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One of the most dramatic indicators of climate change is the reduction in the extent and thickness of Arctic sea ice that has resulted in an increase in wind‐driven sea ice mobility. During April and May 2017, satellite observations indicated that the ice arch that forms between Nares Strait and the Lincoln Sea collapsed. Typically, this collapse occurs in July or August allowing multiyear ice to exit the Arctic through Nares Strait. Here we show that the period of the collapse was associated with the presence of a polynya in northern Nares Strait, thin ice in the Lincoln Sea, and an unusual wind regime characterized by strong northerly flow. We propose that these anomalous conditions resulted in the arch's early collapse. If the ice in the region continues to thin, early collapses may occur more frequently with implications for the regional as well as the downstream climate and ecosystems. During the late winter of 2017, an unusual event occurred at the northern end of Nares Strait where it connects to the Arctic Ocean's Lincoln Sea. Each winter, an ice arch forms in this region and its presence restricts the flow of sea ice down Nares Strait and out into Baffin Bay. The arch usually is maintained until July or August. During 2017, it collapsed in early May. This is the earliest collapse on record. In this paper, we use a variety of satellite observations, as in situ data and model fields to argue that the early collapse during 2017 was the result of anomalously thin sea ice in the Lincoln Sea, a polynya in northern Nares Strait as well as enhanced northerly winds down Nares Strait. If the sea ice in the region continues to thin, such collapses may become more common with potential impacts on the regional as well as the downstream climate and ecosystems. The ice arch that forms each year at the northern end of Nares Strait collapsed 4 months earlier than usual in 2017The collapse is shown to be the result of anomalously thin ice in the Lincoln Sea as well as enhanced northerly flow down Nares StraitContinued thinning of Arctic sea ice may result in a trend toward earlier arch collapse that may have climate impacts on downstream regions

The objective of this study was to explore factors affecting decisions to adopt new technologies into dental practice using a colorimetric rinse test for detection of periodontal disease as a model. Focus groups with key informants in Canadian dentistry and dental hygiene were conducted. A deductive approach used Rogers’s diffusion of innovation theory as a framework for organizing codes and subcodes. Two members of the research team independently reviewed and analyzed the data using NVivo 10. The attributes of the technology itself emerged as primary influencers. Perceived relative advantages of the diagnostic mouth rinse over existing methods were potential time efficiency, low implementation cost, and utility of the tool. Low complexity, compatibility with existing routines/beliefs, and the potential for reinvention—the use of a technology for other than its intended purpose (i.e., patient education, monitoring of disease, screening tool in nondental settings)—were other important features enhancing adoption. An overarching concern was that any new technology benefit the patient. Contextual factors also play a role. Numerous communication channels, including opinion leaders, patients, marketing, continuing education courses, and strength of evidence, influenced clinicians, with peer interaction being a stronger influence than marketing. Similar themes arose from specialist, general dentist, and dental hygienist focus groups. Adopter characteristics also came into play: participants ranged in their self-reported innovativeness with many considering themselves “early adopters” of new technology. Findings of this study suggest that the innovation adoption process is not straightforward, but attributes of the innovation, contextual factors, and adopter characteristics play important roles in the process.Knowledge Transfer Statement:Various factors affect the adoption of new tools into clinical dental practice. These include attributes of the test or tool itself, the context of the settings in which the tool is introduced to practitioners, and the characteristics of the clinicians themselves. A qualitative study of dentists and dental hygienists investigated these factors. Situations in which dentists and hygienists interact with their peers and colleagues—through social networks, continuing education courses, conventions, or personal contact—were a major driver in the decision to adopt new technologies. However, even among “early adopters,” most were reluctant to use new tests or tools unless they perceived a benefit to their patients or practice.

