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Biomedical subjects

M Lake

Publications and source records attributed to M Lake.

At least 19 recordsLinked to original sources
PubMed1999

The relationship between placental histology and cervical ultrasonography in women at risk for pregnancy loss and spontaneous preterm birth.

OBJECTIVE: Our objective was to determine whether there were any differences in the placental lesions of high-risk patients with versus without ultrasonographic evidence of cervical shortening between 15 and 24 weeks' gestation. STUDY DESIGN: Women who were at risk for pregnancy loss and spontaneous preterm birth were followed by serial transvaginal cervical ultrasonography with transfundal pressure between 15 and 24 weeks' gestation. Two groups of women were identified: those in whom progressive cervical shortening developed to below 2 cm, either spontaneously or induced by transfundal pressure, and those in whom it did not. A perinatal pathologist who was blinded to the pregnancy outcome retrospectively examined placental histologic slides. The histologic placental lesions were categorized as acute or chronic inflammatory lesions, decidual vascular lesions, and coagulation-related lesions. RESULTS: There were 278 women who were followed during the study. Placentas were submitted for histologic examination in 189 cases (125 singleton, 45 twin, and 19 triplet gestations). There were 72 pregnancies with and 117 pregnancies without an ultrasonographic diagnosis of cervical shortening, respectively. Overall, there were significantly more acute inflammatory lesions in patients in whom cervical shortening developed, as determined by ultrasonographic examination. However, there were significantly more decidual vascular lesions in women in whom cervical shortening did not develop. When we examined the distribution of the placental histologic lesions in the 64 cases of multiple gestations, the only significant finding was again a greater frequency of acute inflammatory lesions in patients in whom cervical shortening developed. There was no difference in the distribution of the placental histologic lesion categories among women treated with bed rest versus cervical cerclage because of the ultrasound diagnosis of cervical shortening. CONCLUSION: Acute inflammatory lesions of the placenta were more frequent in patients with second-trimester cervical shortening. These findings support that patients with cervical shortening in the second trimester are prone to acute placental inflammation.

Abortion, Spontaneous↗
PubMed1999

Collaborative care: a professional practice model.

Healthcare economics has caused dramatic changes in resource assessment, utilization, and reorganization in hospitals. To address the mismatch between demand and resources and to ensure quality at the bedside, staff members at a 354-bed acute care facility designed and implemented the Collaborative Care Model (CCM). The authors describe this theory-based, collaborative, multidisciplinary professional practice model.

Consultants↗
PubMed1997

Biophysical and biological properties of naturally occurring high molecular weight insulin-like growth factor II variants.

A soluble form of the insulin-like growth factor II/mannose 6-phosphate receptor (sIGF-II/MPR) is present in fetal bovine serum and carries mature 7.5-kDa insulin-like growth factor II (IGF-II) and at least 12 different high molecular weight (Mr) IGF-II isoforms (Valenzano, K. J., Remmler, J., and Lobel, P. (1995) J. Biol. Chem. 270, 16441-16448). In this study, we used gel filtration and anion exchange chromatographies to resolve the isoforms into eight fractions that were characterized with respect to their biochemical, biophysical, and biological properties. Each fraction contained one to three major protein species with apparent sizes ranging from 11 to 17 kDa by SDS-polyacrylamide gel electrophoresis. The 11-kDa species contains no post-translational modifications and consists of an extended IGF-II backbone terminating at Gly-87. The remaining high Mr IGF-II isoforms are also composed of an 87-amino acid IGF-II peptide backbone but contain increasing amounts of sialated, O-linked sugars. Plasmon resonance spectroscopy experiments revealed that all the high Mr isoforms and mature 7.5-kDa IGF-II bound to immobilized recombinant soluble human IGF-I receptor, recombinant human IGF-binding protein 1, and sIGF-II/MPR with similar kinetics. In addition, radiolabeled tracer experiments demonstrated that both mature and high Mr IGF-II isoforms have similar binding profiles in fetal bovine serum and have similar affinities for IGF-II-binding proteins secreted from human fibroblasts. Finally, the biological activity of high Mr IGF-II was shown to be similar to or slightly better than mature IGF-II in stimulating amino acid uptake in fibroblasts and in inducing myoblast differentiation.

