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Biomedical subjects

J Henke

Publications and source records attributed to J Henke.

At least 19 recordsLinked to original sources
PubMed2002

[Experimental endoscopic intrauterine surgery for craniofacial malformations such as the cleft lip and palate].

INDICATION FOR FETAL SURGERY: The widespread use of high-resolution ultrasound in prenatal diagnosis allows nowadays an accurate and early diagnosis of congenital malformations. Some of these can be corrected surgically. In certain cases intrauterine surgery could present functional and aesthetic advantages or be even lifesaving. Due to the extreme sensitiveness of the fetal patient and the fetal membranes, only some defined anomalies currently meet the criteria for intrauterine surgery. However, the list can change in the future since prenatal diagnosis, technical advances, and knowledge of pathophysiology improve constantly. ENDOSCOPIC INTRAUTERINE SURGERY: Additionally, the recent development of endoscopic intrauterine surgery represents a new and more careful possibility for intrauterine surgery. Endoscopic procedures could avoid the disadvantages of open intrauterine surgery and thus make fetal operations safer, in life-threatening as well as in non-life-threatening malformations such as cleft lip and palate (CLP). The main advantages of these procedures are (1) scarless wound healing and bone healing without callus formation that leave to expect normal growth of the midface and (2) lower fetal and maternal morbidity. DISCUSSION: Based on the results achieved until now, it can be stated that at present the intrauterine operation of CLP on humans cannot be recommended. The high morbidity and mortality risk for mother and fetus cannot be counterbalanced by the unsatisfactory results of a prenatal operation. CONCLUSION: In this study first results of an experimental investigation with the new endoscopic techniques are presented, whereby the possibilities for optimization and quality improvement of the intrauterine surgical procedures are analyzed in detail.

Animals↗
PubMed2002

Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo.

Low efficiencies of nonviral gene vectors, the receptor-dependent host tropism of adenoviral or low titers of retroviral vectors limit their utility in gene therapy. To overcome these deficiencies, we associated gene vectors with superparamagnetic nanoparticles and targeted gene delivery by application of a magnetic field. This potentiated the efficacy of any vector up to several hundred-fold, allowed reduction of the duration of gene delivery to minutes, extended the host tropism of adenoviral vectors to nonpermissive cells and compensated for low retroviral titer. More importantly, the high transduction efficiency observed in vitro was reproduced in vivo with magnetic field-guided local transfection in the gastrointestinal tract and in blood vessels. Magnetofection provides a novel tool for high throughput gene screening in vitro and can help to overcome fundamental limitations to gene therapy in vivo.

Adenoviridae↗
PubMed2001

Large-scale analysis of the Alu Ya5 and Yb8 subfamilies and their contribution to human genomic diversity.

We have utilized computational biology to screen GenBank for the presence of recently integrated Ya5 and Yb8 Alu family members. Our analysis identified 2640 Ya5 Alu family members and 1852 Yb8 Alu family members from the draft sequence of the human genome. We selected a set of 475 of these elements for detailed analyses. Analysis of the DNA sequences from the individual Alu elements revealed a low level of random mutations within both subfamilies consistent with the recent origin of these elements within the human genome. Polymerase chain reaction assays were used to determine the phylogenetic distribution and human genomic variation associated with each Alu repeat. Over 99 % of the Ya5 and Yb8 Alu family members were restricted to the human genome and absent from orthologous positions within the genomes of several non-human primates, confirming the recent origin of these Alu subfamilies in the human genome. Approximately 1 % of the analyzed Ya5 and Yb8 Alu family members had integrated into previously undefined repeated regions of the human genome. Analysis of mosaic Yb8 elements suggests gene conversion played an important role in generating sequence diversity among these elements. Of the 475 evaluated elements, a total of 106 of the Ya5 and Yb8 Alu family members were polymorphic for insertion presence/absence within the genomes of a diverse array of human populations. The newly identified Alu insertion polymorphisms will be useful tools for the study of human genomic diversity.

