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Biomedical subjects

J Beck

Publications and source records attributed to J Beck.

At least 37 records · Page 2Linked to original sources
PubMed1996

Chromosomal assignment of 2900 tri- and tetranucleotide repeat markers using NIGMS somatic cell hybrid panel 2.

Two thousand nine hundred and thirty-one tri- and tetranucleotide short tandem repeat polymorphisms (STRPs) developed by the Cooperative Human Linkage Center were assigned to chromosomes using the NIGMS somatic cell hybrid mapping panel 2 and an efficient pooling strategy. Approximately 82% of all STRPs tested were assigned by this method, with 96.7% accuracy. Many of the single chromosome cell lines contained portions of additional chromosomes, confirming previous reports. The cell lines for chromosomes 6, 14, and 20 contained extensive portions of other chromosomes. Five previously unreported chromosomal contaminants were identified and are reported. A new pooling strategy was designed to minimize ambiguous assignments.

Animals↗
PubMed1996

Rhodamine 123-efflux from hematopoietic subpopulations and leukaemic blast populations marked by PerCP-conjugated monoclonal antibodies.

A representative functional assay for determination of drug transporting proteins (e.g. P-glycoprotein) in leukaemic blasts could help to evaluate effects of chemotherapy combined with chemosensitizers. Since subpopulations of normal peripheral blood or bone marrow cells show distinct P-glycoprotein levels, the presence of these cells in leukaemic samples causes a major problem in determination of rhodamine 123 efflux in these types of malignant cells. Additional staining of blasts with specific monoclonal antibodies (marked with FITC (fluorescein) or PE (phycoerythrin) might ensure a selective analysis of a particular subpopulation by flow cytometry, but the emission spectrum of rhodamine 123 interferes with FITC and PE signals and vice versa. This can be avoided by using monoclonal antibodies (mab) conjugated with the newly developed dye PerCP (peridnine chlorophyll protein; Becton/Dickinson), devoid of interfering with the rhodamine 123 fluorescence emission spectrum. Therefore we established an assay for the determination of rhodamine 123 efflux from peripheral blood CD4+, CD8+ or CD56+ subpopulations by detection with PerCP-conjugated mab, followed by electronic gating. The problems of varying signal intensities or the need to recompensate during measurement which normally occurred using FITC- or PE-conjugated mab did not emerge by the use of PerCP-marked mab. Moreover we could correlate MDR1 gene expression and modulation of rhodamine 123 efflux from the leukaemic blasts by proven P-gp MDR chemosensitizing agents such as SDZ PSC 833, dexverapamil and dexniguldipine. This method gives highly reproducible results of P-gp function in patient samples which should be compared with patient outcome after combined chemotherapy including chemosensitizers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

An Arg-Lys insertion at the hemagglutinin cleavage site of an H5N2 avian influenza isolate.

Recent isolations of H5N2 subtype avian influenza (AI) viruses in North America have raised questions concerning their origin, transmission to commercial poultry, and potential for virulence. One ratite-origin isolate of low pathogenicity, A/emu/TX/39924/93 (H5N2), was subjected to a procedure that rapidly selects and/or amplifies highly pathogenic (HP) strains. The resulting highly virulent derivative had an altered hemagglutinin (HA) gene containing an additional six nucleotides at position 970-975 in the HA1 coding region. This resulted in an arg-lys insertion near the proteolytic cleavage site of the HA protein. The remainder of the HA sequence differed by an additional seven amino acids from the parent. The HA precursor of the derivative, but not the parent, was readily cleaved during replication in cell culture without addition of trypsin. In experimentally infected chickens, the derivative produced lesions typical of highly pathogenic avian influenza. A reverse transcriptase-polymerase chain reaction (RT-PCR) primer set was designed to amplify exclusively from molecules with the inserted six nucleotides. The set yielded product only from the selected derivative samples and not the parent. Thus, the levels of the HP variants in the parent stock were undetectable, or the insertion occurred rapidly during the selection process.

Animals↗
PubMed1996

Sexual behavior in male rats after nitric oxide synthesis inhibition.

