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J Klein

Publications and source records attributed to J Klein.

At least 91 records · Page 5Linked to original sources
PubMed2001

Two-gap state density in MgB(2): a true bulk property or a proximity effect?

We report on the temperature dependence of the quasiparticle density of states in the simple binary compound MgB(2) directly measured using scanning tunneling microscope (STM). To achieve high quality tunneling conditions, a small crystal of MgB(2) is used as a tip in the STM experiment. The "sample" is chosen to be a 2H- NbSe(2) single crystal presenting an atomically flat surface. At low temperature the tunneling conductance spectra show a gap at the Fermi energy followed by two well-pronounced conductance peaks on each side. They appear at voltages V(S) approximately +/-3.8 mV and V(L) approximately +/-7.8 mV. With rising temperature both peaks disappear at the T(C) of the bulk MgB(2), a behavior consistent with the model of two-gap superconductivity. The possibility of a particular proximity effect is also discussed.

Journal Article↗
PubMed2001

Fluidity of water confined to subnanometre films.

The fluidity of water in confined geometries is relevant to processes ranging from tribology to protein folding, and its molecular mobility in pores and slits has been extensively studied using a variety of approaches. Studies in which liquid flow is measured directly suggest that the viscosity of aqueous electrolytes confined to films of thickness greater than about 2-3 nm remains close to that in the bulk; this behaviour is similar to that of non-associative organic liquids confined to films thicker than about 7-8 molecular layers. Here we observe that the effective viscosity of water remains within a factor of three of its bulk value, even when it is confined to films in the thickness range 3.5 +/- 1 to 0.0 +/- 0.4 nm. This contrasts markedly with the behaviour of organic solvents, whose viscosity diverges when confined to films thinner than about 5-8 molecular layers. We attribute this to the fundamentally different mechanisms of solidification in the two cases. For non-associative liquids, confinement promotes solidification by suppressing translational freedom of the molecules; however, in the case of water, confinement seems primarily to suppress the formation of the highly directional hydrogen-bonded networks associated with freezing.

Journal Article↗
PubMed2001

Phase I trial of a twice-daily regimen of amifostine with ifosfamide, carboplatin, and etoposide chemotherapy in children with refractory carcinoma.

BACKGROUND: Amifostine protects normal tissues against chemotherapy and radiation-induced toxicity without loss of antitumor effects. Evidence suggests that multiple daily doses of amifostine may improve its cytoprotective effects. The purpose of this study was to assess the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of twice-daily doses of amifostine with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy for children with refractory malignancies and to determine the pharmacokinetic properties of amifostine, WR-1065, and the disulfide metabolites of amifostine. METHODS: Patients with refractory malignancies were treated with amifostine 15 minutes before and 2 hours after chemotherapy with ifosfamide (3 g/m(2) per dose on Days 1 and 2) and carboplatin (635 mg/m(2) on Day 3). Etoposide was administered on Days 1 and 2 (150 mg/m(2)). The starting dose of amifostine was 740 mg/m(2). Pharmacokinetic studies were performed after the first dose of amifostine. RESULTS: Twelve patients received 23 courses of ICE and amifostine. Dose-limiting toxicities for amifostine at 740 mg/m(2) were somnolence and anxiety. The other Grade 3 and 4 toxicities included asymptomatic, reversible hypocalcemia, vomiting, and reversible hypotension. At a dose of 600 mg/m(2), amifostine was well tolerated. Hypocalcemia, due to rapid, transient suppression of parathyroid hormone production, required close monitoring and aggressive intravenous calcium supplementation. Pharmacokinetic studies revealed high interpatient variability with rapid plasma clearance of amifostine and WR-1065. The median elimination half-life of amifostine (9.3 minutes) and WR-1065 (15 minutes) was much shorter than the disulfide metabolites (74.4 minutes). CONCLUSIONS: The recommended pediatric dose of amifostine for a twice-daily regimen is 600 mg/m(2) per dose (1200 mg/m(2)/day) with DLTs of anxiety and somnolence, lower than the previously recommended single dose of 1650 mg/m(2).

Adolescent↗
PubMed2001

Isoproterenol inhibits resistin gene expression through a G(S)-protein-coupled pathway in 3T3-L1 adipocytes.