Animals↗
PubMed1997

Clinical and genetic analysis of a family affected with dominant optic atrophy (OPA1)

OBJECTIVES: To refine the dominant optic atrophy locus, OPA1, on chromosome 3q and to characterize the phenotype of a 6-generation family pedigree affected with this disease. METHODS: Fifty-six family members had a complete eye examination. Clinical records of an additional 3 patients were reviewed. Goldmann perimetry and a 21-chip subtest of the Farnsworth-Munsell 100-Hue test were performed on selected patients. Affected patients, unaffected siblings, and potentially informative spouses were genotyped with short tandem repeat polymorphisms located on chromosome 3. The genotypic data were subjected to linkage analysis. RESULTS: Thirty-four family members were found to be clinically affected. Most experienced vision loss (20/40 or poorer) in the first decade of life. Most (9 of the 16 eyes) progressed to 20/800 or poorer visual acuity by age 60 years, while 2 patients maintained visual acuities of 20/40 at that age. Affected patients had a 2- to 10-fold increase in the error score of a 21-chip subtest of the Farnsworth-Munsell 100-Hue test compared with age-matched unaffected family members. The optic nerve examination revealed temporal pallor and excavation in all affected individuals. Linkage analysis revealed significant lod scores with 9 markers. The highest lod score, 10.1 (theta = 0) [corrected], was obtained with marker D3S2305. Analysis of recombinants narrowed the disease interval to approximately 3.8 centimorgans, flanked by D3S3669 (centromeric) and D3S1305 (telomeric). CONCLUSIONS: Most patients affected with dominant optic atrophy in this family progressed to legal blindness by middle age. Color vision testing is a sensitive method for detection of affected patients. The dominant optic atrophy locus, OPA1, has been refined by the identification of new flanking markers: D3S3669 (centromeric) and D3S1305 (telomeric).

Adolescent↗
PubMed1997

Growth of artificially fed infant rats: effect of supplementation with insulin-like growth factor I.

Insulin-like growth factor I (IGF-I), a potent mitogenic peptide, is present in considerable quantities in most mammalian milks, but its importance for the neonate is unknown. To test the hypothesis that milk-borne IGF-I is an important factor in the regulation of neonatal growth, as well as that of the gastrointestinal tract, rat pups were fed a rat milk substitute (RMS) devoid of growth factors via gastrostomy. These animals were compared with those given RMS supplemented with recombinant human IGF-I added at a concentration of 500 ng/ml. Animals given RMS + IGF-I gained mere weight than controls, although skeletal growth as represented by elongation of the tail was no different. Animals fed RMS + IGF-I had increased brain and liver wet weights as well as increased liver and small intestine protein contents. Serum IGF-I concentrations in the IGF-I-supplemented group were more than twofold above RMS controls and were similar to dam-fed rat pups. Semiquantification of serum IGF-binding proteins (IGFBP) in these animals documented that in IGF-I-supplemented pups the amount of 38- to 40-kDa molecular mass IGFBP species was also greater than in RMS controls. The rate of migration of enterocytes from crypts in duodenum and proximal jejunum was greater in IGF-I-supplemented animals than in rats fed RMS alone. These studies suggest that milk-borne IGF-I is important in modulation of somatic and gastrointestinal tract growth in the neonatal rat.

Animals↗
PubMed1997

Organ distribution and biliary excretion of intravenously injected insulin-like growth factor-I in suckling rats.