The influence of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) on the copulatory behavior of sexually experienced male Wistar rats was investigated. L-NAME was injected i.p. 10 min before the onset of a session using a dose of 30 mg/kg (L-NAME 30 group), or 60 mg/kg (L-NAME 60 group). The copulatory sessions were terminated after the third ejaculation in the control group or after 1500 s in the L-NAME 30 and L-NAME 60 groups. L-NAME administration reduced the number of rats that achieved ejaculation by 43% and 86% in the L-NAME 30 and 60 groups, respectively. In both experimental groups only a few intromissions and an increased number of mountings were observed. An increase in the number of ultrasonic vocalizations in the 50 kHz band, a dose-dependent effect, was observed. The level of sexual motivation evaluated by mount latency was not influenced by inhibition of NO synthesis.

Animals↗
PubMed1996

Perceived texture segregation in chromatic element-arrangement patterns: high intensity interference.

An element-arrangement pattern is composed of two types of elements that differ in the ways in which they are arranged in different regions of the pattern. We report experiments on the perceived segregation of chromatic element-arrangement patterns composed of equal-size red and blue squares as the luminances of the surround, the interspaces and the background (surround plus interspaces) are varied. Perceived segregation was markedly reduced by increasing the luminance of the interspaces. Perceived segregation was approximately constant for constant ratios of interspace luminance to square luminance and increased with the contrast ratio of the squares. Unlike achromatic element-arrangement patterns composed of squares differing in lightness [Beck et al (1991). Vision Research, 32, 719-743] perceived segregation did not decrease when the luminance of the interspaces was below that of the squares. Similar results were obtained for red and yellow, red and green, green and yellow, green and blue, and blue and yellow squares. Perceived segregation based on edge alignment was not interfered with by high intensity interspaces. Stereoscopic cues that caused the squares composing the element-arrangement pattern to be seen in front of the interspaces did not greatly improve perceived segregation. One explanation of the results is in terms of inhibitory interactions among achromatic and chromatic cortical cells tuned to spatial frequency and orientation. Alternately, the results may be explained in terms of how the luminance of the interspaces affects the grouping of the squares for encoding surface representations. Neither explanation accounts fully for the data and both mechanisms may be involved.

Color Perception↗
PubMed1996

Is delayed surgery really better for congenital diaphragmatic hernia?: a prospective randomized clinical trial.

Delayed surgery has become widely accepted in the management of congenital diaphragmatic hernia after comparing outcomes only with historical retrospective controls. It was the aim of this study to compare early and delayed hernia repair in a randomized prospective clinical trial. Fifty-four infants were randomized to receive either early repair (within 4 hours of admission) or delayed repair (more than 24 hours after birth). The survival rate was higher for the delayed group (57% v 46%), but the difference was not significant (difference: -11; 95% confidence limits: -37.5, 15.5). There were no significant differences between the two groups with respect to length of hospital stay, ventilator dependency, or survival time. Recorded preoperative risk factors were similar for the two groups. Eight infants in the delayed repair group died without having undergone surgery. The optimum time for surgery still needs clarification.

Blood Gas Analysis↗
PubMed1996

Superantigen-mediated cellular cytotoxicity is dependent on antigen expression, but independent of the P-glycoprotein multidrug resistance phenotype.

Superantigen-activated T cells can be targeted by monoclonal antibodies (mAb) to lyse MHC class II negative tumour cells. In this study we determined the susceptibility of the T-lymphoblastoid leukaemic cell line CCRF-CEM and its multidrug resistant sublines CCRF VCR100, CCRF VCR1000 and CCRF ADR5000 to lysis by monoclonal antibody-targeted and superantigen-activated T cells (superantigen-dependent cellular cytotoxicity, SDCC). A recombinant fusion protein of protein A and the superantigen Staphylococcus enterotoxin A (SEA) was used together with the mAbs anti-CD7, anti-CD38, anti-CD45RA and 4E3 (anti-P-glycoprotein) to correlate susceptibility to SDCC with expression of the MDR1-gene product. Our results demonstrated SDCC to be independent of MDR1-gene expression. This was further confirmed by blocking the function of Pgp in the leukaemic cell lines with a cyclosporine A derivative, which had no influence on SDCC. As expected, expression of the respective cell surface antigens on target cells had a strong impact on SDCC, although other factors seem to influence efficiency of SDCC as well.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Influence of bipolar esophageal electrode positioning on measurements of human crural diaphragm electromyogram.