Resistin was recently identified as a hormone secreted by adipocytes which leads to insulin resistance in vivo and in vitro and might therefore be an important link between obesity and diabetes. To clarify the regulation of resistin gene expression, 3T3-L1 adipocytes were treated with various agents known to modulate insulin sensitivity, and resistin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, isoproterenol treatment reduced the level of resistin mRNA to 20% of non-treated control cells. This effect was dose-dependent with significant inhibition occurring at concentrations as low as 10 nM isoproterenol. Moreover, pretreatment of adipocytes with the beta-adrenergic antagonist propranolol almost completely reversed the inhibitory effect of isoproterenol, whereas addition of the alpha-adrenergic antagonist phentolamine did not have any effect. Furthermore, the effect of isoproterenol could be mimicked by activation of G(S)-proteins and adenylyl cyclase. Thus, both cholera toxin and forskolin decreased resistin mRNA expression in a dose-dependent fashion by up to 90% of control levels. Taken together, these results suggest that resistin gene expression is regulated by a protein kinase A-dependent pathway in 3T3-L1 adipocytes.

3T3 Cells↗
PubMed2001

Functional classification of patients with idiopathic scoliosis assessed by the Quantec system: a discriminant functional analysis to determine patient curve magnitude.

STUDY DESIGN: A stepwise discriminant analysis was used to define a spinal deformity score based on three-dimensional measurements by the Quantec spinal image system (raster stereophotograph). OBJECTIVE: To provide functional classification of spinal deformity in patients with mild idiopathic scoliosis without using radiographs. SUMMARY OF BACKGROUND DATA: Most studies classify the degree of spinal deformity in terms of coronal plane radiograph without analyzing transverse rotation. To the authors' knowledge, no studies investigating classification of spinal deformity in idiopathic scoliosis using Quantec system measurements have been documented. METHODS: In this study, 129 patients with a single curve and 119 patients with a double curve were divided into three groups according to Cobb angle: Group 1 (less than 10 degrees ), Group 2 (10-20 degrees ), and Group 3 (greater than 20 degrees ). RESULTS: The patients were assigned to the group with the highest scores after application of a stepwise discriminant analysis. The accuracy of the classification system by functional scores for the patients with a single curve was 85% for Group 1, 63.5% for Group 2, and 71.7% for Group 3. The accuracy of classification by functional scores for the patients with a double curve was 87.1% for Group 2 and 76.1% for Group 3. CONCLUSION: The back surface image study is a method for providing a quantitative assessment of mild spinal deformity, allowing evaluation of patients by integrated three-dimensional parameters with no reference to radiographs.

Adolescent↗
PubMed2001

Self-similarity and pattern selection in the roughening of binary liquid films.

Films of spinodally decomposing binary liquid mixtures show transient wetting of both confining interfaces by one of the phases, and rupture, with characteristic wavelength lambda(c) and time tau(rupture), leading to flat droplets of the nonwetting phase encapsulated by the wetting phase. Over the entire range of film thicknesses d approximately 100-3500 nm, we find tau(rupture)~d(1.01+/-0.08), indicating film structures that scale self-similarly with d, and find also that lambda(c) approximately 60d(0.97+/-0.03), the large prefactor suggesting a rupture wavelength which minimizes the interfacial tension of the roughened film.

Journal Article↗
PubMed2001

A novel linear amphipathic beta-sheet cationic antimicrobial peptide with enhanced selectivity for bacterial lipids.

All known naturally occurring linear cationic peptides adopt an amphipathic alpha-helical conformation upon binding to lipids as an initial step in the induction of cell leakage. We designed an 18-residue peptide, (KIGAKI)3-NH2, that has no amphipathic character as an alpha-helix but can form a highly amphipathic beta-sheet. When bound to lipids, (KIGAKI)3-NH2 did indeed form a beta-sheet structure as evidenced by Fourier transform infrared and circular dichroism spectroscopy. The antimicrobial activity of this peptide was compared with that of (KIAGKIA)3-NH2, and it was better than that of GMASKAGAIAGKIAKVALKAL-NH2 (PGLa) and (KLAGLAK)3-NH2, all of which form amphipathic alpha-helices when bound to membranes. (KIGAKI)3-NH2 was much less effective at inducing leakage in lipid vesicles composed of mixtures of the acidic lipid, phosphatidylglycerol, and the neutral lipid, phosphatidylcholine, as compared with the other peptides. However, when phosphatidylethanolamine replaced phosphatidylcholine, the lytic potency of PGLa and the alpha-helical model peptides was reduced, whereas that of (KIGAKI)3-NH2 was improved. Fluorescence experiments using analogs containing a single tryptophan residue showed significant differences between (KIGAKI)3-NH2 and the alpha-helical peptides in their interactions with lipid vesicles. Because the data suggest enhanced selectivity between bacterial and mammalian lipids, linear amphipathic beta-sheet peptides such as (KIGAKI)3-NH2 warrant further investigation as potential antimicrobial agents.