Progress toward the realization of an external combustion dynamic micro heat engine is documented. First, the development of a thermal switch suitable to control heat transfer to and from the micro heat engine is described. Second, the integration of a thermal switch with an engine is detailed. The thermal switch is shown to be an effective means to control heat transfer into the engine from a continuous heat source and out of the engine to a continuous heat sink. The use of the thermal switch is shown to enable engine cycle speeds up to 100 Hz, engine efficiencies up to 0.095% and power output up to 1.0 mW. The internal irreversibility of the engine is measured to be 23%.

The interaction of IGF binding protein-2 (IGFBP-2) with IGF-I and -II has been investigated in solution using nuclear magnetic resonance (NMR) spectroscopy. Chemical shift perturbations in 15N- and 2H/15N-labelled IGF-I or -II upon binding to unlabelled thioredoxin-tagged bovine IGFBP-2 (Trx1–279IGFBP-2) have been monitored to identify residues involved directly in the binding interaction as well as any affected by conformational changes associated with the interaction. A key step in obtaining high-quality spectra of the complexes was the use of transverse relaxation optimised spectroscopy (TROSY) methods with partially deuterated ligands. Indeed, because the effects of conformational averaging and aggregation are eliminated in IGF-I and -II bound to IGFBP-2, the spectra of the complexes are actually superior to those of the free ligands. Comparison of our results with the crystal structure of the complex between IGF-I and an N-terminal fragment of IGFBP-5 allowed identification of those residues perturbed by the C-domain of IGFBP-2. Other perturbations, such as those of Gly19and Asp20of IGF-I (and the corresponding residues in IGF-II) – which are located in a reverse turn linking N-domain and C-domain interactive surfaces – are due to local conformational changes in the IGF-I and -II. Our results confirm that the C-domain of IGFBP-2 plays a key role in binding regions of IGF-I and -II that are also involved in binding to the type-1 IGF receptor and thereby blocking ligand binding to this receptor.

Background: Diabetic emergencies associated with ketoacidosis (DKA) and a hyperosmolar, hyper­glycaemic state (HHS) are both acute life‐threatening metabolic disturbances. Traditionally, DKA and HHS have been classified as distinct entities but there is evidence to suggest that patients can present with elements of both conditions. Aims: To examine the presentation profiles, mortality rates and prognostic factors associated with a fatal outcome for diabetic patients admitted with keto­acidosis and/or hyperosmolarity. Methods: A retrospective analysis of 312 admissions to an Australian tertiary referral hospital between 1986 and 1999. Results: Of the patients surveyed, DKA was the diagnosis for 171 presentations (55%), HHS was the diagnosis for 47 presentations (15%) and combined DKA and HHS (DKA−HHS) was diagnosed for 94 presentations (30%). Age at presentation for DKA patients (33 ± 1.2 years) was significantly less (P< 0.01) than DKA−HHS patients (44 ± 2.4 years). This, in turn, was significantly less (P< 0.01) than HHS patients (69 ± 1.7 years). There were 15 deaths for the 312 presentations, resulting in an overall ­mortality rate of 4.8%. Combined mortality rates according to age at presentation were: (i) 0/134 for patients aged <35 years, (ii) 1/85 (1.2%) for patients aged 35−55 years and (iii) 14/93 (15.0%) for patients aged >55 years. For the three categories of diabetic emergencies, mortality rates were: (i) 2/171 (1.2%) for DKA, (ii) 5/94 (5.3%) for DKA−HHS and (iii) 8/47 (17%) for HHS. For all presentations associated with ketoacidosis − regardless of the degree of hyperosmolarity − the mortality rate was 7/264 (2.7%), however for all presentations with hyperosmolarity − regardless of the degree of acidosis − the mortality rate was 13/141 (9.2%). When the associations between age, category of diabetic emergency, serum osmolarity and various other biochemical parameters with mortality were assessed by logistic regression analysis, age and the degree of hyperosmolarity were found to be the most powerful predictors of a fatal outcome. In particular, patients aged >65 years presenting with a serum osmolarity >375 mOsmol/L were at greatest risk. However, in a multivariate analy­sis only age emerged as a significant independent predictor of mortality (P< 0.01). Conclusions: The mixed state of ketoacidosis and hyperosmolarity was observed in 30% of presen­tations for diabetic hyperglycaemic emergencies. Although age and degree of hyperosmolarity both influenced mortality rates, only age was found to be an independent predictor of mortality. The mortality rate for diabetic emergencies associated with keto­acidosis remained low, in keeping with other studies. By contrast, the mortality rate for diabetic emergencies associated with a hyperosmolar state remained considerably higher. This higher mortality will most likely persist because deaths associated with a hyperosmolar state were in elderly patients with significant comorbidity. (Intern Med J 2002; 32: 379−385)