Alu Elements↗
PubMed2001

Online reference database of European Y-chromosomal short tandem repeat (STR) haplotypes.

The reference database of highly informative Y-chromosomal short tandem repeat (STR) haplotypes (YHRD), available online at http://ystr.charite.de, represents the largest collection of male-specific genetic profiles currently available for European populations. By September 2000, YHRD contained 4688 9-locus (so-called "minimal") haplotypes, 40% of which have been extended further to include two additional loci. Establishment of YHRD has been facilitated by the joint efforts of 31 forensic and anthropological institutions. All contributing laboratories have agreed to standardize their Y-STR haplotyping protocols and to participate in a quality assurance exercise prior to the inclusion of any data. In view of its collaborative character, and in order to put YHRD to its intended use, viz. the support of forensic caseworkers in their routine decision-making process, the database has been made publicly available via the Internet in February 2000. Online searches for complete or partial Y-STR haplotypes from evidentiary or non-probative material can be performed on a non-commercial basis, and yield observed haplotype counts as well as extrapolated population frequency estimates. In addition, the YHRD website provides information about the quality control test, genotyping protocols, haplotype formats and informativity, population genetic analysis, literature references, and a list of contact addresses of the contributing laboratories.

Databases, Factual↗
PubMed2001

Sequence analysis and population data on the 'new' short tandem repeat locus D5S2360.

We have studied the sequence structure and population genetics of a 'new' short tandem repeat polymorphism at locus D5S2360 in German Caucasians. Sequencing at this locus revealed a considerable variation, which is characterized by a tetranucleotide (AGAT)(n) repeat pattern with (GAT), (AGATT), and (AG) repeats dispersed throughout the alleles. These microvariations do not necessarily alter the size of the alleles. They may vary by one or two pairs or they may remain unchanged in size. At locus D5S2360 we observed 33 allelic lengths comprising at least 36 different alleles. Population data revealed a high polymorphism with a heterozygosity rate of approximately 92.5%.

Alleles↗
PubMed2001

Characterization of genomic rearrangements of the alpha1-acid glycoprotein/orosomucoid gene in Ghanaians.

In this study, the structure of the alpha1-acid glycoprotein (AGP), or orosomucoid (ORM), gene was investigated in a Ghanaian mother and her child, who shared an unusual variant, ORM1 S2(C), found by isoelectric focusing. Three remarkable changes of nucleotide sequence were observed: (1) The two ORM1 alleles, ORMI*S and ORMI*S2(C), had the AGP2 gene-specific sequence at one and three regions, respectively, in exon 5 to intron 5. The variant allele originating from ORMi*S was characterized by a G-to-A transition, resulting in an amino acid change from valine to methionine, which is also detected in ORM1 F2, a form that is common in Europeans. (2) The AGP2 gene of the child, inherited from the father, was duplicated, as revealed by long-range polymerase chain reaction. (3) Three new mutations were observed in two exons of the AGP2 genes of the mother and child. All of these novel genomic rearrangements, which were not observed in Japanese subjects, may have arisen through point mutation, gene conversion, and unequal crossover events. It is likely that the rearrangement of the AGP gene has often occurred in Africans.

Alleles↗
PubMed2001

Plasma epinephrine levels after epinephrine administration using different tracheal administration techniques in an adult CPR porcine model.

The aim of the study was to compare arterial plasma epinephrine levels after tracheal epinephrine application using three different tracheal instillation techniques at different tracheal levels in a porcine adult cardiopulmonary resuscitation model. In the prospective, randomized study, electrically-induced cardiopulmonary arrest was applied to 32 anaesthetized and paralyzed domestic pigs. After 3 min of cardiopulmonary arrest and 2 min of external chest compressions using a pneumatic compression device and mechanical ventilation, epinephrine was administered intravenously (20 microg/kg) or tracheally (50 microg/kg): using either direct injection into the upper end of the tracheal tube, via a catheter placed into the bronchial system and using a special tracheal application tube. In each group, there were eight pigs. Arterial blood samples were taken before and up to 10 min after epinephrine administration. Regression analysis was performed of the correlated data. The values of mean arterial blood pressure and end-tidal CO(2) during the time of observation did not differ between groups. Total plasma epinephrine concentrations showed a significant increase in all groups, but with no difference between the tracheal groups. However, peak epinephrine levels in the intravenous group were significantly higher than in tracheal groups. We conclude that administration using three different tracheal instillation levels result in similar onset and peak plasma epinephrine levels in this setting and therefore the preferred method of tracheal epinephrine application for cardiopulmonary resuscitation may be selected by other criteria.