Amino Acid Sequence↗
PubMed2001

Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group.

BACKGROUND: In patients with xeroderma pigmentosum the frequency of all forms of skin cancer is higher than in the general population, owing to a genetic defect in DNA repair. The bacterial DNA repair enzyme, T4 endonuclease V, delivered intracellularly, increases the rate of repair of sunlight-induced DNA damage in human cells. We tested the ability of this enzyme in a liposomal delivery vehicle applied topically (T4N5 liposome lotion) to lower the rate of new skin cancers in patients with xeroderma pigmentosum. METHODS: 30 patients were enrolled in this prospective, multicentre, double-blind study. Patients were randomly assigned T4N5 liposome lotion or a placebo liposome lotion, to be applied daily for 1 year. At 3-monthly visits, new actinic keratoses and basal-cell carcinomas were identified and removed. Analyses were by intention to treat. FINDINGS: 20 patients were assigned T4N5 liposome lotion and ten placebo lotion; one placebo-group patient withdrew before treatment and one withdrew with progressive disease at 9 months. The annualised rate of new actinic keratoses was 8.2 among the patients assigned T4N5 liposome lotion and 25.9 among those assigned placebo (difference 17.7 [95% CI 11.8-26.5]; p=0.004 by Poisson modelling). For basal-cell carcinoma, the annualised rates of new lesions were 3.8 in the treatment group and 5.4 in the placebo group (difference 1.6 [0.38-2.82]). No significant adverse effects were found among any of the patients. INTERPRETATION: DNA damage has an important role in the development of skin cancer and precancerous skin lesions. The topical application of DNA repair enzymes to sun-damaged skin of patients with xeroderma pigmentosum lowered the rate of development of two forms of these lesions during a year of treatment.

Administration, Topical↗
PubMed2001

Low infectious morbidity after intensive chemotherapy and autologous peripheral blood progenitor cell transplantation in the outpatient setting for women with breast cancer.

Autologous peripheral blood progenitor cell (PBPC) transplantation is increasingly employed in the outpatient setting, yet data on early complications following PBPC transplantation are scant. We evaluated 105 women with high-risk primary or metastatic breast cancer who were treated at a single institution during 1996--1997. The mean duration of neutropenia (absolute neutrophil count, <500 cells/mm(3)) was 7.5 days. Twenty-nine percent of women remained afebrile throughout the neutropenic period. Of the remaining 71%, most (64 of 75) had fever of unknown origin. Infections, mostly of mild severity, occurred in 34% of women; these infections included bacteremia due to gram-positive organisms, catheter site infection, cellulitis, pneumonia, oral candidiasis, herpes simplex virus infection, and vaginitis. Fifty percent of PBPC transplant recipients required hospital admission, usually because of persistent fever; the mean duration of hospitalization was 3 days. No deaths or serious adverse events occurred. Such reduced infectious morbidity may be a consequence of minimal oral and/or gastrointestinal mucositis associated with the conditioning regimen and broad-spectrum antimicrobial prophylaxis used for this patient population.

Adult↗
PubMed2001

Analysis of the prostate cancer-susceptibility locus HPC20 in 172 families affected by prostate cancer.

A recent study of hereditary prostate cancer has provided evidence for a prostate cancer-susceptibility locus, HPC20, which maps to 20q13. To assess further the potential contribution of this locus to prostate cancer susceptibility, we studied 172 unrelated families affected by prostate cancer, using 17 polymorphic markers across a 98.5-cM segment of chromosome 20 that contains the candidate region. Parametric analysis, allowing for heterogeneity, resulted in an overall HLOD score of 0.09 (P=.39) at D20S171, under the assumption of linkage in 6% of families. Mode-of-inheritance-free analysis of the entire data set resulted in a maximal Zlr score of 0.76 (LOD 0.13; P=.22) at the same location. The strongest evidence for linkage was seen in the subset of 16 black families (LOD 0.86; Zlr=1.99; P=.023) between markers D20S893 and D20S120, near the putative location of HPC20. Although some positive results were observed, our linkage study does not provide statistically significant support for the existence of a prostate cancer-susceptibility locus HPC20 at 20q13.

Aged↗
PubMed2001

Classification and phylogenetic relationships of African tilapiine fishes inferred from mitochondrial DNA sequences.

