may have a potential overlapping function with Ypt3 in addition to its role in recycling.

Acid Phosphatase↗

PubMed1993

Parameters of tooth mobility in cases of normal function and functional disorders of the masticatory system.

Tooth mobility was measured mechano-electronically with the aid of quasi-static and dynamic methods in 309 patients comprising 2650 teeth being periodontally healthy. Besides, clinical and roentgenographic findings were ascertained to relate functional features to each periodontium. In general the result was that teeth loaded excessively show increased mobility parameters compared to those loaded normally. However, the mobility of teeth loaded poorly or deficiently was even greater compared to teeth stressed excessively. Moreover, follow-up studies showed that tooth mobility decreases after removal of functional disorders of the masticatory system or an immobilisation of splinted teeth. An experimental trauma of the periodontal ligament also brings on an increased tooth mobility which decreases to the original values some days after the trial.

Adolescent↗

PubMed1993

C-terminal truncation of the transcriptional activator encoded by areA in Aspergillus nidulans results in both loss-of-function and gain-of-function phenotypes.

Mutations truncating as many as 143 C-terminal residues from the transcriptional activator encoded by the areA gene, mediating nitrogen metabolite repression in Aspergillus nidulans, do not significantly reduce the ability of the areA product to activate expression of most genes under areA control. Such mutations can even have a gain-of-function, derepressed phenotype, consistent with a critical role for this region in modulating the activity of the areA protein. However, expression of a few genes under areA control is substantially impaired by such C-terminal truncations, indicating that regions of an activator protein can play differing roles in the control of different structural genes. This underlines the advantages of being able to monitor effects of areA mutations on expression of large numbers of structural genes. Additionally, it is shown that truncation of as many as 153 C-terminal residues, virtually all amino acids C-terminal to the DNA-binding region, is compatible with retention of some areA function.

Amino Acid Sequence↗