We aimed to describe how the human diaphragm electromyogram (EMGdi) is filtered at different positions within the esophageal hiatus, i.e., in the close proximity of the diaphragm, when obtained with an array of bipolar electrode pairs mounted on an esophageal catheter. We defined the electrically active crural diaphragm musculature that covers the esophagus as the electrically active region of the diaphragm (EARdi) and its center as the EARdi center. EMGdi signals were obtained via a multiple-array esophageal catheter consisting of seven sequential electrode pairs with three different electrode configurations. Subjects (n = 5) performed voluntary contractions of the diaphragm at functional residual capacity. Visual inspection of the signals revealed reversal of signal polarity on either side of the EARdi center. Extreme correlation values (r values close to -1 at 0-ms time offset) were observed for the correlation of signals on either side of the EARdi center. The root mean square (RMS) was reduced at the EARdi center; moving peripherally from the EARdi center (caudally and cephalad), the RMS increased to a peak (range of 2.1-4.1 dB for the different electrode configurations) and then decreased for the most peripheral electrode pairs. From a position where the RMS values peaked, center frequency values increased at the EARdi center (range of 26-29 Hz for the different electrode configurations). Computer simulation yielded similar data to the experimental results. We conclude that electrode positioning within the EARdi severely influences center frequency and RMS values and that the center of the EARdi can be identified via cross-correlation analysis.

Diaphragm↗
PubMed1996

Reversible encephalopathy with cerebral vasospasm in a Guillain-Barré syndrome patient treated with intravenous immunoglobulin.

We report a patient with a reversible multifocal encephalopathy that developed 3 days after completion of treatment with intravenous immunoglobulin for Guillain-Barré syndrome. Magnetic resonance imaging showed reversible bioccipital white matter changes, and transcranial Doppler demonstrated transiently increased flow rates in all major cerebral arteries. We conclude that intravenous immunoglobulin therapy caused cerebral arterial vasospasm and a reversible encephalopathy.

Adult↗
PubMed1996

Periodontal infection as a possible risk factor for preterm low birth weight.

Peridontal diseases are gram-negative anaerobic infections that can occur in women of childbearing age (18 to 34 years). In the present investigation we sought to determine whether the prevalence of maternal periodontal infection could be associated with preterm low birth weight (PLBW), controlling for known risk factors and potential covariates. A case-control study of 124 pregnant or postpartum mothers was performed. PLBW cases were defined as a mother with a birth of less than 2,500 g and one or more of the following: gestational age < 37 weeks, preterm labor (PTL), or premature rupture of membranes (PROM). Controls were normal birth weight infants (NBW). Assessments included a broad range of known obstetric risk factors, such as tobacco use, drug use, alcohol consumption, level of prenatal care, parity, genitourinary infections, and nutrition. Each subject received a periodontal examination to determine clinical attachment level. PLBW cases and primiparous PLBW cases (n = 93) had significantly worse periodontal disease than the respective NBW controls. Multivariate logistic regression models, controlling for other risk factors and covariates, demonstrated that periodontal disease is a statistically significant risk factor for PLBW with adjusted odds ratios of 7.9 and 7.5 for all PLBW cases and primiparous PLBW cases, respectively. These data indicate that periodontal diseases represent a previously unrecognized and clinically significant risk factor for preterm low birth weight as a consequence of either PTL or preterm PROM.

Adolescent↗
PubMed1996

Periodontal disease and cardiovascular disease.

It is our central hypothesis that periodontal diseases, which are chronic Gram-negative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL-1 beta, PGE2, and TNF-alpha) which serve to initiate and exacerbate atherogenesis and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease.