Animals↗
PubMed2001

Diagnosing acute liver graft rejection: experimental application of an implantable telemetric impedance device in native and transplanted porcine livers.

BACKGROUND AND AIMS: Diagnosis of acute rejection is a complex and persistent problem in liver transplantation. Focused on the use of proprietary impedance technology a porcine liver model was designed to provide immediate information for differentiation of normal and acute rejecting tissue by an implantable telemetric device. METHODS: Electrical impedance was analyzed by electrodes implanted in vitro and in vivo in the liver of pigs, where impedance is derived from measurements of voltage transients produced in response to programmed current pulses. Consequent electric recordings in porcine livers after transplantation and after mere laparotomy were evaluated in relation to biochemical parameters and histological results of liver biopsies. RESULTS: Acute rejection was correctly predicted in all cases and correctly excluded in the remaining 32 biopsy related impedance recordings (P<0.004). Impedance measurements not only correlated with the diagnosis from liver biopsy specimen (r=0.84, P<0.0001) but also exemplified the severity of histological acute rejection. CONCLUSION: Impedance analysis reveals evident physiologic relation of acute liver graft rejection and electrical organ properties. Electrodes implanted in transplanted porcine livers allow running less invasive monitoring and thus early detection of rejection. The technology may have broad value in providing an immediate diagnosis of acute rejection, reducing unnecessary patient anxiety and eliminating the significant expenses associated with multiple referrals, expensive sample handling and tissue analysis.

Acute Disease↗
PubMed2001

Haplotype analysis of the human alpha2-HS glycoprotein (fetuin) gene.

Alpha2-HS glycoprotein (AHSG), which is equivalent to fetuin in other species, is a protein found in human plasma. AHSG is polymorphic with two common alleles and many variants. To examine the intragenic haplotypes and their diversity at this locus, a contiguous genomic DNA sequence (10.3 kb) was analyzed in 20 samples (40 chromosomes), and haplotypes were determined for 309 subjects. Judging from the aligned nucleotide sequences and the conserved amino acid residues comparing human and chimpanzee AHSG, it was concluded that the type 1 allele is probably older and has evolved into four major suballeles. The type 2 allele was generated from one branch of the type 1 allele. AHSG*3 and *5 variants were each found to have a single nucleotide change in exon 7, resulting in the change of an amino acid residue from Arg299 to Cys and from Asp258 to Asn, respectively. It was noted that the AHSG*3 mutation gives rise to an additional cysteine residue, which possibly affects the conformation of the protein. The AHSG gene was found to have a low mutation rate and no apparent recombination events. Furthermore, the detected substitutions were nonhomogeneously distributed at this locus. In particular, four nonsynonymous substitutions were concentrated in the carboxyl-terminal domain.

Alleles↗
PubMed2001

Application of Y-chromosomal STR haplotypes to forensic genetics.

This paper delivers population genetic data on Y-chromosomal short tandem repeat (STR) polymorphisms along with reports of unusual observations and casework. Population studies were carried out on the Y-specific STR polymorphisms DYS19, DYS385 I+II, DYS389 I+II, DYS390, DYS391, DYS392, and DYS393 in population samples from North India, Turkey, and Germany. In all three populations the vast majority of haplotypes was observed only once, especially in the Turkish group. Highly unusual cases are reported. In a German individual, we observed the variant allele DYS392*11.1, whereas a Turkish haplotype revealed a duplication at locus DYS19. Application of Y-chromosomal STR markers to forensic genetics was demonstrated in two cases: 1) a deficient paternity case, and 2) a father/son pair, where the Amelogenin primers failed to amplify the Y-homolog. In forensic genetics, Y-chromosomal STR polymorphisms are highly welcomed as an additional tool.

