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R Kirschner

Publications and source records attributed to R Kirschner.

At least 19 recordsLinked to original sources
PubMed2001

Disruption of an inner arm dynein heavy chain gene results in asthenozoospermia and reduced ciliary beat frequency.

Impaired ciliary and flagellar functions resulting in male infertility and recurrent respiratory tract infections are found in patients suffering from primary ciliary dyskinesia (PCD). In most cases, axonemal defects are present, i.e. PCD patients often lack inner and/or outer dynein arms in their sperm tails and cilia, supporting the hypothesis that mutations in dynein genes may cause PCD. However, to date it is unclear whether mutations in dynein heavy chain genes are responsible for impaired flagellar and ciliary motility in mammals. To elucidate the role of the mouse dynein heavy chain 7 (MDHC7) gene, which encodes a component of the inner dynein arm, we have generated mice lacking this dynein heavy chain isoform. Both MDHC7(+/-) and MDHC7(-/-) mice are viable and show no malformations; however, homozygous males produce no offspring. In comparison to MDHC7(+/-) and wild-type mice the spermatozoa of MDHC7(-/-) mice revealed a dramatic reduced straight line velocity and progressive movement, resulting in the inability of MDHC7-deficient sperm to move from the uterus into the oviduct. Additionally, we measured the beat frequency of tracheal cilia and observed a decrease in the beat frequency of approximately 50% in MDHC7(-/-) mice. The reduction in both ciliary and flagellar motility is not correlated with any gross defects in the axonemal structure. The phenotype of MDHC7(-/-) mice is similar to that observed in some patients suffering from PCD, and our data strongly suggest that in some patients this disease could be due to mutations in the homologous human gene DNAH1 (HDHC7).

Animals↗
PubMed2001

Towards a solution of the charmonium production controversy: k( perpendicular) factorization versus color-octet mechanism.

The cross section of chi(cJ) hadroproduction is calculated in the k( perpendicular)-factorization approach. We find a significant contribution of the chi(c1) state due to non-applicability of the Landau-Yang theorem because of off-shell gluons. The results are in agreement with data and, in contrast to the collinear factorization, show a dominance of the color-singlet part and a strong suppression of the color octet contribution. Our results could therefore lead to a solution of the long-standing controversy between the color-singlet model and the color-octet mechanism.

Journal Article↗
PubMed2001

DNA sequence comparison of human and mouse retinitis pigmentosa GTPase regulator (RPGR) identifies tissue-specific exons and putative regulatory elements.

Retinitis pigmentosa 3 (RP3) is a progressive retinal degeneration due to mutations in the X-linked RPGR gene. Transcription studies in human and mouse tissues have revealed ubiquitously expressed transcripts and also an exceptional high number of tissue-specific alternative splice variants. However, regulation of tissue-specific expression and splicing is unclear, but this is of particular interest as mutations in this ubiquitously expressed gene lead to severe retinal degeneration, while other tissues are unaffected. To elucidate the conservation pattern of RPGR and to identify additional tissue-specific exons and putative regulatory elements we performed comparative genomic sequencing of the human and mouse RPGR gene. Each of the genes spans a region of nearly 59 kb, and all previously identified exons are conserved between the two species. DNA sequence comparison identified 28 conserved sequence elements (CSEs) in introns, upstream of exon 1, within the promotor region, and downstream of the most 3' exon. Some of the intronic CSEs flank tissue-specific exons and therefore may represent important regulatory elements for alternative splicing. Comparative northern blot hybridization of ubiquitous and tissue-specific RPGR probes identified high molecular weight transcripts with similar expression patterns in both human and mouse. These transcripts range from 6 to 15 kb in size and suggest the presence of additional transcribed sequences within RPGR. Our cross-species sequence comparison enables us to define candidate regions that may explain these large transcripts and will therefore contribute to the understanding of RPGR expression and splicing.

Alternative Splicing↗
PubMed2001

Cuniculitrema polymorpha (Tremellales, gen. nov. and sp. nov.), a heterobasidiomycete vectored by bark beetles, which is the teleomorph of Sterigmatosporidium polymorphum.

In a study of the mycobiota associated with bark beetles, a dimorphic fungus producing longitudinally septate basidia of the Tremella-type and yeast cells budding off from stalks, was collected. Detailed morphological, physiological and molecular studies revealed that this fungus represents the teleomorph of Sterigmatosporidium polymorphum. Consequently, a new genus, Cuniculitrema gen. nov., and a new species, C. polymorpha sp. nov., are proposed. Comparative morphological and molecular studies indicated that the new taxon belongs to a group that also comprises species of the stalk-forming anamorphic genera Fellomyces and Kockovaella. The new family Cuniculitremaceae is proposed for this group.

Animals↗
PubMed2001

Adequacy of pain assessment and pain relief and correlation of patient satisfaction in 68 ED fast-track patients.