African cichlid fishes are composed of two major lineages, the haplochromines and the tilapiines. Whereas the phylogenetic relationships of the haplochromines have been studied extensively, primarily because of their spectacular adaptive radiations in the Great Lakes of East Africa, little is known about the relationships among the tilapiine species, despite the fact that they have become an important component of African, indeed world, aquaculture. To remedy this situation, molecular phylogenetic analysis of tilapiine fishes was undertaken. A segment of mitochondrial DNA encompassing the terminal part of the tRNA(Pro) gene and the most variable part of the control region was amplified by the polymerase chain reaction with DNA samples isolated from 42 tilapiine species, and the amplification products were subjected to heteroduplex analysis and sequencing. Phylogenetic trees based on 68 sequences revealed the existence of 11 sequence groups and 11 single-sequence branches. The groups, designated Ti1 through Ti11, were distinguished by specific combinations of diagnostic substitutions, formation of monophyletic clusters, and separation by genetic distances in excess of 0.04. Although the relationships among the groups could not be resolved, the sequences separated Oreochromis and Sarotherodon from Tilapia, as defined by Trewavas. The Oreochromis sequences clustered with the Sarotherodon sequences and thus supported the hypothesis that the mouthbrooding behavior of the tilapiine fishes evolved only once from the substrate-spawning behavior. Since on phylogenetic trees the O. alcalicus (sub)species were always separated from O. amphimelas by other Oreochromis species, it was concluded that the adaptation to life in water with a high salt concentration and high pH values evolved independently at least twice in the tilapiine fishes. The tilapiines diverged from the haplochromines more than 8 million years ago; most of the intragroup divergences among the tilapiines took place an estimated 1.1 to 6 million years ago.

Animals↗
PubMed2001

Independent origin of functional MHC class II genes in humans and New World monkeys.

In previous studies, major histocompatibility complex (MHC) class II DP, DQ, and DR families of genes were characterized in different primate species mostly on the basis of their second exon sequences. Resemblances were found between Old World monkey (OWM) and New World monkey (NWM) genes and were interpreted as being the result of transspecies evolution. Subsequent analysis of intron sequences of catarrhine and platyrrhine DRB genes, however, revealed that the amplifiable genes were not, in fact, orthologous. To test other DRB genes and other families of the class II region Southern blot hybridizations were carried out with tamarin genomic DNA using probes specific for the third exons of the tamarin DQA, DQB, DPB, and DRB genes. The hybridizing bands were extracted from the gel and the third exons of the genes were amplified by PCR, cloned, and sequenced. With two exceptions, all NWM class II genes were found to group separately from the human sequences. Only the sequences of one nonfunctional DQB locus appeared to be more closely related to human genes than to other platyrrhine DQB genes. In the DRB family one gene was found that grouped with sheep and strepsirhine DRB sequences and might represent an old gene lineage. To extend the sequences to the second exon, long PCRs were performed on tamarin genomic DNA. This approach was successful for five of the ten third exon sequences. From these data, we conclude that at least the functional MHC class II genes have expanded independently in catarrhines and platyrrhines.

Amino Acid Sequence↗
PubMed2001

New technique for emboli detection and discrimination based on nonlinear characteristics of gas bubbles.

Detection and characterization of emboli in the blood stream is of high clinical importance for making decisions after surgery. In this study, a new technique based on the nonlinear oscillations of gas bubbles was applied to gaseous emboli detection, characterization and sizing. To simulate gaseous emboli, an experimental system was developed to produce air bubbles of uniform diameters ranging from 19 microm up to 200 microm. The ultrasonic setup consisted of low-frequency transducers operating at 130 kHz and 250 kHz and using low acoustic pressures (30 kPa and 55 kPa). The experimental and theoretical results show that, depending on the transmitted frequency and the bubble sizes, higher harmonic components were produced in the frequency spectrum of the backscattered echo. Nonresonating bubbles scatter either linearly when their sizes are far away from the resonance size or nonlinearly at the second or third harmonic frequency when their sizes are getting close to the resonance size. Only resonant bubbles or bubbles very close to the resonance size are able to scatter at higher harmonic frequencies (fourth and fifth). This property is used to discriminate resonating bubbles from other bubble sizes. The appearance of harmonic component in the frequency spectrum seems to be an unambiguous tool to differentiate gaseous emboli from solid emboli that scatter linearly.

Acoustics↗
PubMed2001

Glucose plus choline improve passive avoidance behaviour and increase hippocampal acetylcholine release in mice.