Female↗
PubMed2000

Malignant hyperthermia mutation Arg615Cys in the porcine ryanodine receptor alters voltage dependence of Ca2+ release.

Ca2+ inward current and fura-2 Ca2+ transients were simultaneously recorded in porcine myotubes. Myotubes from normal pigs and cells from specimens homozygous for the Arg615Cys (malignant hyperthermia) mutation of the skeletal muscle ryanodine receptor RyR1 were investigated. We addressed the question whether this mutation alters the voltage dependence of Ca2+ release from the sarcoplasmic reticulum. The time course of the total flux of Ca2+ into the myoplasm was estimated. Analysis showed that the largest input Ca2+ flux occurred immediately after depolarization. Amplitude and time course of the Ca2+ flux at large depolarizations were not significantly different in the Arg615Cys myotubes. Ca2+ release from the sarcoplasmic reticulum was activated at more negative potentials than the L-type Ca2+ conductance. In the controls, the potentials for half-maximal activation V 1/2 were -9.0mV and 16.5 mV, respectively. In myotubes expressing the Arg615Cys mutation, Ca2+ release was activated at significantly lower depolarizing potentials (V = -23.5 mV) than in control myotubes. In contrast, V of conductance activation (13.5 mV) was not significantly different from controls. The specific shift in the voltage dependence of Ca2+ release caused by this mutation can be well described by altering a voltage-independent reaction of the ryanodine receptor that is coupled to the voltage-dependent transitions of the L-type Ca2+ channel.

Amino Acid Substitution↗
PubMed2000

Characteristics and frequency of germline mutations at microsatellite loci from the human Y chromosome, as revealed by direct observation in father/son pairs.

A number of applications of analysis of human Y-chromosome microsatellite loci to human evolution and forensic science require reliable estimates of the mutation rate and knowledge of the mutational mechanism. We therefore screened a total of 4,999 meioses from father/son pairs with confirmed paternity (probability >/=99. 9%) at 15 Y-chromosomal microsatellite loci and identified 14 mutations. The locus-specific mutation-rate estimates were 0-8. 58x10-3, and the average mutation rate estimates were 3.17x10-3 (95% confidence interval [CI] 1.89-4.94x10-3) across 8 tetranucleotide microsatellites and 2.80x10-3 (95% CI 1.72-4.27x10-3) across all 15 Y-chromosomal microsatellites studied. Our data show a mutational bias toward length increase, on the basis of observation of more repeat gains than losses (10:4). The data are in almost complete agreement with the stepwise-mutation model, with 13 single-repeat changes and 1 double-repeat change. Sequence analysis revealed that all mutations occurred in uninterrupted homogenous arrays of >/=11 repeats. We conclude that mutation rates and characteristics of human Y-chromosomal microsatellites are consistent with those of autosomal microsatellites. This indicates that the general mutational mechanism of microsatellites is independent of recombination.

Adolescent↗
PubMed2000

Molecular analysis of the human orosomucoid gene ORM1*Q0köln responsible for incompatibility in a German paternity case.

In a German paternity test, an alleged father was excluded only by reverse homozygosity of ORM1 phenotypes (mother ORM1 S, child ORM1 S and alleged father ORM1 F1) out of the 28 classical and DNA markers investigated. Without the ORM1 system the biostatistical probability of paternity was calculated to exceed 99.999%. The intensity of the immunoprinted bands of the ORM1 protein for the child and alleged father after isoelectric focusing appeared to be reduced to about half. To identify a possible null allele, gene-specific amplification followed by single-strand conformation polymorphism and sequencing analyses were carried out. Deletion of one of the two copies of a 4 bp direct repeat sequence (GTCT) in exon 4 of the consensus sequence of ORM1*F1 was observed in the child and alleged father. Thus, the sharing of a rare mutant gene, ORM1*Q0köln, increased the probability of paternity.

