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PubMed1993

Bovine gallbladder mucin accelerates cholesterol monohydrate crystal growth in model bile.

BACKGROUND: Gallbladder mucin accelerates cholesterol crystal nucleation, an early step in the pathogenesis of gallstones. To examine the role of gallbladder mucin in postnucleation gallstone maturation, the influence of mucin on cholesterol monohydrate crystal growth was studied in a novel model system. METHODS: Cholesterol crystals of a uniform size were incubated in model biles at 37 degrees C with varying cholesterol saturation indices. Crystal size was quantitated by measuring the width and length of individual crystals under polarizing light microscopy and calculating average crystal area. RESULTS: Crystal growth was dependent on the degree of cholesterol supersaturation of bile. Bovine gallbladder mucin (0.5-8 mg/mL) accelerated crystal growth in supersaturated model bile in a concentration- and time-dependent fashion compared with control incubations with bovine serum albumin or model bile alone (P < 0.05). Cholesterol crystal growth was accompanied by a progressive decrease in cholesterol saturation and an increase in total cholesterol crystal mass. Crystal growth was also accompanied by a decrease in total crystal number, suggesting net transfer of cholesterol to larger crystals. CONCLUSIONS: The acceleration of cholesterol crystal growth by gallbladder mucin may be of pathophysiological importance in the postnucleation maturation of cholesterol gallstones.

Animals↗

PubMed1995

Mechanism of accelerated gastric emptying of liquids and hyperglycemia in patients with type II diabetes mellitus.

BACKGROUND & AIMS: The roles of hyperglycemia in diabetic gastroparesis and gastric delivery in postprandial hyperglycemia of diabetic patients are unclear. The aims of this study were to assess gastric emptying and its relation to postprandial glucose metabolism in patients with asymptomatic non-insulin-dependent diabetes mellitus (NIDDM) and no autonomic neuropathy and to identify motor mechanisms responsible for any accelerated gastric emptying. METHODS: Autonomic function, gastric emptying, postprandial glucose metabolism, and hormone levels (glucagon, insulin, cholecystokinin, glucose-dependent insulinotropic polypeptide, neurotensin, and peptide YY) were assessed in healthy volunteers and patients with NIDDM. In a second study, gastric tone and motility were measured in patients with accelerated gastric emptying and in controls. RESULTS: Gastric emptying of solids did not differ in the two groups, but liquids emptied faster in patients with NIDDM (P < 0.02). The rate of entry of ingested glucose into the systemic circulation was similar, but higher postprandial glucagon and lower insulin concentrations led to greater (P < 0.01) postprandial hepatic glucose release. Levels of other enteropeptides, gastric accommodation, and antral motility were similar, but patients with NIDDM had greater proximal gastric phasic contractions than controls (P < 0.05). CONCLUSIONS: Excessive hepatic glucose release, not rapid entry of ingested glucose, is the primary cause of postprandial hyperglycemia in patients with NIDDM. Accelerated gastric emptying in patients with nonneuropathic NIDDM is associated with increased proximal stomach phasic contractions.

Autonomic Nervous System↗

PubMed1987

Isolation of decay-accelerating factor (DAF) from rabbit erythrocyte membranes.

A regulatory protein purified from rabbit erythrocyte stroma had decay-accelerating activity to C5 convertases on hemolytic intermediate cells (EAC1-3b, P). Its molecular weight was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions to be 66,000, slightly smaller than that of human decay-accelerating factor (DAF). The amino acid composition of the protein resembled that of human DAF. The protein was incorporated into sheep erythrocytes. The incorporation and the decay-accelerating activity were inhibited by low density lipoprotein. It did not bind to rabbit C3-Sepharose in a column under conditions in which human CR1 bound, but its interaction with rabbit C3 was evident from the retardation of its elution from the column. These results indicate that the protein purified from rabbit erythrocyte stroma was DAF.

Amino Acids↗

PubMed1991

Complementary recognition in condensed DNA: accelerated DNA renaturation.

The functional consequences of DNA condensation are investigated. The recognition of complementary strands is profoundly modified by this critical phenomenon. (1) Condensation of denatured DNA greatly accelerates the kinetics of DNA renaturation. We propose a unifying explanation for the effects of several accelerating solvents studied here including polymers, di- and multivalent cations, as well as effects seen with the phenol emulsions and single-stranded nucleic acid binding proteins. Optimal conditions for renaturation at or above the calculated three dimensional diffusion limit are theoretically consistent with a limited search space in the condensed phases. (2) In addition to these effects on association of two single strands, similar condensation acceleration effects can be seen in strand exchange experiments with double stranded DNA without proteins. These may model a mechanism of recombinational protein function.

