An update on the management of uterine fibroids.
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Americas↗
Biomedical subjects
J Frederick
Publications and source records attributed to J Frederick.
Characterization of GRK2-catalyzed phosphorylation of the human substance P receptor in Sf9 membranes.
G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied G protein-coupled receptors (GPCRs), resulting in GPCR desensitization. GRK2 is one of the better studied of the six known GRKs and phosphorylates several GPCRs. In a previous study, we documented that GRK2 and GRK3 phosphorylate purified and reconstituted rat substance P receptor (rSPR) [Kwatra et al. (1993) J. Biol. Chem. 268, 9161-9164]. Here, we characterize in detail GRK2-catalyzed phosphorylation of human SPR (hSPR) in intact membranes. GRK2 phosphorylates hSPR in urea-washed Sf9 membranes in an agonist-dependent manner with a stoichiometry of 19 +/- 1 mol of phosphate/mol of receptor, which increases slightly (1.3-fold increase) in the presence of G beta gamma. Kinetic analyses indicate that receptor phosphorylation occurs with a Km of 6.3 +/- 0.4 nM and a Vmax of 1.8 +/- 0.1 nmol/min/mg; these kinetic parameters are only slightly affected by G beta gamma [Km = 3.6 +/- 1.0 nM and Vmax = 2.2 +/- 0.2 nmol/min/mg]. The lack of a strong stimulatory effect of G beta gamma on GRK2-catalyzed phosphorylation of hSPR is surprising since G beta gamma potently stimulates GRK2-catalyzed phosphorylation of beta 2-adrenergic receptor and rhodopsin. Involvement of G beta gamma endogenously present in membranes is ruled out as a source of high levels of hSPR phosphorylation, since receptor phosphorylation was not affected by guanine nucleotides that suppress or enhance the release of endogenous G beta gamma. The present study determines, for the first time, the kinetics of phosphorylation of a receptor substrate of GRK2 in intact membranes. Further, our results identify hSPR as a unique substrate of GRK2 whose phosphorylation is strong even in the absence of G beta gamma.
Amino Acid Sequence↗
Human substance P receptor expressed in Sf9 cells couples with multiple endogenous G proteins.
To identify the G proteins involved in the function of human substance P receptor (hSPR), the receptor was expressed in Sf9 cells using the baculovirus expression system. Maximal hSPR expression was up to 65 pmol/mg membrane protein. The following data indicated that hSPR in Sf9 membranes is coupled to endogenous G proteins: 1) binding of agonist radioligand [125I]BHSP to the receptor was sensitive to guanine nucleotides; and 2) stimulation of the receptor increased [35S]GTPgammaS binding. The hSPR-associated G proteins were identified by photoaffinity labeling with [alpha-32P]-azidoanilido GTP ([alpha-32P]AAGTP), followed by immunoprecipitation of the labeled G proteins with antibodies specific for various Galpha-subunits. These experiments showed that stimulation of hSPR in Sf9 membranes activated multiple endogenous G proteins including Galpha(o), Galpha(q/11), and Galpha(s). While hSPR's ability to associate with Gq/11 is well-documented, the present study provides the first evidence of hSPR's potential to activate Galpha(o) and Galpha(s).
Animals↗
A randomized comparison of vasopressin and tourniquet as hemostatic agents during myomectomy.
OBJECTIVE: To assess the comparative efficacy of perivascular vasopressin and tourniquet in minimizing bleeding and its sequelae at myomectomy. METHODS: Between March 1994 and February 1995, 52 women with symptomatic uterine leiomyomas scheduled for myomectomy were entered into a randomized trial comparing vasopressin (26 patients) and tourniquet (26 patients) for hemostasis. Myomectomy was performed after either the perivascular injection of 20 U of vasopressin diluted to 20 mL with normal saline or with the use of a Foley catheter tourniquet around both uterine vessels. The efficacy of each method was measured by comparing differences in pre- and postoperative hemoglobin levels, intraoperative blood pressure, measured blood loss, need for blood transfusion, evidence of postoperative febrile morbidity, complications, and length of hospital stay. RESULTS: Vasopressin resulted in less blood loss (mean 287.3 mL [standard deviation (SD) 195] versus 512.7 mL [SD 400] for tourniquet [P = .036]). Six of 26 patients in the tourniquet group lost more than 1000 mL of blood, whereas all of the vasopressin subjects lost less than this amount (P = .023). However, there were no significant differences between the two groups in the fall in the hemoglobin level, number of blood transfusions given, intraoperative blood pressure, highest postoperative pulse and temperature, or other complications. CONCLUSION: Vasopressin prevents blood loss better than using the tourniquet during myomectomy.
