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At least 199 records · Page 11Linked to original sources
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMedDate not supplied

Aortic valve replacement in osteogenesis imperfecta--technical and practical considerations for a successful outcome.

Osteogenesis imperfecta is a connective tissue disorder that is rarely associated with isolated aortic insufficiency. Surgery on such patients carries high morbidity and mortality, which are mostly associated with bleeding tendencies secondary to increased tissue and capillary fragility. We report a 42-year-old male with isolated aortic incompetence, who underwent aortic valve replacement (AVR) with a mechanical prosthesis. The postoperative course was uneventful, and the patient was discharged home on the seventh postoperative day (POD 7). He remains well on follow-up 6 months later. We highlight the importance of a meticulous surgical technique, together with a strategy for management of anticipated perioperative complications to ensure a successful outcome.

Adult↗
PubMed1998

Association between hyperflexibility of the thumb and an unexplained bleeding tendency: is it a rule of thumb?

A bleeding tendency manifested by petechiae and ecchymoses is one of the most common causes for referral of patients to haematology clinics. Vessel wall pathology is not usually considered to be a cause for deranged haemostasis, although coexistence of increased capillary fragility and joint hypermobility have been reported. We determined the frequency of thumb hyperextensibility and scored the findings in a series of 44 patients referred because of ecchymoses and petechiae, as well as 261 control children and their mothers. All 44 patients had normal coagulation studies. Thumb flexibility score was +4 in 30 patients, +3 in eight patients, +2 in five patients and +1 in one of the index patients. In the control group, only one of 261 had a +4, and three had a +3 score, and two of 260 mothers had a +4 score. Ecchymoses were not observed in any of these subjects, nor in the +1 patients. Based on clinical presentation and normal coagulation studies, we suggest that our patients had an underlying subtype of Ehlers-Danlos syndrome. In view of the dramatically high occurrence of thumb hyperextensibility in patients with unexplained mild bleeding tendency, costly haemostatic and coagulation studies on such patients may not be necessary.

Child↗
PubMed2000

Acute pulmonary haemorrhage in an infant during induction of general anaesthesia.

Pulmonary haemorrhage is a rare, life-threatening complication of anaesthesia. This report describes the anaesthetic management of an infant who developed laryngospasm and pulmonary haemorrhage during general anaesthesia. The infant was subsequently found to have prior exposure to a fungus, Stachybotrys chartarum, which produces mycotoxins that may have produced capillary fragility in the infant's rapidly growing lungs.

Acute Disease↗
PubMed2000

Pathogenesis of classical swine fever: renal haemorrhages and erythrodiapedesis.

Thirty pigs were inoculated with a virulent isolate (Quillota strain) of classical swine fever (hog cholera) virus to establish the chronological occurrence of lesions in the kidney and to determine the mechanism responsible for renal haemorrhages. The study included the use of histopathological, ultrastructural, immunohistochemical (detection of viral antigen gp55, MAC387, lambda chains, CD3 and C1q) and morphometrical techniques (vascular area). Renal interstitial oedema and haemorrhages were detected from 7 days post-inoculation (dpi), associated with a slight interstitial mononuclear infiltrate and evidence of viral infection in macrophages and fibroblasts, and in a small proportion of lymphocytes. Viral infection was not detected in capillary endothelial cells. An intense mononuclear infiltrate, with B cells, T cells and small numbers of macrophages, was detected from 10 dpi. In the final phase of the experiment (14 dpi), slight proliferation and degranulation of mast cells were observed. Increased expression of the C1q component of complement was also detected. A significant increase in vascular area was observed from 7 dpi. These results suggest that haemorrhages observed in the kidneys of pigs inoculated with the Quillota strain resulted from erythrodiapedesis and increased vascular permeability, probably aggravated by mast cell degranulation in the final stage of the experiment. The results suggested that mast cell degranulation was linked to activation of the complement system.

Animals↗
PubMed2000

Ruscus aculeatus (butcher's broom) as a potential treatment for orthostatic hypotension, with a case report.

