Growth advantage of human leiomyoma cells compared to normal smooth-muscle cells due to enhanced sensitivity toward insulin-like growth factor I

Human uterine leiomyomas exhibit increased IGF-I binding compared to myometrium, while both tissues show IGF-I gene expression. In this study we have examined the functional importance of these findings by testing the presence of IGF-I in 15 leiomyoma biopsies and in 18 myometrium biopsies and the capacity of smooth-muscle cells cultured from these tissues to react to IGF-I. The mean IGF-I peptide concentration in leiomyomas was 3 times higher than in myometrium. This resulted from increased IGF-I uptake in leiomyomas rather than from increased synthesis, as these tissues contain higher concentrations of type-I IGF receptors, as detected by immunohistochemistry, and equal levels of IGF-I mRNA. Blocking IGF-I transport with cytochalasin-B and with the type-I IGF receptor blocking antibody alpha IR3 in cultured cells induced decreased immunostaining intensity for IGF-I in most myometrium and leiomyoma cultures, indicating that the detected IGF-I is internalized. Depending on the culture conditions, IGF-I administration yielded increased survival or a higher proliferation rate in leiomyoma cultures than in myometrium cultures, indicating the increased importance of exogenous IGF-I for the growth of transformed smooth-muscle cells. We conclude that the increased concentrations of type-I IGF receptors in leiomyoma compared to myometrial smooth-muscle cells are functional with respect to the enhanced internalization of IGF-I and that they provide these tumor cells with a growth advantage compared to their normal counterparts.     

Preoperative biliary drainage, colonisation of bile and postoperative complications in patients with tumours of the pancreatic head: a retrospective analysis of 241 consecutive patients

OBJECTIVE: To analyse the outcome of preoperative biliary drainage in patients being operated on for a tumour in the pancreatic head. DESIGN: Retrospective study. SETTING: University hospital, The Netherlands. SUBJECTS: Consecutive series of 241 patients. MAIN OUTCOME MEASURES: Decline in bilirubin concentrations and bacterial contamination of bile as a result of preoperative drainage. Incidence of postoperative complications in patients who underwent preoperative drainage and those who did not. RESULTS: 184/241 patients underwent preoperative biliary drainage. Endoscopic drainage was the most effective, shown by a median reduction in bilirubin concentrations of 82%, 74%, and 50% after endoscopic drainage (n = 149), papillotomy (n = 25) and external drainage (n = 10), respectively. Bacterial contamination of bile was significantly more common when an endoprosthesis was used, but did not result in a higher rate of infective complications. 163 Whipple's resections, 33 total pancreatectomies, and 45 biliary-enteric bypasses were performed. 137/241 (57%) patients had postoperative complications. There was no significant difference in the incidence of postoperative complications between patients who had preoperative biliary drainage and those who did not (p = 0.4).     

Mutation of serine-46 to aspartate in the histidine-containing protein of Escherichia coli mimics the inactivation by phosphorylation of serine-46 in HPrs from gram-positive bacteria