The organ distribution of intravenously injected 125I-IGF-I at a dose of 2-4 x 10(6) cpm or 5-10 ng/animal was studied in 10- to 12-day-old Sprague-Dawley rats at 5 and 30 min after injection. Results of the study suggest that, although the main portion of intravenous IGF-I remains in the circulation, significant amounts are also found in the carcass, liver and kidney. Blood radioactivity fell by 50% 30 min after injection, but concentrations in the carcass, liver, kidney and skin either remained stable or increased. Gel chromatography demonstrated that significant portions of radioactivity recovered from serum, liver and kidney coeluted in a position identical to the injected IGF-I. In addition, the extracted peptide bound competitively to a membrane IGF-I receptor preparation. Studies performed on liver and kidney from these animals 5 min after injection showed that on a per gram wet weight basis, these organs contained equivalent amounts of 125I-IGF-I. However, although by 30 min, 65% of the intact labelled IGF-I has been removed from the liver, the amount remaining in kidney tissue was equal to that noted 5 min after injection. Bile was collected over a 2-hour period and contained approximately 2% of the injected radioactivity and a significant portion (30%) of this radioactivity coeluted with native IGF-I. This material also bound competitively in a radioreceptor assay, suggesting 'intactness' of this peptide. From this study, we conclude that (a) IGF-I, when administered intravenously, remains for at least 30 min in a receptor-active form in blood and several organs; (b) IGF-I derived from the circulation is cleared from the liver more quickly than from the kidney of suckling rats, and (c) that IGF-I is transferred from blood to bile.

Analysis of Variance↗
PubMed1996

A novel MAP kinase phosphatase is localised in the branchial arch region and tail tip of Xenopus embryos and is inducible by retinoic acid.

Using a differential display strategy, we have isolated a cDNA corresponding to a mRNA which is induced by retinoic acid treatment of late gastrula Xenopus embryos, and much more strongly induced by retinoic acid and cycloheximide. The cDNA, designated X17C, encodes a novel mitogen-activated protein (MAP) kinase phosphatase of 378 amino acid residues which is only distantly related to other known MAP kinase phosphatases. In normal embryogenesis, the X17C mRNA is expressed after the midblastula transition and accumulates during gastrulation. In neurula and tailbud stage embryos the mRNA is localised in two domains, one in the anterior region of the embryo, and one at the tail tip. When expressed from synthetic mRNA injected into oocytes, the X17C protein is found within the cytosolic fraction and not in the nucleus. The X17C protein dephosphorylates and inactivates Xenopus MAP kinase in oocytes stimulated to undergo maturation by progesterone. We indicate the application of X17C as a tool for interfering with MAP kinase signaling in somatic cells of embryos, using FGF receptor-mediated MAP kinase activation in animal cap explants.

Amino Acid Sequence↗
PubMed1995

Intrapartum electronic fetal heart rate monitoring versus intermittent auscultation: a meta-analysis.

OBJECTIVE: To use a meta-analysis of all published randomized trials to determine whether the use of continuous electronic fetal heart rate monitoring (EFM) as the main method of intrapartum fetal surveillance is associated with improved pregnancy outcome compared to intermittent auscultation. DATA SOURCES: We used the MEDLINE data base and reference lists of articles to identify all published randomized trials of EFM versus intermittent auscultation. METHODS OF STUDY SELECTION: A total of nine randomized trials published in peer-review journals were identified. The selection criterion was the use of EFM or intermittent auscultation as the main intrapartum fetal surveillance technique. DATA EXTRACTION AND SYNTHESIS: A total of 18,561 patients were included in the nine published randomized trials, 9398 in the EFM group and 9163 in the auscultation group. Measures of pregnancy outcome included cesarean delivery, cesarean for suspected fetal distress, overall use of forceps or vacuum, use of forceps or vacuum for suspected fetal distress, overall perinatal mortality, and perinatal mortality due to fetal hypoxia (intrapartum or early neonatal death) attributable to the method of intrapartum monitoring. The meta-analysis showed that the patients monitored electronically had a significantly higher overall cesarean rate (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.17-2.01), higher cesarean rate for fetal distress (OR 2.55, 95% CI 1.81-3.53), overall increased use of forceps or vacuum (OR 1.23, 95% CI 1.02-1.49), increased use of forceps or vacuum for suspected fetal distress (OR 2.50, 95% CI 1.97-3.18), and decreased perinatal mortality due to fetal hypoxia (OR 0.41, 95% CI 0.17-0.98). CONCLUSION: Electronic fetal monitoring is associated with increased rates of surgical intervention and decreased perinatal mortality due to fetal hypoxia.