Adult↗
Foreign-body reaction to absorbable fixation devices.
While it is evident that poly-p-dioxanon is less reactive than polyglycolide, recent studies, including the case above, have shown that Orthosorb pins are not exempt from the same type of foreign-body reaction as the Biofix products.
Adult↗
Feigned adverse drug reaction to radiographic contrast material.
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Child↗
Intramyometrial vasopressin as a haemostatic agent during myomectomy.
OBJECTIVE: To assess the efficacy of intramyometrial vasopressin for minimising bleeding and its sequelae at myomectomy. DESIGN: A randomised placebo controlled trial. SETTING: University Hospital of the West Indies, Kingston, Jamaica. SUBJECTS: Twenty women with symptomatic uterine fibroids scheduled for myomectomy who satisfied entry criteria: 10 randomised to the vasopressin group and 10 to the control group. INTERVENTION: Myomectomy was performed after the intramyometrial injection of either 20 units vasopressin diluted to 20 ml in normal saline or placebo (20 ml normal saline). MAIN OUTCOME MEASURES: The efficacy of vasopressin was measured by comparing pre- and post-operative haemoglobin levels and haematocrit, changes in intra-operative pulse and blood pressure, measured blood loss, need for blood transfusion and post-operative febrile morbidity in the treatment and control groups. RESULTS: The use of vasopressin resulted in median blood loss of 225 ml (range 150-400 ml) compared with 675 ml (range 500-800 ml) in the placebo group (P < 0.001). The vasopressin group had a correspondingly lower fall in haemoglobin level (median 1.7 g/dl vs 5.3 g/dl, P < 0.001) and haematocrit (median 5% vs 13%, P < 0.001) compared with the controls. Fifty percent of the placebo group had blood transfusions compared with none in the vasopressin group (P = 0.03). There were no significant differences between the groups in intra-operative pulse and blood pressure or post-operative white blood cell counts or temperature. CONCLUSION: The results indicate that vasopressin is effective in preventing blood loss and reducing the need for blood transfusion during myomectomy.
Adult↗
Intravaginal misoprostol versus dinoprostone as cervical ripening and labor-inducing agents.
OBJECTIVE: To compare dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for ripening the cervix and inducing labor at term. METHODS: Sixty-three women were randomized to receive 100 micrograms misoprostol or 3 mg dinoprostone, both as intravaginal tablets. RESULTS: There was no statistical difference between the groups for pre-induction status. The mean Bishop scores before drug insertion were almost identical. Twelve hours after insertion, the mean change in the Bishop score was significantly higher in those receiving misoprostol (5.0 versus 3.3) (P = .008). However, there were no significant differences in induction-to-delivery interval, spontaneous labor rates, type of delivery, fetal outcome, or maternal complications. CONCLUSION: Misoprostol is as effective as dinoprostone for inducing labor at term.
Administration, Intravaginal↗
Intravaginal misoprostol as a cervical ripening agent.