Alveolar Bone Loss↗
PubMed1996

Control of islet intercellular adhesion molecule-1 expression by interferon-alpha and hypoxia.

The ability of interferon-alpha (IFN-alpha) to induce the adhesion molecules that characterize the islets of patients with type I diabetes has been investigated. We have found that all tested recombinant IFN-as will induce major histocompatibility complex (MHC) class I on arterial endothelial cells. Some but not all IFN-as will induce intercellular adhesion molecule-1 (ICAM-1). However, there is only a transient and modest increase in VCAM on arterial endothelial cells. IFN-alpha has very little effect on endothelial MHC class II expression but will induce these proteins on monocytes. Thus, there is a close concordance between the biological actions of IFN-alpha and the appearance of those adhesion molecules induced in the islets of patients with type I diabetes. IFN-alpha is also produced in normal human islets during short-term cultures, probably as a result of the ischemia present at the center of the islet. This induction of IFN-alpha by hypoxia may explain the previously reported spontaneous induction of ICAM-1 in human islets and may also be a contributing factor to the failure of islet grafts.

Arteries↗
PubMed1996

Expression of PKC isozyme and MDR-associated genes in primary and relapsed state AML.

For investigation of relative differences in mRNA expression levels and of correlations in the expression of genes possibly involved in multidrug resistance (MDR) of acute myelogenous leukemias (AML), a complementary DNA polymerase chain reaction (cDNA-PCR) analysis was established for the genes encoding MDR1/P-glycoprotein, the multidrug resistance-associated protein (MRP), topoisomerase II alpha, topoisomerase II beta, topoisomerase I, glutathione S-transferase pi, protein kinase C (PKC) isozymes alpha, beta 1, beta 2, epsilon, eta, theta and cyclin A. In a first descriptive study comprising samples of childhood or adult AML we calculated the mean values from primary (n=14) or relapsed (n=23) states of the diseases, respectively. We found in the latter significant increases of MDR1, MRP, gst pi, and PKC theta gene expression. MDR1 and MRP gene expression levels were generally correlated (rs= +0.4128, P<0.02, n=37), as well as topoisomerase II alpha and cyclin A gene expression levels (rs= +0.8727, P<0.0001, n=35). Within the group of relapsed state AML a significant negative correlation between the gene expression levels of MDR1 and topoisomerase II alpha (rs= -0.5500, P<0.01, n=22) was observed. Remarkably, highly significant positive correlations were found for MDR1/PKC eta (rs= +0.5560, P<0.001, n=32), MRP/PKC theta (rs= +0.6573, P<0.0001, n=34) and MRP/PKC eta (rs= +0.5241, P<0.005, n=32).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

MDR1, MRP, topoisomerase IIalpha/beta, and cyclin A gene expression in acute and chronic leukemias.

Gene expression was analyzed by cDNA-PCR at the mRNA level in bone marrow samples (>80% blasts) from ALL (28 primary, 22 first relapses, 10 recurrent relapses), from AML (14 primary, 23 relapses), In peripheral blood lymphocytes from CLL (five untreated, 10 treated), in one CML in blast crisis in the course of the disease (four samples), and in bone marrow samples from healthy donors (12 specimens). We found low mean MDR1 expression in primary ALL, first relapses of ALL, and primary AML. Significantly higher mean relative MDR1 expression levels were seen in recurrent relapses of ALL, and in the group of relapsed state AML. MDR1 expression measured intermediate in bone marrow samples from healthy donors. The CLL lymphocytes showed generally relatively high MDR1 expression levels. MRP gene expression measured very similar in primary ALL, first relapses of ALL, primary AML, and normal bone marrow. Significantly increased MRP mRNA levels were observed in the groups of recurrent ALL and relapsed state AML. CLL lymphocytes also showed high MRP expression levels. A combined increase of MDRI (about 20-fold) and MRP (about four-fold) was monitored in samples obtained from the CML in blast crisis after chemotherapy. While no significant differences of the mean topoisomerase IIbeta mRNA levels were found throughout, a significantly decreased topoisomerase IIalpha gene expression was measured in first and recurrent relapses of ALL. In CLL lymphocytes either the expression of the topoisomerase IIalpha gene was not detectable by cDNA-PCR, or it measured very low. Topoisomerase IIalpha gene expression was correlated to cyclin A gene expression in the samples of acute leukemias, Indicating the link of topoisomerase IIalpha expression to the proliferative activity of these leukemic blast cells. Our results point to a potentially multifactorial emergence of multidrug resistance in particular states and types of leukemias.