Cardiotocography↗
PubMed1995

Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine.

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocyte growth and contractility in vitro. This study was designed to investigate the effect of exogenous IGF-II on regional myocardial function at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anaesthetized pigs by affigel blue beads, embolizing microvessels of the left anterior descending coronary artery distribution. In the experimental group (n = 6), IGF-II (0.12 microgram.kg-1 in two animals and 0.6 microgram.kg-1 in four) was incorporated into the beads and delivered by them to the infarct area. Myocardial function was followed echocardiographically, and the excised heart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to an echocardiographic segmental wall motion score (mean +/- SEM), was similar between the two groups at baseline, but at 4 weeks post-infarction was significantly (P = 0.008) reduced in the control group (0.58 +/- 0.38 vs 3.42 +/- 0.84), in contrast to nearly baseline values in the experimental group (0.58 +/- 0.33 vs 1.17 +/- 0.42, P = 0.41). Cardiac performance in injured segments was significantly better after myocardial injury in the experimental group (P = 0.04). Tissue samples from both groups (4 weeks post-infarction), stained with haematoxylin and eosin demonstrated peri-infarct myocyte hypertrophy, corresponding to regions selectively stained by an antibody for CD56, which highlights growing cardiac myocytes. By image analysis semi-quantification, staining for CD56 was significantly (P = 0.04) higher in the peri-infarct region of the experimental group, as compared with controls (106.5 +/- 2.8 vs 92 +/- 4.4 gray level units). Microvessels stained for von-Willebrand factor were similar in number in both groups (P = 0.8), as were mesenchymal cells stained for vimentin (P = 0.7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area ameliorates regional cardiac function in the pig, perhaps by inducing peri-infarct myocyte growth.

Animals↗
PubMed1995

Presence of insulin-like growth factor I but absence of the binding proteins in the bile of rats.

Whereas insulin-like growth factor I (IGF-I) has been found in various body fluids from different species, the presence or absence of IGF and associated binding proteins (IGFBPs) in bile has not been clearly defined. Bile concentration of IGF-I was measured in this study and found to be highest in the neonate and lowest in adult rats [133 +/- 15.9, 79.4 +/- 10.5, 45.3 +/- 12.7 ng/ml (mean +/- SE) in 12-day-old, 33-day-old, and adult rats, respectively]. When bile delivery rates of IGF-I (i.e., the product of IGF-I concentration in bile and the biliary flow rate) were calculated, IGF-I delivery was highest in weanling rats (469 pg.h-1.g body wt-1). When expressed as amount of IGF-I in bile delivered per day, however, delivery rates rose from 0.2 micrograms/day in the suckling and remained constant at 1.6-1.7 micrograms/day in both weanling and adult animals. Bile samples exposed to a placental membrane IGF receptor preparation showed significant dose-dependent inhibition of binding of native IGF-I. Because no IGF binding proteins were identified by Western ligand blot or by Sephadex gel chromatography, the results suggest the presence of biologically significant quantities of bioactive IGF-I in bile. We speculate that IGF-I in bile may play an important role in the growth of the gastrointestinal tract, both in the suckling as well as later in life.

Animals↗
PubMed1995

Fate of insulin-like growth factors I and II administered orogastrically to suckling rats.