CONTEXT: Chronic orthostatic hypotension (OH) is frequently a severely debilitating disease that affects large groups of the population with autonomic insufficiency--the elderly; patients with diabetes, Parkinson's disease, and chronic fatigue syndrome; and anyone on drugs that affect the autonomic nervous system. Unfortunately, even though more than 60 medications are currently being used to treat OH, none of them is particularly or consistently effective. Ruscus aculeatus, a phytotherapeutic agent that is well known in Europe, may, however, change this. Its vasoconstrictive and venotonic properties make it ideally suited to treat the pooling of blood in the limbs, lack of venous tone, and lack of neurally mediated vasoconstriction that frequently characterize OH. Although it has never been suggested as a treatment for OH, it already has a long, proven record of use in Europe for treating a variety of circulatory disorders. OBJECTIVE: To provide evidence for what appears to be an effective, safe, inexpensive botanical therapy for OH and encourage further studies on the efficacy of Ruscus for OH patients. DESIGN: Review of OH and therapies currently available for OH and evaluation of the properties of Ruscus aculeatus, its mechanism of action, and its suitability as a therapeutic agent for treatment of OH. RESULTS: A review of the many pharmacologic and nonpharmacologic agents for treating OH reveals that all of the drug therapies are disappointing and marginally useful. Although nonpharmacologic management is preferred, in the many cases in which OH becomes debilitating, pharmacologic intervention becomes a last resort. But drug therapy may not always be necessary, because Ruscus aculeatus, a phytotherapeutic agent containing ruscogenins and flavonoids, may prove useful for the treatment of OH if denervation is not so advanced that it has compromised receptor activity at the venous wall. Ruscus aculeatus is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall. It also possesses venotonic properties: it reduces venous capacity and pooling of blood in the legs and exerts protective effects on capillaries, the vascular endothelium, and smooth muscle. Its flavonoid content strengthens blood vessels, reduces capillary fragility, and helps maintain healthy circulation. Unlike most of the drug therapies used to treat OH, Ruscus aculeatus does not cause supine hypertension. It also appears to do something no other therapy can offer--alleviate the worsening effects of OH in environmentally hot conditions. Finally, it is an extremely safe, inexpensive, over-the-counter botanical medicine. CONCLUSION: With proven phlebotherapeutic properties, including vasoconstrictive action and venotonic properties, Ruscus aculeatus shows great promise for ameliorating the symptoms of OH and improving the quality of life for large groups in the population. It clearly deserves to be the object of wider research and study as a treatment for OH.

Aged↗
PubMed2006

The use of vitamin A-deficient diets and jugular vein ligation to increase intracranial pressure in chickens (Gallus gallus).

A technique was developed to record intracranial cerebrospinal fluid pressure (iCSFp) in chicks and mature chickens. Using that procedure, 2 methods were found to effect a significant elevation in intracranial pressure: 1) feeding a purified diet to roosters for 40 d containing 25% of the bird's requirement for vitamin A, and 2) ligating both jugular veins in birds. The purified diet significantly reduced plasma retinol levels from 1.080 to 0.046 microg/mL, and iCSFp was significantly elevated from 63.0 to 106.0 mmH2O (P < or = 0.05). Two limitations for using hypovitaminosis A diets were capillary fragility and a cisterna magna that did not develop to the size of that structure in birds of the same age fed control diets with adequate vitamin A content. The second procedure, a reversible surgical technique, showed that within 2.5 h from jugular vein ligation, intracranial pressure rose to 109.7 mmH2O, comparable with levels attained following feeding a vitamin A deficient diet to roosters. Bilateral clamping of the jugular veins overnight resulted in an elevation of iCSFp to 127 +/- 8.86 mmH2O. Results suggest that the chicken may be a useful animal model to investigate intracranial hypertension and its accompanying headaches known to occur in humans.

Aging↗
PubMed1980

Stress hormones, lipids, and factors of hemostasis in trauma patients with and without fat embolism syndrome: a comparative study at least one year after severe trauma.

The pathophysiologic mechanism of fat embolism syndrome (FES) has been thought to depend on mechanical blockage of capillaries by fat emboli or on the toxic effect of free fatty acids on the capillary endothelium. Aggregation of platelets, microembolism, disseminated intravascular coagulation, and vasoactive amines are considered to be involved. The question of why some patients develop fat embolism while other patients with similar injuries do not remains to be solved. Blood tests in ten patients who developed FES and their reaction to stress were compared to the same tests in ten patients with similar injuries without FES at least 1 year after trauma. The following were measured: blood Hb, leucocytes, platelets, protein and lipid electrophoresis, ACTH, cortisol, TSH, GH, insulin, glucose, NEFA, certain coagulation and fibrinolytic studies, alpha 1 antitrypsin, and antithrombin III. The platelet values, especially after stress, and P + P values were higher in the FES-patients. The alpha-beta lipoprotein ratio was lower and the blood glucose values were higher in half of those FES-patients in whom a diabetic heredity was discovered. The U-catecholamines were also somewhat higher in the FES-patients. Disturbances of the lipid and carbohydrate metabolism as well as a high platelet count and high P + P values may predispose to thrombosis and DIC. More numerous petechiae in Rumpel-Leede's stasis test in fat embolism patients suggest increased capillary fragility. Low growth hormone values in FES-patients and a different cortisol reaction to stress compared to control patients suggests a disturbed neurohumoral regulation in FES.

