Crkl is constitutively tyrosine phosphorylated in platelets from chronic myelogenous leukemia patients and inducibly phosphorylated in normal platelets stimulated by thrombopoietin

Platelet functions such as aggregation and clot retraction are often abnormal in chronic mylogenous leukemia (CML) patients. However, the molecular mechanisms of these altered functions are unknown. As expression of the p210bcr-abl oncogene product, a constitutively active tyrosine kinase, is known to have an essential role in the pathogenesis of CML and tyrosine phosphorylation is intimately involved in various aspects of platelet activation, we examined the pattern of protein tyrosine phosphorylation in platelets from 15 CML patients by immunoblotting with a monoclonal antiphosphotyrosine antibody (4G10). Before and after stimulation with thrombin, the only consistent difference between normal and CML platelets was the presence of a tyrosine phosphorylated protein with a relative molecular weight of 39 kD. This tyrosine phosphorylated protein was identified as crid, an SH2, SH3 containing adapter protein. Thus, as previously demonstrated for neutrophils from CML patients, tyrosine phosphorylation of p39crkl persists in mature platelets. No tyrosine phosphorylation of crid was detected following stimulation with thrombin in normal platelets. However, crkl became incorporated into the Triton X-100 insoluble residue following thrombin stimulation in a manner dependent on platelet aggregation. Further, we found that crkl is an endogenous substrate for calpain, a protease that may be involved in postaggregation signaling processes. This suggests that crkl may be involved in the reorganization of the cytoskeleton during normal platelet aggregation and its tyrosine phosphorylation in CML platelets may contribute to the abnormal platelet function in CML patients. Finally, we found that thrombopoietin induces tyrosine phosphorylation of crk1 in normal platelets and FDCP cells genetically engineered to express human c-Mpl. This suggests that crk1 can be phosphorylated by a kinase other than p210bcr-abl and that crk1 may have a role in signaling by thrombopoietin.     

Normal acetabular anatomy for acetabular fracture assessment: CT and plain film correlation

The computed tomographic (CT) and conventional radiographic appearances of the acetabulum are correlated for assessment of acetabular fractures according to the Judet and Letournel classification system, a system widely used by orthopedic surgeons performing fracture reduction and external fixation of the acetabulum. A desiccated pelvis was marked along the acetabular borders with lead solder, and anteroposterior (AP) and oblique radiographs were obtained. The solder was then replaced by barium-impregnated string, and the acetabulum was scanned by CT. Radiographic-CT correlations of acetabular landmarks should aid the orthopedist by providing a useful interpretation of acetabular fractures according to the Judet and Letournel system.     

Growth hormone therapy in pre-pubertal children with Noonan syndrome: first year growth response and comparison with Turner syndrome

We studied the growth-promoting effect of treatment with recombinant human growth hormone in 23 prepubertal children with Noonan syndrome, aged between 5. 4 and 14. 3 y, and all with a height < 1. 4 SD for Tanner standards. The growth response and skeletal maturation after 1 y of recombinant human growth hormone treatment (0. 15 U/kg/day given by daily injection) in the Noonan syndrome patients was compared with the auxological changes observed in a group of 17 girls with Turner syndrome with a comparable age and height deficit who were treated with recombinant human growth hormone in a similar way. During 1 y of treatment, the mean ± SD height velocity increased by 4. 0 ± 1. 6 cm/y in the Noonan syndrome group and by 3. 6 ± 1. 3 cm/y in the Turner syndrome group. Height SDS for chronological age in the Noonan syndrome group increased by 0. 53 ± 0. 46 ( p < 0. 001). In the Noonan syndrome patients the changes in height velocity were positively related to birthweight ( r = 0. 48, p < 0. 05). The changes in height velocity or height SDS were not related to the age, height deficit or a delay in bone age maturation at start of treatment. In neither the patients with Noonan syndrome nor Turner syndrome was an acceleration of bone maturation found. We conclude that treatment with recombinant human growth hormone in pre-pubertal NS patients induces an increase in height velocity and height SDS comparable to that observed in Turner syndrome girls.     