OBJECTIVE: To determine if misoprostol (exogenous prostaglandin E1 PGE1) used vaginally was of value in improving the Bishop score, leading to an early safe vaginal delivery in women in whom the cervix is unripe and delivery is indicated. DESIGN: A double-blind clinical trial. SETTING: Antenatal and labour wards of the University Hospital of the West Indies, Jamaica. SUBJECTS: Forty-five women in the third trimester with various obstetric indications for induction of labour and with no contra-indications to prostaglandins. INTERVENTIONS: The women were randomly assigned to receive treatment or a placebo. The treated group had 100 micrograms misoprostol inserted vaginally while the placebo was similarly inserted. MAIN OUTCOME MEASURES: Efficacy of the misoprostol was measured by the increase in the Bishop score 12 h after giving the treatment, the time between insertion and delivery, the need for oxytocin, and the outcome of the pregnancy. RESULTS: The prostaglandin was superior to the placebo in ripening the cervix and inducing labour. The change in Bishop score was 5.3 in the misoprostol group compared with 1.5 in the placebo group (P < 0.001). The mean time from insertion to delivery was 15.6 h in the former while it was 43.2 h in the placebo group (P < or = 0.001). The need for oxytocin was also significantly less in the women receiving the prostaglandin compared with those who received the placebo (29% vs 62%, P < 0.02). There was no difference in the two groups in the delivery outcome in terms of complications, Apgar scores and mode of delivery. CONCLUSIONS: Intravaginal misoprostol is an effective and cheap method of inducing labour in the third trimester.
Administration, Intravaginal↗
Co-existing leiomyoma and benign cystic teratoma of the ovary.
A case of benign cystic teratoma and a leiomyoma in the same ovary is described. The leiomyoma was confirmed by immunohistochemical methods. The occurrence of leiomyoma and a teratoma within the same ovary is very rare.
Adolescent↗
Increased intestinal protein synthesis during sepsis and following the administration of tumour necrosis factor alpha or interleukin-1 alpha.
The influence of sepsis on intestinal protein synthesis was studied in rats. Sepsis was induced by caecal ligation and puncture (CLP); control rats were sham-operated. Protein synthesis was measured in vivo in the jejunum and ileum following a flooding dose of [14C]leucine. At 8 h after CLP the protein synthesis rate was increased by approx. 15% in jejunal mucosa, and at 16 h after CLP, the protein synthesis rate was increased by 50-60% in the mucosa and seromuscular layer of both jejunum and ileum. In a second series of experiments, rats were treated with recombinant tumour necrosis factor alpha (rTNF alpha) or recombinant interleukin-1 alpha (rIL-1 alpha) administered at a total dose of 300 micrograms/kg body weight over 16 h. Control rats received corresponding volumes of solvent. Treatment with rTNF alpha resulted in an approx. 25% increase in mucosal protein synthesis in jejunum. Following treatment with rIL-1 alpha, protein synthesis increased by 25% in jejunal mucosa and almost doubled in ileal mucosa. The results suggest that sepsis stimulates intestinal protein synthesis and that this response may, at least in part, be mediated by TNF and/or IL-1.
Animals↗
Evidence that tumor necrosis factor participates in the regulation of muscle proteolysis during sepsis.
The role of tumor necrosis factor (TNF) in the regulation of muscle protein turnover was studied in rats. Protein synthesis and total and myofibrillar protein breakdown rates were measured in incubated extensor digitorum longus muscles. Intraperitoneal administration of recombinant TNF-alpha (300 micrograms/kg of body weight) increased total and myofibrillar protein breakdown rates by 28% and threefold, respectively, with no effect on protein synthesis. In subsequent experiments, sepsis was induced by cecal ligation and puncture or a sham-operation was performed. Rats received TNF antiserum (1 mL/100 g of body weight) or control serum 2 hours before cecal ligation and puncture or sham-operation. Treatment with TNF antiserum reduced the mortality rate from 25% to 5% following cecal ligation and puncture. The treatment had no effect on protein synthesis but reduced total and myofibrillar protein breakdown rates by 26% and 39%, respectively, in septic animals. Results suggest TNF is involved in the regulation of sepsis-induced muscle proteolysis.
Animals↗
Intravenous leiomyomatosis with massive ascites.
A case of intravenous leiomyomatosis with massive ascites is reported. This is the first such recorded case. The patient was treated with a subtotal abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathological examination established a vessel wall origin. There is no evidence of recurrence up to 20 months after initial treatment.
Ascites↗
Radical vulvectomy--a 21-year review.
