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P Goebel

Publications and source records attributed to P Goebel.

At least 19 recordsLinked to original sources
PubMed2001

Localized gene-specific induction of accessibility to V(D)J recombination induced by E2A and early B cell factor in nonlymphoid cells.

Accessibility of immunoglobulin (Ig) gene segments to V(D)J recombination is highly regulated and is normally only achieved in B cell precursors. We previously showed that ectopic expression of E2A or early B cell factor (EBF) with recombination activating gene (RAG) induces rearrangement of IgH and IgL genes in nonlymphoid cells. VkappaI genes throughout the locus were induced to rearrange after transfection with E2A, suggesting that the entire Vkappa locus was accessible. However, here we show that Ig loci are not opened globally but that recombination is localized. Gene families are interspersed in the D(H), Vkappa, and Vlambda loci, and we show that certain families and individual genes undergo high levels of recombination after ectopic expression of E2A or EBF, while other families within the same locus are not induced to rearrange. Furthermore, in some families, induction of germline transcription correlates with the level of induced recombination, while in others there is no correlation, suggesting that recombination is not simply initiated by induction of germline transcription. The induced repertoire seen at 24 hours does not change significantly over time indicating the absence of many secondary rearrangements and also suggesting a direct targeting mechanism. We propose that accessibility occurs in a local manner, and that binding sites for factors facilitating accessibility are therefore likely to be associated with individual gene segments.

Animals↗
PubMed2000

E2A and EBF act in synergy with the V(D)J recombinase to generate a diverse immunoglobulin repertoire in nonlymphoid cells.

Immunoglobulin (Ig) and T cell receptor (TCR) genes are assembled during lymphocyte maturation through site-specific V(D)J recombination events. Here we show that E2A proteins act in concert with RAG1 and RAG2 to activate Ig VK1J but not Iglambda VlambdaIII-Jlambda1 rearrangement in an embryonic kidney cell line. In contrast, EBF, but not E2A, promotes VlambdaIII-Jlambda1 recombination. Either E2A or EBF activate IgH DH4J recombination but not V(D)J rearrangement. The Ig coding joints are diverse, contain nucleotide deletions, and lack N nucleotide additions. IgK VJ recombination requires the presence of the E2A transactivation domains. These observations indicate that in nonlymphoid cells a diverse Ig repertoire can be generated by the mere expression of the V(D)J recombinase and a transcriptional regulator.

Basic Helix-Loop-Helix Proteins↗
PubMed2000

Effect of PEEP and suction via chest drain on functional residual capacity and lung compliance after surgical repair of congenital diaphragmatic hernia: preliminary observations in 5 patients.

BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia that limits survival. The authors' knowledge on lung mechanics and lung volumes in these patients with hypoplastic lungs is still limited. Therefore, the authors performed measurements of functional residual capacity (FRC), compliance of the respiratory system (CRS), and tidal volume in 5 full-term infants (gestational age, 38 to 40 weeks; birth weight, 2,800 to 3,530 g) before and after surgical repair of neonatal CDH. METHODS: The authors studied the influence of different levels of positive end-expiratory pressure (PEEP) and suction via inserted ipsilateral chest tube connected to a water seal on lung volume and lung mechanics. A computerized tracer gas (SF6) washout method was used for serial measurements of FRC. Compliance of the respiratory system was determined according to insufflatory method. RESULTS: The authors found a preoperative compliance between 1.5 and 3.9 mL/kPa/kg and a preoperative FRC between 9.1 and 12.9 mL/kg indicating severe hypoplasia of the lungs in all patients. Immediately after surgical repair of CDH, compliance decreased to 85% (78% to 91%) of preoperative value, and FRC increased to 132% (110% to 150%) of preoperative value under mechanical ventilation while at 4 cm of water of PEEP and at -10 cm of water of suction via chest drain with the need of high fraction of inspired oxygen. After reduction of PEEP from 4 to 2 or 1 cm of water and lowering suction from -10 cm of water to -2 or 0 cm of water FRC decreased to 103% (80% to 122%) of preoperative value and compliance, and tidal volume improved to 135% (110% to 147%) of preoperative value resulting in increased alveolar ventilation, correction of acidosis and improvement in oxygenation. During the first days after surgery inadequate high PEEP or strong suction via chest tube drainage resulted in increase in FRC paralleled by decrease in compliance indicating overdistension of these hypoplastic lungs. CONCLUSIONS: The data show that overdistension of hypoplastic lungs in infants with CDH can be detected and excluded by repeated measurements of FRC and compliance in these critical ill infants. These data might help setting appropriate ventilator parameters, adequate suction via chest drain, and thereby improve gas exchange and outcome.