Chronic rejection is a leading cause of graft loss in thoracic transplant recipients. Studies on the pathogenesis of chronic rejection have suggested a contributory role for certain cytokines and growth factors. The activity of these mediators is subject to genetic variation if a polymorphism alters expression, or function, of the ligand or its receptor. Here we have asked if certain cytokine and growth factor gene polymorphisms correlate with chronic rejection in recipients of thoracic allografts. In a retrospective analysis of 179 recipients of thoracic organ transplants (128 heart; 36 heart-lung; and 15 lung), polymorphisms in 8 genes that influence the inflammatory process, namely IL1B, IL1R1, IL1RN, IL6, IL10, TNFA, TGFB1 and FCGRIIA, were examined. Genotypic data from recipients who had either died or been re-transplanted as a result of chronic rejection (n = 96) were then compared to those of recipients who had a functioning graft for more than 11 years (n = 83). In the heart graft recipients, only those polymorphisms that influenced expression of the IL1 receptor antagonist gene had a significant correlation with graft survival, with homozygosity for the IL1RN*1 allele being associated with rejection. The alternative, less frequent IL1RN alleles emerged as genomic predictors of long-term allograft survival. This association was especially strong when IL1 region haplotypes were considered, particularly when analysis was confined to heart transplant recipients who had had multiple acute rejection episodes (OR > 20). This case-control study indicates that gene polymorphisms which influence IL1 bioactivity also influence the progression of chronic rejection in heart grafts.

The underlying specificity of the interaction between insulin-like growth factor-II (IGF-II) and mammalian Type 2 insulin-like growth factor/cation-independent mannose 6 phosphate receptor (IGF2R) is not understood. We have mutated residues A54 and L55 of IGF-II in the second A domain helix to arginine (found in the corresponding positions of IGF-I) and measured IGF2R binding. There is a 4- and 3.3-fold difference in dissociation constants for A54R IGF-II and L55R IGF-II, respectively, and a 6.6-fold difference for A54R L55R IGF-II compared with IGF-II as measured by BIAcore analysis using purified rat IGF2R. This is also confirmed using cross-linking and soluble rat placental membrane receptor binding assays. Binding to the type 1 IGF receptor (IGF1R) and IGF binding protein-2 (IGFBP-2) is not altered. We can, therefore, conclude that residues at positions 54 and 55 in IGF-II are important for and equally contribute to IGF2R binding.

Some boronated molecules have shown surprising physiological action; however, the mode of action of these compounds is not understood. Our hypothesis is that the boron moiety is attracted to Lewis base sites on an enzyme and the resulting interaction causes an inhibition of the physiological pathway. To study this problem, quantum mechanical calculations of boron−nitrogen bond dissociation energies for 12 molecules have been calculated and compared with physiological activities including anti-hyperlipidemic and anti-neoplastic behavior. Results of linear correlation analysis between bond dissociation energy and physiological action have shown evidence that our hypothesis has merit. Possible locations of enzyme inhibition by boronated compounds are inferred. In addition, structural and energetic features of boronated molecules, including intramolecular electrostatic interactions and Lewis acidity, are discussed.

AbstractCytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart‐lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody‐negative heart‐lung transplant patients receiving organs from CMV antibody‐positive donors (CMV‐mismatched patients) that in 1986 we adopted the policy of not transplanting CMV‐positive organs into CMV‐negative heart‐lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV‐mismatched heart recipients and CMV antibody‐positive heart‐lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P =0.0006) and CMV disease (17 % vs 74%, P =0.0004) among CMV antibody‐positive heart‐lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart‐lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups.

1. Insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) together with a truncated form of IGF-1 were purified to homogeneity from bovine colostrum. 2. Two forms of IGF-1 were totally resolved from IGF-2 in the purification by h.p.l.c. involving cation-exchange and reverse-phase columns. 3. The complete amino acid sequences for all three forms of IGF were determined. The sequence of bovine IGF-1 was found to be identical with that of human IGF-1, and that of the variant lacked the N-terminal tripeptide Gly-Pro-Glu (-3N:IGF-1). Bovine IGF-2 was found to differ in three residues of the C-domain compared with human IGF-2, with serine, isoleucine and asparagine substituted for alanine, valine and serine respectively at positions 32, 35 and 36. 4. Protein synthesis in L6 rat myoblasts was stimulated and protein degradation inhibited in a co-ordinate response with all three IGFs. The relative potency in both processes was −3N:IGF-1 greater than IGF-1 greater than IGF-2. A similar order of potency was obtained for the stimulation of DNA synthesis by −3N:IGF-1 and IGF-1. The approximately 10-fold effect on biological activity of removing the N-terminal tripeptide is unexpected in view of current information on IGF-1 structure and function.

We have investigated which region(s) of bovine insulin-like growth factor binding protein-2 (bIGFBP-2) interact with insulin-like growth factors (IGFs) using C-terminally truncated forms of bIGFBP-2. Initially to aid in mutant design, we defined the disulfide bonding pattern of bIGFBP-2 C-terminal region using enzymatic digestion. The pattern is Cys186-Cys220, Cys231-Cys242, and Cys244-Cys265. In addition, cyanogen bromide cleavage of bIGFBP-2 revealed that the N- and C-terminal cysteine-rich domains were not linked by disulfide bonds. Taking the disulfide bonding pattern into consideration, C-terminal truncation mutants were designed and expressed in COS-1 mammalian cells. Following IGF binding assays, a region between residues 222 and 236 was identified as important in IGF binding. Specifically, mutants truncated by 14, 36, and 48 residues from the C terminus bound IGFs to the same extent as wild type (WT) bIGFBP-2. Removal of 63 residues resulted in a greatly reduced (up to 80-fold) ability to bind IGF compared with WT bIGFBP-2. Interestingly this mutant lacked the IGF-II binding preference of WT bIGFBP-2. Residues 236-270 also appeared to play a role in determining IGF binding specificity as their removal resulted in mutants with higher IGF-II binding affinity.

Given the internationally recognized definition of bronchiolitis obliterans syndrome (BOS) and longer follow up of heart-lung transplant recipients, it is possible to establish some of the major risk factors for development and progression of BOS. Between April 1984 and 31 December 1993, 157 patients underwent heart-lung transplantation; 126 survived at least six months after operation and so were at risk of developing BOS. The following early risk factors were assessed for development of BOS grade 1 (21-35% decline in FEV1), and progression from grade 1 to grade 2 (36-50% decline in FEV1): age, gender and underlying diagnosis of the recipient, evidence of acute rejection and cytomegalovirus (CMV) infection within 6 months of operation, peak FEV1achieved, age and gender of the donor, cold ischemic time of the graft, and matching of CMV serological status and HLA antigens of donor and recipient. The number of acute rejection episodes observed remained the single most important determinant of development of BOS grade 1 (relative risk 1.17 (1.06, 1.29),P=0.002) and progression to BOS grade 2 (relative risk 1.58 (1.02, 2.46), P=0.03). No other factors were significantly related to development or progression of BOS, although both evidence of CMV infection and disease and the number of HLA mismatches increased the risk. Bronchiolitis obliterans syndrome is a major problem for medium-to-long-term survivors of cardiothoracic transplantation. Acute rejection early after transplantation is a sensitive prognostic indicator of subsequent functional decline and requires prompt attention.