Bacteriophage lambda↗

PubMed1982

Biofeedback training of cardiac acceleration; effects on airway resistance in bronchial asthma.

Twenty-four volunteers adolescent and adult asthmatics were pre-tested for suggestibility and retained for an investigation of the airway effects of biofeedback induced voluntary cardiac acceleration. Eight subjects were successful in achieving large magnitude voluntary cardiac acceleration after 2-5 training sessions. Eight matched control group subjects received one session of biofeedback assisted training in cardiac constancy. Results revealed that large magnitude heart rate increase was accompanied by a statistically significant increase in Peak Expiratory Flow Rate for experimental group subjects. Control group subjects showed a drop in heart rate and a statistically insignificant drop in PEFR. Clinical records for experimental and control group subjects during the pre- and post-training periods revealed that a significant reduction in the incidence of attacks, the use of p.r.n. medication, and the index of medication use per attack occurred in trained subjects. No change on any of these criteria occurred for control group subjects. The acquisition of the cardiac acceleration response of asthmatic experimental group subjects was compared with the acquisition rate of a matched group of normal subjects receiving one session of biofeedback training. No differences were revealed between the groups in the rate of acquisition. However, symptom-free asthmatics were shown to have PEFR readings significantly below those of the normal group, thus supporting previous findings. The possible implications of these findings for the clinical management of bronchial asthma, are discussed.

Adolescent↗

PubMed1985

Effect of surgery on tumor-induced accelerated coagulation in a rat carcinoma.

Accelerated coagulation detected by thromboelastography has been reported in early stages of tumor growth. The present investigation was conducted to determine the changes in tumor-induced accelerated coagulation following complete and partial resection of the tumor. Male Fisher rats were divided into four groups: (1) control, (2) tumor-bearing rats, (3) complete resection, (4) partial resection. In groups 2, 3, and 4 a 2-mm3 piece of squamous cell carcinoma (NCI 11095) was implanted subcutaneously in the left flank. Seven days later blood samples were obtained from the tumor and control groups and tested on a thromboelastograph to determine the effect of the tumor on the coagulation of the hosts. Six weeks following the initial tumor implantation a sham operation was performed on group 2, complete resection on group 3, and a partial resection on group 4. After a rest period of 3 weeks blood samples were obtained from the four groups of rats and tested on a thromboelastograph. The results indicate that there is a significant acceleration of coagulation in tumor-bearing animals. The effect of surgery on this tumor-induced phenomenon depends on the type of procedure performed. Complete resection returns the coagulation status toward normal whereas sham operation or a partial resection do not. In this tumor model, hypercoagulability of the blood, therefore, indicates the presence of residual tumor.

Animals↗

PubMed1992

Pretransplant sensitization with major histocompatibility complex class I+ class II- hepatocytes leads to accelerated skin graft rejection.

The immunogenicity of major histocompatibility complex (MHC) class I+ class II- hepatocytes is controversial. We studied the effect of pretransplant donor-specific sensitization with either purified hepatocytes (HC) or splenocytes (Spl) on subsequent skin allograft survival. Five million Percoll-purified DBA HC or 10 x 10(6) DBA Spl were injected into C57BL/6 recipients either intraperitoneally (ip) or into a sponge matrix allograft. Twelve days later, sensitized mice received a DBA skin graft. On the same day, allogeneic (DBA) and syngeneic (BL/6) skin grafts were placed on naive BL/6 mice. In naive BL/6 mice, allogeneic skin graft survival was 7.8 +/- 0.5 days (n = 4), and syngeneic survival was indefinite (n = 5). Skin graft survival (mean +/- SD in days) in recipients sensitized with hepatocytes ip was 6.0 +/- 1.2 days (n = 5) compared with 5.6 +/- 0.5 days in recipients sensitized with splenocytes ip. Similarly, graft survival in recipients that received hepatocytes into a sponge matrix allograft was 5.67 +/- 1 days (n = 6) compared with 5.2 +/- 1.1 days (n = 8) in those that received splenocytes into the sponge. There was no difference in graft survival between mice sensitized with HC vs Spl, nor between mice injected ip vs with the sponge. All sensitized mice experienced accelerated graft rejection compared with naive controls (P less than 0.000). These results demonstrate that purified MHC class I+, class II- murine HCs are immunogenic in vivo. Sensitization with donor-specific HCs led to accelerated rejection of subsequent skin grafts, similar to the accelerated rejection seen after sensitization with MHC class I+ and class II+ splenocytes.