ATP-Binding Cassette Transporters↗
PubMed1996

Colostomy complications in infants and children.

This study analyses the morbidity and mortality of colostomy formation and closure over a 17-year period during which 138 consecutive infants and children had a colostomy formed as the initial management of Hirschsprung's disease or anorectal malformation. Complications after colostomy formation were encountered in 38 (27.5%) patients and included colostomy prolapse, stenosis, retraction, dysfunction, skin excoriation and parastomal hernia. The complication rate with transverse colostomies was higher than with other types. Colostomy closure was associated with complications in nine patients (6.5%), the most serious of which was adhesive small bowel obstruction (5). The mortality was less than 1%, but significant morbidity still exists. Refinements in surgical technique may help reduce the incidence of complications, but stoma prolapse, particularly with transverse colostomies, remains a major challenge.

Anal Canal↗
PubMed1995

Efficient hammerhead ribozyme-mediated cleavage of the structured hepatitis B virus encapsidation signal in vitro and in cell extracts, but not in intact cells.

Hepatitis B virus (HBV), the causative agent of B-type hepatitis in man, is a small enveloped DNA virus that replicates through reverse transcription of an RNA intermediate, the terminally redundant RNA pregenome. An essential highly conserved cis-element present twice on this RNA is the encapsidation signal epsilon, a stem-loop structure that is critical for pregenome packaging and reverse transcription. Epsilon is hence an attractive target for antiviral therapy. Its structure, however, is a potential obstacle to antivirals whose action depends on hybridization, e.g. ribozymes. Here we demonstrate effective in vitro cleavage inside epsilon by hammerhead ribozymes containing flanking sequences complementary to an adjacent less structured region. Upon co-transfection with a HBV expression construct corresponding ribozymes embedded in a U6 snRNA context led to a significant, though modest, reduction in the steady-state level of HBV pregenomes. Inactive ribozyme mutants revealed that antisense effects contributed substantially to this reduction, however, efficient epsilon cleavage by the intracellularly expressed ribozymes was observed in Mg(2+)-supplemented cell lysates. Artificial HBV pregenomes carrying the ribozymes in cis and model RNAs lacking all HBV sequences except epsilon exhibited essentially the same behaviour. Hence, neither the absence of co-localization of ribozyme and target nor a viral component, but rather a cellular factor(s), is responsible for the strikingly different ribozyme activities inside cells and in cellular extracts.

Base Sequence↗
PubMed1995

The leukotriene LTD4 receptor antagonist MK571 specifically modulates MRP associated multidrug resistance.

The multidrug resistant cell lines HL60/AR and GLC4/ADR show high overexpression of the gene encoding the multidrug resistance associated protein MRP compared to their drug sensitive parental counterparts. This and the virtual absence of mdr1/P-glycoprotein gene expression was proven by a complementary DNA polymerase chain reaction (cDNA-PCR) approach. Applying a 72-hour tetrazolium based colorimetric MTT-assay we demonstrate on both MDR sublines a dose-dependent modulation of drug resistances by the leukotriene LTD4 receptor antagonist MK571. A complete reversal of vincristine resistances was achieved at final MK571 concentrations of 30 microM (HL60/AR) or 50 microM (GLC4/ADR) which by itself did not disturb cellular proliferation. The drug resistance of a mdr1/P-gp overexpressing multidrug-resistant HL60 subline, in contrast, was not significantly affected by MK571. Similar effects were seen using the glutathione (GSH) synthesis inhibitor buthionine sulfoximine (BSO). Our results point to a relationship between MRP and a conjugate transporter and identify MK571 as a new tool structure for developing modulators specific for a MRP associated multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