Histidine-containing protein (HPr) is a phosphocarrier protein of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. HPr is phosphorylated at the active site residue, His15, by phosphoenolpyruvate-dependent enzyme I in the first enzyme reaction in the process of phosphoryl transfer to sugar. In many Gram-positive bacterial species HPr may also be phosphorylated at Ser46 by an ATP-dependent protein kinase but not in the Gram-negative Escherichia coli and Salmonella typhimurium. One effect of the phosphorylation at Ser46 is to make HPr a poor acceptor for phosphorylation at His15. In Bacillus subtilis HPr, the mutation Ser46Asp mimics the effects of phosphorylation. A series of mutations were made at Ser46 in E. coli HPr: Ala, Arg, Asn, Asp, Glu, and Gly. The two acidic replacements mimic the effects of phosphorylation of Ser46 in HPrs from Gram-positive bacteria. In particular, when mutated to Asp46, the His 15 phosphoacceptor activity (enzyme I Km/Kcat) decreases by about 2000-fold (enzyme I Km, 4 mM HPr; Kcat, approximately 30%). The alanine and glycine mutations had near-wild-type properties, and the asparagine and arginine mutations yielded small changes to the Km values. The crystallographic tertiary structure of Ser46Asp HPr has been determined at 1.5 A resolution, and several changes have been observed which appear to be the effect of the mutation. There is a tightening of helix B, which is demonstrated by a consistent shortening of hydrogen bond lengths throughout the helix as compared to the wild-type structure. There is a repositioning of the Gly54 residue to adopt a 3(10) helical pattern which is not present in the wild-type HPr. In addition, the higher resolution of the mutant structure allows for a more definitive placement of the carbonyl of Pro11. The consequence of this change is that there is no torsion angle strain at residue 16. This result suggests that there is no active site torsion angle strain in wild-type E. coli HPr. The lack of substantial change at the active center of E. coli HPr Ser46Asp HPr suggests that the effect of the Ser46 phosphorylation in HPrs from Gram-positive bacteria is due to an electrostatic interference with enzyme I binding.     

The parallel process in clinical supervision with a schizophrenic client

The authors analyze a male nurse's account of how he experienced his interaction with a female schizophrenic client during sessions of systematic clinical supervision. Notes taken during 15 sessions were analyzed by means of open coding. The analysis revealed the importance of being aware of the parallel process that occurs among the client, the primary nurse, and the unit staff.     

Effects of exercise on fluid exchange and body composition in man during 14-day bed rest

To determine the cause of the body weight loss during bed rest (BR), fluid balance and anthropometric measurements were taken from seven men (19-21 yr) during three 2-wk BR periods which were separated by 3-wk ambulatory recovery periods. Caloric intake was 3,073 +/- 155 (SD) kcal/day. During two of the three BR periods they performed supine isotonic exercise at 68% of VO2max on the ergometer for 1 h/day; or supine isometric exercise at 21% of maximal leg extension force for 1 min followed by a 1-min rest for 1 h/day. No prescribed exercise was given during the other BR period. During BR, body weight decreased slightly with no exercise (-0.43 kg, NS), but decreased significantly (P less than 0.05) by -0.91 kg with isometric and by -1.77 kg with isotonic exercise. About one-third of the weight reduction with isotonic exercise was due to fat loss (-0.69 kg) and, the remainder, to loss of lean body mass (-0.98 kg). It is concluded that the reduction in body weight during bed rest has two major components: First, a loss of lean body mass caused by assumption of the horizontal body position that is independent of the metabolic rate. Second, a loss of body fat content that is proportional to the metabolic rate.     

Juvenile aponeurotic fibroma

Juvenile aponeurotic fibroma is an uncommon benign tumor which occurs mostly in the hands and wrists of young children. It has a tendency to recur, especially in younger individuals, and this, combined with a rather cellular microscopic appearance, has led to mistaken diagnoses of malignancy. No instances of metastasis have been reported. Conservative therapy, consisting of excisional biopsy without sacrifice of vital structures, is indicated.     

EFficacy of albendazole for treatment of naturally acquired fasciola hepatica in calves

In calves given various doses of albendazole as a 4.55% (w/v) drench suspension, removal efficacies against mature Fasciola hepatica were 77.5% with the dose of 7.5 mg/kg; 92.3%, with 10 mg/kg; and 85.9%, with 15 mg/kg. Against immature F hepatica, drug efficacies with these doses were 32.7%, 20.0%, and 36.7%, respectively. Reductions in length and width measurements of mature and immature flukes recovered from the bile ducts correlated with the larger doses reflected a greater efficacy against mature flukes or a possible inhibiting effect of the drug on fluke size or growth. Numbers of eggs recovered in bile at necropsy were reduced by 87.8% with the dose of 7.5 mg/kg; 91.8%, with 10 mg/kg; and 95.6%, with 15 mg/kg.