The factors surrounding patients subjected to radical vulvectomy were examined. Most patients were over the age of 40 years. The standard butterfly incision was used in all but 2 cases. The histology in all cases was invasive squamous cell carcinoma. The main complications were primary haemorrhage, urinary tract infection and wound dehiscence. The mean hospital stay was 50 days and the mortality rate was 4 per cent.
Adult↗
Hepatitis A virus attachment to cultured cell lines.
Identification of a hepatitis A virus (HAV) receptor is important for understanding HAV tissue tropism and replication sites and in the design of vaccines and antiviral therapy. The attachment of HAV to cultured cell lines was evaluated: Calcium-dependent specific attachment of four HAV strains to permissive cells occurred, whereas binding to nonpermissive cells did not. Investigation of HAV antigenic variant strains (neutralization escape mutants) demonstrated identical attachment properties with neutralization-susceptible strains, suggesting that the immunodominant neutralization antigenic site of HAV is not directly involved in cell attachment. Unlike foot-and-mouth-disease virus, a related picornavirus, RGD peptides (arginine-glycine-aspartic acid) were unable to interfere with HAV attachment. These studies demonstrate that HAV has a calcium-dependent receptor on cultured cell lines and suggest that the HAV binding region does not involve an RGD sequence or the HAV immunodominant neutralization site.
Amino Acid Sequence↗
Expression of recombinant TGF-beta 2(442) precursor and detection in BSC-40 cells.
Analysis of cDNA clones encoding transforming growth factor (TGF)-beta 2 predicts two different precursor proteins derived by alternative mRNA splicing; a 414 amino acid precursor [TGF-beta 2(414)] and a 442 amino acid precursor [TGF-beta 2(442)]. The two proteins differ by a 28 amino acid insertion within the pro-region of TGF-beta 2(442). In order to characterize the TGF-beta 2-related proteins encoded by the TGF-beta 2(442) cDNA and determine whether it could, in fact, direct the synthesis of active growth factor, we have expressed this gene in Chinese hamster ovary (CHO) cells and, after amplification with methotrexate, obtained stable clones secreting TGF-beta 2(442). The TGF-beta 2 secreted by these cells was latent as acidification was necessary to detect optimal biological activity. In addition to mature TGF-beta 2, high molecular weight pro-region containing proteins were also secreted as analyzed by immunoblotting using site-specific anti-peptide antibodies. These proteins migrated differently than those secreted by CHO cells transfected with cDNA encoding TGF-beta 2(414), indicating that structural differences exist between the two complexes. An anti-peptide antiserum was produced in rabbits against the 28 amino acid insert region of TGF-beta 2(442). This sera was then used to detect the presence of TGF-beta 2(442) in serum-free media conditioned by BSC-40 cells. Since the TGF-beta 2(442) precursor is produced and secreted by a non-recombinant cell line, this suggests that it may play a physiological role in regulating the activity of TGF-beta 2.
Animals↗
Successful pregnancy after conservative surgery for ovarian papillary serous cystadenocarcinoma of low malignant potential.
Conservative surgery was performed on a 28-year-old patient with an ovarian serous cystadenocarcinoma of low malignant potential who became pregnant one year later. The good prognosis of these tumours makes conservative surgical management the treatment of choice when preservation of child-bearing potential is deemed appropriate.
Adult↗
Effect of hydration on random levels of urinary pregnanediol glucuronide.
To determine the effect hydration has upon the relationship between serum progesterone and its urinary metabolite pregnanediol-3 alpha-glucuronide (PDG) we measured spot samples from patients (n = 207) presenting in the 1st trimester of pregnancy. Serum and urine specimens were obtained simultaneously and measured for progesterone and PDG by radioimmunoassay (RIA). Urine specific gravity was also measured at the time of sample collection. Results demonstrated that in samples where the urine specific gravity was greater than or equal to 1.015 there was a strong positive correlation between serum progesterone and PDG (r greater than 0.60, p less than 0.001). However, when urine samples were below a specific gravity of 1.015, serum and urinary steroid values correlated poorly or not at all. We conclude that the measurement of specific gravity should be routinely performed when determining random values of urinary PDG, since only samples in which the urine is adequately concentrated accurately reflect corresponding serum progesterone concentrations.
Adolescent↗