Injury prevention measures in households with children in the United States, 1990.
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Accident Prevention↗
Biomedical subjects
M Mayer
Publications and source records attributed to M Mayer.
Regulation of fibrinolysis by non-esterified fatty acids.
The ability of oleic acid to modulate fibrinolysis was measured by following the urokinase-mediated and plasminogen-dependent cleavage of 125I-labelled fibrin clots. Oleic acid levels within the physiological range exerted a concentration-dependent inhibition of urokinase-mediated fibrinolytic activity. SDS/PAGE revealed that oleic acid enhances urokinase activity but simultaneously increases the autolytic cleavage of the newly formed low-molecular-mass subunit of plasmin. Oleic acid-induced cleavage of this subunit containing the catalytic site of plasmin was suppressed by the plasmin substrate H-D-valyl-L-leucyl-L-lysine-p-nitroanilide (S-2251) and was prevented by alpha 2-antiplasmin. A concentration-dependent inhibition of the activity of purified plasmin on 125I-labelled fibrin clot was also observed; 93% and 50% inhibition was noted with 150 microM and 32 microM oleic acid respectively. Oleic acid at 200 microM also effectively displaced plasmin prebound to a polylysine-Sepharose column. Examination of the fatty acid specificity showed that a minimal chain length of 16 carbon atoms and the presence of at least one double bond, preferably in a cis configuration, were required for inhibition of the fibrinolytic activity of plasmin. Oleic acid at a concentration that produced only a minimal inhibition of plasmin activity induced a marked inhibition by palmitic acid, while palmitic acid alone is ineffective. The findings suggest that oleic acid stimulates plasminogen activation and modulates the fibrinolytic and autolytic activities of plasmin.
Amino Acid Sequence↗
Inhibition of neutrophil activation by fibrinogen.
Physiological levels of human fibrinogen markedly inhibited the chemotactic activity of human neutrophils triggered by zymosan-activated serum (ZAS), C5a, or IL-8 in a Boyden chamber assay. Fibrinogen also slightly inhibited the N-formyl-methionyl leucyl-phenylalanine (FMLP)-induced migration of human neutrophils. Albumin was devoid of the inhibitory activities displayed by fibrinogen in this system. The inhibition of chemotaxis by fibrinogen was dose-dependent and saturable. Fibrinogen placed in the upper compartment of the Boyden chamber produced a larger inhibition than that obtained with fibrinogen placed in the lower compartment. Lysine as well as the lysine analog 6-aminohexanoic acid (AHA) decreased the inhibitory capacity of fibrinogen. In contrast, both arginine and glutamine failed to suppress the fibrinogen-mediated inhibition of neutrophil chemotaxis. AHA counteracts the inhibition of ZAS-induced chemotaxis by anti-CD18 monoclonal antibody, suggesting that lysine binding sites are required for integrin function in chemotaxis. Fibrinogen also inhibited, in a dose-dependent manner, the oxygen consumption of neutrophils activated by opsonized zymosan. Taken together, the present results indicate that fibrinogen modulates neutrophil functions and suggest that in addition to its role in blood coagulation, circulating fibrinogen may be involved in regulation of the inflammatory response.
Amino Acids↗
Cytokine-mediated regulation of rat ovarian function: interleukin-1 inhibits plasminogen activator activity through the induction of plasminogen activator inhibitor-1 (PAI-1).
Intraovarian IL-1 has recently been implicated as a mediator in the ovulatory process. Since PA activation is an established component of the ovulatory cascade, consideration was given in this report to the possibility that IL-1 may modulate ovarian PA economy. Whole ovarian dispersates from immature rats (25-27-days-old) were cultured under serum-free conditions for 48 h in the absence or presence of IL-1beta. Cellular PA activity was measured by plasminogen-dependent cleavage of 14C-labeled globin. Cells grown in the absence of IL-1 exhibited appreciable PA activity, as assessed by the cleavage of 0.074 +/- 0.026 mg [14C]-globin/5 x 10(5) cells (mean +/- SD). Exposure to IL-1 (10 ng/ml) led to a 30% reduction in cell-associated PA activity (p < 0.001). The IL-1-mediated inhibition occurred concurrently with a 10-fold increase in the ability of the corresponding conditioned media to inhibit exogenous urokinase activity. At similar cell densities of 5 x 10(5) cells/well, isolated cultures of theca and granulosa cells exhibited comparable PA activity in the absence of IL-1. However, only theca cells responded to IL-1 with inhibition of plasminogen activation and enhancement of urokinase inhibitory activity. Granulosa cells in turn failed to respond to IL-1. Both the inhibition of PA activity and the increase in urokinase inhibitory activity proved cell-density- and IL-1 dose-dependent. The IL-1-induced inhibition of urokinase was abolished by the administration of a polyclonal anti-rat PAI-1 IgG. Both effects of IL-1 were counteracted in a dose-dependent fashion by the soluble IL-1 receptor (which specifically complexes with IL-1), and by a highly-specific IL-1 receptor antagonist suggesting that the IL-1 effects are receptor-mediated. The present observations indicate that ovarian PA activity is subject to inhibition by IL-1 probably by way of PAI-1 of theca-interstitial origin. Inasmuch as IL-1 may be involved in initiating and maintaining the preovulatory cascade, the periovulatory activation of plasminogen must be accomplished by agents other than IL-1.