In this paper we present a quantum statistical analysis of a non-linear optical system with a mode coupled to its second harmonic, studied semiclassically in a previous paper. Quantum fluctuations are included via a Fokker-Planck equation for a generalized P representation. The spectrum of the light is shown to split into two peaks for critical values of the input fields. It is found that under certain conditions the non-classical effect of photon antibunching is possible in the steady state. In certain limits exact solutions for the generalized P representation are possible which allows an estimate of lifetimes in the metastable region to be calculated.

Porcine insulin-like growth factor-I (IGF-I) and IGF-II have been characterized to help define the roles of these peptides in the growth process. The amino acid sequence of porcine IGF-I was found to be identical to the human and bovine peptides. Porcine IGF-II was more similar to human IGF-II than to forms of this growth factor in other mammalian species, differing only in the replacement of asparagine for serine at residue 36. In a biological assay that measures the stimulation of protein synthesis in rat L6 myoblasts, porcine IGF-I was approximately ninefold more potent than porcine IGF-II or bovine IGF-II, while recombinant human IGF-I and IGF-II had half the potency of the respective natural peptides. Porcine and recombinant human IGF-I showed essentially equal competition for binding in a human IGF-I radioimmunoassay while between 0·6 and 1·5% cross-reactivity was observed with human, bovine or porcine IGF-II. A receptor assay for IGF-II demonstrated similar potencies for the three IGF-II peptides, while the cross-reactivity of recombinant human IGF-I was only 0·05%. Porcine IGF-I exhibited a higher cross-reactivity, presumably due to very slight contamination with IGF-II.Journal of Endocrinology(1989) 122,681–687

The far from equilibrium steady states of a simple nonlinear chemical system are analyzed. A standard macroscopic analysis shows that the nonlinearity introduces an instability which causes a transition analogous to a thermodynamic second-order phase transition. Fluctuations are introduced into this model through a stochastic master equation approach. The solution of this master equation in the steady state reveals that the system goes into a more ordered state above the transition point. An analogy is drawn with the nonequilibrium phase transition occurring in the laser at threshold.

Recombinant insulin-like growth factor-II (IGF-II) and two structural analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were produced to investigate the role of N-terminal residues in binding to IGF-binding proteins (IGFBPs) and hence the biological properties of the modified peptides. The growth factors were modelled on two previously characterized variants of IGF-I, des(1-3)IGF-I and [Arg3]-IGF-I, which both show substantially decreased binding to IGFBPs and were expressed as fusion proteins in Escherichia coli. The biological activities of the corresponding analogues of IGF-I and IGF-II were compared in rat L6 myoblasts and H35B hepatoma cells. In the L6-myoblast protein-synthesis assay, the IGF-II analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were slightly more potent than IGF-II but about 10-fold less potent than IGF-I and 100-fold less potent than the respective IGF-I analogues, des(1-3)IGF-I and [Arg3]IGF-I. In H35 hepatoma cells the anabolic response measured was the inhibition of protein breakdown, and the potency order was insulin >>> [Arg3]-IGF-I > des(1-3)IGF-I > [Arg6]-IGF-II > des(1-6)IGF-II > IGF-I > IGF-II. Binding of the IGFs and their analogues to the type 1 IGF receptor in L6 myoblasts and to the insulin receptor in H35 hepatoma cells did not fully explain the observed anabolic potency differences. Moreover, binding of all four analogues to the IGFBPs secreted by L6 myoblasts and H35B hepatoma cells was greatly decreased compared with the parent IGF. We conclude that the observed anabolic response to each IGF was determined by their relative binding to the competing cell receptor and IGFBP binding sites present.