Chest Tubes↗
PubMed1999

Unusual amino acid usage in the variable regions of mercury-binding antibodies.

Monoclonal antibodies (mAb) specific for mercuric ions were isolated from BALB/c mice injected with a mercury-containing, hapten-carrier complex. The antibodies reacted by enzyme-linked immunosorbent assay with bovine serum albumin-glutathione-mercuric chloride (BSA-GSH-HgCl) but not with BSA-GSH without mercury. Nucleotide sequences from polymerase chain reaction products encoding six of the antibody heavy-chain variable regions and seven light-chain variable regions revealed that all the antibodies contained an unpaired cysteine residue in one hypervariable region, which is unusual for murine antibodies. Mutagenesis of the cysteine to either tyrosine or serine in one of the Hg-binding antibodies, mAb 4A10, eliminated mercury binding. However, of two influenza-specific antibodies that contain cysteine residues at the same position as mAb 4A10, one reacted with mercury, although not so strongly as 4A10, whereas the other did not react at all. These results suggested that, in addition to an unpaired cysteine, there are other structural features, not yet identified, that are important for creating an appropriate environment for mercury binding. The antibodies described here could be useful for investigating mechanisms of metal-protein interactions and for characterizing antibody responses to structurally simple haptens.

Amino Acid Sequence↗
PubMed1999

The impact of cultural and familial context on behavioral and emotional problems of preschool Latino children.

This study examined the impact of financial, cultural, and family variables on the incidence of behavioral and emotional problems in a group of two- and three-year-old Latino children. The vulnerability of these children to mental health problems stems from the many challenges faced by their families, especially those associated with acculturation and poverty. Results indicate that most problems experienced by the children were related to depression and social withdrawal. Children were at greatest risk whose parents had immigrated from Central America, whose families relied more extensively on internal coping strategies such as passive resignation, and whose parents were dissatisfied with their family's interactions.

Central America↗
PubMed1996

Metal binding properties of a monoclonal antibody directed toward metal-chelate complexes.

A monoclonal antibody that recognizes cadmium-EDTA complexes has been produced by the injection of BALB/c mice with a metal-chelate complex covalently coupled to a carrier protein. The ability of purified antibody to recognize 16 different metal-EDTA complexes was assessed by measuring equilibrium binding constants using a KinExATM immunoassay instrument. The antibody bound to cadmium- and mercury-EDTA complexes with equilibrium dissociation constants of 21 and 26 nM, respectively. All other metal-EDTA complexes tested, including those of Mn(II), In(III), Ni(II), Zn(II), Co(II), Cu(II), Ag(I), Fe(III), Pb(II), Au(III), Tb(III), Ga(III), Mg(II), and Al(III) bound with affinities from 20- to 40,000-fold less than that determined for the cadmium-EDTA complex. With the exception of mercury and magnesium, the binding of divalent metal-chelate complexes was well-correlated with the size of the metal ion. The amino acid sequences of the heavy and light chain variable regions were deduced from polymerase chain reaction-amplified regions of the corresponding genes and subsequently used to construct molecular models of the antigen binding region. The key residue for cadmium binding in the model for 2A81G5 appeared to be histidine 96 in the heavy chain.

Amino Acid Sequence↗
PubMed1996

Clinical correlates of an elevated diffusing capacity for carbon monoxide corrected for alveolar volume.

The diffusing capacity for carbon monoxide is partially dependent on lung volume at which it is measured. As a consequence, the diffusing capacity for carbon monoxide is often indexed to the simultaneously measured lung volume (VA), giving rise to the term DL/VA. This reflects the diffusing capacity of carbon monoxide per unit area of lung parenchyma. The authors investigated the pulmonary function of 18 patients who had an elevated DL/VA in order to identify factors that could account for this abnormality. Sixteen of the 18 had a reduction in vital capacity. The vital capacity was reduced because of obesity, pleural disease, and diaphragmatic dysfunction. Eight of nine patients with a body mass index > 30 kg/m2 had a reduction in vital capacity. On the basis of these findings, we believe that an elevated DL/VA should alert the physician to the possibility of 1) an increase in pulmonary capillary blood volume (Vc) (obesity, polycythemia, negative pleural pressure), and 2) reduced VA that does not directly affect the pulmonary capillary bed (pleural disease, neuromuscular disease).