Animals↗
Pathogenic factors in early recurrence of cholesterol gallstones.
BACKGROUND/AIMS: Supersaturation of bile with cholesterol, rapid nucleation of cholesterol crystals, and/or incomplete emptying of the gallbladder are believed to be required for gallstone formation. The importance of these factors for the recurrence of gallbladder stones was studied. METHODS: Twenty patients, untreated after successful shock wave therapy, were studied in a matched case-control design for bile acid turnover, composition of duodenal bile, and gallbladder emptying. In 10 of them, gallstones had recurred within 12 +/- 2 months (X +/- SEM); the other 10 had been free of stones since 22 +/- 3 months. RESULTS: In each group, duodenal bile was supersaturated with cholesterol in 8 of 10 patients and showed abnormal nucleation time of cholesterol crystals in half of the patients. Patients with recurrent stones had smaller pool sizes of cholic acid (-43%) and enhanced conversion of cholic acid to deoxycholic acid. The odds for stone recurrence were ninefold increased in the presence of excessive deoxycholic acid (exceeding cholic acid) in the bile acid pool or incomplete emptying of the gallbladder (residual volume > 5 mL) in response to cholecystokinin. The odds ratio was over 20-fold increased when incomplete emptying of the gallbladder coincided with supersaturated bile or with excessive deoxycholic acid. CONCLUSIONS: Enhanced conversion of cholic acid to deoxycholic acid and incomplete emptying of the gallbladder could be important cofactors for the recurrence of gallstones.
Bile↗
Pulsatile growth pattern during catch-up growth in childhood coeliac disease.
Catch-up growth in coeliac disease was thought to be a continuous process and hence linear models have been proposed to interpret the pattern of catch-up growth. Observed longitudinal data do not fit a linear model adequately. The aim of this study is to clarify the pattern of short-term catch-up growth in coeliac patients. Twenty-one coeliac children (aged 6-24 months) entered the study and were monitored at short-time intervals. All showed a "pulsatile" pattern of growth velocity for height, weight, leg length, subscapular and triceps skinfolds. Peaks alternated with troughs at a mean time of 62 days for the whole set of measurements. The periodicity was remarkably stable. The size of the peaks decreased with time on a gluten-free diet. Catch-up growth is a discontinuous process made up of a sequence of bursts of growth followed by a resting phase. This provides strong evidence for the possibility that short-term growth may be pulsatile.
Body Height↗
Polymorphonuclear leukocyte functions in multiple sclerosis.
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Humans↗
Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro.
We have found that CNTF and LIF are pleiotropic modulators of development in the O-2A lineage. Both molecules enhanced the generation of oligodendrocytes in cultures of dividing O-2A progenitors. CNTF and LIF also promoted oligodendrocyte maturation, as determined by expression of myelin basic protein, and could promote oligodendrocyte survival to an extent comparable with insulin-like growth factor-1 or insulin. In addition, LIF and CNTF both promoted the differentiation of O-2A progenitors into type-2 astrocytes but only when applied in the presence of extracellular matrix (EnMx) derived from cultures of endothelial cells. The ability of CNTF and LIF to enhance differentiation of O-2A progenitors along either of the alternative pathways of oligodendrocyte and astrocyte differentiation suggests that these proteins are able to enhance the process of differentiation per se, while the actual path of differentiation promoted is determined by the presence or absence of additional molecules in the extracellular environment.
Animals↗
[Nitric oxide and mechanisms of vascular and tissue damage. New hope for research and therapy of multiple sclerosis].
Nitric oxide (NO) was recently recognized as a--from a biological point of view rather unusual--signalling molecule and ubiquitous mediator. Soon after the discovery of the significance of NO for intercellular communication and intracellular regulations, it became apparent that the NO-dependent processes play a part also in the immune and inflammatory mechanisms of vascular and tissue damage, including affections of the CNS. In higher concentrations, NO acts directly as a toxic factor and co-factor, and in lower concentrations it has rather more regulatory and even protective properties. In the present article the role played by NO in some mechanisms that, according to present knowledge, participate in the pathogenesis of multiple sclerosis is reviewed. These are as follows: The production and action of cytokines, especially interferon-gamma, tumour necrosis factor and interleukins; Interactions between leukocytes, thrombocytes and endothelial cells; The arachidonic acid cascade, metabolism and effects of reactive oxygen species and actions of corticosteroids; Glia-dependent cytotoxic and immunopathological events; Virus-host interactions. It has become increasingly clear that the research focused on NO and related problems brings significant progress in our understanding of the pathogenesis of many neurological diseases and, moreover, may provide new stimuli in the search for novel therapeutic approaches in multiple sclerosis.