A comprehensive study of correlations in linear and nonlinear chemical reactions is presented using coupled chemical and diffusion master equations. As a consequence of including correlations in linear reactions the approach to the steady-state Poisson distribution from an initial non-Poissonian distribution is given by a power law rather than the exponential predicted by neglecting correlations. In nonlinear reactions we show that a steadystate Poisson distribution is achieved in small volumes, whereas in large volumes a non-Poissonian distribution is built up via the correlation. The spatial correlation function is calculated for two examples, one which exhibits an instability, the other which exhibits a second-order phase transition, and correlation length and correlation time are calculated and shown to become infinite as the critical point is approached. The critical exponents are found to be classical.

The quantum dynamics of a coherently driven nonlinear oscillator are studied by solving the Schrödinger equation numerically. The results are used to examine the effect of increasingly strong driving on the mean number, squeezing, the second-order correlation function and the general behaviour of the Q function. For comparison, the corresponding quantities for the classical Liouville dynamics are also computed. It is found that while the dynamics do maintain some quantum aspects as the strength of the driving is increased, the spectacular quantum features of the undriven nonlinear oscillator are in fact progressively lost.

In this, the first of two papers on the subject, we present an analysis of a non-linear optical system with a mode coupled to its second harmonic, exhibiting a rich variety of non-equilibrium steady-state transitions. Here we use a semiclassical analysis to examine the steady states and their stability, and thus predict the existence of various instabilities. We find that this system exhibits both first- and second-order phase transition-like behaviour, as well as having a hard mode transition. The application of this system as a switching device is also considered.

This study describes the biosynthesis of a human epidermal growth factor fusion protein, Long EGF, that has a 53 amino acid extension peptide derived from the 46 N-terminal amino acids of porcine GH. The approach allowed the production of Long EGF at high efficiency due to the expression of the fusion protein in high yield as inclusion bodies in Escherichia coli. Long EGF had a slightly lower potency compared with native EGF in a range of assays, including binding to anti-EGF antibodies or the EGF receptor, stimulation of Balb/3T3 fibroblast and rat intestinal epithelial cell growth, as well as counteracting the inhibition of mink lung epithelial cell proliferation by transforming growth factor-β1.Degradation of Long EGF and native EGF was compared in gastrointestinal flushings as an indication of whether the EGF domain of the fusion protein would be protected from proteolytic cleavage and be useful as a trophic agent in the gut. Incubation with flushings from the stomach or jejunum of rats caused rapid cleavage of the extension peptide, releasing native EGF. A C-terminal truncation of Arg53in the stomach and a removal of the C-terminal pentapeptide (49Trp-Trp-Glu-Leu-Arg53) in the small bowel was demonstrated by N-terminal sequencing and mass spectrometry. The degradation patterns were reflected by changes in migration of products on SDS-PAGE and in subsequent binding activities to the EGF receptor and anti-EGF antibodies. The data show that a human EGF fusion protein can be produced efficiently in a bacterial expression system and that it retains biological activity in vitro. Although the extension peptide was rapidly cleaved from Long EGF in both stomach and small bowel producing similar biological activity to native EGF, it could not prevent subsequent degradation of the EGF domain. Other strategies are being investigated to develop an effective oral form of EGF that resists digestion by proteases in the gastrointestinal tract.

Domino cardiac transplantation affords flexible and optimal organ utilization, provides hearts unaffected by brain death, allows prospective tissue matching, and subsequent transplantation with short allograft ischemic times. A retrospective review of our experience with domino cardiac transplantation has been made.