INTRODUCTION: The new standards of the joint commission on accreditation of healthcare organizations specify the patient's right to appropriate assessment and management of pain. With this impetus, we looked at our own practice to see how well we assess and manage patients with pain. METHODS: Patients who presented with minor nonemergent pain were interviewed on arrival, and then again before discharge, with use of a structured questionnaire. A total of 68 completed pain surveys were analyzed. RESULTS: With use of a visual analog scale, patients rated their pain on arrival and at discharge; they also rated pain they were willing to accept when it was time for discharge. Sixty percent of the patients went home with more pain than they were willing to accept. Fifty-one percent of the patients were offered something for pain, and only half of them said the pain relief was adequate. The median time from arrival to administration of pain medication was 104 minutes. Surprisingly, the median patient satisfaction rating for overall care was "very good." DISCUSSION: This survey revealed that acute pain conditions are underevaluated and undertreated in one fast-track setting, suggesting that ED staff need more education about the management of acute pain. It also showed that relying on patient satisfaction surveys as surrogate markers for how well we manage pain is erroneous.

Acute Disease↗
PubMed2000

A trial of etomidate for rapid sequence intubation in the emergency department.

A number of pharmacologic agents have been used for induction during rapid sequence intubation (RSI). Some of these agents may have adverse effects that can limit their use in certain clinical settings. This study was undertaken to determine the safety and utility of etomidate in patients with a range of underlying clinical conditions. Thirty-four patients underwent RSI in the emergency department (ED). Hemodynamic measurements and clinical assessments were recorded before and after intubation. The results suggest that etomidate is a safe and effective agent for use in a range of patients undergoing RSI in the ED.

Aged↗
PubMed1999

RPGR transcription studies in mouse and human tissues reveal a retina-specific isoform that is disrupted in a patient with X-linked retinitis pigmentosa.

X-linked retinitis pigmentosa (XLRP) is a genetically heterogeneous group of progressive retinal degenerations. The disease process is initiated by premature apoptosis of rod photoreceptor cells in the retina, which leads to reduced visual acuity and, eventually, complete blindness. Mutations in the retinitis pigmentosa GTPase regulator ( RPGR ), a ubiquitously expressed gene at the RP3 locus in Xp21.1, account for approximately 20% of all X-linked cases. We have analysed the expression of this gene by northern blot hybridization, cDNA library screening and RT-PCR in various organs from mouse and man. These studies revealed at least 12 alternatively spliced isoforms. Some of the transcripts are tissue specific and contain novel exons, which elongate or truncate the previously reported open reading frame of the mouse and human RPGR gene. One of the newly identified exons is expressed exclusively in the human retina and mouse eye and contains a premature stop codon. The deduced polypeptide lacks 169 amino acids from the C-terminus of the ubiquitously expressed variant, including an isoprenylation site. Moreover, this exon was found to be deleted in a family with XLRP. Our results indicate tissue-dependent regulation of alternative splicing of RPGR in mouse and man. The discovery of a retina-specific transcript may explain why phenotypic abberations in RP3 are confined to the eye.

Adult↗
PubMed1999

The Philadelphia story: the 22q11.2 deletion: report on 250 patients.

A submicroscopic deletion of chromosome 22q11.2 has been identified in the majority of patients with the DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes, and in some patients with the Opitz G/BBB and Cayler cardiofacial syndromes. We have been involved in the analysis of DiGeorge syndrome and related diagnoses since 1982 and have evaluated a large number of patients with the deletion. We describe our cohort of 250 patients whose clinical findings help to define the extremely variable phenotype associated with the 22q11.2 deletion and may assist clinicians in providing genetic counseling and guidelines for clinical management based on these findings.

Abnormalities, Multiple↗
PubMed1998

Positional cloning of the gene for X-linked retinitis pigmentosa 2.

X-linked retinitis pigmentosa (XLRP) results from mutations in at least two different loci, designated RP2 and RP3, located at Xp11.3 and Xp21.1, respectively. The RP3 gene was recently isolated by positional cloning, whereas the RP2 locus was mapped genetically to a 5-cM interval. We have screened this region for genomic rearrangements by the YAC representation hybridization (YRH) technique and detected a LINE1 (L1) insertion in one XLRP patient. The L1 retrotransposition occurred in an intron of a novel gene that consisted of five exons and encoded a polypeptide of 350 amino acids. Subsequently, nonsense, missense and frameshift mutations, as well as two small deletions, were identified in six additional patients. The predicted gene product shows homology with human cofactor C, a protein involved in the ultimate step of beta-tubulin folding. Our data provide evidence that mutations in this gene, designated RP2, are responsible for progressive retinal degeneration.

Amino Acid Sequence↗
PubMed1998

[Physician practice patterns and attitudes to euthanasia in Germany. A representative survey of physicians].