DNA Mutational Analysis↗
PubMed2000

Acute electrophysiologic effects and antifibrillatory actions of the long linear lesions in the right atrium in a sheep model.

UNLABELLED: Linear lesions (LL) represent an option for curing of atrial fibrillation (AF) with ablation techniques. METHODS AND RESULTS: In 11 sheep (w. 72+/-16 kg), LL were created with radiofrequency ablation in the lateral, posterior and septal walls of the right atrium (RA). AF was induced before and after LL with burst pacing. Mapping of the AF was performed with a 64-electrode basket catheter deployed in the RA. Quantitative analysis was performed with a custom-made software program. LL were confirmed histologically 7 to 10 days after the procedure. LL were transmural in 78% of their length. Stimulation thresholds and right atrial activation times were increased after LL compared to preablation values. Effective refractory periods of the RA were prolonged significantly in 7 out of 12 regions after generation of LL. Conduction velocities in the RA segments between LL were reduced in lateral, posterior and septal walls. During paced rhythms double potentials were recorded in all animals. AF could be induced in all animals of this model despite the presence of LL in the RA. AF episodes were significantly more regular after LL throughout the RA due to a significant reduction of the number of the wave fronts in the RA. During AF episodes, in the presence of LL, the RA was driven by wave fronts of left atrial origin entering the right side of the septum through interatrial connections. CONCLUSIONS: 1) LL profoundly affect electrophysiologic parameters of RA. 2) In the presence of LL, AF manifest a higher degree of regularity as compared to preablation episodes. 3) Dissociation between wave fronts of left atrial origin entering the RA through the interatrial connections is an important mechanism of the antifibrillatory action of the septal LL.

Animals↗
PubMed2000

Endohyperthermia--experimental evaluation of a new therapeutic approach for treatment of biliary carcinoma.

BACKGROUND AND STUDY AIMS: To improve the prognosis of patients with unresectable, locally advanced bile duct carcinoma, new treatment strategies need to be evaluated. Hyperthermia has been successfully applied as part of multimodal therapy in esophageal and rectal carcinoma. We performed in-vitro and in-vivo experiments with a new intraluminal hyperthermia system in the biliary tract. METHODS: A radiofrequency system (13.56 MHz, Endoradiotherm XERT-200A; Olympus Optical Co., Tokyo, Japan) was used with a special intraluminal microelectrode (diameter 4.5 mm, length 40 mm) covered by a silicone balloon with cooling water and a large counter electrode for focusing the electromagnetic field around the electrode. The heating capacity of the endohyperthermia unit was examined in vitro in a muscle-equivalent phantom (agar 4 %), in isolated livers of pigs and cows, as well as in vivo in anesthetized sheep. Continuous thermometry was done with thermosensors at the applicator surface, and with multichannel thermocouple probes in the environment of the applicator. RESULTS: Endohyperthermia induced a homogeneous heating of the phantom and the isolated liver bile duct preparation to a temperature > or = 40 degrees C in an area at least 10 mm in depth. After placement of the applicator into the common bile duct of anesthetized sheep, endohyperthermia led to a consistent and repeatable heating of the surrounding tissue to 40.5 +/- 0.5 degrees C at 1 cm distance, and 39.9 +/- 0.7 degrees C at 2 cm distance. Blood pressure, heart rate, and systemic temperature did not change in vivo. Histological examination of the bile duct showed superficial mucosal necrosis (depth 100-200 microm), microvascular damage with petechiae, congestion and edema of the bile duct wall and adventitia after hyperthermia treatment in vivo. CONCLUSIONS: The intraluminal endohyperthermia system produces consistent and repeatable heating of the surrounding tissue. Since effective thermal power can reach a depth of up to 2 cm, tumors may also be heated adequately.

Animals↗