Milk-borne insulin-like growth factors I and II (IGF-I and -II) may be of importance in the differentiation of the gastrointestinal tract of the suckling. To test this hypothesis, 10- to 11-d-old suckling rats were given via an orogastric tube 125I-IGF-I (n = 6) or 125I-IGF-II (n = 6) in rat milk and killed 30 min later. The results of this study demonstrated that approximately 40% of the radioactivity administered was detected in the gastrointestinal tract for both 125I-IGF-I and 125I-IGF-II experiments. Gel chromatography of acid extracts of homogenates of gastrointestinal tissues and luminal contents demonstrated that a significant fraction of recovered radioactivity eluted in a position identical to "native" IGF. These findings were confirmed by subjecting similarly treated samples to high performance liquid chromatography. In addition, radioactive material recovered from M(r) 7,500 fractions bound specifically to crude membrane IGF-I and -II receptor preparations, further suggesting the preservation of biologic activity of the recovered peptides. Although skin homogenates contained large peptide fragments of 125I-IGF-I, no "intact" IGF was found in the blood or other tissues. These findings suggest that milk-borne IGFs are stable in the neonatal gastrointestinal tract and remain biologically active for as long as 30 min postingestion.

Administration, Oral↗
PubMed1994

Insulin like growth factor-1 and -2 and their role in the re-epithelialisation of wounds; interactions with insulin like growth factor binding protein type 1.

Insulin like growth factor (IGF) 1 and 2 which are present and actively synthesised in the wound fluid stimulate several cell types involved in the process of wound healing. To investigate the role of IGF-1 and 2 and in addition, the association between IGF and their carrier proteins, IGF binding proteins (IGFBP), we have used a newly established model for human wound healing in fresh biopsy material. Histological examination shows that IGF-1 stimulates efficient reepithelialisation of the wounds both alone and in the presence of recombinant IGFBP-1. In contrast, IGF-2 stimulates healing only when used in combination with IGFBP-1. These findings suggest that the two IGFs and their carrier proteins may function during different phases of wound healing and that both IGF-1 and 2 act as potent inducers of wound healing; this may have direct clinical implications.

Carrier Proteins↗
PubMed1993

Comparative studies of the granulopoietic enhancing effects of biosynthetic human insulin-like growth factors I and II.

The effect of biosynthetic human insulin-like growth factor I (IGF-I) and IGF-II on the in vitro growth of human marrow myeloid progenitors in the presence of recombinant human granulocyte colony stimulating factor (rhG-CSF), granulocyte-macrophage CSF (rhGM-CSF), or interleukin-3 (rhIL-3), was investigated. IGF-I and IGF-II similarly enhanced the growth of myeloid progenitors in cultures stimulated with any of the above hemopoietic regulators. Analysis of colony composition showed an increase in the numbers of granulocyte colonies, but no alteration in the numbers of macrophage or granulocyte/macrophage colonies. IGF-I induced an increase of 62 +/- 16%, 84 +/- 13%, and 107 +/- 18% in granulocyte colony numbers in the presence of G-CSF, GM-CSF, or IL-3, respectively. The values for IGF-II were 66 +/- 13%, 96 +/- 12%, and 91 +/- 12%. Similar enhancement of myeloid colony formation by both peptides was also detected in G-CSF and GM-CSF-stimulated cultures of marrow cells that had been depleted of accessory cells, while neither peptide exerted any effect in the presence of IL-3 in such cultures. The growth-promoting effects of IGF-I and IGF-II were completely abrogated by monoclonal antibodies directed against the IGF-I (Type I) membrane receptor. IGF-I and IGF-II thus appear to exert their effects on human marrow myeloid progenitors via a direct mechanism involving the Type I receptor.

Antibodies↗
PubMed1993

Biosynthesis of 10 kDa and 7.5 kDa insulin-like growth factor II in a human rhabdomyosarcoma cell line.