Adult↗
PubMed1995

Db-binding peptides from influenza virus: effect of non-anchor residues on stability and immunodominance.

Relative affinities were determined for the interaction of H-2Db with all the peptides from the A/PR/8/34 strain of influenza virus that contained the Db-binding motif. The results indicated that, even though 23 peptides with the appropriate motif were identified and analysed, binding of only five of them could be detected at peptide concentrations lower than 10(-7) M. Of these five, only one, TGICNQNII, bound with better affinity than the nucleoprotein-derived natural epitope, ASNENMETM. The origin of the higher binding peptide was the influenza neuraminidase, a protein for which little cytosolic processing would be expected since it is a surface glycoprotein. To establish why many of the influenza-derived peptides did not bind, the role of non-anchor residues on Db-peptide interactions was analysed, using a scheme where QDIENEEKI, a non-binding peptide from the influenza virus polymerase 1, was sequentially converted to ASNENMETI, which binds to Db with an affinity similar to that of ASNENMETM. Although all positions examined influenced peptide binding, peptide residue no. 2 (P2) was of particular importance. Therefore, each of the 20 naturally occurring amino acids were inserted at this position to investigate their effects on peptide-MHC interaction. The results indicated that amino acids having side chains with charged or ring structures were deleterious, while non-polar and polar residues were either neutral or facilitated binding to different degrees. Our data also indicated that every residue of the peptide contributes to the stability of the MHC-peptide complex, and the final affinity is dependent on the nature of the amino acids at each position, not just on those at a small number of anchor positions. The results also suggested that increased stability, as indicated by the half-life of the peptide-MHC class I complex, might play an important role in selecting the immunodominant epitope.

Amino Acid Sequence↗
PubMed1995

Increased norepinephrine variability in patients with sleep apnea syndrome.

OBJECTIVE: To assess the plasma arterial catecholamine response to nocturnal desaturation in a group of patients with a history suggestive of sleep apnea. PATIENTS AND METHODS: At a Veterans Affairs hospital, 10 patients who had a history consistent with sleep apnea syndrome were involved in the study. Arterial plasma catecholamines were measured at varying intervals during a 5 1/2-hour sleep study. Eighteen samples per patient were analyzed. RESULTS: As the hemoglobin saturation decreased, the variability in plasma norepinephrine increased significantly (r = -.78, P = 0.004). As the hemoglobin saturation fell, there was a trend towards higher concentrations of plasma norepinephrine (r = -.53, P = 0.06). As the hemoglobin saturation decreased, the variability in plasma epinephrine concentration was not significant (r = .42). CONCLUSION: The association between the degree of desaturation and the variability in norepinephrine suggests that norepinephrine is released in response to nocturnal desaturation.

Adult↗
PubMed1993

Survival following mechanical ventilation for acute respiratory failure in adult men.

STUDY DESIGN: Survival following mechanical ventilation for acute respiratory failure has important implications for medical decision-making and allocation of expensive resources for critical care. PROCEDURE: We reviewed a 5-year experience with mechanical ventilation in 383 men with acute respiratory failure and studied the impact of patient age, cause of acute respiratory failure, and duration of mechanical ventilation on survival. Survival rates were 66.6 percent to weaning, 61.1 percent to ICU discharge, 49.6 percent to hospital discharge, and 30.1 percent to 1 year after hospital discharge. When our data were combined with 10 previously reported series, mean survival rates were calculated to be 62 percent to ventilator weaning, 46 percent to ICU discharge, 43 percent to hospital discharge, and 30 percent to 1 year after discharge. Of 255 patients weaned from mechanical ventilation, 44 (17.3 percent) required an additional period of mechanical ventilation during the same hospitalization. RESULTS: Age had a significant influence on survival to hospital discharge and on that to 1 year after hospital discharge, and the cause of acute respiratory failure had a significant influence on survival only to weaning. Survival was best in younger patients and those with COPD or postoperative respiratory failure and worst in patients resuscitated after cardiac or respiratory arrest. Increased duration of mechanical ventilation significantly reduced survival only to hospital discharge. Overall survival was significantly affected by age and cause of acute respiratory failure, but not by duration of mechanical ventilation. CONCLUSION: We conclude that age, cause of acute respiratory failure, and duration of mechanical ventilation have specific influences on the generally poor outcome of mechanical ventilation for acute respiratory failure.