The present study tests the effects of glucose and choline, the biosynthetic precursors of acetylcholine, on passive avoidance behaviour and hippocampal acetylcholine release measured by microdialysis in awake mice. Glucose (10 and 30mg/kg) or choline chloride (6-60mg/kg), given by i.p. injection immediately after training, dose-dependently enhanced retention in an inhibitory avoidance task. Combinations of low doses of glucose (10mg/kg) and choline chloride (20mg/kg) which alone were submaximally effective significantly increased retention latencies in a synergistic manner, an effect which was sensitive to atropine (0.5mg/kg). This beneficial effect vanished when higher doses of glucose or choline were combined. Basal hippocampal acetylcholine release in mice habituated to their environment was not affected by administration of glucose and choline. However, when hippocampal acetylcholine release was stimulated either by infusion of scopolamine (0.3microM) or by transferring the mice into a novel environment, the combination of glucose plus choline further increased acetylcholine release to a significant extent. We conclude that low doses of glucose and choline act synergistically to improve memory storage, an effect which is due to facilitation of acetylcholine release. This finding reinforces the view that central cholinergic functions are influenced under certain conditions by dietary intake of precursors.

Acetylcholine↗
PubMed2001

Where do adolescents get their condoms?

PURPOSE: To determine where adolescents obtain their condoms; the availability and accessibility of condoms; condom availability in relationship to different sexually transmitted disease (STD) rates; and the availability of safer sex information in places where condoms are sold. METHODS: We conducted a random digit-dialed telephone survey of 259 14-19-year-old adolescents in Monroe County, New York. Self-reported health services use, knowledge and use of confidential services, and where adolescents obtained or intended to obtain condoms were assessed. Research assistants visited all retail establishments in five areas of similar population size with gonorrhea rates from 887 to 12,427 per 100,000 adolescents to assess how available and accessible condoms were in each store. Perceived access and actual condom availability and accessibility were compared using Chi-square and Student's t-tests. RESULTS: Trained interviewers dialed 11,800 numbers in 1993, identifying 4449 (40%) households among 11,065 numbers reached successfully. Of these, 393 (8.8%) had eligible adolescents and 259 (66%) completed interviews. Most adolescents reported obtaining, or planning to obtain, condoms in stores rather than from free health care settings. Adolescents who have used condoms more often reported having obtained them without cost than having purchased them. Condoms were available at 101 (83%) of 122 stores identified. All drug stores and 75% of supermarkets sold condoms and displayed them openly. Most small grocery stores also sold condoms (92%), but were less likely to openly display them. No stores displayed or provided safer sex information. Areas with higher STD rates had more stores (p <.01), and more stores that sold condoms (p <.01). There was no difference in condom cost by area. CONCLUSIONS: Many adolescents obtain their condoms in retail stores. Condom accessibility varied by store type and area STD rate. Increasing condom visibility in private grocery stores may increase the accessibility of condoms to adolescents in areas with highest STD rates.

Adolescent↗
PubMed2001

Loss of renal function following bone marrow transplantation: an analysis of angiotensin converting enzyme D/I polymorphism and other clinical risk factors.

Chronic renal failure is an acknowledged late complication of BMT. It is related to the intensive chemotherapy, radiation and supporting medications. Polymorphism in the angiotensin converting enzyme (ACE) gene is associated with progression of nephropathy caused by diabetes and IgA nephropathy. We sought to determine whether ACE genotype and other clinical factors were associated with loss of renal function after BMT. We determined the genotype of 106 adult allogeneic BMT recipients, who received a similar preparative regimen, survived 1 year, and had assessment of renal function up to 3 years after BMT. We found that the distribution of genotypes was similar to the general population; 29%, 51%, and 20% for the DD, DI, and II genotypes, respectively. There was no statistical difference in patient survival between the three groups. Among all patients, the average creatinine clearance declined from 124 (95% CI 117, 131) to 89 (95% CI 78, 100) ml/min over the 36 months after BMT. Decline in renal function over time was less for patients with the DD compared to the II genotype (P = 0.040). Renal function in patients with the DD genotype was also better than those with the DI genotype, but this was of borderline statistical significance (P = 0.055). Renal shielding reduced decline in renal function compared to no shielding (P = 0.026). We conclude that the ACE genotype does not seem to influence survival, but the DD genotype may be protective against renal injury after BMT. Furthermore, we confirm that renal shielding during TBI reduces the renal injury after BMT.

Adolescent↗
PubMed2001

Socio-economic disparities in preterm birth: causal pathways and mechanisms.

Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.

Adult↗