Control of colonic variceal haemorrhage with a somatostatin analogue

A 64 year old caucasian male with known alcoholic liver disease presented with rectal bleeding. The patient bled repeatedly despite resuscitation. A sigmoid colectomy was performed following an angiogram. Large colonic, rectal and mesenteric variceal vessels were noted at surgery. Further bleeding postoperatively was rapidly controlled with octreotide infusion. Octreotide may be as useful in the control of colonic variceal bleeding as it is in the control of oesophageal variceal bleeding.     

Dietary strategies and uptake of reduced fat foods

AIM: This research has sought to identify factors determining consumer uptake and rejection of reduced fat foods. Initial qualitative research implied that use of reduced fat products could be dependent upon which dietary health strategies people adopt. This analysis therefore explores the degree to which various dietary strategies predict uptake of reduced fat products. METHOD: Items were derived from prior qualitative findings and responses to relevant issues surveyed by interview (n = 1004) within selected retail outlets throughout Northern Ireland and England. RESULTS: Logistic regression analysis indicated that concern over health, drive to reduce calorie consumption, to increase intake of fish and poultry and fruit and vegetables consistently predicted consumption across a range of reduced fat products. These dietary strategies appeared to predict uptake of reduced fat foods to a greater degree than perceived taste or price. CONCLUSION: The findings imply that for reduced fat foods to achieve universal acceptance promotional messages need to be translated into commonly adopted dietary health strategies.     

Human plasma extrinsic pathway inhibitor activity: I. Standardization of assay and evaluation of physiologic variables

An assay was standardized to measure extrinsic pathway inhibitor (EPI) activity in human plasma. Variables that could potentially influence its measurement were systematically examined. The coefficient of variation of the assay was 6.3% for the same sample assayed on different days. The linear regression line for a plot of observed v expected values of mixtures of plasmas with different EPI levels was Y = 1.01X - 2.7%. Single samples from 21 healthy adults under 60 years of age varied between 74% and 159% of a pooled reference plasma. The plasma level of a given individual (eight subjects) did not vary on repeat sampling over weeks to months. EPI activity was significantly lower in plasma from umbilical cord blood (64.3% +/- 12.7%, n = 16) than in plasma from adults. Mean EPI activity in adults greater than or equal to 60 years of age was slightly but significantly higher (112% +/- 16.8%, n = 23) than in adults less than 60 years of age (97.2% +/- 19.0%, n = 21). EPI levels in the third trimester of pregnancy were slightly higher than in nonpregnant women. Plasma EPI levels fell slightly after surgical procedures that caused fibrinogen levels to rise, which suggests that EPI is not an acute phase reactant. Administration of 1-desamino-8-d-arginine vasopressin (DDAVP) did not alter plasma EPI levels. In two patients subjected to plasmapheresis and volume replacement with albumin and isotonic saline, plasma EPI levels returned to one-half of the levels before pheresis within about one day.     

Obtaining funding for fertility services through the NHS

There is considerable anecdotal evidence that where a coherent, consistent and concise message, coupled with an active and resilient lobby campaign has been taken to a health authority and local MPs, funding has followed. The key feature of these efforts has been clinicians and patients working together. Also, campaigns are the more successful with the more patients that can be involved and this is an area where clinicians could play a major role in motivating patients to apply pressure on health authorities. Many infertility specialists and other professional colleagues have been very active in arguing the case both on their own account and when backing the work of the National Infertility Awareness Campaign and patients generally. Others have not. For them, this article is their call to arms.      

Dummies and the sudden infant death syndrome

The association between dummy use and sudden infant death syndrome (SIDS) was investigated in 485 deaths due to SIDS in the postneonatal age group and compared with 1800 control infants. Parental interviews were completed in 87% of subjects. The prevalence of dummy use in New Zealand is low and varies within New Zealand. Dummy use in the two week period before death was less in cases of SIDS than in the last two weeks for controls (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.57 to 1.02). Use of a dummy in the last sleep for cases of SIDS or in the nominated sleep for controls was significantly less in cases than controls (OR 0.44, 95% CI 0.26 to 0.73). The OR changed very little after controlling for a wide range of potential confounders. It is concluded that dummy use may protect against SIDS, but this observation needs to be repeated before dummies can be recommended for this purpose. If dummy sucking is protective then it is one of several factors that may explain the higher mortality from SIDS in New Zealand than in other countries, and may also explain in part the regional variation within New Zealand.