Adolescent↗
PubMed1976

Blood coagulation, fibrinolysis and plasma proteins in women with normal and with excessive menstrual blood loss.

A group of women with excessive menstrual blood loss (menorrhagia) without any known local or general underlying disease was studied and compared to a group of women with normal menstrual blood loss. Blood coagulation, platelet function and fibrinolysis as well as a variety of plasma proteins were analyzed on six occasions during one menstrual cycle. Women with menorrhagia were found to have a slightly higher concentration of fibrinogen--fibrin degradation products, a higher factor V and VIII activity, higher antithrombin III, alpha 1-antitrypsin concentrations and higher antifibrinolytic activity than the normal women. The concentration of albumin, beta IE-globulin, orosomucoid, ceruloplasmin and IgG were lower in women with memorrhagia than in normals. The capillary fragility did not differ significantly between the groups. The observed differences in clotting factors between the groups could not have caused the differences in blood losses.

Adult↗
PubMed1996

Does diabetes mellitus increase the requirement for vitamin C?

This paper reviews the scientific evidence regarding the vitamin C status of people with diabetes mellitus and whether they might have increased dietary vitamin C requirements. English language articles published from 1935 to the present that either compare ascorbic acid concentrations of persons with and without diabetes mellitus or assess the impact of vitamin C supplementation on various health outcomes among persons with diabetes mellitus were examined. Most studies have found people with diabetes mellitus to have at least 30% lower circulating ascorbic acid concentrations than people without diabetes mellitus. Vitamin C supplementation had little impact on blood glucose concentrations, but was found to lower cellular sorbitol concentrations and to reduce capillary fragility. Much of the past research in this area has been methodologically weak. To further understand the relation of ascorbic acid and diabetes mellitus, randomized clinical trials of ascorbic acid supplementation should be a high priority for research.

Ascorbic Acid↗
PubMed1996

Openings in frog microvascular endothelium induced by high intravascular pressures.

1. We have investigated the effects of microvascular pressures, high enough to rupture the vessel wall, upon the ultrastructure and permeability of mesenteric capillaries in pithed frogs. 2. The vessels were perfused via micropipettes with Ringer solutions containing bovine serum albumin (1 mg ml-1) and a few human red cells. After a perfused section of vessel had been closed downstream, pressure (applied via the micropipette) was raised in a series of steps of 10 mmHg, each lasting approximately 10 s, until the vessel ruptured. Fluid filtration through the vessel wall prior to rupture was estimated from the movements of the red cells. 3. Seven vessels were fixed in glutaraldehyde immediately after rupture and prepared for electron microscopy. The electron micrographs revealed openings in the vessel walls and thirty-six of these gaps were completely defined in runs of serial sections made on four of the vessels. Twenty-nine of these gaps passed through the endothelial cells (transcellular) and seven were intercellular. 4. The pressure at which a vessel ruptured, Pb, was measured in twenty-nine vessels and had a mean +/- S.E.M. value of 79.6 +/- 5.0 cmH2O. In ten of these vessels, which had a mean +/- S.E.M. Pb of 84.2 +/- 6.5 cmH2O, microvascular pressure was lowered immediately after the initial rupture and the vessel perfused at a pressure of 20 cmH2O. Pb was then remeasured and found to be 69.9 +/- 8.4 cmH2O, which was not significantly different from its initial value. 5. Hydraulic permeability (Lp) was measured in six vessels over the range of 15-30 cmH2O before and 10 min after the vessel wall ruptured at high pressure. Mean values were 5.5 x 10(-7) and 4.0 x 10(-7) cms-1 cmH2O-1 and were not significantly different. 6. At pressures equal to and 10 mmHg below Pb, small short-lived increases in filtration rate were observed. It is suggested that these may correspond to the increased permeability to fluid and macromolecules observed at high microvascular pressures in intact capillary beds.

Animals↗