Animals↗

PubMed1986

The development of kindled seizures is accelerated in the genetically epilepsy-prone rat.

The kindling phenomenon was examined in genetically epilepsy-prone (GEPR) and non-epileptic control Sprague-Dawley rats. Kindling stimulations were administered three times a day until each rat had exhibited three Class 5 kindled motor seizures. The mean total number of kindling stimulations required for each experimental group to exhibit three motor seizures of each motor seizure class was determined. The results indicated that the early stage of kindling development was accelerated significantly in both the GEPR-3 and GEPR-9 rats, compared to non-epileptic control rats. Later stages of kindling development were accelerated in GEPR-9 but not GEPR-3 rats. Thus a differential acceleration of kindling development was exhibited by GEPR-3 and GEPR-9 rats. The results suggest the possibility that some brain region(s) involved in the early stages of kindling development may be hyperexcitable in both GEPR-3 and GEPR-9 rats. Other brain region(s) involved with the later stages of kindling development may be more excitable in GEPR-9 rats. These putative alterations may, in part, contribute to the seizure prone state of GEPR rats and the differential seizure responses of GEPR-3 and GEPR-9 rats.

Acoustic Stimulation↗

PubMed1996

Taurine accelerates the regression of hypercholesterolemia in stroke-prone spontaneously hypertensive rats.

The effects of taurine on the regression of pre-established hypercholesterolemia were examined in stroke-prone spontaneously hypertensive rats (SHRSP). Hypercholesterolemia was induced by feeding a hypercholesterolemic diet to SHRSP for 30 days. Then, the diet was switched to normal chow with or without 3% taurine, and the effects were followed up for another 30 days. During regression serum cholesterol level was rapidly decreased, and was accelerated by taurine. A similar accelerated decrease in cholesterol content by taurine was seen also in tissues including the liver, intestine, and aorta. In the liver, acyl-CoA:cholesterol acyltransferase (ACAT) activity was significantly low in the taurine-supplemented group, parallel with the hepatic cholesteryl ester content. On the other hand, hepatic cholesterol 7 alpha-hydoxylase activity maintained a higher level in the taurine-supplemented group. These results showed that taurine accelerates the regression of hypercholesterolemia, and suggested that this effect is related to the increase in cholesterol catabolism to bile acid through the enhancement of 7 alpha-hydoxylase activity.

Animals↗

PubMed1993

Dichloroacetic acid accelerates initial development of 2-cell murine embryos in vitro.

Preimplantation embryos up to the 8-cell stage of development use lactate and pyruvate but not glucose or Krebs cycle intermediates to support growth, development, and cleavage. The dominant effect of dichloroacetic acid (DCA) is the irreversible stimulation of pyruvate dehydrogenase (PDH) activity, thus accelerating the oxidative metabolism of pyruvate and lactate. To test the hypothesis that early induction of oxidative metabolism in 2-cell murine embryos accelerates preimplantation embryo cleavage rates, female B6C3F1 mice at 6 to 8 weeks of age were superovulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) and mated. All 2-cell stage embryos were randomly assigned to culture media with or without 130 micrograms/mL DCA. The developmental stage of all embryos was then noted every 24 hours for a total of 72 hours. Chi-square analysis and the method of average rank sum were used to compare the distribution of embryos at each observation point. At 24 hours, DCA-exposed embryos had achieved an advanced stage of growth and development relative to controls (average rank sum, P = .026; chi-square distribution, P = .047). Subsequently, at 48 and 72 hours, neither the average rank sum nor the chi-square distribution was different. Our data suggest that DCA accelerates early growth and development of murine embryos before implantation, possibly through the early induction of oxidative metabolism.

Animals↗

PubMed1996

Accelerated fetal lung maturity profiles and maternal cocaine exposure.

OBJECTIVE: To determine the effect of maternal cocaine exposure on fetal lung maturity as measured by surfactant-albumin ratios determined by the TDx-FLM test. METHODS: A case-control study design was used to compare fetal lung maturity as assessed by a surfactant-albumin ratio assay (TDx-FLM) in amniotic fluid (AF) obtained from women who were known to use cocaine and those who were not known to use cocaine during the study pregnancy. Multiple logistic regression procedures were used to control for gestational age and possible confounders, such as obstetric and nonobstetric complications, other substance abuse, race, infant sex, and payer status. RESULTS: Maternal cocaine use during pregnancy was associated with an accelerated fetal lung maturity profile (adjusted odds ratio [OR] 2.04, 95% confidence interval [CI] 1.04-4.00) as determined by the TDx-FLM test. Other variables found to be statistically significant predictors of a mature fetal lung profile were cigarette smoking during the current pregnancy (OR 1.61, 95% CI 1.02-2.56). Preterm labor, preterm rupture of membranes, nonobstetric illness during pregnancy, and exposure to other abused substances were not associated with accelerated fetal lung maturity. CONCLUSION: Maternal cocaine use during pregnancy is associated with a doubling of the probability of a mature fetal lung profile as determined by TDx-FLM analysis of AF. Tobacco use is also a predictor of accelerated fetal lung maturity profiles.