Acute Disease↗
PubMed1991

[Creativeness and creative personalities--a study of successful entrepreneurs].

The term creativity is defined, and the underlying creative process is described. The creative process is developed with the help of the new metaphors. The two most successful and creative from over 130 entrepreneurs involved in a research project are taken as examples. The essentials of the creative process the inexhaustible process of the phantasy concerning certain ideas and problems is enlarged in connection with the results of the Giessen Test S and the two above-mentioned entrepreneurs.

Achievement↗
PubMed1987

[Catamnestic study of 96 couples with heterologous insemination].

96 couples who had made an artificial insemination with donor sperm within 1968 and were interviewed in 1984, regardless whether the treatment was successful or not. The aim of the inquiry was to see how the partnership and the children developed as well as the actual feeling of the decision made. Three groups resulted which can be compared with each other: a) couples with successful treatment and children conceived by artificial insemination, b) couples with unsuccessful treatment by artificial insemination and consequent adoption of a child, c) couples with unsuccessful treatment by artificial insemination and without adoption of a child. 63 (65.6%) had at least one conception. 68 children were born to 55 couples. In the case of 9 men a normal conception took place after completion of the treatment. About 10% became divorced in the groups a and b and about 35% in group c. No couple regretted the treatment. The fathers of the divorced couples experienced themselves as fathers. The development of the children conceived in artificial insemination with donor sperm has not been showing any signs of unusual disturbances.

Adoption↗
PubMed1987

[Vasectomy and partnership status--an empirical study of 156 males (couples)].

In the USA voluntary male sterilization is wide-spread since years. In the Federal Republic of Germany the frequency of demanding vasectomy is increasing. All who are involved have to assure whether the request for vasectomy bases upon a mature or a neurotic decision which might be regretted one day. The research is based on the hypothesis that the decision for vasectomy is made in context with the personal structure, the partner relationship, and the family background. Therefore a process of interviews is made which are established on psychoanalytic and couple and family dynamic questions. The sociopsychological data give an impression of the situation in which the decision is made. Different couples with typical behavior patterns are characterized to show the special part of couples interaction in the decision-making process. The sequelae of vasectomy is expected to be largely determined by the development of the partner relationship. This is a subject for a planned follow-up study.

Adaptation, Psychological↗
PubMed1987

[Animal experiment studies of the effect of peracetic acid on bladder urothelium].

Animal experimenters investigations on the influence of various solutions of peracetic acid on the epithelium of the urinary bladder were carried out on rabbits. The results of the experiments showed that solutions of peracetic acid up to 0.01% are tolerated nearly without any reaction also under extreme experimental conditions. Higher concentrations of active substances lead to considerable changes of the epithelium of the urinary bladder in form of partly focal, partly diffuse haemorrhagic necrotizing urocystitides. No differences were the result when the commercial 40 percent peracetic acid Wofasteril and a 20 percent peracetic acid without admixture of a stabilizer as primary solution were used. The possible application of peracetic acid as antiseptic for the mucous membrane is discussed.

Acetates↗
PubMed1987

[Risk factors in vasectomy--a comparison of satisfied vasectomized males with dissatisfied males seeking refertilization].

Ninety-two men were explored by depth psychological interviews before vasectomy and 12-15 months later. Eighty-six of them were completely satisfied with the operation. Six men were dissatisfied and would not undergo the operation again. Forty men requesting refertilization were also explored by depth psychological interviews one day before operation. The comparison of these two groups shows that vasectomy is problematic for men who are younger than 30 years, being in training, and whose partners are not willing to undergo sterilization as well. Men without partners and without children should reconsider their decision for vasectomy and particularly those who show the above-mentioned characteristics and/or those who make the decision without being able to use condoms and/or are unable to handle the situation in case of an abortion. The length of partnership is not important for the sequelae of vasectomy.

Abortion, Induced↗
PubMed1986

[Symbol and metaphor].

Taking Jones' work--A Theory of Symbolism as a Basis--it is attempted to elaborate on the basic underlying hypotheses of his symbol concept and to show the partiality of his metaphor concept. Prominence is given the concepts of similarity, identification and structure of experience. The insufficient definition of the metaphor complicates, the understanding of the connection between symbol, symptom and language. The metaphor phenomenon is explained and its organization principles pointed out; principles which are also found in the organisation of experience formation. Freunds theses of primitive language and the use of language as a bridge to symbolism is clarified. The connection between metaphor and symbol is represented as a circular process.

Affect↗