In the present study we have analysed the expression of insulin-like growth factor II (IGF-II) in the human rhabdomyosarcoma cell line IN157.IN157 cells express high levels of three IGF-II mRNAs of 6.0 kb, 4.8 kb and 4.2 kb. In contrast, normal skeletal muscle expresses a negligible amount of IGF-II mRNA. Two forms of IGF-II with molecular masses of 7.5 kDa and 10 kDa, corresponding to the mature IGF-II and IGF-II with a C-terminal extension of 21 amino acids (IGF-IIE21), were secreted into the culture medium at amounts of 17 ng/ml (2.3 nM) and 15 ng/ml (1.5 nM), respectively. IN157 cells also produce IGF binding protein-2. The bioactivity of recombinant IGF-IIE21 was compared with human IGF-I and IGF-II. IGF-I, IGF-II and IGF-IIE21 bound with high affinity to human IGF-I receptors (Kd approximately 1 nM), whereas the human IGF-II/mannose 6-phosphate (IGF-II/Man 6-P) receptor bound IGF-II and IGF-IIE21 with Kd values of 0.5 nM and 2 nM, respectively, and IGF-I with about 500 times lower affinity. IGF-II and IGF-IIE21 stimulated DNA synthesis via the IGF-I receptor, whereas the IGF-II/Man 6-P receptor mediated their rapid internalization and inactivation. During culture of IN157 cells about 50% of their IGF-I receptors were occupied by endogenous IGF-II. We conclude that IN157 cells express high levels of bioactive 10 kDa IGF-II and 7.5 kDa IGF-II that may stimulate the proliferation of rhabdomyosarcomas by interaction with IGF-I receptors on the cells.

Animals↗
PubMed1993

Presence of multiple forms of peptidase inhibitors in rat milk.

Peptides such as somatostatin (SS14), epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and insulin-like growth factors (IGF-I and IGF-II) are present in breast milk from various species, and their significance in the developing gastrointestinal tract has been suggested. Our recent studies have indicated that rat milk soluble fraction (RMSF) protects SS14 in the gastrointestinal lumen by inhibiting in vitro the luminal peptidolysis. In the present studies, we have shown that RMSF inhibited in vitro degradation by midjejunal luminal flushings of suckling rats of 125I-labeled somatostatin 14[Tyr11], EGF, TGF alpha, IGF-I and IGF-II, as well as trypsin activity in vitro against benzoyl-L-arginyl-p-nitroanilide. The inhibitory factors present in the RMSF were further fractionated by gel filtration on Sephadex G100, ion-exchange chromatography on DEAE-Sephadex, and fast protein liquid chromatography (FPLC). Gel filtration of Sephadex G100 separated RMSF into three peaks of proteins: G1, G2, and G3; peptidase inhibitor activities were present exclusively in G1. Ion-exchange chromatography on DEAE-Sephadex column resolved peptidase inhibitory activity (G1) into three different peaks, D1, D2, and D3, eluted at sodium chloride concentrations of 0.05 M, 0.1 M, and 0.2 M, respectively. Further purification of D2 by FPLC resulted in a fraction rich in peptidase inhibitory activity, which was essentially free of trypsin inhibitory activity. Results indicate the presence of at least three peptidase inhibitors in rat milk, which may play a role in the protection of milk-borne peptides in the gastrointestinal lumen.

Animals↗
PubMed1992

An evaluation of different enzymatic cleavage methods for recombinant fusion proteins, applied on des(1-3)insulin-like growth factor I.

Different enzymatic methods for cleavage of recombinant fusion proteins were compared. To find an efficient cleavage method, five different fusion proteins were produced. The fusion proteins differed only in the linker region between the fusion partner and the desired product, human des(1-3)insulin-like growth factor I. A cleavage study was performed with enterokinase, plasmin, thrombin, urokinase, and recombinant H64A subtilisin. Significant cleavage was obtained using thrombin, H64A subtilisin, and enterokinase. Thrombin cleavage was studied on a larger scale and des(1-3)IGF-I was recovered at a final yield of 3 mg/L growth medium. Thrombin and enterokinase were also studied as immobilized proteases and they cleaved the fusion proteins with retained activity. To further improve thrombin cleavage, a continuous reactor was constructed, consisting of a closed system with a thrombin column and an ion exchange column in series. Here, the fusion protein circulated while free des(1-3)IGF-I was bound to the ion exchange column after release from the fusion protein. In the reactor, thrombin was as efficient as the free enzyme but gave a diminished rate of product degradation.

Amino Acid Sequence↗