Adolescent↗

PubMed1988

Acceleration of reproductive development in female Djungarian hamsters by adult males.

Housing young female Djungarian hamsters (Phodopus campbelli) with an adult male accelerates uterine and ovarian development and there is a strong relationship between uterine weight and ovarian measures (e.g., follicular size). Uterine weights of females housed with an adult male for 10 days following weaning are comparable to values from females housed alone for 25 days. Removal of endogenous androgens by castration eliminated the capacity of adult males to accelerate reproductive development in young females and treatment of castrated males with exogenous androgens maintained the production of the acceleratory chemosignal. When adult male urine and ventral gland sebum were examined as possible sources for the acceleratory chemosignal, only male urine had an acceleratory effect on reproductive development. Thus, female Djungarian hamsters respond with accelerated reproductive development to androgen-dependent chemosignals in the urine of adult males. These mechanisms are similar to those found in several other rodents but contrast with the lack of such effects in the golden hamster (Mesocricetus auratus).

Animals↗

PubMed1994

The role of serum testosterone in the accelerated extinction of a conditioned taste aversion in fluid deprived male rats.

Fluid deprivation decreases serum testosterone (T) levels and increases the rate of extinction of a conditioned taste aversion in Sprague-Dawley male rats. It has been suggested that the decreased serum levels may be the primary factor responsible for the accelerated extinction rates during fluid deprivation. To test the generality of this hypothesis, the effect of fluid deprivation on T levels and extinction rate was investigated in Fischer 344 male rats. Extinction rates were accelerated in Fischer 344 rats but T levels were not decreased. In a second study, the behavioral and hormonal responses of Fischer 344 and Sprague-Dawley males to fluid deprivation were compared. Extinction rates were increased in both strains of rat by fluid deprivation, but serum T levels were decreased in fluid-deprived Sprague-Dawley males and not Fischer 344 males. It was suggested that the accelerated extinction in fluid-deprived Sprague-Dawley males was primarily due to decreases in serum T levels, while the faster extinction in deprived Fisher 344 males could be accounted for by decreases in sensitivity to T.

Animals↗

PubMed1984

Specific integration of recombinant proviral sequences in ecotropic Gross virus-accelerated AKR thymomas.

Integration and amplification of ecotropic and recombinant proviral sequences in high-molecular-weight cellular DNAs from ecotropic Gross virus-accelerated AKR thymomas were analyzed using an ecotropic-specific probe, p400, and an envelope-specific probe, pAKV-5. New ecotropic proviral sequences were detected at three sites in the DNAs from eight Gross virus-accelerated thymomas following EcoRI restriction endonuclease digestion and at six sites following PvuII restriction endonuclease digestion. The integration of these new ecotropic proviral sequences appeared to be random. Recombinant 3' proviral-cellular DNA junction fragments were detected at 30 sites following digestion with EcoRI. These new recombinant fragments ranged in size from 9.0 to 2.5 kb with 6/8 thymoma DNAs containing a fragment of 2.7 kb. PvuII generated new recombinant 3' proviral-cellular junction fragments that ranged in size from 12.5 to 2.1 kb with 5/8 thymoma DNAs containing a fragment of 2.5 kb. It appears that the leukemia-accelerating ecotropic Gross virus is responsible for the generation of a unique 3' recombinant proviral-cellular junction fragment. This fragment can be detected against a background of randomly integrated ecotropic and recombinant proviruses.

AKR murine leukemia virus↗

PubMed1993

Perforin expression localizing cytotoxic lymphocytes in the intimas of coronary arteries with transplant-related accelerated arteriosclerosis.