Brain↗
Effects of flupirtine coadministration on phenprocoumon plasma concentrations and prothrombin time.
The influence of flupirtine, a non-opioid, centrally acting analgesic agent on phenprocoumon plasma levels and protein binding as well as prolongation of prothrombin time has been investigated in 12 healthy male volunteers. Subjects received phenprocoumon 1.5 mg od over 28 days. From day 15 to 28 oral flupirtine 100mg tid was added. Phenprocoumon plasma levels and prothrombin time (Quick time), measured at trough before the morning drug intake, were chosen as primary pharmacokinetic and pharmacodynamic variables. In addition, phenprocoumon protein binding and the eudismic ratio of phenprocoumon were determined. The mean values from data obtained on day 12 to 15 (i.e. measurements under phenprocoumon alone) and the mean values from those data obtained from day 25 to 28 (i.e. under comedication with flupirtine) were subject to subsequent statistical procedures. Phenprocoumon plasma concentrations came to 1.38 +/- 0.28 micrograms/ml on day 12 to 15 and were not significantly altered under flupirtine coadministration with 1.48 +/- 0.36 micrograms/ml on day 25 to 28 (95% confidence interval: 1.02-1.11, point estimator: 1.06). The average Quick time came to 68 +/- 10% on day 12-15 and 73 +/- 15% on day 25-28. The nonparametric 95%-confidence interval for the ratio ranged between 0.96 and 1.14, the point estimator was determined to 1.04. Protein binding of phenprocoumon was determined to 88.8% +/- 0.5 on day 14 and to 88.9 +/- 0.5% on day 28. The ratio of S/R-phenprocoumon was 1:0.84 on day 14 and 1:0.84 on day 28. These results do not provide any evidence for a pharmacokinetic and/or pharmacodynamic interaction between flupirtine and phenprocoumon.
Administration, Oral↗
[Herniation of the cecum and ascending colon through the Winslowi foramen in the bursa omentalis].
Herniation through the foramen of Winslow (HFW) is exceedingly rare, the ileum, coecum or ascending colon is involved mostly. One new case is presented here to illustrate the clinical findings, which are often discreet, and the characteristical radiographic features, which can lead to definitive preoperative diagnosis. Treatment is by surgical reduction of the hernia, resection of non-viable bowel or fixation of coecum and ascending colon. Closure of the foramen is generally considered unnecessary. Without delay in diagnosis and treatment, the former high letality rate of the condition is now nearly zero.
Anastomosis, Surgical↗
[Cystic lymphangioma of the transverse mesocolon].
Intraabdominal cystic lymphangiomas are very rare. One new case of the disease is presented here: a 10-year-old boy undergoes laparotomy because of suspected appendicitis acuta, a cystic tumor in the transverse mesocolon is found and a segmental colon resection with primary anastomosis performed. Histologic examination of the tumor leads to the diagnosis of cystic lymphangioma. The postoperative course is uneventful. History, clinical features, diagnosis, therapy and pathologic-anatomical findings are discussed and the literature is reviewed.
Appendicitis↗
Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells.
The transplantation of well defined populations of precursor cells offers a means of repairing damaged tissue and of delivering therapeutic compounds to sites of injury or degeneration. For example, a functional immune system can be reconstituted by transplantation of purified haematopoietic stem cells, and transplanted skeletal myoblasts and keratinocytes can participate in the formation of normal tissue in host animals. Cell transplantation in the central nervous system (CNS) has been proposed as a means of correcting neuronal dysfunction in diseases associated with neuronal loss; it might also rectify glial cell dysfunction, with transplanted oligodendrocyte precursor cells eventually allowing repair of demyelinating damage in the CNS. Here we use co-operating growth factors to expand purified populations of oligodendrocyte type-2 astrocyte (O-2A) progenitor cells for several weeks in vitro. When injected into demyelinating lesions in spinal cords of adult rats, created in such a way as to preclude host-mediated remyelination, these expanded populations are capable of producing extensive remyelination. In addition, transplantation of O-2A progenitor cells genetically modified to express the bacterial beta-galactosidase gene gives rise to beta-galactosidase-positive oligodendrocytes which remyelinate demyelinated axons within the lesion. These results offer a viable strategy for the manipulation of neural precursor cells which is compatible with attempts to repair damaged CNS tissue by precursor transplantation.