An efficient expression system in Escherichia colifor several biologically active insulin-like growth factor-I (IGF-I) fusion peptide analogues is described. These novel IGF-I fusion protein analogues have properties that make them very useful reagents in the investigation of IGF-I action. The analogues comprise an IGF-I sequence and the first 11 amino acids of methionyl porcine growth hormone (pGH) and include [Met1]-pGH(1–11)-Val-Asn-IGF-I, which contains the authentic IGF-I sequence, and two analogues, [Met1]-pGH(1–11)-Val-Asn-[Gly3]-IGF-I and [Met1]-pGH(1–11)-Val-Asn-[Arg3]-IGF-I, where Glu3 in the human IGF-I sequence has been replaced by Gly or Arg respectively. The three peptides are referred to as Long IGF-I, Long [Gly3]-IGF-I or Long [Arg3]-IGF-I depending on the IGF-I sequence present. Production of the purified fusion peptides was aided by folding the reduced and denatured fusion peptide sequence under conditions that gave very high yields of biologically active product. Introduction of a hydrophobic N-terminal extension peptide appears to facilitate the correct folding of the IGF-I analogues compared with that obtained previously when folding normal-length IGFs. The biological activities of the IGF-I fusion peptides were compared with authentic IGF-I and the truncated analogue, des(1–3)IGF-I. In L6 rat myoblasts, all the analogues were more potent than authentic IGF-I in their abilities to stimulate protein and DNA synthesis and inhibit protein breakdown. In H35 hepatoma cells, where the IGFs act through the insulin receptor, the Long IGF-I analogues maintained a similar potency relative to IGF-I as was observed in the L6 myoblasts. The order of biological potency in cell lines secreting IGF-binding proteins (IGFBPs) into the medium was Long [Arg3]IGF-I-des(1–3)IGF-I>Long [Gly3]-IGF-I>Long IGF-I>IGF-I. In chicken embryo fibroblasts, a cell line that does not secrete detectable IGFBPs into the medium, Long [Arg3]-IGF-I, was less potent than IGF-I. Investigation of receptor and IGFBP association by these analogues reinforced our previous findings that N-terminal analogues of IGF-I show increased biological potency due to changes in the degree of their IGFBP interactions.

ABSTRACTOne hundred twenty-six urease-negative gastric biopsy specimens were evaluated for the presence of Helicobactergenus-specific 16S ribosomal DNA (rDNA) and H. pylori-specific glmMDNA sequences by PCR. The species specificity of the glmMPCR assay was demonstrated, as H. pyloriwas the only Helicobacterspecies that yielded the expected glmMamplicon. Most urease-negative specimens (118 of 126 specimens) lacked HelicobacterDNA. However, 8 of 126 urease-negative specimens contained Helicobacter16S rDNA. In order to identify the Helicobacterspecies present in urease-negative gastric biopsy specimens, 16S rDNA amplicons were cloned and sequenced. Sequence comparisons were performed by analyses of the sequences in public sequence databases. Two samples contained 16S rDNA that was identified as H. cinaediwith 100% identity and that spanned approximately 400 bp (398 and 398 bp, respectively). In contrast, multiple differences (97% identity; 390 of 398 bp) were observed with H. pylori16S rDNA in this region. This finding was verified by sequencing an overlapping 537-bp fragment within the 5' portion of 16S rDNA. Although the clinical findings were consistent with H. pyloriinfection (e.g., duodenal ulcer disease), rapid urease testing and DNA sequence analyses suggested the presence of H. cinaediorganisms and the absence of H. pyloriin two human antral biopsy specimens. This study represents the first report of an enteric urease-negative helicobacter in the human stomach. Although these organisms were previously associated with extragastric infections, the roles of these organisms in the pathogenesis of chronic gastritis or peptic ulcer disease remain unclear.

Levan production by strains of Erwinia herbicola is common, and this property has some taxonomic significance for species differentiation within the "herbicola" group. The extracellular polysaccharide elaborated by strain 403 was characterized by nuclear magnetic resonance spectroscopy and methylation analysis. Results showed it to be a typical bacterial levan.