Growing life expectancy and increasing pharmaceutical and technical methods in medicine are leading to more and more discussions among the general population and among physicians as to whether methods to shorten the sufferings of mortally ill persons should be legalised further. In Australia 60% of physicians wish to be able to perform active euthanasia if this would be legal. In the Netherlands physicians do not commit an offence if they perform euthanasia on the basis of ethically consented rules. In the FRG the National Board of Physicians (Bundesärztekammer) still rejects any liberalisation concerning active euthanasia. However, little is known of the attitudes and behaviour of physicians concerning the questions of active and passive euthanasia. Sponsored by Gruner and Jahr publishers for a magazine "Stern" publication we conducted a representative study among physicians working in hospitals and their colleagues in free practices concerning this topic. Beginning with qualitative interviews with 50 physicians we tested the questionnaire developed and looked for the data production method best fitting for this difficult matter resulting in telephone interviews or a self-administered questionnaire. In the main study a representative sample of n = 282 physicians in free practices and n = 191 physicians in hospitals were interviewed. The response rates were 94% and 51% respectively. Analysis of non-responses did not indicate any bias. Half of the physicians think that a broader discussion on euthanasia is necessary, 34% disagree and 17% consider even a discussion already dangerous. 6% of the physicians in hospitals and 11% in free practices have already experienced methods of active euthanasia. Half of the physicians have seen patients who strongly wished euthanasia, a situation which happens once in every two years. The majority of physicians feel a deep understanding but only a minority of 4% comply with the wish. The vast majority of physicians advocate indirect euthanasia. However, they experience difficulties in defining the difference between active and passive euthanasia in a concrete situation. Summing up, our data indicate that a broader and open discussion on euthanasia seems necessary even if this discussion in Germany will be even more difficult than in other countries due to our recent past. The discussion will be reopened by a proposal on guidelines concerning euthanasia launched by the German National Board of Physician

Aged↗
PubMed1997

Identification of dynein heavy chain genes expressed in human and mouse testis: chromosomal localization of an axonemal dynein gene.

Dynein heavy chains are involved in microtubule-dependent transport processes. While cytoplasmic dyneins are involved in chromosome or vesicle movement, axonemal dyneins are essential for motility of cilia and flagella. Here we report the isolation of dynein heavy chain (DHC)-like sequences in man and mouse. Using polymerase chain reaction and reverse-transcribed human and mouse testis RNA cDNA fragments encoding the conserved ATP binding region of dynein heavy chains were amplified. We identified 11 different mouse and eight human dynein-like sequences in testis which show high similarity to known dyneins of different species such as rat, sea urchin or green algae. Sequence similarities suggest that two of the mouse clones and one human clone encode putative cytoplasmic dynein heavy chains, whereas the other sequences show higher similarity to axonemal dyneins. Two of nine axonemal dynein isoforms identified in the mouse testis are more closely related to known outer arm dyneins, while seven clones seem to belong to the inner arm dynein group. Of the isolated human isoforms three clones were classified as outer arm and four clones as inner arm dynein heavy chains. Each of the DHC cDNAs corresponds to an individual gene as determined by Southern blot experiments. The alignment of the deduced protein sequences between human (HDHC) and mouse (MDHC) dynein fragments reveals higher similarity between single human and mouse sequences than between two sequences of the same species. Human and mouse cDNA fragments were used to isolate genomic clones. Two of these clones, gHDHC7 and gMDHC7, are homologous genes encoding axonemal inner arm dyneins. While the human clone is assigned to 3p21, the mouse gene maps to chromosome 14.

Amino Acid Sequence↗
PubMed1997

The human hepatocyte nuclear factor 3/fork head gene FKHL13: genomic structure and pattern of expression.

We describe the isolation and characterization of the cDNA for FKHL13, the human homologue of the mouse hepatocyte nuclear factor 3/fork head homologue 4 (HFH-4) gene, a member of the HNF-3/fork head (also called winged helix) gene family. Members of this gene family contain a conserved DNA binding region of approx. 110 amino acids and are thought to play an important role in cell-specific differentiation. Previous analysis of the mouse and rat HFH-4 cDNAs revealed a distinct pattern of expression for this gene, suggesting that the gene plays an important role in the differentiation of lung and oviduct/ampulla epithelial cells and testicular spermatids. Analysis of the human FKHL13 gene confirmed this pattern of expression. We also found expression in adult human brain cortex, which we were able to confirm for the mouse. The expression pattern of FKHL13/HFH-4, confined to cilia/flagella-producing cells, leads us to believe that the gene plays an important role in the regulation of axonemal structural proteins. We show that the human gene for FKHL13 lies on chromosome 17 (comparison with the chromosomal location of the mouse gene strongly suggests 17q22-q25) and that the gene, which is approx. 6 kb, contains a single intron disrupting the fork head DNA binding domain. Such a disruption of a functional unit provides strong evidence for the theory of intron insertion during gene evolution. The expression of the gene is probably controlled by the CpG island, which is located in the promoter region of the gene. We also demonstrate that the FKHL13 gene is highly conserved among a wide variety of species, including birds.

Adult↗
PubMed1995

[A cost-benefit analysis of different therapeutic methods in menorrhagia].

When deciding the right forms of treatment for various medical conditions it has been usual to consider medical knowledge, norms and experience. Increasingly, economic factors and principles are being introduced by the management, in the form of health economics and pharmaco-economic analyses, enforced as budgetary cuts and demands for rationalisation and measures to increase efficiency. Economic evaluations require construction of models for analyses. We have used DRG-information, National Health reimbursements and pharmacological retail prices to make a cost-efficiency analysis of treatments of menorrhagia. The analysis showed better cost-efficiency for certain pharmacological treatments than for surgery.

Adult↗