Animals↗
The effect of ultrasonic irradiation and temperature on fibrinolytic activity in vitro.
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Fibrinolysis↗
Mycoplasma cells stimulate in vitro activation of plasminogen by purified tissue-type plasminogen activator.
In an in vitro direct assay with tissue-type plasminogen activator (tPA), plasminogen and the chromogenic substrate S-2251, the ability of Mycoplasma fermentans KL4 to stimulate tPA-mediated activation of plasminogen to plasmin was studied. Mycoplasma cells markedly enhanced the activation of plasminogen by tPA in a concentration-, temperature- and pH-dependent manner. Nonidet P-40 (0.01%), sonication, and freezing and thawing of the cells substantially increased the stimulatory effect of mycoplasma on tPA activity. In contrast, the activation of plasminogen by urokinase was refractory to mycoplasma cells. The mycoplasma-mediated stimulation of tPA activity was prevented by epsilon-aminocaproic acid (EACA), a lysine analogue known to block lysine-binding sites (LBS) in plasminogen and tPA. Among several Mycoplasma fermentans strains tested, incognitus strain demonstrated the highest stimulation activity. These results suggest that mycoplasma cells interact with LBS in tPA and plasminogen to enhance plasminogen activation.
Enzyme Activation↗
The inhibition of oligodendrocytic differentiation of O-2A progenitors caused by basic fibroblast growth factor is overridden by astrocytes.
The inhibition of differentiation of oligodendrocyte-type-2 astrocyte (O-2A) progenitors into oligodendrocytes caused by basic fibroblast growth factor (bFGF) can be overcome by non-O-2A lineage cells present in the optic nerve and by astrocytes purified from cerebral cortices. Although purified O-2A progenitors grown in the presence of bFGF for up to 6 days were inhibited from differentiating into oligodendrocytes, O-2A progenitors growing in heterogeneous optic nerve cultures did not show a similar inhibition of differentiation. The factor(s) responsible for overriding the inhibitory effects of bFGF appeared to be secreted by astrocytes, as extensive generation of oligodendrocytes was seen in cultures of purified O-2A progenitors exposed to bFGF+ medium conditioned by purified astrocytes (ACM). In addition, purified O-2A progenitors displayed a remarkable sensitivity to bFGF, which extended at least down to concentrations of 0.03 ng/ml, a concentration of < 2 x 10(-12) M. At a bFGF concentration of just 0.1 ng/ml, this mitogen still promoted DNA synthesis in as many O-2A progenitors as in cultures exposed to 1-30 ng/ml of this growth factor, but exhibited a reduced ability to promote DNA synthesis in oligodendrocytes. In addition, although concentrations of bFGF as low as 0.03 ng/ml were a potent stimulator of DNA synthesis in O-2A progenitors, application of this amount of bFGF no longer inhibited the differentiation of progenitors into oligodendrocytes as effectively as application of higher bFGF concentrations. Thus, the induction of DNA synthesis by bFGF can be uncoupled from the inhibition of differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Hemostatic and metabolic effects of lowering the ethinyl-estradiol dose from 30 mcg to 20 mcg in oral contraceptives containing desogestrel.
The metabolic and hemostatic effects of two oral contraceptives containing 150 mcg desogestrel and 20 mcg ethinyl-estradiol (EE) (MERCILON) or 30 mcg EE (MARVELON) were compared in order to examine the effect of reducing the EE dose in contraceptive pills. Forty-nine women participated in this randomized study during 6 cycles. In both groups, there was a significant increase in triglycerides, HDL-cholesterol and apoprotein A1; the same increase was observed for SBP and CBG. Slight and transient variations of fasting blood glucose levels were seen in the 30 mcg EE group and in the two groups for fasting insulin levels. The increase in renin substrate was significantly higher with the 30 mcg EE than with the 20 mcg EE pill. In both groups, plasminogen increased significantly, but antithrombin III, total and free protein S and fibrinogen decreased significantly only in women taking the 30 mcg EE pill, whereas there was no significant change in the 20 mcg EE group. Reducing the dose of EE in oral contraceptives from 30 mcg to 20 mcg minimizes their impact on renin substrate and hemostatic parameters.
Apolipoprotein A-I↗
Elevated serum aminotransferase activity as an early manifestation of gluten-sensitive enteropathy.
Six children in whom long-standing hypertransaminasemia of unknown cause led to an initial diagnosis of chronic or protracted cryptogenic hepatitis were found to have asymptomatic celiac disease. Administration of a gluten-free diet caused a prompt improvement of both hepatic and intestinal biochemical/histologic abnormalities. Hepatic damage may be another "atypical" form of celiac disease in children.
Celiac Disease↗