Accelerated arteriosclerosis is the major long-term complication of cardiac transplantation. It has been demonstrated recently that accelerated arteriosclerosis is caused, in part, by rejection-related, cell-mediated immunity. However, the role of cytotoxic T lymphocytes in this process is a subject of controversy. Perforin is a specific marker of functionally active cytotoxic lymphocytes because it is a functional component of the cytotoxic granules of these cells. We examined 11 coronary arteries from seven autopsied and four retransplanted heart transplant recipients for the presence of perforin-containing lymphocytes. Immunohistochemical stains for perforin were performed using a monoclonal antibody against human perforin. Eight of the 11 coronary arteries examined were found to contain perforin-positive cells. These perforin-positive cells were present in subendothelial spaces of the coronary arteries, and the staining seen was cytoplasmic and granular. The granules often were polarized to the endothelial surface. Furthermore, the cells identified were usually in close proximity to, or in direct contact with, coronary artery endothelial cells. These results suggest that cell-mediated endothelial injury by perforin-positive cytotoxic lymphocytes may contribute to the development of accelerated arteriosclerosis in heart transplant recipients.

Adolescent↗

PubMed1993

Evidence for accelerated skin wrinkling among developmentally delayed individuals with Down's syndrome.

Down's Syndrome (DS) is a genetic disorder involving mental retardation which is reported to be a condition of accelerated aging. However, few studies exist which examine age-dependent changes in DS and these studies fail to include a control group. In the present study a non-invasive, painless, and easily obtainable measure reflecting age-dependent topographical changes of the skin (skin wrinkling) was obtained in 15 DS subjects, 14 developmentally disabled (DD) (mentally retarded) controls (DD controls) and 16 healthy controls of similar ages ranging from 22 to 51 years. The healthy control group failed to show correlations of skin measures with age, as predicted for the age-range of these subjects, based on results of previous studies. However, the DS group showed significant correlations of all skin measures from relatively non-sun-exposed and sun-exposed skin sites, with age. The DD control also showed significant correlations with age of several but not all skin sites and the correlation coefficients tended to be less than that of the DS; at least, when contrasted with the healthy controls the DS showed greater values of several skin measures suggestive of accelerated skin wrinkling. These results provide evidence for accelerated aging of the skin, and possibly greater effects of sun-exposure on skin wrinkling, in DS and possibly (DD) individuals in contrast to healthy individuals without a genetic disorder and without mental retardation.

Adult↗

PubMed1996

Early changes in the expression of GLUT4 protein in the heart of senescence-accelerated mouse.

The content of facilitative glucose transporter proteins in the heart, lung, liver, testis and cerebellum of SAMP8, a substrain of senescence-accelerated prone mouse, was investigated. The increase in the expression of facilitative glucose transporter proteins, estimated by the D-glucose inhibitable cytochalasin B binding assay, was observed only in the heart of 4-8 week old SAMP8 in comparison with SAMR1, a substrain of senescence-accelerated resistant mouse. The increase in cytochalasin B binding protein in SAMP8 was restricted at 4-8 weeks old, thereafter no significant difference was observed between the two substrains. Furthermore, the immunoblotting revealed that the content of the GLUT4 (glucose transporter isoform 4) protein in the crude membranes prepared from 4-8 week old SAMP8 was greater than that of SAMR1, without the difference in the content of the GLUT1 (glucose transporter isoform 1) protein. Additionally, the increased GLUT4 protein in SAMP8 was localized in the intracellular membranes. These results suggest that an accelerated ageing of SAMP8 is possibly related to the overproduction of the energy in the heart through the increase in glucose uptake after the translocation of GLUT4 from the intracellular pools to the plasma membranes.

Aging↗

PubMed1985

Species specificity in the acceleration of tissue-type plasminogen activator-mediated activation of plasminogens, by fibrinogen cyanogen bromide fragments.

Activation of human plasminogen by human tissue-type plasminogen activator (t-PA) is accelerated in the presence of cyanogen bromide digests of human fibrin(ogen). In the present study a possible species specificity of this phenomenon was investigated. All combinations of the plasminogens, fibrin monomers and cyanogen bromide digests of the fibrinogens of man, pig, rat, cat and monkey (Macaca mulatta), and three t-PA species (man, rat and pig) were studied. No species differences were noted with the fibrin monomers i.e. the activation rate of all five plasminogens increased more than 20-fold in the presence of all five fibrin monomer species, irrespective if man, rat or pig t-PA was used. However, we found that species specificities come to expression when cyanogen bromide digests of the corresponding fibrinogens were used as accelerators. Our results indicate that the plasminogen species and not the source of t-PA or fibrinogen dictates if accelerated activation occurs in the presence of a fibrinogen CNBr digest. The plasminogens can be roughly divided in two groups: --One group, comprising human, monkey and cat plasminogen, which are activated at a higher rate by all three t-PA species in the presence of fibrinogen digest independent on the fibrinogen species from which the digest was prepared. --Another group, comprising pig and rat plasminogen, which is not or only marginally more quickly activated by the 3 t-PA species, irrespective of the fibrinogen species from which the CNBr digest was prepared.

Animals↗